The emergence of antibiotic-resistant bacterial pathogens is an all-too-common consequence of antibiotic use. Although antibiotic resistance among virulent bacterial pathogens is a growing concern, ...the highest levels of antibiotic resistance occur among less pathogenic but more common bacteria that are prevalent in healthcare settings. Patient-to-patient transmission of these antibiotic-resistant bacteria is a perpetual concern in hospitals. Many of these resistant microbes, such as vancomycin-resistant
and carbapenem-resistant
, emerge from the intestinal lumen and invade the bloodstream of vulnerable patients, causing disseminated infection. These infections are associated with preceding antibiotic administration, which changes the intestinal microbiota and compromises resistance to colonization by antibiotic-resistant bacteria. Recent and ongoing studies are increasingly defining commensal bacterial species and the inhibitory mechanisms they use to prevent infection. The use of next-generation probiotics derived from the intestinal microbiota represents an alternative approach to prevention of infection by enriching colonization with protective commensal species, thereby reducing the density of antibiotic-resistant bacteria and also reducing patient-to-patient transmission of infection in healthcare settings.
CpG islands (CGIs) are vertebrate genomic landmarks that encompass the promoters of most genes and often lack DNA methylation. Querying their apparent importance, the number of CGIs is reported to ...vary widely in different species and many do not co-localise with annotated promoters. We set out to quantify the number of CGIs in mouse and human genomes using CXXC Affinity Purification plus deep sequencing (CAP-seq). We also asked whether CGIs not associated with annotated transcripts share properties with those at known promoters. We found that, contrary to previous estimates, CGI abundance in humans and mice is very similar and many are at conserved locations relative to genes. In each species CpG density correlates positively with the degree of H3K4 trimethylation, supporting the hypothesis that these two properties are mechanistically interdependent. Approximately half of mammalian CGIs (>10,000) are "orphans" that are not associated with annotated promoters. Many orphan CGIs show evidence of transcriptional initiation and dynamic expression during development. Unlike CGIs at known promoters, orphan CGIs are frequently subject to DNA methylation during development, and this is accompanied by loss of their active promoter features. In colorectal tumors, however, orphan CGIs are not preferentially methylated, suggesting that cancer does not recapitulate a developmental program. Human and mouse genomes have similar numbers of CGIs, over half of which are remote from known promoters. Orphan CGIs nevertheless have the characteristics of functional promoters, though they are much more likely than promoter CGIs to become methylated during development and hence lose these properties. The data indicate that orphan CGIs correspond to previously undetected promoters whose transcriptional activity may play a functional role during development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The use of face masks has become ubiquitous. Although mask wearing is a convenient way to reduce the spread of disease, it is important to know how the mask affects our communication via facial ...expression. For example, when we are wearing the mask and meet a friend, are our facial expressions different compared to when we are not? We investigated the effect of face mask wearing on facial expression, including the area around the eyes. We measured surface electromyography from zygomaticus major, orbicularis oculi, and depressor anguli oris muscles, when people smiled and talked with or without a mask. Only the actions of the orbicularis oculi were facilitated by wearing the mask. We thus concluded that mask wearing may increase the recruitment of the eyes during smiling. In other words, we can express joy and happiness even when wearing a face mask.
During the pandemic, many institutions shifted to online teaching, and in some cases, this included existing peer learning programs. As the pandemic receded, some of these peer learning programs ...returned to face-to-face operation and others adopted a blended format, while others remained online. Interestingly, the literature suggests that online peer learning is somewhat more effective than face-to-face peer learning. This might be because online peer learning enables responses at any time (which might be more thoughtful), anonymity, and a wider nexus of relationships, although it can create issues regarding the initial development of trust. There are a great many studies of both face-to-face and online peer learning, but relatively few that directly compare both. By way of addressing this gap, this paper aims to systematically review 17 papers that directly compare both, informed by and updating the only previous review in this area. Online performs better than offline learning in terms of cognitive outcomes, with a small to moderate effect size. However, the associated socio-emotional issues are more complex. Online learning offers flexibility regarding response time, but sacrifices the immediate dialogue of offline learning. Some cultures found accepting peer learning more difficult. Few studies undertook longer-term follow-up, although with more practice motivation, this might well improve. The results have implications for the type of peer learning chosen by pedagogical designers as appropriate to their own learning context.
Business models providing used clothing to consumers have the potential to increase the use of each garment and thereby reduce pressure on raw materials and primary production. This research used ...in-depth interviews complemented by a literature review to improve the understanding of the business models and the ways in which they can impact the environment. In total, the interviews were carried out with seven business owners and six experts in clothing sustainability, product lifespan extension, and circular business models. Examples of business models of interest include businesses selling secondhand clothes and businesses renting clothes to customers. A typology of business models is used to understand how each model impacts the environment and to highlight the factors that contribute most to the impacts that need to be managed. Business models vary in how they impact the environment, through differences in the way they manage transport, storage, and cleaning. Business models also vary in how successfully they reduce the environmental impacts from the production of new garments by increasing the number of times different wearers wear a garment and reducing the need to buy new garments. This effect is referred to as displacement, and the displacement rate provides an indication of the efficiency of reuse models in reducing total volumes of throughput. Indeed, some new business models may not have reduced throughput as a goal at all, and appraisal of this is crucial to understanding the environmental impacts of the various models.
