Vacuum-UV negative photoion spectroscopy of CH4

Using synchrotron radiation in the range 12-35 eV, negative ions are detected by mass spectrometry following vacuum-UV photoexcitation of methane. Ion yields for H$^-$, CH$^-$ and CH$_2^-$ are recorded, the spectra of CH$^-$ and CH$_2^-$ for the first time. All ions display a linear dependence of signal with pressure, showing that they arise from unimolecular ion-pair dissociation. Cross sections for ion-pair formation are put onto an absolute scale by calibrating the signal strengths with those of F$^-$ from SF$_6$ and CF$_4$. Following normalisation to total vacuum-UV absorption cross sections, quantum yields for anion production are reported. There is a major discrepancy in the H$^-$ cross section with an earlier measurement, which remains unresolved. The anions arise from both direct and indirect ion-pair mechanisms. For a generic polyatomic molecule AB, the former is defined as AB $\rightarrow$ A$^-$ + B$^+$ (+ neutrals), the latter as the predissociative crossing of an initially-excited Rydberg state of AB by an ion-pair state. In a separate experiment, the threshold photoelectron spectrum of the second valence band of CH$_4$, ionisation to CH$_4^+$ A $^2$A$_1$ at 22.4 eV, is recorded with an instrumental resolution of 0.004 eV; many of the Rydberg states observed in indirect ion-pair formation converge to this state. The widths of the peaks are lifetime limited, increasing with increasing $v$ in the $v_1$ (a$_1$) vibrational ladder. They are the first direct measurement of an upper value to the dissociation rate of these levels into fragment ions

Resistance to antibiotics of clinical relevance in the fecal microbiota of Mexican wildlife.

There are a growing number of reports of antibiotic resistance (ATBR) in bacteria living in wildlife. This is a cause for concern as ATBR in wildlife represents a potential public health threat. However, little is known about the factors that might determine the presence, abundance and dispersion of ATBR bacteria in wildlife. Here, we used culture and molecular methods to assess ATBR in bacteria in fecal samples from howler monkeys (Alouatta palliata), spider monkeys (Ateles geoffroyi), tapirs (Tapirus bairdii) and felids (jaguars, Panthera onca; pumas, Puma concolor; jaguarundis, Puma yagouaroundi; and ocelots, Leopardus pardalis) living freely in two regions of the Mexican state of Veracruz under different degrees of human influence. Overall, our study shows that ATBR is commonplace in bacteria isolated from wildlife in southeast Mexico. Most of the resistances were towards old and naturally occurring antibiotics, but we also observed resistances of potential clinical significance. We found that proximity to humans positively affected the presence of ATBR and that ATBR was higher in terrestrial than arboreal species. We also found evidence suggesting different terrestrial and aerial routes for the transmission of ATBR between humans and wildlife. The prevalence and potential ATBR transfer mechanisms between humans and wildlife observed in this study highlight the need for further studies to identify the factors that might determine ATBR presence, abundance and distribution.The authors acknowledge the National Council of Science of Technology (CONACYT) in Mexico and the Veracruz State Government for providing partial financial support to JCA (Grant Number 108990). JCD was supported by grants from the Isaac Newton Trust and The Cambridge Humanities Research Grant Scheme. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final published version. It originally appeared in PLOS One at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0107719

Perturbation with Intrabodies Reveals That Calpain Cleavage Is Required for Degradation of Huntingtin Exon 1

Background: Proteolytic processing of mutant huntingtin (mHtt), the protein that causes Huntington's disease (HD), is critical for mHtt toxicity and disease progression. mHtt contains several caspase and calpain cleavage sites that generate N-terminal fragments that are more toxic than full-length mHtt. Further processing is then required for the degradation of these fragments, which in turn, reduces toxicity. This unknown, secondary degradative process represents a promising therapeutic target for HD. Methodology/Principal Findings: We have used intrabodies, intracellularly expressed antibody fragments, to gain insight into the mechanism of mutant huntingtin exon 1 (mHDx-1) clearance. Happ1, an intrabody recognizing the proline-rich region of mHDx-1, reduces the level of soluble mHDx-1 by increasing clearance. While proteasome and macroautophagy inhibitors reduce turnover of mHDx-1, Happ1 is still able to reduce mHDx-1 under these conditions, indicating Happ1-accelerated mHDx-1 clearance does not rely on these processes. In contrast, a calpain inhibitor or an inhibitor of lysosomal pH block Happ1-mediated acceleration of mHDx-1 clearance. These results suggest that mHDx-1 is cleaved by calpain, likely followed by lysosomal degradation and this process regulates the turnover rate of mHDx-1. Sequence analysis identifies amino acid (AA) 15 as a potential calpain cleavage site. Calpain cleavage of recombinant mHDx-1 in vitro yields fragments of sizes corresponding to this prediction. Moreover, when the site is blocked by binding of another intrabody, V_L12.3, turnover of soluble mHDx-1 in living cells is blocked. Conclusions/Significance: These results indicate that calpain-mediated removal of the 15 N-terminal AAs is required for the degradation of mHDx-1, a finding that may have therapeutic implications

