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Endogenous viral elements (EVEs)-viruses that have integrated their genomes into those of their hosts-are prevalent in eukaryotes and have an important role in genome evolution1,2. The vast majority of EVEs that have been identified to date are small genomic regions comprising a few genes2, but recent evidence suggests that some large double-stranded DNA viruses may also endogenize into the genome of the host1. Nucleocytoplasmic large DNA viruses (NCLDVs) have recently become of great interest owing to their large genomes and complex evolutionary origins3-6, but it is not yet known whether they are a prominent component of eukaryotic EVEs. Here we report the widespread endogenization of NCLDVs in diverse green algae; these giant EVEs reached sizes greater than 1 million base pairs and contained as many as around 10% of the total open reading frames in some genomes, substantially increasing the scale of known viral genes in eukaryotic genomes. These endogenized elements often shared genes with host genomic loci and contained numerous spliceosomal introns and large duplications, suggesting tight assimilation into host genomes. NCLDVs contain large and mosaic genomes with genes derived from multiple sources, and their endogenization represents an underappreciated conduit of new genetic material into eukaryotic lineages that can substantially impact genome composition.
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Clorófitas/genética , Clorófitas/virologia , Genoma/genética , Vírus Gigantes/genética , Genes Virais , Íntrons/genética , Mosaicismo , Phycodnaviridae/genética , FilogeniaRESUMO
Large DNA viruses of the phylum Nucleocytoviricota have recently emerged as important members of ecosystems around the globe that challenge traditional views of viral complexity. Numerous members of this phylum that cannot be classified within established families have recently been reported, and there is presently a strong need for a robust phylogenomic and taxonomic framework for these viruses. Here, we report a comprehensive phylogenomic analysis of the Nucleocytoviricota, present a set of giant virus orthologous groups (GVOGs) together with a benchmarked reference phylogeny, and delineate a hierarchical taxonomy within this phylum. We show that the majority of Nucleocytoviricota diversity can be partitioned into 6 orders, 32 families, and 344 genera, substantially expanding the number of currently recognized taxonomic ranks for these viruses. We integrate our results within a taxonomy that has been adopted for all viruses to establish a unifying framework for the study of Nucleocytoviricota diversity, evolution, and environmental distribution.
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Biodiversidade , Evolução Molecular , Vírus Gigantes/genética , Filogenia , Genes Virais , Marcadores Genéticos , Vírus Gigantes/classificaçãoRESUMO
Vertically aligned ZnO nanorods (NRs) were grown hydrothermally on the wide bandgap (â¼3.86 - 4.04 eV) seed layers (SLs) of grain size â¼162 ± 35 nm, prepared using ball-milled derived ZnO powder. The synthesized ZnO NRs were further decorated with ZnS nanocrystals to achieve a ZnO NR-ZnS core-shell (CS)-like nano-scaffolds by a subsequent hydrothermal synthesis at 70 °C for 1 h. UV-Vis-NIR spectroscopy, x-ray diffractometry (XRD), Raman spectroscopy and Field emission scanning electron microscopy (FESEM) coupled with Energy dispersive x-ray spectroscopy (EDX) analyses confirmed the formation of ZnS atop the vertically aligned ZnO NR arrays of â¼1.79 ± 0.17µm length and â¼165 ± 27 nm diameter. Transmission electron microscopy (TEM)/EDX analyses revealed that vertically aligned ZnO NRs (core dia. â¼181 ± 12 nm) arrays are conformally coated by an ultrathin ZnS (â¼25 ± 7 nm) shell layer with a preferential ZnS{111}/ZnO{10-10}-like partial epitaxy. The ZnO NRs exhibited a sharp band edge near â¼384 nm having optical bandgap energy (Eg) of â¼3.23 eV. However, the ZnO NR-ZnS CS exhibited double absorption bands atEgâ¼ 3.20 eV (ZnO-core) andEgâ¼ 3.78 eV (ZnS-shell). The ZnS{111}/ZnO{10-10}-nano-scaffolds could be utilized to facilitate the enhanced absorption of UV photons as well as the radial junction formation between the Pb-free perovskite absorber and ZnS/ZnO NRs layers.
