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At least 19 recordsLinked to original sources

PubMed2026

Molecular characterization of 16 MAPK genes in silver carp (Hypophthalmichthys molitrix) and the differences of their mRNA expression between Qiandao Lake and Taihu Lake.

Mitogen-activated protein kinase (MAPK), a serine-threonine protein kinase, is involved in a variety of stress-induced responses and also plays an important regulatory role in cell metabolism. In the study the open reading frames (ORFs) of 16 MAPK genes in silver carp (Hypophthalmichthys molitrix) were obtained and verified, with the evaluations of their taxonomy, structures, conserved motifs, and evolutionary linkages. And the expression patterns of these genes in the silver carp from Qiandao Lake and Taihu Lake were explored for better understanding the response of MAPK genes to different water environment. MAPK genes of silver carp were divided into three subfamilies, including extracellular signal-regulated kinase (ERK) subfamily, p38 subfamily and C-Jun N-terminal kinase (JNK) subfamily. All these genes possessed similar structures and conserved motifs of MAPK family. Realtime qPCR revealed that the expression patterns of 10 MAPK genes (ScMAPK1, ScMAPK3, ScMAPK4, ScMAPK7, ScMAPK15, ScMAPK8a, ScMAPK8b, ScMAPK9, ScMAPK10 and ScMAPK11) in head kidney, spleen and gill of silver carp in Taihu Lake and Qiandao Lake were different. These findings provide a basis for further research on the function of MAPK in silver carp.

Animals↗

PubMed2025

Role of AprA and pyocyanin from Pseudomonas aeruginosa on Staphylococcus aureus tolerance to silver.

The opportunistic pathogens Staphylococcus aureus and Pseudomonas aeruginosa are often found together causing persistent infections where they exhibit complex interactions that affect their virulence and resistance to treatment. We sought to clarify how interactions between these organisms affect their resistance to the antimicrobial metal silver (AgNO3). As previous work showed that cell-free supernatant from P. aeruginosa enhances the resistance of S. aureus, we aimed to identify the exact factor(s) responsible for this increase. Using molecular weight cutoff filters and proteomics, we identified the protein AprA and pyocyanin as the responsible factors. Transposon-mediated disruption of aprA led to the production of supernatant which could not enhance the silver tolerance of S. aureus. These findings suggest that the protease AprA from P. aeruginosa plays an important role in increasing the tolerance of S. aureus to AgNO3 via in part by mediating the levels of pyocyanin which in turn reduces Ag2+ to detoxify it.

Pseudomonas aeruginosa↗

PubMed2025

Biogenic Synthesis and Characterization of Hypecoum pendulum Mediated Silver Nanoparticles: Revealed Outstanding Anticancer and Genotoxic Potentials.

Fabrication of silver nanoparticles by green approach is the most effective and eco-friendly technique in recent technologies. The current study aimed to generate a simple, valid, and justifiable method for biogenic synthesis of silver nanoparticles (HP-AgNPs) using aqueous extract of Hypecoum pendulum L.(HP) and to assess their in vitro anticancer and genotoxic potentials on baby hamster kidney cell (BHK-21) and human blood lymphocytes using 3-(4,5-dimethylthiazol-2-yl-)-2,5-di-phenyltetrazolium bromide (MTT) and alkaline comet assay, respectively. HP-AgNP characterization was done using UV-vis spectrometry, EDX, SEM, XRD, and FTIR techniques. The crystalline nature of HP-AgNPs with a particle size of 36.3 nm was assessed using the XRD technique. The surface morphologies with a particle size of 80 nm were verified by SEM analysis. UV spectroscopy verified the existence of HP-AgNPs by yielding a sharp peak at 417 nm with an absorbance intensity of 1.54. FTIR assessment revealed the existence of different functional moieties that contribute to the HP-AgNPs stabilization and reduction. Similarly, EDX analysis revealed Ag as a principal element (49%). MTT assay showed significant cytotoxicity by Doxorubicin and HP-AgNPs with a smaller IC50 value of 104.21 ± 4.33 and 134.91 ± 6.33 μg/mL correlated to HP extract (229.84 ± 4.66 μg/mL). The outcomes of the comet assay revealed potential DNA damage in a positive trend with concentration (25-600 μg/mL). HP-AgNP-treated lymphocytes showed higher DNA damage as compared to HP extract-treated cells, but less damage as compared to a positive control, H2O2. These outcomes showed that HP-AgNPs have demonstrated promising anticancer and genotoxic action than HP extract due to their size and shape.

