The bacteriohopanepolyol inventory of novel aerobic methane oxidising bacteria reveals new biomarker signatures of aerobic methanotrophy in marine systems

Aerobic methane oxidation (AMO) is one of the primary biologic pathways regulating the amount of methane (CH4) released into the environment. AMO acts as a sink of CH4, converting it into carbon dioxide before it reaches the atmosphere. It is of interest for (paleo)climate and carbon cycling studies to identify lipid biomarkers that can be used to trace AMO events, especially at times when the role of methane in the carbon cycle was more pronounced than today. AMO bacteria are known to synthesise bacteriohopanepolyol (BHP) lipids. Preliminary evidence pointed towards 35-aminobacteriohopane-30,31,32,33,34-pentol (aminopentol) being a characteristic biomarker for Type I methanotrophs. Here, the BHP compositions were examined for species of the recently described novel Type I methanotroph bacterial genera Methylomarinum and Methylomarinovum, as well as for a novel species of a Type I Methylomicrobium. Aminopentol was the most abundant BHP only in Methylomarinovum caldicuralii, while Methylomicrobium did not produce aminopentol at all. In addition to the expected regular aminotriol and aminotetrol BHPs, novel structures tentatively identified as methylcarbamate lipids related to C-35 amino-BHPs (MCBHPs) were found to be synthesised in significant amounts by some AMO cultures. Subsequently, sediments and authigenic carbonates from methane-influenced marine environments were analysed. Most samples also did not contain significant amounts of aminopentol, indicating that aminopentol is not a useful biomarker for marine aerobic methanotophic bacteria. However, the BHP composition of the marine samples do point toward the novel MC-BHPs components being potential new biomarkers for AMO

Neuroactive substances specifically modulate rhythmic body contractions in the nerveless metazoon Tethya wilhelma (Demospongiae, Porifera)

BACKGROUND: Sponges (Porifera) are nerve- and muscleless metazoa, but display coordinated motor reactions. Therefore, they represent a valuable phylum to investigate coordination systems, which evolved in a hypothetical Urmetazoon prior to the central nervous system (CNS) of later metazoa. We have chosen the contractile and locomotive species Tethya wilhelma (Demospongiae, Hadromerida) as a model system for our research, using quantitative analysis based on digital time lapse imaging. In order to evaluate candidate coordination pathways, we extracorporeally tested a number of chemical messengers, agonists and antagonists known from chemical signalling pathways in animals with CNS. RESULTS: Sponge body contraction of T. wilhelma was induced by caffeine, glycine, serotonine, nitric oxide (NO) and extracellular cyclic adenosine monophosphate (cAMP). The induction by glycine and cAMP followed patterns varying from other substances. Induction by cAMP was delayed, while glycine lead to a bi-phasic contraction response. The frequency of the endogenous contraction rhythm of T. wilhelma was significantly decreased by adrenaline and NO, with the same tendency for cAMP and acetylcholine. In contrast, caffeine and glycine increased the contraction frequency. The endogenous rhythm appeared irregular during application of caffeine, adrenaline, NO and cAMP. Caffeine, glycine and NO attenuated the contraction amplitude. All effects on the endogenous rhythm were neutralised by the washout of the substances from the experimental reactor system. CONCLUSION: Our study demonstrates that a number of chemical messengers, agonists and antagonists induce contraction and/or modulate the endogenous contraction rhythm and amplitude of our nerveless model metazoon T. wilhelma. We conclude that a relatively complex system of chemical messengers regulates the contraction behaviour through auto- and paracrine signalling, which is presented in a hypothetical model. We assume that adrenergic, adenosynergic and glycinergic pathways, as well as pathways based on NO and extracellular cAMP are candidates for the regulation and timing of the endogenous contraction rhythm within pacemaker cells, while GABA, glutamate and serotonine are candidates for the direct coordination of the contractile cells

