Distinct Genes Research Articles

Decoding Peroxidase Gene Function in Heat Stress Adaptation of Tetranychus urticae: Unraveling Molecular Mechanisms of Short-Term Thermal Tolerance

Tetranychus urticae (Acari: Tetranychidae) is a widely distributed agricultural pest, and it possesses an exceptional capacity to withstand or adapt to short-term heat stress. To investigate the molecular mechanisms underlying this heat tolerance, using both transcriptome and whole-genome data, we identified six distinct POD genes in T. urticae and characterized their physicochemical properties and structural features. Real-time quantitative PCR (RT-qPCR) was utilized to analyze the expression profiles of these genes under short-term heat stress. Our results show that T. urticae mitigates heat-induced oxidative stress through the upregulation of POD gene expression, highlighting the critical role of these genes in the mite’s adaptive response to thermal stress. These findings contribute to a deeper understanding of the molecular pathways that enable T. urticae to survive in fluctuating thermal environments, which is increasingly relevant in the context of global climate change. Furthermore, this study provides a foundation for future research utilizing RNA interference (RNAi) technology to further investigate the functional roles of these POD genes and their potential as targets for pest control strategies.

Divergent Genetic Pathways Underlying Convergent Parasitic Behaviours in Blowflies.

Blowfly (Diptera: Calliphoridae) exhibit diverse feeding strategies, with most species developing on decomposing organic matter. However, parasitism has evolved within the family, and some species convergently gained the ability to explore the tissues of living vertebrate hosts, which imposes critical veterinary, medical, and agricultural issues worldwide. It is yet unknown how this phenotype has evolved and whether it is determined by the same genetic architecture in different species or not. To address these questions, we evaluated key behavioural phenotypes in species with contrasting feeding habits, focusing on female oviposition preferences and larval survival on distinct diets, both critical aspects of their life cycles. These assays allowed us to propose hypotheses of how oviposition and larval behaviours contribute to feeding habits displayed in nature for parasitic and saprophagous species. Additionally, a transcriptome-wide analysis revealed genes and functional pathways potentially linked to parasitic behaviour by comparing gene expression profiles and coding sequence evolution. In the genetic analysis, we identified genes with important functions related to the measured behaviours, revealing that distinct genes may underlie each independent case of parasitism evolution, suggesting a non-parallel evolutionary pathway for this convergent trait.

Energy metabolism, antioxidant defense system, metal transport, and ion homeostasis are key contributors to Cd tolerance in SSSL derived from wild rice.

Energy metabolism, antioxidant defense system, metal transport, and ion homeostasis are key contributors to Cd tolerance in SSSL derived from wild rice.

Microbial laden mobile phones from international conference attendees pose potential risks to public health and biosecurity

IntroductionMobile phones, contaminated with pathogenic microorganisms, have the potential to act as “trojan horses”. The microbial signatures present on their surfaces most probably vary across different geographical regions. As a result, mobile phones belonging to international conference attendees may serve as a model for global microbial dissemination, posing potential risks to public health and biosecurity. AimThis study aimed to profile the microbes present on mobile phones belonging to delegates attending an international scientific conference through use of metagenomic shotgun DNA sequencing. MethodsTwenty mobile phones, representing ten different geographical zones from around the world, were swabbed and pooled together into ten geographical-specific samples for high definition next-generation DNA sequencing. WONCA council members were invited to participate and provided verbal consent. Following DNA extraction, next generation sequencing, to a depth of approximately 10Gbp per sample, was undertaken on a v1.5 Illumina NovaSeq6000 system. Bioinformatic analysis was performed via the CosmosID platform. ResultsA total of 2204 microbial hits were accumulated across 20 mobile phones inclusive of 882 bacteria, 1229 viruses, 88 fungi and 5 protozoa. Of particular concern was the identification of 65 distinct antibiotic resistance genes and 86 virulence genes. Plant, animal and human pathogens, including ESKAPE and HACEK bacteria were found on mobile phones. Discussion/conclusionMobile phones of international attendees are contaminated with many & varied microorganisms. Further research is required to characterize the risks these devices pose for biosecurity and public health. Development of new policies which appropriately address and prevent such risks maybe warranted.

