Previous Issue

Table of Contents

Genes, Volume 9, Issue 4 (April 2018)

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
View options order results:
result details:
Displaying articles 1-51
Export citation of selected articles as:

Editorial

Jump to: Research, Review, Other

Open AccessEditorial Special Issue Introduction: Inherited Retinal Disease: Novel Candidate Genes, Genotype–Phenotype Correlations, and Inheritance Models
Genes 2018, 9(4), 215; doi:10.3390/genes9040215
Received: 5 April 2018 / Accepted: 13 April 2018 / Published: 16 April 2018
PDF Full-text (498 KB) | HTML Full-text | XML Full-text
Abstract
Inherited retinal diseases (IRDs) are genetically and clinically heterogeneous disorders.[...] Full article
Figures

Figure 1

Research

Jump to: Editorial, Review, Other

Open AccessArticle A Toxin-Antitoxin System VapBC15 from Synechocystis sp. PCC 6803 Shows Distinct Regulatory Features
Genes 2018, 9(4), 173; doi:10.3390/genes9040173
Received: 29 January 2018 / Revised: 13 March 2018 / Accepted: 15 March 2018 / Published: 21 March 2018
PDF Full-text (2722 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Type II toxin–antitoxin (TA) systems play important roles in bacterial stress survival by regulating cell growth or death. They are highly abundant in cyanobacteria yet remain poorly characterized. Here, we report the identification and regulation of a putative type II TA system from
[...] Read more.
Type II toxin–antitoxin (TA) systems play important roles in bacterial stress survival by regulating cell growth or death. They are highly abundant in cyanobacteria yet remain poorly characterized. Here, we report the identification and regulation of a putative type II TA system from Synechocystis PCC6803, VapBC15. The VapBC15 system is encoded by the chromosomal operon vapBC15. Exogenous expression of VapC15 dramatically arrested cell growth of Escherichia coli and reduced the numbers of colony-forming units (CFU). The VapC15 toxicity could be neutralized by simultaneous or delayed production of VapB15. Biochemical analysis demonstrated the formation of VapB15-VapC15 complexes by the physical interaction between VapB15 and VapC15. Notably, the VapB15 antitoxin up-regulated the transcription of the vapBC15 operon by directly binding to the promoter region, and the VapC15 toxin abolished the up-regulatory effect by destabilizing the binding. Moreover, VapB15 can be degraded by the proteases Lons and ClpXP2s from Synechocystis PCC6803, thus activating the latent toxicity of VapBC15. These findings suggest that VapBC15 represents a genuine TA system that utilizes a distinct mechanism to regulate toxin activity. Full article
(This article belongs to the Section Microbial Genetics and Genomics)
Figures

Figure 1

Open AccessArticle Bioprinting Perfusion-Enabled Liver Equivalents for Advanced Organ-on-a-Chip Applications
Genes 2018, 9(4), 176; doi:10.3390/genes9040176
Received: 5 February 2018 / Revised: 8 March 2018 / Accepted: 19 March 2018 / Published: 22 March 2018
PDF Full-text (9764 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Many tissue models have been developed to mimic liver-specific functions for metabolic and toxin conversion in in vitro assays. Most models represent a 2D environment rather than a complex 3D structure similar to native tissue. To overcome this issue, spheroid cultures have become
[...] Read more.
Many tissue models have been developed to mimic liver-specific functions for metabolic and toxin conversion in in vitro assays. Most models represent a 2D environment rather than a complex 3D structure similar to native tissue. To overcome this issue, spheroid cultures have become the gold standard in tissue engineering. Unfortunately, spheroids are limited in size due to diffusion barriers in their dense structures, limiting nutrient and oxygen supply. Recent developments in bioprinting techniques have enabled us to engineer complex 3D structures with perfusion-enabled channel systems to ensure nutritional supply within larger, densely-populated tissue models. In this study, we present a proof-of-concept for the feasibility of bioprinting a liver organoid by combining HepaRG and human stellate cells in a stereolithographic printing approach, and show basic characterization under static cultivation conditions. Using standard tissue engineering analytics, such as immunohistology and qPCR, we found higher albumin and cytochrome P450 3A4 (CYP3A4) expression in bioprinted liver tissues compared to monolayer controls over a two-week cultivation period. In addition, the expression of tight junctions, liver-specific bile transporter multidrug resistance-associated protein 2 (MRP2), and overall metabolism (glucose, lactate, lactate dehydrogenase (LDH)) were found to be stable. Furthermore, we provide evidence for the perfusability of the organoids’ intrinsic channel system. These results motivate new approaches and further development in liver tissue engineering for advanced organ-on-a-chip applications and pharmaceutical developments. Full article
(This article belongs to the Special Issue From the Lab-on-a-Chip to the Organ-on-a-Chip)
Figures

Figure 1

Open AccessArticle Resistance to 6-Methylpurine is Conferred by Defective Adenine Phosphoribosyltransferase in Tetrahymena
Genes 2018, 9(4), 179; doi:10.3390/genes9040179
Received: 19 February 2018 / Revised: 16 March 2018 / Accepted: 20 March 2018 / Published: 23 March 2018
PDF Full-text (22939 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
6-methylpurine (6mp) is a toxic analog of adenine that inhibits RNA and protein synthesis and interferes with adenine salvage mediated by adenine phosphoribosyltransferase (APRTase). Mutants of the ciliated protist Tetrahymena thermophila that are resistant to 6mp were isolated in 1974, but the mechanism
[...] Read more.
6-methylpurine (6mp) is a toxic analog of adenine that inhibits RNA and protein synthesis and interferes with adenine salvage mediated by adenine phosphoribosyltransferase (APRTase). Mutants of the ciliated protist Tetrahymena thermophila that are resistant to 6mp were isolated in 1974, but the mechanism of resistance has remained unknown. To investigate 6mp resistance in T. thermophila, we created 6mp-resistant strains and identified a mutation in the APRTase genomic locus (APRT1) that is responsible for 6mp resistance. While overexpression of the mutated APRT1 allele in 6mp-sensitive cells did not confer resistance to 6mp, reduced wild-type APRT1 expression resulted in a significant decrease in sensitivity to 6mp. Knocking out or reducing the expression of APRT1 by RNA interference (RNAi) did not affect robust cell growth, which indicates that adenine salvage is redundant or that de novo synthesis pathways provide sufficient adenosine monophosphate for viability. We also explored whether 6mp resistance could be used as a novel inducible selection marker by generating 6mp- and paromomycin-resistant double mutants. While 6mp- and paromomycin-resistant double mutants did express fluorescent proteins in an RNAi-based system, the system requires optimization before 6mp resistance can be used as an effective inducible selection marker. Full article
(This article belongs to the Section Microbial Genetics and Genomics)
Figures

Figure 1

Open AccessFeature PaperArticle Non-Pleiotropic Coupling of Daily and Seasonal Temporal Isolation in the European Corn Borer
Genes 2018, 9(4), 180; doi:10.3390/genes9040180
Received: 30 January 2018 / Revised: 15 March 2018 / Accepted: 20 March 2018 / Published: 26 March 2018
PDF Full-text (3408 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Speciation often involves the coupling of multiple isolating barriers to produce reproductive isolation, but how coupling is generated among different premating barriers is unknown. We measure the degree of coupling between the daily mating time and seasonal mating time between strains of European
[...] Read more.
Speciation often involves the coupling of multiple isolating barriers to produce reproductive isolation, but how coupling is generated among different premating barriers is unknown. We measure the degree of coupling between the daily mating time and seasonal mating time between strains of European corn borer (Ostrinia nubilalis) and evaluate the hypothesis that the coupling of different forms of allochrony is due to a shared genetic architecture, involving genes with pleiotropic effects on both timing phenotypes. We measure differences in gene expression at peak mating times and compare these genes to previously identified candidates that are associated with changes in seasonal mating time between the corn borer strains. We find that the E strain, which mates earlier in the season, also mates 2.7 h earlier in the night than the Z strain. Earlier daily mating is correlated with the differences in expression of the circadian clock genes cycle, slimb, and vrille. However, different circadian clock genes associate with daily and seasonal timing, suggesting that the coupling of timing traits is maintained by natural selection rather than pleiotropy. Juvenile hormone gene expression was associated with both types of timing, suggesting that circadian genes activate common downstream modules that may impose constraint on future evolution of these traits. Full article
(This article belongs to the Special Issue Evolutionary Genetics of Reproductive Isolation)
Figures

Open AccessArticle Genome-Wide Identification of the Alba Gene Family in Plants and Stress-Responsive Expression of the Rice Alba Genes
Genes 2018, 9(4), 183; doi:10.3390/genes9040183
Received: 8 December 2017 / Revised: 26 January 2018 / Accepted: 29 January 2018 / Published: 28 March 2018
PDF Full-text (35961 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Architectural proteins play key roles in genome construction and regulate the expression of many genes, albeit the modulation of genome plasticity by these proteins is largely unknown. A critical screening of the architectural proteins in five crop species, viz., Oryza sativa, Zea
[...] Read more.
Architectural proteins play key roles in genome construction and regulate the expression of many genes, albeit the modulation of genome plasticity by these proteins is largely unknown. A critical screening of the architectural proteins in five crop species, viz., Oryza sativa, Zea mays, Sorghum bicolor, Cicer arietinum, and Vitis vinifera, and in the model plant Arabidopsis thaliana along with evolutionary relevant species such as Chlamydomonas reinhardtii, Physcomitrella patens, and Amborella trichopoda, revealed 9, 20, 10, 7, 7, 6, 1, 4, and 4 Alba (acetylation lowers binding affinity) genes, respectively. A phylogenetic analysis of the genes and of their counterparts in other plant species indicated evolutionary conservation and diversification. In each group, the structural components of the genes and motifs showed significant conservation. The chromosomal location of the Alba genes of rice (OsAlba), showed an unequal distribution on 8 of its 12 chromosomes. The expression profiles of the OsAlba genes indicated a distinct tissue-specific expression in the seedling, vegetative, and reproductive stages. The quantitative real-time PCR (qRT-PCR) analysis of the OsAlba genes confirmed their stress-inducible expression under multivariate environmental conditions and phytohormone treatments. The evaluation of the regulatory elements in 68 Alba genes from the 9 species studied led to the identification of conserved motifs and overlapping microRNA (miRNA) target sites, suggesting the conservation of their function in related proteins and a divergence in their biological roles across species. The 3D structure and the prediction of putative ligands and their binding sites for OsAlba proteins offered a key insight into the structure–function relationship. These results provide a comprehensive overview of the subtle genetic diversification of the OsAlba genes, which will help in elucidating their functional role in plants. Full article
(This article belongs to the Section Plant Genetics and Genomics)
Figures

Figure 1

Open AccessArticle Engineering the Salt-Inducible Ectoine Promoter Region of Halomonas elongata for Protein Expression in a Unique Stabilizing Environment
Genes 2018, 9(4), 184; doi:10.3390/genes9040184
Received: 31 January 2018 / Revised: 19 March 2018 / Accepted: 21 March 2018 / Published: 28 March 2018
PDF Full-text (57895 KB) | HTML Full-text | XML Full-text
Abstract
It has been firmly established that organic osmolytes (compatible solutes) of halophilic Bacteria and Archaea have positive effects on conformation and activity of proteins, and may therefore improve their functional production. In particular, the amino acid derivative ectoine is known for its conformational
[...] Read more.
It has been firmly established that organic osmolytes (compatible solutes) of halophilic Bacteria and Archaea have positive effects on conformation and activity of proteins, and may therefore improve their functional production. In particular, the amino acid derivative ectoine is known for its conformational stabilization, aggregation suppression, and radical protection properties. The natural producer and industrial production strain Halomonas elongata accumulates ectoine in the cytoplasm, and as a result offers a unique stabilizing environment for recombinant proteins. For the construction of broad hoast range vector systems with fluorescent reporter proteins, we chose the salt-inducible promoter region of the ectoine gene cluster (promA). A closer inspection of the genetic background revealed that its combination of sigma 38 (σ38) and sigma 70 (σ70) promoters was followed by a weak ribosomal binding site (RBS). This inspired a systematic approach for the construction of a promA-based vector series with a synthetic RBS region using the RBS Calculator v2.0, which resulted in a greatly improved salt-dependent expression—even in a deletion construct lacking the σ38 promoter. To expand the application range of this expression system, we looked further into the possible export of recombinant proteins into the periplasm. Both sec and tat leader sequences from H. elongata proved to be suitable for directed periplasmic transport into an extreme environment of freely selectable ionic strength. Full article
(This article belongs to the Special Issue Genetics and Genomics of Extremophiles)
Figures

