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Genes, Volume 8, Issue 12 (December 2017)

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Open AccessArticle Ancient DNA Resolves the History of Tetragnatha (Araneae, Tetragnathidae) Spiders on Rapa Nui
Genes 2017, 8(12), 403; https://doi.org/10.3390/genes8120403
Received: 11 October 2017 / Revised: 2 December 2017 / Accepted: 13 December 2017 / Published: 20 December 2017
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Abstract
Rapa Nui is one of the most remote islands in the world. As a young island, its biota is a consequence of both natural dispersals over the last ~1 million years and recent human introductions. It therefore provides an opportunity to study a
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Rapa Nui is one of the most remote islands in the world. As a young island, its biota is a consequence of both natural dispersals over the last ~1 million years and recent human introductions. It therefore provides an opportunity to study a unique community assemblage. Here, we extract DNA from museum-preserved and newly field-collected spiders from the genus Tetragnatha to explore their history on Rapa Nui. Using an optimized protocol to recover ancient DNA from museum-preserved spiders, we sequence and assemble partial mitochondrial genomes from nine Tetragnatha species, two of which were found on Rapa Nui, and estimate the evolutionary relationships between these and other Tetragnatha species. Our phylogeny shows that the two Rapa Nui species are not closely related. One, the possibly extinct, T. paschae, is nested within a circumtropical species complex (T. nitens), and the other (Tetragnatha sp. Rapa Nui) appears to be a recent human introduction. Our results highlight the power of ancient DNA approaches in identifying cryptic and rare species, which can contribute to our understanding of the global distribution of biodiversity in all taxonomic lineages. Full article
(This article belongs to the Special Issue Novel and Neglected Areas of Ancient DNA Research)
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Open AccessArticle SlbZIP38, a Tomato bZIP Family Gene Downregulated by Abscisic Acid, Is a Negative Regulator of Drought and Salt Stress Tolerance
Genes 2017, 8(12), 402; https://doi.org/10.3390/genes8120402
Received: 6 November 2017 / Revised: 7 December 2017 / Accepted: 13 December 2017 / Published: 20 December 2017
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Abstract
The basic leucine zipper (bZIP) transcription factors have crucial roles in plant stress responses. In this study, the bZIP family gene SlbZIP38 (GenBank accession No: XM004239373) was isolated from a tomato (Solanum lycopersicum cv. Ailsa Craig) mature leaf cDNA library. The DNA
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The basic leucine zipper (bZIP) transcription factors have crucial roles in plant stress responses. In this study, the bZIP family gene SlbZIP38 (GenBank accession No: XM004239373) was isolated from a tomato (Solanum lycopersicum cv. Ailsa Craig) mature leaf cDNA library. The DNA sequence of SlbZIP38 encodes a protein of 484 amino acids, including a highly conserved bZIP DNA-binding domain in the C-terminal region. We found that SlbZIP38 was differentially expressed in various organs of the tomato plant and was downregulated by drought, salt stress, and abscisic acid (ABA). However, overexpression of SlbZIP38 significantly decreased drought and salt stress tolerance in tomatoes (Ailsa Craig). The findings that SlbZIP38 overexpression reduced the chlorophyll and free proline content in leaves but increased the malondialdehyde content may explain the reduced drought and salt tolerance observed in these lines. These results suggest that SlbZIP38 is a negative regulator of drought and salt resistance that acts by modulating ABA signaling. Full article
(This article belongs to the Special Issue Genetic Regulation of Abiotic Stress Responses)
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Open AccessArticle Using Human iPSC-Derived Neurons to Uncover Activity-Dependent Non-Coding RNAs
Genes 2017, 8(12), 401; https://doi.org/10.3390/genes8120401
Received: 10 November 2017 / Revised: 5 December 2017 / Accepted: 13 December 2017 / Published: 20 December 2017
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Abstract
Humans are arguably the most complex organisms present on Earth with their ability to imagine, create, and problem solve. As underlying mechanisms enabling these capacities reside in the brain, it is not surprising that the brain has undergone an extraordinary increase in size
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Humans are arguably the most complex organisms present on Earth with their ability to imagine, create, and problem solve. As underlying mechanisms enabling these capacities reside in the brain, it is not surprising that the brain has undergone an extraordinary increase in size and complexity within the last few million years. Human induced pluripotent stem cells (hiPSCs) can be differentiated into many cell types that were virtually inaccessible historically, such as neurons. Here, we used hiPSC-derived neurons to investigate the cellular response to activation at the transcript level. Neuronal activation was performed with potassium chloride (KCl) and its effects were assessed by RNA sequencing. Our results revealed the involvement of long non-coding RNAs and human-specific genetic variants in response to neuronal activation and help validate hiPSCs as a valuable resource for the study of human neuronal networks. In summary, we find that genes affected by KCl-triggered activation are implicated in pathways that drive cell proliferation, differentiation, and the emergence of specialized morphological features. Interestingly, non-coding RNAs of various classes are amongst the most highly expressed genes in activated hiPSC-derived neurons, thus suggesting these play crucial roles in neural pathways and may significantly contribute to the unique functioning of the human brain. Full article
(This article belongs to the Special Issue Non-coding RNAs)
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Open AccessArticle Structural Characterization and Association of Ovine Dickkopf-1 Gene with Wool Production and Quality Traits in Chinese Merino
Genes 2017, 8(12), 400; https://doi.org/10.3390/genes8120400
Received: 20 October 2017 / Revised: 6 December 2017 / Accepted: 15 December 2017 / Published: 20 December 2017
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Abstract
Dickkopf-1 (DKK1) is an inhibitor of canonical Wnt signaling pathway and regulates hair follicle morphogenesis and cycling. To investigate the potential involvement of DKK1 in wool production and quality traits, we characterized the genomic structure of ovine DKK1, performed polymorphism detection and