Deciphering the heterogeneous glucosinolates composition in leaves and seeds: strategies for developing Brassica napus genotypes with low seed glucosinolates content but high leaf glucosinolates content

Rapeseed cakes with low glucosinolates content (GC) possess high feeding value. However, the pursuit of low-GC seeds has inadvertently resulted in a reduction of GC in leaves, making plants more susceptible to stress and lowering their nutritional quality. Therefore, it is imperative to disrupt the tight association between GC in these two tissues and ultimately develop genotypes with low-GC seeds but high-GC leaves. The distinct mechanisms underlying glucosinolate (GSL) synthesis in these two tissues remain unclear. Here, we discovered that aliphatic and aromatic GSLs, rather than indole GSLs, contribute to the positive correlation between GC in seeds and leaves. We performed selective-sweep analyses and identified the genomic footprints left after decades of intense selection for low-GC seeds. By conducting genome-wide association studies and analyzing differentially expressed genes in high- and low-GC seeds and leaves, we compiled lists of distinct genes involved in GSL synthesis in leaves and seeds separately. In particular, BnMYB28 plays a key role in regulating GC in both seeds and leaves. Selection and manipulation of BnaC09.MYB28 would affect GC in both tissues. However, downregulation of BnaA02.MYB28 and/or BnaC02.MYB28 would likely reduce GC in seeds without causing a concurrent reduction in GC in leaves.

Enhancing cancer subtype classification through convolutional neural networks: a deepinsight analysis of TCGA gene expression data.

This study investigates the adaptation of DeepInsight for cancer subtype classification using high-dimensional gene expression data. Originally designed for non-image data, DeepInsight has been adapted for cancer classification. We evaluated DeepInsight's performance against several models, including support vector machines, LightGBM, neural networks, and decision trees, with and without the application of the Synthetic Minority Oversampling Technique. The study utilized gene expression data from breast, lung, and colon cancers. A novel multi-class feature selection method was introduced, using modified aggregated class activation maps to identify key genes across different cancer subtypes. These critical genes were further analyzed through Gene Ontology to explore their roles in significant biological processes. DeepInsight consistently outperformed traditional models in terms of F1 score across breast, lung, and colon cancer datasets, effectively addressing multi-class classification challenges. Notably, several top genes were identified as significant across multiple methods. Furthermore, we conducted a Gene Ontology analysis on the critical genes, including the top genes identified by DeepInsight and the common genes recognized through multiple methods. The adaptation of DeepInsight provides an approach to cancer subtype classification by transforming high-dimensional gene expression data into image representations. Utilizing aggregated class activation maps, it effectively identifies critical pixels within these images, enabling the discovery of distinct genes that may not be highlighted by other methods. DeepInsight demonstrates potential as a valuable tool for classifying cancer subtypes and critical genes.

Conserved sites on the influenza H1 and H3 hemagglutinin recognized by human antibodies.

Monoclonal antibodies (mAbs) targeting the influenza hemagglutinin (HA) can be used as prophylactics or templates for next-generation vaccines. Here, we isolated broad, subtype-neutralizing mAbs from human B cells recognizing the H1 or H3 HA "head" and a mAb engaging the conserved stem. The H1 mAbs bind the lateral patch epitope on HAs from 1933 to 2021 and a prepandemic swine H1N1 virus. We improved neutralization potency using directed evolution toward a contemporary H1 HA. Deep mutational scanning of four antigenically distinct H1N1 viruses identified potential viral escape pathways. For the H3 mAbs, we used cryo-electron microscopy to define their epitopes: One mAb binds the side of the HA head, accommodating the N133 glycan and a pocket underneath the receptor binding site; the other mAb recognizes an HA stem epitope that partially overlaps with previously characterized mAbs but with distinct antibody variable genes. Collectively, these mAbs identify conserved sites recognized by broadly-reactive mAbs that may be elicited by next-generation vaccines.