Figure 1

Open AccessArticle Assembly of the Boechera retrofracta Genome and Evolutionary Analysis of Apomixis-Associated Genes
Genes 2018, 9(4), 185; doi:10.3390/genes9040185
Received: 14 February 2018 / Revised: 21 March 2018 / Accepted: 22 March 2018 / Published: 28 March 2018
PDF Full-text (32129 KB) | HTML Full-text | XML Full-text
Abstract
Closely related to the model plant Arabidopsis thaliana, the genus Boechera is known to contain both sexual and apomictic species or accessions. Boechera retrofracta is a diploid sexually reproducing species and is thought to be an ancestral parent species of apomictic species.
[...] Read more.
Closely related to the model plant Arabidopsis thaliana, the genus Boechera is known to contain both sexual and apomictic species or accessions. Boechera retrofracta is a diploid sexually reproducing species and is thought to be an ancestral parent species of apomictic species. Here we report the de novo assembly of the B. retrofracta genome using short Illumina and Roche reads from 1 paired-end and 3 mate pair libraries. The distribution of 23-mers from the paired end library has indicated a low level of heterozygosity and the presence of detectable duplications and triplications. The genome size was estimated to be equal 227 Mb. N50 of the assembled scaffolds was 2.3 Mb. Using a hybrid approach that combines homology-based and de novo methods 27,048 protein-coding genes were predicted. Also repeats, transfer RNA (tRNA) and ribosomal RNA (rRNA) genes were annotated. Finally, genes of B. retrofracta and 6 other Brassicaceae species were used for phylogenetic tree reconstruction. In addition, we explored the histidine exonuclease APOLLO locus, related to apomixis in Boechera, and proposed model of its evolution through the series of duplications. An assembled genome of B. retrofracta will help in the challenging assembly of the highly heterozygous genomes of hybrid apomictic species. Full article
(This article belongs to the Special Issue Evolution and Biodiversity of the Plant Genome Architecture)
Figures

Open AccessArticle The Human Tyrosyl-DNA Phosphodiesterase 1 (hTdp1) Inhibitor NSC120686 as an Exploratory Tool to Investigate Plant Tdp1 Genes
Genes 2018, 9(4), 186; doi:10.3390/genes9040186
Received: 1 February 2018 / Revised: 16 March 2018 / Accepted: 23 March 2018 / Published: 28 March 2018
PDF Full-text (2910 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The hTdp1 (human tyrosyl-DNA phosphodiesterase 1) inhibitor NSC120686 has been used, along with topoisomerase inhibitors, as a pharmacophoric model to restrain the Tdp1 activity as part of a synergistic treatment for cancer. While this compound has an end-point application in medical research, in
[...] Read more.
The hTdp1 (human tyrosyl-DNA phosphodiesterase 1) inhibitor NSC120686 has been used, along with topoisomerase inhibitors, as a pharmacophoric model to restrain the Tdp1 activity as part of a synergistic treatment for cancer. While this compound has an end-point application in medical research, in plants, its application has not been considered so far. The originality of our study consists in the use of hTdp1 inhibitor in Medicago truncatula cells, which, unlike human cells, contain two Tdp1 genes. Hence, the purpose of this study was to test the hTdp1 inhibitor NSC120686 as an exploratory tool to investigate the plant Tdp1 genes, since their characterization is still in incipient phases. To do so, M. truncatula calli were exposed to increasing (75, 150, 300 μM) concentrations of NSC120686. The levels of cell mortality and DNA damage, measured via diffusion assay and comet assay, respectively, were significantly increased when the highest doses were used, indicative of a cytotoxic and genotoxic threshold. In addition, the NSC120686-treated calli and untreated MtTdp1α-depleted calli shared a similar response in terms of programmed cell death (PCD)/necrosis and DNA damage. Interestingly, the expression profiles of MtTdp1α and MtTdp1β genes were differently affected by the NSC120686 treatment, as MtTdp1α was upregulated while MtTdp1β was downregulated. The NSC120686 treatment affected not only the MtTdp1 genes but also other genes with roles in alternative DNA repair pathways. Since the expression patterns of these genes were different than what was observed in the MtTdp1α-depleted plants, it could be hypothesized that the NSC120686 treatment exerts a different influence compared to that resulting from the lack of the MtTdp1α gene function. Full article
(This article belongs to the Special Issue DNA Damage Responses in Plants)
Figures

Figure 1

Open AccessArticle UBE2C Is a Transcriptional Target of the Cell Cycle Regulator FOXM1
Genes 2018, 9(4), 188; doi:10.3390/genes9040188
Received: 8 January 2018 / Revised: 21 March 2018 / Accepted: 27 March 2018 / Published: 29 March 2018
PDF Full-text (12685 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
FOXM1 (forkhead box protein M1) is a transcription factor that participates in all stages of tumor development, mainly through the control of cell cycle and proliferation, regulating the expression of genes involved in G1/S and G2/M transition and M phase progression. The ubiquitin
[...] Read more.
FOXM1 (forkhead box protein M1) is a transcription factor that participates in all stages of tumor development, mainly through the control of cell cycle and proliferation, regulating the expression of genes involved in G1/S and G2/M transition and M phase progression. The ubiquitin conjugating enzyme E2 (UBE2C) is a member of the anaphase promoting complex/cyclosome, promoting the degradation of several target proteins along cell cycle progression, during metaphase/anaphase transition. FOXM1 and UBE2C have been found overexpressed in a wide range of different solid tumors. Therefore, the aim of this study was to investigate whether UBE2C is a transcriptional target of FOXM1, using esophageal squamous cell carcinoma (ESCC) as a model, in addition to several cancer-deposited data. Our results show that FOXM1 and UBE2C expression present a positive correlation in normal tissues and in 25 distinct tumor types, including ESCC, where these genes are overexpressed. Moreover, FOXM1 binds to UBE2C promoter region in ESCC cell line and transcriptionally activates it, leading to UBE2C upregulation. In conclusion, this study provides evidences that FOXM1 transcriptionally regulates UBE2C expression in ESCC and their deregulation may be a general phenomenon in human neoplasias. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
Figures

Figure 1

Open AccessArticle Sequence and Haplotypes Variation of the Ovine Uncoupling Protein-1 Gene (UCP1) and Their Association with Growth and Carcass Traits in New Zealand Romney Lambs
Genes 2018, 9(4), 189; doi:10.3390/genes9040189
Received: 5 February 2018 / Revised: 12 March 2018 / Accepted: 28 March 2018 / Published: 30 March 2018
PDF Full-text (2108 KB) | HTML Full-text | XML Full-text
Abstract
Uncoupling protein-1 gene (UCP1) plays an important role in the regulation of thermogenesis, energy expenditure, and protection against oxidative stress. In this study, six separate UCP1 regions: region-1 and region-2 (two parts of the promoter), region-3 and region-4 (two parts of
[...] Read more.
Uncoupling protein-1 gene (UCP1) plays an important role in the regulation of thermogenesis, energy expenditure, and protection against oxidative stress. In this study, six separate UCP1 regions: region-1 and region-2 (two parts of the promoter), region-3 and region-4 (two parts of intron 1), region-5 (spanning part of intron 5 and part of exon 6), and region-6 (spanning part of exon 6 and part of the 3′-UTR) from a variety of sheep breeds, were analysed using polymerase chain reaction-single-stranded conformational polymorphism (PCR-SSCP) analyses. In total, 30 single nucleotide polymorphisms (SNPs) were detected. Of these, 14 were located in the promoter, eight were found in intron 1, six were found in intron 5, and one was found in the 3′-UTR. One substitution in exon 6 (c.910A/G) would putatively result in an amino acid change (p.Thr304Ala). Twenty-eight novel SNPs and nine new haplotypes spanning region-2 to region-5 were identified. Of these nine haplotypes, five were common (B2-A5, C2-A5, C2-C5, A2-A5, and A2-B5) and four were rare (C2-B5, A2-C5, B2-C5, and B2-B5) in the sheep investigated. Of the five common haplotypes found in 314 New Zealand Romney sheep for which growth and carcass trait data were available, the presence of A2-B5 was associated with decreased hot carcass weight (HCW) and loin lean-meat yield (p = 0.006, p = 0.032, respectively), and the presence of C2-C5 was associated with a decreased proportion of leg lean-meat yield (p = 0.047) in the carcasses. No associations were found with growth traits. These results confirm that ovine UCP1 is a variable gene and may have value as a genetic marker for sheep breeding. Full article
(This article belongs to the Section Animal Genetics and Genomics)
Figures

Figure 1

Open AccessArticle Kinetics and Thermodynamics of DNA Processing by Wild Type DNA-Glycosylase Endo III and Its Catalytically Inactive Mutant Forms
Genes 2018, 9(4), 190; doi:10.3390/genes9040190
Received: 27 February 2018 / Revised: 22 March 2018 / Accepted: 27 March 2018 / Published: 30 March 2018
PDF Full-text (20739 KB) | HTML Full-text | XML Full-text
Abstract
Endonuclease III (Endo III or Nth) is one of the key enzymes responsible for initiating the base excision repair of oxidized or reduced pyrimidine bases in DNA. In this study, a thermodynamic analysis of structural rearrangements of the specific and nonspecific DNA-duplexes during
[...] Read more.
Endonuclease III (Endo III or Nth) is one of the key enzymes responsible for initiating the base excision repair of oxidized or reduced pyrimidine bases in DNA. In this study, a thermodynamic analysis of structural rearrangements of the specific and nonspecific DNA-duplexes during their interaction with Endo III is performed based on stopped-flow kinetic data. 1,3-diaza-2-oxophenoxazine (tCO), a fluorescent analog of the natural nucleobase cytosine, is used to record multistep DNA binding and lesion recognition within a temperature range (5–37 °C). Standard Gibbs energy, enthalpy, and entropy of the specific steps are derived from kinetic data using Van’t Hoff plots. The data suggest that enthalpy-driven exothermic 5,6-dihydrouracil (DHU) recognition and desolvation-accompanied entropy-driven adjustment of the enzyme–substrate complex into a catalytically active state play equally important parts in the overall process. The roles of catalytically significant amino acids Lys120 and Asp138 in the DNA lesion recognition and catalysis are identified. Lys120 participates not only in the catalytic steps but also in the processes of local duplex distortion, whereas substitution Asp138Ala leads to a complete loss of the ability of Endo III to distort a DNA double chain during enzyme–DNA complex formation. Full article
(This article belongs to the Special Issue Nucleic Acid Dynamics and Structure)
Figures

