Kinetics of viral self-assembly: the role of ss RNA antenna

A big class of viruses self-assemble from a large number of identical capsid proteins with long flexible N-terminal tails and ss RNA. We study the role of the strong Coulomb interaction of positive N-terminal tails with ss RNA in the kinetics of the in vitro virus self-assembly. Capsid proteins stick to unassembled chain of ss RNA (which we call "antenna") and slide on it towards the assembly site. We show that at excess of capsid proteins such one-dimensional diffusion accelerates self-assembly more than ten times. On the other hand at excess of ss RNA, antenna slows self-assembly down. Several experiments are proposed to verify the role of ss RNA antenna.Comment: 4 pages, 3 figures, several experiments are proposed, a new idea of experiment is adde

Notorious places: image, reputation, stigma: the role of newspapers in area reputations for social housing estates

This paper reviews work in several disciplines to distinguish between image, reputation and stigma. It also shows that there has been little research on the process by which area reputations are established and sustained through transmission processes. This paper reports on research into the portrayal of two social housing estates in the printed media over an extended period of time (14 years). It was found that negative and mixed coverage of the estates dominated, with the amount of positive coverage being very small. By examining the way in which dominant themes were used by newspapers in respect of each estate, questions are raised about the mode of operation of the press and the communities' collective right to challenge this. By identifying the way regeneration stories are covered and the nature of the content of positive stories, lessons are drawn for programmes of area transformation. The need for social regeneration activities is identified as an important ingredient for changing deprived-area reputations

Quantum mechanics and geodesic deviation in the brane world

We investigate the induced geodesic deviation equations in the brane world models, in which all the matter forces except gravity are confined on the 3-brane. Also, the Newtonian limit of induced geodesic deviation equation is studied. We show that in the first Randall-Sundrum model the Bohr-Sommerfeld quantization rule is as a result of consistency between the geodesic and geodesic deviation equations. This indicates that the path of test particle is made up of integral multiples of a fundamental Compton-type unit of length $h/mc$.Comment: 5 pages, no figure

Homophilic binding of PTP mu, a receptor-type protein tyrosine phosphatase, can mediate cell-cell aggregation

The receptor-like protein tyrosine phosphatase, PTPmu, displays structural similarity to cell-cell adhesion molecules of the immunoglobulin superfamily. We have investigated the ability of human PTPmu to function in such a capacity. Expression of PTPmu, with or without the PTPase domains, by recombinant baculovirus infection of Sf9 cells induced their aggregation. However, neither a chimeric form of PTPmu, containing the extracellular and transmembrane segments of the EGF receptor and the intracellular segment of PTPmu, nor the intracellular segment of PTPmu expressed as a soluble protein induced aggregation. PTPmu mediates aggregation via a homophilic mechanism, as judged by lack of incorporation of uninfected Sf9 cells into aggregates of PTPmu-expressing cells. Homophilic binding has been demonstrated between PTPmu-coated fluorescent beads (Covaspheres) and endogenously expressed PTPmu on MvLu cells. Additionally the PTPmu-coated beads specifically bound to a bacterially expressed glutathione-S-transferase fusion protein containing the extracellular segment of PTPmu (GST/PTPmu) adsorbed to petri dishes. Covaspheres coated with the GST/PTPmu fusion protein aggregated in vitro and also bound to PTPmu expressed endogenously on MvLu cells. These results suggest that the ligand for this transmembrane PTPase is another PTPmu molecule on an adjacent cell. Thus homophilic binding interactions may be an important component of the function of PTPmu in vivo

A study protocol for a randomised crossover study evaluating the effect of diets differing in carbohydrate quality on ileal content and appetite regulation in healthy humans

