Search Results (16,651)

β-D-Xylosidases (BXLs) are members of glycoside hydrolase family 3. They play essential roles in cell wall remodeling, plant development, and abiotic stress responses. BXL gene families have been systematically characterized in several crop species. However, a comprehensive analysis of BXL genes in cotton (Gossypium hirsutum), a globally important fiber and oilseed crop, is still lacking. In this study, we performed a genome-wide identification of BXL genes in allotetraploid cotton. A total of 25 GhBXL genes were identified and classified into six phylogenetic clades. Gene structure and conserved domain analyses showed that all GhBXL proteins possess the characteristic tripartite GH3 domain architecture. Chromosomal distribution and synteny analyses indicated that the expansion of the cotton BXL family may be associated with whole-genome duplication and allopolyploidization. Promoter cis-element analysis detected stress-responsive regulatory motifs in the GhBXL promoters, including STRE, W-box, DRE core, and as-1 elements. Under PEG-simulated drought and salt stress, expression profiling, independently confirmed by qRT-PCR, showed distinct temporal response patterns among GhBXL members. Weighted gene co-expression network analysis (WGCNA) further identified GhBXL-8, GhBXL-9, and GhBXL-20 as hub genes in stress-responsive modules. Their co-expressed partners were enriched in transcription factors, kinases, and stress-related proteins. These findings provide a systematic foundation for understanding the evolutionary dynamics and functional roles of BXL genes in cotton. They also highlight candidate genes for future functional investigation. Full article

Interferons (IFNs) are a family of cytokines which serve as the first line of defense against pathogen infections while also exerting critical immunomodulatory roles. IFNs can induce hundreds of IFN-stimulated genes (ISGs) with cell-specificity, yet a high-resolution comparison of time-serial ISG induction across cell types is lacking. By using RNA sequencing, we conducted a comparative transcriptomic profiling during time-serial IFN-γ stimulation for up to 24 h in HeLa and HEK293T cells, the two most widely used immortalized human cell lines. We uncovered remarkably stronger IFN responses in HeLa cells, regarding the global transcriptomic dynamics, the number of induced ISGs, and the level of ISG expression. Both cell lines share a core set of ISGs associated with canonical JAK-STAT signaling, yet HeLa uniquely activates additional inflammatory and adaptive immunity-related pathways. Despite the much weaker IFN response in HEK293T cells, we also identified a few HEK293T-specific ISGs, including several with crucial immune-related functions. Notably, transposable elements—including many adjacent to ISGs—are also highly up-regulated in HeLa cells, implying their potential links to ISG induction. Collectively, this study provides a high-resolution temporal atlas of IFN-γ-stimulated transcriptomic dynamics in HeLa and HEK293T cells, revealing the shared core module and cell-specific patterns of their interferon responses. Full article

Sulfur is an essential nutrient involved in plant growth, redox regulation, and responses to environmental stresses. Sulfate transporters (SULTRs) control sulfate uptake and distribution, thereby affecting sulfur availability for metabolic processes and stress adaptation. However, the characteristics and stress-responsive functions of SULTRs in the halophyte Sesuvium portulacastrum remain unclear. In this study, we identified and characterized the SULTR family in S. portulacastrum through phylogenetic analysis, gene structure comparison, conserved motif analysis, promoter characterization, synteny analysis, and expression profiling. A total of 22 SpSULTRs were identified and classified into three subfamilies. Most SpSULTRs contained conserved Sulfate_transp and STAS domains and were predicted to localize to the plasma membrane. Transcriptome analysis combined with qRT-PCR validation revealed that SpSULTRs displayed diverse tissue-specific expression patterns under salt, cadmium, and copper stresses. Of these, SpSULTR3;1 and SpSULTR3;2 showed strong responses to salt stress and were mainly expressed in leaves. Protein interaction predictions suggested that these two transporters may be associated with sulfur assimilation, antioxidant metabolism, and stress-related pathways. These results reveal the structural diversification and stress-responsive characteristics of the SULTR family in S. portulacastrum and provide a basis for further investigation of sulfur transport mechanisms underlying halophyte adaptation. Full article

