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Vi capsular polysaccharide (Vi) is a major virulence factor of human typhoid-causing pathogen Salmonella enterica serovar Typhi (S. Typhi). It distinguishes S. Typhi from closely related non-typhoidal Salmonella serovars such as S. Typhimurium which do not normally cause systemic infection in humans. Vi not only forms a capsule around S. Typhi but it is also readily released from this pathogen. We have previously reported that Vi targets prohibitin to inhibit cellular responses activated through immune receptors. Here, we show that engagement of membrane prohibitin with Vi prevents Salmonella-induced activation of small Rho-family GTPases, Rac1, and Cdc42, and suppresses actin cytoskeletal rearrangements resulting in reduced invasion and highly subdued inflammatory responses. Cells infected with S. Typhimurium in the presence of Vi show poor activation of NF-kB and MAP-kinase pathways of intracellular signaling. Treatment with Vi brings about redistribution of Rac-1, prohibitin, and ganglioside GM1 in membrane raft domains. Vi-mediated interference with activation of Rho-family GTPases represents a previously unrecognized mechanism by which S. Typhi can limit its invasion and alarming of the host.

Among the various lipids associated with the cell envelope of the Mycabacterium avium complex, the species-specific glycopeplidolipids (GPL) are responsible for distinguishing one serovar from another. In a continuing effort to study the immunomodulatory capabilities of these mycobacterial lipids, we have examined and compared the effects of the GPL and its lipopeptide fragment (β-lipid) on mononuclear cell function. It was observed that the lymphoproliferative response of murine splenic mononuclear cells lo mitogen stimulation was reduced by both the GPL and its lipopeptide fragment. Although the responsiveness appeared lo be down-regulated to a greater degree by the (β-lipid, treatment with either GPL or β-lipid resulted in the release of soluble factors from peritoneal macrophages that caused suppression of the lymphoproliferative responsiveness of splenic mononuclear cells. Flow cylometric analysis of peritoneal macrophages revealed that treatment with the β-lipid fragment caused a marked decrease in expression of the C3bi complement receptor, Mac-1, on maerophages. whereas treatment with GPL resulted in a marked increase in the expression of Mac-2 receptor on maerophages. Treatment of peritoneal macrophages with either GPL or β-lipid resulted in the release of tumour necrosis factor (TNF), as determined by an L929 biological cytotoxicity assay. Perturbation of macrophage membrane ultrastructure by both GPL and β-lipid was confirmed by electron microscopy, and may be a possible explanation for the resulting alterations in mononuclear cell function observed in this study. [ABSTRACT FROM AUTHOR]

PurposeThe ganglion cell analysis (GCA) of the CIRRUSTM HD-OCT (Carl Zeiss, Meditec; Dublin, CA) provides measurement of the macular ganglion cell-inner plexiform layer (GCIPL) thickness. This study determined the frequency of scan artefacts and errors in GCIPL imaging in individuals undergoing HD-OCT surveillance for glaucoma.MethodA total of 1439 eyes from 721 subjects enrolled in a prospective study assessing predictors of glaucoma progression underwent macular GCIPL imaging with the CIRRUS HD-OCT at recruitment. The prevalence of acquisition errors, segmentation errors, and co-morbid macular pathology was determined.ResultsA total of 87 (6.0%) of the 1439 scans had either acquisition errors, segmentation artefacts, or other macular pathology. The most common co-morbid macular pathology was epiretinal membrane in 2.2% of eyes.ConclusionThe macular GCIPL scan was artefact free in 94% of eyes. However, epiretinal membrane and high myopia can cause scan artefact and should be considered when interpreting the results.

Shigella causes shigellosis that requires antibiotic treatment in severe cases. Sublethal antibiotic concentrations can promote resistance, but their effect on antibiotic-sensitive bacteria before resistance development is unclear. This study investigated the effects of sublethal norfloxacin (NOR) challenges on a NOR-sensitive strain, Shigella sonnei UKMCC1015. Firstly, the whole genome of S. sonnei UKMCC1015 was assembled, and 45 antimicrobial resistance (AMR) genes were identified. Interestingly, transcriptomic analysis showed that low NOR levels do not change either the expression of the AMR genes or NOR targets such as gyrA . Instead, multiple ribosomal protein genes were downregulated, which could be attributed to decreased ribosomal protein promoter activity, modulated by elevated guanosine pentaphosphate and tetraphosphate (ppGpp) levels. This alarmone is involved in the bacterial stringent response during environmental stress, and it is mainly produced from the ppGpp synthetase ( relA ). Additionally, we observed that a relA overexpression (prolonged period of elevated ppGpp levels) may negatively affect the NOR tolerance of the bacteria. In conclusion, this study revealed that a NOR-sensitive strain responds differently to sublethal NOR than commonly reported in resistant strains., Competing Interests: We declare we have no competing interests., (© 2024 The Authors.)