Silver↗

PubMed2026

Biogenic Silver Nanoparticles from the Cell-Free Supernatant of Mychonastes sp. B1: Antibacterial and Antibiofilm Effects, and Wound Healing Activity Supported by Gene and Protein Expression Analysis.

The biogenic synthesis of silver nanoparticles (AgNPs) using microalgae provides a sustainable alternative to conventional physicochemical methods. In this study, AgNPs were synthesized from the cell-free supernatant of the freshwater microalga Mychonastes sp. B1 and characterized by ultraviolet-visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), and field-emission scanning electron microscopy with energy-dispersive X-ray spectroscopy (FE-SEM/EDS). The nanoparticles were predominantly spherical (15-55 nm), highly stable (ζ =  - 42.8 mV), and appeared to be capped by extracellular polymeric substances. The biogenic AgNPs (GS-AgNPs) exhibited potent antibacterial activity, with minimum inhibitory concentrations (MICs) of 2.0 µg/mL against Staphylococcus aureus and 2.5 µg/mL against Pseudomonas aeruginosa, and significantly (p < 0.05) inhibited biofilm formation. Fibroblast viability remained at or above 80% at AgNP concentrations up to 1.5 µg/mL, which promoted cell migration and increased wound closure by 8.1% at 24 h (p < 0.05). Exposure to 1.5 µg/mL AgNPs significantly upregulated extracellular matrix markers (Col1a1 2.3-fold, Fn1 3.3-fold at mRNA level; COL1A1 2.1-fold, FN1 2.7-fold at the protein level). These findings indicate that GS-AgNPs possess antimicrobial and wound healing properties, highlighting their potential as biocompatible nanomaterials for biomedical applications.

Silver↗

PubMed2026

Integrative analysis of transcriptome and DNA methylome dynamics during caudal fin regeneration in silver pomfret (Pampus argenteus).

Caudal fin regeneration in teleost fish is a complex, multi-stage process involving coordinated molecular and cellular changes. While the role of epigenetic regulation particularly DNA methylation has been studied in model freshwater species such as zebrafish, its contribution to regeneration in marine teleosts remains largely unexplored. In this study, we integrated transcriptomic and DNA methylomic data to characterize the temporal dynamics of gene expression and methylation during caudal fin regeneration in the silver pomfret (Pampus argenteus). Using RNA-sequencing and reduced representation bisulfite sequencing (RRBS) at three biologically critical time points 1, 3, and 7 days post-amputation (dpa), we characterized the spatiotemporal molecular landscape of caudal fin regeneration. These time points capture the key transitional phases of wound healing and inflammation (1 dpa), blastema formation and progenitor proliferation (3 dpa), and regenerative outgrowth with tissue remodeling (7 dpa), enabling robust detection of the major molecular programs underlying epimorphic regeneration. Concurrently, CG-methylome analysis identified thousands of dynamically changing differentially methylated regions (DMRs). A strong global inverse correlation was observed between promoter methylation and gene expression. Integrative analysis pinpointed key regeneration genes (fgf20a, msxb, sox9b) whose expression was associated with dynamic methylation changes in their promoters or gene bodies. We conclude that DNA methylation is a dynamic and key regulatory layer that acts in concert with transcriptional reprogramming to coordinate tissue regeneration, providing new insights into the epigenetic mechanisms underlying complex regenerative processes in teleosts.

Animals↗

PubMed2026

The genome sequence of the Silver Colonel, Odontomyia argentata (Fabricius, 1794) (Diptera: Stratiomyidae).

We present a genome assembly from an individual female Odontomyia argentata (Silver Colonel; Arthropoda; Insecta; Diptera; Stratiomyidae). The assembly contains two haplotypes with total lengths of 1 950.48 megabases and 1 937.58 megabases. Most of haplotype 1 (95.92%) is scaffolded into 6 chromosomal pseudomolecules. Haplotype 2 was assembled to scaffold level. The mitochondrial genome has also been assembled, with a length of 17.0 kilobases. This assembly was generated as part of the Darwin Tree of Life project, which produces genomes for eukaryotic species found in Britain and Ireland.