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Dickkopf-1 (DKK1) is an inhibitor of canonical Wnt signaling pathway and regulates hair follicle morphogenesis and cycling. To investigate the potential involvement of DKK1 in wool production and quality traits, we characterized the genomic structure of ovine DKK1, performed polymorphism detection and association analysis of ovine DKK1 with wool production and quality traits in Chinese Merino. Our results showed that ovine DKK1 consists of four exons and three introns, which encodes a protein of 262 amino acids. The coding sequence of ovine DKK1 and its deduced amino acid sequence were highly conserved in mammals. Eleven single nucleotide polymorphisms (SNPs) were identified within the ovine DKK1 genomic region. Gene-wide association analysis showed that SNP5 was significantly associated with mean fiber diameter (MFD) in the B (selected for long wool fiber and high-quality wool), PW (selected for high reproductive capacity, high clean wool yield and high-quality wool) and U (selected for long wool fiber with good uniformity, high wool yield and lower fiber diameter) strains (p < 4.55 × 10−3 = 0.05/11). Single Nucleotide Polymorphisms wide association analysis showed that SNP8 was significantly associated with MFD in A strain and fleece weight in A (selected for large body size), PM (selected for large body size, high reproductive capacity and high meat yield) and SF (selected for mean fiber diameter less than 18 μm and wool fiber length between 5 and 9 cm) strains (p < 0.05), SNP9 was significantly associated with curvature in B and U strains (p < 0.05) and SNP10 was significantly associated with coefficient of variation of fiber diameter in A, PW and PM strains and standard deviation of fiber diameter in A and PM strains (p < 0.05). The haplotypes derived from these 11 identified SNPs were significantly associated with MFD (p < 0.05). In conclusion, our results suggest that DKK1 may be a major gene controlling wool production and quality traits, also the identified SNPs (SNPs5, 8, 9 and 10) might be used as potential molecular markers for improving sheep wool production and quality in sheep breeding. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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Open AccessReview Genome Editing Tools in Plants
Genes 2017, 8(12), 399; https://doi.org/10.3390/genes8120399
Received: 16 November 2017 / Revised: 8 December 2017 / Accepted: 15 December 2017 / Published: 19 December 2017
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Abstract
Genome editing tools have the potential to change the genomic architecture of a genome at precise locations, with desired accuracy. These tools have been efficiently used for trait discovery and for the generation of plants with high crop yields and resistance to biotic
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Genome editing tools have the potential to change the genomic architecture of a genome at precise locations, with desired accuracy. These tools have been efficiently used for trait discovery and for the generation of plants with high crop yields and resistance to biotic and abiotic stresses. Due to complex genomic architecture, it is challenging to edit all of the genes/genomes using a particular genome editing tool. Therefore, to overcome this challenging task, several genome editing tools have been developed to facilitate efficient genome editing. Some of the major genome editing tools used to edit plant genomes are: Homologous recombination (HR), zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), pentatricopeptide repeat proteins (PPRs), the CRISPR/Cas9 system, RNA interference (RNAi), cisgenesis, and intragenesis. In addition, site-directed sequence editing and oligonucleotide-directed mutagenesis have the potential to edit the genome at the single-nucleotide level. Recently, adenine base editors (ABEs) have been developed to mutate A-T base pairs to G-C base pairs. ABEs use deoxyadeninedeaminase (TadA) with catalytically impaired Cas9 nickase to mutate A-T base pairs to G-C base pairs. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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Open AccessReview The Mitochondrial Basis of Aging and Age-Related Disorders
Genes 2017, 8(12), 398; https://doi.org/10.3390/genes8120398
Received: 31 October 2017 / Revised: 9 December 2017 / Accepted: 13 December 2017 / Published: 19 December 2017
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Abstract
Aging is a natural phenomenon characterized by progressive decline in tissue and organ function leading to increased risk of disease and mortality. Among diverse factors that contribute to human aging, the mitochondrial dysfunction has emerged as one of the key hallmarks of aging
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Aging is a natural phenomenon characterized by progressive decline in tissue and organ function leading to increased risk of disease and mortality. Among diverse factors that contribute to human aging, the mitochondrial dysfunction has emerged as one of the key hallmarks of aging process and is linked to the development of numerous age-related pathologies including metabolic syndrome, neurodegenerative disorders, cardiovascular diseases and cancer. Mitochondria are central in the regulation of energy and metabolic homeostasis, and harbor a complex quality control system that limits mitochondrial damage to ensure mitochondrial integrity and function. The intricate regulatory network that balances the generation of new and removal of damaged mitochondria forms the basis of aging and longevity. Here, I will review our current understanding on how mitochondrial functional decline contributes to aging, including the role of somatic mitochondrial DNA (mtDNA) mutations, reactive oxygen species (ROS), mitochondrial dynamics and quality control pathways. I will further discuss the emerging evidence on how dysregulated mitochondrial dynamics, mitochondrial biogenesis and turnover mechanisms contribute to the pathogenesis of age-related disorders. Strategies aimed to enhance mitochondrial function by targeting mitochondrial dynamics, quality control, and mitohormesis pathways might promote healthy aging, protect against age-related diseases, and mediate longevity. Full article
(This article belongs to the Special Issue Mitochondria and Aging)
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Open AccessArticle Proliferation Cycle Causes Age Dependent Mitochondrial Deficiencies and Contributes to the Aging of Stem Cells
Genes 2017, 8(12), 397; https://doi.org/10.3390/genes8120397
Received: 31 October 2017 / Revised: 17 November 2017 / Accepted: 14 December 2017 / Published: 19 December 2017
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Abstract
In addition to chronological aging, stem cells are also subject to proliferative aging during the adult life span. However, the consequences of proliferative cycle and their contributions to stem cells aging have not been well investigated. Using Drosophila female germ line stem cells
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In addition to chronological aging, stem cells are also subject to proliferative aging during the adult life span. However, the consequences of proliferative cycle and their contributions to stem cells aging have not been well investigated. Using Drosophila female germ line stem cells as a model, we found that the replication cycle leads to the age dependent decline of female fecundity, and is a major factor causing developmental abnormalities in the progeny of old females. The proliferative aging does not cause telomere shortening, but causes an accumulation of mitochondrial DNA (mtDNA) mutations or rearrangements at the control region. We propose that damaging mutations on mtDNA caused by accumulation of proliferation cycles in aged stem cells may disrupt mitochondrial respiration chain and impair mtDNA replication and represent a conserved mechanism underlying stem cell aging. Full article
(This article belongs to the Special Issue Mitochondria and Aging)
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Open AccessArticle Genome-Wide Transcriptional Changes and Lipid Profile Modifications Induced by Medicago truncatula N5 Overexpression at an Early Stage of the Symbiotic Interaction with Sinorhizobium meliloti
Genes 2017, 8(12), 396; https://doi.org/10.3390/genes8120396
Received: 30 October 2017 / Revised: 6 December 2017 / Accepted: 11 December 2017 / Published: 19 December 2017
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Abstract
Plant lipid-transfer proteins (LTPs) are small basic secreted proteins, which are characterized by lipid-binding capacity and are putatively involved in lipid trafficking. LTPs play a role in several biological processes, including the root nodule symbiosis. In this regard, the Medicago truncatula nodulin 5
[...] Read more.