Towards Alignment Independent Quantitative Assessment of Homology Detection

Identification of homologous proteins provides a basis for protein annotation. Sequence alignment tools reliably identify homologs sharing high sequence similarity. However, identification of homologs that share low sequence similarity remains a challenge. Lowering the cutoff value could enable the identification of diverged homologs, but also introduces numerous false hits. Methods are being continuously developed to minimize this problem. Estimation of the fraction of homologs in a set of protein alignments can help in the assessment and development of such methods, and provides the users with intuitive quantitative assessment of protein alignment results. Herein, we present a computational approach that estimates the amount of homologs in a set of protein pairs. The method requires a prevalent and detectable protein feature that is conserved between homologs. By analyzing the feature prevalence in a set of pairwise protein alignments, the method can estimate the number of homolog pairs in the set independently of the alignments' quality. Using the HomoloGene database as a standard of truth, we implemented this approach in a proteome-wide analysis. The results revealed that this approach, which is independent of the alignments themselves, works well for estimating the number of homologous proteins in a wide range of homology values. In summary, the presented method can accompany homology searches and method development, provides validation to search results, and allows tuning of tools and methods

Cosmogenic neutron production at the Sudbury Neutrino Observatory

Neutrons produced in nuclear interactions initiated by cosmic-ray muons present an irreducible background to many rare-event searches, even in detectors located deep underground. Models for the production of these neutrons have been tested against previous experimental data, but the extrapolation to deeper sites is not well understood. Here we report results from an analysis of cosmogenically produced neutrons at the Sudbury Neutrino Observatory. A specific set of observables are presented, which can be used to benchmark the validity of geant4 physics models. In addition, the cosmogenic neutron yield, in units of 10-4 cm2/(g·μ), is measured to be 7.28±0.09(stat)-1.12+1.59(syst) in pure heavy water and 7.30±0.07(stat)-1.02+1.40(syst) in NaCl-loaded heavy water. These results provide unique insights into this potential background source for experiments at SNOLAB

Deep gene sequence cluster analyses of multi-virus-infected mucosal tissue reveal enhanced transmission of acute HIV-1

Exposure of the genital mucosa to a genetically diverse viral swarm from the donor HIV-1 can result in breakthrough and systemic infection by a single transmitted/founder (TF) virus in the recipient. The highly diverse HIV-1 envelope (Env) in this inoculating viral swarm may have a critical role in transmission and subsequent immune response. Thus, chronic (Envchronic) and acute (Envacute) Env chimeric HIV-1 were tested using multivirus competition assays in human mucosal penile and cervical tissues. Viral competition analysis revealed that Envchronic viruses resided and replicated mainly in the tissue, while Envacute viruses penetrated the human tissue and established infection of CD4+ T cells more efficiently. Analysis of the replication fitness, as tested in peripheral blood mononuclear cells (PBMCs), showed similar replication fitness of Envacute and Envchronic viruses, which did not correlate with transmission fitness in penile tissue. Further, we observed that chimeric Env viruses with higher replication in genital mucosal tissue (chronic Env viruses) had higher binding affinity to C-type lectins. Data presented herein suggest that the inoculating HIV-1 may be sequestered in the genital mucosal tissue (represented by chronic Env HIV-1) but that a single HIV-1 clone (e.g., acute Env HIV-1) can escape this trapped replication for systemic infection

Chronic pain in primary care. German figures from 1991 and 2006

<p>Abstract</p> <p>Background</p> <p>Until now only limited research has been done on the prevalence of chronic pain in primary care. The aim of this investigation was to study the health care utilisation of patients suffering from pain. How many patients visit an outpatient clinic because of the symptom of pain? These data were compared with data from a similar study in 1991, to investigate whether improvements had been achieved.</p> <p>Methods</p> <p>A total of 1201 consecutive patients visiting outpatient clinics were surveyed in six practices in the western part of Germany on randomly selected days by means of questionnaires. Topics were the point prevalence of pain and the period prevalence of chronic pain, its characteristics and its impact on daily life, as well as data on previous therapies for pain. A retrospective comparison was made with the data from a similar study with same design surveying 900 patients that took place in five practices during 1991.</p> <p>Results</p> <p>In 2006, pain was the main reason for consulting a doctor in 42.5% of all patients (1991: 50.3%). Of all respondents, 62% suffered from pain on the particular day of the consultation, and 40% reported that they had been suffering from pain for more than six months (1991: 36.4%). As many as 88.3% of patients with chronic pain reported a negative impact on their daily life due to this pain (1991: 68%), and 88.1% reported impairment of their working life because of chronic pain (1991: 59.1%).</p> <p>Conclusion</p> <p>Pain, and chronic pain in particular, is a central problem in primary care. Over the last 15 years, the number of patients suffering from chronic pain has not decreased. In nearly half of all cases, pain is still the reason for health care utilisation in outpatient clinics. Pain represents a major primary health care problem with enormous impact on public health. Improvements can only be achieved by improving the quality of health care at the primary care level.</p

SARS-CoV-2 outbreak in a tri-national urban area is dominated by a B.1 lineage variant linked to a mass gathering event.

