21,777 research outputs found

    Association of Staphylococcus aureus genotypes with milk or colonization of extramammary sites in Dutch dairy cattle indicates strain variation in reservoirs for intramammary infections

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    Staphylococcus aureus (S. aureus) is a major mastitis pathogen with a detrimental impact on udder health in dairy cattle. Although S. aureus is generally classified as a contagious mastitis pathogen, control measures aimed at preventing contagious transmission are not always effective. Previous studies showed that various extramammary sites can be colonized with S. aureus and could be a reservoir for S. aureus intramammary infections (IMI). The aim of this study was to determine the prevalence of S. aureus extramammary site colonization in Dutch dairy cattle and to compare the spa genotypes of S. aureus isolates from IMI to spa genotypes of isolates from extramammary sites. Six herds were visited and from cows with a composite milk somatic cell count Ôëą200,000 cells/mL quarter milk samples and swabs from various extramammary sites (hock, groin, udder cleft, nares, and feces) were taken. Extramammary site samples were processed by a two-step high salt selective culture and presence of S. aureus was confirmed by femA PCR. S. aureus isolates from milk and extramammary sites were compared by spa typing. The cow level colonization varied from 0% to 73%, and the prevalence of IMI in the sampled cows varied from 0% to 61% between herds. The extramammary site with the highest prevalence of colonization was the hock (23%) and the lowest prevalence of colonization was found for the nares (5%) and feces (5%). Spa typing of S. aureus isolates from either extramammary sites or milk showed that in most herds there were one or two predominant S. aureus spa genotypes present. Different S. aureus spa genotypes could be categorized into three groups based on the distribution between milk or extramammary sites: i) predominantly milk associated, ii) associated with both milk and extramammary sites, and iii) associated with extramammary sites. In conclusion, we showed that the prevalence of extramammary site colonization differed significantly between herds and extramammary sites and that specific S. aureus spa genotypes were associated with milk (IMI) or extramammary site colonization. Extramammary S. aureus reservoirs could be a source for IMI that cannot be eradicated by intervention measures aimed at contagious mastitis pathogens

    Reduced Seasonal Coronavirus Antibody Responses in Children Following COVID-19 Mitigation Measures, The Netherlands

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    SARS-CoV-2 prevention and control measures did not only impact SARS-CoV-2 circulation, but also the timing and prevalence of other seasonal respiratory viruses. Especially in children, information on exposure and infections to seasonal coronaviruses as well as SARS-CoV-2 in the first year of the pandemic is largely lacking. Therefore, we set up a one-year serological survey in a large tertiary hospital in the Netherlands. We show that seasonal coronavirus seroprevalence significantly decreased in 2021 in children less than one year, most likely due to COVID-19 control measures. The SARS-CoV-2 seroprevalence in children and adolescents increased from 0.4% to 11.3%, the highest in adolescents. This implies higher exposure rates in adolescents as compared to the general population (>18 years old). It is clear that there have been significant changes in the circulation and subsequent immunity against most respiratory pathogens as a result of the mitigation measures. The implications on shorter as well as longer term are still largely unknown, but the impact of the SARS-CoV-2 pandemic and subsequent control measures will continue to affect the dynamics of other pathogens

    The enterovirus genome can be translated in an IRES-independent manner that requires the initiation factors eIF2A/eIF2D

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    RNA recombination in positive-strand RNA viruses is a molecular-genetic process, which permits the greatest evolution of the genome and may be essential to stabilizing the genome from the deleterious consequences of accumulated mutations. Enteroviruses represent a useful system to elucidate the details of this process. On the biochemical level, it is known that RNA recombination is catalyzed by the viral RNA-dependent RNA polymerase using a template-switching mechanism. For this mechanism to function in cells, the recombining genomes must be located in the same subcellular compartment. How a viral genome is trafficked to the site of genome replication and recombination, which is membrane associated and isolated from the cytoplasm, is not known. We hypothesized that genome translation was essential for colocalization of genomes for recombination. We show that complete inactivation of internal ribosome entry site (IRES)-mediated translation of a donor enteroviral genome enhanced recombination instead of impairing it. Recombination did not occur by a nonreplicative mechanism. Rather, sufficient translation of the nonstructural region of the genome occurred to support subsequent steps required for recombination. The noncanonical translation initiation factors, eIF2A and eIF2D, were required for IRES-independent translation. Our results support an eIF2A/eIF2D-dependent mechanism under conditions in which the eIF2-dependent mechanism is inactive. Detection of an IRES-independent mechanism for translation of the enterovirus genome provides an explanation for a variety of debated observations, including nonreplicative recombination and persistence of enteroviral RNA lacking an IRES. The existence of an eIF2A/eIF2D-dependent mechanism in enteroviruses predicts the existence of similar mechanisms in other viruses