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GABA (Gamma-aminobutyric acid) is a non-protein amino acid widely known as major inhibitory neurotransmitter. It is synthesized from glutamate via the enzyme glutamate decarboxylase (GAD). GAD is ubiquitous in all organisms, but only plant GAD has ability to bind Ca2+/calmodulin (CaM). This kind of binding suppresses the auto-inhibition of Ca2+/calmodulin binding domain (CaMBD) when the active site of GAD is unfolded resulting in stimulated GAD activity. OsGAD4 is one of the five GAD genes in rice genome. It was confirmed that OsGAD4 has ability to bind to Ca2+/CaM. Moreover, it exhibits strongest expression against several stress conditions among the five OsGAD genes. In this study, CRISPR/Cas9-mediated genome editing was performed to trim the coding region of CaMBD from the OsGAD4 gene, to remove its autoinhibitory function. DNA sequence analysis of the genome edited rice plants revealed the truncation of CaMBD (216 bp). Genome edited line (#14-1) produced 11.26 mg GABA/100 g grain, which is almost nine-fold in comparison to wild type. Short deletion in the coding region for CaMBD yielded in mutant (#14-6) with lower GABA content than wild type counterpart. Abiotic stresses like salinity, flooding and drought significantly enhanced GABA accumulation in #14-1 at various time points compared to wild-type and #14-6 under the same stress conditions. Moreover, upregulated mRNA expression in vegetative tissues seems correlated with the stress-responsiveness of OsGAD4 when exposed to the above-mentioned stresses. Stress tolerance of OsGAD4 genome edited lines was evidenced by the higher survival rate indicating the gene may induce tolerance against abiotic stresses in rice. This is the first report on abiotic stress tolerance in rice modulated by endogenous GABA. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01460-1.
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Few studies have examined the role of perceived neighborhood characteristics such as neighborhood safety, social cohesion, and contentedness on sedentary behavior (SB) and physical activity (PA) among adolescents. Furthermore, no studies have investigated how these associations are moderated by gender and race. This study aimed to examine the associations of the perceived neighborhood social environment with (SB) and moderate-to-vigorous physical activity (MVPA). Data from 6504 adolescents (aged 15.4 ± 0.03 years) who participated in the National Longitudinal Study of Adolescent Health was used. SB and PA were considered continuously and dichotomously. PNSE variables include safety, social cohesion, and contentedness, where higher values of PNSE indicate a more favorable neighborhood perception. Weighted linear and logistic regression models were used to examine the association of PNSE with continuous total SB (hours/week) and MVPA (bouts/week), and binary excessive SB (14 h/week) and meeting MVPA guidelines (≥ 5 bouts/week), respectively. Associations were stratified by gender and race to test moderation effects. Models were adjusted for demographic, health, parental, and neighborhood covariates. This study found that neighborhood safety and contentedness were negatively associated with SB, whereas neighborhood social cohesion and contentedness were positively associated with PA. Gender-specific and race-specific results remained somewhat consistent with overall findings; however, neighborhood safety was not associated with SB among female and non-White adolescents, respectively. Similarly, neighborhood safety and contentedness were not associated with MVPA for non-White adolescents. Findings suggest that an adolescent's neighborhood environment, gender, and race should be considered when implementing strategies to reduce SB and increase PA.
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Exercício Físico , Características de Residência , Comportamento Sedentário , Meio Social , Humanos , Adolescente , Masculino , Feminino , Estudos Longitudinais , Características de Residência/estatística & dados numéricos , Comportamento do Adolescente/psicologia , Características da Vizinhança , Fatores Sexuais , Estados Unidos , SegurançaRESUMO
Large DNA viruses in the phylum Nucleocytoviricota, sometimes referred to as "giant viruses" owing to their large genomes and virions, have been the subject of burgeoning interest over the last decade. Here, we describe recently adopted taxonomic updates for giant viruses within the order Imitervirales. The families Allomimiviridae, Mesomimiviridae, and Schizomimiviridae have been created to accommodate the increasing diversity of mimivirus relatives that have sometimes been referred to in the literature as "extended Mimiviridae". In addition, the subfamilies Aliimimivirinae, Megamimivirinae, and Klosneuvirinae have been established to refer to subgroups of the Mimiviridae. Binomial names have also been adopted for all recognized species in the order. For example, Acanthamoeba polyphaga mimivirus is now classified in the species Mimivirus bradfordmassiliense.
