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Background: Salmonella, an important foodborne pathogen, was estimated to be responsible for 95.1 million cases and 50,771 deaths worldwide. Sixteen serovars were responsible for approximately 80% of Salmonella infections in humans in China, and infections caused by a few uncommon serovars have been reported in recent years, though not with S. Welikade. This study reports the first clinical case caused by S. Welikade in China and places Chinese S. Welikade isolates in the context of global isolates via genomic analysis. For comparison, S. Welikade isolates were also screened in the Chinese Local Surveillance System for Salmonella (CLSSS). The minimum inhibitory concentrations (MICs) of 28 antimicrobial agents were determined using the broth microdilution method. The isolates were sequenced on an Illumina platform to identify antimicrobial resistance genes, virulence genes, and phylogenetic relationships. Results: The S. Welikade isolate (Sal097) was isolated from a two-year-old boy with acute gastroenteritis in 2021. Along with the other two isolates found in CLSSS, the three Chinese isolates were susceptible to all the examined antimicrobial agents, and their sequence types (STs) were ST5123 (n = 2) and ST3774 (n = 1). Single nucleotide polymorphism (SNP)-based phylogenetic analysis revealed that global S. Welikade strains can be divided into four groups, and these three Chinese isolates were assigned to B (n = 2; Sal097 and XXB1016) and C (n = 1; XXB700). In Group B, the two Chinese ST5123 isolates were closely clustered with three UK ST5123 isolates. In Group C, the Chinese isolate was closely related to the other 12 ST3774 isolates. The number of virulence genes in the S. Welikade isolates ranged from 59 to 152. The galF gene was only present in Group A, the pipB2 gene was only absent from Group A, the avrA gene was only absent from Group B, and the allB, sseK1, sspH2, STM0287, and tlde1 were found only within Group C and D isolates. There were 15 loci unique to the Sal097 isolate. Conclusion: This study is the first to characterize and investigate clinical S. Welikade isolates in China. Responsible for a pediatric case of gastroenteritis in 2021, the clinical isolate harbored no antimicrobial resistance and belonged to phylogenetic Group B of global S. Welikade genomes. [ABSTRACT FROM AUTHOR]

Background Escherichia coli is frequently responsible for bloodstream infections (BSIs). Among digestive BSIs, biliary infections appear to be less severe. Respective roles of host factors, bacterial determinants (phylogroups, virulence, and antibiotic resistance), and portal of entry on outcome are unknown. Methods Clinical characteristics and prognosis of 770 episodes of E coli BSI were analyzed and isolates sequenced (Illumina technology) comparing phylogroups, multilocus sequence type, virulence, and resistance gene content. BSI isolates were compared with 362 commensal E coli from healthy subjects. Results Among 770 episodes, 135 were biliary, 156 nonbiliary digestive, and 479 urinary. Compared to urinary infections, BSIs of digestive origin occurred significantly more in men, comorbid, and immunocompromised patients. Digestive portal of entry was significantly associated with septic shock and death. Among digestive infections, patients with biliary infections were less likely to die (P =.032), despite comparable initial severity. Biliary E coli resembled commensals (phylogroup distribution, sequence type, and few virulence-associated genes) whereas nonbiliary digestive and urinary strains carried many virulence-associated genes. Conclusions Escherichia coli strains responsible for biliary infections exhibit commensal characteristics and are associated with lower mortality rates, despite similar initial severity, than other digestive BSIs. Biliary drainage in addition to antibiotics in the management of biliary infections may explain improved outcome. [ABSTRACT FROM AUTHOR]

SUMMARY: Bermudagrass (Cynodon dactylon) is a globally distributed, extensively used warm‐season turf and forage grass with high tolerance to salinity and drought stress in alkaline environments. However, the origin of the species and genetic mechanisms for salinity tolerance in the species are basically unknown. Accordingly, we set out to study evolution divergence events in the Cynodon genome and to identify genes for salinity tolerance. We developed a 604.0 Mb chromosome‐level polyploid genome sequence for bermudagrass 'A12359' (n = 18). The C. dactylon genome comprises 2 complete sets of homoeologous chromosomes, each with approximately 30 000 genes, and most genes are conserved as syntenic pairs. Phylogenetic study showed that the initial Cynodon species diverged from Oropetium thomaeum approximately 19.7–25.4 million years ago (Mya), the A and B subgenomes of C. dactylon diverged approximately 6.3–9.1 Mya, and the bermudagrass polyploidization event occurred 1.5 Mya on the African continent. Moreover, we identified 82 candidate genes associated with seven agronomic traits using a genome‐wide association study, and three single‐nucleotide polymorphisms were strongly associated with three salt resistance genes: RAP2‐2, CNG channels, and F14D7.1. These genes may be associated with enhanced bermudagrass salt tolerance. These bermudagrass genomic resources, when integrated, may provide fundamental insights into evolution of diploid and tetraploid genomes and enhance the efficacy of comparative genomics in studying salt tolerance in Cynodon. Significance Statement: We have successfully sequenced the first heterozygous, tetraploid genome of Cynodon dactylon, a key warm‐season turfgrass and forage crop. Our GWAS analysis has identified genes linked to vital agronomic traits, enhancing our understanding of bermudagrass cultivation. [ABSTRACT FROM AUTHOR]

Increased use of whole genome sequencing (WGS) in neuro-oncology for diagnostics and research purposes necessitates a renewed conversation about informed consent procedures and governance structures for sharing personal health data. There is currently no consensus on how to obtain informed consent for WGS in this population. In this narrative review, we analyze the formats and contents of frameworks suggested in literature for WGS in oncology and assess their benefits and limitations. We discuss applicability, specific challenges, and legal context for patients with (recurrent) glioblastoma. This population is characterized by the rarity of the disease, extremely limited prognosis, and the correlation of the stage of the disease with cognitive abilities. Since this has implications for the informed consent procedure for WGS, we suggest that the content of informed consent should be tailor-made for (recurrent) glioblastoma patients. [ABSTRACT FROM AUTHOR]

Molluscan mitochondrial genomes are unusual because they show wide variation in size, radical genome rearrangements and frequently show high variation (> 10%) within species. As progress in understanding this variation has been limited, we used whole genome sequencing of a six-generation matriline of the terrestrial snail Cepaea nemoralis, as well as whole genome sequences from wild-collected C. nemoralis, the sister species C. hortensis, and multiple other snail species to explore the origins of mitochondrial DNA (mtDNA) variation. The main finding is that a high rate of SNP heteroplasmy in somatic tissue was negatively correlated with mtDNA copy number in both Cepaea species. In individuals with under ten mtDNA copies per nuclear genome, more than 10% of all positions were heteroplasmic, with evidence for transmission of this heteroplasmy through the germline. Further analyses showed evidence for purifying selection acting on non-synonymous mutations, even at low frequency of the rare allele, especially in cytochrome oxidase subunit 1 and cytochrome b. The mtDNA of some individuals of Cepaea nemoralis contained a length heteroplasmy, including up to 12 direct repeat copies of tRNA-Val, with 24 copies in another snail, Candidula rugosiuscula, and repeats of tRNA-Thr in C. hortensis. These repeats likely arise due to error prone replication but are not correlated with mitochondrial copy number in C. nemoralis. Overall, the findings provide key insights into mechanisms of replication, mutation and evolution in molluscan mtDNA, and so will inform wider studies on the biology and evolution of mtDNA across animal phyla. [ABSTRACT FROM AUTHOR]

Plasmodium parasites, the causal agents of malaria, are eukaryotic organisms that obligately undergo sexual recombination within mosquitoes. In low transmission settings, parasites recombine with themselves, and the clonal lineage is propagated rather than broken up by outcrossing. We investigated whether stochastic/neutral factors drive the persistence and abundance of Plasmodium falciparum clonal lineages in Guyana, a country with relatively low malaria transmission, but the only setting in the Americas in which an important artemisinin resistance mutation (pfk13 C580Y) has been observed. We performed whole genome sequencing on 1,727 Plasmodium falciparum samples collected from infected patients across a five-year period (2016–2021). We characterized the relatedness between each pair of monoclonal infections (n = 1,409) through estimation of identity-by-descent (IBD) and also typed each sample for known or candidate drug resistance mutations. A total of 160 multi-isolate clones (mean IBD ≥ 0.90) were circulating in Guyana during the study period, comprising 13 highly related clusters (mean IBD ≥ 0.40). In the five-year study period, we observed a decrease in frequency of a mutation associated with artemisinin partner drug (piperaquine) resistance (pfcrt C350R) and limited co-occurence of pfcrt C350R with duplications of plasmepsin 2/3, an epistatic interaction associated with piperaquine resistance. We additionally observed 61 nonsynonymous substitutions that increased markedly in frequency over the study period as well as a novel pfk13 mutation (G718S). However, P. falciparum clonal dynamics in Guyana appear to be largely driven by stochastic factors, in contrast to other geographic regions, given that clones carrying drug resistance polymorphisms do not demonstrate enhanced persistence or higher abundance than clones carrying polymorphisms of comparable frequency that are unrelated to resistance. The use of multiple artemisinin combination therapies in Guyana may have contributed to the disappearance of the pfk13 C580Y mutation. Author summary: Malaria is caused by eukaryotic Plasmodium parasites, which undergo sexual recombination within mosquitoes. In settings with low transmission, such as Guyana, these parasites often recombine with themselves, leading to the propagation of identical clones. We explored the population genomics of Plasmodium falciparum malaria parasites in Guyana over five years to characterize clonal transmission dynamics and understand whether they were influenced by local drug resistance mutations under strong selection, including pfk13 C580Y, which confers resistance to artemisinin, and pfcrt C350R, which confers resistance to piperaquine. Based on whole genome sequencing results from 1,409 monoclonal (single-strain) samples, we identified 160 multi-isolate clones, in which all parasites share at least 90% of their genomes through recent common ancestry. We observed a decrease in frequency of the pfcrt C350R mutation, as well as the disappearance of pfk13 C580Y. Our findings contrast with the deterministic rise of drug resistance mutations observed in other geographic regions, sometimes associated with clonality. The simultaneous use of at least two different artemisinin combination therapies may have prevented the spread of an artemisinin-resistant clone in Guyana, suggesting a strategy for resistance management in other geographic regions. [ABSTRACT FROM AUTHOR]

