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PubMed2026

Onchocercidae (Nematoda: Filarioidea) Infecting Colombian Avian Hosts: Insight From Morphotypes of Microfilariae and Molecular Lineages.

Members of the Onchocercidae family are parasites that infect a wide range of tetrapods, including wild birds and other animals. In Colombia, studies on avian blood parasites have diagnosed infections with microfilariae in several species using light microscopy. However, no morphological or molecular analyses of these nematodes have been conducted to date. The present study examined samples from 3820 wild birds with material deposited in the biological collection of the Host-Parasite Relationship Study Group since 1999. Of these individuals, 142 (3.7%) were infected with microfilaria and were analyzed using morphological and morphometric measurements. Additionally, 55 samples with blood or tissue preserved in ethanol were analyzed for sequencing of nuclear marker 18S rDNA and mitochondrial markers 12S rDNA and COI. Morphological analyses showed infection by at least one of 13 designed morphotypes of microfilariae. Twenty-nine sequences were obtained (10 of COI, 6 of 12S, and 13 of 18S), corresponding to 21 molecular lineages associated with Onchocercidae. These sequences were associated with the subfamilies Lemdaninae and Splendidofilariinae, the genera Aproctella Cram, 1931, Splendidofilaria Skrjabin, 1923, and Eufilaria Seurat, 1921, and other sequences did not cluster within any genus for which sequences were available for a particular molecular marker. These findings establish the first framework of morphological and molecular diversity of avian Onchocercidae in the megadiverse Neotropical country Colombia, expanding the known distribution of several genera and highlighting the need for further sampling of adult filariids to refine taxonomic resolution.

Animals↗

PubMed2026

Prevalence of Erysipelothrix rhusiopathiae in tonsils of domestic pigs and wild boars in Sweden.

Erysipelothrix rhusiopathiae (ER) causes erysipelas in multiple animal species and may persist in the environment or be carried asymptomatically. It is estimated that 30-50% of apparently healthy or convalescent pigs harbour ER in their tonsils and other lymphoid tissues. This study aimed to determine the prevalence of ER in the tonsils of healthy Swedish fattening pigs and wild boars. Tonsils were collected from 200 fattening pigs at slaughter from ten abattoirs across Sweden in 2017, with one pig per herd sampled. Wild boars (n = 180) were sampled during hunting, primarily in Östergötland County, in 2018. Cultures were performed using selective media and isolates were confirmed as ER by MALDI-TOF MS. ER was recovered from 6/200 pig tonsils (3.0%), all originating from three abattoirs in southern Sweden. ER was isolated from 76/167 (45.5%) of wild boar tonsils. Whole-genome sequencing revealed a high genetic diversity among the isolates with no dominant clones. Overall, these results indicate that Swedish pig husbandry, characterized by indoor rearing of fattening pigs, age-segregated rearing, sow vaccination, enhanced biosecurity, and restricted straw access largely prevents tonsillar colonization by ER aligning with the low occurrence of clinically diagnosed erysipelas in such herds. For wild boars, the high isolation rate suggests that wild boar could act as a reservoir and potential source of infection for domestic pigs. The potential zoonotic risk should also be considered.

Animals↗

PubMed2020

Tissue specificity of senescent cell accumulation during physiologic and accelerated aging of mice.