Diptera↗

PubMed2025

The chromosome-level genome assembly and annotation of the silver-lipped pearl oyster, Pinctada maxima.

The silver-lipped pearl oyster (Pinctada maxima) is a valuable tropical aquaculture species, playing a crucial economic role in the global pearl industry. However, the lack of genomic reference limits our in-depth understanding of this species in genome-based breeding, conservation, evolution and adaptation. Here, annotated chromosome-level reference genome for P. maxima was generated by integrating PacBio long-read sequencing, Illumina short-read sequencing, and Hi-C sequencing data. The total genome size is 1,264.93 Mb, with contig N50 and scaffold N50 of 649 kb and 89.19 Mb, respectively. The majority (97.94%) of the assembled genome was anchored to the 14 chromosomes by Hi-C analysis. The relatively high genome completeness was observed, with 97.38% (metazoa_odb10 database) and 95.26% (mollusca_odb10 database) in BUSCO analysis. Genome annotation revealed approximately 65.46% of the repeat sequences and 26,315 protein-coding genes. Comparative genome analysis revealed 28 expanded and 48 contracted families (p < 0.05) in P. maxima, with 3.2% of genes (894) being species-specific. This chromosome-level genome serves as an essential resource for research in evolutionary genomics, phylogenetics, and biomineralization.

Animals↗

PubMed2025

Aggregation-induced Electrochemiluminescence of AgNCs Enhanced with AuNPs@MXene Composites for Ultrasensitive Detection of microRNA.

MXene, a two-dimensional nanomaterial, has metal conductivity, high electronegativity, functionalized with surface groups, which make it widely applicable in catalysis and biosensing. However, studies on the principle of enhanced electrochemiluminescence (ECL) by MXene composites and the improvement of their performance in catalyzing the ECL reaction are still in their infancy. In this study, gold nanoparticles (AuNPs) are obtained by mild reductive reduction and loaded in situ on the Ti3C2Tx MXene surface to form the composites (AuNPs@MXene). In oxygenated PBS test buffer, AuNPs@MXene enhance the ECL emission of silver nanoclusters (AgNCs) with aggregation-induced electrochemiluminescence (AIECL) properties as luminophore. Approximately 7.5-fold enhancement of ECL signals is obtained by using two ECL enhancement strategies: an efficient AIECL emitter and a co-reaction accelerator. The special nucleic acid structure with "Three Way Junction (TWJ)" enables an ultra-sensitive detection of microRNA, providing an efficient and ultra-sensitive method for microRNA detection. The biosensor achieves a wide detection range of microRNA-21 from 100 aM to 1 nM, with a low detection limit of 31 aM, and exhibits excellent stability, selectivity and high reproducibility in real samples.

MicroRNAs↗

PubMed2026

Sex-specific ethylene responses drive floral sexual plasticity in Cannabis sativa.

Cannabis sativa L. exhibits pronounced sexual plasticity in which both XX and XY plants can undergo floral phenotypic sex reversal in response to ethylene modulation, yet the underlying molecular mechanisms remain poorly defined. Here, we present the most extensive multi-omic analysis of ethylene-induced sex change in C. sativa to date, integrating over 130 RNA-seq libraries, ethylene pathway metabolite quantification, and whole-genome sequencing across three XX and XY genotypes. Treatments with silver thiosulfate and ethephon induced more than 80% phenotypic conversion, but transcriptomic responses diverged sharply between XX and XY plants. Profiling 47 ERGs revealed 14 high-confidence candidates, including CsACS1, CsACO5, CsERF1, and CsMTN, with sex-specific and temporal expression patterns that show dynamic ethylene mediation of plasticity. Early transcriptional activation occurred prior to the emergence of flowers, within 18 h of sex-change treatments and the photoperiod-induced transition to flowering. As opposite-sex floral tissues emerged, ethylene-related gene expression shifted accordingly within developing floral organs, with distinct sets of genes stabilizing the opposite-sex phenotype in XX and XY plants. Several candidates were located in non-recombining regions of the X chromosome or were absent from the Y chromosome, and most exhibited low nucleotide diversity, consistent with functional constraint. These results provide a high-resolution view of ethylene-responsive sexual plasticity in cannabis and show that the shared capacity for sex reversal in XX and XY plants is implemented through distinct regulatory trajectories that produce opposite-sex floral phenotypes. This work expands the mechanistic understanding of sex expression in dioecious species and identifies candidate genes relevant to the development of sex-stable cultivars.

