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Two-Year Outcomes of a 211 Care Coordination Trial.

BACKGROUND AND OBJECTIVES: Early screening for developmental concerns enables timely diagnosis and referral, yet many families face barriers accessing services. Prior work showed that early childhood care coordination could improve timely service connection. This study assessed developmental outcomes among children participating in a randomized controlled trial of Information and Referral Federation of Los Angeles County (211LA). METHODS: Participants, aged 21-42 months, were randomized to usual care or the 211LA intervention. Developmental and behavioral measures, including the Parental Evaluation of Developmental Status Developmental Milestones Assessment Level (PEDS-DM-AL) and the Child Behavior Checklist (CBCL), were collected at baseline and 24 months later. The sample included 499 participants, 250 in the 211LA intervention and 249 in usual care. Primary analyses examined changes in PEDS-DM-AL and CBCL scores over the 24-month period by study arm. Post hoc analyses compared family characteristics between intervention and control families who enrolled in services. RESULTS: Developmental and behavioral measures showed some clinically insignificant change over time, but these changes did not differ by condition (expressive/receptive language skills mastered: P > .9; autism, attention, aggression, and externalizing behavior T scores: P > .4). Post hoc analyses identified potentially relevant imbalances between the treatment arms at baseline as well as in the subgroup that enrolled in services, with families assigned to the 211LA intervention being more likely to have a non-US born parent and a parent with limited English proficiency compared with families assigned to usual care. Intervention families enrolled in services also used telehealth more frequently and received a lower duration of services than those receiving usual care. CONCLUSIONS: This study measured the indirect influence of service enrollment through 211LA care coordination on developmental outcomes. Although increased service enrollment through 211LA did not affect developmental outcomes, we hypothesize this may be because of several factors, including overrepresentation of a subset of historically underrepresented families in the 211LA intervention, suboptimal performance of our developmental assessment tool, and complexity of conducting a trial of this magnitude during the COVID-19 pandemic, which may have diminished the ability of this trial to demonstrate developmental benefits despite demonstrated service enrollment gains.

Humans

The Key Trichoderma-Induced Gene Encoding a DUF568 Domain-Containing Protein Mediates Defense Responses in Wheat.

Genes encoding DUF568 domain-containing proteins participate in plant stress adaptation. To elucidate the functional role of DUF568 domain-containing genes in Trichoderma-induced wheat defense responses against wheat Fusarium crown rot, we performed a genome-wide identification and characterization of the TaDUF568 gene family in hexaploid wheat (Triticum aestivum L.). In this study, a total of 33 TaDUF568 family genes were systematically identified and characterized at the genome-wide level, exhibiting uneven chromosomal distribution and diverse physicochemical properties. Phylogenetic, structural, and collinearity analyses revealed conserved family characteristics among monocot species. Segmental duplication was verified as the primary driver of gene family expansion. Expression profiling revealed divergent tissue-specific expression patterns among TaDUF568 family members, among which TaDUF568.18 was strongly induced by Trichoderma M2. Subcellular localization assays confirmed that TaDUF568.18 is a plasma membrane-localized protein. Functional validation via stable transgenes demonstrated that overexpression of TaDUF568.18 restricted lesion expansion, improved agronomic traits, and enhanced disease resistance. This study is the first to characterize the wheat DUF568 family and confirm that TaDUF568.18 (annotated as TaAIR12) acts as a positive regulator of Trichoderma-mediated wheat defense, providing a valuable gene resource for wheat disease-resistance breeding.

DUF568

Teaching Engagement and Caregiving Help in the Intensive Care Unit (TEACH-ICU) Scale: Content Validity.

BACKGROUND: Having family members provide care to their loved ones in the intensive care unit (ICU) is a beneficial yet seldom implemented approach. For family members to perform caregiving, nurses must be willing to teach, and such willingness is a developing area of research. OBJECTIVES: To adapt an instrument validated in family members, the Family Willingness for Caregiving Scale, to address nurses' willingness to teach family members caregiving skills. METHODS: Purposive and snowball sampling were used to recruit 10 expert ICU nurses through the American Association of Critical-Care Nurses' research website and social media platforms. The researchers conducted cognitive interviews with the nurses to address the instrument's content validity. RESULTS: The scale was refined based on the participants' feedback. Items were deleted, added, and revised. Furthermore, scale instructions were adjusted to emphasize the willingness to teach families of patients receiving mechanical ventilation. Qualitative themes emerged related to barriers to family engagement, including time constraints, patient acuity, and nurse and family characteristics. CONCLUSIONS: Content validity of the scale was assessed, with future research aimed at pilot testing and evaluating construct validity before using the scale as a research instrument. Practical implications include using the scale as an evaluation tool to determine nurses' willingness to teach family members about caregiving. After evaluation, various strategies could be incorporated to enhance family engagement in adult ICUs.