Organizations worldwide are currently experiencing shifts in the age composition of their workforces. The workforce is aging and becoming increasingly age-diverse, suggesting that organizational ...researchers and practitioners need to better understand how age differences may manifest in the workplace and the implications for human resource practice. Integrating socioemotional selectivity theory with the performance feedback literature and using a time-lagged design, the current study examined age differences in moderating the relationships between the characteristics of performance feedback and employee reactions to the feedback event. The results suggest that older workers had higher levels of feedback orientation on social awareness, but lower levels of feedback orientation on utility than younger workers. Furthermore, the positive associations between favorability of feedback and feedback delivery and feedback reactions were stronger for older workers than for younger workers, whereas the positive association between feedback quality and feedback reactions was stronger for younger workers than for older workers. Finally, the current study revealed that age-related differences in employee feedback orientation could explain the different patterns of relationships between feedback characteristics and feedback reactions across older and younger workers. These findings have both theoretical and practical implications for building theory about workplace aging and improving ways that performance feedback is managed across employees from diverse age groups.
MeCP2 is a nuclear protein with an affinity for methylated DNA that can recruit histone deacetylases. Deficiency or excess of MeCP2 causes severe neurological problems, suggesting that the number of ...molecules per cell must be precisely regulated. We quantified MeCP2 in neuronal nuclei and found that it is nearly as abundant as the histone octamer. Despite this high abundance, MeCP2 associates preferentially with methylated regions, and high-throughput sequencing showed that its genome-wide binding tracks methyl-CpG density. MeCP2 deficiency results in global changes in neuronal chromatin structure, including elevated histone acetylation and a doubling of histone H1. Neither change is detectable in glia, where MeCP2 occurs at lower levels. The mutant brain also shows elevated transcription of repetitive elements. Our data argue that MeCP2 may not act as a gene-specific transcriptional repressor in neurons, but might instead dampen transcriptional noise genome-wide in a DNA methylation-dependent manner.
► Neuronal nuclei have about one molecule of MeCP2 for every two nucleosomes ► MeCP2 in neurons binds chromosome-wide, tracking the density of DNA methylation ► MeCP2 deficiency doubles both histone acetylation and histone H1 only in neurons ► MeCP2 dampens transcriptional “noise” from repetitive elements and satellite DNA
High-density, strand-specific cDNA sequencing (ssRNA-seq) was used to analyze the transcriptome of Salmonella enterica serovar Typhi (S. Typhi). By mapping sequence data to the entire S. Typhi ...genome, we analyzed the transcriptome in a strand-specific manner and further defined transcribed regions encoded within prophages, pseudogenes, previously un-annotated, and 3'- or 5'-untranslated regions (UTR). An additional 40 novel candidate non-coding RNAs were identified beyond those previously annotated. Proteomic analysis was combined with transcriptome data to confirm and refine the annotation of a number of hpothetical genes. ssRNA-seq was also combined with microarray and proteome analysis to further define the S. Typhi OmpR regulon and identify novel OmpR regulated transcripts. Thus, ssRNA-seq provides a novel and powerful approach to the characterization of the bacterial transcriptome.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Increasing antibiotic resistance among bacterial pathogens has rendered some infections untreatable with available antibiotics. Klebsiella pneumoniae, a bacterial pathogen that has acquired ...high-level antibiotic resistance, is a common cause of pulmonary infections. Optimal clearance of K. pneumoniae from the host lung requires TNF and IL-17A. Herein, we demonstrate that inflammatory monocytes are rapidly recruited to the lungs of K. pneumoniae-infected mice and produce TNF, which markedly increases the frequency of IL-17-producing innate lymphoid cells. While pulmonary clearance of K. pneumoniae is preserved in neutrophil-depleted mice, monocyte depletion or TNF deficiency impairs IL-17A-dependent resolution of pneumonia. Monocyte-mediated bacterial uptake and killing is enhanced by ILC production of IL-17A, indicating that innate lymphocytes engage in a positive-feedback loop with monocytes that promotes clearance of pneumonia. Innate immune defense against a highly antibiotic-resistant bacterial pathogen depends on crosstalk between inflammatory monocytes and innate lymphocytes that is mediated by TNF and IL-17A.
Purpose To (a) evaluate whether plaque tissue characteristics determined with conventional computed tomographic (CT) angiography could be quantitated at higher levels of accuracy by using image ...processing algorithms that take characteristics of the image formation process coupled with biologic insights on tissue distributions into account by comparing in vivo results and ex vivo histologic findings and (b) assess reader variability. Materials and Methods Thirty-one consecutive patients aged 43-85 years (average age, 64 years) known to have or suspected of having atherosclerosis who underwent CT angiography and were referred for endarterectomy were enrolled. Surgical specimens were evaluated with histopathologic examination to serve as standard of reference. Two readers used lumen boundary to determine scanner blur and then optimized component densities and subvoxel boundaries to best fit the observed image by using semiautomatic software. The accuracy of the resulting in vivo quantitation of calcification, lipid-rich necrotic core (LRNC), and matrix was assessed with statistical estimates of bias and linearity relative to ex vivo histologic findings. Reader variability was assessed with statistical estimates of repeatability and reproducibility. Results A total of 239 cross sections obtained with CT angiography and histologic examination were matched. Performance on held-out data showed low levels of bias and high Pearson correlation coefficients for calcification (-0.096 mm
and 0.973, respectively), LRNC (1.26 mm
and 0.856), and matrix (-2.44 mm
and 0.885). Intrareader variability was low (repeatability coefficient ranged from 1.50 mm
to 1.83 mm
among tissue characteristics), as was interreader variability (reproducibility coefficient ranged from 2.09 mm
to 4.43 mm
). Conclusion There was high correlation and low bias between the in vivo software image analysis and ex vivo histopathologic quantitative measures of atherosclerotic plaque tissue characteristics, as well as low reader variability. Software algorithms can mitigate the blurring and partial volume effects of routine CT angiography acquisitions to produce accurate quantification to enhance current clinical practice. Clinical trial registration no. NCT02143102
RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on September 15, 2017.
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