Ethylenes↗

PubMed2026

Rapid and exceptionally small-scale adaptation of the alpine plant Cardamine resedifolia to mining-contaminated soils in multi-stress condition.

The mechanisms by which plants tolerate soil contamination have been studied in details in controlled laboratory conditions, but they still remain largely unexplored in natural conditions where mixtures of contaminants are present in soils and their effects might interact with other environmental variables. This is especially true in high-altitude alpine environments, where abiotic stress is naturally heightened, but which so far have received little attention in environmental pollution studies. As we were interested in the tolerance mechanisms at play on very fine spatiotemporal scales for alpine plants growing under multi-stress conditions, we chose Cardamine resedifolia as our biological model. This plant is indeed frequently found in areas contaminated by Trace Metals and Metalloids and Polycyclic Aromatic Hydrocarbons in high elevation. We studied populations from former copper, silver-lead, and coal mines in alpine environments, along with populations growing on nearby reference soils. We measured genetic variability within populations as well as genetic differentiation between them, and tested for local adaptation to soil contamination using reciprocal transplants. Population pairs showing signs of local adaptation were then examined using genome scans to identify genes potentially under selection. We found high levels of genetic differentiation between populations growing on contaminated and reference soils a few dozen meters apart. In most cases local adaptation was detected, especially in former copper mines. Genome scans identified genes involved in metal stress management as potentially being under selection. This study provides evidence for rapid adaptation to human-induced pollution in alpine plants at remarkably small spatial scales. It offers new insights into the short-term ecological and evolutionary consequences of mining activities in alpine ecosystems, particularly in relation to substrate-driven differentiation.

Alpine plants↗

PubMed2024

High yield of monogenic short stature in children from Kurdistan, Iraq: A genetic testing algorithm for consanguineous families.

PURPOSE: Genetic testing in consanguineous families advances the general comprehension of pathophysiological pathways. However, short stature (SS) genetics remain unexplored in a defined consanguineous cohort. This study examines a unique pediatric cohort from Sulaimani, Iraq, aiming to inspire a genetic testing algorithm for similar populations. METHODS: Among 280 SS referrals from 2018-2020, 64 children met inclusion criteria (from consanguineous families; height ≤ -2.25 SD), 51 provided informed consent (30 females; 31 syndromic SS) and underwent investigation, primarily via exome sequencing. Prioritized variants were evaluated by the American College of Medical Genetics and Genomics standards. A comparative analysis was conducted by juxtaposing our findings against published gene panels for SS. RESULTS: A genetic cause of SS was elucidated in 31 of 51 (61%) participants. Pathogenic variants were found in genes involved in the GH-IGF-1 axis (GHR and SOX3), thyroid axis (TSHR), growth plate (CTSK, COL1A2, COL10A1, DYM, FN1, LTBP3, MMP13, NPR2, and SHOX), signal transduction (PTPN11), DNA/RNA replication (DNAJC21, GZF1, and LIG4), cytoskeletal structure (CCDC8, FLNA, and PCNT), transmembrane transport (SLC34A3 and SLC7A7), enzyme coding (CYP27B1, GALNS, and GNPTG), and ciliogenesis (CFAP410). Two additional participants had Silver-Russell syndrome and 1 had del22q.11.21. Syndromic SS was predictive in identifying a monogenic condition. Using a gene panel would yield positive results in only 10% to 33% of cases. CONCLUSION: A tailored testing strategy is essential to increase diagnostic yield in children with SS from consanguineous populations.

Humans↗

PubMed2025

Municipal sewage as a pathway for multidrug-resistant KPC-producing Klebsiella pneumoniae from hospital effluent to urban stream: challenges for wastewater management.

