Bats host many viruses pathogenic to humans, and increasing evidence suggests that rotavirus A (RVA) also belongs to this list. Rotaviruses cause diarrheal disease in many mammals and birds, and ...their segmented genomes allow them to reassort and increase their genetic diversity. Eighteen out of 2,142 bat fecal samples (0.8%) collected from Europe, Central America, and Africa were PCR-positive for RVA, and 11 of those were fully characterized using viral metagenomics. Upon contrasting their genomes with publicly available data, at least 7 distinct bat RVA genotype constellations (GCs) were identified, which included evidence of reassortments and 6 novel genotypes. Some of these constellations are spread across the world, whereas others appear to be geographically restricted. Our analyses also suggest that several unusual human and equine RVA strains might be of bat RVA origin, based on their phylogenetic clustering, despite various levels of nucleotide sequence identities between them. Although SA11 is one of the most widely used reference strains for RVA research and forms the backbone of a reverse genetics system, its origin remained enigmatic. Remarkably, the majority of the genotypes of SA11-like strains were shared with Gabonese bat RVAs, suggesting a potential common origin. Overall, our findings suggest an underexplored genetic diversity of RVAs in bats, which is likely only the tip of the iceberg. Increasing contact between humans and bat wildlife will further increase the zoonosis risk, which warrants closer attention to these viruses.
The increased research on bat coronaviruses after severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) allowed the very rapid identification of SARS-CoV-2. This is an excellent example of the importance of knowing viruses harbored by wildlife in general, and bats in particular, for global preparedness against emerging viral pathogens. The current effort to characterize bat rotavirus strains from 3 continents sheds light on the vast genetic diversity of rotaviruses and also hints at a bat origin for several atypical rotaviruses in humans and animals, implying that zoonoses of bat rotaviruses might occur more frequently than currently realized.
The aim of this study was to isolate the cytotoxic compounds from V. alliariifolia via activity‐guided isolation and to determine the mechanism of actions of the most potent ones. The crude EtOH ...extract as well as CHCl3 and AcOEt subextracts demonstrated remarkable cytotoxic activities against A549, MCF7, HGC27 and PC3 cancer cells. Sequential chromatographic separations on active subextracts yielded 14 secondary metabolites, including 11 iridoids (1–11) most of which belong to non‐glycosidic ester iridoids, two phenylpropanoids (12 and 13) and one lignan (14). The chemical structures of purified compounds were elucidated by NMR and MS analysis. Among the isolates, 7‐deisovaleroylvaltrate (3) was isolated for the first time as a natural product. According to the cytotoxic assay compounds, 2, 4–6 and 8 were found to be the potent cytotoxic compounds (IC50 <10 μM) against at least one of the tested cancer cell lines. Thus, 2, 4–6 and 8 were investigated for their effects on apoptotic, necrotic and autophagic pathways as well as cell cycle progression. They exerted anticancer activities by inducing different cell death mechanisms depending on the cancer cells. The results demonstrated that 2, 4–6 and 8 could be potential anticancer drug leads that deserve further in vivo and clinical studies on the way to discover novel natural compounds with anticancer properties.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Despite the global use of rotavirus vaccines, vaccine breakthrough cases remain a pediatric health problem. In this study, we investigated suspected rotavirus vaccine breakthrough cases using ...next-generation sequencing (NGS)-based viral metagenomics (
= 102) and a panel of semiquantitative reverse transcription-PCR (RT-qPCR) (
= 92) targeting known enteric pathogens. Overall, we identified coinfections in 80% of the cases. Enteropathogens such as adenovirus (32%), enterovirus (15%), diarrheagenic Escherichia coli (1 to 14%), astrovirus (10%),
spp. (10%), parechovirus (9%), norovirus (9%), Clostridioides (formerly
) difficile (9%), Dientamoeba fragilis (9%), sapovirus (8%), Campylobacter jejuni (4%), and Giardia lamblia (4%) were detected. Except for a few reassortant rotavirus strains, unusual genotypes or genotype combinations were not present. However, in addition to well-known enteric viruses, divergent variants of enteroviruses and nonclassic astroviruses were identified using NGS. We estimated that in 31.5% of the patients, rotavirus was likely not the cause of gastroenteritis, and in 14.1% of the patients, it contributed together with another pathogen(s) to disease. The remaining 54.4% of the patients likely had a true vaccine breakthrough infection. The high prevalence of alternative enteropathogens in the suspected rotavirus vaccine breakthrough cases suggests that gastroenteritis is often the result of a coinfection and that rotavirus vaccine effectiveness might be underestimated in clinical and epidemiological studies.