Plant lipid-transfer proteins (LTPs) are small basic secreted proteins, which are characterized by lipid-binding capacity and are putatively involved in lipid trafficking. LTPs play a role in several biological processes, including the root nodule symbiosis. In this regard, the Medicago truncatula nodulin 5 (MtN5) LTP has been proved to positively regulate the nodulation capacity, controlling rhizobial infection and nodule primordia invasion. To better define the lipid transfer protein MtN5 function during the symbiosis, we produced MtN5-downregulated and -overexpressing plants, and we analysed the transcriptomic changes occurring in the roots at an early stage of Sinorhizobium meliloti infection. We also carried out the lipid profile analysis of wild type (WT) and MtN5-overexpressing roots after rhizobia infection. The downregulation of MtN5 increased the root hair curling, an early event of rhizobia infection, and concomitantly induced changes in the expression of defence-related genes. On the other hand, MtN5 overexpression favoured the invasion of the nodules by rhizobia and determined in the roots the modulation of genes that are involved in lipid transport and metabolism as well as an increased content of lipids, especially galactolipids that characterize the symbiosome membranes. Our findings suggest the potential participation of LTPs in the synthesis and rearrangement of membranes occurring during the formation of the infection threads and the symbiosome membrane. Full article
(This article belongs to the Special Issue Genetics and Genomics of the Rhizobium-Legume Symbiosis)
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Open AccessArticle Comparative Analysis of Four Calypogeia Species Revealed Unexpected Change in Evolutionarily-Stable Liverwort Mitogenomes
Genes 2017, 8(12), 395; https://doi.org/10.3390/genes8120395
Received: 11 October 2017 / Revised: 8 December 2017 / Accepted: 12 December 2017 / Published: 19 December 2017
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Abstract
Liverwort mitogenomes are considered to be evolutionarily stable. A comparative analysis of four Calypogeia species revealed differences compared to previously sequenced liverwort mitogenomes. Such differences involve unexpected structural changes in the two genes, cox1 and atp1, which have lost three and two
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Liverwort mitogenomes are considered to be evolutionarily stable. A comparative analysis of four Calypogeia species revealed differences compared to previously sequenced liverwort mitogenomes. Such differences involve unexpected structural changes in the two genes, cox1 and atp1, which have lost three and two introns, respectively. The group I introns in the cox1 gene are proposed to have been lost by two-step localized retroprocessing, whereas one-step retroprocessing could be responsible for the disappearance of the group II introns in the atp1 gene. These cases represent the first identified losses of introns in mitogenomes of leafy liverworts (Jungermanniopsida) contrasting the stability of mitochondrial gene order with certain changes in the gene content and intron set in liverworts. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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Open AccessArticle Study of mcr-1 Gene-Mediated Colistin Resistance in Enterobacteriaceae Isolated from Humans and Animals in Different Countries
Genes 2017, 8(12), 394; https://doi.org/10.3390/genes8120394
Received: 4 October 2017 / Revised: 22 November 2017 / Accepted: 12 December 2017 / Published: 19 December 2017
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Abstract
In this study, we aim to characterize the genetic environment of the plasmid-mediated colistin resistance gene mcr-1 in 25 Escherichia coli and seven Klebsiella pneumoniae strains from different countries and continents. Multilocus sequence typing, conjugation experiments, plasmid typing, and the presence and location
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In this study, we aim to characterize the genetic environment of the plasmid-mediated colistin resistance gene mcr-1 in 25 Escherichia coli and seven Klebsiella pneumoniae strains from different countries and continents. Multilocus sequence typing, conjugation experiments, plasmid typing, and the presence and location of the insertion sequence ISApl1 were investigated. Whole genome sequencing of four E. coli was performed to analyse the genetic environment of the mcr-1 gene. Colistin minimum inhibitory concentration of mcr-1 strains varied from 3 to 32 µg/mL. Six E. coli sequence types were detected: ST 4015, ST 3997, ST 10, ST 93, ST 48, and ST 648. IncHI2, IncI2, and IncP plasmid types were predominant and were unrelated to a specific country of origin. ISApl1 was found in 69% of analysed plasmids that were mainly around the mcr-1 gene. Analysis of four closed mcr-1 plasmids revealed the integration of mcr-1 into hotspots. We found that the spread of mcr-1 gene was due to the diffusion of a composite transposon and not to the diffusion of a specific plasmid or a specific bacterial clone. The ease with which the mcr-1 gene integrates into various regions facilitates its dissemination among bacteria and explains its large diffusion all over the world, both in animals and in humans. Full article
(This article belongs to the Section Microbial Genetics and Genomics)
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Open AccessArticle Comparative Transcriptome Analysis of Male and Female Conelets and Development of Microsatellite Markers in Pinus bungeana, an Endemic Conifer in China
Genes 2017, 8(12), 393; https://doi.org/10.3390/genes8120393
Received: 28 September 2017 / Revised: 11 December 2017 / Accepted: 12 December 2017 / Published: 19 December 2017
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Abstract
The sex determination in gymnosperms is still poorly characterized due to the lack of genomic/transcriptome resources and useful molecular genetic markers. To enhance our understanding of the molecular mechanisms of the determination of sexual recognition of reproductive structures in conifers, the transcriptome of
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The sex determination in gymnosperms is still poorly characterized due to the lack of genomic/transcriptome resources and useful molecular genetic markers. To enhance our understanding of the molecular mechanisms of the determination of sexual recognition of reproductive structures in conifers, the transcriptome of male and female conelets were characterized in a Chinese endemic conifer species, Pinus bungeana Zucc. ex Endl. The 39.62 Gb high-throughput sequencing reads were obtained from two kinds of sexual conelets. After de novo assembly of the obtained reads, 85,305 unigenes were identified, 53,944 (63.23%) of which were annotated with public databases. A total of 12,073 differentially expressed genes were detected between the two types of sexes in P. bungeana, and 5766 (47.76%) of them were up-regulated in females. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enriched analysis suggested that some of the genes were significantly associated with the sex determination process of P. bungeana, such as those involved in tryptophan metabolism, zeatin biosynthesis, and cysteine and methionine metabolism, and the phenylpropanoid biosynthesis pathways. Meanwhile, some important plant hormone pathways (e.g., the gibberellin (GA) pathway, carotenoid biosynthesis, and brassinosteroid biosynthesis (BR) pathway) that affected sexual determination were also induced in P. bungeana. In addition, 8791 expressed sequence tag-simple sequence repeats (EST-SSRs) from 7859 unigenes were detected in P. bungeana. The most abundant repeat types were dinucleotides (1926), followed by trinucleotides (1711). The dominant classes of the sequence repeat were A/T (4942) in mononucleotides and AT/AT (1283) in dinucleotides. Among these EST-SSRs, 84 pairs of primers were randomly selected for the characterization of potential molecular genetic markers. Finally, 19 polymorphic EST-SSR primers were characterized. We found low to moderate levels of genetic diversity (NA = 1.754; HO = 0.206; HE = 0.205) across natural populations of P. bungeana. The cluster analysis revealed two distinct genetic groups for the six populations that were sampled in this endemic species, which might be caused by the fragmentation of habitats and long-term geographic isolation among different populations. Taken together, this work provides important insights into the molecular mechanisms of sexual identity in the reproductive organs of P. bungeana. The molecular genetic resources that were identified in this study will also facilitate further studies in functional genomics and population genetics in the Pinus species. Full article
