Analysis of gas chromatography/mass spectrometry data for catalytic lignin depolymerization using positive matrix factorization

Various catalytic technologies are being developed to efficiently convert lignin into renewable chemicals. However, due to its complexity, catalytic lignin depolymerization often generates a wide and complex distribution of product compounds. Gas chromatography/mass spectrometry (GC-MS) is a common analytical technique to profile the compounds that comprise lignin depolymerization products. GC-MS is applied not only to determine the product composition, but also to develop an understanding of the catalytic reaction pathways and of the relationships among catalyst structure, reaction conditions, and the resulting compounds generated. Although a very useful tool, the analysis of lignin depolymerization products with GC-MS is limited by the quality and scope of the available mass spectral libraries and the ability to correlate changes in GC-MS chromatograms to changes in lignin structure, catalyst structure, and other reaction conditions. In this study, the GC-MS data of the depolymerization products generated from organosolv hybrid poplar lignin using a copper-doped porous metal oxide catalyst and a methanol/dimethyl carbonate co-solvent was analyzed by applying a factor analysis technique, positive matrix factorization (PMF). Several different solutions for the PMF model were explored. A 13-factor solution sufficiently explains the chemical changes occurring to lignin depolymerization products as a function of lignin, reaction time, catalyst, and solvent. Overall, seven factors were found to represent aromatic compounds, while one factor was defined by aliphatic compounds

Genome-wide association study suggests that variation at the RCOR1 locus is associated with tinnitus in UK Biobank

Tinnitus is a prevalent condition in which perception of sound occurs without an external stimulus. It is often associated with pre-existing hearing loss or noise-induced damage to the auditory system. In some individuals it occurs frequently or even continuously and leads to considerable distress and difficulty sleeping. There is little knowledge of the molecular mechanisms involved in tinnitus which has hindered the development of treatments. Evidence suggests that tinnitus has a heritable component although previous genetic studies have not established specific risk factors. From a total of 172,608 UK Biobank participants who answered questions on tinnitus we performed a case-control genome-wide association study for self-reported tinnitus. Final sample size used in association analysis was N = 91,424. Three variants in close proximity to the RCOR1 gene reached genome wide significance: rs4906228 (p = 1.7E-08), rs4900545 (p = 1.8E-08) and 14:103042287_CT_C (p = 3.50E-08). RCOR1 encodes REST Corepressor 1, a component of a co-repressor complex involved in repressing neuronal gene expression in non-neuronal cells. Eleven other independent genetic loci reached a suggestive significance threshold of p < 1E-06

Stability of the fragments and thermalization at peak center-of-mass energy

We simulate the central reactions of nearly symmetric, and asymmetric systems, for the energies at which the maximum production of IMFs occurs (E$_{c.m.}^{peak}$).This study is carried out by using hard EOS along with cugnon cross section and employing MSTB method for clusterization. We study the various properties of fragments. The stability of fragments is checked through persistence coefficient and gain term. The information about the thermalization and stopping in heavy-ion collisions is obtained via relative momentum, anisotropy ratio, and rapidity distribution. We find that for a complete stopping of incoming nuclei very heavy systems are required. The mass dependence of various quantities (such as average and maximum central density, collision dynamics as well as the time zone for hot and dense nuclear matter) is also presented. In all cases (i.e., average and maximum central density, collision dynamics as well as the time zone for hot and dense nuclear matter) a power law dependence is obtained.Comment: 21 Pages, 8 Figure

Does Dysbiosis Play a Role in Age-Related Hearing Impairment?

