Displaying publications 4521 - 4540 of 8213 in total

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  1. Genetic polymorphisms as potential pharmacogenetic biomarkers for platinum-based chemotherapy in non-small cell lung cancer
    Sito H, Tan SC
    Mol Biol Rep, 2024 Jan 13;51(1):102.
    PMID: 38217759 DOI: 10.1007/s11033-023-08915-2
    Platinum-based chemotherapy (PBC) is a widely used treatment for various solid tumors, including non-small cell lung cancer (NSCLC). However, its efficacy is often compromised by the emergence of drug resistance in patients. There is growing evidence that genetic variations may influence the susceptibility of NSCLC patients to develop resistance to PBC. Here, we provide a comprehensive overview of the mechanisms underlying platinum drug resistance and highlight the important role that genetic polymorphisms play in this process. This paper discussed the genetic variants that regulate DNA repair, cellular movement, drug transport, metabolic processing, and immune response, with a focus on their effects on response to PBC. The potential applications of these genetic polymorphisms as predictive indicators in clinical practice are explored, as are the challenges associated with their implementation.
    Matched MeSH terms: Pharmacogenetics; Polymorphism, Genetic/genetics; Polymorphism, Single Nucleotide/genetics
  2. Allozyme polymorphisms and heavy metal levels in the green-lipped mussel Perna viridis (Linnaeus) collected from contaminated and uncontaminated sites in Malaysia
    Yap CK, Tan SG, Ismail A, Omar H
    Environ Int, 2004 Mar;30(1):39-46.
    PMID: 14664863
    It has been widely reported that heavy metal contamination in coastal waters can modify the allozyme profiles of marine organisms. Previous studies have recorded elevated metal concentrations in sediments and mussel tissues off Peninsular Malaysia. In the present study, horizontal starch gel electrophoresis was carried out to estimate the levels of allelic variation of the green-lipped mussel, Perna viridis, collected from one contaminated and three relatively uncontaminated sites off Peninsular Malaysia. Fourteen polymorphic loci were observed. In addition, the concentrations of cadmium, copper, lead, mercury and zinc were determined in the sediments and in the soft tissues of the mussels. Mussels from contaminated site, evidenced by high metal pollution indices (MPI) of the sediment and the mussel tissues, showed the highest percentage of polymorphic loci (78.6%), while those collected from the uncontaminated sites had lower MPI of the sediment and mussel tissue, and exhibited lower percentages of polymorphic loci (35.7-57.1%). The population from the contaminated site showed the highest excess of heterozygosity (0.289) when compared to that of the populations from the three uncontaminated sites (0.108-0.149). Allozyme frequencies at the phosphoglucomutase (PGM; E.C. 2.7.5.1) locus also differed between the contaminated and uncontaminated populations. Previous studies have shown that exposure to heavy metals can select or counter-select for particular alleles at this locus. The present results suggest that allozyme polymorphism in P. viridis is a potential biomonitoring tool for heavy metal contamination but further validation is required.
    Matched MeSH terms: Enzymes/genetics*; Gene Frequency/genetics
  3. Fulltext Towards complete and error-free genome assemblies of all vertebrate species
    Rhie A, McCarthy SA, Fedrigo O, Damas J, Formenti G, Koren S, et al.
    Nature, 2021 Apr;592(7856):737-746.
    PMID: 33911273 DOI: 10.1038/s41586-021-03451-0
    High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are available for only a few non-microbial species1-4. To address this issue, the international Genome 10K (G10K) consortium5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling highly accurate and nearly complete reference genomes. Here we present lessons learned from generating assemblies for 16 species that represent six major vertebrate lineages. We confirm that long-read sequencing technologies are essential for maximizing genome quality, and that unresolved complex repeats and haplotype heterozygosity are major sources of assembly error when not handled correctly. Our assemblies correct substantial errors, add missing sequence in some of the best historical reference genomes, and reveal biological discoveries. These include the identification of many false gene duplications, increases in gene sizes, chromosome rearrangements that are specific to lineages, a repeated independent chromosome breakpoint in bat genomes, and a canonical GC-rich pattern in protein-coding genes and their regulatory regions. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an international effort to generate high-quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences.
    Matched MeSH terms: Sex Chromosomes/genetics; Vertebrates/genetics*
  4. Fulltext TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase
    Liu G, Haw TJ, Starkey MR, Philp AM, Pavlidis S, Nalkurthi C, et al.