Choroid plexus tumors (CPTs) are intraventricular tumors derived from the choroid plexus epithelium and occur frequently in children. The aim of this study was to investigate the genomic and epigenomic characteristics of CPT and identify the differences between choroid plexus papilloma (CPP) and choroid plexus carcinoma (CPC). We conducted multiomics analyses of 20 CPT patients including CPP and CPC. Multiomics analysis included whole-genome sequencing, whole-transcriptome sequencing, and methylation sequencing. Mutually exclusive TP53 and EPHA7 point mutations, coupled with the amplification of chromosome 1, were exclusively identified in CPC. In contrast, amplification of chromosome 9 was specific to CPP. Differential gene expression analysis uncovered a significant overexpression of genes related to cell cycle regulation and epithelial-mesenchymal transition pathways in CPC compared to CPP. Overexpression of genes associated with tumor metastasis and progression was observed in the CPC subgroup with leptomeningeal dissemination. Furthermore, methylation profiling unveiled hypomethylation in major repeat regions, including long interspersed nuclear elements, short interspersed nuclear elements, long terminal repeats, and retrotransposons in CPC compared to CPP, implying that the loss of epigenetic silencing of transposable elements may play a role in tumorigenesis of CPC. Finally, the differential expression of AK1, regulated by both genomic and epigenomic factors, emerged as a potential contributing factor to the histological difference of CPP against CPC. Our results suggest pronounced genomic and epigenomic disparities between CPP and CPC, providing insights into the pathogenesis of CPT at the molecular level. [ABSTRACT FROM AUTHOR]

Disparities in data underlying clinical genomic interpretation is an acknowledged problem, but there is a paucity of data demonstrating it. The All of Us Research Program is collecting data including whole-genome sequences, health records, and surveys for at least a million participants with diverse ancestry and access to healthcare, representing one of the largest biomedical research repositories of its kind. Here, we examine pathogenic and likely pathogenic variants that were identified in the All of Us cohort. The European ancestry subgroup showed the highest overall rate of pathogenic variation, with 2.26% of participants having a pathogenic variant. Other ancestry groups had lower rates of pathogenic variation, including 1.62% for the African ancestry group and 1.32% in the Latino/Admixed American ancestry group. Pathogenic variants were most frequently observed in genes related to Breast/Ovarian Cancer or Hypercholesterolemia. Variant frequencies in many genes were consistent with the data from the public gnomAD database, with some notable exceptions resolved using gnomAD subsets. Differences in pathogenic variant frequency observed between ancestral groups generally indicate biases of ascertainment of knowledge about those variants, but some deviations may be indicative of differences in disease prevalence. This work will allow targeted precision medicine efforts at revealed disparities. A comparison of the frequency of pathogenic mutations in 73 genes in the All of Us cohort highlights the differences in pathogenic variation attributed to ancestry. [ABSTRACT FROM AUTHOR]

Aedes aegypti is vector of many arboviruses including Zika, dengue, yellow fever, West Nile, and Chikungunya. Its control efforts are hampered by widespread insecticide resistance reported in the Americas and Asia, while data from Africa is more limited. Here we use publicly available 729 Ae. aegypti whole-genome sequencing samples from 15 countries, including nine in Africa, to investigate the genetic diversity in four insecticide resistance linked genes: ace-1, GSTe2, rdl and vgsc. Apart from vgsc, the other genes have been less investigated in Ae. aegypti, and almost no genetic diversity information is available. Among the four genes, we identified 1,829 genetic variants including 474 non-synonymous substitutions, some of which have been previously documented, as well as putative copy number variations in GSTe2 and vgsc. Global insecticide resistance phenotypic data demonstrated variable resistance in geographic areas with resistant genotypes. Overall, our work provides the first global catalogue and geographic distribution of known and new amino-acid mutations and duplications that can be used to guide the identification of resistance drivers in Ae. aegypti and thereby support monitoring efforts and strategies for vector control. [ABSTRACT FROM AUTHOR]

Individuals with type 1 diabetes (T1D) carry a markedly increased risk of stroke, with distinct clinical and neuroimaging characteristics as compared to those without diabetes. Using whole-exome or whole-genome sequencing of 1,051 individuals with T1D, we aimed to find rare and low-frequency genomic variants associated with stroke in T1D. We analysed the genome comprehensively with single-variant analyses, gene aggregate analyses, and aggregate analyses on genomic windows, enhancers and promoters. In addition, we attempted replication in T1D using a genome-wide association study (N = 3,945) and direct genotyping (N = 3,263), and in the general population from the large-scale population-wide FinnGen project and UK Biobank summary statistics. We identified a rare missense variant on SREBF1 exome-wide significantly associated with stroke (rs114001633, p.Pro227Leu, p-value = 7.30 × 10–8), which replicated for hemorrhagic stroke in T1D. Using gene aggregate analysis, we identified exome-wide significant genes: ANK1 and LRRN1 displayed replication evidence in T1D, and LRRN1, HAS1 and UACA in the general population (UK Biobank). Furthermore, we performed sliding-window analyses and identified 14 genome-wide significant windows for stroke on 4q33-34.1, of which two replicated in T1D, and a suggestive genomic window on LINC01500, which replicated in T1D. Finally, we identified a suggestively stroke-associated TRPM2-AS promoter (p-value = 5.78 × 10–6) with borderline significant replication in T1D, which we validated with an in vitro cell-based assay. Due to the rarity of the identified genetic variants, future replication of the genomic regions represented here is required with sequencing of individuals with T1D. Nevertheless, we here report the first genome-wide analysis on stroke in individuals with diabetes. [ABSTRACT FROM AUTHOR]

Members of the genus Lysinibacillus attract attention for their mosquitocidal, bioremediation, and plant growth-promoting abilities. Despite this interest, comprehensive studies focusing on genomic traits governing plant growth and stress resilience in this genus using whole-genome sequencing are still scarce. Therefore, we sequenced and compared the genomes of three endophytic Lysinibacillus irui strains isolated from Canary Island date palms with the ex-type strain IRB4-01. Overall, the genomes of these strains consist of a circular chromosome with an average size of 4.6 Mb and a GC content of 37.2%. Comparative analysis identified conserved gene clusters within the core genome involved in iron acquisition, phosphate solubilization, indole-3-acetic acid biosynthesis, and volatile compounds. In addition, genome analysis revealed the presence of genes encoding carbohydrate-active enzymes, and proteins that confer resistance to oxidative, osmotic, and salinity stresses. Furthermore, pathways of putative novel bacteriocins were identified in all genomes. This illustrates possible common plant growth-promoting traits shared among all strains of L. irui. Our findings highlight a rich repertoire of genes associated with plant lifestyles, suggesting significant potential for developing inoculants to enhance plant growth and resilience. This study is the first to provide insights into the overall genomic signatures and mechanisms of plant growth promotion and biocontrol in the genus Lysinibacillus. Key points: • Pioneer study in elucidating plant growth promoting in L. irui through comparative genomics. • Genome mining identified biosynthetic pathways of putative novel bacteriocins. • Future research directions to develop L. irui-based biofertilizers for sustainable agriculture. [ABSTRACT FROM AUTHOR]

Neuronal ceroid lipofuscinosis (NCL) is a group of neurodegenerative disorders that occur in humans, dogs, and several other species. NCL is characterised clinically by progressive deterioration of cognitive and motor function, epileptic seizures, and visual impairment. Most forms present early in life and eventually lead to premature death. Typical pathological changes include neuronal accumulation of autofluorescent, periodic acid‐Schiff‐ and Sudan black B‐positive lipopigments, as well as marked loss of neurons in the central nervous system. Here, we describe a 19‐month‐old Schapendoes dog, where clinical signs were indicative of lysosomal storage disease, which was corroborated by pathological findings consistent with NCL. Whole genome sequencing of the affected dog and both parents, followed by variant calling and visual inspection of known NCL genes, identified a missense variant in CLN6 (c.386T>C). The variant is located in a highly conserved region of the gene and predicted to be harmful, which supports a causal relationship. The identification of this novel CLN6 variant enables pre‐breeding DNA‐testing to prevent future cases of NCL6 in the Schapendoes breed, and presents a potential natural model for NCL6 in humans. [ABSTRACT FROM AUTHOR]