A major component of the digesta reaching the colon from the distal ileum is carbohydrate. This carbohydrate is subject to microbial fermentation and can radically change bacterial populations in the colon and the metabolites they produce, particularly short-chain fatty acids (SCFA). However, very little is currently known about the forms and levels of carbohydrate in the ileum and the composition of the ileal microbiota in humans. Most of our current understanding of carbohydrate that is not absorbed by the small intestine comes from ileostomy models, which may not reflect the physiology of an intact gastrointestinal tract. We will investigate how ileal content changes depending on diet using a randomised crossover study in healthy humans. Participants will be inpatients at the research facility for three separate 4-day visits. During each visit, participants will consume one of three diets, which differ in carbohydrate quality: 1) low-fibre refined diet; 2) high-fibre diet with intact cellular structures; 3) high-fibre diet where the cellular structures have been disrupted (e.g. milling, blending). On day 1, a nasoenteric tube will be placed into the distal ileum and its position confirmed under fluoroscopy. Ileal samples will be collected via the nasoenteric tube and metabolically profiled, which will determine the amount and type of carbohydrate present, and the composition of the ileal microbiota will be measured. Blood samples will be collected to assess circulating hormones and metabolites. Stool samples will be collected to assess faecal microbiota composition. Subjective appetite measures will be collected using visual analogue scales. Breath hydrogen will be measured in real-time as a marker of intestinal fermentation. Finally, an continuous fermentation model will be inoculated with ileal fluid in order to understand the shift in microbial composition and SCFA produced in the colon following the different diets. ISRCTN11327221. [Abstract copyright: Copyright: © 2019 Byrne CS et al.

β-Glucan is a major growth substrate for human gut bacteria related to Coprococcus eutactus

A clone encoding carboxymethyl cellulase activity was isolated during functional screening of a human gut metagenomic library using Lactococcus lactis MG1363 as heterologous host. The insert carried a glycoside hydrolase family 9 (GH9) catalytic domain with sequence similarity to a gene from Coprococcus eutactus ART55/1. Genome surveys indicated a limited distribution of GH9 domains among dominant human colonic anaerobes. Genomes of C. eutactus-related strains harboured two GH9-encoding and four GH5-encoding genes, but the strains did not appear to degrade cellulose. Instead, they grew well on β-glucans and one of the strains also grew on galactomannan, galactan, glucomannan and starch. Coprococcus comes and Coprococcus catus strains did not harbour GH9 genes and were not able to grow on β-glucans. Gene expression and proteomic analysis of C. eutactus ART55/1 grown on cellobiose, β-glucan and lichenan revealed similar changes in expression in comparison to glucose. On β-glucan and lichenan only, one of the four GH5 genes was strongly upregulated. Growth on glucomannan led to a transcriptional response of many genes, in particular a strong upregulation of glycoside hydrolases involved in mannan degradation. Thus, β-glucans are a major growth substrate for species related to C. eutactus, with glucomannan and galactans alternative substrates for some strains

Negative impact of the first COVID-19 lockdown upon health-related behaviours and psychological wellbeing in people living with severe and complex obesity in the UK

BACKGROUND: Coronavirus disease 2019 (COVID-19) has led to unprecedented changes in the way we live, particularly for people at higher risk of severe illness from COVID-19. People with pre-existing health conditions have been markedly impacted and, in some instances, left unsupported due to reduced provision of routine healthcare services. People living with obesity (PLWO) are identified as at higher risk of severe illness from COVID-19 infection. Currently, there is a paucity of evidence about the impact of the first COVID-19 lockdown on PLWO, including those accessing weight management and bariatric surgery services (WMS). METHODS: 543 adults (16–80 years) with obesity (BMI ≥ 30 kg/m2) were recruited between 14th May and 9th July 2020 through social media advertisements, professional and patient obesity organisations and WMS. Participants completed an online survey regarding the impact of the first COVID-19 lockdown upon, mental health, well-being, health-related behaviours, risk mitigating behaviours, access to WMS and weight stigma. FINDINGS: During the first COVID-19 lockdown, the majority of PLWO reported deterioration of their mental health and health-related behaviours such as diet, physical activity (PA) and sleep. With 55% reporting an unhealthier diet, 61% reduced PA and 80% worsening of their sleep. Higher depression and lower wellbeing scores were found to associate with the greatest adverse impact upon health-related behaviours. PLWO who were attending WMS prior to the first lockdown reported a greater deterioration of their diet, with nearly 50% reporting worsening of their diet and PA worsening compared to PLWO who were not attending WMS. Most participants took two or more risk mitigating actions (73%). PLWO attending WMS reported reduced access (44%) with insufficient information (49%) from their clinical service providers. The majority of participants reported no change in perceived weight stigma. INTERPRETATION: This study shows the detrimental impact of the first COVID-19 lockdown on PLWO in relation to health-related behaviours, mental health and access to WMS. Our findings show that PLWO with poor mental health and those attending WMS were most adversely impacted and highlights the need for greater mental health support and continued provision of support from WMS for PLWO during future lockdowns. FUNDING: This research was funded through National Institute for Health Research University College London Hospitals Biomedical Research Centre funding