Mounting evidence implicates dysregulation of the neuroimmune system in Alzheimer’s disease (AD). Neuroimmune cells, namely microglia and astrocytes, have the potential to contribute to AD through mechanisms such as promoting neuroinflammation and propagating amyloid-β (Aβ) and tau aggregates. Human induced pluripotent stem cell (hiPSC)-derived models offer advantages for studying the AD neuroimmune system, such as recapitulating genetic variants associated with the disease and allowing for precise manipulation of human cells in vitro. Here, we provide an overview of modern techniques for generating 2-dimensional (2D) monocultures and co-cultures, 3-dimensional (3D) organoids and assembloids, and chimeras containing hiPSC-derived microglia and astrocytes. Then, we highlight recent studies that have utilized hiPSC-derived neuroimmune models to investigate AD risk variants in genes encoding apolipoprotein E (APOE) and triggering receptor on myeloid cells 2 (TREM2), mutations known to cause familial AD in genes encoding presenilin 1 (PSEN1) and 2 (PSEN2) and amyloid precursor protein (APP), and trisomy 21 leading to Down syndrome-associated AD (DS-AD). We then briefly summarize recent studies that have utilized hiPSC-derived neuroimmune models lacking disease-associated variants to study the clearance of Aβ and tau aggregates. Finally, we discuss notable limitations of these models and reflect on future directions for this area of research, including the use of cultures with increasing cellular diversity and structural complexity, advancements in live-imaging techniques for detecting AD pathology in vitro, and drug screening. Full article

Rose rosette virus (RRV) causes witches’ broom disease in roses. This study examined whether differences in disease in these spatially distinct domains are associated with local changes in defense-related hormones and transcriptional reprogramming. The levels of defense-related phytohormones salicylic acid (SA), jasmonic acid (JA), 9-lipoxygenase (9-LOX), 13-lipoxygenase (13-LOX), and derived oxylipins were different in these distinct tissues. We curated differentially expressed genes involved in the biosynthesis, storage, and signaling of SA, JA, and oxylipins to reveal how specific defense pathways correlate with these distinct disease states. Gene ontology (GO) analysis and the Disease Resistance Analysis and Gene Orthology 3 (DRAGO3) pipeline revealed stress-associated genes and classical resistance (R) gene families that were differently expressed in these distinct tissue domains. Promoter analysis of defense-associated transcription factors and histone modifiers revealed hormone responsive elements, suggesting complex hormone crosstalk is involved in defense-related gene expression. We confirmed by RT-qPCR, a notable subset of defense genes in the chromosome 5 hotspot, specifically in the linkage group 5 (LG5) quantitative trait loci, linked to reduced RRV susceptibility, was altered in both field-infected and greenhouse-inoculated plants. The association of high versus low disease states with distinct defense hormone signatures and gene expression patterns suggests that local immune states, rather than whole-plant defenses, determine whether a cane becomes rosetted or remains asymptomatic. Full article

NAC proteins are a large family of plant transcription factors that play a key role in growth, development and responses to abiotic stress (drought, salinity). Various genomic studies across several species have identified NAC genes with specific responses to cold, drought and salinity. This study conducts a comprehensive genomic and transcriptomic analysis of FaNAC genes in strawberry (Fragaria x ananassa) to elucidate their role in response to drought and salinity. Using RNA-seq and validation by RT-qPCR, thirty-five FaNAC genes were identified that showed differential expression under both stress conditions. Their expression profiles were highly specific to tissue and stimulus type: some were induced in leaves and roots under both conditions, whilst others showed restricted induction. This suggests a specialised regulatory network rather than a uniform response. Phylogenetically, the FaNAC genes showed high homology with Arabidopsis orthologues and conserved collinearity between subgenomes. The promoters contained cis elements associated with hormones and stress, particularly ABA and MeJA. FaNAC6 was selected for its strong induction in leaves and roots in response to drought and salinity, as well as under oxidative stress and ABA. Its overexpression in Nicotiana benthamiana increased stress tolerance, improving photosynthesis and water-use efficiency, and was associated with the upregulation of genes involved in photosystems, electron transport and carbon fixation. Overall, FaNAC6 emerges as a promising candidate for further evaluation in strawberry breeding strategies to improve drought and salinity resilience. Full article