Whole Genome Sequencing (WGS) is a promising tool in the global fight against tuberculosis (TB). The aim of this study was to evaluate the use of WGS in routine conditions for detection of drug resistance markers and transmission clusters in a multidrug-resistant TB hot-spot area in Peru. For this, 140 drug-resistant Mycobacterium tuberculosis strains from Lima and Callao were prospectively selected and processed through routine (GenoType MTBDRsl and BACTEC MGIT) and WGS workflows, simultaneously. Resistance was determined in accordance with the World Health Organization mutation catalogue. Agreements between WGS and BACTEC results were calculated for rifampicin, isoniazid, pyrazinamide, moxifloxacin, levofloxacin, amikacin and capreomycin. Transmission clusters were determined using different cut-off values of Single Nucleotide Polymorphism differences. 100% (140/140) of strains had valid WGS results for 13 anti-TB drugs. However, the availability of final, definitive phenotypic BACTEC MGIT results varied by drug with 10–17% of invalid results for the seven compared drugs. The median time to obtain results of WGS for the complete set of drugs was 11.5 days, compared to 28.6–52.6 days for the routine workflow. Overall categorical agreement by WGS and BACTEC MGIT for the compared drugs was 96.5%. Kappa index was good (0.65≤k≤1.00), except for moxifloxacin, but the sensitivity and specificity values were high for all cases. 97.9% (137/140) of strains were characterized with only one sublineage (134 belonging to "lineage 4" and 3 to "lineage 2"), and 2.1% (3/140) were mixed strains presenting two different sublineages. Clustering rates of 3.6% (5/140), 17.9% (25/140) and 22.1% (31/140) were obtained for 5, 10 and 12 SNP cut-off values, respectively. In conclusion, routine WGS has a high diagnostic accuracy to detect resistance against key current anti-TB drugs, allowing results to be obtained through a single analysis and helping to cut quickly the chain of transmission of drug-resistant TB in Peru. [ABSTRACT FROM AUTHOR]

This paper reports the results of gamma irradiation experiments and whole genome sequencing (WGS) performed on vegetative cells of two radiation resistant bacterial strains, Metabacillus halosaccharovorans (VITHBRA001) and Bacillus paralicheniformis (VITHBRA024) (D10 values 2.32 kGy and 1.42 kGy, respectively), inhabiting the top-ranking high background radiation area (HBRA) of Chavara-Neendakara placer deposit (Kerala, India). The present investigation has been carried out in the context that information on strategies of bacteria having mid-range resistance for gamma radiation is inadequate. WGS, annotation, COG and KEGG analyses and manual curation of genes helped us address the possible pathways involved in the major domains of radiation resistance, involving recombination repair, base excision repair, nucleotide excision repair and mismatch repair, and the antioxidant genes, which the candidate could activate to survive under ionizing radiation. Additionally, with the help of these data, we could compare the candidate strains with that of the extremely radiation resistant model bacterium Deinococccus radiodurans, so as to find the commonalities existing in their strategies of resistance on the one hand, and also the rationale behind the difference in D10, on the other. Genomic analysis of VITHBRA001 and VITHBRA024 has further helped us ascertain the difference in capability of radiation resistance between the two strains. Significantly, the genes such as uvsE (NER), frnE (protein protection), ppk1 and ppx (non-enzymatic metabolite production) and those for carotenoid biosynthesis, are endogenous to VITHBRA001, but absent in VITHBRA024, which could explain the former's better radiation resistance. Further, this is the first-time study performed on any bacterial population inhabiting an HBRA. This study also brings forward the two species whose radiation resistance has not been reported thus far, and add to the knowledge on radiation resistant capabilities of the phylum Firmicutes which are abundantly observed in extreme environment. [ABSTRACT FROM AUTHOR]

The Quercus L. species is widely recognized as a significant group in the broad-leaved evergreen forests of tropical and subtropical East Asia. These plants hold immense economic value for their use as firewood, furniture, and street trees. However, the identification of Quercus species is considered challenging, and the relationships between these species remain unclear. In this study, we sequenced and assembled the chloroplast (cp.) genomes of four Quercus section Cyclobalanopsis species (Quercus disciformis, Quercus dinghuensis, Quercus blackei, and Quercus hui). Additionally, we retrieved six published cp. genome sequences of Cyclobalanopsis species (Quercus fleuryi, Quercus pachyloma, Quercus ningangensis, Quercus litseoides, Quercus gilva, and Quercus myrsinifolia). Our aim was to perform comparative genomics and phylogenetic analyses of the cp. whole genome sequences of ten Quercus section Cyclobalanopsis species. The results revealed that: (1) Quercus species exhibit a typical tetrad structure, with the cp. genome lengths of the newly sequenced species (Q. disciformis, Q. dinghuensis, Q. blakei, and Q. hui) being 160,805 bp, 160,801 bp, 160,787 bp, and 160,806 bp, respectively; (2) 469 SSRs were detected, among which A/T base repeats were the most common; (3) no rearrangements or inversions were detected within the chloroplast genomes. Genes with high nucleotide polymorphism, such as rps14-psaB, ndhJ-ndhK, rbcL-accD, and rps19-rpl2_2, provided potential reference loci for molecular identification within the Cyclobalanopsis section; (4) phylogenetic analysis showed that the four sections of Cyclobalanopsis were grouped into sister taxa, with Q. hui being the first to diverge from the evolutionary branch and Q. disciformis being the most closely related to Q. blackei. The results of this study form the basis for future studies on taxonomy and phylogenetics. [ABSTRACT FROM AUTHOR]

Summary The study aimed to assess Campylobacter jejuni prevalence in chicken meat, biofilm formation, virulence factors, antibiotic resistance, and molecular typing. In the study, 200 chicken meat samples were collected from local outlets and 51 (25.5%) isolates were identified as C. jejuni. Resistance rates to ampicillin, tetracycline, sulfamethoxazole/trimethoprim, and ciprofloxacin were 59%, 60%, 64%, and 64% respectively. Many of the isolates (49%) exhibited multidrug resistance. Beta‐lactamase and tetracycline resistance genes were found in 82.3% and 86.2% of isolates, respectively. Virulence genes were detected in various proportions. Biofilm formation was weak to moderate. ERIC‐PCR showed varied band profiles. Whole genome sequencing confirmed findings. The study highlights C. jejuni presence with antibiotic resistance, virulence and biofilm features in chicken meat, posing public health risks. [ABSTRACT FROM AUTHOR]

• Largest GBS genome sequence sample of Chinese infants. • Baseline data for GBS surveillance and vaccine impact evaluation. Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in young infants worldwide. This study aimed to investigate candidate GBS vaccine targets, virulence factors, and antimicrobial resistance determinants. We used whole-genome sequencing to characterize invasive GBS isolates from infants < 3 months of age obtained from a multicenter population-based study conducted from 2015 to 2021 in China. Overall, seven serotypes were detected from 278 GBS isolates, four (Ia, Ib, III, V) of which accounted for 97.8 %. We detected 30 sequence types (including 10 novel types) that were grouped into six clonal complexes (CCs: CC1, CC10, CC17, CC19, CC23 and CC651); three novel ST groups in CC17 were detected, and the rate of CC17, considered a hyperinvasive neonatal clone complex, was attached to 40.6 % (113/278). A total of 98.9 % (275/278) of isolates harbored at least one alpha-like protein gene. All GBS isolates contained at least one of three pilus backbone determinants and the pilus types PI-2b and PI-1 + PI-2a accounted for 79.8 % of the isolates. The 112 serotype III/CC17 GBS isolates were all positive for hvgA. Most of the isolates (75.2 %) were positive for serine-rich repeat glycoprotein determinants (srr1 or srr2). Almost all isolates possessed cfb (99.6 %), c1IE (100 %), lmb (95.3 %) or pavA (100 %) gene. Seventy-seven percent of isolates harboured more than three antimicrobial resistance genes with 28.4 % (79/278) gyr A quinolone resistance determinants mutation, 83.8 % (233/278) carrying tet cluster genes and 77.3 % (215/278) carrying erm genes which mediated fluoroquinolone, tetracycline and clindamycin resistance, respectively." The findings from this large whole-genome sequence of GBS isolates establish important baseline data required for further surveillance and evaluating the impact of future vaccine candidates. [ABSTRACT FROM AUTHOR]

Soybean is the main oilseed cultivated worldwide. Even though Brazil is the world's largest producer and exporter of soybean, its production is severely limited by biotic factors. Soil borne diseases are the most damaging biotic stressors since they significantly reduce yield and are challenging to manage. In this context, the present study aimed to evaluate the potential of a bacterial strain (Ag109) as a biocontrol agent for different soil pathogens (nematodes and fungi) of soybean. In addition, the genome of Ag109 was wholly sequenced and genes related to secondary metabolite production and plant growth promotion were mined. Ag109 showed nematode control in soybean and controlled 69 and 45% of the populations of Meloidogyne javanica and Pratylenchus brachyurus, respectively. Regarding antifungal activity, these strains showed activity against Macrophomia phaseolina, Rhizoctonia solani, and Sclerotinia sclerotiorum. For S. sclerotiorum, this strain increased the number of healthy plants and root dry mass compared to the control (with inoculation). Based on the average nucleotide identity and digital DNA-DNA hybridization, this strain was identified as Bacillus velezensis. Diverse clusters of specific genes related to secondary metabolite biosynthesis and root growth promotion were identified, highlighting the potential of this strain to be used as a multifunctional microbial inoculant that acts as a biological control agent while promoting plant growth in soybean. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) arises from complex interactions between host and environment, which include the gut and tissue microbiome. It is hypothesized that epigenetic regulation by gut microbiota is a fundamental interface by which commensal microbes dynamically influence intestinal biology. The aim of this study is to explore the interplay between gut and tissue microbiota and host DNA methylation in CRC. Methods: Metagenomic sequencing of fecal samples was performed on matched CRC patients (n = 18) and healthy controls (n = 18). Additionally, tissue microbiome was profiled with 16S rRNA gene sequencing on tumor (n = 24) and tumor-adjacent normal (n = 24) tissues of CRC patients, while host DNA methylation was assessed through whole-genome bisulfite sequencing (WGBS) in a subset of 13 individuals. Results: Our analysis revealed substantial alterations in the DNA methylome of CRC tissues compared to adjacent normal tissues. An extensive meta-analysis, incorporating publicly available and in-house data, identified significant shifts in microbial-derived methyl donor-related pathways between tumor and adjacent normal tissues. Of note, we observed a pronounced enrichment of microbial-associated CpGs within the promoter regions of genes in adjacent normal tissues, a phenomenon notably absent in tumor tissues. Furthermore, we established consistent and recurring associations between methylation patterns of tumor-related genes and specific bacterial taxa. Conclusions: This study emphasizes the pivotal role of the gut microbiota and pathogenic bacteria in dynamically shaping DNA methylation patterns, impacting physiological homeostasis, and contributing to CRC tumorigenesis. These findings provide valuable insights into the intricate host-environment interactions in CRC development and offer potential avenues for therapeutic interventions in this disease. [ABSTRACT FROM AUTHOR]