Emerging applications in mass spectrometry imaging; enablers and roadblocks

Mass spectrometry imaging (MSI) is a powerful and versatile technique able to investigate the spatial distribution of multiple non-labelled endogenous and exogenous analytes simultaneously, within a wide range of samples. Over the last two decades, MSI has found widespread application for an extensive range of disciplines including pre-clinical drug discovery, clinical applications and human identification for forensic purposes. Technical advances in both instrumentation and software capabilities have led to a continual increase in the interest in MSI; however, there are still some limitations. In this review, we discuss the emerging applications in MSI that significantly impact three key areas of mass spectrometry (MS) research—clinical, pre-clinical and forensics—and roadblocks to the expansion of use of MSI in these areas

A Study of Lyman-Alpha Quasar Absorbers in the Nearby Universe

Spectroscopy of ten quasars obtained with the Goddard High Resolution Spectrograph (GHRS) of the Hubble Space Telescope (HST) is presented. A clustering analysis reveals an excess of nearest neighbor line pairs on velocity scales of 250-750 km/s at a 95-98% confidence level. The hypothesis that the absorbers are randomly distributed in velocity space can be ruled out at the 99.8% confidence level. No two-point correlation power is detected (xi < 1 with 95% confidence). Lyman-alpha absorbers have correlation amplitudes on scales of 250-500 km/s at least 4-5 times smaller than the correlation amplitude of bright galaxies. A detailed comparison between absorbers in nearby galaxies is carried out on a limited subset of 11 Lyman- alpha absorbers where the galaxy sample in a large contiguous volume is complete to M_B = -16. Absorbers lie preferentially in regions of intermediate galaxy density but it is often not possible to uniquely assign a galaxy counterpart to an absorber. This sample provides no explicit support for the hypothesis that absorbers are preferentially associated with the halos of luminous galaxies. We have made a preliminary comparison of the absorption line properties and environments with the results of hydrodynamic simulations. The results suggest that the Lyman-alpha absorbers represent diffuse or shocked gas in the IGM that traces the cosmic web of large scale structure. (abridged)Comment: 36 pages of text, 15 figures, 4 tables, 36 file

Damned if they do, damned if they don't: negotiating the tricky context of anti-social behaviour and keeping safe in disadvantaged urban neighbourhoods

Young people's relationship with anti-social behaviour (ASB) is complicated. While their behaviours are often stereotyped as anti-social (e.g. ‘hanging about’), they also experience ASB in their neighbourhood. In this study, we explore young people's own perspectives on ASB, comparing results from ‘go-along’ interviews and focus groups conducted in disadvantaged neighbourhoods in Glasgow, Scotland. This article discusses how young people's everyday experience of ASB was contextualised by social factors such as cultural stereotyping of marginalised groups, poor social connectivity and spatial marginalisation within their neighbourhood. Furthermore, we found that these social factors were mutually reinforcing and interacted in a way that appeared to leave young people in a ‘no-win’ situation regarding their association with ASB. Participation in ASB and attempts to avoid such involvement were seen to involve negative consequences: participation could entail violence and spatial restrictions linked to territoriality, but avoidance could lead to being ostracised from their peer group. Regardless of involvement, young people felt that adults stereotyped them as anti-social. Our findings therefore provide support for policies and interventions aimed at reducing ASB (perpetrated by residents of all ages); in part by better ensuring that young people have a clear incentive for avoiding such behaviours