    Nat Commun, 2023 Nov 14;14(1):7349.
    PMID: 37963864 DOI: 10.1038/s41467-023-42913-z
    Toll-like receptor 7 (TLR7) is known for eliciting immunity against single-stranded RNA viruses, and is increased in both human and cigarette smoke (CS)-induced, experimental chronic obstructive pulmonary disease (COPD). Here we show that the severity of CS-induced emphysema and COPD is reduced in TLR7-deficient mice, while inhalation of imiquimod, a TLR7-agonist, induces emphysema without CS exposure. This imiquimod-induced emphysema is reduced in mice deficient in mast cell protease-6, or when wild-type mice are treated with the mast cell stabilizer, cromolyn. Furthermore, therapeutic treatment with anti-TLR7 monoclonal antibody suppresses CS-induced emphysema, experimental COPD and accumulation of pulmonary mast cells in mice. Lastly, TLR7 mRNA is increased in pre-existing datasets from patients with COPD, while TLR7+ mast cells are increased in COPD lungs and associated with severity of COPD. Our results thus support roles for TLR7 in mediating emphysema and COPD through mast cell activity, and may implicate TLR7 as a potential therapeutic target.
    Matched MeSH terms: Toll-Like Receptor 7/genetics; Tryptases/genetics
  5. A visualized hybrid PCR-LAMP assay for the detection of human Plasmodium species
    Lai MY, Ponnampalavanar SSS, Omar SFS, Lau YL
    Acta Trop, 2024 Mar;251:107120.
    PMID: 38199452 DOI: 10.1016/j.actatropica.2024.107120
    Combining the advantages of PCR and LAMP, we described a new technique, namely PCR-LAMP, for malaria diagnosis. The whole process of DNA amplification can be completed in 35 min. This hybrid amplification technique markedly improved the sensitivity of detection compared to the classic single PCR or LAMP assay alone. PCR-LAMP assay had a detection limit of 1 copy/µL for P. knowlesi and P. ovale, 0.1 copy/µL for P. vivax, P. falciparum and P. malariae, respectively. To facilitate the endpoint detection, xylenol orange was added. Positive samples were indicated in orange while negative reactions were violet. The inclusion of xylenol orange into the LAMP reaction mix significantly reduces the post-amplification workload. Without relying on the use of specific instruments, the color changes of the amplicons could be visualized directly through the naked eye. In conclusion, PCR-LAMP poses the potential to be developed as a new malaria molecular diagnosis tool.
    Matched MeSH terms: Plasmodium falciparum/genetics; Plasmodium vivax/genetics
  6. Epidemiology of multidrug-resistant Klebsiella pneumoniae infection in clinical setting in South-Eastern Asia: a systematic review and meta-analysis
    Salawudeen A, Raji YE, Jibo GG, Desa MNM, Neoh HM, Masri SN, et al.
    Antimicrob Resist Infect Control, 2023 Dec 07;12(1):142.
    PMID: 38062531 DOI: 10.1186/s13756-023-01346-5
    The rising prevalence of multidrug-resistant (MDR) and extended-spectrum beta lactamase-resistant (ESBL) Klebsiella pneumoniae (K. pneumoniae) is an important global public health challenge. This threat is even more pertinent in clinical settings. Morbidity and mortality associated with this condition are alarming particularly in the developing regions of the world. A comprehensive evaluation of the epidemiology of this phenomenon will assist towards the global effort of reducing its burden. So, this systematic review and meta-analysis was conducted to evaluate the epidemiology of MDR K. pneumoniae in South-Eastern Asia (SEA). The study was done under the PRISMA guidelines and was preceded by the development of a priori protocol. The protocol was then registered in PROSPERO-the public registry for systematic reviews. Seven important outcomes which include the assessment of the overall MDR K. pneumoniae prevalence were designed to be evaluated. A literature search was carried out in five selected electronic databases and 4389 were screened. Of these articles, 21 studies that met the eligibility criteria were included in the review. Relevant data were extracted from the included studies. By conducting a quality effect meta-analysis, the pooled prevalence for MDR and ESBL K. pneumoniae in SEA was estimated at 55% (CI 9-96) and 27% (CI 32-100) respectively. The review also identified ESBL genes types of allodemic situations occurring mostly in respiratory tract infections. The high prevalence of MDR and ESBL K. pneumoniae in this subregion is highly significant and of both public health and clinical relevance. Overall, the findings of this review will assist in the effective prevention and control of this threat in SEA.