Infection caused by KPC and NDM carbapenemases co-producing Klebsiella pneumoniae (KPC_NDM_CRKP) poses serious public health concerns. Here, we elucidate the prevalence of a hypertransmissible lncM1 plasmid, pKPC_NDM, co-carrying blaKPC-2 and blaNDM-1 genes in sequence type 1049 K_locus 5 (ST1049-KL5) KPC_NDM_CRKP isolates. Genetic and clonal relatedness analyses using pulsed-field gel electrophoresis, single nucleotide polymorphism analysis and core genome multilocus sequence typing suggested clonal dissemination of ST1049-KL5 KPC_NDM_CRKP strains in our hospital. Whole genome sequencing identified an identical 76,517 bp- blaKPC-2 and blaNDM-1 genes co-carrying IncM1 plasmid pKPC_NDM and a pLVPK-like hypervirulent plasmid in all ST1049-KL5 KPC_NDM_CRKP isolates. pKPC_NDM shared 100% identity with a previously sequenced plasmid CRKP35_unnamed4, demonstrating high transferability in conjugation assay, with conjugation frequencies reaching 10-4 and 10-5 in Escherichia coli and K. pneumoniae recipients, respectively. It also maintained favorable stability and flexible compatibility, with retention rates exceeding 80% after 10 days of continuous passage, and could be compatible with pre-existing blaKPC- or blaNDM-carrying plasmids in recipient strains. This study summarizes the characteristics of KPC_NDM_CRKP outbreaks and highlights the importance of ongoing surveillance and infection control strategies to address the challenges posed by ST1049 K. pneumoniae strains. The study focuses on a blaKPC-2 and blaNDM-1 co-carrying hypertransmissible IncM1 plasmid in ST1049 CRKP strains, highlights the importance of ongoing surveillance and infection control strategies to address the challenges posed by ST1049 K. pneumoniae. [ABSTRACT FROM AUTHOR]

Oxford Nanopore Technologies (ONT) sequencing is a promising technology. We assessed the performance of the new ONT R10 flowcells and V14 rapid sequencing chemistry for Mtb whole genome sequencing of Mycobacterium tuberculosis (Mtb) DNA extracted from clinical primary liquid cultures (CPLCs). Using the recommended protocols for MinION Mk1C, R10.4.1 MinION flowcells, and the ONT Rapid Sequencing Kit V14 on six CPLC samples, we obtained a pooled library yield of 10.9 ng/μl, generated 1.94 Gb of sequenced bases and 214k reads after 48h in a first sequencing run. Only half (49%) of all generated reads met the Phred Quality score threshold (>8). To assess if the low data output and sequence quality were due to impurities present in DNA extracted directly from CPLCs, we added a pre-library preparation bead-clean-up step and included purified DNA obtained from an Mtb subculture as a control sample in a second sequencing run. The library yield for DNA extracted from four CPLCs and one Mtb subculture (control) was similar (10.0 ng/μl), 2.38 Gb of bases and 822k reads were produced. The quality was slightly better with 66% of the produced reads having a Phred Quality >8. A third run of DNA from six CPLCs with bead clean-up pre-processing produced a low library yield (±1 Gb of bases, 166k reads) of low quality (51% of reads with a Phred Quality score >8). A median depth of coverage above 10× was only achieved for five of 17 (29%) sequenced libraries. Compared to Illumina WGS of the same samples, accurate lineage predictions and full drug resistance profiles from the generated ONT data could not be determined by TBProfiler. Further optimization of the V14 ONT rapid sequencing chemistry and library preparation protocol is needed for clinical Mtb WGS applications. [ABSTRACT FROM AUTHOR]

Vaccine-related myocarditis associated with the BNT162b2 vaccine is a rare complication, with a higher risk observed in male adolescents. However, the contribution of genetic factors to this condition remains uncertain. In this study, we conducted a comprehensive genetic association analysis in a cohort of 43 Hong Kong Chinese adolescents who were diagnosed with myocarditis shortly after receiving the BNT162b2 mRNA COVID-19 vaccine. A comparison of whole-genome sequencing data was performed between the confirmed myocarditis cases and a control group of 481 healthy individuals. To narrow down potential genomic regions of interest, we employed a novel clustering approach called ClusterAnalyzer, which prioritised 2,182 genomic regions overlapping with 1,499 genes for further investigation. Our pathway analysis revealed significant enrichment of these genes in functions related to cardiac conduction, ion channel activity, plasma membrane adhesion, and axonogenesis. These findings suggest a potential genetic predisposition in these specific functional areas that may contribute to the observed side effect of the vaccine. Nevertheless, further validation through larger-scale studies is imperative to confirm these findings. Given the increasing prominence of mRNA vaccines as a promising strategy for disease prevention and treatment, understanding the genetic factors associated with vaccine-related myocarditis assumes paramount importance. Our study provides valuable insights that significantly advance our understanding in this regard and serve as a valuable foundation for future research endeavours in this field. [ABSTRACT FROM AUTHOR]

Objectives: The Bengal tiger Panthera tigris tigris, is an emblematic animal for Bangladesh. Despite being the apex predator in the wild, their number is decreasing due to anthropogenic activities such as hunting, urbanization, expansion of agriculture and deforestation. By contrast, captive tigers are flourishing due to practical conservation efforts. Breeding within the small captive population can produce inbreeding depression and genetic bottlenecks, which may limit the success of conservation efforts. Despite past decades of research, a comprehensive database on genetic variation in the captive and wild Bengal tigers in Bangladesh still needs to be included. Therefore, this research aimed to investigate the White Bengal tiger genome to create a resource for future studies to understand variation underlying important functional traits. Data description: Blood samples from Chattogram Zoo were collected for three white Bengal tigers. Genomic DNA for all collected samples were extracted using a commercial DNA extraction kit. Whole genome sequencing was performed using a DNBseq platform. We generated 77 Gb of whole-genome sequencing (WGS) data for three white Bengal tigers (Average 11X coverage/sample). The data we generated will establish a paradigm for tiger research in Bangladesh by providing a genomic resource for future functional studies on the Bengal white tiger. [ABSTRACT FROM AUTHOR]

Background: The crossbreeding of specialized beef cattle breeds with Chinese indigenous cattle is a common method of genetic improvement. Xia'nan cattle, a crossbreed of Charolais and Nanyang cattle, is China's first specialized beef cattle breed with independent intellectual property rights. After more than two decades of selective breeding, Xia'nan cattle exhibit a robust physique, good environmental adaptability, good tolerance to coarse feed, and high meat production rates. This study analyzed the population genetic structure, genetic diversity, and genomic variations of Xia'nan cattle using whole-genome sequencing data from 30 Xia'nan cattle and 178 published cattle genomic data. Result: The ancestry estimating composition analysis showed that the ancestry proportions for Xia'nan cattle were mainly Charolais with a small amount of Nanyang cattle. Through the genetic diversity studies (nucleotide diversity and linkage disequilibrium decay), we found that the genomic diversity of Xia'nan cattle is higher than that of specialized beef cattle breeds in Europe but lower than that of Chinese native cattle. Then, we used four methods to detect genome candidate regions influencing the excellent traits of Xia'nan cattle. Among the detected results, 42 genes (θπ and CLR) and 131 genes (FST and XP-EHH) were detected by two different detection strategies. In addition, we found a region in BTA8 with strong selection signals. Finally, we conducted functional annotation on the detected genes and found that these genes may influence body development (NR6A1), meat quality traits (MCCC1), growth traits (WSCD1, TMEM68, MFN1, NCKAP5), and immunity (IL11RA, CNTFR, CCL27, SLAMF1, SLAMF7, NAA35, and GOLM1). Conclusion: We elucidated the genomic features and population structure of Xia'nan cattle and detected some selection signals in genomic regions potentially associated with crucial economic traits in Xia'nan cattle. This research provided a basis for further breeding improvements in Xia'nan cattle and served as a reference for genetic enhancements in other crossbreed cattle. [ABSTRACT FROM AUTHOR]