Fungal Argonaute proteins act in bidirectional cross-kingdom RNA interference during plant infection

Argonaute (AGO) proteins bind to small RNAs to induce RNA interference (RNAi), a conserved gene regulatory mechanism in animal, plant, and fungal kingdoms. Small RNAs of the fungal plant pathogen Botrytis cinerea were previously shown to translocate into plant cells and to bind to the host AGO, which induced cross-kingdom RNAi to promote infection. However, the role of pathogen AGOs during host infection stayed elusive. In this study, we revealed that members of fungal plant pathogen B. cinerea BcAGO family contribute to plant infection. BcAGO1 binds to both fungal and plant small RNAs during infection and acts in bidirectional cross-kingdom RNAi, from fungus to plant and vice versa. BcAGO2 also binds fungal and plant small RNAs but acts independent from BcAGO1 by regulating distinct genes. Nevertheless, BcAGO2 is important for infection, as it is required for effective pathogen small RNA delivery into host cells and fungal induced cross-kingdom RNAi. Providing these mechanistic insights of pathogen AGOs promises to improve RNAi-based crop protection strategies.

Abstract 1089: Developing subtype-specific pediatric cancer molecular targets by aggregating diverse genomic data resources to the pediatric cancer (PeCan) knowledge base portal

Abstract Knowledge about molecular targets for pediatric cancer has accelerated exponentially in recent years thanks to the increased application of multi-omics profiling in both research and clinical settings. The efficacy of genomic-based clinical interventions may depend on whether observed genomic abnormalities are fundamental to the pathogenesis of a specific cancer subtype. At present such information is limited in pediatric cancer due to the rapid evolution of subtype discovery and classification as well as disease heterogeneity owing to the presence of many rare cancer types. To develop a comprehensive resource of molecular targets in pediatric cancer subtypes, we have integrated somatic variants in pediatric cancer samples (n=∼5, 500) currently hosted in PeCan Portal (http://pecan.stjude.coud) with those (n=∼1, 400) profiled by NCI’s Childhood Cancer Data Initiative (CCDI) molecular characterization program. To leverage the recently developed WHO CNS5 classification of CNS tumors, we reclassified 2, 167 relevant samples based on molecular drivers and histology as a major update to our pediatric cancer ontology definitions, which have recently become a shared standard in the CCDI community. To determine driver genes in disease pathways relevant to specific cancer types, we analyzed the pathogenicity of SNVs and indels, CNVs, SVs and gene fusions and integrated the findings with driver genes reported in 176 publications. A total of 469 distinct driver genes were mapped to 40 pathways across the 22 major pediatric cancer types, which include 3 types of hematological malignancies (HM), 10 types of CNS tumor and 9 types of solid tumor (ST). Pathways with driver genes disrupted across the broad spectrum of cancer types include cell cycle, chromatin remodeling, PI-3K, RAS signaling and telomere maintenance. By contrast the vast majority (>90%) of the transcription factors (TF) are lineage-specific— among the 128 TF genes identified as driver genes, only 11 affect multiple lineages. These include MYC/MYCN which affect HM, ST and CNS tumors; ERG, EWSR1, FLI1 and WT1 which affect HM and ST; and KLF4, MED12, MN1, MYB and TCF4 which affect CNS and HM. These results highlight the importance of developing an infrastructure for exploring mutation prevalence in driver genes and pathways at the cancer subtype level, which will be supported in the upcoming release of the PeCan portal. This, coupled with new features for dynamic exploration of mutational signatures, global expression maps and gene-level transcription across the cancer subtype classification tree, will greatly expand our knowledge of molecular targets and vulnerabilities in pediatric cancer, paving the way for novel therapeutic advancements Citation Format: David B. Finkelstein, Delaram Rahbarinia, Ramzi Alsallaq, Stephanie Sandor, Michael Macias, Jian Wang, Sue Qiu, Brian Curran, Michael Edmonson, Andrew Thrasher, Jobin Sunny, James Madson, Scott Foy, Brent Orr, Mark R. Wilkinson, Clay McLeod, Michael Rusch, Xiaotu Ma, Jinghui Zhang. Developing subtype-specific pediatric cancer molecular targets by aggregating diverse genomic data resources to the pediatric cancer (PeCan) knowledge base portal [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1089.