    Proteomic analysis of metronidazole resistance in the human facultative pathogen Bacteroides fragilis

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    The anaerobic gut bacteria and opportunistic pathogen Bacteroides fragilis can cause life-threatening infections when leaving its niche and reaching body sites outside of the gut. The antimicrobial metronidazole is a mainstay in the treatment of anaerobic infections and also highly effective against Bacteroides spp. Although resistance rates have remained low in general, metronidazole resistance does occur in B. fragilis and can favor fatal disease outcomes. Most metronidazole-resistant Bacteroides isolates harbor nim genes, commonly believed to encode for nitroreductases which deactivate metronidazole. Recent research, however, suggests that the mode of resistance mediated by Nim proteins might be more complex than anticipated because they affect the cellular metabolism, e.g., by increasing the activity of pyruvate:ferredoxin oxidoreductase (PFOR). Moreover, although nim genes confer only low-level metronidazole resistance to Bacteroides, high-level resistance can be much easier induced in the laboratory in the presence of a nim gene than without. Due to these observations, we hypothesized that nim genes might induce changes in the B. fragilis proteome and performed comparative mass-spectrometric analyses with B. fragilis 638R, either with or without the nimA gene. Further, we compared protein expression profiles in both strains after induction of high-level metronidazole resistance. Interestingly, only few proteins were repeatedly found to be differentially expressed in strain 638R with the nimA gene, one of them being the flavodiiron protein FprA, an enzyme involved in oxygen scavenging. After induction of metronidazole resistance, a far higher number of proteins were found to be differentially expressed in 638R without nimA than in 638R with nimA. In the former, factors for the import of hemin were strongly downregulated, indicating impaired iron import, whereas in the latter, the observed changes were not only less numerous but also less specific. Both resistant strains, however, displayed a reduced capability of scavenging oxygen. Susceptibility to metronidazole could be widely restored in resistant 638R without nimA by supplementing growth media with ferrous iron sulfate, but not so in resistant 638R with the nimA gene. Finally, based on the results of this study, we present a novel hypothetic model of metronidazole resistance and NimA function

    Regulation of Phagocytosis in Macrophages

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    When the first line of defenceÔÇöthe integumentary system fails, the immune system protects us from infections by pathogens. Macrophages are crucial for mediating effects in the innate immune system by eliminating impaired cells and harmful micro-organisms through phagocytosis. Although other cells undergo phagocytosis, the cellular processes that regulate phagocytosis may vary from cell to cell. These include metabolic changes, signal transduction, and changes in molecular expression or post-translational modifications. This chapter will comprehensively review biological processes that regulate phagocytosis in macrophages, including; changes in metabolic processes, signal transduction, molecular expression, and post-translational modifications