Background: Bisulfite sequencing (BS-Seq) is a fundamental technique for characterizing DNA methylation profiles. Genotype calling from bisulfite-converted BS-Seq data allows allele-specific methylation analysis and the concurrent exploration of genetic and epigenetic profiles. Despite various methods have been proposed, single nucleotide polymorphisms (SNPs) calling from BS-Seq data, particularly for SNPs on chromosome X and in the presence of contaminative data, poses ongoing challenges. Results: We introduce bsgenova, a novel SNP caller tailored for bisulfite sequencing data, employing a Bayesian multinomial model. The performance of bsgenova is assessed by comparing SNPs called from real-world BS-Seq data with those from corresponding whole-genome sequencing (WGS) data across three human cell lines. bsgenova is both sensitive and precise, especially for chromosome X, compared with three existing methods. Moreover, in the presence of low-quality reads, bsgenova outperforms other methods notably. In addition, bsgenova is meticulously implemented, leveraging matrix imputation and multi-process parallelization. Compared to existing methods, bsgenova stands out for its speed and efficiency in memory and disk usage. Furthermore, bsgenova integrates bsextractor, a methylation extractor, enhancing its flexibility and expanding its utility. Conclusions: We introduce bsgenova for SNP calling from bisulfite-sequencing data. The source code is available at https://github.com/hippo-yf/bsgenova under license GPL-3.0. [ABSTRACT FROM AUTHOR]

The diversity of marine cyanobacteria has been extensively studied due to their vital roles in ocean primary production. However, little is understood about the diversity of cyanobacterial species involved in symbiotic relationships. In this study, we successfully sequenced the complete genome of a cyanobacterium in symbiosis with Citharistes regius, a dinoflagellate species thriving in the open ocean. A phylogenomic analysis revealed that the cyanobacterium (CregCyn) belongs to the marine picocyanobacterial lineage, akin to another cyanobacterial symbiont (OmCyn) of a different dinoflagellate closely related to Citharistes. Nevertheless, these two symbionts are representing distinct lineages, suggesting independent origins of their symbiotic lifestyles. Despite the distinct origins, the genome analyses of CregCyn revealed shared characteristics with OmCyn, including an obligate symbiotic relationship with the host dinoflagellates and a degree of genome reduction. In contrast, a detailed analysis of genome subregions unveiled that the CregCyn genome carries genomic islands that are not found in the OmCyn genome. The presence of the genomic islands implies that exogenous genes have been integrated into the CregCyn genome at some point in its evolution. This study contributes to our understanding of the complex history of the symbiosis between dinoflagellates and cyanobacteria, as well as the genomic diversity of marine picocyanobacteria. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Circ-ZEB1 promotes PIK3CA expression by silencing miR-199a-3p and affects the proliferation and apoptosis of hepatocellular carcinoma" published in the journal Molecular Cancer. The correction addresses two errors in the figures of the original article, specifically a typo in the subscript of the X-axis in Fig. 1B and an incorrect image in Fig. 3C. The authors provide the correct figures and state that these errors do not affect the overall results and conclusions of the study. The corrected figures show the expression of circ-ZEB1 and PIK3CA in hepatocellular carcinoma tissues and cells, as well as the effects of circ-ZEB1 downregulation on cell proliferation. The correction notice is authored by Weiwei Liu, Lu zheng, Rongguiyi Zhang, Ping Hou, Jiakun Wang, Linquan Wu, and Jing Li. [Extracted from the article]

Extended-spectrum beta-lactamase (ESBL) Escherichia coli (E. coli) is an emerging pathogen of high concern given its resistance to extended-spectrum cephalosporins. Broiler chicken, which is the number one consumed meat in the United States and worldwide, can be a reservoir of ESBL E. coli. Backyard poultry ownership is on the rise in the United States, yet there is little research investigating prevalence of ESBL E. coli in this setting. This study aims to identify the prevalence and antimicrobial resistance profiles (phenotypically and genotypically) of ESBL E. coli in some backyard and commercial broiler farms in the U.S. For this study ten backyard and ten commercial farms were visited at three time-points across flock production. Fecal (n = 10), litter/compost (n = 5), soil (n = 5), and swabs of feeders and waterers (n = 6) were collected at each visit and processed for E. coli. Assessment of ESBL phenotype was determined through using disk diffusion with 3rd generation cephalosporins, cefotaxime and ceftazidime, and that with clavulanic acid. Broth microdilution and whole genome sequencing were used to investigate both phenotypic and genotypic resistance profiles, respectively. ESBL E. coli was more prevalent in backyard farms with 12.95% of samples testing positive whereas 0.77% of commercial farm samples were positive. All isolates contained a blaCTX-M gene, the dominant variant being blaCTX-M-1, and its presence was entirely due to plasmids. Our study confirms concerns of growing resistance to fourth generation cephalosporin, cefepime, as roughly half (51.4%) of all isolates were found to be susceptible dose-dependent and few were resistant. Resistance to non-beta lactams, gentamicin and ciprofloxacin, was also detected in our samples. Our study identifies prevalence of blaCTX-M type ESBL E. coli in U.S. backyard broiler farms, emphasizing the need for interventions for food and production safety. [ABSTRACT FROM AUTHOR]

Escherichia coli can harbor a broad repertoire of virulence and antimicrobial resistance (AMR) genes, which can be exchanged across the human gastrointestinal microflora, thus posing a public health risk. In this study, 6 batches of artisanal soft cheese and a 6-month ripened fermented dried sausage were investigated to assess the occurrence, phylogeny, and genomic traits (AMR, virulence, and mobilome) of E. coli. 30 and 3 strains isolated from salami and cheese food chains, respectively, were confirmed as E. coli by whole genome sequencing. The accumulation of single nucleotide polymorphism differences within small clusters of strains encompassing batches or processing stages, combined with high serotype and phylogroup diversity, suggested the occurrence of different contamination phenomena among the facilities. A total of 8 isolates harbored plasmid-mediated resistance genes, including one cheese strain that carried an IncQ1 plasmid carrying AMR determinants to macrolides [mph(B)], sulfonamides (sul1, sul2), trimethoprim (dfrA1), and aminoglycosides [aph(3")-Ib and aph(6)-Id]. A pool of virulence-associated genes in the class of adhesion, colonization, iron uptake, and toxins, putative ColV-positive iron uptake systems sit, iro, or iuc (8 salami and 2 cheese), plasmid-encoded hemolysin operon hlyABCD (one salami), and potential atypical enteropathogenic E. coli (3 salami environment) were reported. Overall, our findings underscore the importance of routine surveillance of E. coli in the artisanal food chain to prevent the dissemination of AMR and virulence. [ABSTRACT FROM AUTHOR]

Key message: Inheritance of the presence/absence of seeds in Annona squamosa is mediated by a single fully recessive gene and is caused by a deletion of the INNER NO OUTER (INO) locus. For some fruits, seedless varieties are desirable for consumption and processing. In the sugar apple tree (Annona squamosa L.), the seedless trait in the Thai seedless (Ts) and Brazilian seedless (Bs) accessions was associated with defective ovules and an apparent deletion of the INNER NO OUTER (INO) ovule development gene locus. Segregation analysis of F2 and backcross descendants of crosses of Bs to fertile wild-type varieties in this species with a multi-year generation time showed that seedlessness was recessive and controlled by a single locus. Comparison of whole genome sequence of a wild-type plant and a third accession, Hawaiian seedless (Hs), identified a 16 kilobase deletion including INO in this line. Ts and Bs lines were shown to have an identical deletion, indicating a common origin from a single deletion event. Analysis of microsatellite markers could not preclude the possibility that all three seedless accessions are vegetatively propagated clones. The sequence of the deletion site enabled a codominant assay for the wild-type and mutant genes allowing observation of complete cosegregation of the seedless/defective ovule phenotype with the INO deletion, showing maximal separation of less than 3.5 cM. The observed deletion is the only significant difference between the wild-type and Hs line over 587 kilobases, likely encompassing much more than 3.5 cM, showing that the deletion is the cause of seedless trait. The codominant markers and obtained progenies will be useful for introgression of the seedless trait into elite sugar apple lines and into other Annonas through interspecific crossings. [ABSTRACT FROM AUTHOR]

Phenotypic susceptibility testing of the Mycobacterium tuberculosis complex (MTBC) isolate requires culture growth, which can delay rapid detection of resistant cases. Whole genome sequencing (WGS) and data analysis pipelines can assist in predicting resistance to antimicrobials used in the treatment of tuberculosis (TB). This study compared phenotypic susceptibility testing results and WGS-based predictions of antimicrobial resistance (AMR) to four first-line antimicrobials—isoniazid, rifampin, ethambutol, and pyrazinamide—for MTBC isolates tested between the years 2018–2022. For this 5-year retrospective analysis, the WGS sensitivity for predicting resistance for isoniazid, rifampin, ethambutol, and pyrazinamide using Mykrobe was 86.7%, 100.0%, 100.0%, and 47.8%, respectively, and the specificity was 99.4%, 99.5%, 98.7%, and 99.9%, respectively. The predictive values improved slightly using Mykrobe corrections applied using TB Profiler, i.e., the WGS sensitivity for isoniazid, rifampin, ethambutol, and pyrazinamide was 92.31%, 100%, 100%, and 57.78%, respectively, and the specificity was 99.63%. 99.45%, 98.93%, and 99.93%, respectively. The utilization of WGS-based testing addresses concerns regarding test turnaround time and enables analysis for MTBC member identification, antimicrobial resistance prediction, detection of mixed cultures, and strain genotyping, all through a single laboratory test. WGS enables rapid resistance detection compared to traditional phenotypic susceptibility testing methods using the WHO TB mutation catalog, providing an insight into lesser-known mutations, which should be added to prediction databases as high-confidence mutations are recognized. The WGS-based methods can support TB elimination efforts in Canada and globally by ensuring the early start of appropriate treatment, rapidly limiting the spread of TB outbreaks. [ABSTRACT FROM AUTHOR]