Intestinal parasitic infections (IPIs) can lead to significant morbidity and mortality in cancer patients. While they are unlikely to cause severe disease and are self-limiting in healthy individuals, cancer patients are especially susceptible to opportunistic parasitic infections. The gut microbiota plays a crucial role in various aspects of health, including immune regulation and metabolic processes. Parasites occupy the same environment as bacteria in the gut. Recent research suggests intestinal parasites can disrupt the normal balance of the gut microbiota. However, there is limited understanding of this co-infection dynamic among cancer patients in Malaysia. A study was conducted to determine the prevalence and relationship between intestinal parasites and gut microbiota composition in cancer patients. Stool samples from 134 cancer patients undergoing active treatment or newly diagnosed were collected and examined for the presence of intestinal parasites and gut microbiota composition. The study also involved 17 healthy individuals for comparison and control. Sequencing with 16S RNA at the V3-V4 region was used to determine the gut microbial composition between infected and non-infected cancer patients and healthy control subjects. The overall prevalence of IPIs among cancer patients was found to be 32.8%. Microsporidia spp. Accounted for the highest percentage at 20.1%, followed by Entamoeba spp. (3.7%), Cryptosporidium spp. (3.0%), Cyclospora spp. (2.2%), and Ascaris lumbricoides (0.8%). None of the health control subjects tested positive for intestinal parasites. The sequencing data analysis revealed that the gut microbiota diversity and composition were significantly different in cancer patients than in healthy controls (p < 0.001). A significant dissimilarity was observed in the bacterial composition between parasite-infected and non-infected patients based on Bray-Curtis (p = 0.041) and Jaccard (p = 0.021) measurements. Bacteria from the genus Enterococcus were enriched in the parasite-infected groups, while Faecalibacterium prausnitzii reduced compared to non-infected and control groups. Further analysis between different IPIs and non-infected individuals demonstrated a noteworthy variation in Entamoeba-infected (unweighted UniFrac: p = 0.008), Cryptosporidium-infected (Bray-Curtis: p = 0.034) and microsporidia-infected (unweighted: p = 0.026; weighted: p = 0.019; Jaccard: p = 0.031) samples. No significant dissimilarity was observed between Cyclospora-infected groups and non-infected groups. Specifically, patients infected with Cryptosporidium and Entamoeba showed increased obligate anaerobic bacteria. Clostridiales were enriched with Entamoeba infections, whereas those from Coriobacteriales decreased. Bacteroidales and Clostridium were found in higher abundance in the gut microbiota with Cryptosporidium infection, while Bacillales decreased. Additionally, bacteria from the genus Enterococcus were enriched in microsporidia-infected patients. In contrast, bacteria from the Clostridiales order, Faecalibacterium, Parabacteroides, Collinsella, Ruminococcus, and Sporosarcina decreased compared to the non-infected groups. These findings underscore the importance of understanding and managing the interactions between intestinal parasites and gut microbiota for improved outcomes in cancer patients., (© 2024. The Author(s).)

West and South Asian populations profoundly influenced Eurasian genetic and cultural diversity. We investigate the genetic history of the Y chromosome haplogroup L1-M22, which, while prevalent in these regions, lacks in-depth study. Robust Bayesian analyses of 165 high-coverage Y chromosomes favor a West Asian origin for L1-M22 ∼20.6 thousand years ago (kya). Moreover, this haplogroup parallels the genome-wide genetic ancestry of hunter-gatherers from the Iranian Plateau and the Caucasus. We characterized two L1-M22 harboring population groups during the Early Holocene. One expanded with the West Asian Neolithic transition. The other moved to South Asia ∼8-6 kya but showed no expansion. This group likely participated in the spread of Dravidian languages. These South Asian L1-M22 lineages expanded ∼4-3 kya, coinciding with the Steppe ancestry introduction. Our findings advance the current understanding of Eurasian historical dynamics, emphasizing L1-M22's West Asian origin, associated population movements, and possible linguistic impacts., Competing Interests: D.M.B. declares stock ownership at Gene by Gene, Ltd. All other authors declare no competing interests., (© 2024 The Author(s).)

Archaic admixture has had a substantial impact on human evolution with multiple events across different clades, including from extinct hominins such as Neanderthals and Denisovans into modern humans. In great apes, archaic admixture has been identified in chimpanzees and bonobos but the possibility of such events has not been explored in other species. Here, we address this question using high-coverage whole-genome sequences from all four extant gorilla subspecies, including six newly sequenced eastern gorillas from previously unsampled geographic regions. Using approximate Bayesian computation with neural networks to model the demographic history of gorillas, we find a signature of admixture from an archaic 'ghost' lineage into the common ancestor of eastern gorillas but not western gorillas. We infer that up to 3% of the genome of these individuals is introgressed from an archaic lineage that diverged more than 3 million years ago from the common ancestor of all extant gorillas. This introgression event took place before the split of mountain and eastern lowland gorillas, probably more than 40 thousand years ago and may have influenced perception of bitter taste in eastern gorillas. When comparing the introgression landscapes of gorillas, humans and bonobos, we find a consistent depletion of introgressed fragments on the X chromosome across these species. However, depletion in protein-coding content is not detectable in eastern gorillas, possibly as a consequence of stronger genetic drift in this species., (© 2023. The Author(s).)

Acinetobacter species are widely known opportunistic pathogens causing severe community and healthcare-associated infections. One such emerging pathogen, Acinetobacter colistiniresistens, is known to exhibit intrinsic resistance to colistin. We investigated the molecular characteristics of A. colistiniresistens strain C-214, isolated from the fecal sample of a healthy community member, as part of a cohort study being conducted in Segamat, Malaysia. Comparison of the whole genome sequence of C-214 with other A. colistiniresistens sequences retrieved from the NCBI database showed 95% sequence identity or more with many of the genome sequences representing that species. Use of the Galleria mellonella killing assay showed that C-214 was pathogenic in this model infection system. The strain C-214 had a colistin and polymyxin B MIC of 32 and 16 mg/L, respectively. Besides, it was resistant to cefotaxime, amikacin, and tetracycline and showed moderate biofilm-producing ability. Different genes associated with virulence or resistance to major classes of antibiotics were detected. We observed mutations in lpxA/C/D in C-214 and other A. colistiniresistens strains as probable causes of colistin resistance, but the biological effects of these mutations require further investigation. This study provides genomic insights into A. colistiniresistens, a potentially pathogenic bacterium isolated from a community member and notes the public health threat it may pose., (© 2023. Springer Nature Limited.)