Senescent cells accumulate with age in vertebrates and promote aging largely through their senescence-associated secretory phenotype (SASP). Many types of stress induce senescence, including genotoxic stress. ERCC1-XPF is a DNA repair endonuclease required for multiple DNA repair mechanisms that protect the nuclear genome. Humans or mice with reduced expression of this enzyme age rapidly due to increased levels of spontaneous, genotoxic stress. Here, we asked whether this corresponds to an increased level of senescent cells. p16Ink4a and p21Cip1 mRNA were increased ~15-fold in peripheral lymphocytes from 4- to 5-month-old Ercc1-/∆ and 2.5-year-old wild-type (WT) mice, suggesting that these animals exhibit a similar biological age. p16Ink4a and p21Cip1 mRNA were elevated in 10 of 13 tissues analyzed from 4- to 5-month-old Ercc1-/∆ mice, indicating where endogenous DNA damage drives senescence in vivo. Aged WT mice had similar increases of p16Ink4a and p21Cip1 mRNA in the same 10 tissues as the mutant mice. Senescence-associated β-galactosidase activity and p21Cip1 protein also were increased in tissues of the progeroid and aged mice, while Lamin B1 mRNA and protein levels were diminished. In Ercc1-/Δ mice with a p16Ink4a luciferase reporter, bioluminescence rose steadily with age, particularly in lung, thymus, and pancreas. These data illustrate where senescence occurs with natural and accelerated aging in mice and the relative extent of senescence among tissues. Interestingly, senescence was greater in male mice until the end of life. The similarities between Ercc1-/∆ and aged WT mice support the conclusion that the DNA repair-deficient mice accurately model the age-related accumulation of senescent cells, albeit six-times faster.

Aging↗

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

Genetic basis of escape-related locomotor performance in a wild-introgressed sheep population.

Rapid running and jumping are core components of escape responses in prey animals and provide measurable traits for studying locomotor performance in large mammals. The genetic basis of these escape-related locomotor traits remains poorly understood in large mammals, partly because repeated, standardized phenotyping under field conditions is challenging. Here, we leveraged a sheep population carrying argali-introgressed genetic components to map genetic variations associated with running speed and jumping height. Through controlled field experiments, automated high-resolution phenotyping, whole-genome analysis, and gene-edited mouse models, we identified two loci associated with escape-related locomotor traits: one in ABCC4 (Chr10:71,849,347; p = 5.03 × 10-7) linked to maximum running speed and another in GRID2 (Chr6:32,120,477; p = 1.30 × 10-9) associated with jumping height. Functional assays in knockout mice reveal that disruption of Grid2 reduces jumping ability, whereas Abcc4 knockout and knockdown increase running speed through enhanced heart contractility under stress. These results elucidated the genetic bases of wild-derived variations in affecting locomotor performance.

Animals↗

PubMed2025

Hatching of whipworm eggs induced by bacterial contact is serine-protease dependent.

Whipworms (Trichuris spp) are ubiquitous parasites of humans and domestic and wild mammals that cause chronic disease, considerably impacting human and animal health. Egg hatching is a critical phase in the whipworm life cycle that marks the initiation of infection, with newly hatched larvae rapidly migrating to and invading host intestinal epithelial cells. Hatching is triggered by the host microbiota; however, the physical and chemical interactions between bacteria and whipworm eggs, as well as the bacterial and larval responses that result in the disintegration of the polar plug and larval eclosion, are not completely understood. Here, we examined hatching in the murine whipworm, Trichuris muris, and investigated the role of specific bacterial and larval structures and molecules in this process. Using scanning and transmission electron microscopy, we characterised the physical interactions of both fimbriated (Escherichia coli, Salmonella typhimurium and Pseudomonas aeruginosa) and non-fimbriated (Staphylococcus aureus) bacteria with the egg polar plugs during the induction/initiation stage, and visualised the effects of structural changes in the polar plugs, leading to larval eclosion. Further, we found that protease inhibitors blocked whipworm hatching induced by both fimbriated and non-fimbriated bacteria in a dose-dependent manner, suggesting the partial involvement of bacterial enzymes in this process. In addition, we identified the minimal egg developmental timing required for whipworm hatching, and transcriptomic analysis of T. muris eggs through embryonation revealed the specific upregulation of serine proteases (S01A family) in fully embryonated eggs containing 'hatch-ready' L1 larvae. Finally, we demonstrated that inhibition of serine proteases with the serine-protease inhibitor Pefabloc ablated T. muris egg hatching induced by bacteria. Collectively, our findings unravel the temporal and physicochemical bacterial-egg interactions leading to whipworm hatching and indicate serine proteases of both bacterial and larval origin mediate these processes.