In this study, our primary aim was to explore the genomic landscape of Barka cattle, a breed recognized for high milk production in a semi-arid environment, by focusing on genes with known roles in milk production traits. We employed genome-wide analysis and three selective sweep detection methods (ZFST, θπ ratio, and ZHp) to identify candidate genes associated with milk production and composition traits. Notably, ACAA1, P4HTM, and SLC4A4 were consistently identified by all methods. Functional annotation highlighted their roles in crucial biological processes such as fatty acid metabolism, mammary gland development, and milk protein synthesis. These findings contribute to understanding the genetic basis of milk production in Barka cattle, presenting opportunities for enhancing dairy cattle production in tropical climates. Further validation through genome-wide association studies and transcriptomic analyses is essential to fully exploit these candidate genes for selective breeding and genetic improvement in tropical dairy cattle. [ABSTRACT FROM AUTHOR]

• The occurrence of structural variants leading to duchenne muscular dystrophy is remarkably infrequent. • Our findings emphasize the need for long-read sequence genetic testing in atypical cases of muscle dystrophy. • We report for the first time a novel inversion and balanced translocation in the DMD gene via long-read whole-genome sequencing in a chinese family. • This case underscores the importance of considering structural variants in cases where conventional molecular techniques fail to identify pathogenic variants. Structural variants (SVs) are infrequently observed in Duchenne muscular dystrophy (DMD), a condition mainly marked by deletions and point mutations in the DMD gene. SVs in DMD remain difficult to reliably detect due to the limited SV-detection capacity of conventionally used short-read sequencing technology. Herein, we present a family, a boy and his mother, with clinical signs of muscular dystrophy, elevated creatinine kinase levels, and intellectual disability. A muscle biopsy from the boy showed dystrophin deficiency. Routine molecular techniques failed to detect abnormalities in the DMD gene, however, dystrophin mRNA transcripts analysis revealed an absence of exons 59 to 79. Subsequent long-read whole-genome sequencing identified a rare complex structural variant, a 77 kb novel intragenic inversion, and a balanced translocation t(X;1)(p21.2;p13.3) rearrangement within the DMD gene, expanding the genetic spectrum of dystrophinopathy. Our findings suggested that SVs should be considered in cases where conventional molecular techniques fail to identify pathogenic variants. [ABSTRACT FROM AUTHOR]

[Display omitted] • Whole-genome sequencing and comparative genomic analysis were performed on Cryptosporidium xiaoi. • Cryptosporidium xiaoi and the bovine-specific C. bovis have 96% genomic identity and undergo similar genome reduction. • The species-specific and divergent genes between C. xiaoi and C. bovis may contribute to their different host preferences. • These genes may be targets for in-depth study of Cryptosporidium biology. Cryptosporidium spp. are important diarrhea-associated pathogens in humans and livestock. Among the known species, Cryptosporidium xiaoi , which causes cryptosporidiosis in sheep and goats, was previously recognized as a genotype of the bovine-specific Cryptosporidium bovis based on their high sequence identity in the ssrRNA gene. However, the lack of genomic data has limited characterization of the genetic differences between the two closely related species. In this study, we sequenced the genomes of two C. xiaoi isolates and performed comparative genomic analysis to identify the sequence uniqueness of this ovine-adapted species compared with other Cryptosporidium spp. Our results showed that C. xiaoi is genetically related to C. bovis as shown by their 95.8% genomic identity and similar gene content. Consistent with this, both C. xiaoi and C. bovis appear to have fewer genes encoding mitochondrial metabolic enzymes and invasion-related protein families. However, they appear to possess several species-specific genes. Further analysis indicates that the sequence differences between these two Cryptosporidium spp. are mainly in 24 highly polymorphic genes, half of which are located in the subtelomeric regions. Some of these subtelomeric genes encode secretory proteins that have undergone positive selection. In addition, the genomes of two C. xiaoi isolates, identified as subtypes XXIIIf and XXIIIh, share 99.9% nucleotide sequence identity, with six highly divergent genes encoding putative secretory proteins. Therefore, these species-specific genes and sequence polymorphism in subtelomeric genes probably contribute to the different host preference of C. xiaoi and C. bovis. [ABSTRACT FROM AUTHOR]

Simple Summary: Simple Summary: Local breeds of pigs often do not require special housing and feeding conditions. This makes it possible to obtain high-quality meat products under eco-friendly conditions. The Livni breed is a local Russian pig breed, which is the only one adapted to pasture-based housing and produces pork of excellent quality in environmentally friendly conditions. We evaluated the genetic diversity of the Livni breed in comparison with the Large White and Landrace breeds and investigated changes in the Livni breed populations' structure over the period from the 1970s to the present, using whole-genome single nucleotide polymorphisms. Both the museum and modern Livni pig populations are characterized by higher genetic diversity and were subject to less selection pressure than commercial pig populations. Present-day populations of the Livni pigs have retained their historical genomic components despite the use of commercial breeds in breeding efforts. This suggests their potential suitability for future breeding programs. The pig industry is usually considered an intensive livestock industry, mainly supported by hybrid breeding between commercial pig breeds. However, people's pursuit of a more natural environment and higher meat quality has led to an increasing demand for eco-friendly and diverse pig feeding systems. Therefore, the importance of rearing and conserving local pig breeds is increasing. The Livni pig is a local breed with good adaptability to the environmental and fodder conditions in central Russia. In this study, we aimed to analyze the genetic diversity and population structure of Livni pigs using whole-genome single nucleotide polymorphism (SNP) data. We utilized the Porcine GGP HD BeadChip on genotype samples from old (n = 32, 2004) and modern (n = 32, 2019) populations of Livni pigs. For the museum samples of Livni pigs (n = 3), we extracted DNA from their teeth, performed genomic sequencing, and obtained SNP genotypes from the whole-genome sequences. SNP genotypes of Landrace (n = 32) and Large White (n = 32) pigs were included for comparative analysis. We observed that the allelic richness of Livni pigs was higher than those of Landrace and Large White pigs (AR = 1.775–1.798 vs. 1.703 and 1.668, respectively). The effective population size estimates (NE5 = 108 for Livni pigs, NE5 = 59 for Landrace and Large White pigs) confirmed their genetic diversity tendency. This was further supported by the length and number of runs of homozygosity, as well as the genomic inbreeding coefficient (almost twofold lower in Livni pigs compared to Landrace and Large White pigs). These findings suggest that the Livni pig population exhibits higher genetic diversity and experiences lower selection pressure compared to commercial pig populations. Furthermore, both principal component and network tree analyses demonstrated a clear differentiation between Livni pigs and transboundary commercial pigs. The TreeMix results indicated gene flow from Landrace ancestors to Livni pigs (2019) and from Large White ancestors to Livni pigs (2004), which was consistent with their respective historical breeding backgrounds. The comparative analysis of museum, old, and modern Livni pigs indicated that the modern Livni pig populations have preserved their historical genomic components, suggesting their potential suitability for future design selection programs. [ABSTRACT FROM AUTHOR]

Simple Summary: Simple Summary: Sheep breeding has important economic value in China's animal husbandry industry, and growth traits represent an important factor affecting the economic benefits of the industry. This study is based on a functional 168 bp SINE element insertion upstream of the HOXB13 gene discovered in GWAS. By using whole-genome sequencing (WGS) data, we analyzed the frequency of the HOXB13 gene in 33 different sheep breeds worldwide, and we genotyped 6 specific sheep breeds by using PCR and agarose gel electrophoresis. We also associated the polymorphism of the HOXB13 gene with the growth traits of Luxi black-headed sheep and found that the 168 bp insertion showed a certain correlation with the growth traits in sheep. This may provide effective assistance for improving the economic benefits of the sheep industry. In recent years, genome-wide association studies (GWAS) have uncovered that the HOXB13 gene is a key regulatory factor for the tail length trait of sheep. Further research has found that there is a functional 168 bp SINE element insertion upstream of the HOXB13 gene, which leads to the occurrence of long tails in sheep. However, the frequency of mutations in the 168 bp SINE element of the HOXB13 gene among different sheep breeds around the world and its relationship with growth traits are still unclear. This study used whole-genome sequencing (WGS) data, including 588 samples from 33 different sheep breeds around the world, to evaluate the frequency of HOXB13 gene mutations in different sheep breeds globally. At the same time, this study also selected 3392 sheep samples from six breeds. The genetic variation in the 168 bp InDel locus in the HOXB13 gene was determined through genotyping, and its association with the growth traits of Luxi black-headed sheep was analyzed. The research results indicate that the polymorphism of the 168 bp InDel locus is significantly correlated with the hip width of adult ewes in the Luxi black-headed sheep breed (p < 0.05) and that the hip width of adult ewes with the DD genotype is significantly larger than that of adult ewes with the ID genotype (p < 0.05). This study indicates that there is consistency between the research results on the sheep tail length trait and growth traits, which may contribute to the promotion of sheep breed improvement. [ABSTRACT FROM AUTHOR]

