Now more than ever, the understanding of the genetics and evolution of the gene mechanisms and the networks of different molecular pathways acting on plant abiotic stress tolerance has an important role in the finding of new solutions and approaches mitigating the effects of global climate changes, thus contributing to a correct equilibrium among human needs, food security and human health and wellbeing [...] Full article

The study was conducted with C31 and C80 genotypes of the potato (Solanum tuberosum L.), which are tolerant and susceptible to phosphite (Phi, H₂PO₃), respectively. To decipher the molecular mechanisms underlying tolerance and susceptibility to Phi in the potato, RNA sequencing was used to study the global transcriptional patterns of the two genotypes. Media were prepared with 0.25 and 0.50 mM Phi, No-phosphorus (P), and 1.25 mM (phosphate, Pi as control). The values of fragments per kilobase of exon per million mapped fragments of the samples were also subjected to a principal component analysis, grouping the biological replicates of each sample. Using stringent criteria, a minimum of 819 differential (DEGs) were detected in both C80-Phi-0.25_vs_C80-Phi-0.50 (comprising 517 upregulated and 302 downregulated) and C80-Phi-0.50_vs_C80-Phi-0.25 (comprising 302 upregulated and 517 downregulated) and a maximum of 5214 DEGs in both C31-Con_vs_C31-Phi-0.25 (comprising 1947 upregulated and 3267 downregulated) and C31-Phi-0.25_vs_C31-Con (comprising 3267 upregulated and 1947 downregulated). DEGs related to the ribosome, plant hormone signal transduction, photosynthesis, and plant–pathogen interaction performed important functions under Phi stress, as shown by the Kyoto Encyclopedia of Genes and Genomes annotation. The expressions of transcription factors increased significantly in C31 compared with C80. For example, the expressions of Soltu.DM.01G047240, Soltu.DM.08G015900, Soltu.DM.06G012130, and Soltu.DM.08G012710 increased under P deficiency conditions (Phi-0.25, Phi-0.50, and No-P) relative to the control (P sufficiency) in C31. This study adds to the growing body of transcriptome data on Phi stress and provides important clues to the Phi tolerance response of the C31 genotype. Full article

Genetic background may partly explain differences in muscle responses to internal or external stimuli. Muscle disuse involves various degrees of skeletal muscle atrophy due to inactivity and mechanical unloading. Whether and to which extent genetic background impacts disuse atrophy and retraining in individuals of different ages are currently unclear. Here, we provide a brief overview of relevant literature on the contribution of genetics to muscle disuse, retraining, and aging, and offer a perspective on unanswered questions on the subject that may open new venues for research. Full article

The capsalid monogeneans are important pathogens that generally infect marine fishes and have a substantial impact on fish welfare in aquaculture systems worldwide. However, the current mitogenome information on capsalids has received little attention, limiting the understanding of their evolution and phylogenetic relationships with other monogeneans. This paper reports the complete mitochondrial genomes of Capsala katsuwoni and Capsala martinieri for the first time, which we obtained using a next-generation sequencing method. The mitogenomes of C. katsuwoni and C. martinieri are 13,265 and 13,984 bp in length, respectively. Both species contain the typical 12 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and a control region. The genome compositions show a moderate A+T bias (66.5% and 63.9% for C. katsuwoni and C. martinieri, respectively) and exhibit a negative AT skew but a positive GC skew in both species. One gene block rearrangement was found in C. katsuwoni in comparison with other capsalid species. Instead of being basal to the Gyrodactylidea and Dactylogyridea or being clustered with Dactylogyridea, all species of Capsalidea are grouped into a monophyletic clade. Our results clarify the gene rearrangement process and evolutionary status of Capsalidae and lay a foundation for further phylogenetic studies of monogeneans. Full article