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Vírus Gigantes , Mimiviridae , Humanos , Vírus Gigantes/genética , Vírus de DNA/genética , Mimiviridae/genética , Genoma Viral , VírionRESUMO
Cell envelope plays a dual role in the life of bacteria by simultaneously protecting it from a hostile environment and facilitating access to beneficial molecules. At the heart of this ability lie the restrictive properties of the cellular membrane augmented by efflux transporters, which preclude intracellular penetration of most molecules except with the help of specialized uptake mediators. Recently, kinetic properties of the cell envelope came into focus driven on one hand by the urgent need in new antibiotics and, on the other hand, by experimental and theoretical advances in studies of transmembrane transport. A notable result from these studies is the development of a kinetic formalism that integrates the Michaelis-Menten behavior of individual transporters with transmembrane diffusion and offers a quantitative basis for the analysis of intracellular penetration of bioactive compounds. This review surveys key experimental and computational approaches to the investigation of transport by individual translocators and in whole cells, summarizes key findings from these studies and outlines implications for antibiotic discovery. Special emphasis is placed on Gram-negative bacteria, whose envelope contains two separate membranes. This feature sets these organisms apart from Gram-positive bacteria and eukaryotic cells by providing them with full benefits of the synergy between slow transmembrane diffusion and active efflux.
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Bactérias Gram-Negativas/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Membrana Externa Bacteriana/metabolismo , Membrana Celular/química , Membrana Celular/metabolismo , Bactérias Gram-Negativas/química , Bactérias Gram-Negativas/efeitos dos fármacos , Humanos , Lipídeos de Membrana/química , Lipídeos de Membrana/metabolismo , Proteínas de Membrana Transportadoras/química , Modelos Biológicos , Simulação de Dinâmica MolecularRESUMO
Honey inhibits bacterial growth due to the high sugar concentration, hydrogen peroxide generation, and proteinaceous compounds present in it. In this study, the antibacterial activity of stingless and sting honey against foodborne pathogenic bacteria isolated from spoiled milk samples was examined. The isolated bacterial strains were confirmed as Bacillus cereus and Listeriamonocytogenes through morphological, biochemical, and 16 s RNA analysis. Physiochemical characterizations of the honey samples revealed that both of the honey samples had an acidic pH, low water content, moderate reducing sugar content, and higher proline content. Through the disc diffusion method, the antibacterial activities of the samples were assayed and better results were observed for the 50 mg/disc honey. Both stingless and sting honey showed the most positive efficacy against Bacillus cereus. Therefore, an in silico study was conducted against this bacterium with some common compounds of honey. From several retrieved constituents of stingless and sting honey, 2,4-dihydroxy-2,5-dimethyl 3(2H)-furan-3-one (furan) and 4H-pyran-4-one,2,3-dihydro of both samples and beta.-D-glucopyranose from the stingless revealed high ligand-protein binding efficiencies for the target protein (6d5z, hemolysin II). The root-mean-square deviation, solvent-accessible surface area, the radius of gyration, root-mean-square fluctuations, and hydrogen bonds were used to ensure the binding stability of the docked complexes in the atomistic simulation and confirmed their stability. The combined effort of wet and dry lab-based work support, to some extent, that the antimicrobial properties of honey have great potential for application in medicine as well as in the food industries.
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Anti-Infecciosos , Mel , Antibacterianos/análise , Antibacterianos/farmacologia , Anti-Infecciosos/análise , Bacillus cereus , Furanos , Proteínas Hemolisinas , Mel/análise , Peróxido de Hidrogênio/farmacologia , Ligantes , Testes de Sensibilidade Microbiana , Prolina , Piranos , RNA , Solventes/análise , Açúcares , ÁguaRESUMO
This study examined the effects of feeding fermented tuna by-product (FTBP) on the growth, non-specific immune response, liver and intestinal morphology, and disease resistance of olive flounder Paralichthys olivaceus. Olive flounders (n = 20; 2 g) were randomly assigned into four dietary groups in triplicates. Fish were fed four test diets (50% crude protein; 10% crude lipid) for 10 weeks in which unprocessed tuna by-product (TBP) meal was replaced (on a protein basis) with 0% (FTBP0 as the control diet), 15% (FTBP15), 30% (FTBP30), and 60% (FTBP60) of FTBP protein. Results showed that growth performance, blood parameters, and proximate composition were not influenced by FTBP inclusion. Non-specific immune parameters such as superoxide dismutase activity in the FTBP30 and FTBP60 groups were significantly higher than in the FTBP15 and the control groups, whereas lysozyme and myeloperoxidase activities were not different. Liver histopathology revealed normal architecture in groups fed FTBP0 and FTBP15 diets although mild alterations were noted in the FTBP30- and FTBP60-fed groups. Intestinal villi height and muscular thickness were not significantly altered with FTBP inclusion. Moreover, higher cumulative survival rate was observed in the FTBP60-fed group than fish fed with the other diets following the 13-day challenge with E. tarda. Together, these results demonstrate that fermented tuna by-product meal could be included at 60% in olive flounder diets.
