Diverse hepatitis C virus glycoproteins mediate viral infection in a CD81-dependent manner

We recently reported that retroviral pseudotypes bearing the hepatitis C virus (HCV) strain H and Con1 glycoproteins, genotype 1a and 1b, respectively, require CD81 as a coreceptor for virus-cell entry and infection. Soluble truncated E2 cloned from a number of diverse HCV genotypes fail to interact with CD81, suggesting that viruses of diverse origin may utilize different receptors and display altered cell tropism. We have used the pseudotyping system to study the tropism of viruses bearing diverse HCV glycoproteins. Viruses bearing these glycoproteins showed a 150-fold range in infectivity for hepatoma cells and failed to infect lymphoid cells. The level of glycoprotein incorporation into particles varied considerably between strains, generally reflecting the E2 expression level within transfected cells. However, differences in glycoprotein incorporation were not associated with virus infectivity, suggesting that infectivity is not limited by the absolute level of glycoprotein. All HCV pseudotypes failed to infect HepG2 cells and yet infected the same cells after transduction to express human CD81, confirming the critical role of CD81 in HCV infection. Interestingly, these HCV pseudotypes differed in their ability to infect HepG2 cells expressing a panel of CD81 variants, suggesting subtle differences in the interaction of CD81 residues with diverse viral glycoproteins. Our current model of HCV infection suggests that CD81, together with additional unknown liver specific receptor(s), mediate the virus-cell entry process

1916-09-23; Letter, from E. T. Meredith, Topeka (Kan.), to Oscar W. Schaeffer, Girard (Kan.)

Typewritten letter from E. T. Meredith, President, to Oscar W. Schaeffer, dated September 23, 1916

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

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.

Remarkably robust and correlated coherence and antiferromagnetism in (Ce1−x_{1-x}Lax_x)Cu2_2Ge2_2

We present magnetic susceptibility, resistivity, specific heat, and thermoelectric power measurements on (Ce$_{1-x}$La$_x$)Cu$_2$Ge$_2$ single crystals (0 $\leq x\leq$ 1). With La substitution, the antiferromagnetic temperature $T_N$ is suppressed in an almost linear fashion and moves below 0.36 K, the base temperature of our measurements for $x>$ 0.8. Surprisingly, in addition to robust antiferromagnetism, the system also shows low temperature coherent scattering below $T_{coh}$ up to $\sim$ 0.9 of La, indicating a small percolation limit $\sim$ 9$\%$ of Ce that separates a coherent regime from a single-ion Kondo impurity regime. $T_{coh}$ as a function of magnetic field was found to have different behavior for $x$ 0.9. Remarkably, $(T_{coh})^2$ at $H$ = 0 was found to be linearly proportional to $T_N$. The jump in the magnetic specific heat $\delta C_{m}$ at $T_N$ as a function of $T_K/T_N$ for (Ce$_{1-x}$La$_x$)Cu$_2$Ge$_2$ follows the theoretical prediction based on the molecular field calculation for the $S$ = 1/2 resonant level model

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

Individual aggregates of amyloid beta induce temporary calcium influx through the cell membrane of neuronal cells.

Local delivery of amyloid beta oligomers from the tip of a nanopipette, controlled over the cell surface, has been used to deliver physiological picomolar oligomer concentrations to primary astrocytes or neurons. Calcium influx was observed when as few as 2000 oligomers were delivered to the cell surface. When the dosing of oligomers was stopped the intracellular calcium returned to basal levels or below. Calcium influx was prevented by the presence in the pipette of the extracellular chaperone clusterin, which is known to selectively bind oligomers, and by the presence a specific nanobody to amyloid beta. These data are consistent with individual oligomers larger than trimers inducing calcium entry as they cross the cell membrane, a result supported by imaging experiments in bilayers, and suggest that the initial molecular event that leads to neuronal damage does not involve any cellular receptors, in contrast to work performed at much higher oligomer concentrations.Herchel Smith (Postdoctoral Fellowship), Engineering and Physical Sciences Research Council (studentship), European Research Council (Advanced Grant (669237)), Augustus Newman Foundatio