Figure 1

Open AccessArticle Exposure to Formaldehyde Perturbs the Mouse Gut Microbiome
Genes 2018, 9(4), 192; doi:10.3390/genes9040192
Received: 8 February 2018 / Revised: 20 March 2018 / Accepted: 28 March 2018 / Published: 3 April 2018
PDF Full-text (32259 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Exposure to Formaldehyde (FA) results in many pathophysiological symptoms, however the underlying mechanisms are not well understood. Given the complicated modulatory role of intestinal microbiota on human health, we hypothesized that interactions between FA and the gut microbiome may account for FA’s toxicity.
[...] Read more.
Exposure to Formaldehyde (FA) results in many pathophysiological symptoms, however the underlying mechanisms are not well understood. Given the complicated modulatory role of intestinal microbiota on human health, we hypothesized that interactions between FA and the gut microbiome may account for FA’s toxicity. Balb/c mice were allocated randomly to three groups: a control group, a methanol group (0.1 and 0.3 ng/mL MeOH subgroups), and an FA group (1 and 3 ng/mL FA subgroups). Groups of either three or six mice were used for the control or experiment. We applied high-throughput sequencing of 16S ribosomal RNA (rRNA) gene approaches and investigated possible alterations in the composition of mouse gut microbiota induced by FA. Changes in bacterial genera induced by FA exposure were identified. By analyzing KEGG metabolic pathways predicted by PICRUSt software, we also explored the potential metabolic changes, such as alpha-Linolenic acid metabolism and pathways in cancer, associated with FA exposure in mice. To the best of our knowledge, this preliminary study is the first to identify changes in the mouse gut microbiome after FA exposure, and to analyze the relevant potential metabolisms. The limitation of this study: this study is relatively small and needs to be further confirmed through a larger study. Full article
(This article belongs to the Section Microbial Genetics and Genomics)
Figures

Figure 1

Open AccessArticle Identification and Characterization of the MADS-Box Genes and Their Contribution to Flower Organ in Carnation (Dianthus caryophyllus L.)
Genes 2018, 9(4), 193; doi:10.3390/genes9040193
Received: 5 March 2018 / Revised: 22 March 2018 / Accepted: 22 March 2018 / Published: 4 April 2018
PDF Full-text (24332 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Dianthus is a large genus containing many species with high ornamental economic value. Extensive breeding strategies permitted an exploration of an improvement in the quality of cultivated carnation, particularly in flowers. However, little is known on the molecular mechanisms of flower development in
[...] Read more.
Dianthus is a large genus containing many species with high ornamental economic value. Extensive breeding strategies permitted an exploration of an improvement in the quality of cultivated carnation, particularly in flowers. However, little is known on the molecular mechanisms of flower development in carnation. Here, we report the identification and description of MADS-box genes in carnation (DcaMADS) with a focus on those involved in flower development and organ identity determination. In this study, 39 MADS-box genes were identified from the carnation genome and transcriptome by the phylogenetic analysis. These genes were categorized into four subgroups (30 MIKCc, two MIKC*, two Mα, and five Mγ). The MADS-box domain, gene structure, and conserved motif compositions of the carnation MADS genes were analysed. Meanwhile, the expression of DcaMADS genes were significantly different in stems, leaves, and flower buds. Further studies were carried out for exploring the expression of DcaMADS genes in individual flower organs, and some crucial DcaMADS genes correlated with their putative function were validated. Finally, a new expression pattern of DcaMADS genes in flower organs of carnation was provided: sepal (three class E genes and two class A genes), petal (two class B genes, two class E genes, and one SHORT VEGETATIVE PHASE (SVP)), stamen (two class B genes, two class E genes, and two class C), styles (two class E genes and two class C), and ovary (two class E genes, two class C, one AGAMOUS-LIKE 6 (AGL6), one SEEDSTICK (STK), one B sister, one SVP, and one ). This result proposes a model in floral organ identity of carnation and it may be helpful to further explore the molecular mechanism of flower organ identity in carnation. Full article
(This article belongs to the Section Plant Genetics and Genomics)
Figures

Figure 1

Open AccessArticle A Key Gene, PLIN1, Can Affect Porcine Intramuscular Fat Content Based on Transcriptome Analysis
Genes 2018, 9(4), 194; doi:10.3390/genes9040194
Received: 13 February 2018 / Revised: 22 March 2018 / Accepted: 27 March 2018 / Published: 4 April 2018
PDF Full-text (21429 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Intramuscular fat (IMF) content is an important indicator for meat quality evaluation. However, the key genes and molecular regulatory mechanisms affecting IMF deposition remain unclear. In the present study, we identified 75 differentially expressed genes (DEGs) between the higher (H) and lower (L)
[...] Read more.
Intramuscular fat (IMF) content is an important indicator for meat quality evaluation. However, the key genes and molecular regulatory mechanisms affecting IMF deposition remain unclear. In the present study, we identified 75 differentially expressed genes (DEGs) between the higher (H) and lower (L) IMF content of pigs using transcriptome analysis, of which 27 were upregulated and 48 were downregulated. Notably, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the DEG perilipin-1 (PLIN1) was significantly enriched in the fat metabolism-related peroxisome proliferator-activated receptor (PPAR) signaling pathway. Furthermore, we determined the expression patterns and functional role of porcine PLIN1. Our results indicate that PLIN1 was highly expressed in porcine adipose tissue, and its expression level was significantly higher in the H IMF content group when compared with the L IMF content group, and expression was increased during adipocyte differentiation. Additionally, our results confirm that PLIN1 knockdown decreases the triglyceride (TG) level and lipid droplet (LD) size in porcine adipocytes. Overall, our data identify novel candidate genes affecting IMF content and provide new insight into PLIN1 in porcine IMF deposition and adipocyte differentiation. Full article
(This article belongs to the Section Animal Genetics and Genomics)
Figures

Open AccessArticle Identification of a WNT5A-Responsive Degradation Domain in the Kinesin Superfamily Protein KIF26B
Genes 2018, 9(4), 196; doi:10.3390/genes9040196
Received: 19 February 2018 / Revised: 24 March 2018 / Accepted: 26 March 2018 / Published: 5 April 2018
PDF Full-text (2014 KB) | HTML Full-text | XML Full-text
Abstract
Noncanonical WNT pathways function independently of the β-catenin transcriptional co-activator to regulate diverse morphogenetic and pathogenic processes. Recent studies showed that noncanonical WNTs, such as WNT5A, can signal the degradation of several downstream effectors, thereby modulating these effectors’ cellular activities. The protein domain(s)
[...] Read more.
Noncanonical WNT pathways function independently of the β-catenin transcriptional co-activator to regulate diverse morphogenetic and pathogenic processes. Recent studies showed that noncanonical WNTs, such as WNT5A, can signal the degradation of several downstream effectors, thereby modulating these effectors’ cellular activities. The protein domain(s) that mediates the WNT5A-dependent degradation response, however, has not been identified. By coupling protein mutagenesis experiments with a flow cytometry-based degradation reporter assay, we have defined a protein domain in the kinesin superfamily protein KIF26B that is essential for WNT5A-dependent degradation. We found that a human disease-causing KIF26B mutation located at a conserved amino acid within this domain compromises the ability of WNT5A to induce KIF26B degradation. Using pharmacological perturbation, we further uncovered a role of glycogen synthase kinase 3 (GSK3) in WNT5A regulation of KIF26B degradation. Lastly, based on the identification of the WNT5A-responsive domain, we developed a new reporter system that allows for efficient profiling of WNT5A-KIF26B signaling activity in both somatic and stem cells. In conclusion, our study identifies a new protein domain that mediates WNT5A-dependent degradation of KIF26B and provides a new tool for functional characterization of noncanonical WNT5A signaling in cells. Full article
(This article belongs to the Special Issue Wnt Signaling in Stem Cells)
Figures

Figure 1a

Open AccessArticle Transgenic Xenopus laevis Line for In Vivo Labeling of Nephrons within the Kidney
Genes 2018, 9(4), 197; doi:10.3390/genes9040197
Received: 28 February 2018 / Revised: 29 March 2018 / Accepted: 4 April 2018 / Published: 6 April 2018
PDF Full-text (27553 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Xenopus laevis embryos are an established model for studying kidney development. The nephron structure and genetic pathways that regulate nephrogenesis are conserved between Xenopus and humans, allowing for the study of human disease-causing genes. Xenopus embryos are also amenable to large-scale screening, but
[...] Read more.
Xenopus laevis embryos are an established model for studying kidney development. The nephron structure and genetic pathways that regulate nephrogenesis are conserved between Xenopus and humans, allowing for the study of human disease-causing genes. Xenopus embryos are also amenable to large-scale screening, but studies of kidney disease-related genes have been impeded because assessment of kidney development has largely been limited to examining fixed embryos. To overcome this problem, we have generated a transgenic line that labels the kidney. We characterize this cdh17:eGFP line, showing green fluorescent protein (GFP) expression in the pronephric and mesonephric kidneys and colocalization with known kidney markers. We also demonstrate the feasibility of live imaging of embryonic kidney development and the use of cdh17:eGFP as a kidney marker for secretion assays. Additionally, we develop a new methodology to isolate and identify kidney cells for primary culture. We also use morpholino knockdown of essential kidney development genes to establish that GFP expression enables observation of phenotypes, previously only described in fixed embryos. Taken together, this transgenic line will enable primary kidney cell culture and live imaging of pronephric and mesonephric kidney development. It will also provide a simple means for high-throughput screening of putative human kidney disease-causing genes. Full article
(This article belongs to the Special Issue DNA Variations in Evolution and Human Diseases)
Figures

Open AccessArticle Ancient DNA from Giant Panda (Ailuropoda melanoleuca) of South-Western China Reveals Genetic Diversity Loss during the Holocene
Genes 2018, 9(4), 198; doi:10.3390/genes9040198
Received: 24 February 2018 / Revised: 26 March 2018 / Accepted: 27 March 2018 / Published: 6 April 2018
PDF Full-text (6825 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The giant panda was widely distributed in China and south-eastern Asia during the middle to late Pleistocene, prior to its habitat becoming rapidly reduced in the Holocene. While conservation reserves have been established and population numbers of the giant panda have recently increased,
[...] Read more.
The giant panda was widely distributed in China and south-eastern Asia during the middle to late Pleistocene, prior to its habitat becoming rapidly reduced in the Holocene. While conservation reserves have been established and population numbers of the giant panda have recently increased, the interpretation of its genetic diversity remains controversial. Previous analyses, surprisingly, have indicated relatively high levels of genetic diversity raising issues concerning the efficiency and usefulness of reintroducing individuals from captive populations. However, due to a lack of DNA data from fossil specimens, it is unknown whether genetic diversity was even higher prior to the most recent population decline. We amplified complete cytb and 12s rRNA, partial 16s rRNA and ND1, and control region sequences from the mitochondrial genomes of two Holocene panda specimens. We estimated genetic diversity and population demography by analyzing the ancient mitochondrial DNA sequences alongside those from modern giant pandas, as well as from other members of the bear family (Ursidae). Phylogenetic analyses show that one of the ancient haplotypes is sister to all sampled modern pandas and the second ancient individual is nested among the modern haplotypes, suggesting that genetic diversity may indeed have been higher earlier during the Holocene. Bayesian skyline plot analysis supports this view and indicates a slight decline in female effective population size starting around 6000 years B.P., followed by a recovery around 2000 years ago. Therefore, while the genetic diversity of the giant panda has been affected by recent habitat contraction, it still harbors substantial genetic diversity. Moreover, while its still low population numbers require continued conservation efforts, there seem to be no immediate threats from the perspective of genetic evolutionary potential. Full article
(This article belongs to the Special Issue Novel and Neglected Areas of Ancient DNA Research)
Figures