Animals↗

PubMed2026

A bireporter recombinant SARS-CoV-2 Omicron BA.5 for in vitro and in vivo studies.

The continuous emergence of variants of concern (VoCs) represents a significant challenge to effectively control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although FDA-approved vaccines and antivirals have been successfully developed and implemented for the prophylactic and therapeutic intervention of SARS-CoV-2 infection, recent VoCs could escape protection garnered by previous vaccine and antiviral approaches. Determining the efficacy of prophylactics and/or therapeutics against recent VoCs will assist in efficiently controlling currently circulating SARS-CoV-2 strains. We used our previously described bacterial artificial chromosome-based reverse genetics approach for Omicron BA.5 to generate a recombinant SARS-CoV-2 BA.5 encoding a fusion of ZsGreen to Nanoluciferase (rBA.5 ZsG-Nluc) from the locus of the viral nucleocapsid (N) protein separated by the porcine teschovirus-1 2A proteolytic cleavage site. The rBA.5 ZsG-Nluc replicates to levels comparable to recombinant BA.5 wild type (rBA.5 WT) and expresses high levels of ZsG and Nluc in cultured cells. This facilitates tracking viral infection and the identification of antivirals and neutralizing antibodies with EC50 and NT50 values, respectively, similar to those obtained with rBA.5 WT. Importantly, in Keratin-18 human angiotensin-converting enzyme-2 mice, rBA.5 ZsG-Nluc retains the same pathogenicity and ability to replicate in the lungs of infected mice as rBA.5 WT. Using rBA.5 ZsG-Nluc, we detected Nluc activity systemically and Nluc and ZsG expression in the lungs of infected mice using an in vivo imaging system. Our results demonstrate the feasibility of using rBA.5 ZsG-Nluc to track viral infections and identify prophylactics and therapeutics against recent SARS-CoV-2 VoCs in vitro, ex vivo, and in vivo.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of the coronavirus disease 2019 pandemic, is continually evolving to escape immunity acquired by previous natural infections or vaccinations. Moreover, recent SARS-CoV-2 variants of concern (VoCs) have acquired antiviral-resistant mutations to FDA-approved drugs. The emergence of these VoCs highlights the importance of identifying new prophylactics and therapeutics against currently circulating SARS-CoV-2 strains. We generated a recombinant bireporter Omicron BA.5 SARS-CoV-2 (rBA.5 ZsG-Nluc) that expresses reporter proteins, which are useful for cellular and whole animal studies, and has similar viral replication and pathogenicity to a wild-type recombinant Omicron BA.5 SARS-CoV-2. In Keratin-18 human angiotensin-converting enzyme-2 mice, rBA.5 ZsG-Nluc infection can be tracked systemically or in the lungs of infected mice using an in vivo imaging system. We establish a proof-of-concept platform of rBA.5 ZsG-Nluc in combination with an ancestral SARS-CoV-2 strain expressing mCherry to simultaneously identify antivirals and neutralizing antibodies against original and recent SARS-CoV-2 strains.

SARS-CoV-2↗

PubMed2026

Integrative multi-omics analysis reveals lipid/metabolite dysregulation and temporal decoupling in disease progression.

