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The meiosis-specific kinase Mek1 regulates key steps in meiotic recombination in the budding yeast, Saccharomyces cerevisiae. MEK1 limits resection at double-strand break (DSB) ends and is required for preferential strand invasion into homologs, a process known as interhomolog bias. After strand invasion, MEK1 promotes phosphorylation of the synaptonemal complex protein Zip1 that is necessary for DSB repair mediated by a crossover-specific pathway that enables chromosome synapsis. In addition, Mek1 phosphorylation of the meiosis-specific transcription factor, Ndt80 , regulates the meiotic recombination checkpoint that prevents exit from pachytene when DSBs are present. Mek1 interacts with Ndt80 through a 5-amino acid sequence, RPSKR, located between the DNA-binding and activation domains of Ndt80. AlphaFold Multimer modeling of a fragment of Ndt80 containing the RPSKR motif and full-length Mek1 indicated that RPSKR binds to an acidic loop located in the Mek1 FHA domain, a noncanonical interaction with this motif. A second protein, the 5′-3′ helicase Rrm3 , similarly interacts with Mek1 through an RPAKR motif and is an in vitro substrate of Mek1. Genetic analysis using various mutants in the MEK1 acidic loop validated the AlphaFold model, in that they specifically disrupt 2-hybrid interactions with Ndt80 and Rrm3. Phenotypic analyses further showed that the acidic loop mutants are defective in the meiotic recombination checkpoint and, in certain circumstances, exhibit more severe phenotypes compared to the NDT80 mutant with the RPSKR sequence deleted, suggesting that additional, as yet unknown, substrates of Mek1 also bind to Mek1 using an RPXKR motif. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis’s (Mtb) autarkic lifestyle within the host involves rewiring its transcriptional networks to combat host-induced stresses. With the help of RNA sequencing performed under various stress conditions, we identified that genes belonging to Mtb sulfur metabolism pathways are significantly upregulated during oxidative stress. Using an integrated approach of microbial genetics, transcriptomics, metabolomics, animal experiments, chemical inhibition, and rescue studies, we investigated the biological role of non-canonical L-cysteine synthases, CysM and CysK2. While transcriptome signatures of RvΔcysM and RvΔcysK2 appear similar under regular growth conditions, we observed unique transcriptional signatures when subjected to oxidative stress. We followed pool size and labelling (34S) of key downstream metabolites, viz. mycothiol and ergothioneine, to monitor L-cysteine biosynthesis and utilization. This revealed the significant role of distinct L-cysteine biosynthetic routes on redox stress and homeostasis. CysM and CysK2 independently facilitate Mtb survival by alleviating host-induced redox stress, suggesting they are not fully redundant during infection. With the help of genetic mutants and chemical inhibitors, we show that CysM and CysK2 serve as unique, attractive targets for adjunct therapy to combat mycobacterial infection. [ABSTRACT FROM AUTHOR]

The formation of biofilm in different places and the failure to effectively remove it by the usual disinfection methods is due to its structure and the rich genetic resource available in it to deal with disinfectants. These impenetrable structures and diverse microbial genetics have caused biofilm pollution in different industries like the food industry, the medicine industry, the hospitals and the water distribution system, resulting in pathogenicity and reduction of industrial quality. An efficient way to deal with the resistant population of biofilm‐forming microbes is the use of hurdle technology including enzymes and essential oils. Enzymes reduce the resistance of the biofilm structure due to degradation of its extracellular polymer matrix (EPS) by their abilities to break down the organic molecules, and then the essential oils weaken the cells by penetrating the lipid membrane of the cell and destroying its integrity; as a result, the biofilm will be destroyed. The advantage of this hurdle technology is the environmental friendly of both methods, which reduces concerns about the use of chemical disinfection methods, but on the other hand, due to the sensitivity of enzymes as biological agents also the expensiveness of this technique and the considerations of working with essential oils as volatile and unstable liquids should abandon the routine methods of applying this disinfectant to biofilm and go for the microencapsulation method, which as a protective system increases the effectiveness of enzymes and essential oils as antibiofilm agents. [ABSTRACT FROM AUTHOR]

Background: Periodontitis is the sixth-most common disease worldwide. The oral microbiome composition and its association with Periodontal disease (PD) have been largely explored; however, limited studies have explored the microbial profiles of both oral and toothbrushes in patients with PD. Thus, this study aimed to ascertain the oral and toothbrushes microbial composition in high-altitude populations, hypothesizing that their correlation with periodontal health would differ from those at lower altitudes, potentially indicating links between environmental factors, microbial colonization patterns, and periodontal health in distinct geographic contexts. Methods: In the present study, we enrolled 35 individuals including 21 healthy and 14 diagnosed with PD from the Lhasa region of Tibet, China. Saliva and toothbrush samples were collected from each participant to assess the association between toothbrush usage and oral microbiome with PD using 16 S rRNA gene-specific V3-V4 regions sequencing. To assess the oral and toothbrush microbiome composition and diversity and its possible link to PD. Results: Significantly higher Alpha diversity (Shannon index) was observed between the PD group and PD toothbrushes (p = 0.00021) and between the PD group and Healthy toothbrushes (p = 0.00041). The predominant species were Proteobacteria, Bacteroidota, Firmicutes, Actinobacteria, and Fusobacteria, with genera Pseudomonas, Veillonella, Neisseria, Acinetobacter, and Haemophilus. In addition, PICRUST2 analysis unveiled 44 significant pathways differentiating the disease and healthy groups, along with 29 pathways showing significant differences between their respective toothbrush microbial profiles. The distinct oral and toothbrush microbial composition among high-altitude populations suggests potential adaptations to the challenges of high-altitude environments. Conclusion: This study emphasizes the importance of tailored dental care strategies, accounting for altitude and racial factors, to effectively manage periodontal health in these communities. Further research is warranted to investigate the specific microbial mechanisms and develop targeted interventions for optimizing oral health in populations across varying altitudes. [ABSTRACT FROM AUTHOR]

Background: Metagenomic next-generation sequencing (mNGS) of circulating cell-free DNA from plasma is a hypothesis-independent broadband diagnostic method for identification of potential pathogens. So far, it has only been investigated in special risk populations (e.g. patients with neutropenic fever). Purpose: To investigate the extent to which mNGS (DISQVER® platform) can be used in routine clinical practice. Methods: We collected whole blood specimens for mNGS testing, blood cultures (BC), and pathogen-specific PCR diagnostics. Clinical data and pathogen diagnostics were retrospectively reviewed by an infectious disease expert panel regarding the adjustment of anti-infective therapy. Results: In 55 selected patients (median age 53 years, 67% male) with heterogeneous diagnoses, a total of 66 different microorganisms and viruses were detected using mNGS (51% viruses, 38% bacteria, 8% fungi, 3% parasites). The overall positivity rate of mNGS was 53% (29/55). Fifty-two out of 66 (79%) potential pathogens detected by mNGS were found in patients with primary or secondary immunodeficiency. The concordance rates of BC and pathogen-specific PCR diagnostics with mNGS testing were 14% (4/28) and 36% (10/28), respectively (p < 0.001). An additional bacterial pathogen (Streptococcus agalactiae) could only be detected by BC. Therapeutic consequences regarding anti-infective therapy were drawn from 23 pathogens (35% of detections), with 18 of these detections occurring in patients with immunodeficiency. Conclusions: We conclude that mNGS is a useful diagnostic tool, but should only be performed selectively in addition to routine diagnostics of infectious diseases. The limited number of patients and the retrospective study design do not allow any further conclusions. [ABSTRACT FROM AUTHOR]