Figure 1

Open AccessArticle Alteration of Hepatic Gene Expression along with the Inherited Phenotype of Acquired Fatty Liver in Chicken
Genes 2018, 9(4), 199; doi:10.3390/genes9040199
Received: 8 February 2018 / Revised: 17 March 2018 / Accepted: 28 March 2018 / Published: 8 April 2018
PDF Full-text (25546 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Fatty liver is a widespread disease in chickens that causes a decrease in egg production and even death. The characteristics of the inherited phenotype of acquired fatty liver and the molecular mechanisms underlying it, however, are largely unknown. In the current study, fatty
[...] Read more.
Fatty liver is a widespread disease in chickens that causes a decrease in egg production and even death. The characteristics of the inherited phenotype of acquired fatty liver and the molecular mechanisms underlying it, however, are largely unknown. In the current study, fatty liver was induced in 3 breeds by a high-fat (HF) diet and a methionine choline-deficient (MCD) diet. The results showed that the dwarf Jingxing-Huang (JXH) chicken was more susceptible to fatty liver compared with the layer White Leghorns (WL) and local Beijing-You (BJY) breeds. In addition, it was found that the paternal fatty livers induced by HF diet in JXH chickens were inherited. Compared to birds without fatty liver in the control group, both offsprings and their sires with fatty livers in the paternal group exhibited altered hepatic gene expression profiles, including upregulation of several key genes involved in fatty acid metabolism, lipid metabolism and glucose metabolism (ACACA, FASN, SCD, ACSL5, FADS2, FABP1, APOA4 and ME1). This study uniquely revealed that acquired fatty liver in cocks can be inherited. The hepatic gene expression profiles were altered in chickens with the inherited phenotype of acquired paternal fatty liver and several genes could be candidate biomarkers. Full article
(This article belongs to the Section Animal Genetics and Genomics)
Figures

Figure 1

Open AccessArticle A Possible Trifunctional β-Carotene Synthase Gene Identified in the Draft Genome of Aurantiochytrium sp. Strain KH105
Genes 2018, 9(4), 200; doi:10.3390/genes9040200
Received: 14 February 2018 / Revised: 27 March 2018 / Accepted: 27 March 2018 / Published: 9 April 2018
PDF Full-text (16583 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Labyrinthulomycetes have been regarded as a promising industrial source of xanthophylls, including astaxanthin and canthaxanthin, polyunsaturated fatty acids such as docosahexaenoic acid and docosapentaenoic acid, ω-3 oils, and terpenic hydrocarbons, such as sterols and squalene. A Thraustochytrid, Aurantiochytrium sp. KH105 produces carotenoids, including
[...] Read more.
Labyrinthulomycetes have been regarded as a promising industrial source of xanthophylls, including astaxanthin and canthaxanthin, polyunsaturated fatty acids such as docosahexaenoic acid and docosapentaenoic acid, ω-3 oils, and terpenic hydrocarbons, such as sterols and squalene. A Thraustochytrid, Aurantiochytrium sp. KH105 produces carotenoids, including astaxanthin, with strong antioxidant activity. To gain genomic insights into this capacity, we decoded its 97-Mbp genome and characterized genes for enzymes involved in carotenoid biosynthesis. Interestingly, all carotenogenic genes, as well as other eukaryotic genes, appeared duplicated, suggesting that this strain is diploid. In addition, among the five genes involved in the pathway from geranylgeranyl pyrophosphate to astaxanthin, geranylgeranyl phytoene synthase (crtB), phytoene desaturase (crtI) and lycopene cyclase (crtY) were fused into single gene (crtIBY) with no internal stop codons. Functionality of the trifunctional enzyme, CrtIBY, to catalyze the reaction from geranylgeranyl diphosphate to β-carotene was confirmed using a yeast assay system and mass spectrometry. Furthermore, analyses of differential gene expression showed characteristic up-regulation of carotenoid biosynthetic genes during stationary and starvation phases under these culture conditions. This suggests genetic engineering events to promote more efficient production of carotenoids. We also showed an occurrence of crtIBY in other Thraustochytrid species. Full article
(This article belongs to the Special Issue Microbial Metabolic Engineering)
Figures

Figure 1

Open AccessCommunication In Silico Functional Networks Identified in Fish Nucleated Red Blood Cells by Means of Transcriptomic and Proteomic Profiling
Genes 2018, 9(4), 202; doi:10.3390/genes9040202
Received: 19 February 2018 / Revised: 22 March 2018 / Accepted: 29 March 2018 / Published: 9 April 2018
PDF Full-text (9390 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Nucleated red blood cells (RBCs) of fish have, in the last decade, been implicated in several immune-related functions, such as antiviral response, phagocytosis or cytokine-mediated signaling. RNA-sequencing (RNA-seq) and label-free shotgun proteomic analyses were carried out for in silico functional pathway profiling of
[...] Read more.
Nucleated red blood cells (RBCs) of fish have, in the last decade, been implicated in several immune-related functions, such as antiviral response, phagocytosis or cytokine-mediated signaling. RNA-sequencing (RNA-seq) and label-free shotgun proteomic analyses were carried out for in silico functional pathway profiling of rainbow trout RBCs. For RNA-seq, a de novo assembly was conducted, in order to create a transcriptome database for RBCs. For proteome profiling, we developed a proteomic method that combined: (a) fractionation into cytosolic and membrane fractions, (b) hemoglobin removal of the cytosolic fraction, (c) protein digestion, and (d) a novel step with pH reversed-phase peptide fractionation and final Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometric (LC ESI-MS/MS) analysis of each fraction. Combined transcriptome- and proteome- sequencing data identified, in silico, novel and striking immune functional networks for rainbow trout nucleated RBCs, which are mainly linked to innate and adaptive immunity. Functional pathways related to regulation of hematopoietic cell differentiation, antigen presentation via major histocompatibility complex class II (MHCII), leukocyte differentiation and regulation of leukocyte activation were identified. These preliminary findings further implicate nucleated RBCs in immune function, such as antigen presentation and leukocyte activation. Full article
(This article belongs to the Section Technologies and Resources for Genetics)
Figures

Figure 1

Open AccessArticle The Brown Midrib Leaf (bml) Mutation in Rice (Oryza sativa L.) Causes Premature Leaf Senescence and the Induction of Defense Responses
Genes 2018, 9(4), 203; doi:10.3390/genes9040203
Received: 12 March 2018 / Revised: 30 March 2018 / Accepted: 30 March 2018 / Published: 9 April 2018
PDF Full-text (3138 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Isolating and characterizing mutants with altered senescence phenotypes is one of the ways to understand the molecular basis of leaf aging. Using ethyl methane sulfonate mutagenesis, a new rice (Oryza sativa) mutant, brown midrib leaf (bml), was isolated from
[...] Read more.
Isolating and characterizing mutants with altered senescence phenotypes is one of the ways to understand the molecular basis of leaf aging. Using ethyl methane sulfonate mutagenesis, a new rice (Oryza sativa) mutant, brown midrib leaf (bml), was isolated from the indica cultivar ‘Zhenong34’. The bml mutants had brown midribs in their leaves and initiated senescence prematurely, at the onset of heading. The mutants had abnormal cells with degraded chloroplasts and contained less chlorophyll compared to the wild type (WT). The bml mutant showed excessive accumulation of reactive oxygen species (ROS), increased activities of superoxide dismutase, catalase, and malondialdehyde, upregulation of senescence-induced STAY-GREEN genes and senescence-related transcription factors, and down regulation of photosynthesis-related genes. The levels of abscisic acid (ABA) and jasmonic acid (JA) were increased in bml with the upregulation of some ABA and JA biosynthetic genes. In pathogen response, bml demonstrated higher resistance against Xanthomonas oryzae pv. oryzae and upregulation of four pathogenesis-related genes compared to the WT. A genetic study confirmed that the bml trait was caused by a single recessive nuclear gene (BML). A map-based cloning using insertion/deletion markers confirmed that BML was located in the 57.32kb interval between the L5IS7 and L5IS11 markers on the short arm of chromosome 5. A sequence analysis of the candidate region identified a 1 bp substitution (G to A) in the 5′-UTR (+98) of bml. BML is a candidate gene associated with leaf senescence, ROS regulation, and disease response, also involved in hormone signaling in rice. Therefore, this gene might be useful in marker-assisted backcrossing/gene editing to improve rice cultivars. Full article
(This article belongs to the Section Plant Genetics and Genomics)
Figures

Figure 1

Open AccessFeature PaperArticle Portrait of Matrix Gene Expression in Candida glabrata Biofilms with Stress Induced by Different Drugs
Genes 2018, 9(4), 205; doi:10.3390/genes9040205
Received: 6 March 2018 / Revised: 29 March 2018 / Accepted: 5 April 2018 / Published: 10 April 2018
PDF Full-text (1705 KB) | HTML Full-text | XML Full-text
Abstract
(1) Background: Candida glabrata is one of the most significant Candida species associated with severe cases of candidiasis. Biofilm formation is an important feature, closely associated with antifungal resistance, involving alterations of gene expression or mutations, which can result in the failure of
[...] Read more.
(1) Background: Candida glabrata is one of the most significant Candida species associated with severe cases of candidiasis. Biofilm formation is an important feature, closely associated with antifungal resistance, involving alterations of gene expression or mutations, which can result in the failure of antifungal treatments. Hence, the main goal of this work was to evaluate the role of a set of genes, associated with matrix production, in the resistance of C. glabrata biofilms to antifungal drugs. (2) Methods: the determination of the expression of BGL2, XOG1, FKS1, FKS2, GAS2, KNH1, UGP1, and MNN2 genes in 48-h biofilm’s cells of three C. glabrata strains was performed through quantitative real-time PCR (RT-qPCR), after contact with Fluconazole (Flu), Amphotericin B (AmB), Caspofungin (Csf), or Micafungin (Mcf). (3) Results: Mcf induced a general overexpression of the selected genes. It was verified that the genes related to the production of β-1,3-glucans (BGL2, XOG1, GAS2) had the highest expressions. (4) Conclusion: though β-1,6-glucans and mannans are an essential part of the cell and biofilm matrix, C. glabrata biofilm cells seem to contribute more to the replacement of β-1,3-glucans. Thus, these biopolymers seem to have a greater impact on the biofilm matrix composition and, consequently, a role in the biofilm resistance to antifungal drugs. Full article
(This article belongs to the Special Issue Fungal Pathogenesis in Humans: The Growing Threat)
Figures

Figure 1

Open AccessArticle Transcriptome Analysis of Two Rice Varieties Contrasting for Nitrogen Use Efficiency under Chronic N Starvation Reveals Differences in Chloroplast and Starch Metabolism-Related Genes
Genes 2018, 9(4), 206; doi:10.3390/genes9040206
Received: 24 February 2018 / Revised: 3 April 2018 / Accepted: 6 April 2018 / Published: 11 April 2018
PDF Full-text (6579 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The nitrogen use efficiency (NUE) of crop plants is limited and enhancing it in rice, a major cereal crop, would be beneficial for farmers and the environment alike. Here we report the genome-wide transcriptome analysis of two rice genotypes, IR 64 (IR64) and
[...] Read more.
The nitrogen use efficiency (NUE) of crop plants is limited and enhancing it in rice, a major cereal crop, would be beneficial for farmers and the environment alike. Here we report the genome-wide transcriptome analysis of two rice genotypes, IR 64 (IR64) and Nagina 22 (N22) under optimal (+N) and chronic starvation (-N) of nitrogen (N) from 15-day-old root and shoot tissues. The two genotypes were found to be contrasting in their response to -N; IR64 root architecture and root dry weight remained almost equivalent to that under +N conditions, while N22 showed high foraging ability but a substantial reduction in biomass under -N. Similarly, the photosynthetic pigments showed a drastic reduction in N22 under low N, while IR64 was more resilient. Nitrate reductase showed significantly low specific activity under -N in both genotypes. Glutamate synthase (GOGAT) and citrate synthase CS activity were highly reduced in N22 but not in IR64. Transcriptome analysis of these genotypes revealed nearly double the number of genes to be differentially expressed (DEGs) in roots (1016) compared to shoots (571). The response of the two genotypes to N starvation was distinctly different reflecting their morphological/biochemical response with just two and eight common DEGs in the root and shoot tissues. There were a total of 385 nitrogen-responsive DEGs (106 in shoots and 279 in roots) between the two genotypes. Fifty-two of the 89 DEGs identified as specific to N22 root tissues were also found to be differentially expressed between the two genotypes under -N. Most of these DEGs belonged to starch and chloroplast metabolism, followed by membrane and signaling proteins. Physical mapping of DEGs revealed 95 DEGs in roots and 76 in shoots to be present in quantitative trait loci (QTL) known for NUE. Full article
(This article belongs to the Section Plant Genetics and Genomics)
Figures

