Stress-triggered Activation of the Metalloprotease Oma1 Involves Its C-terminal Region and Is Important for Mitochondrial Stress Protection in Yeast

Background: Oma1 is a conserved membrane-bound protease that forms a high molecular mass complex. Results: Oma1 activity is induced by stress stimuli and required for survival. The activation is linked to changes in Oma1 oligomer stability and involves its C-terminal region. Conclusion: Oma1 function is activated by mitochondrial stress and is important for stress tolerance. Significance: Novel insights into Oma1 function and a potential stress activation mechanism are provided

Oma1 Links Mitochondrial Protein Quality Control and TOR Signaling To Modulate Physiological Plasticity and Cellular Stress Responses

ACKNOWLEDGMENTS We thank Dennis Winge (University of Utah) and the members of the Khalimonchuk laboratory for critical comments. We also thank Christoph Schuller (University of Natural Resources, Austria) and Paul Herman (Ohio State University) for reagents. We acknowledge the expert technical assistance of Nataliya Zahayko. We also thank Donna MacCallum for help with the Candida virulence assays. This research was supported by grants from the NIH (P30GM103335 and 5R01GM108975 [O.K.], GM071775-06 and GM105781-01 [A.B.], DK079209 [J.L.]), the U.K. Biotechnology and Biological Research Council (BB/K017365/1 [A.J.P.B.]), the U.K. Medical Research Council (MR/ M026663/1 [A.J.P.B.]), and the European Research Council (C-2009- AdG-249793 [A.J.P.B.]). We declare that we have no competing financial interests. FUNDING INFORMATION This work, including the efforts of Alistair J. P. Brown, was funded by Biotechnology and Biological Research Counsil (BB/K017365/1). This work, including the efforts of Oleh Khalimonchuk, was funded by HHS | National Institutes of Health (NIH) (5R01GM108975). This work, including the efforts of Oleh Khalimonchuk, was funded by HHS | National Institutes of Health (NIH) (P30GM103335).This work, including the efforts of Antoni Barrientos, was funded by HHS | National Institutes of Health (NIH) (GM071775-06). This work, including the efforts of Antoni Barrientos, was funded by HHS | National Institutes of Health (NIH) (GM105781-01). This work, including the efforts of Jaekwon Lee, was funded by HHS | National Institutes of Health (NIH) (DK079209). This work, including the efforts of Alistair J. P. Brown, was funded by Medical Research Council (MRC) (MR/M026663/1). This work, including the efforts of Alistair J. P. Brown, was funded by EC | European Research Council (ERC) (C-2009-AdG-249793).Peer reviewedPublisher PD

Stress-triggered Activation of the Metalloprotease Oma1 Involves Its C-terminal Region and Is Important for Mitochondrial Stress Protection in Yeast

Background: Oma1 is a conserved membrane-bound protease that forms a high molecular mass complex. Results: Oma1 activity is induced by stress stimuli and required for survival. The activation is linked to changes in Oma1 oligomer stability and involves its C-terminal region. Conclusion: Oma1 function is activated by mitochondrial stress and is important for stress tolerance. Significance: Novel insights into Oma1 function and a potential stress activation mechanism are provided

Supercritical fluid extraction of corn germ oil: Study of the influence of process parameters on the extraction yield and oil quality

The supercritical fluid extraction of corn germ oil has been studied in this work. Extractions were carried out at different pressure, temperature and flow rate to analyze the influence of these variables on the extraction kinetics and the oil quality obtained. Extraction curves are initially linear with a slope close to the oil solubility value in supercritical CO2. Based on these results a mathematical model was successfully applied to describe the extraction curves. Characterization of supercritical crude corn oil was performed by determining some physical parameters such as refraction index, density and color. Additionally, the fatty acid composition, neutral lipids, the content of tocopherols, acid index, peroxide value, antioxidant capacity and the oxidative stability were determined in the corn oil extracted. Fatty acid composition was compared with that for crude germ oil and no significant differences between the oils extracted by both methods were found. Oxidative stability test using the Rancimat showed that supercritical CO2 extracted corn oil is less protected against oxidation than n-hexane extracted oils

The FLUXNET2015 dataset and the ONEFlux processing pipeline for eddy covariance data

The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.Peer reviewe

Elevated protein concentrations in newborn blood and the risks of autism spectrum disorder, and of social impairment, at age 10 years among infants born before the 28th week of gestation

Among the 1 of 10 children who are born preterm annually in the United States, 6% are born before the third trimester. Among children who survive birth before the 28th week of gestation, the risks of autism spectrum disorder (ASD) and non-autistic social impairment are severalfold higher than in the general population. We examined the relationship between top quartile inflammation-related protein concentrations among children born extremely preterm and ASD or, separately, a high score on the Social Responsiveness Scale (SRS total score ≥65) among those who did not meet ASD criteria, using information only from the subset of children whose DAS-II verbal or non-verbal IQ was ≥70, who were assessed for ASD, and who had proteins measured in blood collected on ≥2 days (N = 763). ASD (N = 36) assessed at age 10 years is associated with recurrent top quartile concentrations of inflammation-related proteins during the first post-natal month (e.g., SAA odds ratio (OR); 95% confidence interval (CI): 2.5; 1.2–5.3) and IL-6 (OR; 95% CI: 2.6; 1.03–6.4)). Top quartile concentrations of neurotrophic proteins appear to moderate the increased risk of ASD associated with repeated top quartile concentrations of inflammation-related proteins. High (top quartile) concentrations of SAA are associated with elevated risk of ASD (2.8; 1.2–6.7) when Ang-1 concentrations are below the top quartile, but not when Ang-1 concentrations are high (1.3; 0.3–5.8). Similarly, high concentrations of TNF-α are associated with heightened risk of SRS-defined social impairment (N = 130) (2.0; 1.1–3.8) when ANG-1 concentrations are not high, but not when ANG-1 concentrations are elevated (0.5; 0.1–4.2)