Humans

Breast Cancer Risk Stratification in Black Women: Current Status and Potential Solutions to Improve Accuracy.

Breast cancer risk stratification models identify individuals at increased risk, allowing earlier screening than for those at average risk and potentially improving health outcomes. Due to the increasing rates of breast cancer in individuals aged <40 years, especially among Black females, the American College of Radiology now recommends all females initiate breast cancer risk assessment by age 25 years. Several breast cancer risk prediction models are readily available, including the Gail Model, Breast Cancer Surveillance Consortium Risk Calculator, BOADICEA, and Tyrer-Cuzick Model. However, because these models were primarily developed using data from White women of European ancestry, they may underestimate risk in Black women. Indeed, current evidence suggests that these models underpredict breast cancer risk among Black women, particularly those of African ancestry. Although cancer risk prediction models typically incorporate personal characteristics, family history of cancer, and hormonal and lifestyle factors, inherited breast cancer genes can also increase risk for breast cancer. Beyond monogenic inherited breast cancer genes that increase breast cancer risk, emerging data suggest that single nucleotide polymorphisms identified through genome-wide association studies (GWAS) may be used to generate polygenic risk scores, which may further refine breast cancer risk. However, GWAS data are also primarily gathered from European ancestry females, further reducing the ability to accurately stratify breast cancer risk in non-European ancestry populations. Current data highlight the importance of ensuring representation from all populations in developing cancer risk prediction models, conducting genomics research, and designing effective implementation strategies to enhance the use of these models in routine clinical care. Although new analytic methods and models are being developed to improve breast cancer risk stratification across populations, it remains critical to assess the utility and calibration of existing and new models to ensure applicability across non-European ancestry populations.

Humans

A novel start-loss mutation of the SLC29A3 gene in a consanguineous family with H syndrome: clinical characteristics, in silico analysis and literature review.

BACKGROUND: The SLC29A3 gene, which encodes a nucleoside transporter protein, is primarily located in intracellular membranes. The mutations in this gene can give rise to various clinical manifestations, including H syndrome, dysosteosclerosis, Faisalabad histiocytosis, and pigmented hypertrichosis with insulin-dependent diabetes. The aim of this study is to present two Iranian patients with H syndrome and to describe a novel start-loss mutation in SLC29A3 gene. METHODS: In this study, we employed whole-exome sequencing (WES) as a method to identify genetic variations that contribute to the development of H syndrome in a 16-year-old girl and her 8-year-old brother. These siblings were part of an Iranian family with consanguineous parents. To confirmed the pathogenicity of the identified variant, we utilized in-silico tools and cross-referenced various databases to confirm its novelty. Additionally, we conducted a co-segregation study and verified the presence of the variant in the parents of the affected patients through Sanger sequencing. RESULTS: In our study, we identified a novel start-loss mutation (c.2T&#x2009;>&#x2009;A, p.Met1Lys) in the SLC29A3 gene, which was found in both of two patients. Co-segregation analysis using Sanger sequencing confirmed that this variant was inherited from the parents. To evaluate the potential pathogenicity and novelty of this mutation, we consulted various databases. Additionally, we employed bioinformatics tools to predict the three-dimensional structure of the mutant SLC29A3 protein. These analyses were conducted with the aim of providing valuable insights into the functional implications of the identified mutation on the structure and function of the SLC29A3 protein. CONCLUSION: Our study contributes to the expanding body of evidence supporting the association between mutations in the SLC29A3 gene and H syndrome. The molecular analysis of diseases related to SLC29A3 is crucial in understanding the range of variability and raising awareness of H syndrome, with the ultimate goal of facilitating early diagnosis and appropriate treatment. The discovery of this novel biallelic variant in the probands further underscores the significance of utilizing genetic testing approaches, such as WES, as dependable diagnostic tools for individuals with this particular condition.