Figure 1

Open AccessArticle Identifying Patients with Atrioventricular Septal Defect in Down Syndrome Populations by Using Self-Normalizing Neural Networks and Feature Selection
Genes 2018, 9(4), 208; doi:10.3390/genes9040208
Received: 15 March 2018 / Revised: 28 March 2018 / Accepted: 3 April 2018 / Published: 12 April 2018
PDF Full-text (7271 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Atrioventricular septal defect (AVSD) is a clinically significant subtype of congenital heart disease (CHD) that severely influences the health of babies during birth and is associated with Down syndrome (DS). Thus, exploring the differences in functional genes in DS samples with and without
[...] Read more.
Atrioventricular septal defect (AVSD) is a clinically significant subtype of congenital heart disease (CHD) that severely influences the health of babies during birth and is associated with Down syndrome (DS). Thus, exploring the differences in functional genes in DS samples with and without AVSD is a critical way to investigate the complex association between AVSD and DS. In this study, we present a computational method to distinguish DS patients with AVSD from those without AVSD using the newly proposed self-normalizing neural network (SNN). First, each patient was encoded by using the copy number of probes on chromosome 21. The encoded features were ranked by the reliable Monte Carlo feature selection (MCFS) method to obtain a ranked feature list. Based on this feature list, we used a two-stage incremental feature selection to construct two series of feature subsets and applied SNNs to build classifiers to identify optimal features. Results show that 2737 optimal features were obtained, and the corresponding optimal SNN classifier constructed on optimal features yielded a Matthew’s correlation coefficient (MCC) value of 0.748. For comparison, random forest was also used to build classifiers and uncover optimal features. This method received an optimal MCC value of 0.582 when top 132 features were utilized. Finally, we analyzed some key features derived from the optimal features in SNNs found in literature support to further reveal their essential roles. Full article
(This article belongs to the Special Issue Computational Approaches for Disease Gene Identification)
Figures

Figure 1

Open AccessArticle A Novel G-Protein-Coupled Receptors Gene from Upland Cotton Enhances Salt Stress Tolerance in Transgenic Arabidopsis
Genes 2018, 9(4), 209; doi:10.3390/genes9040209
Received: 1 March 2018 / Revised: 28 March 2018 / Accepted: 3 April 2018 / Published: 12 April 2018
PDF Full-text (47248 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Plants have developed a number of survival strategies which are significant for enhancing their adaptation to various biotic and abiotic stress factors. At the transcriptome level, G-protein-coupled receptors (GPCRs) are of great significance, enabling the plants to detect a wide range of endogenous
[...] Read more.
Plants have developed a number of survival strategies which are significant for enhancing their adaptation to various biotic and abiotic stress factors. At the transcriptome level, G-protein-coupled receptors (GPCRs) are of great significance, enabling the plants to detect a wide range of endogenous and exogenous signals which are employed by the plants in regulating various responses in development and adaptation. In this research work, we carried out genome-wide analysis of target of Myb1 (TOM1), a member of the GPCR gene family. The functional role of TOM1 in salt stress tolerance was studied using a transgenic Arabidopsis plants over-expressing the gene. By the use of the functional domain PF06454, we obtained 16 TOM genes members in Gossypium hirsutum, 9 in Gossypium arboreum, and 11 in Gossypium raimondii. The genes had varying physiochemical properties, and it is significant to note that all the grand average of hydropathy (GRAVY) values were less than one, indicating that all are hydrophobic in nature. In all the genes analysed here, both the exonic and intronic regions were found. The expression level of Gh_A07G0747 (GhTOM) was significantly high in the transgenic lines as compared to the wild type; a similar trend in expression was observed in all the salt-related genes tested in this study. The study in epidermal cells confirmed the localization of the protein coded by the gene TOM1 in the plasma membrane. Analysis of anti-oxidant enzymes showed higher concentrations of antioxidants in transgenic lines and relatively lower levels of oxidant substances such as H2O2. The low malondialdehyde (MDA) level in transgenic lines indicated that the transgenic lines had relatively low level of oxidative damage compared to the wild types. The results obtained indicate that Gh_A07G0747 (GhTOM) can be a putative target gene for enhancing salt stress tolerance in plants and could be exploited in the future for the development of salt stress-tolerant cotton cultivars. Full article
(This article belongs to the Section Plant Genetics and Genomics)
Figures

Figure 1

Open AccessArticle Transcriptomic Analysis of Flower Bud Differentiation in Magnolia sinostellata
Genes 2018, 9(4), 212; doi:10.3390/genes9040212
Received: 12 February 2018 / Revised: 8 April 2018 / Accepted: 11 April 2018 / Published: 16 April 2018
PDF Full-text (31425 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Magnolias are widely cultivated for their beautiful flowers, but despite their popularity, the molecular mechanisms regulating flower bud differentiation have not been elucidated. Here, we used paraffin sections and RNA-seq to study the process of flower bud differentiation in Magnolia sinostellata. Flower
[...] Read more.
Magnolias are widely cultivated for their beautiful flowers, but despite their popularity, the molecular mechanisms regulating flower bud differentiation have not been elucidated. Here, we used paraffin sections and RNA-seq to study the process of flower bud differentiation in Magnolia sinostellata. Flower bud development occurred between 28 April and 30 May 2017 and was divided into five stages: undifferentiated, early flower bud differentiation, petal primordium differentiation, stamen primordium differentiation, and pistil primordium differentiation. A total of 52,441 expressed genes were identified, of which 11,592 were significantly differentially expressed in the five bud development stages. Of these, 82 genes were involved in the flowering. In addition, MADS-box and AP2 family genes play critical roles in the formation of flower organs and 20 differentially expressed genes associated with flower bud differentiation were identified in M. sinostellata. A qRT-PCR analysis verified that the MADS-box and AP2 family genes were expressed at high levels during flower bud differentiation. Consequently, this study provides a theoretical basis for the genetic regulation of flowering in M. sinostellata, which lays a foundation for further research into flowering genes and may facilitate the development of new cultivars. Full article
(This article belongs to the Section Plant Genetics and Genomics)
Figures

Figure 1

Open AccessArticle Genome Sequence of the Freshwater Yangtze Finless Porpoise
Genes 2018, 9(4), 213; doi:10.3390/genes9040213
Received: 26 February 2018 / Revised: 6 April 2018 / Accepted: 11 April 2018 / Published: 16 April 2018
PDF Full-text (591 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The Yangtze finless porpoise (Neophocaena asiaeorientalis ssp. asiaeorientalis) is a subspecies of the narrow-ridged finless porpoise (N. asiaeorientalis). In total, 714.28 gigabases (Gb) of raw reads were generated by whole-genome sequencing of the Yangtze finless porpoise, using an Illumina
[...] Read more.
The Yangtze finless porpoise (Neophocaena asiaeorientalis ssp. asiaeorientalis) is a subspecies of the narrow-ridged finless porpoise (N. asiaeorientalis). In total, 714.28 gigabases (Gb) of raw reads were generated by whole-genome sequencing of the Yangtze finless porpoise, using an Illumina HiSeq 2000 platform. After filtering the low-quality and duplicated reads, we assembled a draft genome of 2.22 Gb, with contig N50 and scaffold N50 values of 46.69 kilobases (kb) and 1.71 megabases (Mb), respectively. We identified 887.63 Mb of repetitive sequences and predicted 18,479 protein-coding genes in the assembled genome. The phylogenetic tree showed a relationship between the Yangtze finless porpoise and the Yangtze River dolphin, which diverged approximately 20.84 million years ago. In comparisons with the genomes of 10 other mammals, we detected 44 species-specific gene families, 164 expanded gene families, and 313 positively selected genes in the Yangtze finless porpoise genome. The assembled genome sequence and underlying sequence data are available at the National Center for Biotechnology Information under BioProject accession number PRJNA433603. Full article
(This article belongs to the Special Issue Conservation Genetics and Genomics)
Figures

Open AccessArticle Identification of Major Rhizobacterial Taxa Affected by a Glyphosate-Tolerant Soybean Line via Shotgun Metagenomic Approach
Genes 2018, 9(4), 214; doi:10.3390/genes9040214
Received: 22 January 2018 / Revised: 19 March 2018 / Accepted: 13 April 2018 / Published: 16 April 2018
PDF Full-text (4320 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The worldwide commercial cultivation of transgenic crops, including glyphosate-tolerant (GT) soybeans, has increased widely during the past 20 years. However, it is accompanied with a growing concern about potential effects of transgenic crops on the soil microbial communities, especially on rhizosphere bacterial communities.
[...] Read more.
The worldwide commercial cultivation of transgenic crops, including glyphosate-tolerant (GT) soybeans, has increased widely during the past 20 years. However, it is accompanied with a growing concern about potential effects of transgenic crops on the soil microbial communities, especially on rhizosphere bacterial communities. Our previous study found that the GT soybean line NZL06-698 (N698) significantly affected rhizosphere bacteria, including some unidentified taxa, through 16S rRNA gene (16S rDNA) V4 region amplicon deep sequencing via Illumina MiSeq. In this study, we performed 16S rDNA V5–V7 region amplicon deep sequencing via Illumina MiSeq and shotgun metagenomic approaches to identify those major taxa. Results of these processes revealed that the species richness and evenness increased in the rhizosphere bacterial communities of N698, the beta diversity of the rhizosphere bacterial communities of N698 was affected, and that certain dominant bacterial phyla and genera were related to N698 compared with its control cultivar Mengdou12. Consistent with our previous findings, this study showed that N698 affects the rhizosphere bacterial communities. In specific, N698 negatively affects Rahnella, Janthinobacterium, Stenotrophomonas, Sphingomonas and Luteibacter while positively affecting Arthrobacter, Bradyrhizobium, Ramlibacter and Nitrospira. Full article
(This article belongs to the Special Issue Emerging Applications for Next Generation Sequencing)
Figures

Figure 1

Open AccessArticle Accurate Classification of NF1 Gene Variants in 84 Italian Patients with Neurofibromatosis Type 1
Genes 2018, 9(4), 216; doi:10.3390/genes9040216
Received: 22 February 2018 / Revised: 27 March 2018 / Accepted: 3 April 2018 / Published: 17 April 2018
PDF Full-text (5710 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant genetic diseases. It is caused by mutations in the NF1 gene encoding for the large protein, neurofibromin. Genetic testing of NF1 is cumbersome because 50% of cases are sporadic, and there
[...] Read more.
Neurofibromatosis type 1 (NF1) is one of the most common autosomal dominant genetic diseases. It is caused by mutations in the NF1 gene encoding for the large protein, neurofibromin. Genetic testing of NF1 is cumbersome because 50% of cases are sporadic, and there are no mutation hot spots. In addition, the most recognizable NF1 clinical features—café-au-lait (CALs) spots and axillary and/or inguinal freckling—appear early in childhood but are rather non-specific. Thus, the identification of causative variants is extremely important for early diagnosis, especially in paediatric patients. Here, we aimed to identify the underlying genetic defects in 72 index patients referred to our centre for NF1. Causative mutations were identified in 58 subjects, with 29 being novel changes. We evaluated missense and non-canonical splicing mutations with both protein and splicing prediction algorithms. The ratio of splicing mutations detected was higher than that reported in recent patients’ series and in the Human Gene Mutation Database (HGMD). After applying in silico predictive tools to 41 previously reported missense variants, we demonstrated that 46.3% of these putatively missense mutations were forecasted to alter splicing instead. Our data suggest that mutations affecting splicing can be frequently underscored if not analysed in depth. We confirm that hamartomas can be useful for diagnosing NF1 in children. Lisch nodules and cutaneous neurofibromas were more frequent in patients with frameshifting mutations. In conclusion, we demonstrated that comprehensive in silico analysis can be a highly specific method for predicting the nature of NF1 mutations and may help in assuring proper patient care. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
Figures