Background: Hepatocellular carcinoma (HCC) is the second most common malignancy with increasing cancer deaths worldwide. HCC is mainly diagnosed at its advanced stage, and treatment with FDA-approved sorafenib, the multikinase inhibitor drug, is advised. Acquired resistance against sorafenib develops through several pathways involving hypoxia, autophagy, high glycolysis, or glutaminolysis. Small non-coding RNAs, similar to microRNAs (miRNAs), are also known to affect sorafenib resistance in HCC. However, there is a lack of information regarding the significance of differentially expressed miRNA (if any) on autophagy and glutamine regulation in sorafenib-resistant HCC. Methods: The expression of autophagy and glutaminolysis genes was checked in both parental and sorafenib resistant HepG2 cell lines by real-time PCR. MTT and Annexin/PI assays were also performed in the presence of inhibitors such as chloroquine (autophagy inhibitor) and BPTES (glutaminolysis inhibitor). Next generation sequencing and in silico analysis were performed to select autophagy and glutamine addiction-specific microRNA. Selected miRNA were transfected into both HepG2 cells to examine its effect on autophagy and glutamine addiction in regulating sorafenib-resistant HCC. Results: Our in vitro study depicted a higher expression of genes encoding autophagy and glutaminolysis in sorafenib-resistant HepG2 cells. Moreover, inhibitors for autophagy (chloroquine) and glutaminolysis (BPTES) showed a diminished level of cell viability and augmentation in cell apoptosis of sorafenib-resistant HepG2 cells. NGS and real-time PCR demonstrated the downregulated expression of miR-23b-3p in sorafenib-resistant cells compared to parental cells. In silico analysis showed that miR-23b-3p specifically targeted autophagy through ATG12 and glutaminolysis through GLS1. In transfection assays, mimics of miR-23b-3p demonstrated reduced gene expression for both ATG12 and GLS1, decreased cell viability, and increased cell apoptosis of sorafenib-resistant HepG2 cells, whereas the antimiRs of miR-23b-3p demonstrated contrasting results. Conclusion: Our study highlights the cytoprotective role of autophagy and glutamine addiction modulated by miR-23b-3p (tumor suppressor), suggesting new approaches to curb sorafenib resistance in HCC. Full article

Immunophenotypic characterization of leukemic cells with the use of flow cytometry (FC) is a fundamental tool in acute lymphoblastic leukemia (ALL) diagnostics. A variety of genetic aberrations underlie specific B-cell precursor ALL (BCP-ALL) subtypes and their identification is of great importance for risk group stratification. These aberrations include: ETV6::RUNX1 fusion gene, Philadelphia chromosome (BCR::ABL1 fusion gene), rearrangements of the KMT2A, TCF3::PBX1 fusion gene and changes in chromosome number (hyperdiploidy and hypodiploidy). Diagnostic panels for BCP-ALL usually include B-cell lineage specific antigens: CD19, CD10, CD20, maturation stage markers: CD34, CD10, CD38, TdT, IgM and other markers useful for possible genetic subtype indication. Some genetic features of leukemic cells (blasts) are associated with expression of certain antigens. This review comprehensively summarizes all known research data on genotype-immunophenotype correlations in BCP-ALL. In some cases, single molecules are predictive of particular genetic subtypes, i.e., NG2 with KMT2A gene rearrangements or CD123 with hyperdiploidy. However, much more information on possible genotype or prognosis can be obtained with wider (≥8-color) panels. In several studies, a quantitative antigen expression scale and advanced statistical analyses were used to further increase the specificity and sensitivity of genotype/immunophenotype correlation detection. Fast detection of possible genotype/immunophenotype correlations makes multicolor flow cytometry an essential tool for initial leukemia diagnostics and stratification. Full article

Background: The pathogenesis of ankylosing spondylitis (AS) remains undetermined. Ferroptosis is a newly discovered form of regulated cell death involved in multiple autoimmune diseases. Currently, there are no reports on the connection between ferroptosis and AS. Methods: AS samples from the Gene Expression Omnibus were divided into two subgroups using consensus clustering of ferroptosis-related genes (FRGs). Weighted gene co-expression network analysis (WGCNA) of the intergroup differentially expressed genes (DEGs) and protein–protein interaction (PPI) analysis of the key module were used to screen out hub genes. A multifactor regulatory network was then constructed based on hub genes. Results: The 52 AS patients in dataset GSE73754 were divided into cluster 1 (n = 24) and cluster 2 (n = 28). DEGs were mainly enriched in pathways related to mitochondria, ubiquitin, and neurodegeneration. Candidate hub genes, screened by PPI and WGCNA, were intersected. Subsequently, 12 overlapping genes were identified as definitive hub genes. A multifactor interaction network with 45 nodes and 150 edges was generated, comprising the 12 hub genes and 32 non-coding RNAs. Conclusions: AS can be divided into two subtypes according to FRG expression. Ferroptosis might play a regulatory role in AS. Tailoring treatment according to the ferroptosis status of AS patients can be a promising direction. Full article