Our study presents and applies a metabolomics-driven multi-omics integration strategy to elucidate dynamic pathway interactions during disease progression. We analyzed longitudinal metabolomics datasets from a Duchenne muscular dystrophy (DMD) mouse model (6-30 weeks) and an acute Bothrops asper envenomation model (1-24 h) to contrast chronic versus acute inflammation. In the DMD model, we predicted phased cross-talk between sphingolipid metabolism and neurotrophin signaling: an early proteomic surge followed by lipid-mediated amplification and a late convergence at the protein level. Arginine and proline metabolism exhibited early metabolite accumulation preceding delayed inferred protein changes, consistent with impaired nitric oxide synthesis and argininemia-like effect. We also predicted late-stage activation of the AGE-RAGE pathway in DMD, likely triggered by ceramide buildup, and an autophagy-related lipid metabolic shift at mid-stage. In the envenomation model, tryptophan-kynurenine and nicotinamide pathways for NAD⁺ biosynthesis were rapidly perturbed at the metabolite level (1-3 h) but induced corresponding predicted enzymes only by 24 h. Thyroid hormone signaling showed an early coupling of substrate availability (tyrosine surge at 1 h) with predicted stress-response proteins and a second, delayed wave of inferred transcriptional regulators at 24 h. Acute envenomation also triggered immediate glycine/serine utilization possibly for antioxidant defense and glycerophospholipid breakdown (via phospholipase A₂), whereas chronic DMD showed sustained glycine/serine engagement and inferred, unresolved phospholipid perturbation without protein-level compensation, which may result from chronic oxidative stress. Overall, our integrative analysis revealed time-specific, multi-layer molecular perturbations distinguishing acute toxin injury from chronic muscle degeneration. Key metabolic control points (ceramide accumulation, arginine flux diversion, autophagy-lipid cross-talk, NAD⁺ salvage timing) were identified, highlighting potential targets for stage-specific therapeutic or nutritional interventions.

Animals↗

PubMed2026

Optimized AAV5-RPGR ORF15 Gene Therapy Rescues Photoreceptor Structure and Function in X-Linked Retinitis Pigmentosa Mouse Model.

PURPOSE: To develop and evaluate an rAAV5-based gene therapy vector expressing an optimized human RPGR ORF15 transgene (rAAV5-RPGR) for the treatment of X-linked retinitis pigmentosa caused by RPGR mutations, addressing the challenges of cloning the unstable wild-type ORF15 sequence. DESIGN: This was a prospective experimental study. SUBJECTS: This was an animal study. METHODS: An optimized RPGR ORF15 sequence was designed to eliminate problematic secondary structures and cryptic splice sites. In vitro expression was validated in HEK 293T and photoreceptor-like 661 W cells. A complete Rpgr knockout mouse model (Rpgr-knockout [KO]) was generated and characterized phenotypically. Therapeutic efficacy was assessed in Rpgr-KO mice via subretinal injection of rAAV5-RPGR at low (1 × 10⁹ vg/eye), medium (3 × 10⁹ vg/eye), or high (1 × 10¹⁰ vg/eye) doses. Structural and functional outcomes were evaluated at 12- and 14-month postinjection. Short-term safety was assessed in rabbits 1 month after subretinal injection. MAIN OUTCOME MEASURES: Level of RPGR protein expression and Protein isoform profile (elimination of truncated isoforms), Cellular localization of transgene expression and Dose-dependence of expression, outer nuclear layer thickness, and electroretinography parameters. RESULTS: (1) The optimized vector increased RPGR protein expression 3.3-fold in vitro compared to wild-type and eliminated truncated isoforms. (2) Subretinal delivery of rAAV5-RPGR in mice demonstrated dose-dependent transgene expression localized correctly to photoreceptor inner segments. (3) In Rpgr-KO mice, high-dose treatment significantly preserved outer nuclear layer thickness at the injection site (42% greater than controls at 14 months, P < .01) and central retina (P < .05), reduced aberrant rhodopsin mislocalization (P < .01), and partially restored retinal function. ERG showed significantly improved scotopic a-wave (≥100 vs <90 µV in controls at 10 cd·s/m²) and photopic b-wave amplitudes (49-66 vs 31-46 µV at 30 cd·s/m²) in treated mice. (4) No vector-related toxicity was observed in rabbits. CONCLUSIONS: rAAV5-RPGR mediated efficiently, targeted expression of optimized RPGR-ORF15, significantly preserved photoreceptor structure and function in a severe X-linked retinitis pigmentosa mouse model, and demonstrated a favorable safety profile. This study provides preclinical proof-of-concept for RPGR-targeted gene replacement therapy.