Carbapenemase-producing Klebsiella pneumoniae is among the mainly reasons for death from bacterial infection associated with antibiotic resistance. Its widespread dissemination, especially due to KPC enzyme, is one of the main challenges in One Health perspective. Here, we studied 42 KPC-producing K. pneumoniae isolates from hospital wastewater, municipal wastewater from wastewater treatment plant (WWTP), and urban stream which receives treated municipal effluent. The isolates presented broad resistance to β-lactams antibiotics, as well as to fluoroquinolones, and show antibiotic resistance profile very similar, even those from out-of-hospital settings. Along to blaKPC gene, blaCTX-M-1 (33,3 %, n = 14), blaCTX-M-8 (19 %, n = 8), qnrB (52,3 %, n = 22), qnrS (2,38 %, n = 1), and rmtB (19 %, n = 8) were detected. There was a predominance of gene that confers tolerance to silver and copper metals, as well as to virulence factor related to enterobactin and colibactin production. Macrorestriction genomic analysis by XbaI enzyme demonstrated several pulsotype, but some ones are related. Isolates from hospital wastewater were detected after 4 months at the same sampling point, as well as similar to those detected in WWTP and urban stream demonstrating the effluents role as spreaders of antibiotic resistance. This study provides data on the characterization of KPC-producing K. pneumoniae, which contributes to the epidemiological characterization of human pathogens transmitted by aquatic matrices. In view of the universal sanitation and control of antimicrobial resistance in the One Health perspective, greater investment in effluent treatment is necessary to avoid contamination and environmental dissemination of antibiotic-resistant bacteria.

Klebsiella pneumoniae↗

PubMed2026

Subchronic benzo[a]pyrene exposure disrupts APOE4-regulated lipid metabolism to induce Tau hyperphosphorylation and cognitive deficits.

BACKGROUND: Benzo[a]pyrene (B[a]P) is both a carcinogen and a potent neurotoxic pollutant. Despite growing evidence linking B[a]P to neurological dysfunction, the responsible mechanisms have not been elucidated. METHODS: Here, we employed human apolipoprotein E4 (hAPOE4) transgenic mice and APOE knockout (APOE-KO) mice to evaluate the influence of APOE on B[a]P-mediated neurotoxicity. hAPOE4 mice overexpress the human APOE4 isoform, whereas APOE-KO mice lack APOE expression; wild-type C57BL/6 J mice served as controls. Animals received intraperitoneal injections of B[a]P at 0, 2.5, or 6.25 mg/kg on alternate days for 3 months. Spatial memory and learning were examined via Morris Water Maze (MWM). Neuronal morphology, including dendritic branching and spine density in the CA1 region of the hippocampus and dentate gyrus (DG), was assessed using Golgi-Cox staining. Neurofibrillary tangles were detected by silver glycine staining. Tau, phosphorylated Tau (Ser199 and Ser396), and LRP1 were evaluated using Western blot and immunohistochemical analyses. Chromatin immunoprecipitation PCR (ChIP-PCR) was undertaken to examine the regulation of APOE4 expression by the aryl hydrocarbon receptor (AHR). In addition, both untargeted metabolomics and lipidomics analyses were conducted following B[a]P exposure. RESULTS: B[a]P led to pronounced impairments in mouse spatial memory and learning, shown by greater escape latency, less time in the target quadrant, and a decreased number of platform crossings in MWM tests. Structural analyses revealed a significant reduction in dendritic branching within the hippocampal CA1 and DG regions. These neurobehavioral and morphological deficits were most severe in hAPOE4 mice, which displayed greater cognitive impairment and more extensive dendritic loss than B[a]P-treated wild-type mice, indicating that APOE4 amplifies B[a]P-induced neurotoxicity. ChIP assays demonstrated that B[a]P modulates APOE4 transcription through AHR-dependent mechanisms. Additionally, metabolomics and lipidomics analyses revealed widespread B[a]P-induced metabolic remodeling, suggesting that disrupted lipid metabolism and altered neuronal membrane integrity may contribute to the observed neurotoxicity and cognitive dysfunction. CONCLUSION: Collectively, the results indicate that B[a]P-mediated neurotoxicity may be facilitated, at least in part, by APOE4-dependent dysregulation of lipid metabolic pathways.

Animals↗

PubMed2026

Subcellular interactions of neuropeptide Y and corticotropin-releasing factor in the central nucleus of the amygdala in the mouse.