A paradigm shift in preclinical evaluations of new anticancer GBM drugs should occur in favour of 3D cultures. This study leveraged the vast genomic data banks to investigate the suitability of 3D cultures as cell-based models for GBM. We hypothesised that correlating genes that are highly upregulated in 3D GBM models will have an impact in GBM patients, which will support 3D cultures as more reliable preclinical models for GBM. Using clinical samples of brain tissue from healthy individuals and GBM patients from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Chinese Glioma Genome Atlas (CGGA), and Genotype-Tissue Expression (GTEx) databases, several genes related to pathways such as epithelial-to-mesenchymal transition (EMT)-related genes ( CD44 , TWIST1 , SNAI1 , CDH2 , FN1 , VIM ), angiogenesis/migration-related genes ( MMP1 , MMP2 , MMP9 , VEGFA ), hypoxia-related genes ( HIF1A , PLAT ), stemness-related genes ( SOX2 , PROM1 , NES , FOS ), and genes involved in the Wnt signalling pathway ( DKK1 , FZD7 ) were found to be upregulated in brain samples from GBM patients, and the expression of these genes were also enhanced in 3D GBM cells. Additionally, EMT-related genes were upregulated in GBM archetypes (wild-type IDH1 R132 ) that historically have poorer treatment responses, with said genes being significant predictors of poorer survival in the TCGA cohort. These findings reinforced the hypothesis that 3D GBM cultures can be used as reliable models to study increased epithelial-to-mesenchymal transitions in clinical GBM samples.

Acinetobacter baumannii is a common cause of multidrug-resistant (MDR) nosocomial infections around the world. However, little is known about the persistence and dynamics of A. baumannii in a healthy community. This study investigated the role of the community as a prospective reservoir for A. baumannii and explored possible links between hospital and community isolates. A total of 12 independent A. baumannii strains were isolated from human faecal samples from the community in Segamat, Malaysia, in 2018 and 2019. Another 15 were obtained in 2020 from patients at the co-located tertiary public hospital. The antimicrobial resistance profile and biofilm formation ability were analysed, and the relatedness of community and hospital isolates was determined using whole-genome sequencing (WGS). Antibiotic profile analysis revealed that 12 out of 15 hospital isolates were MDR, but none of the community isolates were MDR. However, phylogenetic analysis based on single-nucleotide polymorphisms (SNPs) and a pangenome analysis of core genes showed clustering between four community and two hospital strains. Such clustering of strains from two different settings based on their genomes suggests that these strains could persist in both. WGS revealed 41 potential resistance genes on average in the hospital strains, but fewer ( n =32) were detected in the community strains. In contrast, 68 virulence genes were commonly seen in strains from both sources. This study highlights the possible transmission threat to public health posed by virulent A. baumannii present in the gut of asymptomatic individuals in the community.

Methicillin-resistant Staphylococcus aureus (MRSA) is a World Health Organization-listed priority pathogen. Scarce genomic data are available for MRSA isolates from Malaysia. Here, we present the complete genome sequence of a multidrug-resistant MRSA strain SauR3, isolated from the blood of a 6-year-old patient hospitalized in Terengganu, Malaysia, in 2016. S. aureus SauR3 was resistant to five antimicrobial classes comprising nine antibiotics. The genome was sequenced on the Illumina and Oxford Nanopore platforms and hybrid assembly was performed to obtain its complete genome sequence. The SauR3 genome consists of a circular chromosome of 2,800,017 bp and three plasmids designated pSauR3-1 (42,928 bp), pSauR3-2 (3011 bp), and pSauR3-3 (2473 bp). SauR3 belongs to sequence type 573 (ST573), a rarely reported sequence type of the staphylococcal clonal complex 1 (CC1) lineage, and harbors a variant of the staphylococcal cassette chromosome mec (SCC mec ) type V (5C2&5) element which also contains the aac(6')-aph(2″) aminoglycoside-resistance genes. pSauR3-1 harbors several antibiotic resistance genes in a 14,095 bp genomic island (GI), previously reported in the chromosome of other staphylococci. pSauR3-2 is cryptic, whereas pSauR3-3 encodes the ermC gene that mediates inducible resistance to macrolide-lincosamide-streptogramin B (iMLS B ). The SauR3 genome can potentially be used as a reference genome for other ST573 isolates.

Urban-dwelling birds can be useful biomonitors to assess the impact of the urbanisation on both public and wildlife health. Widely distributed urban bird species, the House crow, was studied for heavy metal accumulation levels from nine cities of South Asia, Southeast Asia and Africa that border the Indian Ocean. Feathers were spectroscopically investigated for the deposition of ten heavy metals, i.e. As, Zn, Pb, Cd, Ni, iron Fe, Mn, Cr, Cu and Li. Fe and Zn were found to be the most prevalent metals in all sites. Measured concentrations of Pb (4.38-14.77 mg kg -1 ) overall, and Fe (935.66 mg kg -1 ) and Cu (67.17 mg kg -1 ) at some studied sites were above the toxicity levels reported lethal in avian toxicological studies. Multivariate analysis and linear models supported geographical location as a significant predictor for the level of most of the metals. Zn and Cu, generally and Pb, Cd, Mn, Cr at some sites exhibited potential bioaccumulation from surrounding environments. Inter-species comparisons strengthen the inference that the House crow is a reliable bioindicator species for the qualitative assessment of local urban environmental pollution and could be a useful tool for inter-regional monitoring programs., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Bioactive peptides are naturally found in various foods and were shown to have various distinct physiological as well as medicinal benefits. In this study shrimp peptide hydrolysate (SPH) was prepared to investigate its immunomodulatory effect against cyclophosphamide (CTX) induced immunosuppressed mice. The SPH effect was also analyzed on murine macrophage (RAW264.7 cells). The findings show that SPH stimulates macrophages to form multiple pseudopodia, has no cytotoxic effect, and increases phagocytic activity in RAW264.7 cells. Furthermore, the immunosuppressed in-vivo model illustrates the improvement in various aspects, that is body weight, escalation in immune organ index, and ameliorates histopathological transformation of thymus along with the spleen. SPH enhances cell-mediated immunity by facilitating splenocyte proliferation and inhibit excessive apoptosis. Moreover, the significant outcome had been observed with the upregulation of cytokines interferon-gamma (IFN-ϒ), interleukin-2 (IL-2) level and simultaneously downregulate certain genes include interleukin-4 (IL-4) and interleukin-10 (IL-10). Additionally, SPH expedites cellular immunity by enhancing the regulation of immunoglobulin A (IgA) and immunoglobulin M (IgM). However, these findings support the hypothesis that SPH is an effective immunomodulatory agent capable of preventing immune system hypofunction. It is necessary to investigate the detailed mechanism to rule out any unforeseen effects of SPH in future research. PRACTICAL APPLICATIONS: Chemotherapy medications, despite their dominating detrimental effects of damaging immunological organs such as the spleen and thymus, extend the treatment process as well as the destruction of the self-immune system. This study found that SPH is an effective immunomodulatory agent capable of avoiding immune organ hypofunction and improving cell mediate immunity by enhancing macrophage activation, phagocytosis, spleenocyte proliferation, suppressing apoptosis, and elevating cytokines and antibodies. As a result, SPH can be utilized as a nutritional and functional dietary supplement to boost immunological modulation in combination with chemotherapy medications in order to lessen their adverse effects., (© 2022 Wiley Periodicals LLC.)