    Matched MeSH terms: beta-Lactamases/genetics; Drug Resistance, Multiple, Bacterial/genetics
  7. Fulltext Characterization of the inheritance of field-evolved resistance to diamides in the fall armyworm (Spodoptera frugiperda) (Lepidoptera: Noctuidae) population from Puerto Rico
    Posos-Parra O, Mota-Sanchez D, Pittendrigh BR, Wise JC, DiFonzo CD, Patterson E
    PLoS One, 2024;19(2):e0295928.
    PMID: 38394153 DOI: 10.1371/journal.pone.0295928
    The fall armyworm (Spodoptera frugiperda) is one of the most destructive pests of corn. New infestations have been reported in the East Hemisphere, reaching India, China, Malaysia, and Australia, causing severe destruction to corn and other crops. In Puerto Rico, practical resistance to different mode of action compounds has been reported in cornfields. In this study, we characterized the inheritance of resistance to chlorantraniliprole and flubendiamide and identified the possible cross-resistance to cyantraniliprole and cyclaniliprole. The Puerto Rican (PR) strain showed high levels of resistance to flubendiamide (RR50 = 2,762-fold) and chlorantraniliprole (RR50 = 96-fold). The inheritance of resistance showed an autosomal inheritance for chlorantraniliprole and an X-linked inheritance for flubendiamide. The trend of the dominance of resistance demonstrated an incompletely recessive trait for H1 (♂ SUS × ♀ PR) × and an incompletely dominant trait for H2 (♀ SUS × ♂ PR) × for flubendiamide and chlorantraniliprole. The PR strain showed no significant presence of detoxification enzymes (using synergists: PBO, DEF, DEM, and VER) to chlorantraniliprole; however, for flubendiamide the SR = 2.7 (DEM), SR = 3.2 (DEF) and SR = 7.6 (VER) indicated the role of esterases, glutathione S- transferases and ABC transporters in the metabolism of flubendiamide. The PR strain showed high and low cross-resistance to cyantraniliprole (74-fold) and cyclaniliprole (11-fold), respectively. Incomplete recessiveness might lead to the survival of heterozygous individuals when the decay of diamide residue occurs in plant tissues. These results highlight the importance of adopting diverse pest management strategies, including insecticide rotating to manage FAW populations in Puerto Rico and other continents.
    Matched MeSH terms: Insecticide Resistance/genetics; Spodoptera/genetics
  8. Antibiotic resistance and determination of resistant genes among cockle (Anadara granosa) isolates of Vibrio alginolyticus
    Shahimi S, Elias A, Abd Mutalib S, Salami M, Fauzi F, Mohd Zaini NA, et al.
    Environ Sci Pollut Res Int, 2021 Aug;28(32):44002-44013.
    PMID: 33846919 DOI: 10.1007/s11356-021-13665-4
    A total of 24 strains of Vibrio alginolyticus were isolated from cockles (Anadara granosa) and identified for VibA and gyrB genes. All V. alginolyticus isolates were then tested against nine different antibiotics. In this study, the highest percentage of antibiotic resistance was obtained against penicillin (37.50%), followed by ampicillin, vancomycin (12.50%) and erythromycin (8.33%). All of V. alginolyticus isolates were susceptible against streptomycin, kanamycin, tetracycline, chloramphenicol and sulfamethoxazole. Polymerase chain reaction (PCR) assay has confirmed the presence of four antibiotic resistance genes of penicillin (pbp2a), ampicillin (blaOXA), erythromycin (ermB) and vancomycin (vanB). Out of 24 V. alginolyticus isolates, 2 isolates possessed the tdh-related hemolysin (trh) (strains VA15 and VA16) and none for the thermostable direct hemolysin (tdh) gene. Both strains of the tdh-related hemolysin (trh) were susceptible to all antibiotics tested. The multiple antibiotic resistance (MAR) index ranging between 0.2 and 0.3 with 5 antibiograms (A1-A5) was observed. Combination of enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) and antibiotic resistance indicated 18 genome types which showed genetic heterogeneity of those V. alginolyticus isolates. The results demonstrated the presence of V. alginolyticus strain found in cockles can be a potential risk to consumers and can contribute to the deterioration of human health in the study area. Thus, it is essential for local authority to provide the preventive measures in ensuring the cockles are safe for consumption.
