Live-attenuated vaccine sCPD9 elicits superior mucosal and systemic immunity to SARS-CoV-2 variants in hamsters

Vaccines play a critical role in combating the COVID-19 pandemic. Future control of the pandemic requires improved vaccines with high efficacy against newly emerging SARS-CoV-2 variants and the ability to reduce virus transmission. Here we compare immune responses and preclinical efficacy of the mRNA vaccine BNT162b2, the adenovirus-vectored spike vaccine Ad2-spike and the live-attenuated virus vaccine candidate sCPD9 in Syrian hamsters, using both homogeneous and heterologous vaccination regimens. Comparative vaccine efficacy was assessed by employing readouts from virus titrations to single-cell RNA sequencing. Our results show that sCPD9 vaccination elicited the most robust immunity, including rapid viral clearance, reduced tissue damage, fast differentiation of pre-plasmablasts, strong systemic and mucosal humoral responses, and rapid recall of memory T cells from lung tissue after challenge with heterologous SARS-CoV-2. Overall, our results demonstrate that live-attenuated vaccines offer advantages over currently available COVID-19 vaccines

From biomedicine to natural history research: EST resources for ambystomatid salamanders

BACKGROUND: Establishing genomic resources for closely related species will provide comparative insights that are crucial for understanding diversity and variability at multiple levels of biological organization. We developed ESTs for Mexican axolotl (Ambystoma mexicanum) and Eastern tiger salamander (A. tigrinum tigrinum), species with deep and diverse research histories. RESULTS: Approximately 40,000 quality cDNA sequences were isolated for these species from various tissues, including regenerating limb and tail. These sequences and an existing set of 16,030 cDNA sequences for A. mexicanum were processed to yield 35,413 and 20,599 high quality ESTs for A. mexicanum and A. t. tigrinum, respectively. Because the A. t. tigrinum ESTs were obtained primarily from a normalized library, an approximately equal number of contigs were obtained for each species, with 21,091 unique contigs identified overall. The 10,592 contigs that showed significant similarity to sequences from the human RefSeq database reflected a diverse array of molecular functions and biological processes, with many corresponding to genes expressed during spinal cord injury in rat and fin regeneration in zebrafish. To demonstrate the utility of these EST resources, we searched databases to identify probes for regeneration research, characterized intra- and interspecific nucleotide polymorphism, saturated a human – Ambystoma synteny group with marker loci, and extended PCR primer sets designed for A. mexicanum / A. t. tigrinum orthologues to a related tiger salamander species. CONCLUSIONS: Our study highlights the value of developing resources in traditional model systems where the likelihood of information transfer to multiple, closely related taxa is high, thus simultaneously enabling both laboratory and natural history research

Design of Experiments for Screening

The aim of this paper is to review methods of designing screening experiments, ranging from designs originally developed for physical experiments to those especially tailored to experiments on numerical models. The strengths and weaknesses of the various designs for screening variables in numerical models are discussed. First, classes of factorial designs for experiments to estimate main effects and interactions through a linear statistical model are described, specifically regular and nonregular fractional factorial designs, supersaturated designs and systematic fractional replicate designs. Generic issues of aliasing, bias and cancellation of factorial effects are discussed. Second, group screening experiments are considered including factorial group screening and sequential bifurcation. Third, random sampling plans are discussed including Latin hypercube sampling and sampling plans to estimate elementary effects. Fourth, a variety of modelling methods commonly employed with screening designs are briefly described. Finally, a novel study demonstrates six screening methods on two frequently-used exemplars, and their performances are compared

The symptom experience of people living with HIV and AIDS in the Eastern Cape, South Africa

<p>Abstract</p> <p>Background</p> <p>Symptom management for persons living with HIV (PLHIV) or AIDS is an important part of care management. Limited information about symptom prevalence exists about HIV infected persons in South Africa, in particular in the context of antiretroviral treatment (ART). The aim of this study was to assess HIV symptoms and demographic, social and disease variables of people living with HIV in South Africa.</p> <p>Methods</p> <p>In 2007 607 PLHIV, sampled by all districts in the Eastern Cape Province and recruited through convenience sampling, were interviewed by PLHIV at health facilities, key informants in the community and support groups.</p> <p>Results</p> <p>Two-thirds of the PLHIV (66%) classified themselves with being given an AIDS (advanced stage of HIV) diagnosis, 48% were currently on ART, 35% were currently on a disability grant for HIV/AIDS and for 13% the disability grant had been stopped. Participants reported that on the day of the interview, they were experiencing an average of 26.1 symptoms out of a possible 64. In a regression model with demographic and social variables, higher HIV symptom levels were associated with lower educational levels, higher age, urban residence and not on a disability grant, lack of enough food and having a health insurance, and in a regression model with demographic, social and disease variables only being on ART, lack of enough food and having a health insurance were associated with HIV symptoms.</p> <p>Conclusion</p> <p>Symptom assessment provides information that may be valuable in evaluating AIDS treatment regimens and defining strategies to improve quality of life. Because of the high levels of symptoms reported, the results imply an urgent need for effective health care, home- and community-based as well as self-care symptom management to help patients and their families manage and control AIDS symptoms.</p