Animals↗

PubMed2026

Mitsuokella apri sp. nov., a novel species of the family Selenomonadaceae isolated from faeces of a wild boar (Sus scrofa).

A Gram-stain-negative, rod-shaped, obligately anaerobic strain, designated WILCCON 0060T, was isolated from the faecal sample of a wild boar (Sus scrofa) collected on the Island of Ubin (Pulau Ubin), Singapore (1.4126°N, 103.9577°E). Phylogenetic and comparative analyses based on 16S rRNA gene and whole-genome sequences indicated that strain WILCCON 0060T belongs to the genus Mitsuokella, within the family Selenomonadaceae. Notably, the average nucleotide identity and digital DNA-DNA hybridization values between strain WILCCON 0060T and the type strains of two existing Mitsuokella species, Mitsuokella multacida DSM 20544T and Mitsuokella jalaludinii DSM 13811T, only ranged from 84.6-84.9% and 24.1-24.7%, respectively, both well below the recommended species delineation thresholds of 95.0% and 70.0%. Supported by additional physiological, biochemical and genomic differences, these findings collectively indicate that strain WILCCON 0060T represents a novel species within the genus Mitsuokella. We propose the species name Mitsuokella apri sp. nov., pertaining the isolation of the type strain WILCCON 0060T (= DSM 120052T = LMG 33761T) from a faecal sample of a wild boar.

Animals↗

PubMed2024

Genome-wide association studies with experimental validation identify a protective role for B lymphocytes against chronic post-surgical pain.

BACKGROUND: Chronic post-surgical pain (CPSP) significantly impacts patients' recovery and quality of life. Although environmental risk factors are well-established, genetic risk remains less understood. METHODS: A meta-analysis of genome-wide association studies followed by partitioned heritability was performed on 1350 individuals across five surgery types: hysterectomy, mastectomy, abdominal, hernia, and knee. In subsequent animal studies, withdrawal thresholds to evoked mechanical stimulation were measured in Rag1 null mutant and wild-type mice after plantar incision and laparotomy. Cell sorting by flow cytometry tracked recruitment of immune cell types. RESULTS: We discovered 77 genome-wide significant single-nucleotide polymorphism (SNP) hits, distributed among 24 loci and 244 genes. Meta-analysis of all cohorts estimated a SNP-based narrow-sense heritability for CPSP at ∼39%, indicating a substantial genetic contribution. Partitioned heritability analysis across a wide variety of tissues revealed enrichment of heritability in immune system-related genes, particularly those associated with B and T cells. Rag1 null mutant mice lacking both T and B cells exhibited exacerbated and prolonged allodynia up to 42 days after surgery, which was rescued by B-cell transfer. Recruitment patterns of B cells but not T cells differed significantly during the first 7 days after injury in the footpad, lymph nodes, and dorsal root ganglia. CONCLUSIONS: These findings suggest a key protective role for the adaptive immune system in the development of chronic post-surgical pain.

Animals↗

PubMed2026

Biological mechanisms of atropine in myopia control (Review).

Myopia is now recognized as a progressive, potentially sight‑threatening disease rather than just a refractive error, with its prevalence rising rapidly worldwide due to its high occurrence, major vision losses and huge public health cost. The World Health Organization estimates that 2.6 billion individuals in the world were myopic in 2020 this figure is projected to increase to 3.364 billion by 2030. Although myopia may be better controlled in its early stages, it may not be completely reversed at this time. Of all of the methods for controlling myopia, atropine, a muscarinic receptor antagonist, remains an effective pharmacological option for slowing myopia progression in children. However, the mechanisms of action of atropine remain to be fully elucidated. This review provided a systematic review for myopia epidemiology, pathogenesis, the effects and side effects, as well as up‑to‑date possible mechanisms, in the hope of facilitating that researchers in this field elucidate its underlying mechanisms so that clinical ophthalmologists may be able to better control this disease.

