120 research outputs found
Problematic mukbang watching and its relationship to disordered eating and internet addiction: a pilot study among emerging adult mukbang watchers
Internet technology has facilitated the use of a wide variety of different activities and applications in online contexts. One such activity is watching mukbang (i.e., watching videos of “eating broadcasts” where someone eats a large amount of food while interacting with viewers). In the present study, the relationship of problematic mukbang watching with disordered eating and internet addiction was examined. Participants were 140 emerging adults who watched mukbang at least once in the past 30 days (66% female; Mage = 21.66, SD = 1.88, range = 19–29 years). Structural equation modeling indicated that problematic mukbang watching was positively associated with both disordered eating and internet addiction. The present study is the first to explore the predictive role of problematic mukbang watching on adverse consequences, and suggests that mukbang watching may be problematic for a minority of emerging adults and that problematic mukbang watching warrants further examination of its impact on mental health and wellbeing
Transcriptome analysis of extended-spectrum ß-lactamase-producing Escherichia coli and methicillin-resistant Staphylococcus aureus exposed to cefotaxime
Previous studies on bacterial response to antibiotics mainly focused on susceptible strains. Here we characterized the transcriptional responses of distinct cephalosporin-resistant bacteria of public health relevance to cefotaxime (CTX), a cephalosporin widely used in clinical practice. Adaptation to therapeutic concentrations of CTX (30 µg/ml) was investigated by RNA sequencing in mid-exponential phase cultures of a methicillin-resistant Staphylococcus aureus (MRSA) and two genetically diverse E. coli producing CTX-M-15 or CMY-2 β-lactamase following genome sequencing and annotation for each strain. MRSA showed the most notable adaptive changes in the transcriptome after exposure to CTX, mainly associated with cell envelope functions. This reprogramming coincided with a transient reduction in cell growth, which also occurred in the CMY-2-producing E. coli but not in the CTX-M-15-producing strain. Re-establishment of growth in the CMY-2 producer proceeded without any notable adaptive transcriptional response, while limited reprogramming of gene transcription was observed in the CTX-M-15 producer. Our data show that the transcriptional response of CTX-resistant bacteria to CTX depends on the bacterial species, level of resistance and resistance determinant involved. Gene products induced in the presence of CTX may play an essential role for bacterial survival during therapy and merit further investigation as possible targets for potentiating CTX
Susceptibility to COPD:Differential Proteomic Profiling after Acute Smoking
Cigarette smoking is the main risk factor for COPD (Chronic Obstructive Pulmonary Disease), yet only a subset of smokers develops COPD. Family members of patients with severe early-onset COPD have an increased risk to develop COPD and are therefore defined as "susceptible individuals". Here we perform unbiased analyses of proteomic profiles to assess how "susceptible individuals" differ from age-matched "non-susceptible individuals" in response to cigarette smoking. Epithelial lining fluid (ELF) was collected at baseline and 24 hours after smoking 3 cigarettes in young individuals susceptible or non-susceptible to develop COPD and older subjects with established COPD. Controls at baseline were older healthy smoking and non-smoking individuals. Five samples per group were pooled and analysed by stable isotope labelling (iTRAQ) in duplicate. Six proteins were selected and validated by ELISA or immunohistochemistry. After smoking, 23 proteins increased or decreased in young susceptible individuals, 7 in young non-susceptible individuals, and 13 in COPD in the first experiment; 23 proteins increased or decreased in young susceptible individuals, 32 in young non-susceptible individuals, and 11 in COPD in the second experiment. SerpinB3 and Uteroglobin decreased after acute smoke exposure in young non-susceptible individuals exclusively, whereas Peroxiredoxin I, S100A9, S100A8, ALDH3A1 (Aldehyde dehydrogenase 3A1) decreased both in young susceptible and non-susceptible individuals, changes being significantly different between groups for Uteroglobin with iTRAQ and for Serpin B3 with iTRAQ and ELISA measures. Peroxiredoxin I, SerpinB3 and ALDH3A1 increased in COPD patients after smoking. We conclude that smoking induces a differential protein response in ELF of susceptible and non-susceptible young individuals, which differs from patients with established COPD. This is the first study applying unbiased proteomic profiling to unravel the underlying mechanisms that induce COPD. Our data suggest that SerpinB3 and Uteroglobin could be interesting proteins in understanding the processes leading to COPD
Gender Based Within-Household Inequality in Childhood Immunization in India: Changes over Time and across Regions
Background and Objectives: Despite India’s substantial economic growth in the past two decades, girls in India are discriminated against in access to preventive healthcare including immunizations. Surprisingly, no study has assessed the contribution of gender based within-household discrimination to the overall inequality in immunization status of Indian children. This study therefore has two objectives: to estimate the gender based within-household inequality (GWHI) in immunization status of Indian children and to examine the inter-regional and inter-temporal variations in the GWHI. Data and Methods: The present study used households with a pair of male-female siblings (aged 1–5 years) from two rounds of National Family Health Survey (NFHS, 1992–93 and 2005–06). The overall inequality in the immunization status (after controlling for age and birth order) of children was decomposed into within-households and between-households components using Mean log deviation to obtain the GWHI component. The analysis was conducted at the all-India level as well as for six specified geographical regions and at two time points (1992–93 and 2005–06). Household fixed-effects models for immunization status of children were also estimated. Results and Conclusions: Findings from household fixed effects analysis indicated that the immunization scores of girls were significantly lower than that of boys. The inequality decompositions revealed that, at the all-India level, the absolute level of GWHI in immunization status decreased from 0.035 in 1992–93 to 0.023 in 2005–06. However, as a percentage o