    Matched MeSH terms: Drug Resistance, Bacterial/genetics; Vibrio alginolyticus/genetics
  9. Fulltext Unravelling the role of HAS2, GREM1, and PTGS2 gene expression in cumulus cells: implications for human oocyte development competency - a systematic review and integrated bioinformatic analysis
    Faizal AM, Elias MH, Jin NM, Abu MA, Syafruddin SE, Zainuddin AA, et al.
    Front Endocrinol (Lausanne), 2024;15:1274376.
    PMID: 38524634 DOI: 10.3389/fendo.2024.1274376
    The leading indicator for successful outcomes in in-vitro fertilization (IVF) is the quality of gametes in oocytes and sperm. Thus, advanced research aims to highlight the parameter in assessing these qualities - DNA fragmentation in sperm and oocyte development capacity (ODC) via evaluation of microenvironments involving its maturation process. Regarding oocytes, most evidence reveals the role of cumulus cells as non-invasive methods in assessing their development competency, mainly via gene expression evaluation. Our review aims to consolidate the evidence of GDF-9 derivatives, the HAS2, GREM1, and PTGS2 gene expression in cumulus cells used as ODC markers in relevant publications and tailored to current IVF outcomes. In addition to that, we also added the bioinformatic analysis in our review to strengthen the evidence aiming for a better understanding of the pathways and cluster of the genes of interest - HAS2, GREM1, and PTGS2 in cumulus cell level. Otherwise, the current non-invasive method can be used in exploring various causes of infertility that may affect these gene expressions at the cumulus cell level. Nevertheless, this method can also be used in assessing the ODC in various cohorts of women or as an improvement of markers following targeted tools or procedures by evaluating the advancement of these gene expressions following the targeted intervention.
    Matched MeSH terms: Intercellular Signaling Peptides and Proteins/genetics; Cyclooxygenase 2/genetics
  10. Fulltext Molecular Cloning and Functional Expression of a Δ9- Fatty Acid Desaturase from an Antarctic Pseudomonas sp. A3
    Garba L, Mohamad Ali MS, Oslan SN, Rahman RN
    PLoS One, 2016;11(8):e0160681.
    PMID: 27494717 DOI: 10.1371/journal.pone.0160681
    Fatty acid desaturase enzymes play an essential role in the synthesis of unsaturated fatty acids. Pseudomonas sp. A3 was found to produce a large amount of palmitoleic and oleic acids after incubation at low temperatures. Using polymerase Chain Reaction (PCR), a novel Δ9- fatty acid desaturase gene was isolated, cloned, and successfully expressed in Escherichia coli. The gene was designated as PA3FAD9 and has an open reading frame of 1,185 bp which codes for 394 amino acids with a predicted molecular weight of 45 kDa. The activity of the gene product was confirmed via GCMS, which showed a functional putative Δ9-fatty acid desaturase capable of increasing the total amount of cellular unsaturated fatty acids of the E. coli cells expressing the gene. The results demonstrate that the cellular palmitoleic acids have increased two-fold upon expression at 15°C using only 0.1 mM IPTG. Therefore, PA3FAD9 from Pseudomonas sp.A3 codes for a Δ9-fatty acid desaturase-like protein which was actively expressed in E. coli.
    Matched MeSH terms: Open Reading Frames/genetics*; Fatty Acid Desaturases/genetics
  11. Fulltext R54C Mutation of NOTCH3 Gene in the First Rungus Family with CADASIL
    Lim KS, Tan AH, Lim CS, Chua KH, Lee PC, Ramli N, et al.
    PLoS One, 2015;10(8):e0135470.