Comparative Genomics of Canadian Epidemic Lineages of Methicillin-Resistant Staphylococcus aureus▿ †

Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen that has disseminated throughout Canadian hospitals and communities. Pulsed-field gel electrophoresis of over 9,300 MRSA isolates obtained from the Canadian Nosocomial Infection Surveillance Program has identified 10 epidemic strain types in Canada (CMRSA1 to CMRSA10). In an attempt to determine specific genetic factors that have contributed to their high prevalence in community and/or hospital settings, the genomic content of representative isolates for each of the 10 Canadian epidemic types was compared using comparative genomic hybridizations. Comparison of the community-associated Canadian epidemic isolates (CMRSA7 and CMRSA10) with the hospital-associated Canadian epidemic isolates revealed one open reading frame (ORF) (SACOL0046) encoding a putative protein belonging to a metallo-beta-lactamase family, which was present only in the community-associated Canadian epidemic isolates. A more restricted comparison involving only the most common hospital-associated Canadian epidemic isolates (CMRSA1 and CMRSA2) with the community-associated Canadian epidemic isolates did reveal additional factors that might be contributing to their prevalence in the community and hospital settings, which included ORFs encoding potential virulence factors involved in capsular biosynthesis, serine proteases, epidermin, adhesion factors, regulatory functions, leukotoxins, and exotoxins

Smokeless tobacco and oral potentially malignant disorders in South Asia: a protocol for a systematic review

INTRODUCTION: Oral potentially malignant disorders (OPMDs) are chronic lesions or conditions characterized by a potential for malignant transformation. Apart from being possible pre-cursors to oral cancer, OPMDs themselves are usually painful and debilitating conditions having an influence on the quality of life, both in terms of pain and social disability. Smokeless tobacco (SLT) use is considered a major risk factor for OPMDs. SLT use is a culturally and socially acceptable habit in South Asia. According to a recent report, 90 % of the SLT burden of the whole world lies in the South Asian countries of Pakistan, India, Sri Lanka, Bangladesh, Bhutan, Nepal, Afghanistan, and Maldives. This review aims to assess the association between the use of various SLT products in South Asia and risk of OPMDs. METHODS: This review will focus on epidemiological studies on the use of SLT and risk modification for OPMDs, which have been carried out in the human population of South Asian countries. Articles reporting estimates of relative risk, e.g., odds ratio (OR) or relative risk (RR) with their 95 % confidence intervals (CI) for SLT users versus non-users. Articles reporting data from which these effect estimates can be computed will be included in the review. We will search MEDLINE, the Science Citation Index (SCI), Scopus, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases for relevant literature using a combination of keywords and MeSH terms, where applicable. Appropriate sources of gray literature will also be included in the search. The electronic searches will be supplemented by a hand search of the bibliographies of the included articles. The included studies will be assessed for their quality using an established quality assessment tool. All relevant data from the included articles will be recorded in an MS Excel spread sheet and then transferred to Rev Man 5.3 to carry out a meta-analysis. Heterogeneity among the estimates will be assessed through the I(2) statistic. Sensitivity and subgroup analysis will be carried out to see the effects of individual or group of studies on the pooled effect estimate. Results of the review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. DISCUSSION: This review may have a potential limitation with regard to the designs of the studies included as we expect that most of the included studies will be of the observational types. We will however try to address this issue by conducting sensitivity and subgroup analysis of similar quality studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015029705. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13643-016-0320-7) contains supplementary material, which is available to authorized users

Time-to-Detection of Inducible Macrolide Resistance in Mycobacterium abscessus Subspecies and Its Association with the Erm(41) Sequevar.

Mutations in the erm(41) gene of M.abscessus group organisms are associated with differences in inducible macrolide resistance, with current recommendations being to hold rapidly growing isolates for up to 14 days in order to ensure that resistance which develops more slowly can be detected. This study aimed to determine the ideal incubation time for accurate identification of inducible macrolide resistance as well as to determine if there was an association between the time taken to detect inducible resistance in M.abscessus group organisms and their erm(41) sequevar. We amplified and sequenced the erm(41) genes of a total of 104 M.abscessus group isolates and determined their sequevars. The isolates were tested for phenotypic clarithromycin resistance at days 7, 10, 14 and 21, using Trek Diagnostics Sensititre RAPMYCO microbroth dilution plates. Associations between erm(41) gene sequevars and time to detection of resistance were evaluated using Fisher's exact test in R. The samples included in this study fell into 14 sequevars, with the majority of samples falling into Sequevar02 (16), Sequevar06 (15), Sequevar08 (7) and Sequvar 15 (31), and several isolates that were in small clusters, or unique. The majority (82.7%) of samples exhibiting inducible macrolide resistance were interpreted as resistant by day 7. Two isolates in Sequevar02, which has a T28C mutation that is associated with sensitivity, showed intermediate resistance at day 14, though the majority (13) were sensitive at day 14. The majority of isolates with inducible macrolide resistance fell into Sequevars 06,08 and 15, none of which contain the T28C mutation. These sequevars were analyzed to determine if there was any correlation between sequevar and time to detection of resistance. None was found. Based on these findings, we recommend the addition of a day 7 read to the CLSI guidelines to improve turn-around-times for these isolates. It is also recommended that erm(41) gene sequencing be added to routine phenotypic testing for the resolution of cases with difficult-to-interpret phenotypic results