Humans↗

PubMed2026

Rare variant analysis of whole genome sequenced juvenile idiopathic arthritis multiplex pedigrees identifies rare variants in NOD2 and ACVR1.

Juvenile idiopathic arthritis is a complex rheumatic disease that is influenced by environmental and genetic factors. Linkage and genome-wide association studies have identified genes that contribute to the risk of developing juvenile idiopathic arthritis but are limited in their ability to identify disease-risk variants of large effect. Penetrant, heritable risk variants can be detected in high-risk families, but such cases are uncommon due to the low prevalence of juvenile idiopathic arthritis. This study utilizes whole-genome sequencing of 23 multiplex families, the largest such cohort to date, to discover variants and genes relevant to JIA pathogenesis. Pathogenic variants in NOD2 associated with Blau syndrome, an ultra-rare Mendelian inflammatory disorder, are the most recurrent variants in the cohort, consistent with previous reports that milder presentations of Blau syndrome are oftentimes misdiagnosed as juvenile idiopathic arthritis. For the first time, however, rare variants in ACVR1 and SMAD6, integral components of the Bone Morphogenic Protein pathway, are found to be associated with juvenile idiopathic arthritis. Identified ACVR1 variants map to critical protein domains. AlphaFold modeling predicts that the ACVR1 interaction with its inhibitor OGT is disrupted by these variants, indicating that the patient-mutated protein has a gain-of-function phenotype. Drosophila melanogaster expressing either a wild-type or patient-mutated version of ACVR1 exhibit embryonic lethality, with the mutant exhibiting 1.4-fold greater lethality than wild-type. The combination of family-based cohorts for gene discovery, AI-based computational tools, and animal model studies for tests of variant function underscores shared disease pathogenesis between JIA and monogenic disorders of immunity and connective tissue.

Arthritis, Juvenile↗

PubMed2025

Cellular imbalance in proximal and distal lung of CFTR-/- sheep in utero and at birth.

BACKGROUND: The Lung is the major focus of therapeutic approaches for the inherited disorder cystic fibrosis (CF) as without treatment lung disease is life-limiting. However, the initiating events that predispose the CF lung to cycles of infection, inflammation and resultant tissue damage are still unclear. Inflammation may occur in the CF lung prior to birth in human and several large animal models suggesting an in utero origin for the disease and encouraging further studies prior to birth. METHODS: Here we used the sheep model of CF (CFTR-/-) and age-matched wild-type (WT) sheep of the same breed to investigate the single cell transcriptomes of proximal and distal lung tissue at 80 days and 120 days of gestation and at term (147 days). Single cell RNA-seq was performed on tissues from 4 to 7 animals of each genotype (WT and CFTR-/-) at each time point. RESULTS: At term, FOXJ1-expressing ciliated cells are overrepresented in both lung regions from CFTR-/- lambs, while secretory epithelial and basal cells are underrepresented in proximal lung, as are T cells and monocytes in distal lung. The imbalance in ciliated and basal cells was confirmed by immunohistochemistry. At 120 days of gestation, lymphoid cells are slightly more abundant in proximal and distal lung from CFTR-/- animals compared to WT, consistent with the transient CF-associated inflammatory response in utero. At 80 days of gestation, T and B cells are underrepresented in both lung regions. CONCLUSIONS: The differences in epithelial cell abundance observed in the CFTR-/- lambs at term may reflect sequelae from the loss of CFTR on lung development and differentiation in utero. These findings provide novel insights into the cellular mechanisms of pathology and may be relevant to the design of new therapeutic approaches for CF lung disease.

Animals↗

PubMed2025

Streptomyces huangiella sp. nov., an endophytic actinomycete isolated from Pheretima aspergillum, a promising candidate for biological pathogen control.