Introduction: Cytomegalovirus (CMV) infection is present in a latent state in 70–90% of the immunocompetent population, and its reactivation might be triggered by inflammatory conditions such as post-COVID multisystem inflammatory syndrome (MIS-C) or by immunosuppression induced by steroids. The aim of this paper was to highlight the unexpected complications associated with SARS-CoV-2 infection that require a complex clinical approach for accurate diagnosis. Materials and Methods: We present the case of a 4-year-old male patient who, during an initially favorable course of PIMS, experienced symptoms of respiratory failure. Results: The patient initially presented with clinical and paraclinical signs of PIMS with cardiac involvement, for which high-dose corticosteroid therapy was initiated, followed by gradual tapering, along with immunoglobulins, anticoagulants, antiplatelet agents, and symptomatic treatment. After 10 days of favorable progress, the patient's general condition deteriorated, showing tachypnea, desaturation, and a ground-glass appearance on thoracic CT. Negative inflammatory markers and favorable cardiac lesion evolution ruled out MIS-C relapse. The presence of anti-CMV IgM antibodies and viral DNA in the blood confirmed acute CMV infection, likely triggered by prior severe-acute-respiratory-syndrome-related coronavirus 2 (SARS-CoV-2) infection and secondary immunosuppression due to steroids. Non-specific immunomodulatory treatment was initiated but led to worsening of pulmonary lesions, prompting the initiation of specific antiviral treatment with ganciclovir, resulting in rapid clinical and imaging improvement. Conclusions: CMV infection can be reactivated by immunosuppression induced by corticosteroid therapy for MIS-C and may require specific etiological treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: In meat production, the fat within an animal's muscles, known as intramuscular fat (IMF), is key to quality. This study investigated how breeding rabbits for higher or lower IMF levels affect their gut microorganisms. We focused on a rabbit population that was bred over 10 generations to achieve either high-IMF or low-IMF levels. Our findings show that genetic selection changes the gut's microbial composition, with more noticeable differences at the genus level than at the broader phylum level. High-IMF rabbits had different abundances of Escherichia, Methanobrevibacter, and Hungateiclostridium microorganisms compared to low-IMF rabbits, amongst others. We identified four specific microorganisms that could predict a rabbit's IMF genetic line with 78% accuracy. This research highlights the link between muscle fat genetics and gut microorganisms, opening the possibility of developing microbiome modulation strategies to influence IMF in animals, which could improve meat quality. Intramuscular fat (IMF) content is important for meat production and human health, where the host genetics and its microbiome greatly contribute to its variation. The aim of this study is to describe the consequences of the genetic modification of IMF by selecting the taxonomic composition of the microbiome, using rabbits from the 10th generation of a divergent selection experiment for IMF (high (H) and low (L) lines differ by 3.8 standard deviations). The selection altered the composition of the gut microbiota. Correlated responses were better distinguished at the genus level (51 genera) than at the phylum level (10 phyla). The H-line was enriched in Hungateiclostridium, Limosilactobacillus, Legionella, Lysinibacillus, Phorphyromonas, Methanosphaera, Desulfovibrio, and Akkermansia, while the L-line was enriched in Escherichia, Methanobrevibacter, Fonticella, Candidatus Amulumruptor, Methanobrevibacter, Exiguobacterium, Flintibacter, and Coprococcus, among other genera with smaller line differences. A microbial biomarker generated from the abundance of four of these genera classified the lines with 78% accuracy in a logit regression. Our results demonstrate different gut microbiome compositions in hosts with divergent IMF genotypes. Furthermore, we provide a microbial biomarker to be used as an indicator of hosts genetically predisposed to accumulate muscle lipids, which opens up the opportunity for research to develop probiotics or microbiome-based breeding strategies targeting IMF. [ABSTRACT FROM AUTHOR]

Summary Shotgun metagenomics allows for direct analysis of microbial community genetics, but scalable computational methods for the recovery of bacterial strain genomes from microbiomes remains a key challenge. We introduce Floria, a novel method designed for rapid and accurate recovery of strain haplotypes from short and long-read metagenome sequencing data, based on minimum error correction (MEC) read clustering and a strain-preserving network flow model. Floria can function as a standalone haplotyping method, outputting alleles and reads that co-occur on the same strain, as well as an end-to-end read-to-assembly pipeline (Floria-PL) for strain-level assembly. Benchmarking evaluations on synthetic metagenomes show that Floria is   >   3 × faster and recovers 21% more strain content than base-level assembly methods (Strainberry) while being over an order of magnitude faster when only phasing is required. Applying Floria to a set of 109 deeply sequenced nanopore metagenomes took <20 min on average per sample and identified several species that have consistent strain heterogeneity. Applying Floria's short-read haplotyping to a longitudinal gut metagenomics dataset revealed a dynamic multi-strain Anaerostipes hadrus community with frequent strain loss and emergence events over 636 days. With Floria, accurate haplotyping of metagenomic datasets takes mere minutes on standard workstations, paving the way for extensive strain-level metagenomic analyses. Availability and implementation Floria is available at https://github.com/bluenote-1577/floria , and the Floria-PL pipeline is available at https://github.com/jsgounot/Floria%5fanalysis%5fworkflow along with code for reproducing the benchmarks. [ABSTRACT FROM AUTHOR]

Simple Summary: Medullary thyroid carcinoma (MTC) is driven by a small number of pathogenic genetic variants and tumours usually exhibit a correspondingly low tumour mutational burden. This reduces tumour visibility to the immune system and impacts the immune cell profile of the tumour microenvironment. In the last decade targeted pathway inhibitors have revolutionized the therapeutic landscape for patients with advanced disease, with increasing options for systemic therapy tailored to the molecular signature of the tumour. Therefore, understanding the molecular basis of disease, pathogenesis of immune evasion and mechanisms of escape of pathway inhibition is of paramount importance. Here, we summarize genetic and molecular drivers of MTC and their relevance to tumour immunogenicity, the cellular milieu of the tumour microenvironment, and response to targeted therapy. In this review, we explore the underlying molecular biology of medullary thyroid carcinoma (MTC) and its interplay with the host immune system. MTC is consistently driven by a small number of specific pathogenic variants, beyond which few additional genetic events are required for tumorigenesis. This explains the exceedingly low tumour mutational burden seen in most MTC, in contrast to other cancers. However, because of the low tumour mutational burden (TMB), there is a correspondingly low level of tumour-associated neoantigens that are presented to the host immune system. This reduces tumour visibility and vigour of the anti-tumour immune response and suggests the efficacy of immunotherapy in MTC is likely to be poor, acknowledging this inference is largely based on the extrapolation of data from other tumour types. The dominance of specific RET (REarranged during Transfection) pathogenic variants in MTC tumorigenesis rationalizes the observed efficacy of the targeted RET-specific tyrosine kinase inhibitors (TKIs) in comparison to multi-kinase inhibitors (MKIs). Therapeutic durability of pathway inhibitors is an ongoing research focus. It may be limited by the selection pressure TKI treatment creates, promoting survival of resistant tumour cell clones that can escape pathway inhibition through binding-site mutations, activation of alternate pathways, and modulation of the cellular and cytokine milieu of the tumour microenvironment (TME). [ABSTRACT FROM AUTHOR]

Background: Multidrug resistant bacterial pathogens employ different mechanisms in evading the action of antibiotics. Multidrug resistance is wide spread among strains of Escherichia coli implicated in several infections including urinary tract infections, gastrointestinal infections, meningitis and bacteraemia. Aim/Objective: This study investigates the antibiotic resistance profile, efflux pump activity and biofilm formation ability of E. coli strains isolated from clinical samples. Methods: A total of 32 E. coli strains isolated from clinical samples were characterized and subjected to antibiotic susceptibility testing using standard methods. Isolates were screened phenotypically for biofilm formation and efflux pump activity. While molecular detection of genes encoding curli fimbriae and efflux pump activity was done by PCR. Results: All 32 (100%) E. coli isolates were resistant to ceftazidime, cefuroxime, cefixime, amoxicillin-clavulanate, ofloxacin and ciprofloxacin. While 30 (93.8%) were resistant to gentamicin, 27 (84.4%) were resistant to cefepime and the least resistance of 15.6% was to imipenem. Efflux pump encoding gene tolC was detected in 13(40.6%) of the isolates, while 1(3.1%) harboured acrA gene. acrB gene was not detected in any of the isolates. Seven (21.9%) of the isolates were strong biofilm formers, while 5 (15.6%) and 20 (62.5%) were moderate and weak biofilm formers respectively. csgA gene was detected in all E. coli isolates. Discussion: High antibiotic resistance of E. coli strains observed in this study is of public health significance.. It is therefore important to scale up efforts in regular monitoring of antibiotic resistance in both community and hospital settings. [ABSTRACT FROM AUTHOR]