(This article belongs to the Special Issue Evolution and Biodiversity of the Plant Genome Architecture)
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Open AccessArticle Deciphering the Relationship between Obesity and Various Diseases from a Network Perspective
Genes 2017, 8(12), 392; https://doi.org/10.3390/genes8120392
Received: 20 October 2017 / Revised: 2 December 2017 / Accepted: 13 December 2017 / Published: 18 December 2017
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Abstract
The number of obesity cases is rapidly increasing in developed and developing countries, thereby causing significant health problems worldwide. The pathologic factors of obesity at the molecular level are not fully characterized, although the imbalance between energy intake and consumption is widely recognized
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The number of obesity cases is rapidly increasing in developed and developing countries, thereby causing significant health problems worldwide. The pathologic factors of obesity at the molecular level are not fully characterized, although the imbalance between energy intake and consumption is widely recognized as the main reason for fat accumulation. Previous studies reported that obesity can be caused by the dysfunction of genes associated with other diseases, such as myocardial infarction, hence providing new insights into dissecting the pathogenesis of obesity by investigating its associations with other diseases. In this study, we investigated the relationship between obesity and diseases from Online Mendelian Inheritance in Man (OMIM) databases on the protein–protein interaction (PPI) network. The obesity genes and genes of one OMIM disease were mapped onto the network, and the interaction scores between the two gene sets were investigated on the basis of the PPI of individual gene pairs, thereby inferring the relationship between obesity and this disease. Results suggested that diseases related to nutrition and endocrine are the top two diseases that are closely associated with obesity. This finding is consistent with our general knowledge and indicates the reliability of our obtained results. Moreover, we inferred that diseases related to psychiatric factors and bone may also be highly related to obesity because the two diseases followed the diseases related to nutrition and endocrine according to our results. Numerous obesity–disease associations were identified in the literature to confirm the relationships between obesity and the aforementioned four diseases. These new results may help understand the underlying molecular mechanisms of obesity–disease co-occurrence and provide useful insights for disease prevention and intervention. Full article
(This article belongs to the Special Issue Diabetes, Obesity and the Gut Microbiome)
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Open AccessArticle Isolation and Characterization of Ftsz Genes in Cassava
Genes 2017, 8(12), 391; https://doi.org/10.3390/genes8120391
Received: 18 October 2017 / Revised: 1 December 2017 / Accepted: 12 December 2017 / Published: 15 December 2017
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Abstract
The filamenting temperature-sensitive Z proteins (FtsZs) play an important role in plastid division. In this study, three FtsZ genes were isolated from the cassava genome, and named MeFtsZ1, MeFtsZ2-1, and MeFtsZ2-2, respectively. Based on phylogeny, the MeFtsZs were classified into two groups (FtsZ1
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The filamenting temperature-sensitive Z proteins (FtsZs) play an important role in plastid division. In this study, three FtsZ genes were isolated from the cassava genome, and named MeFtsZ1, MeFtsZ2-1, and MeFtsZ2-2, respectively. Based on phylogeny, the MeFtsZs were classified into two groups (FtsZ1 and FtsZ2). MeFtsZ1 with a putative signal peptide at N-terminal, has six exons, and is classed to FtsZ1 clade. MeFtsZ2-1 and MeFtsZ2-2 without a putative signal peptide, have seven exons, and are classed to FtsZ2 clade. Subcellular localization found that all the three MeFtsZs could locate in chloroplasts and form a ring in chloroplastids. Structure analysis found that all MeFtsZ proteins contain a conserved guanosine triphosphatase (GTPase) domain in favor of generate contractile force for cassava plastid division. The expression profiles of MeFtsZ genes by quantitative reverse transcription-PCR (qRT-PCR) analysis in photosynthetic and non-photosynthetic tissues found that all of the MeFtsZ genes had higher expression levels in photosynthetic tissues, especially in younger leaves, and lower expression levels in the non-photosynthetic tissues. During cassava storage root development, the expressions of MeFtsZ2-1 and MeFtsZ2-2 were comparatively higher than MeFtsZ1. The transformed Arabidopsis of MeFtsZ2-1 and MeFtsZ2-2 contained abnormally shape, fewer number, and larger volume chloroplasts. Phytohormones were involved in regulating the expressions of MeFtsZ genes. Therefore, we deduced that all of the MeFtsZs play an important role in chloroplast division, and that MeFtsZ2 (2-1, 2-2) might be involved in amyloplast division and regulated by phytohormones during cassava storage root development. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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Open AccessArticle Requirements for Efficient Thiosulfate Oxidation in Bradyrhizobium diazoefficiens
Genes 2017, 8(12), 390; https://doi.org/10.3390/genes8120390
Received: 8 November 2017 / Revised: 7 December 2017 / Accepted: 12 December 2017 / Published: 15 December 2017
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Abstract
One of the many disparate lifestyles of Bradyrhizobium diazoefficiens is chemolithotrophic growth with thiosulfate as an electron donor for respiration. The employed carbon source may be CO2 (autotrophy) or an organic compound such as succinate (mixotrophy). Here, we discovered three new facets
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One of the many disparate lifestyles of Bradyrhizobium diazoefficiens is chemolithotrophic growth with thiosulfate as an electron donor for respiration. The employed carbon source may be CO2 (autotrophy) or an organic compound such as succinate (mixotrophy). Here, we discovered three new facets of this capacity: (i) When thiosulfate and succinate were consumed concomitantly in conditions of mixotrophy, even a high molar excess of succinate did not exert efficient catabolite repression over the use of thiosulfate. (ii) Using appropriate cytochrome mutants, we found that electrons derived from thiosulfate during chemolithoautotrophic growth are preferentially channeled via cytochrome c550 to the aa3-type heme-copper cytochrome oxidase. (iii) Three genetic regulators were identified to act at least partially in the expression control of genes for chemolithoautotrophic thiosulfate oxidation: RegR and CbbR as activators, and SoxR as a repressor. Full article
(This article belongs to the Special Issue Genetics and Genomics of the Rhizobium-Legume Symbiosis)
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Open AccessArticle Transcriptome Analysis of Paraburkholderia phymatum under Nitrogen Starvation and during Symbiosis with Phaseolus Vulgaris
Genes 2017, 8(12), 389; https://doi.org/10.3390/genes8120389
Received: 31 October 2017 / Revised: 29 November 2017 / Accepted: 4 December 2017 / Published: 15 December 2017
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Abstract