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Doenças dos Peixes , Linguado , Animais , Atum , Dieta , Resistência à Doença , Ração Animal/análiseRESUMO
Amyloid-ß (Aß) is the major component of senile plaques in Alzheimer's disease (AD) brains. Senile plaques are generally observed in cerebral cortex (CTX) rather than cerebellum (CBL) in AD patients. However, it is not clear why CBL has less Aß deposition than CTX. It is very important to elucidate the mechanism of suppressing Aß deposition in CBL, because it contributes to understanding of not only AD pathogenesis but also prevention and cure of AD. In this study, we explored to figure out the potential mechanism of reducing Aß deposition in CBL. We observed higher age-dependent elevation of Aß level in CTX rather than CBL of human APP knock-in AD model mice, although we detected no significant differences in the levels of interstitial fluid Aß in these brain tissues. These data imply that less Aß deposition in CBL is due to enhanced Aß clearance rather than altered Aß production in CBL. To gain insights into Aß clearance in CBL, we injected fluorescence-labeled Aß in brain tissues. Importantly diffusion area of fluorescent Aß in CBL was roughly six-times larger than that in CTX within 2 h of injection. In addition, injected Aß area in CBL decreased sharply after 24 h and CBL-injected Aß was robustly detected in deep cervical lymph nodes (DcLNs). In contrast, diffusion area of fluorescent Aß in CTX was consistent up to 72 h and CTX-injected Aß was faintly detected in DcLNs. Our data suggest that enhanced Aß drainage in association with meningeal lymphatic system is responsible for less Aß deposition in CBL.
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Peptídeos beta-Amiloides/metabolismo , Cerebelo/metabolismo , Animais , Córtex Cerebral/metabolismo , Vértebras Cervicais/metabolismo , Líquido Extracelular/metabolismo , Humanos , Linfonodos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Rodaminas , Ácidos SulfônicosRESUMO
The B12 derivative, heptamethyl cobyrinate, -mediated electrochemical synthesis of cyanoformamides has been developed. Aerobic oxygenation of the carbon-centered radical initiated in situ generation of the reactive acyl chloride intermediate, which led to cyanoformamides in the presence of an amine. This one-pot and scalable synthetic method has been demonstrated with 41 examples up to 94% yields with 21 new compounds. The mechanism of electrolysis mediated by the B12 derivative has been proposed based on the DFT calculations.
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Aminas , Eletrólise , Acetonitrilas , CatáliseRESUMO
Local rice parboiling industries of Bangladesh are burdened with heavy emission. Despite recent modification in the rice-parboiling boiler, the amount of stack emission (especially particulate matter) from local rice parboiling industry is still considerably high to jeopardize public health and environmental sustainability. There is no provision of flue gas cleaning in these industries since flue gas cleaning often requires significant investment, complicated installation and heavy-maintenance. Therefore, a modified flue gas cleaning system, namely Ash removal unit (ARU) was designed for simultaneously and synergistically removing particulate matter (PM), SO2, NOx, CO2 and heat from flue gas of local rice parboiling industries. In this study, ARU was incorporated in a local rice parboiling industry in order to evaluate the co-removal efficiency achieved by the ARU. Installation of ARU eliminated PM from flue gas by 91.8%, while it removed 78.5% SO2, 78.3% NOx and 23.9% CO2 respectively from the emitting stack. Other than flue gas cleaning , ARU also facilitates heat exchange between flue gas and boiler feed water. Hence, flue gas temperature was dropped by 42.1%, while boiler feed water temperature was raised by 36% in 30 min. Moreover, adopting ARU also improved the ambient air quality surrounding the industrial area, since it reduced SO2, NOx, SPM, PM2.5 and PM10 level in ambient air by 81.7%, 78.2%, 21.1%, 22.9% and 43.1% respectively.