Dual Mutations in MSMEG_0965 and MSMEG_1380 Confer High-Level Resistance to Bortezomib and Linezolid by Both Reducing Drug Intake and Increasing Efflux in Mycobacterium smegmatis.

The emergence of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis strains poses serious challenges to global tuberculosis control, highlighting the urgent need to elucidate the mechanisms underlying multidrug resistance. In this study, we screened for spontaneous bortezomib (BTZ)-resistant Mycobacterium smegmatis (Msm) mutants and identified a strain, Msm-R1-2, exhibiting 16- and 64-fold increases in minimum inhibitory concentrations (MICs) to BTZ and linezolid (LZD), respectively, compared to the parental strain. Whole-genome sequencing revealed resistance-associated mutations in two functionally distinct genes: MSMEG_1380, encoding a transcriptional regulator involved in efflux pump expression, and MSMEG_0965, encoding a porin protein. CRISPR-Cpf1-assisted gene knockout and editing experiments confirmed that single mutations in either MSMEG_1380 or MSMEG_0965 caused low-level resistance (4-fold MIC increase) to BTZ and LZD, while dual mutations conferred resistance levels comparable to Msm-R1-2, with 16- and 64-fold increases in MICs for BTZ and LZD, respectively. An ethidium bromide accumulation assay demonstrated that mutations in MSMEG_0965 reduce cell wall permeability, contributing to multidrug resistance. Furthermore, quantitative real-time PCR showed that mutations in MSMEG_1380 upregulate the mmpS5-mmpL5 efflux system. Together, these dual mechanisms function synergistically: restricted drug entry combined with enhanced drug efflux confers robust multidrug resistance. These findings provide novel insights into the evolutionary mechanisms of resistance in mycobacteria.

Virulence genes and antibiotic resistance profiling of staphylococcus species isolated from mastitic dairy cows in and around Bahir dar, Ethiopia

BackgroundMastitis is one of the primary causes of economic and production losses in the dairy cattle industry. Bacterial infections are the most significant contributors to bovine mastitis, with Staphylococcus species among the most prevalent and challenging pathogens. This issue is especially severe in low- and middle-income countries, including Ethiopia, where a comprehensive understanding of Staphylococcus species in clinical and subclinical mastitis remains poorly understood. This is particularly true in the regions surrounding Bahir Dar, where comprehensive data on the genetic determinants of virulence and resistance in Staphylococcus species causing bovine mastitis are notably lacking. The lack of such molecular insights hampers the development of targeted therapeutic and preventive strategies for managing mastitis in the region. Therefore, the present study aimed to investigate the virulence gene profiles and antimicrobial resistance (AMR) patterns of Staphylococcus species isolated from mastitic dairy cows in and around Bahir Dar, Ethiopia.MethodologyA cross-sectional study was conducted from March 2023 to December 2023 to investigate the molecular characteristics of Staphylococcus species and their antimicrobial resistance profiles in dairy cows with mastitis. A total of 150 lactating cows from 21 farms were included in the study, with 600 milk samples collected from the four-quarters of each cow. The samples were screened via the California mastitis test and physical examination. Staphylococcus species isolates were identified and single-plex PCR was used to detect virulence genes. The antimicrobial resistance profile of the isolates was determined via the Kary–Bauer disk diffusion method.ResultsThe overall quarter-level mastitis incidence was 19.83% (119/600). Among 119 mastitis-positive samples, 80 samples were bacteriologically confirmed to harbor Staphylococcus species with eight different Staphylococcus species, of which Staphylococcus chromogenes was the most prevalent isolate (19%), followed by S. aureus, S. hyicus and S. epidermidis (15%), S. hemolyticus (11%), S. simulans and S. xylosus (10%), and S. intermedius (5%). Seven distinct virulence genes were identified with varying frequencies: Coa (35%), seb (33.33%), mecA (31.67%), icaD (31.67%), Hla (20%), Hlb (10%), and sea (8.3%). The icaD and seb genes were observed in all 8 species with respective percentages (S. hemolyticus (62.5, 37.5), S. aureus (44.44, 55.55), S. hyicus (44.44, 44.44), S. epidermidis 2 (22.22, 44.44), chromogenes (9.1, 9.1), S. intermidius (33.33, 33.33), S. simulance (16.67, 16.67) and S. xylosus (16.67, 16.67). Both the Hla and Hlb genes were detected in the same three distinct species, with percentages of S. aureus (44.44; 22.22%), S. hemolyticus (42.5; 25%) and S. hyicus (55.55; 22.22). S. aureus exhibited the highest proportion of mecA-positive isolates, with 6 out of 9 isolates (66.67%) carrying the gene. All the isolated Staphylococcus species were 100% resistant to penicillin, and except for S. chromogenes and S. xylosus, the remaining 6 species of Staphylococcus also exhibited 100% resistance to tetracycline. Among all MDR isolates, 6/9 (66.7%) S. aureus, (5/8; 62.5%) S. hemolyticus, and (6/9; 66.7%) S. hyicus were resistant to up to seven classes of antibiotics. A lower frequency of MDR isolates was detected among S. simulans and S. xylosus (both at 2/6; 33.33%), resistant to up to five antibiotics.ConclusionsAmong the identified Staphylococcus species, S. chromogenes emerged as the dominant isolate. All eight isolated species harbored two or more virulence genes, with nearly one-third of the isolates carrying the mecA gene, underscoring their pathogenic potential in causing bovine mastitis. Furthermore, all the Staphylococcus isolates in this study were resistant to penicillin and were multidrug resistant.