Southeast Asia comprises 11 countries that span mainland Asia across to numerous islands that stretch from the Andaman Sea to the South China Sea and Indian Ocean. This region harbors an impressive diversity of history, culture, religion and biology. Indigenous people of Malaysia display substantial phenotypic, linguistic, and anthropological diversity. Despite this remarkable diversity which has been documented for centuries, the genetic history and structure of indigenous Malaysians remain under-studied. To have a better understanding about the genetic history of these people, especially Malaysian Negritos, we sequenced whole genomes of 15 individuals belonging to five indigenous groups from Peninsular Malaysia and one from North Borneo to high coverage (30X). Our results demonstrate that indigenous populations of Malaysia are genetically close to East Asian populations. We show that present-day Malaysian Negritos can be modeled as an admixture of ancient Hoabinhian hunter-gatherers and Neolithic farmers. We observe gene flow from South Asian populations into the Malaysian indigenous groups, but not into Dusun of North Borneo. Our study proposes that Malaysian indigenous people originated from at least three distinct ancestral populations related to the Hoabinhian hunter-gatherers, Neolithic farmers and Austronesian speakers., (© 2022. The Author(s).)

Northern Pakistan is home to many diverse ethnicities and languages. The region acted as a prime corridor for ancient invasions and population migrations between Western Eurasia and South Asia. Kho, one of the major ethnic groups living in this region, resides in the remote and isolated mountainous region in the Chitral Valley of the Hindu Kush Mountain range. They are culturally and linguistically distinct from the rest of the Pakistani population groups and their genetic ancestry is still unknown. In this study, we generated genome-wide genotype data of ~1 M loci (Illumina WeGene array) for 116 unrelated Kho individuals and carried out comprehensive analyses in the context of worldwide extant and ancient anatomically modern human populations across Eurasia. The results inferred that the Kho can trace a large proportion of their ancestry to the population who migrated south from the Southern Siberian steppes during the second millennium BCE ~110 generations ago. An additional wave of gene flow from a population carrying East Asian ancestry was also identified in the Kho that occurred ~60 generations ago and may possibly be linked to the expansion of the Tibetan Empire during 7th to 9th centuries CE (current era) in the northwestern regions of the Indian sub-continent. We identified several candidate regions suggestive of positive selection in the Kho, that included genes mainly involved in pigmentation, immune responses, muscular development, DNA repair, and tumor suppression., (© 2022. The Author(s), under exclusive licence to European Society of Human Genetics.)

The Orang Asli (OA) of Malaysia have been relatively understudied where little is known about their oral and gut microbiomes. As human health is closely intertwined with the human microbiome, this study first assessed the cardiometabolic health in four OA communities ranging from urban, rural to semi-nomadic hunter-gatherers. The urban Temuan suffered from poorer cardiometabolic health while rural OA communities were undergoing epidemiological transition. The oral microbiota of the OA were characterised by sequencing the V4 region of the 16S rRNA gene. The OA oral microbiota were unexpectedly homogenous, with comparably low alpha diversity across all four communities. The rural Jehai and Temiar PP oral microbiota were enriched for uncharacterised bacteria, exhibiting potential for discoveries. This finding also highlights the importance of including under-represented populations in large cohort studies. The Temuan oral microbiota were also elevated in opportunistic pathogens such as Corynebacterium, Prevotella , and Mogibacterium , suggesting possible oral dysbiosis in these urban settlers. The semi-nomadic Jehai gut microbiota had the highest alpha diversity, while urban Temuan exhibited the lowest. Rural OA gut microbiota were distinct from urban-like microbiota and were elevated in bacteria genera such as Prevotella 2, Prevotella 9 , Lachnospiraceae ND3007, and Solobacterium. Urban Temuan microbiota were enriched in Odoribacter, Blautia, Parabacetroides, Bacteroides and Ruminococcacecae UCG-013. This study brings to light the current health trend of these indigenous people who have minimal access to healthcare and lays the groundwork for future, in-depth studies in these populations., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yeo, Lee, Palanisamy, Khalid, Ayub, Lim, Lim and Phipps.)