Paraburkholderia phymatum belongs to the β-subclass of proteobacteria. It has recently been shown to be able to nodulate and fix nitrogen in symbiosis with several mimosoid and papilionoid legumes. In contrast to the symbiosis of legumes with α-proteobacteria, very little is known about
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Paraburkholderia phymatum belongs to the β-subclass of proteobacteria. It has recently been shown to be able to nodulate and fix nitrogen in symbiosis with several mimosoid and papilionoid legumes. In contrast to the symbiosis of legumes with α-proteobacteria, very little is known about the molecular determinants underlying the successful establishment of this mutualistic relationship with β-proteobacteria. In this study, we performed an RNA-sequencing (RNA-seq) analysis of free-living P. phymatum growing under nitrogen-replete and -limited conditions, the latter partially mimicking the situation in nitrogen-deprived soils. Among the genes upregulated under nitrogen limitation, we found genes involved in exopolysaccharides production and in motility, two traits relevant for plant root infection. Next, RNA-seq data of P. phymatum grown under free-living conditions and from symbiotic root nodules of Phaseolus vulgaris (common bean) were generated and compared. Among the genes highly upregulated during symbiosis, we identified—besides the nif gene cluster—an operon encoding a potential cytochrome o ubiquinol oxidase (Bphy_3646-49). Bean root nodules induced by a cyoB mutant strain showed reduced nitrogenase and nitrogen fixation abilities, suggesting an important role of the cytochrome for respiration inside the nodule. The analysis of mutant strains for the RNA polymerase transcription factor RpoN (σ54) and its activator NifA indicated that—similar to the situation in α-rhizobia—P. phymatum RpoN and NifA are key regulators during symbiosis with P. vulgaris. Full article
(This article belongs to the Special Issue Genetics and Genomics of the Rhizobium-Legume Symbiosis)
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Open AccessArticle Regulatory Elements Located in the Upstream Region of the Rhizobium leguminosarum rosR Global Regulator Are Essential for Its Transcription and mRNA Stability
Genes 2017, 8(12), 388; https://doi.org/10.3390/genes8120388
Received: 18 October 2017 / Revised: 24 November 2017 / Accepted: 7 December 2017 / Published: 15 December 2017
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Abstract
Rhizobium leguminosarum bv. trifolii is a soil bacterium capable of establishing a symbiotic relationship with clover (Trifolium spp.). Previously, the rosR gene, encoding a global regulatory protein involved in motility, synthesis of cell-surface components, and other cellular processes was identified and characterized
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Rhizobium leguminosarum bv. trifolii is a soil bacterium capable of establishing a symbiotic relationship with clover (Trifolium spp.). Previously, the rosR gene, encoding a global regulatory protein involved in motility, synthesis of cell-surface components, and other cellular processes was identified and characterized in this bacterium. This gene possesses a long upstream region that contains several regulatory motifs, including inverted repeats (IRs) of different lengths. So far, the role of these motifs in the regulation of rosR transcription has not been elucidated in detail. In this study, we performed a functional analysis of these motifs using a set of transcriptional rosR-lacZ fusions that contain mutations in these regions. The levels of rosR transcription for different mutant variants were evaluated in R. leguminosarum using both quantitative real-time PCR and β-galactosidase activity assays. Moreover, the stability of wild type rosR transcripts and those with mutations in the regulatory motifs was determined using an RNA decay assay and plasmids with mutations in different IRs located in the 5′-untranslated region of the gene. The results show that transcription of rosR undergoes complex regulation, in which several regulatory elements located in the upstream region and some regulatory proteins are engaged. These include an upstream regulatory element, an extension of the -10 element containing three nucleotides TGn (TGn-extended -10 element), several IRs, and PraR repressor related to quorum sensing. Full article
(This article belongs to the Special Issue Genetics and Genomics of the Rhizobium-Legume Symbiosis)
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Open AccessArticle NAD1 Controls Defense-Like Responses in Medicago truncatula Symbiotic Nitrogen Fixing Nodules Following Rhizobial Colonization in a BacA-Independent Manner
Genes 2017, 8(12), 387; https://doi.org/10.3390/genes8120387
Received: 31 October 2017 / Revised: 4 December 2017 / Accepted: 11 December 2017 / Published: 14 December 2017
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Abstract
Legumes form endosymbiotic interaction with host compatible rhizobia, resulting in the development of nitrogen-fixing root nodules. Within symbiotic nodules, rhizobia are intracellularly accommodated in plant-derived membrane compartments, termed symbiosomes. In mature nodule, the massively colonized cells tolerate the existence of rhizobia without manifestation
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Legumes form endosymbiotic interaction with host compatible rhizobia, resulting in the development of nitrogen-fixing root nodules. Within symbiotic nodules, rhizobia are intracellularly accommodated in plant-derived membrane compartments, termed symbiosomes. In mature nodule, the massively colonized cells tolerate the existence of rhizobia without manifestation of visible defense responses, indicating the suppression of plant immunity in the nodule in the favur of the symbiotic partner. Medicago truncatula DNF2 (defective in nitrogen fixation 2) and NAD1 (nodules with activated defense 1) genes are essential for the control of plant defense during the colonization of the nitrogen-fixing nodule and are required for bacteroid persistence. The previously identified nodule-specific NAD1 gene encodes a protein of unknown function. Herein, we present the analysis of novel NAD1 mutant alleles to better understand the function of NAD1 in the repression of immune responses in symbiotic nodules. By exploiting the advantage of plant double and rhizobial mutants defective in establishing nitrogen-fixing symbiotic interaction, we show that NAD1 functions following the release of rhizobia from the infection threads and colonization of nodule cells. The suppression of plant defense is self-dependent of the differentiation status of the rhizobia. The corresponding phenotype of nad1 and dnf2 mutants and the similarity in the induction of defense-associated genes in both mutants suggest that NAD1 and DNF2 operate close together in the same pathway controlling defense responses in symbiotic nodules. Full article
(This article belongs to the Special Issue Genetics and Genomics of the Rhizobium-Legume Symbiosis)
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Open AccessArticle Absence of Correlation between Chimeric RNA and Aging
Genes 2017, 8(12), 386; https://doi.org/10.3390/genes8120386
Received: 18 November 2017 / Revised: 6 December 2017 / Accepted: 7 December 2017 / Published: 14 December 2017
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Abstract
Chimeric RNAs have been recognized as a phenomenon not unique to cancer cells. They also exist in normal physiology. Aging is often characterized by deregulation of molecular and cellular mechanisms, including loss of heterochromatin, increased transcriptional noise, less tight control on alternative splicing,