Age-related hearing impairment (ARHI) is prevalent in older adults, affecting at least 60% of people by the time they reach 71 to 80 years of age.1 The number of people with ARHI will necessarily increase as humans live longer and a greater proportion of the population is older.2 Hearing loss does not just impact communication; it is associated with loneliness and depression, cognitive decline and dementia, as well as reduced physical well-being.3-6 A decade ago, an international report calculated that hearing loss cost Europe £213 billion annually.7 There is currently no effective drug treatment for hearing loss. Hearing aids (average cost £2,300/pair) are the most commonly prescribed ameliorative therapy, but uptake is low; and among those who obtain hearing aids, a high proportion do not use them or are dissatisfied with them. Hearing loss prevention is therefore of compelling necessity, and genetic studies will help us understand how and why people lose their hearing ability and will inform prevention strategies

Consumer perceptions and purchasing of packaged water products in Sierra Leone

Introduction: access to improved sources of drinking water remains a complex challenge in Sierra Leone and other low and middle income countries. We aimed to qualitatively examine consumer perceptions and purchasing behaviors of packaged water products in Sierra Leone. Methods: we conducted 25 focus groups with 178 consumers and petty traders of packaged water across the four geographic regions of Sierra Leone. Discussions were recorded, transcribed, and coded into themes. The Health Belief Model guided the thematic data analysis. Results: packaged water was broadly perceived as safe, accessible, and convenient. Participants who lived outside of the capital city, Freetown, were more likely to report cost as a barrier. Personal experiences with a brand moderated trust levels. Self-reported handling behaviors of PW products were generally unhygienic. There was widespread belief that packaged water keeps newborn babies healthy. Consumers desired a simple mechanism to better identify government approved PW products. Conclusion: perceived risks, benefits, barriers, self-efficacy, and reinforcing cues to action qualitatively influenced consumers’ purchasing behavior of packaged water. Government regulators should provide consumers with reliable means to identify approved packaged water products. Consumer education efforts should include hygienic handling of packaged water products in order to minimize post-production contamination

Self-reported hearing loss questions provide a good measure for genetic studies: a polygenic risk score analysis from UK Biobank

Age-related hearing impairment (ARHI) is very common in older adults and has major impact on quality of life. The heritability of ARHI has been estimated to be around 50%. The present study aimed to estimate heritability and environmental contributions to liability of ARHI and the extent to which a polygenic risk score (PRS) derived from a recent genome-wide association study of questionnaire items regarding hearing loss using the UK Biobank is predictive of hearing loss in other samples. We examined (1) a sample from TwinsUK who have had hearing ability measured by pure-tone audiogram and the speech-to-noise ratio test as well as questionnaire measures that are comparable with the UK Biobank questionnaire items and (2) European and non-European samples from the UK Biobank which were not part of the original GWAS. Results indicated that the questionnaire items were over 50% heritable in TwinsUK and comparable with the objective hearing measures. In addition, we found very high genetic correlation (0.30–0.84) between the questionnaire responses and objective hearing measures in the TwinsUK sample. Finally, PRS computed from weighted UK Biobank GWAS results were predictive of both questionnaire and objective measures of hearing loss in the TwinsUK sample, as well as questionnaire-measured hearing loss in Europeans but not non-European subpopulations. These results demonstrate the utility of questionnaire-based methods in genetic association studies of hearing loss in adults and highlight the differences in genetic predisposition to ARHI by ethnic background

Flecainide reduces Ca2+ spark and wave frequency via inhibition of the sarcolemmal sodium current

AIMS: Ca(2+) waves are thought to be important in the aetiology of ventricular tachyarrhythmias. There have been conflicting results regarding whether flecainide reduces Ca(2+) waves in isolated cardiomyocytes. We sought to confirm whether flecainide inhibits waves in the intact cardiomyocyte and to elucidate the mechanism. METHODS AND RESULTS: We imaged spontaneous sarcoplasmic reticulum (SR) Ca(2+) release events in healthy adult rat cardiomyocytes. Variation in stimulation frequency was used to produce Ca(2+) sparks or waves. Spark frequency, wave frequency, and wave velocity were reduced by flecainide in the absence of a reduction of SR Ca(2+) content. Inhibition of I(Na) via alternative pharmacological agents (tetrodotoxin, propafenone, or lidocaine) produced similar changes. To assess the contribution of I(Na) to spark and wave production, voltage clamping was used to activate contraction from holding potentials of −80 or −40 mV. This confirmed that reducing Na(+) influx during myocyte stimulation is sufficient to reduce waves and that flecainide only causes Ca(2+) wave reduction when I(Na) is active. It was found that Na(+)/Ca(2+)-exchanger (NCX)-mediated Ca(2+) efflux was significantly enhanced by flecainide and that the effects of flecainide on wave frequency could be reversed by reducing [Na(+)](o), suggesting an important downstream role for NCX function. CONCLUSION: Flecainide reduces spark and wave frequency in the intact rat cardiomyocyte at therapeutically relevant concentrations but the mechanism involves I(Na) reduction rather than direct ryanodine receptor (RyR2) inhibition. Reduced I(Na) results in increased Ca(2+) efflux via NCX across the sarcolemma, reducing Ca(2+) concentration in the vicinity of the RyR2

