Search Results (1,250)

Bonellia viridis, an echiuran polychaete that inhabits infralittoral rocky habitats around the Atlantic, Mediterranean, and Southeastern Pacific coastlines, exhibits environmentally mediated sexual dimorphism: planktonic larvae develop into dwarf males after exposure to bonellin, a green pigment produced by adult females. Bonellin is a chlorin with a structure consistent with derivation from uroporphyrinogen III, the last universal precursor of all known tetrapyrroles, yet its biosynthesis remains unknown. Here, the de novo genome assembly for a single adult female specimen of B. viridis isolated from Okinawa has been generated (via Illumina sequencing) and found to comprise 429.95 Mb across 95,859 contigs, with an N50 of 6505 bp, recovering 83.3% of near-universal metazoan BUSCO orthologs. Homologs of all canonical enzymes of the heme biosynthetic pathway (termed hem genes) were identified across the genome. The genomic resources establish a foundation for research into the biochemical basis of pigment production, chemically mediated sex determination, and the distinct biology of B. viridis. Full article

High-throughput sequencing (HTS) was applied to investigate the virome of European beech (Fagus sylvatica) from asymptomatic leaves and symptomatic leaves exhibiting chlorosis, line patterns and malformation. Total RNA extracted from six samples, including herbarium material collected in 1967 and 1968 and contemporary samples from France, Germany, and The Netherlands, was subjected to Illumina sequencing followed by de novo assembly, sequence similarity searches and phylogenetic analyses. In each sample, contigs belonging to a previously undescribed virus within the genus Carlavirus were obtained. The virus was tentatively named beech carlavirus. No additional virus contigs were detected in the samples. The detection of the virus over more than five decades and in three European countries indicates its long-term and a probable wider occurrence and circulation. Moreover, its prolonged unnoticed presence suggests that it does not induce noticeable and acute disease outbreaks. These findings underscore the value of integrating historical and recent field samples through collaborative data sharing to improve insight into virus diversity and ecology in forest trees. Full article

Background: Chung–Jansen syndrome (CHUJANS) is a rare autosomal dominant genetic condition caused by pathogenic variants in the PHIP gene, which encodes a protein involved in neurodevelopmental processes and IGF-1 signalling. The phenotype is characterised by variable degrees of intellectual disability, early-onset obesity or overweight, distinctive facial dysmorphisms, and behavioural disturbances. We here present a case of Chung–Jansen syndrome with a detailed endocrine work-up, highlighting the metabolic component of this syndrome. Case Presentation: We describe the case of a 21-year-old woman referred to our centre for evaluation of oligomenorrhea in the context of severe obesity (BMI 50.4 kg/m²), short stature (151 cm, <3rd percentile), and moderate-to-severe intellectual disability (full-scale IQ 38). Physical examination revealed dysmorphic features, including a round face, upslanting palpebral fissures, prominent zygomatic bones, anteverted nares, a prominent chin, and bilateral brachydactyly type E1. Laboratory investigations documented subclinical primary hypothyroidism of autoimmune origin, impaired glucose tolerance with associated hyperinsulinism, and polyendocrine metabolic ovarian syndrome (PMOS, previously known as PCOS). Exome analysis by next-generation sequencing (NGS) identified a heterozygous c.328C>T [p.(Arg110Cys)] variant in the PHIP gene, already reported in literature and classified as likely pathogenic (ACMG class 4). Segregation analysis in the mother (father was not available for the test) did not reveal the variant, suggesting a de novo origin in the patient. Concurrently, the same analysis revealed a variant of uncertain significance in the ANKRD17 gene, while array-CGH detected a maternally inherited microdeletion of uncertain significance on chromosome X (Xp11.23). Conclusions: This case confirms the association between the PHIP p.(Arg110Cys) variant and the phenotype of Chung–Jansen syndrome, providing a detailed characterisation of the endocrine and psychiatric comorbidities. Indeed, our report expands the knowledge on the endocrine phenotype providing further suggestion for personalised patient management. It underscores the importance of NGS in the diagnostic workup of syndromic obesity with intellectual disability, especially in the presence of negative family history and prior inconclusive genetic testing. This case suggests the inclusion of comprehensive endocrine evaluations in future studies on patients with Chung–Jansen syndrome, in order to support endocrine work-up and facilitate early identification and appropriate management of potentially treatable alterations. Full article