SARS-CoV-2, the cause of the COVID-19 pandemic, has introduced a challenging era characterized by the persistent emergence of subvariants. Even after the World Health Organization announced the end of the pandemic, the virus continues to evolve, posing significant challenges to public health responses. This comprehensive review examines the multifaceted impacts of these subvariants, emphasizing their significance across diverse dimensions. SARS-CoV-2 has genetic variability, especially at the spike protein region, which has given rise to Variants of Concern, including Beta, Delta, Gamma, Alpha, and the highly mutable Omicron, which differently exhibit varying levels of immune evasion, disease severity, and transmissibility. Subvariants within the Omicron lineage, including BA.1, BA.2, BA.3, and others, further complicate the landscape with distinct genetic signatures and varying infectivity levels. The impacts extend to diagnostic techniques, treatment strategies, and vaccine effectiveness, underscoring the need for a comprehensive public health response emphasizing preventive measures, genomic surveillance, and vaccination campaigns. Sustaining these interventions is critical, necessitating long-term strategies considering socio-political factors, community involvement, continuous adaptation of healthcare approaches, robust monitoring, and sustainable public health interventions to effectively combat the virus's ever-changing landscape. [ABSTRACT FROM AUTHOR]

Microbes constitute the most prevalent life form on Earth, yet their remarkable diversity remains mostly unrecognized. Microbial diversity in vertebrate models presents a significant challenge for investigating host–microbiome interactions. The model organism Caenorhabditis elegans has many advantages for delineating the effects of host genetics on microbial composition. In the wild, the C. elegans gut contains various microbial species, while in the laboratory it is usually a host for a single bacterial species. There is a potential host–microbe interaction between microbial metabolites, drugs, and C. elegans phenotypes. This mini-review aims to summarize the current understanding regarding the microbiome in C. elegans. Examples using C. elegans to study host–microbe–metabolite interactions are discussed. [ABSTRACT FROM AUTHOR]

In the past few decades, there has been a notable rise in the occurrence of several types of candidiasis. Candida albicans is the most common cause of superficial fungal infections in humans. In this study, plumieride, one of the major iridoids from Plumeria obtusa L. leaves, was isolated and investigated for its potential against Candida albicans (CA)-induced dermatitis in mice. qRT-PCR was done to assess the impact of plumieride on the expression of the major virulence genes of CA. Five groups (n = 7) of adult male BALB/c mice were categorized into: group I: non-infected mice; group II: mice infected intradermally with 107–108 CFU/mL of CA; group III: CA-infected mice treated with standard fluconazole (50 mg/kg bwt.); group IV and V: CA-infected mice treated with plumieride (25- and 50 mg/kg. bwt., respectively). All the treatments were subcutaneously injected once a day for 3 days. Skin samples were collected on the 4th day post-inoculation to perform pathological, microbial, and molecular studies. The results of the in vitro study proved that plumieride has better antifungal activity than fluconazole, manifested by a wider zone of inhibition and a lower MIC. Plumieride also downregulated the expression of CA virulence genes (ALS1, Plb1, and Hyr1). CA-infected mice showed extensive dermatitis, confirmed by strong iNOS, TNF-α, IL-1β, and NF-κB genes or immune expressions. Whereas the treatment of CA-infected mice with plumieride significantly reduced the microscopic skin lesions and modulated the expression of all measured proinflammatory cytokines and inflammatory markers in a dose-dependent manner. Plumieride interfered with the expression of C. albicans virulence factors and modulated the inflammatory response in the skin of mice infected with CA. [ABSTRACT FROM AUTHOR]

Giardia is a prevalent single-celled microaerophilic intestinal parasite causing diarrheal disease and significantly impacting global health. Double diploid (essentially tetraploid) Giardia trophozoites have presented a formidable challenge to the development of molecular genetic tools to interrogate gene function. High sequence divergence and the high percentage of hypothetical proteins lacking homology to proteins in other eukaryotes have limited our understanding of Giardia protein function, slowing drug target validation and development. For more than 25 years, Giardia A and B assemblages have been readily amenable to transfection with plasmids or linear DNA templates. Here, we highlight the utility and power of genetic approaches developed to assess protein function in Giardia , with particular emphasis on the more recent clustered regularly interspaced palindromic repeats/Cas9-based methods for knockdowns and knockouts. Robust and reliable molecular genetic approaches are fundamental toward the interrogation of Giardia protein function and evaluation of druggable targets. New genetic approaches tailored for the double diploid Giardia are imperative for understanding Giardia 's unique biology and pathogenesis. [ABSTRACT FROM AUTHOR]

Simple Summary: Discovering new oncoviruses is a main goal of virology research. In addition to its deleterious role in immunocompromised patients and during pregnancy leading to birth defects, the human cytomegalovirus's (HCMV) potential role as an oncogenic agent has garnered significant attention recently. This perspective article focuses on the transforming potential of HCMV based on recently unveiled molecular and cellular characteristics of HCMV-infected cells. Epstein–Barr virus (EBV), Kaposi sarcoma human virus (KSHV), human papillomavirus (HPV), hepatitis B and C viruses (HBV, HCV), human T-lymphotropic virus-1 (HTLV-1), and Merkel cell polyomavirus (MCPyV) are the seven human oncoviruses reported so far. While traditionally viewed as a benign virus causing mild symptoms in healthy individuals, human cytomegalovirus (HCMV) has been recently implicated in the pathogenesis of various cancers, spanning a wide range of tissue types and malignancies. This perspective article defines the biological criteria that characterize the oncogenic role of HCMV and based on new findings underlines a critical role for HCMV in cellular transformation and modeling the tumor microenvironment as already reported for the other human oncoviruses. [ABSTRACT FROM AUTHOR]

The majority of bacteria live and evolve in surface biofilms. Both growth in biofilms and horizontal transfer of DNA are regulated by quorum‐sensing pheromone signals. The common regulation of bacterial surface growth and DNA transfers illustrates how physiology contributes to bacterial evolution. [ABSTRACT FROM AUTHOR]

Sea cucumber-derived fungi have attracted much attention due to their capacity to produce an incredible variety of secondary metabolites. Genome-wide information on Aspergillus micronesiensis H39 obtained using third-generation sequencing technology (PacBio-SMRT) showed that the strain contains nonribosomal peptide synthetase (NRPS)-like gene clusters, which aroused our interest in mining its secondary metabolites. 11 known compounds (1–11), including two γ-aromatic butenolides (γ-AB) and five cytochalasans, were isolated from A. micronesiensis H39. The structures of the compounds were determined by NMR and ESIMS, and comparison with those reported in the literature. From the perspective of biogenetic origins, the γ-butyrolactone core of compounds 1 and 2 was assembled by NRPS-like enzyme. All of the obtained compounds showed no inhibitory activity against drug-resistant bacteria and fungi, as well as compounds 1 and 2 had no anti-angiogenic activity against zebrafish. [ABSTRACT FROM AUTHOR]

Objective: Black groups have increased prevalence and accelerated pathogenicity of systemic lupus erythematosus (SLE) compared to other ethnic/racial groups. The microbiome and systemic microbial translocation are considered contributing factors to SLE disease pathogenesis. However, racial differences in the plasma microbiome and microbial translocation in lupus remain unknown. Methods: In the current study, we investigated plasma levels of microbial translocation (lipopolysaccharide [LPS] and zonulin) and the plasma microbiome using microbial 16S RNA sequencing of Black and White patients with SLE and Black and White healthy controls. Results: Plasma microbial translocation was increased in Black patients versus in White patients and in patients with SLE versus healthy controls regardless of race. Compared to sex, age, and disease status, race had the strongest association with plasma microbiome differences. Black groups (Black controls and Black patients) had lower α‐diversity than White groups (White controls and White patients) and more distinct β‐diversity. Black and White patients demonstrated differences in plasma bacterial presence, including Staphylococcus and Burkholderia. Compared to White patients, Black patients had higher SLE Disease Activity Index (SLEDAI) scores and urinary protein levels as well as a trend for increased anti–double‐stranded DNA (dsDNA) antibody levels consistent with the known increased severity of lupus in Black patients overall. Certain plasma bacteria at the genus level were identified that were associated with the SLEDAI score, urinary protein, and anti‐dsDNA antibody levels. Conclusion: This study reveals racial differences in both quality and quantity of plasma microbial translocation and identified specific plasma microbiome differences associated with SLE disease pathogenesis. Thus, this study may provide new insights into future potential microbiome therapies on SLE pathogenesis. [ABSTRACT FROM AUTHOR]