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Poluentes Atmosféricos , Oryza , Poluentes Atmosféricos/análise , Bangladesh , Temperatura Alta , Material Particulado/análiseRESUMO
PURPOSE: The effects of estradiol on oocyte development seem to be varied among species. The present study investigated the effects of 17ß-estradiol on in vitro maturation of buffalo and goat oocytes. METHODS: Cumulus oocyte complexes (COCs) were aspirated from large antral follicles of slaughtered buffalo and goat ovaries. COCs were cultured in TCM-199 medium supplemented with 0, 0.5, 1, and 1.5 µg/mL of 17ß-estradiol for in vitro maturation. Then, oocytes were used for the examination of state of nuclear maturation and cumulus expansion. RESULTS: In both species, oocytes treated with 17ß-estradiol showed higher cumulus expansion rate than control (0 µg/mL treated). In buffalo, the percentage of oocytes matured to the metaphase II (MII) stage increased in the concentration-dependent manner of 17ß-estradiol. Similarly, estradiol positively influenced nuclear maturation of goat oocytes in vitro. CONCLUSIONS: Estradiol has promoting effects on normalprogress of in vitro oocyte meiosis in buffalos and goats.
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BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is a common subclinical feature of the aging brain. Steps per day may contribute to its prevention. We herein investigated the association between step counts and CSVD in a healthy Japanese male population. METHODS: We analyzed data from 680 men who were free of stroke and participated in this observational study. Seven-day step counts were assessed at baseline (2006-2008) using a pedometer. CSVD was assessed at follow-ups (2012-2015) based on deep and subcortical white matter hyperintensities (WMHs), periventricular hyperintensities, lacunar infarcts, and cerebral microbleeds on magnetic resonance imaging. Using a logistic regression analysis, we computed the adjusted odds ratios, with 95% CIs, of prevalent CSVD according to quartiles of step counts (reference: Q1). We also investigated the association between step counts and WMH volumes using a quantile regression. RESULTS: Steps per day were significantly associated with lower odds ratios, with the lowest at Q3 (8175-10 614 steps/day), of higher (versus low or no burden) deep and subcortical WMHs (odds ratio, 0.52 [95% CI, 0.30-0.89]), periventricular hyperintensities (0.50 [95% CI, 0.29-0.86]), and lacunar infarcts (0.52 [95% CI, 0.30-0.91]) compared with Q1 (≤6060 steps/day) but not cerebral microbleeds. An inverse linear association was observed between step counts and WMH volumes. These associations were independent of age and smoking and drinking status and remained consistent when adjusted for vascular risk factors. CONCLUSIONS: We found a J-shaped relationship between step counts and prevalent CSVD in healthy Japanese men, with the lowest risk being observed among participants with ≈8000 to 10 000 steps/day. Higher steps were also associated with lower WMH volumes.
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Doenças de Pequenos Vasos Cerebrais/epidemiologia , Exercício Físico , Acelerometria , Adulto , Idoso , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/epidemiologia , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Humanos , Japão/epidemiologia , Modelos Logísticos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Acidente Vascular Cerebral Lacunar/diagnóstico por imagem , Acidente Vascular Cerebral Lacunar/epidemiologia , Substância Branca/diagnóstico por imagemRESUMO
BACKGROUND: Bioprocessing of plant feedstuff can be a novel approach for reducing the overwhelming dependence on fish meal in aquaculture. The objective of this study was to evaluate the performance of Pacific white shrimp Litopenaeus vannamei fed solid-state fermented protein concentrates in order to replace fish meal in the diet. RESULTS: In the first trial, a group of 15 shrimp (average 3.88 g) were randomly distributed into aquaria in triplicate according to the experimental diets. Ten isonitrogenous (400 g kg-1 CP) and isolipidic (90 g kg-1 CL) diets were formulated to contain high-protein fish meal (HFM) and low-protein fish meal (LFM), and four types of bioprocessed protein concentrates (BPCs) as a replacement of fish meal (BPC-A, -B, -C and -D) each at 30% and 50% FM replacement levels. BPC-A was a solid-state fermented mixture of soybean and corn gluten meals; BPC-B was pre-treated acid-hydrolyzed BPC-A; BPC-C and BPC-D were BPC-A + 2% shrimp soluble extract (SSE) and BPC-B + 2% SSE, respectively. After 8 weeks, shrimp fed the HFM, BPC-B, BPC-C and BPC-D diets showed significantly higher growth performance at 30% FM replacement than those of shrimp fed the BPC diets at 50% FM replacement. Interestingly, shrimp fed the BPC-D diet could replace up to 50% FM replacement. In the second trial, the results show that apparent digestibility coefficients of feeds and apparent digestibility coefficients of ingredients for crude protein were significantly higher in fish fed the BPC-B, BPC-C and BPC-D diets. CONCLUSIONS: The results demonstrated successful partial replacement of high-protein fish meal using high-quality fermented protein concentrates from plant sources. © 2019 Society of Chemical Industry.