Background/Objectives: Melophagus ovinus is an economically important ectoparasite of small ruminants with a broad global distribution. Although mitochondrial genomes are widely used in population genetic studies, the D-loop region of M. ovinus remains poorly characterized because its high AT content and repetitive structure complicate amplification, assembly, and sequencing. Methods: We sequenced the mitochondrial genome of M. ovinus collected from Qinghai using an integrative approach combining Illumina paired-end sequencing, targeted PCR amplification, and Nanopore long-read sequencing. Comparative genomic analysis was performed against published mitogenomes from Gansu (MH024396) and Xinjiang (NC_037368). Results: The Qinghai mitochondrial genome contained the typical 37 mitochondrial genes within a 14,728 bp conserved region. Comparative analysis revealed exceptionally high conservation (>99.6% sequence identity) among Qinghai, Gansu, and Xinjiang isolates outside the D-loop region. Notably, the D-loop exhibited length polymorphism, with different assembly strategies or samples yielding lengths ranging from 317 bp to 2385 bp. Targeted long-read sequencing of ten individuals identified a predominant D-loop variant of approximately 844 bp in nine samples and a markedly shorter variant of approximately 164 bp in one sample. The short variant was characterized by extensive deletions and a novel 45 bp insertion. Support for this variant was obtained from independent Illumina DNA-seq, RNA-seq, Nanopore sequencing, and de novo assembly analyses. Conclusions: This study provides preliminary evidence for D-loop structural heterogeneity in M. ovinus, suggesting remarkable length polymorphism and complex indel patterns that require further validation. These findings significantly expand the genomic resources available for this important veterinary parasite and establish a foundation for future population genetic and evolutionary studies. Full article

Background/Objectives: Barley malting is an agro-industrial process that produces malt, an essential ingredient for the brewing and distilling industries. Previously, tran-scriptome profiling has revealed mRNA changes during malting but less is known about their regulation. Methods: The spring 2-row barley variety ‘Conrad’ was sampled at five stages of malt-ing. Using small RNA (sRNA)-sequencing and degradome-sequencing data from these malting stages, de novo discovery of mature microRNA (miRNA), as well as cognate mRNAs targeted for slicing, was identified. ShortStack v4.1.0 was used to map sRNA reads to the Hordeum vulgare Morex V3 genome. Results: In total, 33 expressed MIRs were identified, six of which may be novel. Using the degradome-sequencing data from the same malting stages, CleaveLand4 v4.5 pre-dicted 64 sliced mRNA targets, predominantly transcription factors associated with root development. Conclusions: This study provides an overview of post-transcriptional modulations of miRNAs-cognate mRNA targets, as well as plausible interactions between miRNAs during barley malting. Full article

To clarify the cellular origin of matrix metalloproteinase-9 (MMP9) and explore targeted research, we utilized single-cell RNA sequencing analysis, which revealed that MMP9 is predominantly enriched in specific macrophages within the activated B-cell-like (ABC) subtype. Guided by this target information, we applied a generative AI pipeline incorporating RFdiffusion, ProteinMPNN, and AlphaFold to de novo design protein binders targeting the hemopexin (PEX) domain of MMP9. ELISA experiments confirmed the in vitro binding capability of these designs; among them, MMP9-30 displayed the strongest binding, with an apparent EC50 of approximately 1.1 μM, followed by MMP9-34, while MMP9-97 showed the weakest interaction. This study successfully integrates single-cell sequencing with AI-assisted protein design, providing a preliminary exploratory framework for subsequent MMP9-targeted research and protein binder development. Full article