Predicting interactions between microbes and hosts plays critical roles in microbiome population genetics and microbial ecology and evolution. How to systematically characterize the sophisticated mechanisms and signal interplay between microbes and hosts is a significant challenge for global health risks. Identifying microbe-host interactions (MHIs) can not only provide helpful insights into their fundamental regulatory mechanisms, but also facilitate the development of targeted therapies for microbial infections. In recent years, computational methods have become an appealing alternative due to the high risk and cost of wet-lab experiments. Therefore, in this study, we utilized rich microbial metagenomic information to construct a novel heterogeneous microbial network (HMN)-based model named KGVHI to predict candidate microbes for target hosts. Specifically, KGVHI first built a HMN by integrating human proteins, viruses and pathogenic bacteria with their biological attributes. Then KGVHI adopted a knowledge graph embedding strategy to capture the global topological structure information of the whole network. A natural language processing algorithm is used to extract the local biological attribute information from the nodes in HMN. Finally, we combined the local and global information and fed it into a blended deep neural network (DNN) for training and prediction. Compared to state-of-the-art methods, the comprehensive experimental results show that our model can obtain excellent results on the corresponding three MHI datasets. Furthermore, we also conducted two pathogenic bacteria case studies to further indicate that KGVHI has excellent predictive capabilities for potential MHI pairs. [ABSTRACT FROM AUTHOR]

Weedy rice is a major problem in paddy fields around the world. It is well known that weedy rice appears to grow faster and mature earlier than cultivated rice. It is possible that differences in the root microbial genetics are correlated with this characteristic. This study incorporated 16S rRNA amplicon sequencing to study the microbial composition in the rhizosphere and endosphere of rice root. No significant difference was found between the microbiota associated with weedy and cultivated rice lines grown in the same field. It was found that the endosphere had less microbial diversity compared to the rhizosphere. The major groups of bacteria found in the endosphere are from the phylum Proteobacteria, Myxococcota, Chloroflexota, and Actinobacteria. In addition, by analyzing the microbiome of japonica rice grown in the field in a temperate climate, we found that despite differences in genotype and location, some bacterial taxa were found to be common and these members of the putative rice core microbiome can also be detected by in situ hybridization. The delineation of a core microbiome in the endosphere of rice suggests that these bacterial taxa might be important in the life cycle of a wide range of rice types. [ABSTRACT FROM AUTHOR]

Objectives: Gnathodiaphyseal dysplasia (GDD; OMIM#166260) is a rare skeletal genetic disorder characterized by sclerosis of tubular bones and cemento‐osseous lesions in mandibles. TMEM16E/ANO5 gene mutations have been identified in patients with GDD. Here, Ano5 knockout (Ano5−/−) mice with enhanced osteoblastogenesis were used to investigate whether Ano5 disruption affects osteoclastogenesis. Subjects and Methods: The maturation of osteoclasts, formation of F‐actin ring and bone resorption were detected by immunohistochemistry, TRAP, phalloidin staining and Coming Osteo assays. The expression of osteoclast‐related factors was measured by qRT‐PCR. Early signaling pathways were verified by western blot. Results: Ano5−/− mice exhibited inhibitory formation of multinucleated osteoclasts with a reduction of TRAP activity. The expression of Nfatc1, c‐Fos, Trap, Ctsk, Mmp9, Rank and Dc‐stamp was significantly decreased in bone tissues and bone marrow‐derived macrophages (BMMs) of Ano5−/− mice. Ano5−/− osteoclasts manifested disrupted actin ring and less mineral resorption. RANKL‐induced early signaling pathways were suppressed in Ano5−/− osteoclasts and Ano5 knockdown RAW264.7 cells. Moreover, the inhibitory effects of NF‐κB signalling pathway on osteoclastogenesis were partially attenuated with NF‐κB signalling activator. Conclusions: Ano5 deficiency impairs osteoclastogenesis, which leads to enhanced osteogenic phenotypes mediated by bone homeostasis dysregulation. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization announced the end of the Coronavirus Disease of 2019 (COVID-19) global health emergency on May 5, 2023. However, the reports from different countries indicate an elevation in the number of COVID-19-related hospitalizations and deaths through the last months. The subvariant XBB.1.5 (Kraken) was the cause of 49.1% of COVID-19 cases by the end of January 2023. Although, the subvariant EG.5 (Eris) has surpassed the XBB.1.5 recently. EG.5 is a close subvariant descending from XBB.1.9.2 subvariant of Omicron. EG.5.1 is a sublineage carrying two crucial spike mutations F456L and Q52H. Up to now, it is not well-established whether its infectivity, severity, and immune evasion have shown any change or not. Also, BA.2.86 another subvariant of Omicron descending from BA.2 bears over 30 mutations which could affect its infectivity and transmissibility. Methods: Scopus, PubMed, Google Scholar, and Google were searched with six keywords up to 20 November 2023 and highly reliable research and reports were selected to refer to in this article. Purpose: This brief review aims to overview the most reliable data about EG.5 and BA.2.86 based on scientific evidence. Conclusion: Based on the currently available data these two new subvariants have similar features with currently circulating variants of Omicron and are less immune evasive than ancestral SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to comprehensively review the multifaceted factors underlying the successful colonization and infection process of Helicobacter pylori (H. pylori), a prominent Gram-negative pathogen in humans. The focus is on elucidating the functions, mechanisms, genetic regulation, and potential cross-interactions of these elements. Methods: Employing a literature review approach, this study examines the intricate interactions between H. pylori and its host. It delves into virulence factors like VacA, CagA, DupA, Urease, along with phase variable genes, such as babA, babC, hopZ, etc., giving insights about the bacterial perspective of the infection The association of these factors with the infection has also been added in the form of statistical data via Funnel and Forest plots, citing the potential of the virulence and also adding an aspect of geographical biasness to the virulence factors. The biochemical characteristics and clinical relevance of these factors and their effects on host cells are individually examined, both comprehensively and statistically. Results: H. pylori is a Gram-negative, spiral bacterium that successfully colonises the stomach of more than half of the world's population, causing peptic ulcers, gastric cancer, MALT lymphoma, and other gastro-duodenal disorders. The clinical outcomes of H. pylori infection are influenced by a complex interplay between virulence factors and phase variable genes produced by the infecting strain and the host genetic background. A meta-analysis of the prevalence of all the major virulence factors has also been appended. Conclusion: This study illuminates the diverse elements contributing to H. pylori's colonization and infection. The interplay between virulence factors, phase variable genes, and host genetics determines the outcome of the infection. Despite biochemical insights into many factors, their comprehensive regulation remains an understudied area. By offering a panoramic view of these factors and their functions, this study enhances understanding of the bacterium's perspective, i.e. H. pylori's journey from infiltration to successful establishment within the host's stomach. [ABSTRACT FROM AUTHOR]