Treatment response in rheumatoid arthritis is predicted by the microbiome: a large observational study in UK DMARD-naïve patients.

OBJECTIVES: Disease-modifying antirheumatic drugs (DMARDs) are first line treatment in rheumatoid arthritis (RA). Treatment response to DMARDs is patient-specific, dose efficacy is difficult to predict and long-term results variable. The gut microbiota are known to play a pivotal role in prodromal and early-disease RA, manifested by Prevotella spp. enrichment. The clinical response to therapy may be mediated by microbiota, and large-scale studies assessing the microbiome are few. This study assessed whether microbiome signals were associated with, and predictive of, patient response to DMARD-treatment. Accurate early identification of those who will respond poorly to DMARD therapy would allow selection of alternative treatment (e.g. biologic therapy), and potentially improve patient outcome. METHODS: A multicentre, longitudinal, observational study of stool- and saliva microbiome was performed in DMARD-naïve, newly diagnosed RA patients during introduction of DMARD treatment. Clinical data and samples were collected at baseline (n = 144) in DMARD-naïve patients and at six weeks (n = 117) and 12 weeks (n = 95) into DMARD-therapy. Samples collected (n = 365 stool, n = 365 saliva) underwent shotgun sequencing. Disease activity measures were collected at each timepoint and minimal clinically important improvement determined. RESULTS: In total, 26 stool microbes were found to decrease in those manifesting a minimal clinically important improvement. Prevotella spp. and Streptococcus spp. were the predominant taxa to decline following six weeks and 12 weeks of DMARDs, respectively. Furthermore, baseline microbiota of DMARD-naïve patients were indicative of future response. CONCLUSION: DMARDs appear to restore a perturbed microbiome to a eubiotic state. Moreover, microbiome status can be used to predict likelihood of patient response to DMARD

No evidence of association between either Modic change or disc degeneration and five circulating inflammatory proteins.

INTRODUCTION: Intervertebral disc degeneration and Modic change are the main spinal structural changes associated with chronic low back pain (LBP). Both conditions are thought to manifest local inflammation and if inflammatory proteins translocate to the blood circulation could be detected systemically. The work here assesses whether the presence of disc degeneration is associated with detectable blood level changes of five inflammatory markers and whether chronic LBP is associated with these changes. MATERIALS AND METHODS: Two hundred and forty TwinsUK cohort participants with both MRI disc degeneration grade and Modic change extent, and IL-6, IL-8, IL-8 TNF, and CX3CL1 protein blood concentration measurements were included in this work. Linear mixed effects models were used to test the association of blood cytokine concentration with disc degeneration score and Modic change volumetric score. Association of chronic LBP status from questionnaires with disc degeneration, Modic change, and cytokine blood concentration was also tested. RESULTS: No statistically significant association between disc degeneration or Modic change with cytokine blood concentration was found. Instead, regression analysis pointed strong association between cytokine blood concentration with body mass index for IL-6 and with age for IL-6 and TNF. Mild association was found between IL-8 blood concentration and body mass index. Additionally, LBP status was associated with Modic change volumetric score but not associated with any cytokine concentration. CONCLUSIONS: We found no evidence that Modic change and disc degeneration are able to produce changes in tested blood cytokine concentration. However, age and body mass index have strong influence on cytokine concentration and both are associated with the conditions studied which may confound associations found in the literature. It is then unlikely that cytokines produced in the disc or vertebral bone marrow induce chronic LBP