Thermo-electrochemical production of compressed hydrogen from methane with near-zero energy loss

[EN] Conventional production of hydrogen requires large industrial plants to minimize energy losses and capital costs associated with steam reforming, water-gas shift, product separation and compression. Here we present a protonic membrane reformer (PMR) that produces high-purity hydrogen from steam methane reforming in a single-stage process with near-zero energy loss. We use a BaZrO3-based proton-conducting electrolyte deposited as a dense film on a porous Ni composite electrode with dual function as a reforming catalyst. At 800 degrees C, we achieve full methane conversion by removing 99% of the formed hydrogen, which is simultaneously compressed electrochemically up to 50 bar. A thermally balanced operation regime is achieved by coupling several thermo-chemical processes. Modelling of a small-scale (10 kg H-2 day-1) hydrogen plant reveals an overall energy efficiency of >87%. 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Efficient Temporal Processing of Naturalistic Sounds

In this study, we investigate the ability of the mammalian auditory pathway to adapt its strategy for temporal processing under natural stimulus conditions. We derive temporal receptive fields from the responses of neurons in the inferior colliculus to vocalization stimuli with and without additional ambient noise. We find that the onset of ambient noise evokes a change in receptive field dynamics that corresponds to a change from bandpass to lowpass temporal filtering. We show that these changes occur within a few hundred milliseconds of the onset of the noise and are evident across a range of overall stimulus intensities. Using a simple model, we illustrate how these changes in temporal processing exploit differences in the statistical properties of vocalizations and ambient noises to increase the information in the neural response in a manner consistent with the principles of efficient coding

Structure of the St. Louis encephalitis virus postfusion envelope trimer

St. Louis encephalitis virus (SLEV) is a mosquito-borne flavivirus responsible for several human encephalitis outbreaks over the last 80 years. Mature flavivirus virions are coated with dimeric envelope (E) proteins that mediate attachment and fusion with host cells. E is a class II fusion protein, the hallmark of which is a distinct dimer-to-trimer rearrangement that occurs upon endosomal acidification and insertion of hydrophobic fusion peptides into the endosomal membrane. Herein, we report the crystal structure of SLEV E in the posfusion trimer conformation. The structure revealed specific features that differentiate SLEV E from trimers of related flavi- and alphaviruses. SLEV E fusion loops have distinct intermediate spacing such that they are positioned further apart than previously observed in flaviviruses but closer together than Semliki Forest virus, an alphavirus. Domains II and III (DII and DIII) of SLEV E also adopt different angles relative to DI, which suggests that the DI-DII joint may accommodate spheroidal motions. However, trimer interfaces are well conserved among flaviviruses, so it is likely the differences observed represent structural features specific to SLEV function. Analysis of surface potentials revealed a basic platform underneath flavivirus fusion loops that may interact with the anionic lipid head groups found in membranes. Taken together, these results highlight variations in E structure and assembly that may direct virus-specific interactions with host determinants to influence pathogenesis

Beauty photoproduction measured using decays into muons in dijet events in ep collisions at s\sqrt{s}=318 GeV

The photoproduction of beauty quarks in events with two jets and a muon has been measured with the ZEUS detector at HERA using an integrated luminosity of 110 pb$^{- 1}$. The fraction of jets containing b quarks was extracted from the transverse momentum distribution of the muon relative to the closest jet. Differential cross sections for beauty production as a function of the transverse momentum and pseudorapidity of the muon, of the associated jet and of $x_{\gamma}^{jets}$, the fraction of the photon's momentum participating in the hard process, are compared with MC models and QCD predictions made at next-to-leading order. The latter give a good description of the data.Comment: 32 pages, 6 tables, 7 figures Table 6 and Figure 7 revised September 200

Search for CP violation in D+→ϕπ+ and D+s→K0Sπ+ decays

A search for CP violation in D + → ϕπ + decays is performed using data collected in 2011 by the LHCb experiment corresponding to an integrated luminosity of 1.0 fb−1 at a centre of mass energy of 7 TeV. The CP -violating asymmetry is measured to be (−0.04 ± 0.14 ± 0.14)% for candidates with K − K + mass within 20 MeV/c 2 of the ϕ meson mass. A search for a CP -violating asymmetry that varies across the ϕ mass region of the D + → K − K + π + Dalitz plot is also performed, and no evidence for CP violation is found. In addition, the CP asymmetry in the D+s→K0Sπ+ decay is measured to be (0.61 ± 0.83 ± 0.14)%