Invasive infections caused by Streptococcus pyogfenes (iGAS), commonly known as Group A Streptococcus, represent a significant public health concern due to their potential for rapid progression and life-threatening complications. Epidemiologically, invasive GAS infections exhibit a diverse global distribution, affecting individuals of all ages with varying predisposing factors. The pathogenesis of invasive GAS involves an array of virulence factors that contribute to tissue invasion, immune evasion, and systemic dissemination. In pediatrics, in the last few years, an increase in iGAS infections has been reported worldwide becoming a challenging disease to diagnose and treat promptly. This review highlights the current knowledge on pathogenesis, clinical presentations, and therapeutic approaches for iGAS in children. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to identify subspecies of Mycobacterium abscessus complex (MABC) isolates from clinical samples by a molecular technique and to determine mutations responsible for macrolide and aminoglycoside resistance. We also aimed to investigate the correlation of phenotypic and molecular test results by examining the resistance to antimicrobial agents according to CLSI standard using the liquid microdilution test. Methods: 27 MABC isolates from clinical samples were examined. Molecular subspecies identification and mutations responsible for aminoglycoside (rrs mutation) and macrolide resistance (rrl mutation) were determined using the GenoType NTM-DR test. The resistance phenotypes of the strains to various antimicrobial agents were investigated by the Sensititre™ RAPMYCOI AST microdilution test. Results: Of the 27 isolates tested, 21 were M. abscessus subsp. abscessus, three were M. abscessus subsp. bolletii, and three were M. abscessus subsp. massiliense; rrs and rrl mutations were not observed in any strains. Except for one isolate, all M. abscessus subsp. abscessus strains showed the erm(41) T28 genotype, which indicates inducible macrolide resistance. The correlation between the GenoType NTM-DR and phenotypic susceptibility test results was 81% (k=0.5, p=0.02) for inducible macrolide resistance and 89% for acquired macrolide resistance. The most effective antimicrobial agents were amikacin, cefoxitin, imipenem, linezolid, and tigecycline. Conclusion: Although the GenoType NTM-DR test is reliable in identifying and detecting molecular macrolide and aminoglycoside resistance, there were discrepancies in the results. We recommend confirming the results with the phenotypic susceptibility method after growth on culture. Although the M. abscessus complex is resistant to many antimicrobial agents, it has shown high sensitivity to amikacin, cefoxitin, imipenem, linezolid, and tigecycline. High levels of inducible macrolide resistance in isolates indicate the importance of subtyping and sensitivity testing of isolates in patients where culture conversion has not been achieved. [ABSTRACT FROM AUTHOR]

Background and Aim: Acinetobacter baumannii (A. baumannii) is an important bacterium that can cause multidrug-resistant nosocomial infections in the patients who are admitted to different hospital wards. Various factors play role in the resistance of this bacterium to antibiotics, one of the most important of which is the presence of drug efflux pumps. This study aimed to investigate the presence of the AdeABC efflux system and its role in drug resistance by inactivating them. Materials and Methods: Clinical samples were collected from three hospitals in Tehran, Iran for one year. The initial diagnosis and identification of A. baumannii was done by culture and biochemical methods. Finally, the identified prototypes were confirmed by molecular method. To investigate the role of antibiotic efflux pump in the drug resistance, minimum inhibitory concentration (MIC) for ciprofloxacin in the presence and absence of an efflux pump inhibitor, carbonyl cyanide 3- chlorophenylhydrazone (CCCP), was determined by microdilution method. Additionally, the presence of adeB, adeR, and adeS genes related to the AdeABC depletion system was investigated by PCR. Results: The results showed that more than 98% of the isolated bacteria had adeB, adeR, and adeS genes in the AdeABC depletion system. Approximately, 47.18% of these bacteria displayed a fourfold reduction in ciprofloxacin MIC levels in the presence of CCCP. Conclusion: Administration of a suitable antibiotic along with a safe efflux pump inhibitor for the treatment of A. baumannii infections can help to reduce the material and spiritual damages caused by the resistant bacteria. [ABSTRACT FROM AUTHOR]

The utilization of COVID-19-positive donors has expanded the donor pool for transplantation since the initiation of COVID allograft utilization protocols. However, the biopsy-proven PCR transmission rate of COVID-19 from these allografts has not been well documented. In August 2021, an institutional COVID-19-positive allograft protocol was implemented for liver and kidney transplants. Post-reperfusion liver biopsies were obtained intra-operatively to evaluate for COVID-19 RNA, and post-operative day 7 nasopharyngeal reverse transcriptase polymerase chain reaction (RT-PCR) swabs were collected. The primary endpoints evaluated included COVID-19 RNA on biopsy and COVID-19 detected via nasopharyngeal RT-PCR swab on post-operative day 7. A total of 20 vaccinated recipients underwent transplantation (17 liver only, 3 simultaneous liver and kidney) with whole liver allografts from 20 COVID-19-positive deceased donors between August 2021 and April 2022. 95% (19/20) of donors were asymptomatic at the time of donation. On post-reperfusion liver allograft biopsies, COVID-19 RNA was found in 10% (2/20) of the samples. All the recipients were COVID-19-negative on post-operative day 7 nasopharyngeal RT-PCR, showing a 0% transmission rate of COVID-19 from the positive allografts. The use of COVID-19 allografts appears to be a safe practice, with no PCR-detectable transmission of COVID-19 despite 10% of the liver allografts having COVID-19 RNA present on post-reperfusion biopsy. [ABSTRACT FROM AUTHOR]

Objectives: We examined factors contributing to the transmission of an acute respiratory virus within multi-use facilities, focusing on an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a movie theater in the Republic of Korea. Methods: This retrospective cohort study involved a descriptive analysis of 48 confirmed cases. Logistic regression was applied to a cohort of 80 theater attendees to identify risk factors for infection. The infection source and transmission route were determined through gene sequencing data analysis. Results: Of the 48 confirmed cases, 35 were theater attendees (72.9%), 10 were family members of attendees (20.8%), 2 were friends (4.2%), and 1 was an employee (2.1%). Among the 80 individuals who attended the 3rd to 5th screenings of the day, 35 became infected, representing a 43.8% attack rate. Specifically, 28 of the 33 third-screening attendees developed confirmed SARSCoV-2, constituting an 84.8% attack rate. Furthermore, 11 of the 12 cases epidemiologically linked to the theater outbreak were clustered monophyletically within the AY.69 lineage. At the time of the screening, 35 individuals (72.9%) had received 2 vaccine doses. However, vaccination status did not significantly influence infection risk. Multivariate analysis revealed that close contacts had a 15.9-fold higher risk of infection (95% confidence interval, 4.37-78.39) than casual contacts. Conclusion: SARS-CoV-2 transmission occurred within the theater, and extended into the community, via a moviegoer who attended the 3rd screening during the viral incubation period after contracting the virus from a family member. This study emphasizes the importance of adequate ventilation in theaters. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to compare metagenomic next-generation sequencing (mNGS) with other methods, including Xpert MTB/RIF, Mycobacterium tuberculosis (MTB) culture, and acid-fast bacillus (AFB) staining in the diagnosis of pulmonary tuberculosis (PTB) using bronchoalveolar lavage fluid (BALF). Methods The data of 186 patients with suspected PTB were retrospectively collected from January 2020 to May 2021 at Tongji Hospital. BALF samples were collected from all patients and analyzed using AFB staining, MTB culture, Xpert MTB/RIF, and mNGS. Results Of the 186 patients, 38 patients were ultimately diagnosed as PTB. Metagenomic next-generation sequencing exhibited a sensitivity of 78.95%, which was higher than AFB staining (27.59%) and MTB culture (44.12%) but similar to Xpert MTB/RIF (72.73%). Utilization of combined methods demonstrates improvement for PTB diagnosis. In support of this, the area under the receiver operating characteristic curve for the combination of mNGS and MTB culture (0.933, 95% CI: 0.871, 0.995) was larger than those of mNGS, Xpert MTB/RIF, MTB culture, and the combination of Xpert MTB/RIF and MTB culture. Conclusion The sensitivity of mNGS in the diagnosis of PTB using BALF specimen is similar to Xpert MTB/RIF. Metagenomic next-generation sequencing in combination with MTB culture may further improve the diagnosis of pulmonary tuberculosis. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The COVID-19 pandemic, as the most important health challenge in the world today, has made numerous irretrievable damages to the social, economic, and health dimensions of societies, especially in developing countries. An essential measure that can be taken to prevent and control the disease is to identify risk factors related to its prognosis and mortality rate. Therefore, this study aimed at investigating COVID-19 survival and mortality risk factors and their relationship with the demographic characteristics of the subjects diagnosed with the disease. MATERIAL AND METHODS: The present study is cross-sectional and descriptive. The samples consist of 1395 patients diagnosed with COVID-19 admitted to medical centers affiliated with Fasa University of Medical Sciences. The subjects were selected by census sampling. Data were collected using demographic information forms, paraclinical and radiological tests, and clinical examinations. Data were analyzed using SPSS version 18 via descriptive tests, paired t-tests, one-way ANOVA, and post hoc tests. RESULTS: According to the data, the participants' average age was 57.72 ± 4.63 years, and most of them (56.41%) were male. The mortality rate among the participants was estimated to be 13.19%. The results of the study showed a significant relationship between the survival status of patients with COVID-19 and underlying chronic diseases such as diabetes and cardiovascular and renal diseases (p < 0.05). CONCLUSIONS: Identifying high-risk groups is an important measure that health professionals should consider in controlling epidemics. The findings of this study showed that the presence of underlying chronic diseases such as diabetes and cardiac and renal conditions, which are associated with immune system defects, are among the most important factors related to the COVID-19 mortality. [ABSTRACT FROM AUTHOR]