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Chimeric RNAs have been recognized as a phenomenon not unique to cancer cells. They also exist in normal physiology. Aging is often characterized by deregulation of molecular and cellular mechanisms, including loss of heterochromatin, increased transcriptional noise, less tight control on alternative splicing, and more stress-induced changes. It is thus assumed that chimeric RNAs are more abundant in older people. In this study, we conducted a preliminary investigation to identify any chimeric RNAs with age-based trends in their expression levels in blood samples. A chimeric RNA candidate list generated by bioinformatic analysis indicated the possibility of both negative and positive trends in the expression of chimeric RNAs. Out of this candidate list, five novel chimeric RNAs were successfully amplified in multiple blood samples and then sequenced. Although primary smaller sample sizes displayed some weak trends with respect to age, analysis of quantitative PCR data from larger sample sizes showed essentially no relationship between expression levels and age. Altogether, these results indicate that, contradictory to the common assumption, chimeric RNAs as a group are not all higher in older individuals and that placing chimeric RNAs in the context of aging will be a much more complex task than initially anticipated. Full article
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Open AccessArticle High-Throughput Sequencing of Small RNA Transcriptomes in Maize Kernel Identifies miRNAs Involved in Embryo and Endosperm Development
Genes 2017, 8(12), 385; https://doi.org/10.3390/genes8120385
Received: 2 November 2017 / Revised: 7 December 2017 / Accepted: 7 December 2017 / Published: 14 December 2017
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Abstract
Maize kernel development is a complex biological process that involves the temporal and spatial expression of many genes and fine gene regulation at a transcriptional and post-transcriptional level, and microRNAs (miRNAs) play vital roles during this process. To gain insight into miRNA-mediated regulation
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Maize kernel development is a complex biological process that involves the temporal and spatial expression of many genes and fine gene regulation at a transcriptional and post-transcriptional level, and microRNAs (miRNAs) play vital roles during this process. To gain insight into miRNA-mediated regulation of maize kernel development, a deep-sequencing technique was used to investigate the dynamic expression of miRNAs in the embryo and endosperm at three developmental stages in B73. By miRNA transcriptomic analysis, we characterized 132 known miRNAs and six novel miRNAs in developing maize kernel, among which, 15 and 14 miRNAs were commonly differentially expressed between the embryo and endosperm at 9 days after pollination (DAP), 15 DAP and 20 DAP respectively. Conserved miRNA families such as miR159, miR160, miR166, miR390, miR319, miR528 and miR529 were highly expressed in developing embryos; miR164, miR171, miR393 and miR2118 were highly expressed in developing endosperm. Genes targeted by those highly expressed miRNAs were found to be largely related to a regulation category, including the transcription, macromolecule biosynthetic and metabolic process in the embryo as well as the vitamin biosynthetic and metabolic process in the endosperm. Quantitative reverse transcription-PCR (qRT-PCR) analysis showed that these miRNAs displayed a negative correlation with the levels of their corresponding target genes. Importantly, our findings revealed that members of the miR169 family were highly and dynamically expressed in the developing kernel, which will help to exploit new players functioning in maize kernel development. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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Open AccessReview The Tumor Suppressor p53 in Mucosal Melanoma of the Head and Neck
Genes 2017, 8(12), 384; https://doi.org/10.3390/genes8120384
Received: 9 November 2017 / Revised: 4 December 2017 / Accepted: 5 December 2017 / Published: 13 December 2017
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Abstract
Despite worldwide prevention programs, the incidence for cutaneous melanoma is continuously increasing. Mucosal melanoma (MM) represents a rare but highly aggressive phenotype of common melanoma with predilection in the sinonasal system. Far away from ultraviolet sun exposure, the molecular mechanisms underlying tumorigenesis and
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Despite worldwide prevention programs, the incidence for cutaneous melanoma is continuously increasing. Mucosal melanoma (MM) represents a rare but highly aggressive phenotype of common melanoma with predilection in the sinonasal system. Far away from ultraviolet sun exposure, the molecular mechanisms underlying tumorigenesis and the highly aggressive clinical behavior are poorly understood. In many solid malignomas of the head and neck region, p53 tumor suppressor functions as oncogene due to p53 protein stabilizing mutation. Interestingly, the vast majority of MM demonstrates constitutively expressed p53 protein, with protein stabilizing mutations being rare. Abrogated activation of p53 target genes results in derogation of the apoptotic signal cascade and contributes to the strong resistance against chemotherapeutic agents activating p53 dependent apoptosis. The current review illustrates the role of p53 and its pathway in MM. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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Open AccessArticle Differential Expression of Serum MicroRNAs Supports CD4+ T Cell Differentiation into Th2/Th17 Cells in Severe Equine Asthma
Genes 2017, 8(12), 383; https://doi.org/10.3390/genes8120383
Received: 11 October 2017 / Revised: 21 November 2017 / Accepted: 1 December 2017 / Published: 12 December 2017
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Abstract
MicroRNAs (miRNAs) regulate post-transcriptional gene expression and may be exported from cells via exosomes or in partnership with RNA-binding proteins. MiRNAs in body fluids can act in a hormone-like manner and play important roles in disease initiation and progression. Hence, miRNAs are promising
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MicroRNAs (miRNAs) regulate post-transcriptional gene expression and may be exported from cells via exosomes or in partnership with RNA-binding proteins. MiRNAs in body fluids can act in a hormone-like manner and play important roles in disease initiation and progression. Hence, miRNAs are promising candidates as biomarkers. To identify serum miRNA biomarkers in the equine model of asthma we investigated small RNA derived from the serum of 34 control and 37 asthmatic horses. These samples were used for next generation sequencing, novel miRNA identification and differential miRNA expression analysis. We identified 11 significantly differentially expressed miRNAs between case and control horses: eca-miR-128, eca-miR-744, eca-miR-197, eca-miR-103, eca-miR-107a, eca-miR-30d, eca-miR-140-3p, eca-miR-7, eca-miR-361-3p, eca-miR-148b-3p and eca-miR-215. Pathway enrichment using experimentally validated target genes of the human homologous miRNAs showed a significant enrichment in the regulation of epithelial-to-mesenchymal transition (key player in airway remodeling in asthma) and the phosphatidylinositol (3,4,5)-triphosphate (PIP3) signaling pathway (modulator of CD4+ T cell maturation and function). Downregulated miR-128 and miR-744 supports a Th2/Th17 type immune response in severe equine asthma. Full article
(This article belongs to the Special Issue Non-coding RNAs)
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Open AccessArticle Evolution of Karyotypes in Chameleons
Genes 2017, 8(12), 382; https://doi.org/10.3390/genes8120382
Received: 1 November 2017 / Revised: 29 November 2017 / Accepted: 30 November 2017 / Published: 12 December 2017
Cited by 2 | Viewed by 1418 | PDF Full-text (20537 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The reconstruction of the evolutionary dynamics of karyotypes and sex determining systems in squamate reptiles is precluded by the lack of data in many groups including most chameleons (Squamata: Acrodonta: Chamaeleonidae). We performed cytogenetic analysis in 16 species of chameleons from 8 genera