    PMID: 26270344 DOI: 10.1371/journal.pone.0135470
    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary stroke caused by mutations in NOTCH3 gene. We report the first case of CADASIL in an indigenous Rungus (Kadazan-Dusun) family in Kudat, Sabah, Malaysia confirmed by a R54C (c.160C>T, p.Arg54Cys) mutation in the NOTCH3. This mutation was previously reported in a Caucasian and two Korean cases of CADASIL. We recruited two generations of the affected Rungus family (n = 9) and found a missense mutation (c.160C>T) in exon 2 of NOTCH3 in three siblings. Two of the three siblings had severe white matter abnormalities in their brain MRI (Scheltens score 33 and 50 respectively), one of whom had a young stroke at the age of 38. The remaining sibling, however, did not show any clinical features of CADASIL and had only minimal changes in her brain MRI (Scheltens score 17). This further emphasized the phenotype variability among family members with the same mutation in CADASIL. This is the first reported family with CADASIL in Rungus subtribe of Kadazan-Dusun ethnicity with a known mutation at exon 2 of NOTCH3. The penetrance of this mutation was not complete during the course of this study.
    Matched MeSH terms: CADASIL/genetics*; Receptors, Notch/genetics*
  12. Fulltext Characterization of Plaque Variants and the Involvement of Quasi-Species in a Population of EV-A71
    Mandary MB, Masomian M, Ong SK, Poh CL
    Viruses, 2020 Jun 17;12(6).
    PMID: 32560288 DOI: 10.3390/v12060651
    Viral plaque morphologies in human cell lines are markers for growth capability and they have been used to assess the viral fitness and selection of attenuated mutants for live-attenuated vaccine development. In this study, we investigate whether the naturally occurring plaque size variation reflects the virulence of the variants of EV-A71. Variants of two different plaque sizes (big and small) from EV-A71 sub-genotype B4 strain 41 were characterized. The plaque variants displayed different in vitro growth kinetics compared to the parental wild type. The plaque variants showed specific mutations being present in each variant strain. The big plaque variants showed four mutations I97L, N104S, S246P and N282D in the VP1 while the small plaque variants showed I97T, N237T and T292A in the VP1. No other mutations were detected in the whole genome of the two variants. The variants showed stable homogenous small plaques and big plaques, respectively, when re-infected in rhabdomyosarcoma (RD) and Vero cells. The parental strain showed faster growth kinetics and had higher viral RNA copy number than both the big and small plaque variants. Homology modelling shows that both plaque variants have differences in the structure of the VP1 protein due to the presence of unique spontaneous mutations found in each plaque variant This study suggests that the EV-A71 sub-genotype B4 strain 41 has at least two variants with different plaque morphologies. These differences were likely due to the presence of spontaneous mutations that are unique to each of the plaque variants. The ability to maintain the respective plaque morphology upon passaging indicates the presence of quasi-species in the parental population.
    Matched MeSH terms: Enterovirus A, Human/genetics*; Capsid Proteins/genetics
  13. Fulltext YersiniaBase: a genomic resource and analysis platform for comparative analysis of Yersinia
    Tan SY, Dutta A, Jakubovics NS, Ang MY, Siow CC, Mutha NV, et al.
    BMC Bioinformatics, 2015;16:9.
    PMID: 25591325 DOI: 10.1186/s12859-014-0422-y
    Yersinia is a Gram-negative bacteria that includes serious pathogens such as the Yersinia pestis, which causes plague, Yersinia pseudotuberculosis, Yersinia enterocolitica. The remaining species are generally considered non-pathogenic to humans, although there is evidence that at least some of these species can cause occasional infections using distinct mechanisms from the more pathogenic species. With the advances in sequencing technologies, many genomes of Yersinia have been sequenced. However, there is currently no specialized platform to hold the rapidly-growing Yersinia genomic data and to provide analysis tools particularly for comparative analyses, which are required to provide improved insights into their biology, evolution and pathogenicity.
    Matched MeSH terms: Virulence/genetics*; Yersinia/genetics*
  14. Isolation and Identification of novel toxins from a new mosquitocidal isolate from Malaysia, Bacillus thuringiensis subsp. jegathesan
    Kawalek MD, Benjamin S, Lee HL, Gill SS
    Appl Environ Microbiol, 1995 Aug;61(8):2965-9.