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Ração Animal/análise , Proteínas de Peixes/metabolismo , Glycine max/metabolismo , Penaeidae/crescimento & desenvolvimento , Penaeidae/metabolismo , Proteínas de Plantas/metabolismo , Animais , Aquicultura , Dieta/veterinária , Digestão , Proteínas de Peixes/análise , Peixes/metabolismo , Proteínas de Plantas/análise , Glycine max/químicaRESUMO
Cylindrospermopsis (Raphidiopsis) raciborskii is an invasive, filamentous, nitrogen-fixing cyanobacterium that forms frequent blooms in freshwater habitats. While viruses play key roles in regulating the abundance, production and diversity of their hosts in aquatic ecosystems, the role(s) of viruses in the ecology of C. raciborskii is almost unexplored. Progress in this field has been hindered by the absence of a characterized virus-host system in C. raciborskii. To bridge this gap, we sequenced the genome of CrV-01T, a previously isolated cyanosiphovirus, and its host, C. raciborskii strain Cr2010. Analyses suggest that CrV-01T represents a distinct clade of siphoviruses infecting, and perhaps lysogenizing, filamentous cyanobacteria. Its genome contains unique features that include an intact CRISPR array and a 12 kb inverted duplication. Evidence suggests CrV-01T recently gained the ability to infect Cr2010 and recently lost the ability to form lysogens. The cyanobacterial host contains a CRISPR-Cas system with CRISPR spacers matching protospacers within the inverted duplication of the CrV-01T genome. Examination of metagenomes demonstrates that viruses with high genetic identity to CrV-01T, but lacking the inverted duplication, are present in C. raciborskii blooms in Australia. The unique genomic features of the CrV/Cr2010 system offers opportunities to investigate in more detail virus-host interactions in an ecologically important bloom-forming cyanobacterium.
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Cianobactérias/virologia , Especificidade de Hospedeiro , Vírus/isolamento & purificação , Austrália , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Cianobactérias/fisiologia , Ecossistema , Água Doce/microbiologia , Água Doce/virologia , Genoma Viral , Genômica , Nitrogênio , Fenômenos Fisiológicos Virais , Vírus/genéticaRESUMO
γ-Secretase complex, the assembly of nicastrin (NCT), Presenilin (PS), Presenilin Enhancer-2 (PEN-2) and Anterior pharynx defective 1 (Aph-1), catalyzes the cleavage of amyloid precursor protein to generate amyloid-ß protein (Aß), the main culprit of Alzheimer's disease. NCT becomes matured through complex glycosylation and play important role in γ-secretase activity by interacting with catalytic subunit PS. However, the role of NCT glycosylation on γ-secretase activity and substrate specificity is still unknown. The purpose of this study is to investigate the effect of NCT glycosylation on γ-secretase activity and substrate specificity in a group of glycosylation mutant lectin resistant CHO (Lec) cells. CHO Lec-1â¯cells lack glycosyltransferase-I, GnT-I, thus N-glycan on NCT are all oligomannose type, whereas CHO Lec-2â¯cells synthesize NCT containing sialic acid deficient oligosaccharides due to the impairment of cytidine 5'-monophosphate-sialic acid transporter. Here, we reported that mutant CHO Lec-1 and Lec-2 reduced γ-secretase activity in both cell-based and biochemical assays, and that CHO Lec-1 preferentially reduced Aß generation. Endogenous level of γ-secretase complex, subcellular distribution of γ-secretase subunits and the level of functional γ-secretase complex remained unchanged in mutants. Interestingly, Coimmunoprecipitation study revealed that mutant γ-secretase could recognize substrate as well as parental γ-secretase. Our data suggests that thorough glycosylation of NCT is critical for enzymatic activity and substrate preference of γ-secretase.