Objectives: This study profiled the prevalence of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-EC) in the community and compared their resistome and genomic profiles with isolates from clinical patients through whole-genome sequencing., Methods: Fecal samples from 233 community dwellers from Segamat, a town in southern Malaysia, were obtained between May through August 2018. Putative ESBL strains were screened and tested using antibiotic susceptibility tests. Additionally, eight clinical ESBL-EC were obtained from a hospital in the same district between June through October 2020. Whole-genome sequencing was then conducted on selected ESBL-EC from both settings (n = 40) for pan-genome comparison, cluster analysis, and resistome profiling., Results: A mean ESBL-EC carriage rate of 17.82% (95% CI: 10.48%- 24.11%) was observed in the community and was consistent across demographic factors. Whole-genome sequences of the ESBL-EC (n = 40) enabled the detection of multiple plasmid replicon groups (n = 28), resistance genes (n = 34) and virulence factors (n = 335), with no significant difference in the number of genes carried between the community and clinical isolates (plasmid replicon groups, p = 0.13; resistance genes, p = 0.47; virulence factors, p = 0.94). Virulence gene marker analysis detected the presence of extraintestinal pathogenic E. coli (ExPEC), uropathogenic E. coli (UPEC), and enteroaggregative E. coli (EAEC) in both the community and clinical isolates. Multiple blaCTX-M variants were observed, dominated by blaCTX-M-27 (n = 12), blaCTX-M-65 (n = 10), and blaCTX-M-15 (n = 9). The clinical and community isolates did not cluster together based on the pan-genome comparison, suggesting isolates from the two settings were clonally unrelated. However, cluster analysis based on carried plasmids, resistance genes and phenotypic susceptibility profiles identified four distinct clusters, with similar patterns between the community and clinical isolates., Conclusion: ESBL-EC from the clinical and community settings shared similar resistome profiles, suggesting the frequent exchange of genetic materials through horizontal gene transfer., Competing Interests: The authors have declared that no competing interests exist.

The gut microbiota is important in regulating host metabolism, maintaining physiology, and protecting immune homeostasis. Gut microbiota dysbiosis affects the development of the gut microenvironment, as well as the onset of various external systemic diseases and metabolic syndromes. Cyclophosphamide (CTX) is a commonly used chemotherapeutic drug that suppresses the host immune system, intestinal mucosa inflammation, and dysbiosis of the intestinal flora. Immunomodulators are necessary to enhance the immune system and prevent homeostasis disbalance and cytotoxicity caused by CTX. In this study, shrimp peptide hydrolysate (SPH) was evaluated for immunomodulation, intestinal integration, and microbiota in CTX-induced immunosuppressed mice. It was observed that SPH would significantly restore goblet cells and intestinal mucosa integrity, modulate the immune system, and increase relative expression of mRNA and tight-junction associated proteins (Occludin, Zo-1, Claudin-1, and Mucin-2). It also improved gut flora and restored the intestinal microbiota ecological balance by removing harmful microbes of various taxonomic groups. This would also increase the immune organs index, serum levels of cytokines (IFN-ϒ, IL1β, TNF-α, IL-6), and immunoglobin levels (IgA, IgM). The Firmicutes/Bacteroidetes proportion was decreased in CTX-induced mice. Finally, SPH would be recommended as a functional food source with a modulatory effect not only on intestinal microbiota, but also as a potential health-promoting immune function regulator.

Miscarriage is the spontaneous termination of a pregnancy before 24 weeks of gestation. We studied the genome of euploid miscarried embryos from mothers in the range of healthy adult individuals to understand genetic susceptibility to miscarriage not caused by chromosomal aneuploidies. We developed GP , a pipeline that we used to prioritize 439 unique variants in 399 genes, including genes known to be associated with miscarriages. Among the prioritized genes we found STAG2 coding for the cohesin complex subunit, for which inactivation in mouse is lethal, and TLE4 a target of Notch and Wnt, physically interacting with a region on chromosome 9 associated to miscarriages., (© 2022. The Author(s).)

The human gut contains a complex microbiota dominated by bacteriophages but also containing other viruses and bacteria and fungi. There are a growing number of techniques for the extraction, sequencing, and analysis of the virome but currently no standardized protocols. This study established an effective workflow for virome analysis to investigate the virome of stool samples from two understudied ethnic groups from Malaysia: the Jakun and Jehai Orang Asli. By using the virome extraction and analysis workflow with the Oxford Nanopore Technology, long-read sequencing successfully captured close to full-length viral genomes. The virome composition of the two indigenous Malaysian communities were remarkably different from those found in other parts of the world. Additionally, plant viruses found in the viromes of these individuals were attributed to traditional food-seeking methods. This study establishes a human gut virome workflow and extends insights into the healthy human gut virome, laying the groundwork for comparative studies., (© 2022. The Author(s).)

The history of plants to be utilized as medicines is thousands of years old. Black cumin is one of the most widely examined plant possessing naturally occurring compounds with antimicrobial potential. Foliar application of growth stimulators is a successful strategy to enhance yield and quality in many crops. A field study was planned to apply growth stimulator like moringa leaf extract on black cumin crop grown under field conditions using RCB design with three replications. All other agronomic inputs and practices were uniform. The treatments were moringa leaf extract concentrations (10%, 20%), growth stages (40 days after sowing, 80 DAS, 120 DAS, 40 + 80 DAS, 40 + 120 DAS, 80 + 120 DAS, 40 + 80 + 120 days after sowing) and two controls unsprayed check (i.e. no moringa leaf extract, no water) and sprayed check (no moringa leaf extract + water). Application of 20% moringa leaf extract at stage-7 (40 + 80 + 120 days after sowing) had significantly increased plant height, branches plant -1 , essential oil content, fixed oil content, peroxidase value and iodine value of black cumin oil over unsprayed control. Application of moringa leaf extract showed maximum results and improves growth and yield of black cumin when applied at 40 + 80 + 120 days after sowing. As this study was only conducted using moringa leaf extract, it is advisable to conduct an experiment with various bio stimulants along with fertilizer combinations and growth regulators to check their synergistic effects for more reliable and acceptable recommendations in future., (© 2021. The Author(s).)