UNLABELLED: Pheretima aspergillum (E. Perrier) is an annelid of the genus Pheretima in the family Megascolecidae, a species of earthworm, whose dried body (Guang Dilong) is a traditional Chinese animal medicine. A new actinobacterium strain, named HD1123-B1T, was isolated from the gut contents of Pheretima aspergillum caught in the wild in Guangzhou, China. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the strain was primarily identified as a member of the genus Streptomyces, sharing more than 98% sequence identity to Streptomyces endocoffeicus CA3R110T (98.80%), Streptomyces coffeae CA1R205T (98.47%), and Streptomyces iranensis HM35T (97.93%). The whole genome size of strain HD1123-B1T was approximately 8.9 Mbp, with 7,464 predicted genes and 71.42 mol% DNA C+G content. Comparative genomic analyses based on digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values revealed that strain HD1123-B1T represents a novel species within the genus Streptomyces. Additionally, 38 biosynthetic gene clusters for secondary metabolites were also predicted in the genome of strain HD1123-B1T. Based on LC-MS/MS analysis, the nigericin biosynthesis gene cluster has been completely characterized. The ethyl acetate crude extract of strain HD1123-B1T exhibited remarkable antibacterial activity against gram-positive bacteria (methicillin-resistant Staphylococcus aureus ATCC 25213, etc) and gram-negative bacteria Ralstonia solanacearum GIM 1.70. Based on these results, HD1123-B1T could be confirmed as an isolate that represents a novel species of the genus Streptomyces, for which the name Streptomyces huangiella sp. nov. is proposed. IMPORTANCE: As the largest genus of the phylum Actinomycetes, Streptomyces is a kind of microbial resources with great practical and economic value. Due to their unique physiological properties and metabolic capacity, Streptomyces have become an important source of bioactive compounds in the world and play an indispensable role in medical and industrial fields. With the advancement of molecular biology and genomics, researchers can more deeply explore the metabolic potential of Actinomycetes, discovering and developing new biologically active compounds. These new compounds may possess various biological activities, such as antibacterial, antiviral, antifungal, and antiparasitic properties, further promoting the development of medicine and related industries. Based on genomic analysis and antibacterial activity, the strain HD1123-B1T was indicated to be a promising candidate for biological pathogen control.

Streptomyces↗

PubMed2026

A CRISPR-Cas9 screen identifies LAPTM4A (lysosomal protein transmembrane 4 alpha) as a key host barrier against PRRSV infection.

Porcine reproductive and respiratory syndrome virus (PRRSV) manipulates host intracellular processes, particularly macroautophagy/autophagy and lysosomal function, to facilitate its replication and spread. However, the precise host factors and molecular mechanisms by which PRRSV remodels the autophagy-lysosome axis remain poorly defined. Here, we performed a CRISPR-Cas9 knockout screen targeting 1,332 genes involved in protein degradation, metabolism, and vesicular trafficking, and identified LAPTM4A (lysosomal protein transmembrane 4 alpha) as a critical antiviral factor involved in the lysosomal pathway. A yeast two-hybrid screen identified LAPTM4A as an interactor of PRRSV GP5 (glycoprotein 5). Mechanistically, GP5 recruits the E3 ubiquitin ligase NEDD4 and the autophagy receptor SQSTM1/p62 to promote K63-linked polyubiquitination of LAPTM4A, leading to its autophagic degradation. This selective degradation activates the AMPK-ULK1-MAP1LC3/LC3 signaling cascade, initiating autophagy while facilitating MTOR-lysosome colocalization, thereby suppressing TFEB nuclear translocation and transcription of lysosome-related genes. The resulting incomplete autophagic flux enhances viral replication. Additionally, in terms of host defense, LAPTM4A maintains lysosomal homeostasis by restraining excessive autophagy through AMPK-ULK1-LC3 signaling and promoting TFEB-dependent lysosomal gene expression by impairing the binding of RPTOR/raptor to MTOR, thus providing broad antiviral protection against multiple RNA viruses. Collectively, our findings identify LAPTM4A as a central regulator of lysosome-autophagy homeostasis and reveal a viral strategy that dismantles this defense axis to facilitate infection.Abbreviations: ATG5: autophagy related 5; AMPK: adenosine 5'-monophosphate (AMP)-activated protein kinase; Baf A1: bafilomycin A1; CHX: cycloheximide; Co-IP: co-immunoprecipitation; DMVT library: protein degradation, metabolism, and vesicular trafficking library; LAPTM4A: lysosomal protein transmembrane 4 alpha; MAGeCK: model-based analysis of genome-wide CRISPR-Cas9 knockout; MOI: multiplicity of infection; MTOR: mechanistic target of rapamycin kinase; NC: negative control; PAMs: porcine alveolar macrophages; PRKAA/AMPKα: protein kinase AMP-activated catalytic subunit alpha; PRRSV: porcine reproductive and respiratory syndrome virus; qRT-PCR: quantitative real-time PCR; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; TCID50: 50% tissue culture infective dose; TFEB: transcription factor EB; Ub: ubiquitin; ULK1: unc-51 like autophagy activating kinase 1; WT: wild type.