    Examples of works to practice staccato technique in clarinet instrument

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    Klarnetin staccato tekni─čini g├╝├žlendirme a┼čamalar─▒ eser ├žal─▒┼čmalar─▒yla uygulanm─▒┼čt─▒r. Staccato ge├ži┼člerini h─▒zland─▒racak ritim ve n├╝ans ├žal─▒┼čmalar─▒na yer verilmi┼čtir. ├çal─▒┼čman─▒n en ├Ânemli amac─▒ sadece staccato ├žal─▒┼čmas─▒ de─čil parmak-dilin e┼č zamanl─▒ uyumunun hassasiyeti ├╝zerinde de durulmas─▒d─▒r. Staccato ├žal─▒┼čmalar─▒n─▒ daha verimli hale getirmek i├žin eser ├žal─▒┼čmas─▒n─▒n i├žinde et├╝t ├žal─▒┼čmas─▒na da yer verilmi┼čtir. ├çal─▒┼čmalar─▒n ├╝zerinde titizlikle durulmas─▒ staccato ├žal─▒┼čmas─▒n─▒n ilham verici etkisi ile m├╝zikal kimli─če yeni bir boyut kazand─▒rm─▒┼čt─▒r. Sekiz ├Âzg├╝n eser ├žal─▒┼čmas─▒n─▒n her a┼čamas─▒ anlat─▒lm─▒┼čt─▒r. Her a┼čaman─▒n bir sonraki performans ve tekni─či g├╝├žlendirmesi esas al─▒nm─▒┼čt─▒r. Bu ├žal─▒┼čmada staccato tekni─činin hangi alanlarda kullan─▒ld─▒─č─▒, nas─▒l sonu├žlar elde edildi─či bilgisine yer verilmi┼čtir. Notalar─▒n parmak ve dil uyumu ile nas─▒l ┼čekillenece─či ve nas─▒l bir ├žal─▒┼čma disiplini i├žinde ger├žekle┼čece─či planlanm─▒┼čt─▒r. Kam─▒┼č-nota-diyafram-parmak-dil-n├╝ans ve disiplin kavramlar─▒n─▒n staccato tekni─činde ayr─▒lmaz bir b├╝t├╝n oldu─ču saptanm─▒┼čt─▒r. Ara┼čt─▒rmada literat├╝r taramas─▒ yap─▒larak staccato ile ilgili ├žal─▒┼čmalar taranm─▒┼čt─▒r. Tarama sonucunda klarnet tekni─čin de kullan─▒lan staccato eser ├žal─▒┼čmas─▒n─▒n az oldu─ču tespit edilmi┼čtir. Metot taramas─▒nda da et├╝t ├žal─▒┼čmas─▒n─▒n daha ├žok oldu─ču saptanm─▒┼čt─▒r. B├Âylelikle klarnetin staccato tekni─čini h─▒zland─▒rma ve g├╝├žlendirme ├žal─▒┼čmalar─▒ sunulmu┼čtur. Staccato et├╝t ├žal─▒┼čmalar─▒ yap─▒l─▒rken, araya eser ├žal─▒┼čmas─▒n─▒n girmesi beyni rahatlatt─▒─č─▒ ve isteklili─či daha artt─▒rd─▒─č─▒ g├Âzlemlenmi┼čtir. Staccato ├žal─▒┼čmas─▒n─▒ yaparken do─čru bir kam─▒┼č se├žimi ├╝zerinde de durulmu┼čtur. Staccato tekni─čini do─čru ├žal─▒┼čmak i├žin do─čru bir kam─▒┼č─▒n dil h─▒z─▒n─▒ artt─▒rd─▒─č─▒ saptanm─▒┼čt─▒r. Do─čru bir kam─▒┼č se├žimi kam─▒┼čtan rahat ses ├ž─▒kmas─▒na ba─čl─▒d─▒r. Kam─▒┼č, dil atma g├╝c├╝n├╝ vermiyorsa daha do─čru bir kam─▒┼č se├žiminin yap─▒lmas─▒ gereklili─či vurgulanm─▒┼čt─▒r. Staccato ├žal─▒┼čmalar─▒nda ba┼čtan sona bir eseri yorumlamak zor olabilir. Bu a├ž─▒dan ├žal─▒┼čma, verilen m├╝zikal n├╝anslara uyman─▒n, dil at─▒┼č performans─▒n─▒ rahatlatt─▒─č─▒n─▒ ortaya koymu┼čtur. Gelecek nesillere edinilen bilgi ve birikimlerin aktar─▒lmas─▒ ve geli┼čtirici olmas─▒ te┼čvik edilmi┼čtir. ├ç─▒kacak eserlerin nas─▒l ├ž├Âz├╝lece─či, staccato tekni─činin nas─▒l ├╝stesinden gelinebilece─či anlat─▒lm─▒┼čt─▒r. Staccato tekni─činin daha k─▒sa s├╝rede ├ž├Âz├╝me kavu┼čturulmas─▒ ama├ž edinilmi┼čtir. Parmaklar─▒n yerlerini ├Â─čretti─čimiz kadar belle─čimize de ├žal─▒┼čmalar─▒n kaydedilmesi ├Ânemlidir. G├Âsterilen azmin ve sabr─▒n sonucu olarak ortaya ├ž─▒kan yap─▒t ba┼čar─▒y─▒ daha da yukar─▒ seviyelere ├ž─▒karacakt─▒r
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