    PMID: 7487029
    A new mosquitocidal Bacillus thuringiensis subsp., jegathesan, has recently been isolated from Malaysia. Parasporal crystal inclusions were purified from this strain and bioassayed against fourth-instar larvae of Culex quinquefasciatus, Aedes aegypti, Aedes togoi, Aedes albopictus, Anopheles maculatus, and Mansonia uniformis. The 50% lethal concentration of crystal inclusions for each species was 0.34, 8.08, 0.34, 17.59, 3.91, and 120 ng/ml, respectively. These values show that parasporal inclusions from this new subspecies have mosquitocidal toxicity comparable to that of inclusions isolated from B. thuringiensis subsp. israelensis. Solubilized and chymotrypsin-activated parasporal inclusions possessed low-level hemolytic activity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the crystals were composed of polypeptides of 77, 74, 72, 68, 55, 38, 35, 27, and 23 kDa. Analysis by Western blotting (immunoblotting) with polyclonal antisera raised against toxins purified from B. thuringiensis subsp. israelensis reveals that proteins in parasporal inclusions of subsp. jegathesan are distinct, because little cross-reactivity was shown. Analysis of the plasmid content of B. thuringiensis subsp. jegathesan indicates that the genes for toxin production may be located on 105- to 120-kb plasmids. Cry- clones that have been cured of these plasmids are nontoxic. Southern blot analysis of plasmid and chromosomal DNA from subsp. jegathesan showed little or low homology to the genes coding for CryIVA, CryIVB, and CryIVD from B. thuringiensis subsp. israelensis.
    Matched MeSH terms: Bacillus thuringiensis/genetics; Plasmids/genetics
  15. Fulltext Novel Alphacoronaviruses and Paramyxoviruses Cocirculate with Type 1 and Severe Acute Respiratory System (SARS)-Related Betacoronaviruses in Synanthropic Bats of Luxembourg
    Pauly M, Pir JB, Loesch C, Sausy A, Snoeck CJ, Hübschen JM, et al.
    Appl Environ Microbiol, 2017 09 15;83(18).
    PMID: 28710271 DOI: 10.1128/AEM.01326-17
    Several infectious disease outbreaks with high mortality in humans have been attributed to viruses that are thought to have evolved from bat viruses. In this study from Luxembourg, the genetic diversity and epidemiology of paramyxoviruses and coronaviruses shed by the bat species Rhinolophus ferrumequinum and Myotis emarginatus were evaluated. Feces collection (n = 624) was performed longitudinally in a mixed-species colony in 2015 and 2016. In addition, feces (n = 254) were collected cross-sectionally from six Myotis emarginatus colonies in 2016. By use of degenerate primers in a nested format, overall prevalences of 1.1% (10/878) and 4.9% (43/878) were determined for paramyxoviruses and coronaviruses. Sequences of the partial RNA-dependent RNA polymerase and spike glycoprotein genes of coronaviruses, as well as sequences of the partial L gene of paramyxoviruses, were obtained. Novel paramyxovirus and Alphacoronavirus strains were identified in different Myotis emarginatus colonies, and severe acute respiratory syndrome (SARS)-related Betacoronavirus strains were shed by Rhinolophus ferrumequinum Logistic regression revealed that the level of Alphacoronavirus shedding was highest in July (odds ratio, 2.8; P < 0.01), probably due to periparturient stress. Phylogenetic analyses point to close virus-host coevolution, and the high genetic similarity of the study strains suggests that the Myotis emarginatus colonies in Luxembourg are socially connected. Most interestingly, we show that bats also host Betacoronavirus1 strains. The high similarity of the spike gene sequences of these viruses with mammalian Betacoronavirus 1 strains may be of concern. Both the SARS-related and Betacoronavirus 1 strains detected in bats in Luxembourg may cross the species barrier after a host adaptation process.IMPORTANCE Bats are a natural reservoir of a number of zoonotic pathogens. Several severe outbreaks in humans (e.g., a Nipah virus outbreak in Malaysia in 1998, and the almost global spread of severe acute respiratory syndrome in 2003) have been caused by bat-borne viruses that were transmitted to humans mostly after virus adaptation (e.g., in intermediate animal hosts). Despite the indigenousness of bat species that host viruses with suspected zoonotic potential and despite the zoonotic transmission of European bat 1 lyssavirus in Luxembourg, knowledge about the diversity and epidemiology of bat viruses remains limited in this country. Moreover, in contrast to other European countries, bat viruses are currently not included in the national surveillance activities of this land-locked country. We suggest that this gap in disease surveillance should be addressed, since we show here that synanthropic bats host viruses that may be able to cross the species barrier.