Animals↗

PubMed2025

Genomic insights into the demographic history and local adaptation of wild boars across Eurasia.

Wild boars exhibit genetic and phenotypic diversity shaped by migrations and local adaptations. Their expansion across Eurasia, especially in Central Asia, remains underexplored. Here, we present newly sequenced whole-genome data of 47 wild boars from Eastern Asia, Central Asia, and Europe, combined with 49 existing genomes, creating a comprehensive dataset of 96 individuals. Our analyses show that Asian wild boars and Southeast Asian Suids split ∼3.6 million years ago (mya), with Central Asian and Southern Chinese ancestors diverging ∼1.8 mya. The split between Central Asian and European-Near East ancestors occurred ∼0.9 mya, followed by a European-Near East divergence ∼0.6 mya. We identify signatures of local adaptation in Central Asian populations, including two positively selected variants in LPIN1, associated with lipid metabolism, and a missense mutation in ALPK2, linked to meat traits. These findings provide insights into wild boar dispersal and adaptation and shed light on domestic pig breeding.

Animals↗

PubMed2026

Integrated multi-omics analysis of fluoroquinolone tolerance mechanisms induced by enrofloxacin in Pasteurella multocida.

BACKGROUND: The global prevalence of multidrug-resistant bacteria has been rising at an alarming rate, posing a serious threat to both human and animal health. However, the mechanisms by which bacteria acquire antibiotic tolerance and subsequently develop resistance remain incompletely understood. METHODS: In this study, Pasteurella multocida, a common pathogen in the animal husbandry industry, was exposed to enrofloxacin, and genome resequencing, transcriptomic, and metabolomic analyses were performed to elucidate the adaptive mechanisms of P. multocida under fluoroquinolone-induced stress. RESULTS: Compared with the wild-type strain, the enrofloxacin-tolerant strain exhibited an extended lag phase, a prolonged logarithmic phase, reduced sensitivity to polymyxin B, reduced biofilm formation, and an elongated cellular morphology. Multi-omics analysis revealed a deletion in the dusB gene of the tolerant strain, resulting in a truncated non-functional protein. The deletion of dusB enhanced tolerance by prolonging the lag phase and reducing the growth rate. Moreover, the expression of genes in the CAMP pathway was up-regulated, and deletion of cpxR further promoted tolerance by modulating ribosome-associated genes. Integrated transcriptomic and metabolomic analyses indicated activation of the tricarboxylic acid (TCA) cycle during tolerance development. CONCLUSION: This study identified dusB and cpxR as key genes mediating enrofloxacin tolerance in P. multocida, elucidated the association between the antibiotic tolerance, growth, and gene expression, and may provide potential targets for future strategies aimed at limiting tolerance-associated resistance development.

Enrofloxacin↗