Background: In population genomics, polymorphisms that are highly differentiated between geographically separated populations are often suggestive of Darwinian positive selection. Genomic scans have highlighted several such regions in African and non-African populations, but only a handful of these have functional data that clearly associates candidate variations driving the selection process. Fine-Mapping of Adaptive Variation (FineMAV) was developed to address this in a high-throughput manner using population based whole-genome sequences generated by the 1000 Genomes Project. It pinpoints positively selected genetic variants in sequencing data by prioritizing high frequency, population-specific and functional derived alleles., Results: We developed a stand-alone software that implements the FineMAV statistic. To graphically visualise the FineMAV scores, it outputs the statistics as bigWig files, which is a common file format supported by many genome browsers. It is available as a command-line and graphical user interface. The software was tested by replicating the FineMAV scores obtained using 1000 Genomes Project African, European, East and South Asian populations and subsequently applied to whole-genome sequencing datasets from Singapore and China to highlight population specific variants that can be subsequently modelled. The software tool is publicly available at https://github.com/fadilla-wahyudi/finemav ., Conclusions: The software tool described here determines genome-wide FineMAV scores, using low or high-coverage whole-genome sequencing datasets, that can be used to prioritize a list of population specific, highly differentiated candidate variants for in vitro or in vivo functional screens. The tool displays these scores on the human genome browsers for easy visualisation, annotation and comparison between different genomic regions in worldwide human populations., (© 2021. The Author(s).)

A nonsense allele at rs1343879 in human MAGEE2 on chromosome X has previously been reported as a strong candidate for positive selection in East Asia. This premature stop codon causing ∼80% protein truncation is characterized by a striking geographical pattern of high population differentiation: common in Asia and the Americas (up to 84% in the 1000 Genomes Project East Asians) but rare elsewhere. Here, we generated a Magee2 mouse knockout mimicking the human loss-of-function mutation to study its functional consequences. The Magee2 null mice did not exhibit gross abnormalities apart from enlarged brain structures (13% increased total brain area, P = 0.0022) in hemizygous males. The area of the granular retrosplenial cortex responsible for memory, navigation, and spatial information processing was the most severely affected, exhibiting an enlargement of 34% (P = 3.4×10-6). The brain size in homozygous females showed the opposite trend of reduced brain size, although this did not reach statistical significance. With these insights, we performed human association analyses between brain size measurements and rs1343879 genotypes in 141 Chinese volunteers with brain MRI scans, replicating the sexual dimorphism seen in the knockout mouse model. The derived stop gain allele was significantly associated with a larger volume of gray matter in males (P = 0.00094), and smaller volumes of gray (P = 0.00021) and white (P = 0.0015) matter in females. It is unclear whether or not the observed neuroanatomical phenotypes affect behavior or cognition, but it might have been the driving force underlying the positive selection in humans., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Ethnicity is consistently reported as a strong determinant of human gut microbiota. However, the bulk of these studies are from Western countries, where microbiota variations are mainly driven by relatively recent migration events. Malaysia is a multicultural society, but differences in gut microbiota persist across ethnicities. We hypothesized that migrant ethnic groups continue to share fundamental gut traits with the population in the country of origin due to shared cultural practices despite subsequent geographical separation. To test this hypothesis, the 16S rRNA gene amplicons from 16 studies comprising three major ethnic groups in Malaysia were analysed, covering 636 Chinese, 248 Indian and 123 Malay individuals from four countries (China, India, Indonesia and Malaysia). A confounder-adjusted permutational multivariate analysis of variance (PERMANOVA) detected a significant association between ethnicity and the gut microbiota (PERMANOVA R 2 =0.005, pseudo- F =2.643, P =0.001). A sparse partial least squares - discriminant analysis model trained using the gut microbiota of individuals from China, India and Indonesia (representation of Chinese, Indian and Malay ethnic group, respectively) showed a better-than-random performance in classifying Malaysian of Chinese descent, although the performance for Indian and Malay were modest (true prediction rate, Chinese=0.60, Indian=0.49, Malay=0.44). Separately, differential abundance analysis singled out Ligilactobacillus as being elevated in Indians. We postulate that despite the strong influence of geographical factors on the gut microbiota, cultural similarity due to a shared ethnic origin drives the presence of a shared gut microbiota composition. The interplay of these factors will likely depend on the circumstances of particular groups of migrants.

Although several studies have already been carried out in investigating the general profile of the gut mycobiome across several countries, there has yet to be an officially established baseline of a healthy human gut mycobiome, to the best of our knowledge. Microbial composition within the gastrointestinal tract differ across individuals worldwide, and most human gut fungi studies concentrate specifically on individuals from developed countries or diseased cohorts. The present study is the first culture-dependent community study assessing the prevalence and diversity of gut fungi among different ethnic groups from South East Asia. Samples were obtained from a multi-ethnic semi-rural community from Segamat in southern Malaysia. Faecal samples were screened for culturable fungi and questionnaire data analysis was performed. Culturable fungi were present in 45% of the participants' stool samples. Ethnicity had an impact on fungal prevalence and density in stool samples. The prevalence of resistance to fluconazole, itraconazole, voriconazole and 5-fluorocytosine, from the Segamat community, were 14%, 14%, 11% and 7% respectively. It was found that Jakun individuals had lower levels of antifungal resistance irrespective of the drug tested, and male participants had more fluconazole resistant yeast in their stool samples. Two novel point mutations were identified in the ERG11 gene from one azole resistant Candida glabrata, suggesting a possible cause of the occurrence of antifungal resistant isolates in the participant's faecal sample.