Genomic characteristics and antibiotic resistance profiles of monophasic Salmonella Typhimurium in Shaanxi Province, China.

Monophasic Salmonella Typhimurium, characterized by the absence of phase II flagellar antigens, has become increasingly prevalent as a foodborne pathogen, raising significant public health concerns due to its multidrug resistance. This study investigated the genomic characteristics and antibiotic resistance profiles of the monophasic Salmonella Typhimurium strains isolated from patients and food sources in Shaanxi Province, China. A total of 58 strains were collected between 2020 and 2021, with 4 strains isolated from food and 54 from patients. Whole genome sequencing was performed to assess genomic features. Antimicrobial susceptibility was tested against 17 antimicrobial agents using the broth dilution method, while pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing were employed for genetic characterization and epidemiological analysis. Phylogenetic analysis was conducted using single nucleotide polymorphism clustering. Our results revealed that all the strains belonged to the ST34 and did not carry virulence genes on pSLT (NC_003277). There were 12 strains carrying the STM2757 gene. The isolates exhibited a considerable diversity in PFGE subtypes. Phenotypic antimicrobial resistance showed that the strains were most resistant to tetracycline (94.34%; 50/53) and ampicillin (94.34%; 50/53), followed by streptomycin (88.68%; 47/53) and ampicillin/sulbactam (64.15%; 34/53). Resistance gene prediction highlighted the presence of 64 distinct genes, with aac(6')-Iaa found in all strains (100%) and tet(B) in 93.1% of strains. Notably, the floR gene, relevant for resistance to phenicols, was observed in 44.83% of isolates. Genomic analysis revealed that 96.55% of strains were positive for the sodC1 virulence gene, whereas only 10.34% carried the sopE gene. The most plasmid replicon was IncQ1 (84.48%; 49/58), followed by IncHI2 (32.76%; 19/58) and IncHI2A (32.76%; 19/58). Single nucleotide polymorphism analysis showed that 2 strains were clustered together with SRR17830210 (UK outbreak isolate) with a bootstrap value of 0.949. There were only 12 allelic differences between SNXiAn21SAL011 and the reference strain. Conclusively, the monophasic Salmonella Typhimurium ST34 strains in Shaanxi Province demonstrated unique genomic and antimicrobial resistance traits. This study may help to prevent outbreaks and rationalize salmonellosis antimicrobial therapeutics.

Repeat Expansions with Small TTTCA Insertions in MARCHF6 Cause Familial Myoclonus without Epilepsy.