This editorial highlights the significant contributions of female scientists to the field of microbial physiology and metabolism. It discusses historical discoveries made by female scientists, as well as recent studies led by women in the field. The article emphasizes the importance of diversity and inclusion in the scientific community. It also addresses the issue of bias in microbiology research and encourages readers to critically evaluate information they come across. This article provides a valuable perspective for library patrons conducting research on microbiology. [Extracted from the article]

Introduction: The association between Mycobacterium tuberculosis and the Human Immunodeficiency Virus can accelerate the deterioration of immunological functions. The risks are even more accentuated in the situation of a Non-tuberculous Mycobacterium and Mycobacterium tuberculosis co-infection. Case presentation: We present the case of a 59-year-old male patient, who was admitted at the hospital with non-specific symptoms. Further investigations reveal a remarkable particularity about the case: The infection with Mycobacterium tuberculosis was urogenital, whereas the one with Non-tuberculous mycobacteria was pulmonary. Conclusion: Both Mycobacterium tuberculosis and Non-tuberculous strains can exist within the same infection, posing great difficulties for diagnosis, as well as the treatment scheme. [ABSTRACT FROM AUTHOR]

Nodule bacteria (rhizobia) represent the highly developed model for the evolutionary genetics of symbiotic microorganisms. We propose to divide these polyphyletically originated bacteria into two groups that have arisen through: a) genomic rearrangements in free-living N2-fixers (primary rhizobia originated via the phyletic evolution strategy); b) transfer of symbiotically specialized (sym) genes from rhizobia to various soil and plant-associated bacteria (secondary rhizobia originated via the reticular evolution strategy). Primary rhizobia are represented by genus Bradyrhizobium close to Rhodopsedomonas. Transformation of these phototrophic N2-fixers into plant symbionts is evidenced by transitional (ancestral) Bradyrhizobium genotypes that combine the legume nodulation with photosynthesis. A crucial stage in rhizobia evolution was represented by acquisition of the ability to produce lipochitooligosaccharide Nod factors (NFs) eliciting the nodule development. Acquisition of NF synthesis allowed the ancestral Bradyrhizobium strains to switch from autotrophy to assimilation of the plant photosynthesis products resulted in heterotrophic bradyrhizobia (e.g., B. japonicum, B. elkanii) harboring sym genes in chromosomes. The best studied secondary rhizobia are represented by the Rhizobiaceae (Rhizobium, Sinorhizobium, Neorhizobium) species in which sym genes are located in mobile plasmids or chromids. Interactions of these species with legumes may be addressed as altruistic symbiosis based on development of non-reproducible bacteroids which supply hosts with N compounds. Since the rhizobia evolution involves the "gain-and-loss" genetic strategy, constructing highly active strains for legume crop inoculation should be based on activation of positive regulators of symbiotic N2 fixation and on inactivation of its negative regulators. [ABSTRACT FROM AUTHOR]

Epithelial cells contain polarity complexes on the lateral membrane and are organized in a hexagon-dominated polygonal array. The mechanisms regulating the organization of polygonal architecture in metazoan embryogenesis are not completely understood. Drosophila embryogenesis enables mechanistic analysis of epithelial polarity formation and its impact on polygonal organization. The plasma membrane (PM) of syncytial Drosophila blastoderm embryos is organized as a polygonal array with pseudocleavage furrow formation during the almost synchronous cortical division cycles. We find that polygonal (PM) organization arises in the metaphase (MP) of division cycle 11, and hexagon dominance occurs with an increase in furrow length in the metaphase of cycle 12. There is a decrease in cell shape index in metaphase from cycles 11 to 13. This coincides with Drosophila E-cad (DE-cadherin) and Bazooka enrichment at the edges and the septin, Peanut at the vertices of the furrow. We further assess the role of polarity and adhesion proteins in pseudocleavage furrow formation and its organization as a polygonal array. We find that DE-cadherin depletion leads to decreased furrow length, loss of hexagon dominance, and increased cell shape index. Bazooka and Peanut depletion lead to decreased furrow length, delay in onset of hexagon dominance from cycle 12 to 13, and increased cell shape index. Hexagon dominance occurs with an increase in furrow length in cycle 13 and increased DE-cadherin, possibly due to the inhibition of endocytosis. We conclude that polarity protein recruitment and regulation of endocytic pathways enable pseudocleavage furrow stability and the formation of a hexagon-dominated polygon array. [ABSTRACT FROM AUTHOR]

Objectives: The present study was conducted to assess the pattern of HBV Core/Pre-Core mutations and HBV genotype in Iraqi patients with chronic hepatitis B virus (HBV) infection. Methods: In the current cross-sectional study in an Iraqi province, we evaluated 134 patients diagnosed with HBV hepatitis. We used PCR and, subsequently, Sanger sequencing to assess HBV Core/Pre-Core mutations. Sanger sequencing reads were further used for phylogenetic analysis and multiple sequence alignment. A phylogenetic tree was generated according to the neighbor-joining method. Results: The current study revealed that 58 (45%) of the patients were male, and 72 (55%) of them were female. The mean age of the patients was 36 ± 12.7 years, and the mean duration of infection was 5.2 ± 4.8 years. The results revealed 21 nucleic acid alterations in the samples analyzed. The generated phylogenetic tree divided samples into two genotypes. Pre-core/Core mutations were significantly associated with the treatment received (P= 0.0.001) but not with laboratory parameters. Most samples were matched with the genotype D clade, while only four samples were positioned adjacent to the genotype E clade. Direct nucleic acid translation disclosed five nucleic acid variants (73T>G, 347T>G, 364A>G, 365T>C, and366A>G) on the core protein. Conclusions: This study has detected 21 nucleotide variants and 5 amino acid alterations within the coding sequences of the C gene. This study revealed that genotype D represents the primary genotype for the identified viral infections. The current study highlights the importance of these mutations evaluation for future, more comprehensive studies. [ABSTRACT FROM AUTHOR]

Upon DNA replication stress, cells utilize the postreplication repair pathway to repair single-stranded DNA and maintain genome integrity. Postreplication repair is divided into 2 branches: error-prone translesion synthesis, signaled by proliferating cell nuclear antigen (PCNA) monoubiquitination, and error-free template switching, signaled by PCNA polyubiquitination. In Saccharomyces cerevisiae, Rad5 is involved in both branches of repair during DNA replication stress. When the PCNA polyubiquitination function of Rad5 s disrupted, Rad5 recruits translesion synthesis polymerases to stalled replication forks, resulting in mutagenic repair. Details of how mutagenic repair is carried out, as well as the relationship between Rad5-mediated mutagenic repair and the canonical PCNA-mediated mutagenic repair, remain to be understood. We find that Rad5-mediated mutagenic repair requires the translesion synthesis polymerase ζ but does not require other yeast translesion polymerase activities. Furthermore, we show that Rad5-mediated mutagenic repair is independent of PCNA binding by Rev1 and so is separable from canonical mutagenic repair. In the absence of error-free template switching, both modes of mutagenic repair contribute additively to replication stress response in a replication timing-independent manner. Cellular contexts where error-free template switching is compromised are not simply laboratory phenomena, as we find that a natural variant in RAD5 is defective in PCNA polyubiquitination and therefore defective in error-free repair, resulting in Rad5- and PCNAmediated mutagenic repair. Our results highlight the importance of Rad5 in regulating spontaneous mutagenesis and genetic diversity in S. cerevisiae through different modes of postreplication repair. [ABSTRACT FROM AUTHOR]