Soil-transmitted helminth infections (STHs) are recognized as a major health issue among socio-economically deprived communities. However, information is still lacking regarding the prevalence rates of STHs in the broader community across different countries in the tropics. This community study aimed to determine the prevalence and risk factors for STHs in semi-rural communities in Segamat of Johor, Malaysia. A cross-sectional study was conducted with information collected from the study population through questionnaire. A total of 224 stool samples were examined for intestinal parasites through formalin-ether concentration and Kato-Katz techniques. Overall, only 1.8% (n = 4/224) of participants were infected with soil-transmitted helminths, the extremely low prevalence may be explained by the proper housing conditions with basic amenities and the practices of hygienic habits in daily life, highlighting the importance of adopting good hygienic practices., (© Indian Society for Parasitology 2021.)

A widely distributed urban bird, the house crow (Corvus splendens), was used to assess bioavailable heavy metals in urban and rural environments across Pakistan. Bioaccumulation of arsenic (As), zinc (Zn), lead (Pb), cadmium (Cd), nickel (Ni), iron (Fe), manganese (Mn), chromium (Cr), and copper (Cu) was investigated in wing feathers of 96 crows collected from eight locations and categorized into four groups pertaining to their geographical and environmental similarities. Results revealed that the concentrations of Pb, Ni, Mn, Cu, and Cr were positively correlated and varied significantly among the four groups. Zn, Fe, Cr, and Cu regarded as industrial outputs, were observed in birds both in industrialized cities and in adjoining rural agricultural areas irrigated through the Indus Basin Irrigation System. Birds in both urban regions accrued Pb more than the metal toxicity thresholds for birds. The house crow was ranked in the middle on the metal accumulation levels in feathers between highly accumulating raptor and piscivore and less contaminated insectivore and granivore species in the studied areas,. This study suggests that the house crow is an efficient bioindicator and supports the feasibility of using feathers to discriminate the local pollution differences among terrestrial environments having different levels and kinds of anthropogenic activities.

Sun bear populations are fragmented and at risk from habitat loss and exploitation for body parts. These threats are made worse by significant gaps in knowledge of sun bear population genetic diversity, population connectivity, and taxonomically significant management units. Using a complete sun bear mitochondrial genome, we developed a set of mitochondrial markers to assess haplotype variation and the evolutionary history of sun bears from Peninsular (West) Malaysia and Sabah (East Malaysia). Genetic samples from 28 sun bears from Peninsular Malaysia, 36 from Sabah, and 18 from Thailand were amplified with primers targeting a 1800 bp region of the mitochondrial genome including the complete mitochondrial control region and adjacent genes. Sequences were analyzed using phylogenetic methods. We identified 51 mitochondrial haplotypes among 82 sun bears. Phylogenetic and network analyses provided strong support for a deep split between Malaysian sun bears and sun bears in East Thailand and Yunnan province in China. The Malaysian lineage was further subdivided into two clades: Peninsular Malaysian and Malaysian Borneo (Sabah). Sun bears from Thailand occurred in both Sabah and Peninsular Malaysian clades. Our study supports recent findings that sun bears from Sundaland form a distinct clade from those in China and Indochina with Thailand possessing lineages from the three clades. Importantly, we demonstrate a more recent and clear genetic delineation between sun bears from the Malay Peninsula and Sabah indicating historical barriers to gene flow within the Sundaic region., (© The American Genetic Association. 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The nosocomial pathogen, Acinetobacter baumannii, has acquired clinical significance due to its ability to persist in hospital settings and survive antibiotic treatment, which eventually resulted in the rapid spread of this bacterium with antimicrobial resistance (AMR) phenotypes. This study used a multidrug-resistant A. baumannii (strain ATCC BAA1605) as a model to study the genomic features of this pathogen., Results: One circular chromosome and one circular plasmid were discovered in the complete genome of A. baumannii ATCC BAA1605 using whole-genome sequencing. The chromosome is 4,039,171 bp long with a GC content of 39.24%. Many AMR genes, which confer resistance to major classes of antibiotics (beta-lactams, aminoglycosides, tetracycline, sulphonamides), were found on the chromosome. Two genomic islands were predicted on the chromosome, one of which (Genomic Island 1) contains a cluster of AMR genes and mobile elements, suggesting the possibility of horizontal gene transfer. A subtype I-F CRISPR-Cas system was also identified on the chromosome of A. baumannii ATCC BAA1605. This study provides valuable genome data that can be used as a reference for future studies on A. baumannii. The genome of A. baumannii ATCC BAA1605 has been deposited at GenBank under accession no. CP058625 and CP058626.

Backgrounds: Escherichia coli K1 causes neonatal meningitis. Transcriptome studies are indispensable to comprehend the pathology and biology of these bacteria. Recently, we showed that nanoparticles loaded with Hesperidin are potential novel antibacterial agents against E. coli K1. Here, bacteria were treated with and without Hesperidin conjugated with silver nanoparticles, and silver alone, and 50% minimum inhibitory concentration was determined. Differential gene expression analysis using RNA-seq, was performed using Degust software and a set of genes involved in cell stress response and metabolism were selected for the study., Results: 50% minimum inhibitory concentration with silver-conjugated Hesperidin was achieved with 0.5 μg/ml of Hesperidin conjugated with silver nanoparticles at 1 h. Differential genetic analysis revealed the expression of 122 genes (≥ 2-log FC, P< 0.01) in both E. coli K1 treated with Hesperidin conjugated silver nanoparticles and E. coli K1 treated with silver alone, compared to untreated E. coli K1. Of note, the expression levels of cation efflux genes (cusA and copA) and translocation of ions, across the membrane genes (rsxB) were found to increase 2.6, 3.1, and 3.3- log FC, respectively. Significant regulation was observed for metabolic genes and several genes involved in the coordination of flagella., Conclusions: The antibacterial mechanism of nanoparticles maybe due to disruption of the cell membrane, oxidative stress, and metabolism in E. coli K1. Further studies will lead to a better understanding of the genetic mechanisms underlying treatment with nanoparticles and identification of much needed novel antimicrobial drug candidates.