The first case of SARS-CoV-2 in Basel, Switzerland was detected on February 26th 2020. We present a phylogenetic study to explore viral introduction and evolution during the exponential early phase of the local COVID-19 outbreak from February 26th until March 23rd. We sequenced SARS-CoV-2 naso-oropharyngeal swabs from 746 positive tests that were performed at the University Hospital Basel during the study period. We successfully generated 468 high quality genomes from unique patients and called variants with our COVID-19 Pipeline (COVGAP), and analysed viral genetic diversity using PANGOLIN taxonomic lineages. To identify introduction and dissemination events we incorporated global SARS-CoV-2 genomes and inferred a time-calibrated phylogeny. Epidemiological data from patient questionnaires was used to facilitate the interpretation of phylogenetic observations. The early outbreak in Basel was dominated by lineage B.1 (83·6%), detected first on March 2nd, although the first sample identified belonged to B.1.1. Within B.1, 68·2% of our samples fall within a clade defined by the SNP C15324T ('Basel cluster'), including 157 identical sequences at the root of the 'Basel cluster', some of which we can specifically trace to regional spreading events. We infer the origin of B.1-C15324T to mid-February in our tri-national region. The other genomes map broadly over the global phylogenetic tree, showing several introduction events from and/or dissemination to other regions of the world via travellers. Family transmissions can also be traced in our data. A single lineage variant dominated the outbreak in the Basel area while other lineages, such as the first (B.1.1), did not propagate. A mass gathering event was the predominant initial source of cases, with travel returners and family transmissions to a lesser extent. We highlight the importance of adding specific questions to epidemiological questionnaires, to obtain data on attendance of large gatherings and their locations, as well as travel history, to effectively identify routes of transmissions in up-coming outbreaks. This phylogenetic analysis in concert with epidemiological and contact tracing data, allows connection and interpretation of events, and can inform public health interventions. Trial Registration: ClinicalTrials.gov NCT04351503

Peer role-play and standardised patients in communication training: a comparative study on the student perspective on acceptability, realism, and perceived effect

<p>Abstract</p> <p>Background</p> <p>To assess the student perspective on acceptability, realism, and perceived effect of communication training with peer role play (RP) and standardised patients (SP).</p> <p>Methods</p> <p>69 prefinal year students from a large German medical faculty were randomly assigned to one of two groups receiving communication training with RP (N = 34) or SP (N = 35) in the course of their paediatric rotation. In both groups, training addressed major medical and communication problems encountered in the exploration and counselling of parents of sick children. Acceptability and realism of the training as well as perceived effects and applicability for future parent-physician encounters were assessed using six-point Likert scales.</p> <p>Results</p> <p>Both forms of training were highly accepted (RP 5.32 ± .41, SP 5.51 ± .44, n.s.; 6 = very good, 1 = very poor) and perceived to be highly realistic (RP 5.60 ± .38, SP 5.53 ± .36, n.s.; 6 = highly realistic, 1 = unrealistic). Regarding perceived effects, participation was seen to be significantly more worthwhile in the SP group (RP 5.17 ± .37, SP 5.50 ± .43; p < .003; 6 = totally agree, 1 = don't agree at all). Both training methods were perceived as useful for training communication skills (RP 5.01 ± .68, SP 5.34 ± .47; 6 = totally agree; 1 = don't agree at all) and were considered to be moderately applicable for future parent-physician encounters (RP 4.29 ± 1.08, SP 5.00 ± .89; 6 = well prepared, 1 = unprepared), with usefulness and applicability both being rated higher in the SP group (p < .032 and p < .009).</p> <p>Conclusions</p> <p>RP and SP represent comparably valuable tools for the training of specific communication skills from the student perspective. Both provide highly realistic training scenarios and warrant inclusion in medical curricula. Given the expense of SP, deciding which method to employ should be carefully weighed up. From the perspective of the students in our study, SP were seen as a more useful and more applicable tool than RP. We discuss the potential of RP to foster a greater empathic appreciation of the patient perspective.</p