Functional mutations in spike glycoprotein of Zaire ebolavirus associated with an increase in infection efficiency

Ebola virus (EBOV) is extremely virulent, and its glycoprotein is necessary for viral entry. EBOV may adapt to its new host humans during outbreaks by acquiring mutations especially in glycoprotein, which allows EBOV to spread more efficiently. To identify these evolutionary selected mutations and examine their effects on viral infectivity, we used experimental–phylogenetic–structural interdisciplinary approaches. In evolutionary analysis of all available Zaire ebolavirus glycoprotein sequences, we detected two codon sites under positive selection, which are located near/within the region critical for the host‐viral membrane fusion, namely alanine‐to‐valine and threonine‐to‐isoleucine mutations at 82 (A82V) and 544 (T544I), respectively. The fine‐scale transmission dynamics of EBOV Makona variants that caused the 2014–2015 outbreak showed that A82V mutant was fixed in the population, whereas T544I was not. Furthermore, pseudotype assays for the Makona glycoprotein showed that the A82V mutation caused a small increase in viral infectivity compared with the T544I mutation. These findings suggest that mutation fixation in EBOV glycoprotein may be associated with their increased infectivity levels; the mutant with a moderate increase in infectivity will fix. Our findings showed that a driving force for Ebola virus evolution via glycoprotein may be a balance between costs and benefits of its virulence

A gravitationally unstable gas disk of a starburst galaxy 12 billion years ago

Submillimeter bright galaxies in the early Universe are vigorously forming stars at ~1000 times higher rate than the Milky Way. A large fraction of stars is formed in the central 1 kiloparsec region, that is comparable in size to massive, quiescent galaxies found at the peak of the cosmic star formation history, and eventually the core of giant elliptical galaxies in the present-day Universe. However, the physical and kinematic properties inside a compact starburst core are poorly understood because dissecting it requires angular resolution even higher than the Hubble Space Telescope can offer. Here we report 550 parsec-resolution observations of gas and dust in the brightest unlensed submillimeter galaxy at z=4.3. We map out for the first time the spatial and kinematic structure of molecular gas inside the heavily dust-obscured core. The gas distribution is clumpy while the underlying disk is rotation-supported. Exploiting the high-quality map of molecular gas mass surface density, we find a strong evidence that the starburst disk is gravitationally unstable, implying that the self-gravity of gas overcomes the differential rotation and the internal pressure by stellar radiation feedback. The observed molecular gas would be consumed by star formation in a timescale of 100 million years, that is comparable to those in merging starburst galaxies. Our results suggest that the most extreme starburst in the early Universe originates from efficient star formation due to a gravitational instability in the central 2 kpc region.Comment: Published in Nature on August 30 2018 (submitted version

SARS-CoV-2 ORF3b is a potent interferon antagonist whose activity is increased by a naturally occurring elongation variant

One of the features distinguishing SARS-CoV-2 from its more pathogenic counterpart SARS-CoV is the presence of premature stop codons in its ORF3b gene. Here, we show that SARS-CoV-2 ORF3b is a potent interferon antagonist, suppressing the induction of type I interferon more efficiently than its SARS-CoV ortholog. Phylogenetic analyses and functional assays reveal that SARS-CoV-2-related viruses from bats and pangolins also encode truncated ORF3b gene products with strong anti-interferon activity. Furthermore, analyses of approximately 17,000 SARS-CoV-2 sequences identify a natural variant in which a longer ORF3b reading frame was reconstituted. This variant was isolated from two patients with severe disease and further increased the ability of ORF3b to suppress interferon induction. Thus, our findings not only help to explain the poor interferon response in COVID-19 patients but also describe the emergence of natural SARS-CoV-2 quasispecies with an extended ORF3b gene that may potentially affect COVID-19 pathogenesis

Estratégia Teórico-Prática no Ensino de Enfermagem em Doenças Transmissíveis com o Foco na Vigilância em Saúde

Este relato apresenta a estratégia de ensino teórico-prática para o conteúdo de vigilância em saúde na Disciplina ENS 0425 – Enfermagem em Doenças Transmissíveis com Enfoque em Saúde Coletiva, do curso de bacharelado em Enfermagem, por meio do estágio em unidades de vigilância em saúde localizadas na cidade de São Paulo no ano de 2016. As atividades em campo de estágio tiveram como resultado a produção de relatórios em formato de estudo de caso, tanto no âmbito individual quanto no âmbito populacional de enfrentamento das doenças transmissíveis. A estratégia de ensino pode ser considerada inovadora, porque estimulou o estudante ao desenvolvimento do trabalho articulado com diversos atores envolvidos na vigilância em saúde e ao debate sobre os conceitos de morbidade, letalidade, prevalência e incidência, tendo como ponto de partida a desigualdade territorial das necessidades em saúde com vistas à atuação individual e populacional.This report presents the strategy of theoretical and practical teaching for the content of health surveillance in elective course ENS 0425 – Nursing in Communicable Diseases with a Focus on Collective Health, of the baccalaureate course in Nursing, by means of the internship in localized health surveillance units in the city of São Paulo in 2016. The activities in the field of internships have resulted in the production of reports in a case study format both in the individual and in the population context of coping with communicable diseases. The teaching strategy can be considered innovative because it has stimulated the student to develop the work articulated with several actors involved in health surveillance and the debate on the concepts of morbidity, lethality, prevalence and incidence, starting from the territorial inequality of the needs in health for individual and population performance