The emergence of antimicrobial resistance raises the fear of untreatable diseases. Antimicrobial resistance is a multifaceted and dynamic phenomenon that is the cumulative result of different factors. While Gram-positive pathogens, such as methicillin-resistant Staphylococcus aureus and Clostridium difficile, were previously the most concerning issues in the field of public health, Gram-negative pathogens are now of prime importance. The World Health Organization's priority list of pathogens mostly includes multidrug-resistant Gram-negative organisms particularly carbapenem-resistant Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa, and extensively drug-resistant Acinetobacter baumannii. The spread of Gram-negative bacterial resistance is a global issue, involving a variety of mechanisms. Several strategies have been proposed to control resistant Gram-negative bacteria, such as the development of antimicrobial auxiliary agents and research into chemical compounds with new modes of action. Another emerging trend is the development of naturally derived antibacterial compounds that aim for targets novel areas, including engineered bacteriophages, probiotics, metal-based antibacterial agents, odilorhabdins, quorum sensing inhibitors, and microbiome-modifying agents. This review focuses on the current status of alternative treatment regimens against multidrugresistant Gram-negative bacteria, aiming to provide a snapshot of the situation and some information on the broader context. [ABSTRACT FROM AUTHOR]

Background: The Borna disease virus (BoDV-1) is an emerging zoonotic virus causing severe and mostly fatal encephalitis in humans. Methods and Results: A local cluster of fatal BoDV-1 encephalitis cases was detected in the same village three years apart affecting two children. While the first case was diagnosed late in the course of disease, a very early diagnosis and treatment attempt facilitated by heightened awareness was achieved in the second case. Therapy started as early as day 12 of disease. Antiviral therapy encompassed favipiravir and ribavirin, and, after bioinformatic modelling, also remdesivir. As the disease is immunopathogenetically mediated, an intensified anti-inflammatory therapy was administered. Following initial impressive clinical improvement, the course was also fatal, although clearly prolonged. Viral RNA was detected by qPCR in tear fluid and saliva, constituting a possible transmission risk for health care professionals. Highest viral loads were found post mortem in the olfactory nerve and the limbic system, possibly reflecting the portal of entry for BoDV-1. Whole exome sequencing in both patients yielded no hint for underlying immunodeficiency. Full virus genomes belonging to the same cluster were obtained in both cases by next-generation sequencing. Sequences were not identical, indicating viral diversity in natural reservoirs. Specific transmission events or a common source of infection were not found by structured interviews. Patients lived 750m apart from each other and on the fringe of the settlement, a recently shown relevant risk factor. Conclusion: Our report highlights the urgent necessity of effective treatment strategies, heightened awareness and early diagnosis. Gaps of knowledge regarding risk factors, transmission events, and tailored prevention methods become apparent. Whether this case cluster reflects endemicity or a geographical hot spot needs further investigation. [ABSTRACT FROM AUTHOR]

Summary: Spaceflight is physically demanding and can negatively affect astronauts’ health. It has been shown that the human gut microbiota and cardiac function are affected by spaceflight and simulated spaceflight. This study investigated the effects of the gut microbiota on simulated spaceflight-induced cardiac remodeling using 10° of head-down bed rest (HDBR) in rhesus macaques and 30° of hindlimb unloading (HU) in mice. The gut microbiota, fecal metabolites, and cardiac remodeling were markedly affected by HDBR in macaques and HU in mice, cardiac remodeling in control mice was affected by the gut microbiota of HU mice and that of HU mice was protected by the gut microbiota of control mice, and there was a correlation between cardiac remodeling and the gut microbial-derived metabolite trimethylamine N-oxide. These findings suggest that spaceflight can affect cardiac remodeling by modulating the gut microbiota and fecal metabolites.

Background: Improving feed efficiency is the most important goal for modern animal production. The regulatory mechanisms of controlling feed efficiency traits are extremely complex and include the functions related to host genetics and gut microbiota. Short-chain fatty acids (SCFAs), as significant metabolites of microbiota, could be used to refine the combined effect of host genetics and gut microbiota. However, the association of SCFAs with the gut microbiota and host genetics for regulating feed efficiency is far from understood. Results: In this study, 464 broilers were housed for RFI measuring and examining the host genome sequence. And 300 broilers were examined for cecal microbial data and SCFA concentration. Genome-wide association studies (GWAS) showed that four out of seven SCFAs had significant associations with genome variants. One locus (chr4: 29414391–29417189), located near or inside the genes MAML3, SETD7, and MGST2, was significantly associated with propionate and had a modest effect on feed efficiency traits and the microbiota. The genetic effect of the top SNP explained 8.43% variance of propionate. Individuals with genotype AA had significantly different propionate concentrations (0.074 vs. 0.131 μg/mg), feed efficiency (FCR: 1.658 vs. 1.685), and relative abundance of 14 taxa compared to those with the GG genotype. Christensenellaceae and Christensenellaceae_R-7_group were associated with feed efficiency, propionate concentration, the top SNP genotypes, and lipid metabolism. Individuals with a higher cecal abundance of these taxa showed better feed efficiency and lower concentrations of caecal SCFAs. Conclusion: Our study provides strong evidence of the pathway that host genome variants affect the cecal SCFA by influencing caecal microbiota and then regulating feed efficiency. The cecal taxa Christensenellaceae and Christensenellaceae_R-7_group were identified as representative taxa contributing to the combined effect of host genetics and SCFAs on chicken feed efficiency. These findings provided strong evidence of the combined effect of host genetics and gut microbial SCFAs in regulating feed efficiency traits. 6SQoLRD3ZqDatjTJpeYTJE Video Abstract [ABSTRACT FROM AUTHOR]

Although it has not been much noticed, reproduction is the central theme of François Jacob's important history of biology, La logique du vivant (The Logic of Life). In a book ostensibly devoted to heredity, this molecular biologist had reproduction integrate levels of organization from organisms to molecules and play a major role in each historical transition between them, not just in the influential argument for a shift "from generation to reproduction." Moreover, I claim, La logique was the first general history of (research on) reproduction. Earlier histories had tackled only aspects of generation and reproduction; none historicized the latter. Jacob's innovation came out of the rising prominence of reproduction in neo-Darwinist studies of populations and in his own field, the cellular genetics of bacteria and their viruses, and engagement with history and philosophy of science. The discovery of bacterial "sex" enabled microbial genetics but, ironically, led Jacob to a sexless concept of reproduction. This approach molded a history that reached across the living world but slighted sex and the complexities of reproduction in multicellular organisms. Readers can learn from its strength and limitations. [ABSTRACT FROM AUTHOR]

Simple Summary: Vaccination against human papillomavirus (HPV) helps prevent cancer caused by this virus. Determining which viral genotypes should be included is key for developing successful vaccination strategies. Low-risk genotypes, especially HPV6 and HPV11, are associated with benign warts. However, some studies also report their presence in cancers. We reviewed the scientific literature to estimate the proportion of cancers that bear single or dual HPV6/11 infections. HPV6 and HPV11 have been reported in up to 5.5% of penile and 87.5% of laryngeal cancers; however, they have not been reported in vulvar, vaginal or oral cancers. Next, we compared the HPV6/11 genomes with HPV16, the most common high-risk HPV genotype, and observed that the similarities mainly involved the E7 gene, suggesting a limited ability to interfere with the differentiation of the host cells. These findings support the use of HPV vaccines that cover HPV6/11 not only for preventing genital warts but also for preventing specific types of cancers. High-risk human papillomavirus (HPV) is etiologically related to cervical cancer, other anogenital cancers and oropharyngeal carcinomas. Low-risk HPV, especially HPV6 and HPV11, cause genital warts and laryngeal papillomas. However, the accumulating data suggests that HPV6 and HPV11 may cause malignant lesions at non-cervical anatomic sites. This review aims to estimate the proportions of single and dual HPV6/11 infections in multiple cancers reported in the last 10 years in the Cochrane, Embasa and PubMed databases. Secondly, the genomes of HPV6/11 were compared with the most common high-risk genotype, HPV16, to determine the similarities and differences. A total of 11 articles were selected, including between one and 334 HPV+ cancer patients. The frequencies of single or dual HPV6/11 infections ranged between 0–5.5% for penile and 0–87.5% for laryngeal cancers and were null for vulvar, vaginal and oral cancers. The genomic similarities between HPV6/11 and HPV16 mainly involved the E7 gene, indicating a limited ability to block cell differentiation. The presence of single or dual HPV6/11 infections in variable proportions of penile and laryngeal cancers support the vaccination strategies that cover these genotypes, not only for preventing genital warts but also for cancer prevention. Other risk factors and co-carcinogens are likely to participate in epithelial carcinogenesis associated with low-risk HPV. [ABSTRACT FROM AUTHOR]