Pathogenicity islands (PAIs) are regions of bacterial genomes that harbor genes encoding virulence factors. Identifying molecules that enhance pathogenicity is crucial for understanding the mechanisms pathogens employ to cause disease and their evolution. Corynebacterium pseudotuberculosis (C. pseudotuberculosis) is a pathogenic microorganism that causes caseous lymphadenitis (CLA) in sheep and goats. Despite its prevalence in Mexico, its genetic material has not been analyzed for virulence factors acquired through horizontal gene transfer. Therefore, the aim of this study was to characterize the complete genomes of Mexican C. pseudotuberculosis strains and identify virulence-related genes harbored with PAIs. Seventeen strains of C.pseudotuberculosis biovar ovis isolated from Mexico were whole-genome sequenced using illumina technology, assembled de novo with SPAdes, and annotated using Prokka. PAIs were predicted with GIPSy based on genomic signatures associated with horizontal gene transfer, including G + C deviation, codon usage, virulence factors, transposases, and tRNA-flanking regions. Positive selection was assessed using POTION v1.2 by identifying orthologous groups enriched in non-synonymous substitutions. This represents the first comprehensive PAI analysis of Mexican C. pseudotuberculosis strains, identifying 14 putative pathogenicity islands harboring 51 virulence-associated genes. Additionally, positive selection analysis identified five coding sequences, including radA and rpiB, that are undergoing adaptive evolutionary changes. These findings elucidate the pathogenic mechanisms and genomic plasticity of Mexican C. pseudotuberculosis strains. They also highlight novel genetic targets for vaccine and therapeutic development against CLA. Full article

Under a One Health framework, viruses of veterinary and zoonotic importance pose significant threats to animal and human health, food security, and livelihoods, particularly in regions with intense human–animal interactions. In West Africa, despite recent advances in surveillance programs, important gaps remain in understanding viral diversity and cross-species transmission at wildlife–livestock interfaces. We conducted metagenomic surveillance to characterize viruses circulating across livestock, domestic animals, and wildlife in rural Ghana in 165 animals sampled across five regions. Viral RNA from serum and tissue samples was sequenced with the Illumina platform, and genomes were de novo assembled with MEGAHIT. Phylogenetic relationships were reconstructed using Bayesian approaches. We report the first genomic sequences of porcine parvovirus 3, canine parvovirus, rotavirus A genotype R16, and bovine hepacivirus subtype B from Ghana in over a decade. Phylogenetic analyses revealed intercontinental linkages between Africa and Europe for parvoviruses, persistence of hepacivirus lineages, and evidence of cross-species transmission for rotavirus. Notably, detection in apparently healthy animals highlights underrecognized circulation, gaps in vaccination effectiveness, trade-related biosecurity vulnerabilities, and the role of wildlife in viral maintenance and transmission. Our findings reveal dynamic viral diversity and connectivity across animal populations and ecological interfaces, emphasizing the fluid and interconnected nature of pathogen circulation within One Health systems. By integrating metagenomics and phylogenetics, this study provides a scalable framework for enhancing surveillance capacity, enabling the early detection of emerging threats and informing targeted strategies to mitigate zoonotic and economically important viral diseases in West Africa. Full article

Metagenomics analysis is a critical tool in identifying and typing viral samples to aid surveillance, clinical, epidemiological, and other workflows. Despite advances in sequencing technology and analysis pipelines, there are still limitations that lead to reduced taxonomic resolution or false positives from highly recombinant or challenging samples. Here we describe MGtree, a novel metagenomics pipeline that utilizes a combination of full-length read alignments and phylogenetic analysis to classify samples of interest. We demonstrate that MGtree accurately genotypes viral samples from challenging norovirus and HPV datasets. MGtree outperforms the popular metagenomics programs Kraken2 and Centrifuge, and it succeeds with low-input samples where de novo assembly fails. MGtree’s correct assignments across highly mutant and coinfected samples highlights its ability to resolve viral genotypes and its potential to improve classification precision in complex samples. Full article

A novel quantum algorithm for biological sequence alignment is presented and analyzed. The large volumes of data generated through genome sequencing, de novo assembly, resequencing, and transcriptome sequencing at the DNA and RNA levels foreshadow the growing demand for higher computational power and more sophisticated alignment methodologies. The rapid advancement of modern sequencing technologies in genomics has motivated the reconsideration of existing approaches for the design and implementation of alignment protocols. Emerging quantum computing accelerators may provide transformative solutions in this domain as quantum hardware progressively reaches higher levels of gate-operation maturity. This work proposes a computer-vision-based approach that exploits the unique properties of quantum entanglement within a dot-matrix representation to address the increasing demand for efficient processing of biological data. A quantum-accelerated protocol is developed and evaluated using the Qiskit software framework of IBM. Runtime experiments support the potential of the proposed methodology to provide advantageous sequence-alignment performance in terms of accuracy, completeness, and computational complexity. The system is evaluated under multiple operational conditions and demonstrates promising performance advantages. Full article