The identification of a pathogenic variant (PV) in one of the mismatch repair (MMR) genes confirms the diagnosis of Lynch syndrome (LS). Hence, the correct classification of MMR gene variants is of utmost importance for appropriate counselling, surveillance, and treatment of LS patients and their families. In 7/200 unrelated Tyrolean-suspected LS patients, we identified the rare variant MLH1:c.836T>G. Clinical and tumor data strongly indicate that this founder variant is associated with an increased risk for early-onset LS-associated tumors. We also demonstrate that the variant leads to aberrant mRNA splicing. However, the splice effect’s leakiness together with the small effect of the amino acid change p.(Val297Gly) encoded by the residual full-length transcripts in a functional assay preclude its formal classification as (likely) PV according to internationally accepted variant interpretation guidelines. The family histories of the carriers suggest that the obstacles to classify the variant as (likely) PV may be related with a reduced penetrance. Nonetheless, and despite the formal classification of MLH1:c.836T>G as a variant of uncertain significance, we show that carriers should undergo cancer surveillance and predictive testing should be offered to relatives. This variant illustrates the need for an improved classification framework for appropriate categorization of lower-penetrance alleles. Full article

GPR35 is a member of the G-protein-coupled receptor family and existing studies have shown that its expression may be negatively correlated with fat deposition in mice. However, the exact role of GPR35 in goat intramuscular preadipocytes’ adipogenic differentiation remains unknown. This study is the first to demonstrate that GPR35 inhibits the maturation and differentiation of goat intramuscular preadipocytes via activating the cAMP/PKA signaling pathway under in vitro culture conditions. The functional experimental results showed that GPR35 overexpression suppressed the adipogenic differentiation, lipid synthesis, and proliferation capacity of goat intramuscular preadipocytes, and concurrently downregulated the expression of adipogenic differentiation marker genes and cell proliferation marker genes. Conversely, GPR35 knockdown promoted lipid accumulation, reduced intracellular cAMP levels, and ultimately enhanced the differentiation and proliferation capacity of intramuscular preadipocytes. Treatment with the cAMP inhibitor SQ22536 and PKA phosphorylation inhibitor H89 successfully reversed the phenotypic changes induced by GPR35 overexpression, including abnormal lipid droplet morphology, decreased triglyceride (TG) content, and inhibition of the expression of genes related to adipocyte differentiation/proliferation/metabolism (such as CDK2, PCNA, and HSL). These results confirm that GPR35 mainly regulates intramuscular fat deposition in goats through the cAMP/PKA pathway, providing a new target for elucidating the molecular mechanism of lipid metabolism and goat molecular breeding. Full article

Background/Objectives: Contiguous Xq26.2 deletions involving FRMD7 and IGSF1 are rare and incompletely characterized. FRMD7 loss causes X-linked idiopathic infantile nystagmus (IIN), whereas IGSF1 loss causes central hypothyroidism and other pituitary-related abnormalities. We aimed to define the clinical and molecular spectrum of an Xq26.2 contiguous gene deletion in a large Bedouin kindred with infantile nystagmus. Methods: We clinically evaluated ten family members (3 males and 7 females); genomic analyses included chromosomal microarrays, whole-exome and whole-genome sequencing, breakpoint PCR, and Sanger sequencing. Results: We identified a novel 1.44-Mb Xq26.1-q26.2 deletion, NC_000023.11:g.130756102_132199443del (GRCh38), encompassing complete loss of FRMD7, IGSF1, ARHGAP36, OR13H1, and STK26 and partial deletion of the 5′ end of ENOX2. The deletion was molecularly confirmed in six family members. The kindred exhibited a broad phenotypic spectrum, from an asymptomatic confirmed female carrier to isolated nystagmus and combined ocular–endocrine manifestations. Nystagmus was highly penetrant, whereas endocrine abnormalities were less frequent and variable. Hypoprolactinemia occurred in one confirmed female carrier, and a confirmed hemizygous boy had low-normal free T4 without overt central hypothyroidism. The only relative with overt central hypothyroidism was not genotyped; therefore, co-segregation could not be established. Conclusions: These findings further delineate the clinical spectrum of Xq26.2 deletions, highlight marked intrafamilial variability, and support structural variant analysis in unexplained IIN and/or endocrine abnormalities. Longitudinal endocrine assessment of individuals with Xq26.2 deletions and at-risk relatives in affected families may enable early detection and treatment of hypothyroidism. Full article