•Rotavirus vaccine-derived AGE cases were detected in Belgium in the post-vaccine era.•There was limited evidence for vaccine strain circulation with scarce point mutations in both shed and ...circulating strains.•90% of the mutations were non-synonymous and several amino acid substitutions were shared among patients.•Some substitutions could be revertants towards the unattenuated vaccine precursor strain, albeit with low safety concerns.•In 35% of the cases, the AGE was estimated to be of non-rotavirus etiology.
Since the introduction of live-attenuated rotavirus vaccines in Belgium in 2006, surveillance has routinely detected rotavirus vaccine-derived strains. However, their genomic landscape and potential role in gastroenteritis have not been thoroughly investigated. We compared VP7 and VP4 nucleotide sequences obtained from rotavirus surveillance with the Rotarix vaccine sequence. As a result, we identified 80 vaccine-derived strains in 5125 rotavirus-positive infants with gastroenteritis from 2007 to 2018. Using both viral metagenomics and reverse transcription qPCR, we evaluated the vaccine strains and screened for co-infecting enteropathogens. Among the 45 patients with known vaccination status, 39 were vaccinated and 87% received the vaccine less than a month before the gastroenteritis episode. Reconstruction of 30 near complete vaccine-derived genomes revealed 0–11 mutations per genome, with 88% of them being non-synonymous. This, in combination with several shared amino acid changes among strains, pointed at selection of minor variant(s) present in the vaccine. We also found that some of these substitutions were true revertants (e.g., F167L on VP4, and I45T on NSP4). Finally, co-infections with known (e.g., Clostridioides difficile and norovirus) and divergent or emerging (e.g., human parechovirus A1, salivirus A2) pathogens were detected, and we estimated that 35% of the infants likely had gastroenteritis due to a ‘non-rotavirus’ cause. Conversely, we could not rule out the vaccine-derived gastroenteritis in over half of the cases. Continued studies inspecting reversion to pathogenicity should monitor the long-time safety of live-attenuated rotavirus vaccines. All in all, the complementary approach with NGS and qPCR provided a better understanding of rotavirus vaccine strain evolution in the Belgian population and epidemiology of co-infecting enteropathogens in suspected rotavirus vaccine-derived gastroenteritis cases.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Background
Inflammatory bowel disease IBD is a major debilitating disease. Recently, the gut microbiota has gained attention as an important factor involved in the pathophysiology of IBD. As ...a complement to the established bacterial ‘enterotypes’ associated with IBD, we focused here on viruses. We investigated the intestinal virome of IBD patients undergoing biological therapy for the presence of virome configurations associated with IBD, and to uncover how those configurations are associated with therapeutic success.
Methods
Viral-like particle enrichment followed by deep sequencing was performed on 432 faecal samples from 181 IBD patients starting biological therapy. Redundancy analysis and Dirichlet Multinomial Mixtures were applied to determine covariates of the virome composition and to condense the gut virota into ‘viral community types’, respectively.
Results
Patients were stratified based on unsupervised clustering into two viral community types. Community type CA showed a low α-diversity and a high relative abundance of Caudoviricetes non-CrAss phages and was associated with the dysbiotic Bact2-enterotype. Community type CrM showed a high α-diversity and a high relative abundance of Crassvirales and Malgrandaviricetes phages. During post-interventional analysis, endoscopic outcome was associated with gut virome composition. Remitting UC patients had a high percentage of community type CrM, a high Shannon diversity and a low lysogenic potential. Pre-interventional analyses also identified five novel phages associated with treatment success.
Conclusions
This study proposed two gut virome configurations that may be involved in the pathophysiology of IBD. Interestingly, those viral configurations are further associated with therapeutic success, suggesting a potential clinical relevance.
The purpose of this research study is to compare the effects of digital, dialogic and traditional reading on children’s language development aged 48–66 months. Fifty-six randomly selected children ...enrolled in three different classrooms in a public preschool in Turkey participated in the study. The three classrooms were again randomly assigned as digital, dialogic and traditional reading groups. During the reading activities, a total of 24 storybooks were read by each group every three times in 8 weeks. While the children’s language scores (the receptive and expressive language scores) resulted in a significant increase in dialogic reading, the children’s language scores in a digital and traditional reading group slightly changed during the intervention. Alternatively, qualitative data suggested that the interaction between teacher and children and between children and children were very limited in a digital and traditional reading group and that limited interaction during reading was the underlying cause of the insignificant increase in children’s language scores.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Bu çalışma, Türkiye'de Erken Çocukluk Eğitimini Geliştirme Derneği tarafından yayımlanan Erken Çocukluk Eğitimi Dergisi'nde 1968-1994 yılları arasında yayınlanan makaleleri incelemeyi amaçlamaktadır. ...Nitel araştırma yöntemi ile yapılan çalışmada beş aşamalı bir belge analizi süreci kullanılmıştır. Ayrıca dergide1968-1994 yılları arasında yayınlanmış makaleleri bulunan iki gönüllü akademisyen ile yarı yapılandırılmış görüşmeler yapılmıştır. Bulgular, yayınlanan makalelerin çoğunun üç ile altı yaş arasındaki çocukları hedefleyen derleme makaleler olduğunu, sıfır ile iki yaş arasındaki çocuklarla ilgili makale sayısının çok daha düşük olduğunu göstermektedir. Makaleler derinlemesine incelendiğinde çocuk gelişimi ve eğitimine sıklıkla yer verildiği, ebeveyn katılımı ve çocuk sağlığı ve bakımı konularının ise artarak makalelerde yer aldığını söylemek mümkündür. Son olarak, erken çocukluk eğitiminin önemini, sorunlarını ve gelecek vizyonunu ortaya koyan makaleler, amaç / öneriler teması altında tartışılmıştır.