This study examined the protective mechanisms of oleanolic acid (OA) against high-fat diet (HFD)-induced hepatic steatosis and intestinal dysbiosis in Nile tilapia. Fish were allocated to four groups: normal diet (ND), HFD, and OA-supplemented HFD (50 and 250 mg/kg). After 42 days, physiological, biochemical, and histological assessments demonstrated that OA markedly reduced hepatic lipid accumulation, mitochondrial injury, and intestinal shortening. Transcriptomic analysis revealed that OA alleviated lipid dysregulation by inhibiting de novo lipogenesis and promoting lipid trafficking and β-oxidation, effectively reversing HFD-induced changes in the PPAR, MAPK, mTOR, and autophagy-lysosome signaling pathways. 16S rRNA sequencing indicated that OA increased microbial alpha diversity, suppressing HFD-associated taxa (e.g., Nordella) while enriching beneficial genera such as Clavibacter, Bosea, and Bdellovibrio. Importantly, OA treatment restored HFD-induced depletion of intestinal butyric acid and suppressed hepatic pro-inflammatory cytokines (tnf-α, il-1β), while upregulating growth-related factors (igf1). Correlation analysis confirmed strong associations between microbial alterations (Nordella and Phreatobacter) and hepatic lipid metabolism and inflammatory gene expression. Overall, OA mitigates metabolic stress in Nile tilapia by reconfiguring the gut–liver axis, integrating microbial restoration with precise regulation of hepatic nutrient-sensing and inflammatory pathways, providing a potential therapeutic strategy for lipid metabolism disorders in aquaculture. Full article

Lauric acid is a characteristic component of Litsea cubeba seed oil, but FatB thioesterase candidates with predicted structural compatibility for C12 acyl-substrate accommodation remain insufficiently defined. In this study, seed oil content and fatty acid composition were examined during L. cubeba seed development. The fatty acid profile shifted from a C18:2-rich pattern at the early stage to a C12:0-dominated composition at later stages, providing the biochemical context for FatB candidate prioritization. Three FatB-like candidates were retrieved from a de novo seed transcriptome assembly and named LcFatB1, LcFatB2, and LcFatB3. Phylogenetic analysis, conserved motif comparison, sequence alignment, and homology modeling showed that LcFatB1 and LcFatB2 retained more complete FatB-like sequence and structural features than LcFatB3. S-dodecanoyl-4′-phosphopantetheine was used as a C12 acyl-4′-phosphopantetheine surrogate for molecular docking. Docking analysis indicated that LcFatB1 and LcFatB2 formed more interpretable C12-bound poses than LcFatB3. Subsequent 150 ns molecular dynamics simulations, free energy landscape analysis, residue–ligand interaction profiling, and catalytic tunnel analysis further distinguished the two main candidates. Compared with LcFatB2, LcFatB1 maintained a lower-displacement C12-bound state, a more compact contact environment involving Tyr116, Ser125, and Asn278, and a main tunnel with higher throughput and shorter length in the representative global-minimum conformation. LcFatB2 also retained the C12 surrogate but stabilized it in a distinct rearranged binding environment. These results support LcFatB1 as the strongest structurally prioritized FatB candidate among the three transcriptome-derived proteins, while LcFatB2 remains a plausible FatB-like candidate with a distinct C12-bound state. This prioritization provides computational structural clues for future biochemical testing but should not be interpreted as direct functional confirmation of FatB activity in vivo. Full article