IL-10R Blockade during Chronic Schistosomiasis Mansoni Results in the Loss of B Cells from the Liver and the Development of Severe Pulmonary Disease
In schistosomiasis patients, parasite eggs trapped in hepatic sinusoids become foci for CD4+ T cell-orchestrated granulomatous cellular infiltrates. Since the immune response is unable to clear the infection, the liver is subjected to ongoing cycles of focal inflammation and healing that lead to vascular obstruction and tissue fibrosis. This is mitigated by regulatory mechanisms that develop over time and which minimize the inflammatory response to newly deposited eggs. Exploring changes in the hepatic inflammatory infiltrate over time in infected mice, we found an accumulation of schistosome egg antigen-specific IgG1-secreting plasma cells during chronic infection. This population was significantly diminished by blockade of the receptor for IL-10, a cytokine implicated in plasma cell development. Strikingly, IL-10R blockade precipitated the development of portal hypertension and the accumulation of parasite eggs in the lungs and heart. This did not reflect more aggressive Th2 cell responsiveness, increased hepatic fibrosis, or the emergence of Th1 or Th17 responses. Rather, a role for antibody in the prevention of severe disease was suggested by the finding that pulmonary involvement was also apparent in mice unable to secrete class switched antibody. A major effect of anti-IL-10R treatment was the loss of a myeloid population that stained positively for surface IgG1, and which exhibited characteristics of regulatory/anti-inflammatory macrophages. This finding suggests that antibody may promote protective effects within the liver through local interactions with macrophages. In summary, our data describe a role for IL-10-dependent B cell responses in the regulation of tissue damage during a chronic helminth infection
Substrate Specifity Profiling of the Aspergillus fumigatus Proteolytic Secretome Reveals Consensus Motifs with Predominance of Ile/Leu and Phe/Tyr
The filamentous fungus Aspergillus fumigatus (AF) can cause devastating infections in immunocompromised individuals. Early diagnosis improves patient outcomes but remains challenging because of the limitations of current methods. To augment the clinician's toolkit for rapid diagnosis of AF infections, we are investigating AF secreted proteases as novel diagnostic targets. The AF genome encodes up to 100 secreted proteases, but fewer than 15 of these enzymes have been characterized thus far. Given the large number of proteases in the genome, studies focused on individual enzymes may overlook potential diagnostic biomarkers.As an alternative, we employed a combinatorial library of internally quenched fluorogenic probes (IQFPs) to profile the global proteolytic secretome of an AF clinical isolate in vitro. Comparative protease activity profiling revealed 212 substrate sequences that were cleaved by AF secreted proteases but not by normal human serum. A central finding was that isoleucine, leucine, phenylalanine, and tyrosine predominated at each of the three variable positions of the library (44.1%, 59.1%, and 57.0%, respectively) among substrate sequences cleaved by AF secreted proteases. In contrast, fewer than 10% of the residues at each position of cleaved sequences were cationic or anionic. Consensus substrate motifs were cleaved by thermostable serine proteases that retained activity up to 50°C. Precise proteolytic cleavage sites were reliably determined by a simple, rapid mass spectrometry-based method, revealing predominantly non-prime side specificity. A comparison of the secreted protease activities of three AF clinical isolates revealed consistent protease substrate specificity fingerprints. However, secreted proteases of A. flavus, A. nidulans, and A. terreus strains exhibited striking differences in their proteolytic signatures.This report provides proof-of-principle for the use of protease substrate specificity profiling to define the proteolytic secretome of Aspergillus fumigatus. Expansion of this technique to protease secretion during infection could lead to development of novel approaches to fungal diagnosis
Engineered Toxins “Zymoxins” Are Activated by the HCV NS3 Protease by Removal of an Inhibitory Protein Domain
The synthesis of inactive enzyme precursors, also known as “zymogens,” serves as a mechanism for regulating the execution of selected catalytic activities in a desirable time and/or site. Zymogens are usually activated by proteolytic cleavage. Many viruses encode proteases that execute key proteolytic steps of the viral life cycle. Here, we describe a proof of concept for a therapeutic approach to fighting viral infections through eradication of virally infected cells exclusively, thus limiting virus production and spread. Using the hepatitis C virus (HCV) as a model, we designed two HCV NS3 protease-activated “zymogenized” chimeric toxins (which we denote “zymoxins”). In these recombinant constructs, the bacterial and plant toxins diphtheria toxin A (DTA) and Ricin A chain (RTA), respectively, were fused to rationally designed inhibitor peptides/domains via an HCV NS3 protease-cleavable linker. The above toxins were then fused to the binding and translocation domains of Pseudomonas exotoxin A in order to enable translocation into the mammalian cells cytoplasm. We show that these toxins exhibit NS3 cleavage dependent increase in enzymatic activity upon NS3 protease cleavage in vitro. Moreover, a higher level of cytotoxicity was observed when zymoxins were applied to NS3 expressing cells or to HCV infected cells, demonstrating a potential therapeutic window. The increase in toxin activity correlated with NS3 protease activity in the treated cells, thus the therapeutic window was larger in cells expressing recombinant NS3 than in HCV infected cells. This suggests that the “zymoxin” approach may be most appropriate for application to life-threatening acute infections where much higher levels of the activating protease would be expected
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