    Matched MeSH terms: Paramyxovirinae/genetics; SARS Virus/genetics
  16. Fulltext Genome-Centric Metagenomic Insights into the Impact of Alkaline/Acid and Thermal Sludge Pretreatment on the Microbiome in Digestion Sludge
    Liang Z, Shi J, Wang C, Li J, Liang D, Yong EL, et al.
    Appl Environ Microbiol, 2020 11 10;86(23).
    PMID: 32948522 DOI: 10.1128/AEM.01920-20
    Pretreatment of waste-activated sludge (WAS) is an effective way to destabilize sludge floc structure and release organic matter for improving sludge digestion efficiency. Nonetheless, information on the impact of WAS pretreatment on digestion sludge microbiomes, as well as mechanistic insights into how sludge pretreatment improves digestion performance, remains elusive. In this study, a genome-centric metagenomic approach was employed to investigate the digestion sludge microbiome in four sludge digesters with different types of feeding sludge: WAS pretreated with 0.25 mol/liter alkaline/acid (APAD), WAS pretreated with 0.8 mol/liter alkaline/acid (HS-APAD), thermally pretreated WAS (thermal-AD), and fresh WAS (control-AD). We retrieved 254 metagenome-assembled genomes (MAGs) to identify the key functional populations involved in the methanogenic digestion process. These MAGs span 28 phyla, including 69 yet-to-be-cultivated lineages, and 30 novel lineages were characterized with metabolic potential associated with hydrolysis and fermentation. Interestingly, functional populations involving carbohydrate digestion were enriched in APAD and HS-APAD, while lineages related to protein and lipid fermentation were enriched in thermal-AD, corroborating the idea that different substrates are released from alkaline/acid and thermal pretreatments. Among the major functional populations (i.e., fermenters, syntrophic acetogens, and methanogens), significant correlations between genome sizes and abundance of the fermenters were observed, particularly in APAD and HS-APAD, which had improved digestion performance.IMPORTANCE Wastewater treatment generates large amounts of waste-activated sludge (WAS), which consists mainly of recalcitrant microbial cells and particulate organic matter. Though WAS pretreatment is an effective way to release sludge organic matter for subsequent digestion, detailed information on the impact of the sludge pretreatment on the digestion sludge microbiome remains scarce. Our study provides unprecedented genome-centric metagenomic insights into how WAS pretreatments change the digestion sludge microbiomes, as well as their metabolic networks. Moreover, digestion sludge microbiomes could be a unique source for exploring microbial dark matter. These results may inform future optimization of methanogenic sludge digestion and resource recovery.
    Matched MeSH terms: Archaea/genetics*; Bacteria/genetics*
  17. Fulltext The cry toxin operon of Clostridium bifermentans subsp. malaysia is highly toxic to Aedes Larval Mosquitoes
    Qureshi N, Chawla S, Likitvivatanavong S, Lee HL, Gill SS
    Appl Environ Microbiol, 2014 Sep;80(18):5689-97.
    PMID: 25002432 DOI: 10.1128/AEM.01139-14
    The management and control of mosquito vectors of human disease currently rely primarily on chemical insecticides. However, larvicidal treatments can be effective, and if based on biological insecticides, they can also ameliorate the risk posed to human health by chemical insecticides. The aerobic bacteria Bacillus thuringiensis and Lysinibacillus sphaericus have been used for vector control for a number of decades. But a more cost-effective use would be an anaerobic bacterium because of the ease with which these can be cultured. More recently, the anaerobic bacterium Clostridium bifermentans subsp. malaysia has been reported to have high mosquitocidal activity, and a number of proteins were identified as potentially mosquitocidal. However, the cloned proteins showed no mosquitocidal activity. We show here that four toxins encoded by the Cry operon, Cry16A, Cry17A, Cbm17.1, and Cbm17.2, are all required for toxicity, and these toxins collectively show remarkable selectivity for Aedes rather than Anopheles mosquitoes, even though C. bifermentans subsp. malaysia is more toxic to Anopheles. Hence, toxins that target Anopheles are different from those expressed by the Cry operon.
    Matched MeSH terms: Bacterial Toxins/genetics*; Clostridium bifermentans/genetics*
  18. Fulltext Comprehensive Structural and Molecular Comparison of Spike Proteins of SARS-CoV-2, SARS-CoV and MERS-CoV, and Their Interactions with ACE2
    Hatmal MM, Alshaer W, Al-Hatamleh MAI, Hatmal M, Smadi O, Taha MO, et al.