Humans

Assessment of differentially culturable tubercle bacteria assays for the detection of tuberculosis infection in asymptomatic household contacts and the implications for intra-household transmission: a longitudinal cohort study.

BACKGROUND: Conventional culture methods for tuberculosis diagnosis miss differentially culturable tubercle bacteria (DCTB), which grow only in liquid assays supplemented with growth-enhancing factors. This limitation, combined with inadequate contact tracing and screening, often fails to identify asymptomatic individuals, with live bacilli detectable by enhanced culture methods. This shortfall results in undiagnosed reservoirs of bacteria, potentially fuelling ongoing transmission. In this study, we aimed to investigate whether DCTB assays provide greater sensitivity by detecting more Mycobacterium tuberculosis infections than conventional culture and whether this enhanced detection improves the resolution of intrahousehold transmission mapping. In addition, we sought to evaluate whether DCTB populations can progress to conventional culture positivity, thereby highlighting their clinical and epidemiological relevance. METHODS: In this prospective observational longitudinal cohort study, drug-susceptible or rifampicin-resistant tuberculosis index participants aged 12 years or older, were recruited from primary healthcare clinics from two South African districts. Inclusion criteria were informed consent, Xpert MTB/RIF Ultra-positive results, tuberculosis symptoms (>2 weeks), provision of baseline samples, at least one consenting household contact, and documented HIV status. Household contacts of the index patients and control households were also recruited. Sputum specimens were collected at baseline and 2, 4, 8, 12, and 16 months from the index participants and household contacts. Samples were analysed by conventional mycobacterial growth indicator tube (MGIT) culture, and colony-forming unit assays to identify viable bacteria. Enhanced culture to detect DCTB involved serial dilution of sputum in liquid culture, supplemented with M tuberculosis culture filtrate as a source of growth stimulatory factors. Whole-genome sequencing (WGS) of cultured isolates was performed to trace household transmission. FINDINGS: Between June 1, 2020, and Feb 6, 2024, 293 index participants (183 [62%] male), 701 household contacts (453 [65%] female), and 122 control participants (67 [55%] female) were enrolled. At baseline, 249 (85%) of 293 index participants and 110 (16%) of 701 household contact sputum samples were positive for M tuberculosis by MGIT conventional culture. For baseline MGIT-negative specimens, DCTB assays detected M tuberculosis in an additional 21 (7%) of 293 index participants and 26 (4%) of 701 household contacts. Over 16 months of follow-up, DCTB assays identified 61 (8&#xb7;7%) of 701 additional tuberculosis-positive household contacts not detected by conventional culture. WGS-guided transmission mapping using conventional culture identified transmission in 16 (15%) of 104 households, whereas DCTB assays detected an additional 19 (18%) of 104 transmission events. No evidence of intrahousehold transmission was found in the remaining 69 (66%) of 104 tuberculosis-positive households. Over the 16-month follow-up period, conventional culture identified 233 positive household contacts, of which 195 (84%) were asymptomatic. DCTB assays detected an additional 94 cases of M tuberculosis positivity in household contacts, of which 79 (84%) were asymptomatic. In control households, tuberculosis prevalence at baseline was two (2%) of 122, with an additional three (3%) of 122 identified during follow-up. INTERPRETATION: DCTB assays provide substantial value by detecting asymptomatic individuals missed by conventional culture, revealing a potentially important reservoir of subclinical infection, which could sustain transmission. In addition, DCTB detection uncovers transmission linkages missed by conventional culture, providing a more comprehensive understanding of M tuberculosis transmission dynamics and highlighting the need to incorporate enhanced culture methods into diagnostic and surveillance strategies, to strengthen early case identification and tuberculosis control efforts. FUNDING: National Institutes of Health.

Humans

Acceptability of alcohol-based hand rub during neonatal care in rural Ugandan households: a qualitative study nested within the BabyGel trial.