Simple Summary: Understanding the genetic makeup of microorganisms provides information on their evolutionary relationship with other similar organisms. It also sheds light on their ability to cause disease in susceptible individuals and to resist the hosts' defense mechanisms, including the effects of antimicrobial therapy. In this study, we performed complete genome sequencing and characterization of bacteria called Arcanobacterium hippocoleae, which were isolated from the reproductive tract of infected mares. These bacteria displayed small and large phenotypes when grown on artificial media. The whole genome sequences between the large phenotypes were closely related, while the small and large types were distant from each other in terms of sequence size and identity. Putative genetic elements that might be associated with disease conditions were identified in both bacterial phenotypes. Several genes that express hypothetical proteins with unknown functions were also detected. This study provides the complete genetic structure and analysis of different phenotypes of Arcanobacterium hippocoleae and will serve as a benchmark for future studies to identify the potential function and role of the bacterial proteins in the ability of the bacterium to produce reproductive tract diseases in mares. Arcanobacterium hippocoleae is a Gram-positive fastidious bacterium and is occasionally isolated from the reproductive tract of apparently healthy mares (Equus caballus) or from mares with reproductive tract abnormalities. Apart from a few 16S rRNA gene-based GenBank sequences and one recent report on complete genome assembly, detailed genomic sequence and clinical experimental data are not available on the bacterium. Recently, we observed an unusual increase in the detection of the organism from samples associated with mare reproductive failures in Atlantic Canada. Two colony morphotypes (i.e., small, and large) were detected in culture media, which were identified as A. hippocoleae by MALDI-TOF mass spectrometry and 16S rRNA gene sequencing. Here, we report the whole genome sequencing and characterization of the morphotype variants. The genome length of the large phenotypes was between 2.42 and 2.43, and the small phenotype was 1.99 Mbs. The orthologous nucleotide identity between the large colony phenotypes was ~99%, and the large and small colony phenotypes was between 77.86 and 78.52%, which may warrant the classification of the two morphotypes into different species. Phylogenetic analysis based on 16S rRNA genes or concatenated housekeeping genes grouped the small and large colony variants into two different genotypic clusters. The UvrA protein, which is part of the nucleotide excision repair (NER) system, and 3-isopropoylmalate dehydratase small subunit protein expressed by the leuD gene were identified as potential virulence factors in the large and small colony morphotypes, respectively. However, detailed functional studies will be required to determine the exact roles of these and other identified hypothetical proteins in the cellular metabolism and potential pathogenicity of A. hippocoleae in mares. [ABSTRACT FROM AUTHOR]

The genus Macaca is widely distributed, occupies a variety of habitats, shows diverse phenotypic characteristics, and is one of the best-studied genera of nonhuman primates. Here, we reported five re-sequencing Macaca genomes, including one M. cyclopis, one M. fuscata, one M. thibetana, one M. silenus, and one M. sylvanus. Together with published genomes of other macaque species, we combined 20 genome sequences of 10 macaque species to investigate the gene introgression and genetic differences among the species. The network analysis of the SNV-fragment trees indicates a reticular phylogeny of macaque species. Combining the results from various analytical methods, we identified extensive ancient introgression events among macaque species. The multiple introgression signals between different species groups were also observed, such as between fascicularis group species and silenus group species. However, gene flow signals between fascicularis and sinica group were not as strong as those between fascicularis group and silenus group. On the other hand, the unidirect gene flow in M. arctoides probably occurred between the progenitor of M. arctoides and the common ancestor of fascicularis group. Our study also shows that the genetic backgrounds and genetic diversity of different macaques vary dramatically among species, even among populations of the same species. In conclusion, using whole genome sequences and multiple methods, we have studied the evolutionary history of the genus Macaca and provided evidence for extensive introgression among the species. [ABSTRACT FROM AUTHOR]

Background: Cholesterol ester storage disorder (CESD; OMIM: 278,000) was formerly assumed to be an autosomal recessive allelic genetic condition connected to diminished lysosomal acid lipase (LAL) activity due to LIPA gene abnormalities. CESD is characterized by abnormal liver function and lipid metabolism, and in severe cases, liver failure can occur leading to death. In this study, one Chinese nonclassical CESD pedigree with dominant inheritance was phenotyped and analyzed for the corresponding gene alterations. Methods: Seven males and eight females from nonclassical CESD pedigree were recruited. Clinical features and LAL activities were documented. Whole genome Next-generation sequencing (NGS) was used to screen candidate genes and mutations, Sanger sequencing confirmed predicted mutations, and qPCR detected LIPA mRNA expression. Results: Eight individuals of the pedigree were speculatively thought to have CESD. LAL activity was discovered to be lowered in four living members of the pedigree, but undetectable in the other four deceased members who died of probable hepatic failure. Three of the four living relatives had abnormal lipid metabolism and all four had liver dysfunctions. By liver biopsy, the proband exhibited diffuse vesicular fatty changes in noticeably enlarged hepatocytes and Kupffer cell hyperplasia. Surprisingly, only a newly discovered heterozygous mutation, c.1133T>C (p. Ile378Thr) on LIPA, was found by gene sequencing in the proband. All living family members who carried the p.I378T variant displayed reduced LAL activity. Conclusions: Phenotypic analyses indicate that this may be an autosomal dominant nonclassical CESD pedigree with a LIPA gene mutation. [ABSTRACT FROM AUTHOR]

Incomplete speciation can be leveraged to associate phenotypes with genotypes, thus providing insights into the traits relevant to the reproductive isolation of diverging taxa. We investigate the genetic underpinnings of the phenotypic differences between Sporophila plumbea and Sporophila beltoni. Sporophila beltoni has only recently been described based, most notably, based on differences in bill coloration (yellow vs. black in S. plumbea). Both species are indistinguishable through mtDNA or reduced-representation genomic data, and even whole-genome sequencing revealed low genetic differentiation. Demographic reconstructions attribute this genetic homogeneity to gene flow, despite divergence in the order of millions of generations. We found a narrow hybrid zone in southern Brazil where genetically, yet not phenotypically, admixed individuals appear to be prevalent. Despite the overall low genetic differentiation, we identified 3 narrow peaks along the genome with highly differentiated SNPs. These regions harbor 6 genes, one of which is involved in pigmentation (EDN3) and is a candidate for controlling bill color. Within the outlier peaks, we found signatures of resistance to gene flow, as expected for islands of speciation. Our study shows how genes related to coloration traits are likely involved in generating prezygotic isolation and establishing species boundaries early in speciation. [ABSTRACT FROM AUTHOR]

The renowned horticultural artist and plant breeder Luther Burbank worked with many species of plants. During his 50-year career, he introduced more than 800 cultivars, including more than 150 accessions of plums (Prunus spp.) in the late 1800s and early 1900s. Burbank preferred using wide, interspecific crosses to create a vast range of phenotypic variation and then artificially select from the extremes. Although a great artist, Burbank was a substandard scientist because he was derelict in pedigree note-taking. Although many of his introductions are extinct, hobbyists, enthusiasts, and international collections retain nearly a third of the economically viable cultivars he bred. For a century, many of his hybridizations remained inscrutable mysteries until modern genomic and computational tools developed their resolution and statistical power. Today, genotyping by sequencing (GBS) is a useful tool for pedigree reconstruction in the absence of reliable records. GBS can inform principal component analyses, identity by descent (IBD) kinship, and phylogenetic admixture, revealing complex relationships among taxa. In this study, whole genome sequencing was performed on 53 Prunus taxa used by Burbank in his breeding experiments in the most comprehensive genetic survey of his work to date. Exact parent-offspring relationships between this population may be impossible to discern due to years of back crossing, sibling mating, and open pollination. However, the proportion of genomic similarity among these taxa provides information on the relatedness of the genotypes in Burbank's Prunus experiments, defining four primary lineages within his breeding population. These lineages comprised primarily P. salicina and P. simonii but also have influences from P. americana, P. cerasifera, P. domestica, and P. rivularis. The prevalence of P. simonii in Burbank's Prunus introductions appears to have been vastly underreported, indicating that some of the seedstock founders of his breeding population could have been P. salicina × P. simonii hybrids at the inception of his career. This research has implications for pedigree reconstruction and prioritizing conservation in collections curation for future studies. [ABSTRACT FROM AUTHOR]

Objective: To date, polychaetes remain a poorly studied class of invertebrate animals in terms of the features of functioning of their immune system and, in particular, the biodiversity of antimicrobial peptides (AMPs). AMPs also known as host defense peptides play a key role in host protection from various pathogens and regulation of the species composition of symbiotic microbes. A study of the biosynthesis of AMPs in polychaetes resulted in the discovery of the so-called BRICHOS domain in the structure of the precursor proteins of a number of such peptides. The conserved structure of this domain makes possible the bioinformatic search for AMP precursors in polychaete transcriptomes. In this work, we found and studied a novel BRICHOS-related AMP from the lugworm Arenicola marina, representing a previously undiscovered in polychaetes a structural family of defensin-like peptides stabilized by four disulfide bonds. Methods: The peptide, designated as AmBRI-44a and containing 44 amino acid residues, was obtained by heterologous expression in Escherichia coli. The peptide secondary structure was investigated by CD spectroscopy in water and dodecylphosphocholine (DPC) micelles. The minimum inhibitory concentrations (MICs) against a wide range of bacterial pathogens were assessed using the two-fold serial dilutions method. Cytotoxicity of AmBRI-44a was studied in vitro on human erythrocytes or adherent cell line HEK293T using the hemoglobin release assay or the MTT test, respectively. The AMBRI-44a potential target was discovered by successive daily subculturing of the AmBRI-44a resistant strain followed by whole-genome sequencing. Results and Discussion: According to CD data, AmBRI-44a is a predominantly β-structured peptide. AmBRI-44a was shown to have a specific activity against a narrow spectrum of Gram-positive bacteria and pronounced cytotoxic effects on the eukaryotic cell line HEK293T. The proposed mechanism of the antibacterial action of this peptide is associated with the inhibition of bacterial cell wall biosynthesis, as indicated by the genetic and phenotypic analysis of selected AmBRI-44a-resistant bacteria Bacillus licheniformis B-511. Conclusions: The resulting data allow us to consider the discovered peptide AmBRI-44a as a candidate compound for the development of an antibiotic agent that could potentially be effective in the treatment of infectious diseases mediated by multidrug-resistant Gram-positive bacteria. [ABSTRACT FROM AUTHOR]