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The reconstruction of the evolutionary dynamics of karyotypes and sex determining systems in squamate reptiles is precluded by the lack of data in many groups including most chameleons (Squamata: Acrodonta: Chamaeleonidae). We performed cytogenetic analysis in 16 species of chameleons from 8 genera covering the phylogenetic diversity of the family and also phylogenetic reconstruction of karyotype evolution in this group. In comparison to other squamates, chameleons demonstrate rather variable karyotypes, differing in chromosome number, morphology and presence of interstitial telomeric signal (ITS). On the other hand, the location of rDNA is quite conserved among chameleon species. Phylogenetic analysis combining our new results and previously published data tentatively suggests that the ancestral chromosome number for chameleons is 2n = 36, which is the same as assumed for other lineages of the clade Iguania, i.e., agamids and iguanas. In general, we observed a tendency for the reduction of chromosome number during the evolution of chameleons, however, in Rieppeleon brevicaudatus, we uncovered a chromosome number of 2n = 62, very unusual among squamates, originating from a number of chromosome splits. Despite the presence of the highly differentiated ZZ/ZW sex chromosomes in the genus Furcifer, we did not detect any unequivocal sexual differences in the karyotypes of any other studied species of chameleons tested using differential staining and comparative genomic hybridization, suggesting that sex chromosomes in most chameleons are only poorly differentiated. Full article
(This article belongs to the Special Issue Chromosomal Evolution)
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Open AccessArticle Functional Characterization of the Versatile MYB Gene Family Uncovered Their Important Roles in Plant Development and Responses to Drought and Waterlogging in Sesame
Genes 2017, 8(12), 362; https://doi.org/10.3390/genes8120362
Received: 18 October 2017 / Revised: 22 November 2017 / Accepted: 29 November 2017 / Published: 12 December 2017
Cited by 4 | Viewed by 1226 | PDF Full-text (9548 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The MYB gene family constitutes one of the largest transcription factors (TFs) modulating various biological processes in plants. Although genome-wide analysis of this gene family has been carried out in some species, only three MYB members have been functionally characterized heretofore in sesame
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The MYB gene family constitutes one of the largest transcription factors (TFs) modulating various biological processes in plants. Although genome-wide analysis of this gene family has been carried out in some species, only three MYB members have been functionally characterized heretofore in sesame (Sesamum indicum L.). Here, we identified a relatively high number (287) of sesame MYB genes (SIMYBs) with an uncommon overrepresentation of the 1R-subfamily. A total of 95% of SIMYBs was mapped unevenly onto the 16 linkage groups of the sesame genome with 55 SIMYBs tandemly duplicated. In addition, molecular characterization, gene structure, and evolutionary relationships of SIMYBs were established. Based on the close relationship between sesame and Arabidopsis thaliana, we uncovered that the functions of SIMYBs are highly diverse. A total of 65% of SIMYBs were commonly detected in five tissues, suggesting that they represent key TFs modulating sesame growth and development. Moreover, we found that SIMYBs regulate sesame responses to drought and waterlogging, which highlights the potential of SIMYBs towards improving stress tolerance in sesame. This work presents a comprehensive picture of the MYB gene family in sesame and paves the way for further functional validation of the members of this versatile gene family. Full article
(This article belongs to the Special Issue Genetic Regulation of Abiotic Stress Responses)
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Open AccessCase Report An Expanded Multi-Organ Disease Phenotype Associated with Mutations in YARS
Genes 2017, 8(12), 381; https://doi.org/10.3390/genes8120381
Received: 2 November 2017 / Revised: 24 November 2017 / Accepted: 29 November 2017 / Published: 11 December 2017
Cited by 4 | Viewed by 1034 | PDF Full-text (1335 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Whole exome sequence analysis was performed in a Swedish mother–father-affected proband trio with a phenotype characterized by progressive retinal degeneration with congenital nystagmus, profound congenital hearing impairment, primary amenorrhea, agenesis of the corpus callosum, and liver disease. A homozygous variant c.806T > C,
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Whole exome sequence analysis was performed in a Swedish mother–father-affected proband trio with a phenotype characterized by progressive retinal degeneration with congenital nystagmus, profound congenital hearing impairment, primary amenorrhea, agenesis of the corpus callosum, and liver disease. A homozygous variant c.806T > C, p.(F269S) in the tyrosyl-tRNA synthetase gene (YARS) was the only identified candidate variant consistent with autosomal recessive inheritance. Mutations in YARS have previously been associated with both autosomal dominant Charcot-Marie-Tooth syndrome and a recently reported autosomal recessive multiorgan disease. Herein, we propose that mutations in YARS underlie another clinical phenotype adding a second variant of the disease, including retinitis pigmentosa and deafness, to the spectrum of YARS-associated disorders. Full article
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Open AccessArticle The Alteration of Nasopharyngeal and Oropharyngeal Microbiota in Children with MPP and Non-MPP
Genes 2017, 8(12), 380; https://doi.org/10.3390/genes8120380
Received: 12 October 2017 / Revised: 5 December 2017 / Accepted: 5 December 2017 / Published: 11 December 2017
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Abstract
Background: In recent years, the morbidity of Mycoplasma pneumoniae pneumonia (MPP) has increased significantly in China. A growing number of studies indicate that imbalanced respiratory microbiota is associated with various respiratory diseases. Methods: We enrolled 119 children, including 60 pneumonia patients and 59
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Background: In recent years, the morbidity of Mycoplasma pneumoniae pneumonia (MPP) has increased significantly in China. A growing number of studies indicate that imbalanced respiratory microbiota is associated with various respiratory diseases. Methods: We enrolled 119 children, including 60 pneumonia patients and 59 healthy children. Nasopharyngeal (NP) and oropharyngeal (OP) sampling was performed for 16S ribosomal RNA (16S rRNA) gene analysis of all children. Sputum and OP swabs were obtained from patients for pathogen detection. Results: Both the NP and OP microbiota of patients differ significantly from that of healthy children. Diseased children harbor lower microbial diversity and a simpler co-occurrence network in NP and OP. In pneumonia patients, NP and OP microbiota showed greater similarities between each other, suggesting transmission of NP microbiota to the OP. Aside from clinically detected pathogens, NP and OP microbiota analysis has also identified possible pathogens in seven cases with unknown infections. Conclusion: NP and OP microbiota in MPP and non-MPP are definitely similar. Respiratory infection generates imbalanced NP microbiota, which has the potential to transmit to OP. Microbiota analysis also promises to compliment the present means of detecting respiratory pathogens. Full article
(This article belongs to the Section Microbial Genetics and Genomics)
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Open AccessArticle The Genome of the Northern Sea Otter (Enhydra lutris kenyoni)
Genes 2017, 8(12), 379; https://doi.org/10.3390/genes8120379
Received: 12 September 2017 / Revised: 28 November 2017 / Accepted: 1 December 2017 / Published: 11 December 2017
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Abstract
The northern sea otter inhabits coastal waters of the northern Pacific Ocean and is the largest member of the Mustelidae family. DNA sequencing methods that utilize microfluidic partitioned and non-partitioned library construction were used to establish the sea otter genome. The final assembly