Figure 1

Open AccessArticle The Effects on Parapatric Divergence of Linkage between Preference and Trait Loci versus Pleiotropy
Genes 2018, 9(4), 217; doi:10.3390/genes9040217
Received: 16 February 2018 / Revised: 2 April 2018 / Accepted: 6 April 2018 / Published: 17 April 2018
PDF Full-text (6703 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Attempts to uncover the genetic basis of female mating preferences and male signals involved in reproductive isolation have discovered intriguing cases in which loci contributing to these traits co-localize in their chromosomal positions. Such discoveries raise the question of whether alleles at certain
[...] Read more.
Attempts to uncover the genetic basis of female mating preferences and male signals involved in reproductive isolation have discovered intriguing cases in which loci contributing to these traits co-localize in their chromosomal positions. Such discoveries raise the question of whether alleles at certain loci contribute pleiotropically to male and female components of premating reproductive isolation, versus whether these loci are merely tightly linked. Here we use population genetic models to assess the degree to which these alternatives affect both short term and equilibrium patterns of trait (signal) and preference divergence. We take advantage of the fact that in the case of secondary contact between populations exchanging migrants, patterns of divergence across the range of preference strengths differ markedly when preferences and traits are controlled by the same locus (the case of phenotype matching) versus when they are on separate chromosomes. We find that tight linkage between preference and trait loci can mimic the pleiotropic pattern for many generations (roughly the reciprocal of the recombination rate), but that any recombination ultimately results in equilibrium patterns of divergence far more similar to those found when preferences and traits are on separate chromosomes. In general, our finding that pleiotropy results in quite different long-term patterns from tight linkage highlights the importance of distinguishing between these possibilities in empirical systems. Full article
(This article belongs to the Special Issue Evolutionary Genetics of Reproductive Isolation)
Figures

Figure 1

Open AccessArticle Genetic Evaluation of Natural Populations of the Endangered Conifer Thuja koraiensis Using Microsatellite Markers by Restriction-Associated DNA Sequencing
Genes 2018, 9(4), 218; doi:10.3390/genes9040218
Received: 10 March 2018 / Revised: 9 April 2018 / Accepted: 13 April 2018 / Published: 17 April 2018
PDF Full-text (7281 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Thuja koraiensis Nakai is an endangered conifer of high economic and ecological value in Jilin Province, China. However, studies on its population structure and conservation genetics have been limited by the lack of genomic data. Here, 37,761 microsatellites (simple sequence repeat, SSR) were
[...] Read more.
Thuja koraiensis Nakai is an endangered conifer of high economic and ecological value in Jilin Province, China. However, studies on its population structure and conservation genetics have been limited by the lack of genomic data. Here, 37,761 microsatellites (simple sequence repeat, SSR) were detected based on 875,792 de novo-assembled contigs using a restriction-associated DNA (RAD) approach. Among these SSRs, 300 were randomly selected to test for polymorphisms and 96 obtained loci were able to amplify a fragment of expected size. Twelve polymorphic SSR markers were developed to analyze the genetic diversity and population structure of three natural populations. High genetic diversity (mean NA = 5.481, HE = 0.548) and moderate population differentiation (pairwise Fst = 0.048–0.078, Nm = 2.940–4.958) were found in this species. Molecular variance analysis suggested that most of the variation (83%) existed within populations. Combining the results of STRUCTURE, principal coordinate, and neighbor-joining analysis, the 232 individuals were divided into three genetic clusters that generally correlated with their geographical distributions. Finally, appropriate conservation strategies were proposed to protect this species. This study provides genetic information for the natural resource conservation and utilization of T. koraiensis and will facilitate further studies of the evolution and phylogeography of the species. Full article
(This article belongs to the Section Plant Genetics and Genomics)
Figures

Figure 1

Open AccessArticle Patchoulol Production with Metabolically Engineered Corynebacterium glutamicum
Genes 2018, 9(4), 219; doi:10.3390/genes9040219
Received: 26 March 2018 / Revised: 10 April 2018 / Accepted: 16 April 2018 / Published: 17 April 2018
PDF Full-text (1247 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Patchoulol is a sesquiterpene alcohol and an important natural product for the perfume industry. Corynebacterium glutamicum is the prominent host for the fermentative production of amino acids with an average annual production volume of ~6 million tons. Due to its robustness and well
[...] Read more.
Patchoulol is a sesquiterpene alcohol and an important natural product for the perfume industry. Corynebacterium glutamicum is the prominent host for the fermentative production of amino acids with an average annual production volume of ~6 million tons. Due to its robustness and well established large-scale fermentation, C. glutamicum has been engineered for the production of a number of value-added compounds including terpenoids. Both C40 and C50 carotenoids, including the industrially relevant astaxanthin, and short-chain terpenes such as the sesquiterpene valencene can be produced with this organism. In this study, systematic metabolic engineering enabled construction of a patchoulol producing C. glutamicum strain by applying the following strategies: (i) construction of a farnesyl pyrophosphate-producing platform strain by combining genomic deletions with heterologous expression of ispA from Escherichia coli; (ii) prevention of carotenoid-like byproduct formation; (iii) overproduction of limiting enzymes from the 2-c-methyl-d-erythritol 4-phosphate (MEP)-pathway to increase precursor supply; and (iv) heterologous expression of the plant patchoulol synthase gene PcPS from Pogostemon cablin. Additionally, a proof of principle liter-scale fermentation with a two-phase organic overlay-culture medium system for terpenoid capture was performed. To the best of our knowledge, the patchoulol titers demonstrated here are the highest reported to date with up to 60 mg L−1 and volumetric productivities of up to 18 mg L−1 d−1. Full article
(This article belongs to the Special Issue Microbial Metabolic Engineering)
Figures

Open AccessArticle Full Mitogenomes in the Critically Endangered Kākāpō Reveal Major Post-Glacial and Anthropogenic Effects on Neutral Genetic Diversity
Genes 2018, 9(4), 220; doi:10.3390/genes9040220
Received: 17 March 2018 / Revised: 5 April 2018 / Accepted: 6 April 2018 / Published: 19 April 2018
PDF Full-text (3191 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Understanding how species respond to population declines is a central question in conservation and evolutionary biology. Population declines are often associated with loss of genetic diversity, inbreeding and accumulation of deleterious mutations, which can lead to a reduction in fitness and subsequently contribute
[...] Read more.
Understanding how species respond to population declines is a central question in conservation and evolutionary biology. Population declines are often associated with loss of genetic diversity, inbreeding and accumulation of deleterious mutations, which can lead to a reduction in fitness and subsequently contribute to extinction. Using temporal approaches can help us understand the effects of population declines on genetic diversity in real time. Sequencing pre-decline as well as post-decline mitogenomes representing all the remaining mitochondrial diversity, we estimated the loss of genetic diversity in the critically endangered kākāpō (Strigops habroptilus). We detected a signal of population expansion coinciding with the end of the Pleistocene last glacial maximum (LGM). Also, we found some evidence for northern and southern lineages, supporting the hypothesis that the species may have been restricted to isolated northern and southern refugia during the LGM. We observed an important loss of neutral genetic diversity associated with European settlement in New Zealand but we could not exclude a population decline associated with Polynesian settlement in New Zealand. However, we did not find evidence for fixation of deleterious mutations. We argue that despite high pre-decline genetic diversity, a rapid and range-wide decline combined with the lek mating system, and life-history traits of kākāpō contributed to a rapid loss of genetic diversity following severe population declines. Full article
(This article belongs to the Special Issue Conservation Genetics and Genomics)
Figures

Open AccessArticle Genome-Wide Analyses of Calcium Sensors Reveal Their Involvement in Drought Stress Response and Storage Roots Deterioration after Harvest in Cassava
Genes 2018, 9(4), 221; doi:10.3390/genes9040221
Received: 22 February 2018 / Revised: 1 April 2018 / Accepted: 12 April 2018 / Published: 19 April 2018
PDF Full-text (5694 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Calcium (Ca2+) plays a crucial role in plant development and responses to environmental stimuli. Currently, calmodulins (CaMs), calmodulin-like proteins (CMLs), and calcineurin B-like proteins (CBLs), such as Ca2+ sensors, are not well understood in cassava (Manihot esculenta Crantz), an
[...] Read more.
Calcium (Ca2+) plays a crucial role in plant development and responses to environmental stimuli. Currently, calmodulins (CaMs), calmodulin-like proteins (CMLs), and calcineurin B-like proteins (CBLs), such as Ca2+ sensors, are not well understood in cassava (Manihot esculenta Crantz), an important tropical crop. In the present study, 8 CaMs, 48 CMLs, and 9 CBLs were genome-wide identified in cassava, which were divided into two, four, and four groups, respectively, based on evolutionary relationship, protein motif, and gene structure analyses. Transcriptomic analysis revealed the expression diversity of cassava CaMs-CMLs-CBLs in distinct tissues and in response to drought stress in different genotypes. Generally, cassava CaMs-CMLs-CBLs showed different expression profiles between cultivated varieties (Arg7 and SC124) and wild ancestor (W14) after drought treatment. In addition, numerous CaMs-CMLs-CBLs were significantly upregulated at 6 h, 12 h, and 48 h after harvest, suggesting their possible role during storage roots (SR) deterioration. Further interaction network and co-expression analyses suggested that a CBL-mediated interaction network was widely involved in SR deterioration. Taken together, this study provides new insights into CaMs-CMLs-CBLs-mediated drought adaption and SR deterioration at the transcription level in cassava, and identifies some candidates for the genetic improvement of cassava. Full article
(This article belongs to the Section Plant Genetics and Genomics)
Figures

Figure 1

Open AccessArticle Divergent Roles of RPA Homologs of the Model Archaeon Halobacterium salinarum in Survival of DNA Damage
Genes 2018, 9(4), 223; doi:10.3390/genes9040223 (registering DOI)
Received: 31 January 2018 / Revised: 8 April 2018 / Accepted: 12 April 2018 / Published: 20 April 2018
PDF Full-text (2438 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The haloarchaea are unusual in possessing genes for multiple homologs to the ubiquitous single-stranded DNA binding protein (SSB or replication protein A, RPA) found in all three domains of life. Halobacterium salinarum contains five homologs: two are eukaryotic in organization, two are prokaryotic
[...] Read more.
The haloarchaea are unusual in possessing genes for multiple homologs to the ubiquitous single-stranded DNA binding protein (SSB or replication protein A, RPA) found in all three domains of life. Halobacterium salinarum contains five homologs: two are eukaryotic in organization, two are prokaryotic and are encoded on the minichromosomes, and one is uniquely euryarchaeal. Radiation-resistant mutants previously isolated show upregulation of one of the eukaryotic-type RPA genes. Here, we have created deletions in the five RPA operons. These deletion mutants were exposed to DNA-damaging conditions: ionizing radiation, UV radiation, and mitomycin C. Deletion of the euryarchaeal homolog, although not lethal as in Haloferax volcanii, causes severe sensitivity to all of these agents. Deletion of the other RPA/SSB homologs imparts a variable sensitivity to these DNA-damaging agents, suggesting that the different RPA homologs have specialized roles depending on the type of genomic insult encountered. Full article
(This article belongs to the Special Issue Genetics and Genomics of Extremophiles)
Figures