The SARS-CoV-2 Lambda variant exhibits enhanced infectivity and immune resistance

SARS-CoV-2ラムダ株のウイルス学的・免疫学的性状の解明. 京都大学プレスリリース. 2021-12-23.SARS-CoV-2 Lambda, a variant of interest, has spread in some South American countries; however, its virological features and evolutionary traits remain unknown. In this study, we use pseudoviruses and reveal that the spike protein of the Lambda variant is more infectious than that of other variants due to the T76I and L452Q mutations. The RSYLTPGD246-253N mutation, a unique 7-amino-acid deletion in the N-terminal domain of the Lambda spike protein, is responsible for evasion from neutralizing antibodies and further augments antibody-mediated enhancement of infection. Although this mutation generates a nascent N-linked glycosylation site, the additional N-linked glycan is dispensable for the virological property conferred by this mutation. Since the Lambda variant has dominantly spread according to the increasing frequency of the isolates harboring the RSYLTPGD246-253N mutation, our data suggest that the RSYLTPGD246-253N mutation is closely associated with the substantial spread of the Lambda variant in South America

The role of biomarkers in the management of bone-homing malignancies

Bone represents a common site of metastasis from several solid tumours, including breast, prostate and lung malignancies. The onset of bone metastases (BM) is associated not only with serious skeletal complications, but also shortened overall survival, owing to the lack of curative treatment options for late-stage cancer. Despite the diagnostic advances, BM detection often occurs in the symptomatic stage, underlining the need for novel strategies aimed at the early identification of high-risk patients. To this purpose, both bone turnover and tumour-derived markers are being investigated for their potential diagnostic, prognostic and predictive roles. In this review, we summarize the pathogenesis of BM in breast, prostate and lung tumours, while exploring the current research focused on the identification and clinical validation of BM biomarkers

Increased ion temperature and neutron yield observed in magnetized indirectly driven D_{2}-filled capsule implosions on the national ignition facility

The application of an external 26 Tesla axial magnetic field to a D_{2} gas-filled capsule indirectly driven on the National Ignition Facility is observed to increase the ion temperature by 40% and the neutron yield by a factor of 3.2 in a hot spot with areal density and temperature approaching what is required for fusion ignition [1]. The improvements are determined from energy spectral measurements of the 2.45 MeV neutrons from the D(d,n)^{3}He reaction, and the compressed central core B field is estimated to be ∼4.9  kT using the 14.1 MeV secondary neutrons from the D(T,n)^{4}He reactions. The experiments use a 30 kV pulsed-power system to deliver a ∼3  μs current pulse to a solenoidal coil wrapped around a novel high-electrical-resistivity AuTa_{4} hohlraum. Radiation magnetohydrodynamic simulations are consistent with the experiment

Copy number elevation of 22q11.2 genes arrests the developmental maturation of working memory capacity and adult hippocampal neurogenesis

Working memory capacity, a critical component of executive function, expands developmentally from childhood through adulthood. Anomalies in this developmental process are seen in individuals with autism spectrum disorder (ASD), schizophrenia and intellectual disabilities (ID), implicating this atypical process in the trajectory of developmental neuropsychiatric disorders. However, the cellular and neuronal substrates underlying this process are not understood. Duplication and triplication of copy number variants of 22q11.2 are consistently and robustly associated with cognitive deficits of ASD and ID in humans, and overexpression of small 22q11.2 segments recapitulates dimensional aspects of developmental neuropsychiatric disorders in mice. We capitalized on these two lines of evidence to delve into the cellular substrates for this atypical development of working memory. Using a region- and cell-type-selective gene expression approach, we demonstrated that copy number elevations of catechol-O-methyl-transferase (COMT) or Tbx1, two genes encoded in the two small 22q11.2 segments, in adult neural stem/progenitor cells in the hippocampus prevents the developmental maturation of working memory capacity in mice. Moreover, copy number elevations of COMT or Tbx1 reduced the proliferation of adult neural stem/progenitor cells in a cell-autonomous manner in vitro and migration of their progenies in the hippocampus granular layer in vivo. Our data provide evidence for the novel hypothesis that copy number elevations of these 22q11.2 genes alter the developmental trajectory of working memory capacity via suboptimal adult neurogenesis in the hippocampus.Peer reviewe