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Secretases da Proteína Precursora do Amiloide/metabolismo , Glicoproteínas de Membrana/metabolismo , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Células CHO , Cricetulus , Glicosilação , Subunidades Proteicas/metabolismo , Receptores Notch/metabolismo , Especificidade por SubstratoRESUMO
BACKGROUND: Cardiovascular diseases (CVD) are the main cause of mortality in low- and middle-income countries like Nepal. Different risk factors usually cluster and interact multiplicatively to increase the risk of developing acute cardiovascular events; however, information related to clustering of CVD risk factors is scarce in Nepal. Therefore, we aimed to determine the prevalence of CVD risk factors with a focus on their clustering pattern in a rural Nepalese population. METHODS: A community-based cross-sectional study was conducted among residents aged 40 to 80 years in Lamjung District of Nepal in 2014. A clustered sampling technique was used in steps. At first, four out of 18 wards were chosen at random. Then, one person per household was selected randomly (n = 388). WHO STEPS questionnaires (version 2.2) were used to collect data. Chi-square and independent t-test were used to test significance at the level of p < 0.05. RESULTS: A total 345 samples with complete data were analyzed. Smoking [24.1% (95% CI: 19.5-28.6)], harmful use of alcohol [10.7% (7.4-13.9)], insufficient intake of fruit and vegetable [72% (67.1-76.6)], low physical activity [10.1% (6.9-13.2)], overweight and obesity [59.4% (54.2-64.5)], hypertension [42.9% (37.6-48.1)], diabetes [16.2% (14.0-18.3)], and dyslipidemia [56.0% (53.0-58.7)] were common risk factors among the study population. Overall, 98.2% had at least one risk factor, while 2.0% exhibited six risk factors. Overall, more than a half (63.4%) of participants had at least three risk factors (male: 69.4%, female: 58.5%). Age [OR: 2.3 (95% CI: 1.13-4.72)] and caste/ethnicity [2.0 (95% CI: 1.28-3.43)] were significantly associated with clustering of at least three risk factors. CONCLUSIONS: Cardiovascular risk factors and their clustering were common in the rural population of Nepal. Therefore, comprehensive interventions against all risk factors should be immediately planned and implemented to reduce the future burden of CVD in the rural population of Nepal.
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Doenças Cardiovasculares/epidemiologia , População Rural/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nepal/epidemiologia , Prevalência , Fatores de RiscoRESUMO
BACKGROUND: Low level of physical activity (PA) has become an important public health problem even in low-income countries. The objectives of this study were to measure PA levels, determine the prevalence of low PA and identify socio-demographic factors associated with it in Bangladeshi adults. METHODS: Data from 792 (urban, 395; rural, 397) Bangladeshi adults (25-64 years) were included in this population-based cross-sectional study conducted in 2011. Global Physical Activity Questionnaire version 2 (GPAQ-2) was used to measure PA. The metabolic equivalent task (MET) in minutes per week was calculated to determine total PA. Participants were categorized into low, moderate and high PA groups. Logistic regression was used to assess socio-demographic factors associated with low level of PA. RESULTS: Median MET-minute of total PA per week was almost double in the rural area (1720) than the urban area (960). The overall prevalence of low PA was 50.3% (95% CI: 46.8-53.8), urban 59.5% (54.7-64.3) and rural 41.9% (37.0-46.8). Women in general were more inactive (women 63.1% [58.3-67.9], men 39.3% [34.6-44.0]). The main contributions to total PA were from work (urban 40.0%, rural 77.0%) and active commute (57.0%, 21.0%). Leisure-time PA represented a very small proportion (<3.0%). Multiple logistic regressions found a significant association of urban residence (OR = 2.2; 95% CI: 1.5-3.2), women (2.1; 1.4-3.9), oldest age group 55-64 years (15.6; 7.5-32.2) compared to youngest age group 25-34 years, graduation or further education (8.6; 4.1-17.7), and higher socio-economic class (2.4; 1.4-4.2) compared to poor with insufficient PA. CONCLUSIONS: This study identifies low PA in a rural and urban population in Bangladesh and that further large-scale population studies are warranted.