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The northern sea otter inhabits coastal waters of the northern Pacific Ocean and is the largest member of the Mustelidae family. DNA sequencing methods that utilize microfluidic partitioned and non-partitioned library construction were used to establish the sea otter genome. The final assembly provided 2.426 Gbp of highly contiguous assembled genomic sequences with a scaffold N50 length of over 38 Mbp. We generated transcriptome data derived from a lymphoma to aid in the determination of functional elements. The assembled genome sequence and underlying sequence data are available at the National Center for Biotechnology Information (NCBI) under the BioProject accession number PRJNA388419. Full article
(This article belongs to the Section Technologies and Resources for Genetics)
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Open AccessArticle The Genome of the Beluga Whale (Delphinapterus leucas)
Genes 2017, 8(12), 378; https://doi.org/10.3390/genes8120378
Received: 12 September 2017 / Revised: 28 November 2017 / Accepted: 1 December 2017 / Published: 11 December 2017
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Abstract
The beluga whale is a cetacean that inhabits arctic and subarctic regions, and is the only living member of the genus Delphinapterus. The genome of the beluga whale was determined using DNA sequencing approaches that employed both microfluidic partitioning library and non-partitioned
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The beluga whale is a cetacean that inhabits arctic and subarctic regions, and is the only living member of the genus Delphinapterus. The genome of the beluga whale was determined using DNA sequencing approaches that employed both microfluidic partitioning library and non-partitioned library construction. The former allowed for the construction of a highly contiguous assembly with a scaffold N50 length of over 19 Mbp and total reconstruction of 2.32 Gbp. To aid our understanding of the functional elements, transcriptome data was also derived from brain, duodenum, heart, lung, spleen, and liver tissue. Assembled sequence and all of the underlying sequence data are available at the National Center for Biotechnology Information (NCBI) under the Bioproject accession number PRJNA360851A. Full article
(This article belongs to the Section Technologies and Resources for Genetics)
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Open AccessReview Mitochondria and α-Synuclein: Friends or Foes in the Pathogenesis of Parkinson’s Disease?
Genes 2017, 8(12), 377; https://doi.org/10.3390/genes8120377
Received: 31 October 2017 / Revised: 27 November 2017 / Accepted: 5 December 2017 / Published: 8 December 2017
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Abstract
Parkinson’s disease (PD) is a movement disorder characterized by dopaminergic nigrostriatal neuron degeneration and the formation of Lewy bodies (LB), pathological inclusions containing fibrils that are mainly composed of α-synuclein. Dopaminergic neurons, for their intrinsic characteristics, have a high energy demand that relies
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Parkinson’s disease (PD) is a movement disorder characterized by dopaminergic nigrostriatal neuron degeneration and the formation of Lewy bodies (LB), pathological inclusions containing fibrils that are mainly composed of α-synuclein. Dopaminergic neurons, for their intrinsic characteristics, have a high energy demand that relies on the efficiency of the mitochondria respiratory chain. Dysregulations of mitochondria, deriving from alterations of complex I protein or oxidative DNA damage, change the trafficking, size and morphology of these organelles. Of note, these mitochondrial bioenergetics defects have been related to PD. A series of experimental evidence supports that α-synuclein physiological action is relevant for mitochondrial homeostasis, while its pathological aggregation can negatively impinge on mitochondrial function. It thus appears that imbalances in the equilibrium between the reciprocal modulatory action of mitochondria and α-synuclein can contribute to PD onset by inducing neuronal impairment. This review will try to highlight the role of physiological and pathological α-synuclein in the modulation of mitochondrial functions. Full article
(This article belongs to the Special Issue Mitochondria and Aging)
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Open AccessReview Context-Dependent Role of IKKβ in Cancer
Genes 2017, 8(12), 376; https://doi.org/10.3390/genes8120376
Received: 31 October 2017 / Revised: 29 November 2017 / Accepted: 1 December 2017 / Published: 8 December 2017
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Abstract
Inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) is a kinase principally known as a positive regulator of the ubiquitous transcription factor family Nuclear Factor-kappa B (NF-κB). In addition, IKKβ also phosphorylates a number of other proteins that regulate many cellular processes,
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Inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) is a kinase principally known as a positive regulator of the ubiquitous transcription factor family Nuclear Factor-kappa B (NF-κB). In addition, IKKβ also phosphorylates a number of other proteins that regulate many cellular processes, from cell cycle to metabolism and differentiation. As a consequence, IKKβ affects cell physiology in a variety of ways and may promote or hamper tumoral transformation depending on hitherto unknown circumstances. In this article, we give an overview of the NF-κB-dependent and -independent functions of IKKβ. We also summarize the current knowledge about the relationship of IKKβ with cellular transformation and cancer, obtained mainly through the study of animal models with cell type-specific modifications in IKKβ expression or activity. Finally, we describe the most relevant data about IKKβ implication in cancer obtained from the analysis of the human tumoral samples gathered in The Cancer Genome Atlas (TCGA) and the Catalogue of Somatic Mutations in Cancer (COSMIC). Full article
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Open AccessReview Dualistic Role of BARD1 in Cancer
Genes 2017, 8(12), 375; https://doi.org/10.3390/genes8120375
Received: 24 October 2017 / Revised: 30 November 2017 / Accepted: 1 December 2017 / Published: 8 December 2017
Cited by 3 | Viewed by 1113 | PDF Full-text (786 KB) | HTML Full-text | XML Full-text
Abstract
BRCA1 Associated RING Domain 1 (BARD1) encodes a protein which interacts with the N-terminal region of BRCA1 in vivo and in vitro. The full length (FL) BARD1 mRNA includes 11 exons and encodes a protein comprising of six domains (N-terminal RING-finger domain, three
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BRCA1 Associated RING Domain 1 (BARD1) encodes a protein which interacts with the N-terminal region of BRCA1 in vivo and in vitro. The full length (FL) BARD1 mRNA includes 11 exons and encodes a protein comprising of six domains (N-terminal RING-finger domain, three Ankyrin repeats and two C-terminal BRCT domains) with different functions. Emerging data suggest that BARD1 can have both tumor-suppressor gene and oncogene functions in tumor initiation and progression. Indeed, whereas FL BARD1 protein acts as tumor-suppressor with and without BRCA1 interactions, aberrant splice variants of BARD1 have been detected in various cancers and have been shown to play an oncogenic role. Further evidence for a dualistic role came with the identification of BARD1 as a neuroblastoma predisposition gene in our genome wide association study which has demonstrated that single nucleotide polymorphisms in BARD1 can correlate with risk or can protect against cancer based on their association with the expression of FL and splice variants of BARD1. This review is an overview of how BARD1 functions in tumorigenesis with opposite effects in various types of cancer. Full article
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