BACKGROUND: Poor access to water, sanitation and hygiene exacerbates the spread of infections among newborns. The BabyGel cluster randomised trial assessed the effectiveness of a community-level alcohol-based hand rub with a training component in reducing infection or death rates among newborns in Uganda. OBJECTIVE: Nested in the BabyGel trial, this study investigated the acceptability of the BabyGel intervention among mothers and household members in Eastern Uganda, using the Theoretical Framework of Acceptability. METHODS: In 2022, we conducted individual semistructured interviews with mothers, and group interviews with mothers and other household members, all recruited from intervention-arm clusters. Thematic analysis combined inductive and deductive coding, structured by the framework's seven constructs: affective attitude, burden, ethicality, intervention coherence, opportunity costs, perceived effectiveness and self-efficacy. RESULTS: Twenty mothers and 14&#xa0;household members participated in 10 individual and 10 small group interviews. Participants found the intervention generally acceptable, appreciating its convenience and perceived protection against infection. Many described hand hygiene changes that persisted beyond the intervention period. However, concerns related to its harmful effects, spiritual beliefs and social tensions with visitors occasionally influenced its use. CONCLUSION: Alcohol-based hand rub combined with a training component was generally well accepted, driven by perceived health and practical benefits, although concerns related to safety, belief systems and social dynamics remained. Because data collection coincided with the COVID-19 pandemic, a period of heightened hygiene awareness, the acceptability observed could differ in nonpandemic periods. Culturally adapted education, community engagement and reinforcement of correct use may enhance acceptability and sustainability in similar settings.

Humans

Should neighbours of tuberculosis (TB) cases be prioritised for active case finding in high TB-burden settings? A prospective molecular epidemiological study.

INTRODUCTION: In high tuberculosis (TB)-burden countries, considerable transmission of Mycobacterium tuberculosis (M. tb) likely occurs outside of households. We aimed to estimate the TB prevalence and incidence in households and neighbourhoods around known TB cases and to understand transmission patterns. METHODS: Household and neighbourhood contacts of pulmonary TB index cases from contiguous areas in Bandung, Indonesia, were screened and followed up for 12 months. Sputum samples underwent smear microscopy, M. tb culture, Xpert MTB/RIF, DNA isolation and whole-genome sequencing (WGS). Pairwise single-nucleotide polymorphism (SNP) distance &#x2264;12 defined transmission for pairs with known epidemiological links, or SNP&#x2264;3 for pairs without epidemiological link. An SNP=12 cut-off was used to characterise transmission clusters. RESULTS: From 213 index cases, 514 household and 4141 neighbourhood contacts underwent TB screening: 19 household (3.70%, 95%&#x2009;CI 2.24 to 5.71) and 45 neighbourhood (1.09%, 95%&#x2009;CI 0.79 to 1.45) contacts were identified with TB, of whom 18 (3.50%, 95%&#x2009;CI 2.20 to 5.48) and 38 (0.92%, 95%&#x2009;CI 0.65 to 1.13) respectively, were bacteriologically confirmed. During follow-up, 11 household and 13 neighbourhood contacts were identified with TB (incidence per 100&#x2009;000 person-years: 2286 (95% CI 1286 to 4148) and 350 (95% CI 190 to 563)), of whom 6 and 8, respectively, were bacteriologically confirmed (incidence per 100&#x2009;000 person-years: 1247 (95% CI 560 to 2776) and 201 (95% CI 101 to 402)). A total of 223 patient M. tb isolates underwent WGS. Of 15 intra-household pairs, 8 (53.3%) were transmission pairs. Of 24 neighbour to index case pairs, 1 (4.2%) was a transmission pair. 11 of 19 transmission pairs shared no epidemiological link. We identified 25 M. tb genetic clusters from 205 mono-TB isolates overall. CONCLUSION: Neighbours have lower prevalence and incidence of TB than household contacts, but twice as many cases. Very few received M. tb from their index case, suggesting uncontrolled community-wide transmission. Whole population active case finding may be necessary in high TB-burden settings.

Humans

Unveiling microbial risks in Chinese household dust: a comprehensive analysis from absolute abundance to virulence unit.