Abortion in cattle entails substantial economic loss, and rapid identification of abortigenic pathogens is critical for timely on-farm response and reduction in human exposure risk. In 2024, two Holstein cows from a small farm in Inner Mongolia aborted in close succession without an obvious cause. Vulvar swabs from both cows, one afterbirth sample, and whole blood from one aborted fetus were collected. Shotgun metagenomic sequencing was performed, followed by host-read removal, taxonomic profiling with Kraken2, de novo assembly of Brucella-aligned reads, and whole-genome comparison. Serological tests, Gram-stained smears, and Brucella genus- and species-specific qPCR assays were used as orthogonal verification. Putative resistance and virulence determinants were screened against CARD and VFDB. Brucella reads were detected in all samples, with the highest relative abundance in the 138-afterbirth (96%). qPCR assays detected Brucella DNA and B. abortus-specific signals in all four samples. A draft Brucella genome was assembled from the 138-afterbirth sample and was phylogenetically placed within B. abortus, showing relatedness to previously circulating Chinese lineages. Cows 138 and 198 were RBT-positive with SAT titres of 1:100 (++). No acquired Brucella resistance genes were identified in CARD. Within 72 h of sample receipt, B. abortus was reported to the farm and local authorities and emergency biosecurity measures were implemented. This field investigation shows that metagenomic sequencing, when combined with conventional serology, microscopy, and targeted qPCR, can support rapid etiological investigation when culture is delayed, hazardous, or biosafety level 3 facilities are unavailable. Full article

Goat blood, a major slaughterhouse by-product, was systematically valorized into dual-function bioactive peptides through an optimized four-step process. Four blood preparations—whole blood (HB), anticoagulant-treated blood (HBS), red blood corpuscles (BC), and plasma (PM)—were subjected to heat pretreatment (90 °C, 15 min) and enzymatic hydrolysis. Neutrase hydrolysis of heat-pretreated whole blood at 8% substrate concentration for 4 h (HBN-8) yielded optimal protein recovery (44.38%) with dual ACE (88.24%) and DPP-IV (81.13%) inhibition. Ultrafiltration enriched bioactive peptides in the ≤3 kDa fraction (DPP-IV: 87.8%; ACE: 65.5%). LC-MS/MS de novo sequencing identified 14 novel peptide sequences (4–9 amino acids), with the most potent SEC fraction showing IC₅₀ values of 0.89 and 0.45 mg Leu eq./mL for DPP-IV and ACE inhibition, respectively. Critically, simulated gastrointestinal digestion enhanced rather than diminished bioactivity, with ACE inhibition increasing progressively to 60.91% at the intestinal phase, supported by predicted generation of bioactive fragments from parent sequences. Caco-2 assays confirmed peptide safety (100–1000 µg/mL) and demonstrated 10.47% transepithelial transport with retained dual inhibitory activities. This study establishes goat blood as a sustainable source of orally bioavailable, GI-stable peptides for the development of functional foods targeting hypertension and type 2 diabetes. Full article

Background/Objectives: As a global chromatin organizer, SATB1 is increasingly implicated in neurodevelopmental disorders (NDDs). This study aims to delineate the clinical and molecular characteristics of a novel de novo SATB1 variant in a patient presenting with epilepsy-dominant NDDs phenotypes. Methods: Triggered by the onset of seizures, trio-based whole-exome sequencing (Trio-WES) was performed to identify the genetic etiology. Subsequent sleep electroencephalogram (EEG) and magnetic resonance imaging (MRI) were then conducted to further characterize the patient’s clinical phenotypes. Pathogenicity was assessed through structural modeling and functional characterization. Nonsense-mediated mRNA decay (NMD) status, protein expression profiles, and subcellular localization were determined by reverse-transcription quantitative PCR (RT-qPCR), Western blotting, and immunofluorescence staining. The transcriptional regulatory impacts of the variant were quantified using dual-luciferase reporter system targeting known downstream regulatory elements. Clinical responses to antiepileptic intervention was also monitored. Results: We identified a novel de novo heterozygous pathogenic frameshift variant in SATB1 (NM_002971.5: c.1718_1719insCA; p.Val574Argfs*134) in a patient presenting with early-onset epilepsy, mild intellectual developmental disorder (IDD), speech delay, and dental anomalies. Functional assays demonstrated that the variant-derived transcript escaping NMD, yielding a truncated protein that forms irregular punctate aggregates within nuclei. Dual-luciferase assays revealed significantly increased transcriptional activity, indicating a loss of the protein’s innate transcriptional regulatory capacity. Clinically, treatment with sodium valproate (VPA) successfully stabilized seizures of the patient, markedly reducing both frequency and intensity. Conclusions: The study reports a novel SATB1 frameshift variant that exerts pathogenicity significant functional impairment by disrupting protein localization and transcriptional regulation. These findings expand the genetic spectrum of SATB1-related NDDs and underscore the efficacy of targeted antiepileptic management in genetic diseases. Full article