Basal stem rot (BSR), caused by Ganoderma boninense , is the most devastating oil palm disease in South East Asia, costing US$500 million annually. Various soil physicochemical parameters have been associated with an increase in BSR incidences. However, very little attention has been directed to understanding the relationship between soil microbiome and BSR incidence in oil palm fields. The prokaryotic and eukaryotic microbial diversities of two coastal soils, Blenheim soil (Typic Quartzipsamment-calcareous shell deposits, light texture) with low disease incidence (1.9%) and Bernam soil (Typic Endoaquept-non-acid sulfate) with high disease incidence (33.1%), were determined using the 16S (V3-V4 region) and 18S (V9 region) rRNA amplicon sequencing. Soil physicochemical properties (pH, electrical conductivity, soil organic matter, nitrogen, phosphorus, cation exchange capacity, exchangeable cations, micronutrients, and soil physical parameters) were also analyzed for the two coastal soils. Results revealed that Blenheim soil comprises higher prokaryotic and eukaryotic diversities, accompanied by higher pH and calcium content. Blenheim soil was observed to have a higher relative abundance of bacterial taxa associated with disease suppression such as Calditrichaeota, Zixibacteria, GAL15, Omnitrophicaeota, Rokubacteria, AKYG587 (Planctomycetes), JdFR-76 (Calditrichaeota), and Rubrobacter (Actinobacteria). In contrast, Bernam soil had a higher proportion of other bacterial taxa, Chloroflexi and Acidothermus (Actinobacteria). Cercomonas (Cercozoa) and Calcarisporiella (Ascomycota) were eukaryotes that are abundant in Blenheim soil, while Uronema (Ciliophora) and mammals were present in higher abundance in Bernam soil. Some of the bacterial taxa have been reported previously in disease-suppressive and -conducive soils as potential disease-suppressive or disease-inducible bacteria. Furthermore, Cercomonas was reported previously as potential bacterivorous flagellates involved in the selection of highly toxic biocontrol bacteria, which might contribute to disease suppression indirectly. The results from this study may provide valuable information related to soil microbial community structures and their association with soil characteristics and soil susceptibility to Ganoderma .

The domestication of a wild-caught aquatic animal is an evolutionary process, which results in genetic discrimination at the genomic level in response to strong artificial selection. Although black tiger shrimp ( Penaeus monodon ) is one of the most commercially important aquaculture species, a systematic assessment of genetic divergence and structure of wild-caught and domesticated broodstock populations of the species is yet to be documented. Therefore, we used skim sequencing (SkimSeq) based genotyping approach to investigate the genetic structure of 50 broodstock individuals of P. monodon species, collected from five sampling sites ( n = 10 in each site) across their distribution in Indo-Pacific regions. The wild-caught P. monodon broodstock population were collected from Malaysia (MS) and Japan (MJ), while domesticated broodstock populations were collected from Madagascar (MMD), Hawaii, HI, USA (MMO), and Thailand (MT). After various filtering process, a total of 194,259 single nucleotide polymorphism (SNP) loci were identified, in which 4983 SNP loci were identified as putatively adaptive by the pcadapt approach. In both datasets, pairwise F ST estimates high genetic divergence between wild and domesticated broodstock populations. Consistently, different spatial clustering analyses in both datasets categorized divergent genetic structure into two clusters: (1) wild-caught populations (MS and MJ), and (2) domesticated populations (MMD, MMO and MT). Among 4983 putatively adaptive SNP loci, only 50 loci were observed to be in the coding region. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested that non-synonymous mutated genes might be associated with the energy production, metabolic functions, respiration regulation and developmental rates, which likely act to promote adaptation to the strong artificial selection during the domestication process. This study has demonstrated the applicability of SkimSeq in a highly duplicated genome of P. monodon specifically, across a range of genetic backgrounds and geographical distributions, and would be useful for future genetic improvement program of this species in aquaculture.

Naegleria fowleri causes a deadly infection known as primary amoebic meningoencephalitis (PAM). To our knowledge, there are very few transcriptome studies conducted on these brain-eating amoebae, despite rise in the number of cases. Although the Naegleria genome has been sequenced, currently, it is not well annotated. Transcriptome level studies are needed to help understand the pathology and biology of this fatal parasitic infection. Recently, we showed that nanoparticles loaded with the flavonoid Hesperidin (HDN) are potential novel antimicrobial agents. N. fowleri trophozoites were treated with and without HDN-conjugated with silver nanoparticles (AgNPs) and silver only, and then, 50% minimum inhibitory concentration (MIC) was determined. The results revealed that the MIC of HDN-conjugated AgNPs was 12.5 microg/mL when treated for 3 h. As no reference genome exists for N. fowleri, de novo RNA transcriptome analysis using RNA-Seq and differential gene expression analysis was performed using the Trinity software. Analysis revealed that more than 2000 genes were differentially expressed in response to N. fowleri treatment with HDN-conjugated AgNPs. Some of the genes were linked to oxidative stress response, DNA repair, cell division, cell signalling and protein synthesis. The downregulated genes were linked with processes such as protein modification, synthesis of aromatic amino acids, when compared with untreated N. fowleri. Further transcriptome studies will lead to understanding of genetic mechanisms of the biology and pathogenesis and/or the identification of much needed drug candidates.