BACKGROUND: People spend the majority of their lives indoors, yet the risk and virulence potential of household microbiota remain largely unexplored, particularly in developing countries. RESULTS: Here, we conducted a nationwide survey on both dust samples and health information across 118 Chinese households. The microbiota composition and its functional units were analyzed using absolute 16S rRNA/ITS sequencing, metagenomics, and metaproteomics. Cross-domain network analysis of the core microbial communities revealed robust co-occurrence patterns in household dust. The mean absolute abundance of potentially pathogenic bacteria and fungi in households was 2.39&#x2009;&#xd7;&#x2009;105 and 2.83&#x2009;&#xd7;&#x2009;106 DNA copies/g dust. The potentially pathogenic community was primarily influenced by latitude, relative humidity, and average temperature. Although total absolute abundance was substantially lower in urban areas, the relative abundance of potentially pathogenic bacteria was markedly higher compared to rural environments. While urban-rural differences existed, the underlying statistical drivers were the environmental variables. The absolute abundance of potential pathogens was significantly associated with the prevalence of rhinitis, wheeze, and dermatitis in 266 participants. Children were identified as the highest-risk group from inhalation exposure of average daily dose. A total of 170 bacterial, 223 fungal virulence factors (VFs), and 370 antibiotic resistance genes (ARGs) were detected in dust and dust extracellular vesicle (EV)-associated DNA. EV-associated cargoes contributed 47.13% to the bacterial VF profiles, 11.90% to fungal VF&#xa0;profiles, and 44.45% to ARG profiles. Metaproteomic analysis confirmed the presence of VF profiles in dust EVs, which was further verified by curated proteomics data from 35 household pathogens. CONCLUSIONS: This study provides a comprehensive, quantitative framework linking indoor microbial exposure to health risks, highlighting EVs as a non-negligible, novel, extracellular mechanistic pathway for health impact in household environments. Video Abstract.

Child

The first two complete mitochondrial genomes for the genus Neotrichoporoides (Hymenoptera, Eulophidae) and their phylogenetic analysis.

Neotrichoporoides belongs to the family Eulophidae (Hymenoptera: Chalcidoidea). As a group of parasitic wasps, it plays an indispensable role in the biological control of agricultural and forest pests and in maintaining ecosystem balance. To date, only nine complete mitochondrial genomes of Eulophidae have been sequenced worldwide, including the two newly sequenced species in this study. To enrich our understanding of the mitochondrial genomic diversity of Eulophidae and to provide preliminary insights into its phylogenetic relationships, we sequenced and comparatively analyzed the mitochondrial genomes of two Neotrichoporoides species. The mitogenomes of N. nyemitawus (GenBank: PZ188956; 15,164 bp) and N. viridimaculatus (GenBank: PX794932; 15,297 bp) contain 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), two ribosomal RNAs (rRNAs), and one control region (CR), and exhibit a strong AT bias, with AT contents of 85.5% and 85.0%, respectively. We further analyzed mitochondrial gene rearrangements across 17 species from Encyrtidae, Eulophidae and Pteromalidae and summarized family-specific rearrangement characteristics. tRNA rearrangements were detected in all three families. Eulophidae harbors conserved PCGs, while the inverse transposition of trnA and transposition of trnV are likely reported for the first time within this family. The two Neotrichoporoides species differ only in the arrangement of several tRNAs. Comparative analysis of PCGs revealed differences in molecular evolutionary rates among genes, with ATP8, ND2 and ND4 evolving faster than the others. Phylogenetic analysis based on mitochondrial genome sequences showed that species from two subfamilies formed a monophyletic group, and congeneric species clustered into a single clade. This study contributes to resolving phylogenetic relationships within Eulophidae and further deepens our understanding of this family.

Eulophidae

Drug target ontology to classify and integrate drug discovery data.