Neuropeptide Y (NPY) is ubiquitously distributed throughout the central nervous system. Recognized as a mediator of stress resilience, NPY has been shown to counteract the excitatory effects of the neuropeptide corticotropin-releasing factor (CRF), that orchestrates the stress response. In the mouse, while NPY and CRF exhibit a high degree of neuroanatomical association in the central nucleus of the amygdala (CeA) indicating potential significant interactions, the synaptic organizations of these neuropeptides have not been elucidated. In the present study, we determined the anatomical interactions between NPY and CRF in the CeA. Immunofluorescence microscopy presented that NPY-immunoreactive varicose processes were distributed throughout the CeA and appeared to be closely apposed to CRF-containing neurons. Using electron microscopy, immunoperoxidase labeling for NPY and gold-silver labeling for CRF showed that NPY-labeled axon terminals (NPY-t) form synapses with CRF-labeled dendrites (CRF-d). Semi-quantitative analysis revealed that 247 of NPY-t directly target CRF-d. In addition, approximately 80% of NPY-t form symmetric synapses with CRF-d while approximately 1% form asymmetric synapses. These findings provide the first ultrastructural evidence that NPY-containing axon terminals make direct contact with CRF-containing dendrites in the CeA. This suggests that the CRF-containing neurons in the CeA may be a key site for NPY action, potentially influencing brain regions involved in stress responses and stress-related psychiatric disorders, and alcohol use disorders.

Animals↗

PubMed2025

Unsupervised multiscale clustering of single-cell transcriptomes to identify hierarchical structures of cell subtypes.

BACKGROUND: Cell clustering is an essential step in uncovering cellular architectures in single-cell RNA sequencing (scRNA-seq) data. However, the existing cell clustering approaches are not well designed to dissect complex structures of cellular landscapes at a finer resolution. RESULTS: Here, we develop a multiscale clustering (MSC) approach to construct a sparse cell-cell correlation network for unsupervised identification of de novo cell types and subtypes across multiple resolutions. Based upon simulated silver- and gold-standard data as well as real scRNA-seq data in diseases, MSC demonstrates significantly improved performance compared to established benchmark methods and reveals a biologically meaningful cell hierarchy to facilitate the discovery of novel disease-associated cell subtypes and mechanisms. CONCLUSIONS: We present MSC as a new single-cell multiscale clustering framework as a powerful tool for advancing discoveries in disease-associated cell populations using single-cell sequencing data.

Single-Cell Analysis↗

PubMed2025

Comprehensive analysis of a novel LYST mutation in a Tunisian patient with Chediak-Higashi syndrome.

BACKGROUND: Chediak-Higashi Syndrome (CHS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism, recurrent infections, bleeding tendencies, and progressive neurological impairment. The syndrome is caused by mutations in the LYST gene, which plays a crucial role in lysosomal trafficking. OBJECTIVE: This study aims to characterize the molecular basis of CHS in a Tunisian patient by identifying mutations in the LYST gene and analyzing their impact on the protein function, correlating these findings with the patient's clinical presentation. METHODS: A comprehensive clinical assessment was conducted on the patient, followed by biochemical, hematological, and microbiological analyses. Additionally, LYST protein levels were quantified in the patient and their parents using an ELISA assay. Genomic DNA was extracted from the patient's blood, and Whole Exome Sequencing (WES) was performed to identify mutations in the LYST gene. The findings were confirmed through Sanger sequencing, and bioinformatic tools were employed to predict the functional consequences of the detected mutations. RESULTS: The patient presented with classical symptoms of CHS, including silver hair, hypopigmented skin, recurrent infections, and neurological decline, with an unusually late onset at 18 years. ELISA results demonstrated significantly reduced LYST levels in the patient (1.8 ng/ml) compared to heterozygous parents (7.8 ng/ml and 8.1 ng/ml) and controls (9.2 ng/ml). Genetic analysis revealed a novel homozygous deletion, c.10269_10275del (p.Gly3424SerfsTer15), in the LYST gene, leading to a frameshift mutation and premature termination of the protein. Bioinformatic analysis demonstrated that this mutation leads to the deletion of five out of sven WD40 repeats in the protein's C-terminal region, which are critical for protein-protein interactions and lysosomal trafficking. CONCLUSION: The study identifies a novel LYST mutation in a Tunisian patient with CHS, expanding the spectrum of known genetic variants associated with the disease. The findings highlight the importance of genetic screening in populations with high consanguinity and underscore the need for targeted therapies to address the molecular defects in CHS.