    Cells, 2020 Dec 08;9(12).
    PMID: 33302501 DOI: 10.3390/cells9122638
    The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has recently emerged in China and caused a disease called coronavirus disease 2019 (COVID-19). The virus quickly spread around the world, causing a sustained global outbreak. Although SARS-CoV-2, and other coronaviruses, SARS-CoV and Middle East respiratory syndrome CoV (MERS-CoV) are highly similar genetically and at the protein production level, there are significant differences between them. Research has shown that the structural spike (S) protein plays an important role in the evolution and transmission of SARS-CoV-2. So far, studies have shown that various genes encoding primarily for elements of S protein undergo frequent mutation. We have performed an in-depth review of the literature covering the structural and mutational aspects of S protein in the context of SARS-CoV-2, and compared them with those of SARS-CoV and MERS-CoV. Our analytical approach consisted in an initial genome and transcriptome analysis, followed by primary, secondary and tertiary protein structure analysis. Additionally, we investigated the potential effects of these differences on the S protein binding and interactions to angiotensin-converting enzyme 2 (ACE2), and we established, after extensive analysis of previous research articles, that SARS-CoV-2 and SARS-CoV use different ends/regions in S protein receptor-binding motif (RBM) and different types of interactions for their chief binding with ACE2. These differences may have significant implications on pathogenesis, entry and ability to infect intermediate hosts for these coronaviruses. This review comprehensively addresses in detail the variations in S protein, its receptor-binding characteristics and detailed structural interactions, the process of cleavage involved in priming, as well as other differences between coronaviruses.
    Matched MeSH terms: SARS Virus/genetics; Middle East Respiratory Syndrome Coronavirus/genetics
  19. Autoimmune lymphoproliferative syndrome caused by a homozygous FasL mutation that disrupts FasL assembly
    Sobh A, Crestani E, Cangemi B, Kane J, Chou J, Pai SY, et al.
    J Allergy Clin Immunol, 2016 Jan;137(1):324-327.e2.
    PMID: 26456038 DOI: 10.1016/j.jaci.2015.08.025
    Matched MeSH terms: Fas Ligand Protein/genetics*; Autoimmune Lymphoproliferative Syndrome/genetics*
  20. Fulltext Comparative transcriptome analysis reveals novel insights into transcriptional responses to phosphorus starvation in oil palm (Elaeis guineensis) root
    Kong SL, Abdullah SNA, Ho CL, Musa MHB, Yeap WC
    BMC Genom Data, 2021 02 05;22(1):6.
    PMID: 33568046 DOI: 10.1186/s12863-021-00962-7
    BACKGROUND: Phosphorus (P), in its orthophosphate form (Pi) is an essential macronutrient for oil palm early growth development in which Pi deficiency could later on be reflected in lower biomass production. Application of phosphate rock, a non-renewable resource has been the common practice to increase Pi accessibility and maintain crop productivity in Malaysia. However, high fixation rate of Pi in the native acidic tropical soils has led to excessive utilization of P fertilizers. This has caused serious environmental pollutions and cost increment. Even so, the Pi deficiency response mechanism in oil palm as one of the basic prerequisites for crop improvement remains largely unknown.

    RESULTS: Using total RNA extracted from young roots as template, we performed a comparative transcriptome analysis on oil palm responding to 14d and 28d of Pi deprivation treatment and under adequate Pi supply. By using Illumina HiSeq4000 platform, RNA-Seq analysis was successfully conducted on 12 paired-end RNA-Seq libraries and generated more than 1.2 billion of clean reads in total. Transcript abundance estimated by fragments per kilobase per million fragments (FPKM) and differential expression analysis revealed 36 and 252 genes that are differentially regulated in Pi-starved roots at 14d and 28d, respectively. Genes possibly involved in regulating Pi homeostasis, nutrient uptake and transport, hormonal signaling and gene transcription were found among the differentially expressed genes.

    CONCLUSIONS: Our results showed that the molecular response mechanism underlying Pi starvation in oil palm is complexed and involved multilevel regulation of various sensing and signaling components. This contribution would generate valuable genomic resources in the effort to develop oil palm planting materials that possess Pi-use efficient trait through molecular manipulation and breeding programs.

    Matched MeSH terms: Plant Roots/genetics; Arecaceae/genetics*
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