Unraveling the origin of molecular pathways underlying the evolution of adaptive traits is essential for understanding how new lineages emerge, including the relative contribution of conserved ancestral traits and newly evolved derived traits. Here, we investigated the evolutionary divergence of sex pheromone communication from moths (mostly nocturnal) to butterflies (mostly diurnal) that occurred ~119 million years ago. In moths, it is the females that typically emit pheromones to attract male mates, but in butterflies males emit pheromones that are used by females for mate choice. The molecular bases of sex pheromone communication are well understood in moths, but they have remained relatively unexplored in butterflies. We used a combination of transcriptomics, real time qPCR, and phylogenetics to identify genes involved in the different steps (i.e., production, regulation, and reception) of sex pheromone communication of the butterfly Bicyclus anynana. Our results show that the biosynthesis and reception of sex pheromones relies both on moth-specific gene families (reductases) and on more ancestral insect gene families (desaturases, olfactory receptors, odorant binding proteins). Interestingly, B. anynana appears to use what was believed to be the moth-specific neuropeptide Pheromone Biosynthesis Activating Neuropeptide (PBAN) for regulating sex pheromone production. Altogether, our results suggest that a mosaic pattern best explains how sex pheromone communication evolved in butterflies, with some molecular components derived from moths, and others conserved from more ancient insect ancestors. This is the first large-scale investigation of the genetic pathways underlying sex pheromone communication in a butterfly. Full article

The influence of proinflammatory challenges, such as maternal immune activation (MIA) or postnatal exposure to drugs of abuse, on brain molecular pathways has been reported. On the other hand, the simultaneous effects of MIA and drugs of abuse have been less studied and sometimes offered inconsistent results. The effects of morphine exposure on a pig model of viral-elicited MIA were characterized in the prefrontal cortex of males and females using RNA-sequencing and gene network analysis. Interacting and main effects of morphine, MIA, and sex were detected in approximately 2000 genes (false discovery rate-adjusted p-value < 0.05). Among the enriched molecular categories (false discovery rate-adjusted p-value < 0.05 and −1.5 > normalized enrichment score > 1.5) were the cell adhesion molecule pathways associated with inflammation and neuronal development and the long-term depression pathway associated with synaptic strength. Gene networks that integrate gene connectivity and expression profiles displayed the impact of morphine-by-MIA interaction effects on the pathways. The cell adhesion molecules and long-term depression networks presented an antagonistic effect between morphine and MIA. The differential expression between the double-challenged group and the baseline saline-treated Controls was less extreme than the individual challenges. The previous findings advance the knowledge about the effects of prenatal MIA and postnatal morphine exposure on the prefrontal cortex pathways. Full article

Over the past few decades, gene therapy has gained immense importance in medical research as a promising treatment strategy for diseases such as cancer, AIDS, Alzheimer’s disease, and many genetic disorders. When a gene needs to be delivered to a target cell inside the human body, it has to pass a large number of barriers through the extracellular and intracellular environment. This is why the delivery of naked genes and nucleic acids is highly unfavorable, and gene delivery requires suitable vectors that can carry the gene cargo to the target site and protect it from biological degradation. To date, medical research has come up with two types of gene delivery vectors, which are viral and nonviral vectors. The ability of viruses to protect transgenes from biological degradation and their capability to efficiently cross cellular barriers have allowed gene therapy research to develop new approaches utilizing viruses and their different genomes as vectors for gene delivery. Although viral vectors are very efficient, science has also come up with numerous nonviral systems based on cationic lipids, cationic polymers, and inorganic particles that provide sustainable gene expression without triggering unwanted inflammatory and immune reactions, and that are considered nontoxic. In this review, we discuss in detail the latest data available on all viral and nonviral vectors used in gene delivery. The mechanisms of viral and nonviral vector-based gene delivery are presented, and the advantages and disadvantages of all types of vectors are also given. Full article

Congenital heart disease (CHD) is one of the most common forms of birth defects worldwide, with a prevalence of 1–2% in newborns. CHD is a multifactorial disease partially caused by genetic defects, including chromosomal abnormalities and single gene mutations. Here, we describe the Sidra Cardiac Registry, which includes 52 families and a total of 178 individuals, and investigate the genetic etiology of CHD in Qatar. We reviewed the results of genetic tests conducted in patients as part of their clinical evaluation, including chromosomal testing. We also performed whole exome sequencing (WES) to identify potential causative variants. Sixteen patients with CHD had chromosomal abnormalities that explained their complex CHD phenotype, including six patients with trisomy 21. Moreover, using exome analysis, we identified potential CHD variants in 24 patients, revealing 65 potential variants in 56 genes. Four variants were classified as pathogenic/likely pathogenic based on the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) classification; these variants were detected in four patients. This study sheds light on several potential genetic variants contributing to the development of CHD. Additional functional studies are needed to better understand the role of the identified variants in the pathogenesis of CHD. Full article