Figure 1

Review

Jump to: Editorial, Research, Other

Open AccessReview The Role of microRNAs in Alzheimer’s Disease and Their Therapeutic Potentials
Genes 2018, 9(4), 174; doi:10.3390/genes9040174
Received: 8 January 2018 / Revised: 5 March 2018 / Accepted: 5 March 2018 / Published: 21 March 2018
PDF Full-text (2811 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) are short, endogenous, non-coding RNAs that post-transcriptionally regulate gene expression by base pairing with mRNA targets. Altered miRNA expression profiles have been observed in several diseases, including neurodegeneration. Multiple studies have reported altered expressions of miRNAs in the brains of individuals
[...] Read more.
MicroRNAs (miRNAs) are short, endogenous, non-coding RNAs that post-transcriptionally regulate gene expression by base pairing with mRNA targets. Altered miRNA expression profiles have been observed in several diseases, including neurodegeneration. Multiple studies have reported altered expressions of miRNAs in the brains of individuals with Alzheimer’s disease (AD) as compared to those of healthy elderly adults. Some of the miRNAs found to be dysregulated in AD have been reported to correlate with neuropathological changes, including plaque and tangle accumulation, as well as altered expressions of species that are known to be involved in AD pathology. To examine the potentially pathogenic functions of several dysregulated miRNAs in AD, we review the current literature with a focus on the activities of ten miRNAs in biological pathways involved in AD pathogenesis. Comprehensive understandings of the expression profiles and activities of these miRNAs will illuminate their roles as potential therapeutic targets in AD brain and may lead to the discovery of breakthrough treatment strategies for AD. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
Figures

Figure 1

Open AccessFeature PaperReview Is There Still Any Role for Oxidative Stress in Mitochondrial DNA-Dependent Aging?
Genes 2018, 9(4), 175; doi:10.3390/genes9040175
Received: 1 February 2018 / Revised: 9 March 2018 / Accepted: 16 March 2018 / Published: 21 March 2018
PDF Full-text (1455 KB) | HTML Full-text | XML Full-text
Abstract
Recent deep sequencing data has provided compelling evidence that the spectrum of somatic point mutations in mitochondrial DNA (mtDNA) in aging tissues lacks G > T transversion mutations. This fact cannot, however, be used as an argument for the missing contribution of reactive
[...] Read more.
Recent deep sequencing data has provided compelling evidence that the spectrum of somatic point mutations in mitochondrial DNA (mtDNA) in aging tissues lacks G > T transversion mutations. This fact cannot, however, be used as an argument for the missing contribution of reactive oxygen species (ROS) to mitochondria-related aging because it is probably caused by the nucleotide selectivity of mitochondrial DNA polymerase γ (POLG). In contrast to point mutations, the age-dependent accumulation of mitochondrial DNA deletions is, in light of recent experimental data, still explainable by the segregation of mutant molecules generated by the direct mutagenic effects of ROS (in particular, of HO· radicals formed from H2O2 by a Fenton reaction). The source of ROS remains controversial, because the mitochondrial contribution to tissue ROS production is probably lower than previously thought. Importantly, in the discussion about the potential role of oxidative stress in mitochondria-dependent aging, ROS generated by inflammation-linked processes and the distribution of free iron also require careful consideration. Full article
(This article belongs to the Special Issue Mitochondria and Aging)
Figures

Figure 1

Open AccessReview Role of the Extremolytes Ectoine and Hydroxyectoine as Stress Protectants and Nutrients: Genetics, Phylogenomics, Biochemistry, and Structural Analysis
Genes 2018, 9(4), 177; doi:10.3390/genes9040177
Received: 10 February 2018 / Revised: 13 March 2018 / Accepted: 15 March 2018 / Published: 22 March 2018
PDF Full-text (11418 KB) | HTML Full-text | XML Full-text
Abstract
Fluctuations in environmental osmolarity are ubiquitous stress factors in many natural habitats of microorganisms, as they inevitably trigger osmotically instigated fluxes of water across the semi-permeable cytoplasmic membrane. Under hyperosmotic conditions, many microorganisms fend off the detrimental effects of water efflux and the
[...] Read more.
Fluctuations in environmental osmolarity are ubiquitous stress factors in many natural habitats of microorganisms, as they inevitably trigger osmotically instigated fluxes of water across the semi-permeable cytoplasmic membrane. Under hyperosmotic conditions, many microorganisms fend off the detrimental effects of water efflux and the ensuing dehydration of the cytoplasm and drop in turgor through the accumulation of a restricted class of organic osmolytes, the compatible solutes. Ectoine and its derivative 5-hydroxyectoine are prominent members of these compounds and are synthesized widely by members of the Bacteria and a few Archaea and Eukarya in response to high salinity/osmolarity and/or growth temperature extremes. Ectoines have excellent function-preserving properties, attributes that have led to their description as chemical chaperones and fostered the development of an industrial-scale biotechnological production process for their exploitation in biotechnology, skin care, and medicine. We review, here, the current knowledge on the biochemistry of the ectoine/hydroxyectoine biosynthetic enzymes and the available crystal structures of some of them, explore the genetics of the underlying biosynthetic genes and their transcriptional regulation, and present an extensive phylogenomic analysis of the ectoine/hydroxyectoine biosynthetic genes. In addition, we address the biochemistry, phylogenomics, and genetic regulation for the alternative use of ectoines as nutrients. Full article
(This article belongs to the Special Issue Genetics and Genomics of Extremophiles)
Figures

Open AccessReview Wnt Signalling in Gastrointestinal Epithelial Stem Cells
Genes 2018, 9(4), 178; doi:10.3390/genes9040178
Received: 19 February 2018 / Revised: 16 March 2018 / Accepted: 19 March 2018 / Published: 23 March 2018
PDF Full-text (1116 KB) | HTML Full-text | XML Full-text
Abstract
Wnt signalling regulates several cellular functions including proliferation, differentiation, apoptosis and migration, and is critical for embryonic development. Stem cells are defined by their ability for self-renewal and the ability to be able to give rise to differentiated progeny. Consequently, they are essential
[...] Read more.
Wnt signalling regulates several cellular functions including proliferation, differentiation, apoptosis and migration, and is critical for embryonic development. Stem cells are defined by their ability for self-renewal and the ability to be able to give rise to differentiated progeny. Consequently, they are essential for the homeostasis of many organs including the gastrointestinal tract. This review will describe the huge advances in our understanding of how stem cell functions in the gastrointestinal tract are regulated by Wnt signalling, including how deregulated Wnt signalling can hijack these functions to transform cells and lead to cancer. Full article
(This article belongs to the Special Issue Wnt Signaling in Stem Cells)
Figures

Figure 1

Open AccessReview Karyotype Evolution in Birds: From Conventional Staining to Chromosome Painting
Genes 2018, 9(4), 181; doi:10.3390/genes9040181
Received: 1 February 2018 / Revised: 8 March 2018 / Accepted: 21 March 2018 / Published: 27 March 2018
PDF Full-text (7749 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In the last few decades, there have been great efforts to reconstruct the phylogeny of Neoaves based mainly on DNA sequencing. Despite the importance of karyotype data in phylogenetic studies, especially with the advent of fluorescence in situ hybridization (FISH) techniques using different
[...] Read more.
In the last few decades, there have been great efforts to reconstruct the phylogeny of Neoaves based mainly on DNA sequencing. Despite the importance of karyotype data in phylogenetic studies, especially with the advent of fluorescence in situ hybridization (FISH) techniques using different types of probes, the use of chromosomal data to clarify phylogenetic proposals is still minimal. Additionally, comparative chromosome painting in birds is restricted to a few orders, while in mammals, for example, virtually all orders have already been analyzed using this method. Most reports are based on comparisons using Gallus gallus probes, and only a small number of species have been analyzed with more informative sets of probes, such as those from Leucopternis albicollis and Gyps fulvus, which show ancestral macrochromosomes rearranged in alternative patterns. Despite this, it is appropriate to review the available cytogenetic information and possible phylogenetic conclusions. In this report, the authors gather both classical and molecular cytogenetic data and describe some interesting and unique characteristics of karyotype evolution in birds. Full article
(This article belongs to the Special Issue Chromosomal Evolution)
Figures

Figure 1

Open AccessReview Roles of Mitochondrial DNA Mutations in Stem Cell Ageing
Genes 2018, 9(4), 182; doi:10.3390/genes9040182
Received: 26 February 2018 / Revised: 22 March 2018 / Accepted: 26 March 2018 / Published: 27 March 2018
PDF Full-text (5971 KB) | HTML Full-text | XML Full-text
Abstract
Mitochondrial DNA (mtDNA) mutations accumulate in somatic stem cells during ageing and cause mitochondrial dysfunction. In this review, we summarize the studies that link mtDNA mutations to stem cell ageing. We discuss the age-related behaviours of the somatic mtDNA mutations in stem cell
[...] Read more.
Mitochondrial DNA (mtDNA) mutations accumulate in somatic stem cells during ageing and cause mitochondrial dysfunction. In this review, we summarize the studies that link mtDNA mutations to stem cell ageing. We discuss the age-related behaviours of the somatic mtDNA mutations in stem cell populations and how they potentially contribute to stem cell ageing by altering mitochondrial properties in humans and in mtDNA-mutator mice. We also draw attention to the diverse fates of the mtDNA mutations with different origins during ageing, with potential selective pressures on the germline inherited but not the somatic mtDNA mutations. Full article
(This article belongs to the Special Issue Mitochondria and Aging)
Figures

Figure 1

Open AccessReview Non-Coding RNAs and Endometrial Cancer
Genes 2018, 9(4), 187; doi:10.3390/genes9040187
Received: 21 January 2018 / Revised: 13 March 2018 / Accepted: 27 March 2018 / Published: 29 March 2018
PDF Full-text (2378 KB) | HTML Full-text | XML Full-text
Abstract
Non-coding RNAs (ncRNAs) are involved in the regulation of cell metabolism and neoplastic transformation. Recent studies have tried to clarify the significance of these information carriers in the genesis and progression of various cancers and their use as biomarkers for the disease; possible
[...] Read more.
Non-coding RNAs (ncRNAs) are involved in the regulation of cell metabolism and neoplastic transformation. Recent studies have tried to clarify the significance of these information carriers in the genesis and progression of various cancers and their use as biomarkers for the disease; possible targets for the inhibition of growth and invasion by the neoplastic cells have been suggested. The significance of ncRNAs in lung cancer, bladder cancer, kidney cancer, and melanoma has been amply investigated with important results. Recently, the role of long non-coding RNAs (lncRNAs) has also been included in cancer studies. Studies on the relation between endometrial cancer (EC) and ncRNAs, such as small ncRNAs or micro RNAs (miRNAs), transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), antisense RNAs (asRNAs), small nuclear RNAs (snRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), competing endogenous RNAs (ceRNAs), lncRNAs, and long intergenic ncRNAs (lincRNAs) have been published. The recent literature produced in the last three years was extracted from PubMed by two independent readers, which was then selected for the possible relation between ncRNAs, oncogenesis in general, and EC in particular. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
Figures