A lack of evidence of accuracy for various testing modalities for carbapenem-resistant Enterobacterales (CRE) reduces the efficiency of screening and delays the isolation of carriers. This study examined the performance of phenotypic detection of CRE in comparison to molecular testing. A cross-sectional study was conducted in an academic medical institution in Saudi Arabia on CRE-screened patients during a 36-month period (April 1, 2019, through March 31, 2022). Cases were followed up for their susceptibility status by the phenotypic gradient method and genotypes. Of 3,116 samples tested, 359 carbapenemase genes were detected in 297 strains (9.5%) belonging to 292 patients. Oxacilliniase-48 (OXA-48) was the most frequently detected genotype (n=190, 64%), followed by a combined New Delhi metallo-B-lactamase (NDM)/OXA-48 genotype (n=77, 25.9%). Variable missed isolation days were encountered for various genotypes (0-18.5 days), with an excellent clinical utility index obtained for screening the OXA-48 genotype phenotypically. The data provided some insights into the predictive role and shortcomings of the e-test alone in CRE screening. While it provided a reasonable approach in a CRE population dominated by OXA-48 genotypes, it was more likely to miss the NDM-incurred carbapenemase. Thus, local epidemiology in an institution must be considered when designing a local screening protocol in addition to consideration of cost and turnaround time. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is the fourth most common cancer in women, and human papillomavirus (HPV) is the leading cause of cervical cancer. Cervical cancer screening and HPV vaccination are important factors in the incidence of cervical cancer. Methods: This study was performed on liquid base cytology (LBC) samples of 1214 women in Mashhad who were referred for cervical cancer screening in 2015-2020. Samples were examined by single-step polymerase chain reaction (PCR) and reverse line blot for HPV genotyping. Results: Totally, 386 women (31.8%) were HPV PCR positive. HPV genotyping of 277 samples showed that HPV 31 (3%), 16 (2.5%), 51 (2.2%), 18 (2%), and 66 (1.8%) were the most prevalent high-risk HPV (hrHPV) genotypes. Among low-risk HPV (lrHPV) genotypes, HPV 6 (9.2%), 53 (4.7%), and 42 (2.8%) were the most common genotypes. The range of multiple infections varied between two to eight genotypes and the prevalence of multiple HPV infections (12.4%) was higher than single infections (10.4%). Among women with single HPV infections, HPV 31 and 66 were equally the most common hrHPV genotypes, followed by HPV 16 and 39. In women with multiple HPV infections, HPV 31 was the most common hrHPV genotype, followed by HPV 51 and 16. For both single and multiple HPV infections, HPV 6 was the most common lrHPV genotype, followed by HPV 53 and 42. Conclusion: In conclusion, given the high prevalence of single and multiple HPV infections, the need for governmentally supported HPV vaccination and cervical cancer screening should be emphasized to prevent cervical cancer. [ABSTRACT FROM AUTHOR]

Background: The human gut microbiota is a complex community comprised of trillions of bacteria and is critical for the digestion and absorption of nutrients. Bacterial communities of the intestinal microbiota influence the development of several conditions and diseases. We studied the effect of host genetics on gut microbial composition using Collaborative Cross (CC) mice. CC mice are a panel of mice that are genetically diverse across strains, but genetically identical within a given strain allowing repetition and deeper analysis than is possible with other collections of genetically diverse mice. Results: 16S rRNA from the feces of 167 mice from 28 different CC strains was sequenced and analyzed using the Qiime2 pipeline. We observed a large variance in the bacterial composition across CC strains starting at the phylum level. Using bacterial composition data, we identified 17 significant Quantitative Trait Loci (QTL) linked to 14 genera on 9 different mouse chromosomes. Genes within these intervals were analyzed for significant association with pathways and the previously known human GWAS database using Enrichr analysis and Genecards database. Multiple host genes involved in obesity, glucose homeostasis, immunity, neurological diseases, and many other protein-coding genes located in these regions may play roles in determining the composition of the gut microbiota. A subset of these CC mice was infected with Salmonella Typhimurium. Using infection outcome data, an increase in abundance of genus Lachnospiraceae and decrease in genus Parasutterella correlated with positive health outcomes after infection. Machine learning classifiers accurately predicted the CC strain and the infection outcome using pre-infection bacterial composition data from the feces. Conclusion: Our study supports the hypothesis that multiple host genes influence the gut microbiome composition and homeostasis, and that certain organisms may influence health outcomes after S. Typhimurium infection. 1cB2MLUGvinhfMFtS15p86 Video Abstract [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is one of the most common cancers worldwide. Human bocavirus (HBoV), a recently isolated virus, has been investigated for its role in many respiratory and enteric diseases. Few studies have reported its presence in solid tumors, such as lung and colon cancers. The aim of this study was to detect the presence of the HBoV1 genome in gastric adenocarcinoma, which has not yet been evaluated. Methods: Formalin-fixed paraffin-embedded (FFPE) blocks of 189 gastric tumors and 50 blocks of non-tumor gastric tissue products from elective weight reduction operations were collected. DNA extraction and real-time polymerase chain reaction (PCR) were performed for HBoV1 detection. DNA sequencing was performed using ABI Genetic Analyzer series 3500. Results: The mean age of the patients was 60 ± 13.33 years. Tumors were more common in males than females (2.5/1). HBoV1 PCR was positive in 34 (18%) cases of GC and 10 (20%) cases of chronic gastritis (P > 0.05). There was no association between age, sex, stage, and histologic subtype of the tumor and HBoV1 positivity (P > 0.05) in tumor samples. The rate of intestinal metaplasia and presence of lymphoid stroma were also not more frequent in HBoV1-positive tumors (P > 0.05). Conclusion: The HBoV1 can be detected in a relatively high proportion of Iranian patients with gastric cancer (18%) with no predilection for specific subtypes and no association with the degree of lymphocytic infiltration. HBoV1 can also be observed in approximately 20% of chronic gastritis cases. Further comprehensive studies are needed to elucidate the role of HBoV1 in gastric cancer development. [ABSTRACT FROM AUTHOR]

Background and Aim: Antimicrobial resistance (AMR) is a serious global threat and the World Health Organization (WHO) declared AMR is one of 10 public health threatsfacing humanity. An increase in Carbapenem resistance is the major problem that hinders patient treatment. Various genes are responsible for carbapenem resistance but the gene bla-NDM can inactivate various carbapenem antibiotics namely meropenem and imipenem etc. Therefore, this study aimed to observe the prevalence of the bla-NDM gene in the carbapenem-resistant Klebsiella spp. isolates. Materials and Methods: The isolates of multidrug-resistant Klebsiella spp. were collected from the central diagnostic laboratory, Sree Balaji Medical College and Hospital, India after obtaining ethical clearance. The isolates were screened for carbapenem resistance using the Rapidec Carba NP method. The presence of bla-NDM was confirmed using the conventional PCR technique. Results & Conclusion: Most of the isolates showed resistance to ampicillin, gentamycin, cefazolin, imipenem, and meropenem. 45% of the isolates of K. pneumonia showed resistance to the carbapenem group of antibiotics and 20% of the K. oxytoca showed carbapenem resistance. Among the carbapenem-resistant 23.75% of K. pneumonia showed the presence of the bla-NDM gene and 6.6% of K. oxytoca showed the presence of the bla-NDM gene. Continuous increase in carbapenem drug-resistant organisms is worrisome and the judicious usage of antibiotics should be practiced. [ABSTRACT FROM AUTHOR]