BACKGROUND: One of the most successful approaches to develop new small molecule therapeutics has been to start from a validated druggable protein target. However, only a small subset of potentially druggable targets has attracted significant research and development resources. The Illuminating the Druggable Genome (IDG) project develops resources to catalyze the development of likely targetable, yet currently understudied prospective drug targets. A central component of the IDG program is a comprehensive knowledge resource of the druggable genome. RESULTS: As part of that effort, we have developed a framework to integrate, navigate, and analyze drug discovery data based on formalized and standardized classifications and annotations of druggable protein targets, the Drug Target Ontology (DTO). DTO was constructed by extensive curation and consolidation of various resources. DTO classifies the four major drug target protein families, GPCRs, kinases, ion channels and nuclear receptors, based on phylogenecity, function, target development level, disease association, tissue expression, chemical ligand and substrate characteristics, and target-family specific characteristics. The formal ontology was built using a new software tool to auto-generate most axioms from a database while supporting manual knowledge acquisition. A modular, hierarchical implementation facilitate ontology development and maintenance and makes use of various external ontologies, thus integrating the DTO into the ecosystem of biomedical ontologies. As a formal OWL-DL ontology, DTO contains asserted and inferred axioms. Modeling data from the Library of Integrated Network-based Cellular Signatures (LINCS) program illustrates the potential of DTO for contextual data integration and nuanced definition of important drug target characteristics. DTO has been implemented in the IDG user interface Portal, Pharos and the TIN-X explorer of protein target disease relationships. CONCLUSIONS: DTO was built based on the need for a formal semantic model for druggable targets including various related information such as protein, gene, protein domain, protein structure, binding site, small molecule drug, mechanism of action, protein tissue localization, disease association, and many other types of information. DTO will further facilitate the otherwise challenging integration and formal linking to biological assays, phenotypes, disease models, drug poly-pharmacology, binding kinetics and many other processes, functions and qualities that are at the core of drug discovery. The first version of DTO is publically available via the website http://drugtargetontology.org/ , Github ( http://github.com/DrugTargetOntology/DTO ), and the NCBO Bioportal ( http://bioportal.bioontology.org/ontologies/DTO ). The long-term goal of DTO is to provide such an integrative framework and to populate the ontology with this information as a community resource.

Biological Ontologies

Thyroid-joint crosstalk: a systematic review and meta-analysis of thyroid autoimmunity and dysfunction in juvenile idiopathic arthritis.

BACKGROUND: Recent observational studies outlined the concomitant presence of autoimmune diseases in children with juvenile idiopathic arthritis (JIA), including endocrine autoimmunity. Despite the growing evidence of thyroid involvement in JIA, available data are heterogeneous and fragmented. We aimed to systematically review the available evidence on the prevalence of thyroid autoantibody positivity and thyroid dysfunction in patients with JIA. METHODS: PubMed/Medline, Cochrane, and Scopus databases were approached to identify studies reporting data on thyroid autoantibody positivity and dysfunction in children with JIA. RESULTS: A total of 15 studies were included in the final analysis, encompassing 19 015 children with JIA (13 225 females, 69.6%) with a weighted mean age of 8.0 years (range 1.8-21 years). The pooled prevalence estimates of antithyroid antibody positivity and thyroid dysfunction were 0.04 (95% CI: 0.03-0.05) and 0.04 (95% CI: 0.03-0.08), respectively. The risk difference for thyroid autoantibody positivity between children with JIA and controls was 0.08 (95% CI: 0.02-0.14). Possible risk factors were analyzed: the presence of family history for thyroid autoimmune disease (odds ratio - OR 3.91, 95% CI 1.86-8.25), concurrent Antinuclear Antibodies (ANA) positivity (OR 1.62, 95% CI 1.13-2.31), and older age (MD 2.10 years, 95% CI 1.32-2.89) were associated with thyroid autoantibody positivity and/or thyroid dysfunction in children with JIA. No significant difference emerged for the specific JIA form. CONCLUSION: Thyroid dysfunction may be detected in children with JIA, with a significant risk difference in comparison to healthy controls. Specific clinical characteristics, such as family history, ANA positivity, and older age at JIA onset, may suggest which patients should benefit from thyroid autoantibody screening.

Humans

Characteristics and functions of a cell adhesion molecule PvCadN in Penaeus vannamei during WSSV infection.

Cell adhesion not only maintains the integrity of the organism, but also plays an important role in the immune system, which is involved in modulation in the interaction between host and virus. In this study, a novel cell adhesion molecule from Penaeus vannamei, designated as PvCadN, was investigated. It had the typical molecular characteristics of cadherin family, with multiple extracellular cadherin repeat domains, a transmembrane region, and a conserved &#x3b2;-catenin-binding motif. Pvcadn is expressed ubiquitously across all detected tissues, with the highest transcriptional level in gills. RNA interference-mediated silencing of pvcadn significantly impaired the adhesion ability of shrimp hemocytes. Upon WSSV infection, pvcadn showed a tissue-specific expression pattern, with upregulation in gills and downregulation in hemocytes. Knockdown of pvcadn markedly suppressed the transcription of WSSV immediate-early gene ie1 and replication of the viral genome in vivo, suggesting that PvCadN acted as a potential virus-associated molecule. Furthermore, it was found that PvCadN was regulated by Lv&#x3b2;-catenin, a core molecule in the Wnt signaling pathway that functions in innate immunity, at the transcriptional and protein levels. Silencing of lv&#x3b2;-catenin significantly downregulated pvcadn transcription, and Lv&#x3b2;-catenin bound directly to the Cadherin C domain of PvCadN. In summary, the study revealed that PvCadN was a key cell adhesion molecule involved in WSSV infection, which was regulated by Lv&#x3b2;-catenin. Our findings will provide fundamental data for further investigation into cadherin-mediated immune regulation in shrimp, and offer new insights for the prevention and control of WSSV.