Familial adult myoclonus epilepsy (FAME) is a rare autosomal dominant disorder caused by the same intronic TTTTA/TTTCA repeat expansion in seven distinct genes. TTTTA-only expansions are benign, whereas those containing TTTCA insertions are pathogenic. We investigated the genetic basis of dominant cortical myoclonus without seizures in two unrelated families. Repeat-primed polymerase chain reaction (PCR), long-range PCR, and nanopore sequencing were used to detect and characterize expansions at known FAME loci. We identified a novel repeat expansion in MARCHF6, comprising 388 to 454 elongated TTTTA repeats and 5 to 11 TTTCA repeats at the 3'-terminus, segregating with cortical myoclonus in 8 affected individuals. This configuration shows meiotic stability but low-level somatic variability in blood. We observed an inverse correlation between the number of TTTCA repeats and the age at myoclonus onset. These findings indicate that as little as five TTTCA repeats combined with expanded TTTTA repeats can cause cortical myoclonus without epilepsy, highlighting the potential mechanisms underlying FAME pathophysiology. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Establishment of a Prognostic Risk Score Model Based on Bioinformatics for Ferroptosis and Cuproptosis‐Related Genes in Gastric Cancer

ABSTRACTBackgroundGastric cancer (GC) stands out as one of the most prevalent forms of malignant tumors globally, characterized by a notably high mortality rate. In spite of progress in medical science and treatment alternatives, the survival rate over 5 years continues to stay under 40%. In the realm of cancer biology, ferroptosis and cuproptosis represent two distinctive forms of programmed cell death that are gaining attention for their roles in tumor progression and treatment response. Ferroptosis is characterized by its dependence on lipid peroxidation and the resultant accumulation of reactive oxygen species (ROS) which ultimately induce cellular demise. On the other hand, cuproptosis operates through a different pathway, characterized by the direct interaction of copper ions with the acylating elements of the tricarboxylic acid cycle which ultimately leads to cell death. Ferroptosis and cuproptosis, that are types of programmed cell death associated with metals, play a significant role in the onset and progression of GC.ObjectiveThis study intends to employ bioinformatics techniques to pinpoint genes that are differentially expressed genes (DEGs) linked to ferroptosis and cuproptosis that are significant for the prognosis of GC. Additionally, the study aims to develop a prognostic risk score model that will facilitate the prediction of patient outcomes based on these identified genetic factors.MethodsTranscriptome and clinical data from tissues of 412 patients with gastric adenocarcinoma and 36 adjacent non‐cancerous tissues were obtained from The Cancer Genome Atlas stomach adenocarcinoma collection (TCGA‐STAD) database. This analysis aimed to identify differentially DEGs associated with ferroptosis and cuproptosis that are linked to the prognosis of GC patients. Furthermore, gene expression data along with clinical details from 433 GC patients in the gene expression omnibus (GEO) database were combined to create a prognostic risk score model. Further investigations were carried out, encompassing pathway enrichment analysis, assessment of tumor mutation burden (TMB), evaluation of tumor immune dysfunction and exclusion (TIDE), single‐sample gene set enrichment analysis (ssGSEA), and analysis of the tumor microenvironment (TME). Validation was achieved through immunohistochemical examination of relevant gene expression in samples collected from GC patients.ResultsTwelve DEGs linked to the prognosis of GC were discovered, leading to the creation of a prognostic risk score model that incorporates four genes involved in ferroptosis (NOX4, GLS2, MYB, NNMT) alongside one gene related to cuproptosis (GCSH). Analysis of pathway enrichment revealed a notable accumulation of the DEGs within several signaling pathways associated with the extracellular matrix. In addition, examinations of immune cell infiltration demonstrated significant variations in TMB, the quantity of immune cells present within the tumor, their functional roles, and the TME when contrasting high‐risk and low‐risk groups. Findings from immunohistochemical studies showed that GCSH and GLS2 show varying levels of expression in gastric cancer tissues and have a correlation with patient prognosis.ConclusionA prognostic risk model specifically designed for gastric cancer was developed, comprising five distinct genes. This model demonstrates a strong ability to accurately forecast both the prognosis of gastric cancer patients and the effectiveness of immunotherapy treatments they may undergo.