The role of second messengers in the diversion of cellular processes by pathogens remains poorly studied despite their importance. Among these, Ca2+ virtually regulates all known cell processes, ...including cytoskeletal reorganization, inflammation, or cell death pathways. Under physiological conditions, cytosolic Ca2+ increases are transient and oscillatory, defining the so‐called Ca2+ code that links cell responses to specific Ca2+ oscillatory patterns. During cell invasion, Shigella induces atypical local and global Ca2+ signals. Here, we show that by hydrolyzing phosphatidylinositol‐(4,5)bisphosphate, the Shigella type III effector IpgD dampens inositol‐(1,4,5)trisphosphate (InsP3) levels. By modifying InsP3 dynamics and diffusion, IpgD favors the elicitation of long‐lasting local Ca2+ signals at Shigella invasion sites and converts Shigella‐induced global oscillatory responses into erratic responses with atypical dynamics and amplitude. Furthermore, IpgD eventually inhibits InsP3‐dependent responses during prolonged infection kinetics. IpgD thus acts as a pathogen regulator of the Ca2+ code implicated in a versatility of cell functions. Consistent with this function, IpgD prevents the Ca2+‐dependent activation of calpain, thereby preserving the integrity of cell adhesion structures during the early stages of infection.
Synopsis
During epithelial cell invasion, Shigella induces atypical Ca2+ signaling in the infected cells. The Shigella type III effector IpgD reduces availability of InsP3 precursor PIP2, thus disrupting InsP3‐regulated global Ca2+ response and delaying focal adhesion disassembly.
IpgD down‐regulates InsP3 levels by hydrolizing its precursor PIP2 during cell invasion.
IpgD participates in the confinement of long lasting local Ca2+ responses at Shigella invasion sites.
IpgD prevents InsP3‐mediated global Ca2+ responses at late infection stages.
IpgD delays calpain activation and focal adhesion disassembly during early stages of Shigella infection.
Hydrolysis of the precursor lipid PIP2 by a bacterial effector disrupts InsP3‐regulated global Ca2+ responses to cellular infection.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The role of second messengers in the diversion of cellular processes by pathogens remains poorly studied despite their importance. Among these, Ca
virtually regulates all known cell processes, ...including cytoskeletal reorganization, inflammation, or cell death pathways. Under physiological conditions, cytosolic Ca
increases are transient and oscillatory, defining the so-called Ca
code that links cell responses to specific Ca
oscillatory patterns. During cell invasion,
induces atypical local and global Ca
signals. Here, we show that by hydrolyzing phosphatidylinositol-(4,5)bisphosphate, the
type III effector IpgD dampens inositol-(1,4,5)trisphosphate (InsP
) levels. By modifying InsP
dynamics and diffusion, IpgD favors the elicitation of long-lasting local Ca
signals at
invasion sites and converts
-induced global oscillatory responses into erratic responses with atypical dynamics and amplitude. Furthermore, IpgD eventually inhibits InsP
-dependent responses during prolonged infection kinetics. IpgD thus acts as a pathogen regulator of the Ca
code implicated in a versatility of cell functions. Consistent with this function, IpgD prevents the Ca
-dependent activation of calpain, thereby preserving the integrity of cell adhesion structures during the early stages of infection.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The purpose of this study is to examine the efficacy of a 4-week dialogic reading intervention on the receptive and expressive language skills of 4-5 year old children from low-income families. ...Control group with pretest – posttest model in experimental design was used. Forty-six children attending a public kindergarten in Denizli were randomly placed in an experiment and a control group. Data were collected through “TEDİL-3” and “Personal Information Form.” In the experimental group, 8 picture books were read by the researcher two times a week for four weeks through dialogic reading techniques. In the control group, the same 8 picture books were read by the classroom teacher through traditional reading. The results showed advances in children's language development in favor of the experimental group. Suggestions related to literature were discussed.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PDF