Animals

Genome-wide characterization of the FOX gene family reveals sex-biased expression and FoxO-associated regulation during gonadal development in Bellamya aeruginosa.

Forkhead box (FOX) transcription factors are important regulators of development and reproduction, but their roles in molluscan gonadal development remain unclear. In this study, the FOX gene family was systematically identified in the freshwater gastropod Bellamya aeruginosa, and comparative gonadal transcriptomic analyses were performed across sexes and developmental stages.A total of 35 FOX genes were identified and classified into 19 subfamilies. Phylogenetic and synteny analyses indicated that the FOX gene family is generally conserved among mollusks, whereas FoxG and FoxL2 showed lineage-specific expansion. Structural analyses demonstrated that most BaeFOX proteins retained the conserved Forkhead domain architecture. Transcriptomic analyses revealed that gene expression divergence between testes and ovaries was markedly greater than that between developmental stages within the same gonad, indicating that sexual dimorphism is the major source of gonadal transcriptional variation. Functional enrichment consistently identified the FoxO signaling pathway in sex-biased comparisons. Several FOX genes also displayed clear gonad-biased expression patterns, and network analyses suggested that BaeFoxO, BaeFoxL2, and BaeFoxG may play central regulatory roles in gonadal development. These findings provide the first comprehensive characterization of the FOX gene family in B. aeruginosa and suggest that FOX-related regulatory networks potentially participate in gonadal development in gastropod mollusks.

Animals

TagR, a newly identified member of the MarR family of transcriptional regulators, represses the NRPS operon in Klebsiella oxytoca.

Toxigenic Klebsiella oxytoca strains produce the pyrrolobenzodiazepine enterotoxins tilimycin (TM) and tilivalline (TV), which contribute to the development of antibiotic-associated hemorrhagic colitis. The biosynthesis of these toxins depends on the nonribosomal peptide synthetase (NRPS) operon located within the til pathogenicity island. Although several global and signal-responsive regulators of NRPS operon expression have been identified, the regulatory network governing enterotoxin biosynthesis remains incompletely characterized. In this study, we identified a previously unrecognized transcriptional regulator encoded within the til pathogenicity island of K. oxytoca. This protein, designated TagR (Tilivalline-associated genes repressor), is a member of the MarR family and acts as a negative regulator of NRPS operon expression. Structural prediction, molecular dynamics simulations, and biochemical analyses demonstrated that TagR exhibits the characteristic architecture of MarR family regulators and forms a stable homodimer. Deletion of tagR led to significant upregulation of the NRPS-associated genes npsA, thdA, and npsB, while complementation restored transcriptional repression. Electrophoretic mobility shift assays confirmed that TagR binds directly and specifically to the regulatory region upstream of the NRPS operon, supporting a mechanism of direct transcriptional repression. Consistent with these findings, loss of TagR significantly increased the cytotoxicity of K. oxytoca culture supernatants toward HeLa cells. Collectively, these results identify TagR as a direct repressor of the NRPS operon and expand the regulatory framework governing enterotoxin biosynthesis in toxigenic K. oxytoca. This study provides new insight into the transcriptional control of virulence-associated genes and establishes TagR as a previously unrecognized component of the regulatory network controlling TM and TV production.IMPORTANCEElucidating the mechanisms by which toxigenic Klebsiella oxytoca regulates enterotoxin production is critical for understanding the pathogenesis of antibiotic-associated hemorrhagic colitis. TagR is identified as a previously unrecognized MarR family regulator that directly represses the nonribosomal peptide synthetase (NRPS) operon responsible for tilimycin (TM) and tilivalline (TV) biosynthesis. This discovery uncovers a novel regulatory mechanism governing toxin production and offers new perspectives on virulence regulation in this emerging intestinal pathogen.