The orexigenic hormone ghrelin has multifaceted roles in health and disease. We have reported that ablation of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), protects against metabolic dysfunction of adipose tissues in aging. Our further observation interestingly revealed that GHS-R deficiency phenocopies the effects of myokine irisin. In this study, we aim to determine whether GHS-R affects the metabolic functions of aging skeletal muscle and whether GHS-R regulates the muscular functions via irisin. We first studied the expression of metabolic signature genes in gastrocnemius muscle of young, middle-aged and old mice. Then, old GHS-R knockout (Ghsr^−/−) mice and their wild type counterparts were used to assess the impact of GHS-R ablation on the metabolic characteristics of gastrocnemius and soleus muscle. There was an increase of GHS-R expression in skeletal muscle during aging, inversely correlated with the decline of metabolic functions. Remarkedly the muscle of old GHS-R knockout (Ghsr^−/−) mice exhibited a youthful metabolic profile and better maintenance of oxidative type 2 muscle fibers. Furthermore, old Ghsr^−/− mice showed improved treadmill performance, supporting better functionality. Also intriguing to note was the fact that old GHS-R-ablated mice showed increased expression of the irisin precursor FNDC5 in the muscle and elevated plasma irisin levels in circulation, which supports a potential interrelationship between GHS-R and irisin. Overall, our work suggests that GHS-R has deleterious effects on the metabolism of aging muscle, which may be at least partially mediated by myokine irisin. Full article

In a subset of acute myeloid leukemia (AML) cases, the core binding factor beta subunit gene (CBFB) was rearranged via inv(16)(p13.1q22) or t(16;16)(p13.1;q22), in which the smooth muscle myosin heavy chain 11 gene (MYH11) was the partner (CBFB::MYH11). Rare variants of CBFB rearrangement occurring via non-classic chromosomal aberrations have been reported, such as t(1;16), t(2;16), t(3;16), t(5;16), and t(16;19), but the partners of CBFB have not been characterized. We report a case of AML with a complex karyotype, including t(2;16)(q37;q22), in which the protein phosphatase 1 regulatory subunit 7 gene (PPP1R7) at chromosome 2q37 was rearranged with CBFB (CBFB::PPP1R7). This abnormality was inconspicuous by conventional karyotype and interphase fluorescence in situ hybridization (FISH), thus leading to an initial interpretation of inv(16)(p13.1q22); however, metaphase FISH showed that the CBFB rearrangement involved chromosome 2. Using whole genome and Sanger sequencing, the breakpoints were identified as being located in intron 5 of CBFB and intron 7 of PPP1R7. A microhomology of CAG was found in the break and reconnection sites of CBFB and PPP1R7, thus supporting the formation of CBFB::PPP1R7 by microhomology-mediated end joining. Full article

Several apolipoprotein genes are located at the APOE locus on chromosome 19q13.32. This study explored the genetic determinants of cardiometabolic traits and metabolic syndrome at the APOE locus in a Taiwanese population. A total of 81,387 Taiwan Biobank (TWB) participants were enrolled to undergo genotype–phenotype analysis using data from the Axiom Genome-Wide CHB arrays. Regional association analysis with conditional analysis revealed lead single-nucleotide variations (SNVs) at the APOE locus: APOE rs7412 and rs429358 for total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol levels; CLPTM1 rs3786505 and rs11672748 for LDL and HDL cholesterol levels; and APOC1 rs438811 and APOE-APOC1 rs439401 for serum triglyceride levels. Genotype–phenotype association analysis revealed a significant association of rs429358 and rs438811 with metabolic syndrome and of rs7412, rs438811, and rs439401 with serum albumin levels (p < 0.0015). Stepwise regression analysis indicated that CLPTM1 variants were independently associated with LDL and HDL cholesterol levels (p = 3.10 × 10⁻¹⁵ for rs3786505 and p = 1.48 × 10⁻¹⁵ for rs11672748, respectively). APOE rs429358 and APOC1 rs438811 were also independently associated with metabolic syndrome (p = 2.29 × 10⁻¹⁴) and serum albumin levels (p = 3.80 × 10⁻⁶), respectively. In conclusion, in addition to APOE variants, CLPTM1 is a novel candidate locus for LDL and HDL cholesterol levels at the APOE gene region in Taiwan. Our data also indicated that APOE and APOC1 variants were independently associated with metabolic syndrome and serum albumin levels, respectively. These results revealed the crucial role of genetic variants at the APOE locus in predicting cardiometabolic traits and metabolic syndrome. Full article