Meditation Awareness Training (MAT) for Work-related Wellbeing and Job Performance: A Randomised Controlled Trial

Due to its potential to concurrently improve work-related wellbeing (WRW) and job performance, occupational stakeholders are becoming increasingly interested in the applications of meditation. The present study conducted the first randomized controlled trial to assess the effects of meditation on outcomes relating to both WRW and job performance. Office-based middle-hierarchy managers (n = 152) received an eight-week meditation intervention (Meditation Awareness Training; MAT) or an active control intervention. MAT participants demonstrated significant and sustainable improvements (with strong effect sizes) over control-group participants in levels of work-related stress, job satisfaction, psychological distress, and employer-rated job performance. There are a number of novel implications: (i) meditation can effectuate a perceptual shift in how employees experience their work and psychological environment and may thus constitute a cost-effective WRW intervention, (ii) meditation-based (i.e., present-moment-focussed) working styles may be more effective than goal-based (i.e., future-orientated) working styles, and (iii) meditation may reduce the separation made by employees between their own interests and those of the organizations they work for

Design considerations in a clinical trial of a cognitive behavioural intervention for the management of low back pain in primary care : Back Skills Training Trial

Background Low back pain (LBP) is a major public health problem. Risk factors for the development and persistence of LBP include physical and psychological factors. However, most research activity has focused on physical solutions including manipulation, exercise training and activity promotion. Methods/Design This randomised controlled trial will establish the clinical and cost-effectiveness of a group programme, based on cognitive behavioural principles, for the management of sub-acute and chronic LBP in primary care. Our primary outcomes are disease specific measures of pain and function. Secondary outcomes include back beliefs, generic health related quality of life and resource use. All outcomes are measured over 12 months. Participants randomised to the intervention arm are invited to attend up to six weekly sessions each of 90 minutes; each group has 6–8 participants. A parallel qualitative study will aid the evaluation of the intervention. Discussion In this paper we describe the rationale and design of a randomised evaluation of a group based cognitive behavioural intervention for low back pain

Bias and heteroscedastic memory error in self-reported health behavior: an investigation using covariance structure analysis

BACKGROUND: Frequent use of self-reports for investigating recent and past behavior in medical research requires statistical techniques capable of analyzing complex sources of bias associated with this methodology. In particular, although decreasing accuracy of recalling more distant past events is commonplace, the bias due to differential in memory errors resulting from it has rarely been modeled statistically. METHODS: Covariance structure analysis was used to estimate the recall error of self-reported number of sexual partners for past periods of varying duration and its implication for the bias. RESULTS: Results indicated increasing levels of inaccuracy for reports about more distant past. Considerable positive bias was found for a small fraction of respondents who reported ten or more partners in the last year, last two years and last five years. This is consistent with the effect of heteroscedastic random error where the majority of partners had been acquired in the more distant past and therefore were recalled less accurately than the partners acquired more recently to the time of interviewing. CONCLUSIONS: Memory errors of this type depend on the salience of the events recalled and are likely to be present in many areas of health research based on self-reported behavior

Regulation of Apoptotic Mediators Reveals Dynamic Responses to Thermal Stress in the Reef Building Coral Acropora millepora

Background: Mass coral bleaching is increasing in scale and frequency across the world's coral reefs and is being driven primarily by increased levels of thermal stress arising from global warming. In order to understand the impacts of projected climate change upon corals reefs, it is important to elucidate the underlying cellular mechanisms that operate during coral bleaching and subsequent mortality. In this respect, increased apoptotic cell death activity is an important cellular process that is associated with the breakdown of the mutualistic symbiosis between the cnidarian host and their dinoflagellate symbionts

Clinical course, characteristics and prognostic indicators in patients presenting with back and leg pain in primary care. The ATLAS study protocol

Low-back related leg pain with or without nerve root involvement is associated with a poor prognosis compared to low back pain (LBP) alone. Compared to the literature investigating prognostic indicators of outcome for LBP, there is limited evidence on prognostic factors for low back-related leg pain including the group with nerve root pain. This 1 year prospective consultation-based observational cohort study will describe the clinical, imaging, demographic characteristics and health economic outcomes for the whole cohort, will investigate differences and identify prognostic indicators of outcome (i.e. change in disability at 12 months), for the whole cohort and, separately, for those classified with and without nerve root pain. In addition, nested qualitative studies will provide insights on the clinical consultation and the impact of diagnosis and treatment on patients' symptom management and illness trajectory