Figure 1

Open AccessReview Genomic Signatures of Reinforcement
Genes 2018, 9(4), 191; doi:10.3390/genes9040191
Received: 8 February 2018 / Revised: 27 March 2018 / Accepted: 28 March 2018 / Published: 3 April 2018
PDF Full-text (4620 KB) | HTML Full-text | XML Full-text
Abstract
Reinforcement is the process by which selection against hybridization increases reproductive isolation between taxa. Much research has focused on demonstrating the existence of reinforcement, yet relatively little is known about the genetic basis of reinforcement or the evolutionary conditions under which reinforcement can
[...] Read more.
Reinforcement is the process by which selection against hybridization increases reproductive isolation between taxa. Much research has focused on demonstrating the existence of reinforcement, yet relatively little is known about the genetic basis of reinforcement or the evolutionary conditions under which reinforcement can occur. Inspired by reinforcement’s characteristic phenotypic pattern of reproductive trait divergence in sympatry but not in allopatry, we discuss whether reinforcement also leaves a distinct genomic pattern. First, we describe three patterns of genetic variation we expect as a consequence of reinforcement. Then, we discuss a set of alternative processes and complicating factors that may make the identification of reinforcement at the genomic level difficult. Finally, we consider how genomic analyses can be leveraged to inform if and to what extent reinforcement evolved in the face of gene flow between sympatric lineages and between allopatric and sympatric populations of the same lineage. Our major goals are to understand if genome scans for particular patterns of genetic variation could identify reinforcement, isolate the genetic basis of reinforcement, or infer the conditions under which reinforcement evolved. Full article
(This article belongs to the Special Issue Evolutionary Genetics of Reproductive Isolation)
Figures

Figure 1

Open AccessReview TRAP1 Regulation of Cancer Metabolism: Dual Role as Oncogene or Tumor Suppressor
Genes 2018, 9(4), 195; doi:10.3390/genes9040195
Received: 6 March 2018 / Revised: 28 March 2018 / Accepted: 28 March 2018 / Published: 5 April 2018
PDF Full-text (3160 KB) | HTML Full-text | XML Full-text
Abstract
Metabolic reprogramming is an important issue in tumor biology. An unexpected inter- and intra-tumor metabolic heterogeneity has been strictly correlated to tumor outcome. Tumor Necrosis Factor Receptor-Associated Protein 1 (TRAP1) is a molecular chaperone involved in the regulation of energetic metabolism in cancer
[...] Read more.
Metabolic reprogramming is an important issue in tumor biology. An unexpected inter- and intra-tumor metabolic heterogeneity has been strictly correlated to tumor outcome. Tumor Necrosis Factor Receptor-Associated Protein 1 (TRAP1) is a molecular chaperone involved in the regulation of energetic metabolism in cancer cells. This protein is highly expressed in several cancers, such as glioblastoma, colon, breast, prostate and lung cancers and is often associated with drug resistance. However, TRAP1 is also downregulated in specific tumors, such as ovarian, bladder and renal cancers, where its lower expression is correlated with the worst prognoses and chemoresistance. TRAP1 is the only mitochondrial member of the Heat Shock Protein 90 (HSP90) family that directly interacts with respiratory complexes, contributing to their stability and activity but it is still unclear if such interactions lead to reduced or increased respiratory capacity. The role of TRAP1 is to enhance or suppress oxidative phosphorylation; the effects of such regulation on tumor development and progression are controversial. These observations encourage the study of the mechanisms responsible for the dualist role of TRAP1 as an oncogene or oncosuppressor in specific tumor types. In this review, TRAP1 puzzling functions were recapitulated with a special focus on the correlation between metabolic reprogramming and tumor outcome. We wanted to investigate whether metabolism-targeting drugs can efficiently interfere with tumor progression and whether they might be combined with chemotherapeutics or molecular-targeted agents to counteract drug resistance and reduce therapeutic failure. Full article
Figures

Figure 1

Open AccessReview Epigenetic Mechanisms Impacting Aging: A Focus on Histone Levels and Telomeres
Genes 2018, 9(4), 201; doi:10.3390/genes9040201
Received: 24 February 2018 / Revised: 27 March 2018 / Accepted: 29 March 2018 / Published: 9 April 2018
PDF Full-text (1552 KB) | HTML Full-text | XML Full-text
Abstract
Aging and age-related diseases pose some of the most significant and difficult challenges to modern society as well as to the scientific and medical communities. Biological aging is a complex, and, under normal circumstances, seemingly irreversible collection of processes that involves numerous underlying
[...] Read more.
Aging and age-related diseases pose some of the most significant and difficult challenges to modern society as well as to the scientific and medical communities. Biological aging is a complex, and, under normal circumstances, seemingly irreversible collection of processes that involves numerous underlying mechanisms. Among these, chromatin-based processes have emerged as major regulators of cellular and organismal aging. These include DNA methylation, histone modifications, nucleosome positioning, and telomere regulation, including how these are influenced by environmental factors such as diet. Here we focus on two interconnected categories of chromatin-based mechanisms impacting aging: those involving changes in the levels of histones or in the functions of telomeres. Full article
(This article belongs to the Special Issue The Epigenetics of Aging and Longevity)
Figures

Figure 1

Open AccessReview Wnt Signaling in Thyroid Homeostasis and Carcinogenesis
Genes 2018, 9(4), 204; doi:10.3390/genes9040204
Received: 26 December 2017 / Accepted: 9 March 2018 / Published: 10 April 2018
PDF Full-text (3710 KB) | HTML Full-text | XML Full-text
Abstract
The Wnt pathway is essential for stem cell maintenance, but little is known about its role in thyroid hormone signaling and thyroid stem cell survival and maintenance. In addition, the role of Wnt signaling in thyroid cancer progenitor cells is also unclear. Here,
[...] Read more.
The Wnt pathway is essential for stem cell maintenance, but little is known about its role in thyroid hormone signaling and thyroid stem cell survival and maintenance. In addition, the role of Wnt signaling in thyroid cancer progenitor cells is also unclear. Here, we present emerging evidence for the role of Wnt signaling in somatic thyroid stem cell and thyroid cancer stem cell function. An improved understanding of the role of Wnt signaling in thyroid physiology and carcinogenesis is essential for improving both thyroid disease diagnostics and therapeutics. Full article
(This article belongs to the Special Issue Wnt Signaling in Stem Cells)
Figures

Figure 1

Open AccessReview Gene Therapy for Chronic HBV—Can We Eliminate cccDNA?
Genes 2018, 9(4), 207; doi:10.3390/genes9040207
Received: 15 March 2018 / Revised: 5 April 2018 / Accepted: 9 April 2018 / Published: 12 April 2018
PDF Full-text (2593 KB) | HTML Full-text | XML Full-text
Abstract
Chronic infection with the hepatitis B virus (HBV) is a global health concern and accounts for approximately 1 million deaths annually. Amongst other limitations of current anti-HBV treatment, failure to eliminate the viral covalently closed circular DNA (cccDNA) and emergence of resistance remain
[...] Read more.
Chronic infection with the hepatitis B virus (HBV) is a global health concern and accounts for approximately 1 million deaths annually. Amongst other limitations of current anti-HBV treatment, failure to eliminate the viral covalently closed circular DNA (cccDNA) and emergence of resistance remain the most worrisome. Viral rebound from latent episomal cccDNA reservoirs occurs following cessation of therapy, patient non-compliance, or the development of escape mutants. Simultaneous viral co-infections, such as by HIV-1, further complicate therapeutic interventions. These challenges have prompted development of novel targeted hepatitis B therapies. Given the ease with which highly specific and potent nucleic acid therapeutics can be rationally designed, gene therapy has generated interest for antiviral application. Gene therapy strategies developed for HBV include gene silencing by harnessing RNA interference, transcriptional inhibition through epigenetic modification of target DNA, genome editing by designer nucleases, and immune modulation with cytokines. DNA-binding domains and effectors based on the zinc finger (ZF), transcription activator-like effector (TALE), and clustered regularly interspaced short palindromic repeat (CRISPR) systems are remarkably well suited to targeting episomal cccDNA. This review discusses recent developments and challenges facing the field of anti-HBV gene therapy, its potential curative significance and the progress towards clinical application. Full article
Figures

Figure 1

Open AccessReview Quorum Sensing and Quorum Quenching in Agrobacterium: A “Go/No Go System”?
Genes 2018, 9(4), 210; doi:10.3390/genes9040210
Received: 7 March 2018 / Revised: 8 April 2018 / Accepted: 9 April 2018 / Published: 16 April 2018
PDF Full-text (3884 KB) | HTML Full-text | XML Full-text
Abstract
The pathogen Agrobacterium induces gall formation on a wide range of dicotyledonous plants. In this bacteria, most pathogenicity determinants are borne on the tumour inducing (Ti) plasmid. The conjugative transfer of this plasmid between agrobacteria is regulated by quorum sensing (QS). However, processes
[...] Read more.
The pathogen Agrobacterium induces gall formation on a wide range of dicotyledonous plants. In this bacteria, most pathogenicity determinants are borne on the tumour inducing (Ti) plasmid. The conjugative transfer of this plasmid between agrobacteria is regulated by quorum sensing (QS). However, processes involved in the disturbance of QS also occur in this bacteria under the molecular form of a protein, TraM, inhibiting the sensing of the QS signals, and two lactonases BlcC (AttM) and AiiB that degrade the acylhomoserine lactone (AHL) QS signal. In the model Agrobacterium fabrum strain C58, several data, once integrated, strongly suggest that the QS regulation may not be reacting only to cell concentration. Rather, these QS elements in association with the quorum quenching (QQ) activities may constitute an integrated and complex “go/no go system” that finely controls the biologically costly transfer of the Ti plasmid in response to multiple environmental cues. This decision mechanism permits the bacteria to sense whether it is in a gall or not, in a living or decaying tumor, in stressed plant tissues, etc. In this scheme, the role of the lactonases selected and maintained in the course of Ti plasmid and agrobacterial evolution appears to be pivotal. Full article
Figures

Open AccessReview Chromatin Architectural Changes during Cellular Senescence and Aging
Genes 2018, 9(4), 211; doi:10.3390/genes9040211
Received: 2 March 2018 / Revised: 2 April 2018 / Accepted: 12 April 2018 / Published: 16 April 2018
PDF Full-text (2321 KB) | HTML Full-text | XML Full-text
Abstract
Chromatin 3D structure is highly dynamic and associated with many biological processes, such as cell cycle progression, cellular differentiation, cell fate reprogramming, cancer development, cellular senescence, and aging. Recently, by using chromosome conformation capture technologies, tremendous findings have been reported about the dynamics
[...] Read more.
Chromatin 3D structure is highly dynamic and associated with many biological processes, such as cell cycle progression, cellular differentiation, cell fate reprogramming, cancer development, cellular senescence, and aging. Recently, by using chromosome conformation capture technologies, tremendous findings have been reported about the dynamics of genome architecture, their associated proteins, and the underlying mechanisms involved in regulating chromatin spatial organization and gene expression. Cellular senescence and aging, which involve multiple cellular and molecular functional declines, also undergo significant chromatin structural changes, including alternations of heterochromatin and disruption of higher-order chromatin structure. In this review, we summarize recent findings related to genome architecture, factors regulating chromatin spatial organization, and how they change during cellular senescence and aging. Full article
(This article belongs to the Special Issue The Epigenetics of Aging and Longevity)
Figures

Figure 1

Other

Jump to: Editorial, Research, Review

Open AccessErratum Erratum: Jimena Soledad Cadona, et al.; Pathogenicity Islands Distribution in Non-O157 Shiga Toxin-Producing Escherichia coli (STEC). Genes 2018, 9, 81
Genes 2018, 9(4), 222; doi:10.3390/genes9040222 (registering DOI)
Received: 26 March 2018 / Revised: 26 March 2018 / Accepted: 4 April 2018 / Published: 20 April 2018
PDF Full-text (188 KB) | HTML Full-text | XML Full-text
Abstract
We wish to make the following correction to the paper by Soledad-Cadona et al.[...] Full article
(This article belongs to the Special Issue Genetics and Genomics of Foodborne Pathogens)
Back to Top