Objectives To characterize and elucidate the spread of amikacin-resistant Enterobacteriaceae isolates from environmental samples on a pig farm in the UK, following the previous identification of index Salmonella isolates harbouring the rmtB gene, a 16S rRNA methylase. Methods Environmental samples were collected during two visits to a pig farm in the UK. Isolates were recovered using selective media (amikacin 128 mg/L) followed by real-time PCR and WGS to analyse rmtB -carrying Salmonella and Escherichia coli isolates. Results Salmonella and E. coli isolates harbouring the rmtB gene were detected at both farm visits. All Salmonella isolates were found to be monophasic S. enterica serovar Typhimurium variant Copenhagen of ST34. rmtB -harbouring E. coli isolates were found to be one of three STs: ST4089, ST1684 and ST34. Long-read sequencing identified the rmtB gene to be chromosomally located in Salmonella isolates and on IncFII-type plasmids in E. coli isolates. The results showed the rmtB gene to be flanked by IS 26 elements and several resistance genes. Conclusions We report on the occurrence of rmtB -harbouring Enterobacteriaceae on a pig farm in the UK. rmtB confers resistance to multiple aminoglycosides and this work highlights the need for surveillance to assess dissemination and risk. [ABSTRACT FROM AUTHOR]

Osteosarcoma stratification relies on clinical parameters and histological response. We developed a new personalized stratification using less invasive circulating tumor DNA (ctDNA) quantification. Plasma from patients homogeneously treated in the prospective protocol OS2006, at diagnosis, before surgery and end of treatment, were sequenced using low-passage whole-genome sequencing (lpWGS) for copy number alteration detection. We developed a prediction tool including ctDNA quantification and known clinical parameters to estimate patients' individual risk of event. ctDNA quantification at diagnosis (diagCPA) was evaluated for 183 patients of the protocol OS2006. diagCPA as a continuous variable was a major prognostic factor, independent of other clinical parameters, including metastatic status [diagCPA hazard ratio (HR) = 3.5, P = 0.002 and 3.51, P = 0.012, for progression-free survival (PFS) and overall survival (OS)]. At the time of surgery and until the end of treatment, diagCPA was also a major prognostic factor independent of histological response (diagCPA HR = 9.2, P < 0.001 and 11.6, P < 0.001, for PFS and OS). Therefore, the addition of diagCPA to metastatic status at diagnosis or poor histological response after surgery improved the prognostic stratification of patients with osteosarcoma. We developed the prediction tool PRONOS to generate individual risk estimations, showing great performance ctDNA quantification at the time of surgery and the end of treatment still required improvement to overcome the low sensitivity of lpWGS and to enable the follow-up of disease progression. The addition of ctDNA quantification to known risk factors improves the estimation of prognosis calculated by our prediction tool PRONOS. To confirm its value, an external validation in the Sarcoma 13 trial is underway. • ctDNA detection is a non-invasive procedure. • The use of lpWGS is cost-effective. • This procedure represents a considerable step in reducing therapeutic burden and trauma for patients with cancer. • PRONOS is a tool that estimates relapse risk using ctDNA at diagnosis and known clinical risk factor in osteosarcoma. [ABSTRACT FROM AUTHOR]

Bacteriophages have emerged as promising candidates for the treatment of difficult-to-treat bacterial infections. The aim of this study is to isolate and characterize phages infecting carbapenem-resistant and extended-spectrum beta-lactamase producer Klebsiella pneumoniae isolates. Water samples were taken for the isolation of bacteriophages. One-step growth curve, the optimal multiplicity of infection (MOI), thermal and pH stabilities, transmission electron microscopy and whole-genome sequencing of phages were studied. Four phages were isolated and named Klebsiella phage Kpn02, Kpn17, Kpn74, and Kpn13. The optimal MOI and latent periods of phage Kpn02, Kpn17, Kpn74, and Kpn13 were 10, 1, 0.001, and 100 PFU/CFU and 20, 10, 20, and 30 min, respectively. Burst sizes ranged from 811 to 2363. No known antibiotic resistance and virulence genes were identified. No tRNAs were detected except Klebsiella phage Kpn02 which encodes 24 tRNAs. Interestingly, Klebsiella phage Kpn74 was predicted to be a lysogenic phage whose prophage is a linear plasmid molecule with covalently closed ends. Of the Klebsiella-infecting phages presented in current study, virulent phages suggest that they may represent candidate therapeutic agents against MDR K. pneumoniae, based on short latent period, high burst sizes and no known antibiotic resistance and virulence genes in their genomes. [ABSTRACT FROM AUTHOR]

An aerobic, rod-shaped, non-motile, endospore-forming bacterium, strain V-9T, was found in the frozen volcanic ash, Kamchatka peninsula, Russia. Phylogenies based on 16S rRNA gene and genome sequences demonstrated that strain V-9T was affiliated with the family Paenibacillaceae and clustered outside the clade that includes the type species of this genus, Paenibacillus polymyxa, and closely related species. V-9T showed the highest 16S rRNA gene sequences similarity to Paenibacillus chartarius CCUG 55240T (96.7%). The similarity to type strains of other Paenibacillus species were below 94.7%, with 91.8% determined to Paenibacillus polymyxa IAM 13419T. The AAI and POCP values between V-9T and type species of the genera of Paenibacillaceae with available genomes, including Paenibacillus polymyxa, were below the thresholds for defining novel genera. The cell wall of new strain contained a lysine-based peptidoglycan and two teichoic acids, unsubstituted 1,3-poly(glycerol phosphate) and 1,3-poly(glycerol phosphate) substituted at the C(2) of glycerol by glucose. Acid hydrolysates of the cell wall included glucose, galactose and glycerol. Strain V-9T contained menaquinone MK-7 as the sole isoprenoid quinone, anteiso-C15:0, anteiso-C17:0, iso- C15:0 and iso-C16:0a as the dominant fatty acids, and phosphatidylglycerol, diphosphatidylglycerol, acylphosphatidylglycerol, and phosphatidylinositol as the major polar lipids. The DNA G+C content calculated from the whole genome sequence was 55 mol %. Based on the data obtained, a new genus and species, Gordonibacillus kamchatkensis gen. nov., sp. nov., is proposed with the type strain V-9T (=VKM B-2647T = DSM 26726T). [ABSTRACT FROM AUTHOR]

We report the first North American origin class I avian orthoavulavirus 1 (AOAV-1) isolated from a faecal dropping of wild Eurasian teal (Anas crecca) in South Korea. Whole genome sequencing and comparative phylogenetic analysis revealed that the AOAV-1/Eurasian teal/South Korea/KU1405-3/2017 virus belongs to the sub-genotype 1.2 of class I AOAV-1. Phylogenetic analysis suggested multiple introductions of the North American sub-genotype 1.2 viruses into Asia and its establishment in the wild bird population in East Asia since May 2011. These results provide information on the epidemiology of AOAV-1, particularly the role of migratory wild birds in exchanging viruses between the Eurasian and North American continents. Enhanced genomic surveillance is required to improve our understanding on the evolution and transmission dynamics of AOAV-1 in wild birds. [ABSTRACT FROM AUTHOR]

Qaidam cattle are a typical Chinese native breed inhabiting northwest China. They bear the characteristics of high cold and roughage tolerance, low‐oxygen adaptability and good meat quality. To analyze the genetic diversity of Qaidam cattle, 60 samples were sequenced using whole‐genome resequencing technology, along with 192 published sets of whole‐genome sequencing data of Indian indicine cattle, Chinese indicine cattle, North Chinese cattle breeds, East Asian taurine cattle, Eurasian taurine cattle and European taurine cattle as controls. It was found that Qaidam cattle have rich genetic diversity in Bos taurus, but the degree of inbreeding is also high, which needs further protection. The phylogenetic analysis, principal component analysis and ancestral component analysis showed that Qaidam cattle mainly originated from East Asian taurine cattle. Qaidam cattle had a closer genetic relationship with the North Chinese cattle breeds and the least differentiation from Mongolian cattle. Annotating the selection signals obtained by composite likelihood ratio, nucleotide diversity analysis, integrated haplotype score, genetic differentiation index, genetic diversity ratio and cross‐population extended haplotype homozygosity methods, several genes associated with immunity, reproduction, meat, milk, growth and adaptation showed strong selection signals. In general, this study provides genetic evidence for understanding the germplasm characteristics of Qaidam cattle. At the same time, it lays a foundation for the scientific and reasonable protection and utilization of genetic resources of Chinese local cattle breeds, which has great theoretical and practical significance. [ABSTRACT FROM AUTHOR]