Klebsiella oxytoca

Chromosome-Level Reference Genome of the Desert Night Lizard Xantusia vigilis.

We present a reference-quality genome assembly for the desert night lizard (Xantusia vigilis). The night lizards (Xantusiidae) are a family of small-bodied lizards found in North America (Xantusia), Central America (Lepidophyma), and Cuba (Cricosaura). The night lizard family has an independent evolutionary history of at least 80 million years from its sister taxa within Scincoidea. The Xantusiids have several unique ecological, behavioral and evolutionary characteristics. For instance, the family contains the only squamate species that form diploid, unisexual, parthenogenic lineages. In addition, most night lizards are viviparous and form stable kin groups that are maintained over multiple years, an unusual life history strategy among lizards. Combining PacBio long-read sequencing, Hi-C, and RNAseq data we developed a reference-quality genome for the desert night lizard, X. vigilis. We assembled a complete mitochondrion and&#x2009;~&#x2009;2.2 Gb nuclear genome, with 20 scaffolds that correlate in size to the X. vigilis karyotype. In addition, we found that X. vigilis chromosome 1 aligns with gene content of both of macrochromosome 1 and microchromosome 9 from a genome assembly of a species in the sister family Cordylidae (Hemicordylus capensis).

Xantusia

Molecular evolution and immune expression analysis of ELF transcription factors in Lethenteron reissneri.

As important members of the ETS superfamily, the E74-like factor (ELF) transcription factor family regulates gene transcription through a conserved ETS domain and plays critical roles in immune regulation. However, the evolutionary characteristics and functions of this family in lampreys (Lethenteron reissneri) remain unclear. In this study, the ELF gene family of lampreys (Lr-ELF1, Lr-ELF2, Lr-ELF3, and Lr-ELF5) was systematically identified, and their molecular evolutionary features and immune response functions were investigated. Phylogenetic analysis revealed evolutionary characteristics reflecting the transition from jawless to jawed vertebrates. Domain architecture, gene structure, and three-dimensional structural analyses indicated that these genes appear to be conserved among vertebrates, with their three-dimensional structures showing high similarity to the core secondary structural elements of human homologous proteins. Synteny analysis demonstrated significant differences in the genomic neighborhoods of ELF genes between lampreys and jawed vertebrates. Quantitative real-time PCR (qRT-PCR) was performed with three biological and three technical replicates; relative expression levels were calculated using the &#x394;Ct method, and statistical analysis was carried out with GraphPad Prism 9. Quantitative real-time PCR (qRT-PCR) results suggested that the ELF gene family may be involved in immune defense. This study not only enriches our understanding of the evolution of ELF genes but also provides new insights into the roles of lamprey ELFs in immune defense.

Animals

Genome-wide identification and comparative analysis of Leucine-Rich Repeat Containing (LRRC) gene and their expression responses to Vibrio alginolyticus infection in the Manila clam (Ruditapes philippinarum).

Leucine-rich repeat (LRR) domains are important components of many pattern recognition receptors (PRRs). Previous studies have demonstrated that LRR domain-containing immune receptors, such as nucleotide-binding oligomerization domain-like receptors (NLRs) and Toll-like receptors (TLRs), play important roles in innate immunity in aquatic animals. In addition to these well-characterized LRR-containing receptors, also possesses a group of LRR-containing proteins. These proteins were collectively referred to as leucine-rich repeat-containing (LRRC) proteins in this study, and their genomic characteristics, evolutionary relationships, were systematically analyzed. In this study, a genome-wide identification and characterization of LRRC genes were performed in the Manila clam. A total of 97 unclassified LRR genes were identified and designated as RpLRRCs.. Expression profiling indicated that RpLRRCs are predominantly expressed in the labial palps, digestive gland, and gills, increasing from the blastula stage and peaking at the juvenile stage during development, based on the transcriptome results from V. alginolyticus, V. anguillarum and V. parahaemolyticus, some RpLRRCs were involved in the response to different Vibrio stress. The qPCR analysis following V. alginolyticus challenge demonstrated that different RpLRRC members exhibit diverse response patterns to Vibrio infection. These results suggest that RpLRRCs may play critical roles in immune regulation. The RpLRRC gene family exhibits diverse structural characteristics and regulatory mechanisms and likely plays important roles in the growth, development, and immune response of R. philippinarum.

Immune response