MiR-508-5p regulates macrophage polarization via targeting TSGA10 to promote malignant behavior in esophageal cancer cells

Background Esophageal cancer (EC) is among the deadliest malignancies in humans, with various miRNAs shown to regulate its progression by targeting distinct genes. miR-508-5p was identified as being linked to the malignant behavior of various tumors. Nevertheless, the precise role and mechanism of miR-508-5p in esophageal cancer (EC) remain ambiguous. Objective This investigation focuses on the role and mechanism of the miR-508-5p/TSGA10 axis in the progression of EC. Methods The expression of miR-508-5p and TSGA10 in EC cell lines was evaluated using quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Cell transfection techniques were used to knock down miR-508-5p and observe its effects on cell proliferation, migration, invasion, and apoptosis. A dual-luciferase reporter gene assay was conducted to verify the targeting relationship of miR-508-5p with TSGA10. Co-culture studies were undertaken to examine the regulatory effect of the miR-508-5p/TSGA10 axis on the polarization state of tumor-associated macrophages (TAMs) and the malignant behavior of EC cells. Results The expression of miR-508-5p was significantly elevated in EC cells. Knocking down miR-508-5p curbed cell proliferation, migration, and invasion while promoting apoptosis. TSGA10 was validated as a primary target gene of miR-508-5p. miR-508-5p knockdown could inhibit the M2 polarization of TAMs by upregulating TSGA10, thereby suppressing the tumorigenic behavior of EC cells. Conclusion miR-508-5p promotes the M2 polarization of TAMs and enhances the malignant behavior of EC cells by inhibiting TSGA10.

Suspended detrital particles support a distinct microbial ecosystem in Palmer Canyon, Antarctica, a coastal biological hotspot

The coastal region of the Western Antarctic Peninsula is considered a biological hotspot with high levels of phytoplankton productivity and krill biomass. Recent in situ observations and particle modeling studies of Palmer Canyon, a deep bathymetric feature in the region, demonstrated the presence of a recirculating eddy that traps particles, retaining a distinct particle layer over the summer season. We applied metagenomic sequencing and Imaging Flow Cytobot (IFCB) analysis to characterize the microbial community in the particle layer. We sampled across the upper water column (< 200 m) along a transect to identify the locations of increased particle density, categorizing particles into either living cells or cellular detritus via IFCB. An indicator species analysis of community composition demonstrated the diatom Corethron and the bacteria Sulfitobacter were significantly highly abundant in samples with high levels of living cells, while the mixotrophic dinoflagellate Prorocentrum texanum and prokaryotes Methanomassiliicoccales and Fluviicola taffensis were significantly more abundant in samples with high detritus within the particle layer. From our metagenomic analysis, the significantly differentially abundant metabolic pathway genes in the particle layer of Palmer Canyon included pathways for anaerobic metabolism, such as methanogenesis and sulfate reduction. Overall, our results indicate that distinct microbial species and metabolic pathway genes are present in the retained particle layer of Palmer Canyon.

A systematic review of hereditary neurological disorders diagnosed by whole exome sequencing in Pakistani population: updates from 2014 to November 2024.