The porcine interferon (IFN) system is highly diversified, particularly within Type I subfamilies, yet its evolutionary trajectory across domestication and breed formation remains poorly characterized. We performed a comprehensive comparative genomic and structural analysis of 432 IFN sequences spanning all IFN types across 11 Sus scrofa breeds representing commercial, indigenous, and wild/outgroup lineages. Phylogenetic reconstruction, pairwise dN/dS selection pressure analysis, and AlphaFold2-based 3D structure prediction coupled with DALI structural similarity mapping were integrated to resolve repertoire architecture, evolutionary constraints, and domestication-associated divergence. IFN repertoire organization is governed primarily by family identity rather than breed origin, with Type I IFN-α, -δ, and -ω subfamilies showing pronounced gene expansion in domestic breeds. Phylogenetic clustering and structural similarity consistently grouped sequences by subtype, independent of domestication history. Pervasive purifying selection (median ω = 0.48) maintained functional constraints across all lineages. Commercial breeds exhibited significantly higher within-category structural convergence alongside expanded repertoires, while structural conservation was evolutionarily decoupled from sequence-level selective pressure. Domestication potentially drove coordinated IFN repertoire expansion and structural conservation with related purifying selection at the gene level. These findings establish a genomic framework linking breed-specific IFN architecture to antiviral capacity and provide a foundation for immunogenetic-informed breeding strategies in the swine model. Full article

Heat shock proteins of the HSP70 family and their BAG co-chaperones regulate responses to oxidative stress, inflammation, apoptosis, and ischemia, all central to coronary artery disease (CAD) pathogenesis. The contribution of genetic variants within HSP70-family and BAG co-chaperone genes to CAD susceptibility remains unclear. Thus, we sought to evaluate associations of HSP70- and BAG-related SNPs with CAD risk and to characterize their potential regulatory effects using comprehensive bioinformatic analyses. A case–control cohort of 834 CAD patients and 1328 controls of Russian ethnicity was genotyped for 13 SNPs. Associations with CAD susceptibility and traits were tested using log-additive regression with adaptive permutation. Loci underwent functional annotation. The C allele of BAG1 rs706121 was associated with increased CAD risk overall (OR = 1.24, p_perm = 0.019), in males (OR = 1.39, p_perm = 0.002), and in smokers (OR = 1.39, p_perm = 0.020). BAG3 rs196329 was associated with lower risk in males (A allele: OR = 0.82, p_perm = 0.040), whereas HSPA6 rs753856 was associated with reduced risk in physically active individuals (G allele: OR = 0.61, p_perm = 0.008). Additional associations involved clinical or biochemical traits. Functional annotation identified potential regulatory effects, including eQTL associations, overlap with histone marks, and allele-dependent changes in transcription factor binding. HSP70 and BAG variants may contribute to CAD susceptibility and support sex- and lifestyle-informed risk assessment. Full article

Microbial remediation serves as a cost-effective and eco-friendly tactic for petroleum-contaminated sites. In real-world practices, petroleum-degrading microbial consortia display prominent superiority over single strains. To tap into their intrinsic synergistic degradation capacity, it is essential to dissect microbial commonalities, individual traits and functional complementarity for complicated bioremediation scenarios. This study applied bibliometric approaches to collect 15 well-documented representative petroleum-hydrocarbon-degrading strains, and summarized research progress via comparative genomic analysis. Pseudomonas aeruginosa, Bacillus subtilis and Rhodococcus erythropolis are the most frequently reported degraders with remarkable petroleum removal performance. Moreover, co-occurrence network analysis identifies Pseudomonas, Bacillus, Acinetobacter and Rhodococcus as core co-existing genera sustaining natural pollutant-degrading communities. Genomic evidence indicates these strains harbour abundant functional elements encoding diverse oxygenases, alcohol dehydrogenases, cytochrome P450 monooxygenases and key LuxR-, AraC- and GntR-family regulatory factors. P. aeruginosa has the highest copy numbers of catabolic enzyme genes, consistent with its outstanding degradation phenotype. Degraders from different genera exhibit high genetic heterogeneity, with accessory gene clusters significantly enriched in hydrocarbon degradation pathways. Six strains including P. aeruginosa and R. erythropolis assemble a complete gene cascade targeting recalcitrant polycyclic aromatic hydrocarbons. This work provides reliable genomic support for rational strain screening and synthetic-consortium optimization, facilitating knowledge-driven strategies for efficient petroleum bioremediation. Full article