Adolescent↗

PubMed2026

The antimicrobial gut resistome of the Wayampi reveals a shared background of antibiotic and metal resistance genes with industrialized populations, underscoring the "robust-yet-fragile" architecture of human gut microbiomes.

BACKGROUND: Metagenomics enables detailed profiling of genes encoding antimicrobial resistance. However, most studies focus exclusively on antibiotic resistance genes (ARGs), excluding those associated with non-antibiotic antimicrobials (metals, biocides), and often rely on methods with low-sensitivity and low-specificity. Furthermore, they rarely examine populations exposed to minimal anthropogenic pollution. We analyzed fecal resistomes of 95 Wayampi individuals, an Indigenous community in remote French Guiana, using a targeted metagenomic capture platform covering 8667 genes, including ARGs, metal resistance genes (MRGs) and biocide resistance genes (BRGs) (PMID: 29335005). Resistome profiles were compared with those of Europeans to assess population-level differences. RESULTS: ARG richness was similar between groups (259 in Wayampi vs. 264 in Europeans, 159 shared), but MRGs + BRGs gene richness was significantly higher in Wayampi (11,930 vs. 7419). Most genes appeared in a minority of individuals (mean 5% for ARGs, 2% for MRGs + BRGs), but several ARGs for tetracyclines [tet(32), tet(40), tet(O), tet(Q), tet(W), tet(X), tetAB(P)], aminoglycosides (ant6'-I, aph3-III), macrolides (ermB, ermF, mefA), and sulfonamides (sul2) were present in all individuals. Tetracycline resistance genes predominated overall, while beta-lactam resistance genes were more common in Wayampi, and genes conferring resistance to aminoglycosides, amphenicols, and folate inhibitors were more frequent in Europeans. Among MRGs, copper and arsenic resistance genes prevailed in both groups, followed by those for zinc, iron, cobalt, and nickel. Up to 76% of Wayampiis carried acquired MRGs for copper (pcoABCDRS and tcrB), silver (silACFPRS), arsenic (ars), and mercury (mer) detoxification. Shannon diversity indices were similar for ARGs, MRGs, and BRGs, but composition and evenness differed significantly. UMAP and ADONIS analyses distinguished cohorts based on ARG profiles (p < 0.001), but not on MRGs or BRGs. Correlation analysis revealed conserved gene-sharing networks and introgression of acquired ARGs and MRGs within both gut microbiomes. CONCLUSIONS: The diverse and balanced Wayampi resistome reflects a less perturbed microbiome compared to industrialized populations, and reveals a background of "core" and "shell" acquired ARGs and MRGs, consistent with the "robust-yet-fragile" architecture of scale-free networks. The patchy yet resilient gene distribution suggests varying levels of conserved gene sharing highways among populations, likely shaped by long-term microbial-human evolution, and supports a broader view on acquired antimicrobial resistance. Video Abstract.

Humans↗

PubMed2025

Connexin 43 drives glioblastoma cancer stem cell phenotypes through a WNK lysine-deficient protein kinase 1-c-MYC signaling axis.

The coordination of cellular processes such as growth and survival relies on communication between cells through gap junctions. Connexin proteins comprise gap junctions and also function to mediate protein-protein interactions and communication with the extracellular space via hemichannels. Despite their essential roles, connexin function in cancer is context dependent, with connexin 43 (Cx43) reported to both promote and suppress tumor growth in glioblastoma, the most common primary malignant brain tumor. Here, we detect primarily intracellular expression of Cx43 in glioblastoma patient-derived cancer stem cells and demonstrate that Cx43 is essential for their survival, self-renewal, and tumor initiation. Mechanistically, Cx43 depletion reduces c-MYC expression through reduced levels of the upstream mediator WNK lysine-deficient protein kinase 1 (WNK1). WNK1 depletion phenocopies Cx43 knockdown and reduces c-MYC expression and tumor initiation. Together, these results define a signaling axis downstream of Cx43 that promotes tumor growth and cancer stem cell phenotypes in glioblastoma.

Connexin 43↗