Hereditary neurological disorders (HNDs) are a group of heterogeneous disorders characterized by significant genetic and clinical variability. HNDs are caused by dysfunction of the central or peripheral nervous system due to aberrant electrical impulses. More than 600 types of HNDs have been documented, and overall, these are the second leading cause of death worldwide. This systematic review is based on a retrospective analysis of research articles reporting HNDs diagnosed using whole exome sequencing in Pakistani families from 2014 to November 2024. Original research articles were retrieved through online surveys, notably Google Scholar, PubMed, and the Web of Science. Based on stringent selection criteria, 89 research articles and 188 variants published around 10years were considered. Variants and research articles were cross-checked and further validated in different online databases/resources to confirm their genomic nomenclature and pathogenicity according to the ACMG guidelines. A total of 188 variants in 143 distinct genes in Pakistani families identified through whole exome sequencing have been reported to date that caused genetic and clinically heterogeneous HNDs. Consanguineous parentage was found in around 90% of cases, and approximately 91% of causative alleles were reported in homozygous state showing a predominant burden of HNDs because of blood-related marriages. The most frequent type of pathogenic variants were single nucleotide substitutions (92 missense and 39 nonsense). Among 188 variants, 76 variants were reported in 2024 and 44 variants were observed in 2023. Pakistan is the fifth most populous country in the world having an extreme prevalence of consanguinity resulting in the expression of pathogenic variants due to homozygosity. Therefore, there is a prevalence of genetic disorders particularly rare monogenic or Mendelian disorders. Next-generation sequencing approach is strongly recommended for diagnosis, early therapeutic intervention and genetic counselling.

In silico analysis of betaine aldehyde dehydrogenase (BADH) gene in different cultivars of Chenopodium quinoa.

Chenopodium quinoa is an emerging halophyte plant that has gained significant attention from researchers in recent years due to its high nutritional value and resilience to environmental stress. This plant serves as an excellent substitute for rice and wheat. However, there has been limited research on it, leaving many of its genes still unidentified. The objective of this research was to identify gene patterns and conduct a bioinformatics analysis across various fields. The expression sequence of the betaine aldehyde dehydrogenase (BADH) gene was predicted using bioinformatics software such as PlantCARE and PlantPan. The findings indicated that different cultivars provide valuable information regarding resistance to the binding sites of MYB transcription factors, hormone response regions, and both promoter and enhancer regions, which contain 32 cis-regulatory elements. This emphasized the role of the BADH gene in responding to abiotic stress. Additionally, the research revealed that the BADH gene activates oxidoreductase activity across different cultivars, influencing NAD or NADP receptors that contribute to stress resistance. The protein lengths identified were 454 and 500 amino acids, respectively. Chloroplast analysis revealed that the GC content for the BADH gene was 37%. From this analysis, it was determined that out of 128 distinct functional genes in the genome, approximately 84 are protein-coding genes. An examination of the domains and motifs in the target genes showed that they contain two conserved sequences: Aldedh and DUF1487. Furthermore, miRNA analysis and promoter investigations indicated that the BADH gene plays a vital role in activating processes related to arginase, protein kinases, superoxide dismutase, tubulins, and membrane proteins. The gene is also crucial for activating nuclear transcription factors through receptor activation. In conclusion, the results suggest that BADH genes contribute to the plant's resistance to salt stress through various mechanisms. Stress acts as a trigger for the activation of this gene, effectively safeguarding the plant against the detrimental effects of environmental stresses.

Genetic analysis of two bladder exstrophy populations of South Asian and North American origin.

Genetic analysis of two bladder exstrophy populations of South Asian and North American origin.

Using Residual Newborn Blood Spots to Investigate CpG Methylation in Relation to Air Pollution and Congenital Heart Defects.

The prevalence of tetralogy of Fallot (TOF), a common congenital heart defect, has increased over the last two decades. Genome-wide CpG methylation patterns were assessed and analyzed in relation to gestational air pollution exposure among 24 infants with TOF and 24 sex-matched control infants without a birth defect from a North Carolina population-based, case-control study of major structural birth defects (2006-2011). Air pollution exposure during obstetric weeks 3-8 was assigned based on self-reported residence. DNA was extracted from residual newborn blood spots, and DNA methylation levels were measured using the Illumina EPIC Array. Cases had higher exposure to both PM2 .5 and O3 compared to controls. No specific CpG loci were statistically significantly associated with TOF status or air pollution exposure; however, we observed associations between TOF case status and DNA methylation at specific genomic regions with genes enriched for functions in metabolism. Additionally, there were significant regions that displayed differential DNA methylation in relation to air pollution exposure within genes involved in apoptosis, necrosis, inflammation, and immune response pathways. Generally, air pollution exposure and TOF were associated with differential DNA methylation in distinct genes. These results highlight suggestive links between the environment, epigenome, and TOF to be further investigated in larger studies.