Multiple acyl-CoA dehydrogenase deficiency (MADD) is considered an autosomal recessive disorder; yet, recent findings suggest up to 10% of cases may result from heterozygous electron transfer flavoprotein dehydrogenase (ETFDH) variants exhibiting dominant or dominant-like effects. Here, a novel heterozygous ETFDH variant (c.1798A>C, p.Asn600His) was identified within a three-generation family. The grandfather presented with muscular weakness at age 35, and the father developed similar symptoms at 19 following a tonsillectomy. Both were diagnosed with MADD based on muscle biopsies revealing neutral lipid accumulation and acylcarnitine profiles and responded fully to riboflavin therapy (150 mg/day). The two siblings, aged 8 and 10, carry the same mutation and show increased acyl-carnitine levels but remain asymptomatic due to early riboflavin treatment. Skin fibroblasts from affected individuals were immortalized and subjected to normal and reduced riboflavin levels. Gene expression analysis demonstrated unchanged ETFDH RNA but reduced protein levels in mutant cells, particularly under low riboflavin. Structural modelling suggested the Asn600His substitution destabilizes the protein, diminishing its mitochondrial function. Proximity ligation assays indicated a decreased interaction with mitochondrial complex III, while oxygen consumption via fatty acid oxidation was impaired, especially at reduced riboflavin. The novel ETFDH variant found in this family gives a possible dominant pattern of inheritance for MADD, where a single mutant allele impairs the mitochondrial metabolism, particularly under riboflavin-deficient conditions, and highlights the importance of early riboflavin supplementation in preventing clinical symptoms. Full article

Background: Endophytic fungi are important sources of structurally diverse antimicrobial natural products, but their potential to yield antitubercular scaffolds remains insufficiently explored. This study aimed to uncover new decalin polyketides from the endophytic fungus, Trichoderma longicollum 17007, and to evaluate their biological activity. Methods: Feature-based molecular networking (FBMN) analysis of the ethyl acetate extract from rice-based cultures was performed using trichoharzin as a seed compound to guide targeted isolation. Structures were established by HRMS, 1D and 2D NMR spectroscopy, NOESY analysis, and quantum chemical ECD calculations. Cytotoxicity and activity against the avirulent Mycobacterium tuberculosis H37Ra strain were evaluated, and genome mining was performed to identify a candidate biosynthetic gene cluster. Results: Six new decalin polyketides, tandyukisins K–P (1–6), and two known analogues, trichoharzin (7) and tandyukisin J (8), were isolated. Compounds 1–6 are C1-O-acetylated analogues bearing a 3-methylpentenedioate-type acyl side chain. Comparative ¹³C NMR analysis revealed empirical features useful for assigning side-chain attachment site, double-bond position and geometry. Tandyukisins K (1) and P (6) showed moderate activity against the avirulent M. tuberculosis H37Ra strain, with a MIC value of 12.5 μg/mL. Conclusions: These findings expand the structural diversity of decalin polyketides and provide the first evidence of antitubercular activity by this compound family. Full article

Elevated ammonia nitrogen significantly reduces the survival rate of Litopenaeus vannamei under low-salinity conditions. Low-salinity culture is widely adopted in shrimp farming but susceptible to ammonia accumulation; however, relevant studies mainly focus on juvenile shrimp under single stress or normal salinity. With the aim of exploring how L. vannamei responds physiologically and molecularly to elevated ammonia nitrogen after low-salinity adaptation, shrimp were gradually acclimated to 5‰ salinity. They were reared at 5‰ for one week before being exposed to high levels of ammonia nitrogen for 96 h. Under these conditions, the shrimp’s hepatopancreas showed antioxidant imbalance and oxidative damage. Elevated blood ammonia, urea nitrogen and uric acid reflected activated synthesis pathways that clear excess ammonia. Transcriptomic and metabolomic profiling at 12, 48, and 96 h revealed 112 DEGs and pronounced alterations in lipids and amino acid derivatives. Integrated gene-metabolite correlation analysis uncovered three core pathways, along with 11 key DEGs and 17 associated metabolites. In the secretion pathway, solute carrier family 4 (anion exchanger),member 2 (slc4a3) was strongly correlated with saquinavir and carnitine. In the metabolism pathway, nicotinamide/nicotinate riboside kinase (nmrk1), chitinase (chia), Gamma-glutamyltranspeptidase (ggt1), UDP-glucose 4-epimerase (gale), and spermine oxidase (smox) were linked to L-pyroglutamic acid, betaine, etc. In the immune pathway, mitogen-activated protein kinase 8/9/10 (bsk) and integrin beta 1 (cd29) were associated with leukotriene E4 and niacin. This study reveals that ammonia stress after low-salinity acclimation induces oxidative stress damage, elevated physiological changes in L. vannamei, and further elucidates the regulatory pathways underlying its response to ammonia nitrogen stress. Full article