Community members' perceptions of mass drug administration for control of lymphatic filariasis in rural rural and urban Tanzania

Lymphatic filariasis is one of several neglected tropical diseases with severely disabling and stigmatizing manifestations that are referred to as ‘neglected diseases of poverty’. It is a mosquito-borne disease found endemically and exclusively in low-income contexts where, concomitantly, general public health care is often deeply troubled and fails to meet the basic health needs of impoverished populations. This presents particular challenges for the implementation of mass drug administration (MDA), which currently is the principal means of control and eventual elimination. Several MDA programmes face the dilemma that they are unable to attain and maintain the required drug coverage across target groups. In recognition of this, a qualitative study was conducted in the Morogoro and Lindi regions of Tanzania to gain an understanding of community experiences with, and perceptions of, the MDA campaign implemented in 2011 by the National Lymphatic Filariasis Elimination Programme. The study revealed a wide variation of perceptions and experiences regarding the aim, rationale and justification of MDA. There were positive sentiments about the usefulness of the drugs, but many study participants were sceptical about the manner in which MDA is implemented. People were particularly disappointed with the limited attempts by implementers to share information and mobilize residents. In addition, negative sentiments towards MDA for lymphatic filariasis reflected a general feeling of desertion and marginalization by the health care system and political authorities. However, the results suggest that if the communities are brought on board with genuine respect for their integrity and informed self-determination, there is scope for major improvements in community support for MDA-based control activities

Altered development of the brain after focal herpesvirus infection of the central nervous system

Human cytomegalovirus infection of the developing central nervous system (CNS) is a major cause of neurological damage in newborn infants and children. To investigate the pathogenesis of this human infection, we developed a mouse model of infection in the developing CNS. Intraperitoneal inoculation of newborn animals with murine cytomegalovirus resulted in virus replication in the liver followed by virus spread to the brain. Virus infection of the CNS was associated with the induction of inflammatory responses, including the induction of a large number of interferon-stimulated genes and histological evidence of focal encephalitis with recruitment of mononuclear cells to foci containing virus-infected cells. The morphogenesis of the cerebellum was delayed in infected animals. The defects in cerebellar development in infected animals were generalized and, although correlated temporally with virus replication and CNS inflammation, spatially unrelated to foci of virus-infected cells. Specific defects included decreased granular neuron proliferation and migration, expression of differentiation markers, and activation of neurotrophin receptors. These findings suggested that in the developing CNS, focal virus infection and induction of inflammatory responses in resident and infiltrating mononuclear cells resulted in delayed cerebellar morphogenesis

Identifying oceanic thermal anomalies in the coral triangle region

Mass coral bleaching has historically been linked to episodes of thermal stress. While locationspecific time-series data have been examined, the oceanic thermal anomalies that underlie broad-scale thermal stress events are apparently unstudied quantitatively in terms of their spatial extent, temporal development, and intensity. Knowledge of the spatial and temporal parameters that characterise anomalies can be useful in understanding how bleaching-level stress develops, providing context for and a basis for modelling of future events. Here we examine historical satellite sea-surface temperature (SST) data with the goal of identifying and characterising oceanic anomalies in the Coral Triangle region. This region is of interest because it is influenced by the Indian and Pacific Oceans and is the centre of coral ecosystem diversity and significant coral reef conservation efforts. Oceanic anomalies are defined here using the HotSpot metric, which is the positive variation in temperature above the maximum of the monthly mean climatology values. This metric describes thermal stress that has been linked to coral bleaching episodes. It is proposed that the method for identifying oceanic anomalies described here be applied to datasets of varying spatial resolutions to evaluate if, and how, the characterisations are resolution-dependent. If these anomalies can be comparably identified and characterised at a coarser spatial resolution, this could open the way to examining the likely impact of oceanic thermal anomalies further back in time using historical datasets or in the future using climate models, both of which are available only at lower spatial and temporal resolutions

Comparative Assessment of Peer Review: Project Outcomes Report

This report discusses the Comparative Assessment of Peer Review (CAPR) project outcomes. The authors investigate the review process for agencies that fund scientific research

Limits and patterns of cytomegalovirus genomic diversity in humans

Human cytomegalovirus (HCMV) exhibits surprisingly high genomic diversity during natural infection although little is known about the limits or patterns of HCMV diversity among humans. To address this deficiency, we analyzed genomic diversity among congenitally infected infants. We show that there is an upper limit to HCMV genomic diversity in these patient samples, with approximately 25% of the genome being devoid of polymorphisms. These low diversity regions were distributed across 26 loci that were preferentially located in DNA-processing genes. Furthermore, by developing, to our knowledge, the first genome-wide mutation and recombination rate maps for HCMV, we show that genomic diversity is positively correlated with these two rates. In contrast, median levels of viral genomic diversity did not vary between putatively single or mixed strain infections. We also provide evidence that HCMV populations isolated from vascular compartments of hosts from different continents are genetically similar and that polymorphisms in glycoproteins and regulatory proteins are enriched in these viral populations. This analysis provides the most highly detailed map of HCMV genomic diversity in human hosts to date and informs our understanding of the distribution of HCMV genomic diversity within human hosts

Physical Properties of (2) Pallas

We acquired and analyzed adaptive-optics imaging observations of asteroid (2) Pallas from Keck II and the Very Large Telescope taken during four Pallas oppositions between 2003 and 2007, with spatial resolution spanning 32-88 km (image scales 13-20 km/pix). We improve our determination of the size, shape, and pole by a novel method that combines our AO data with 51 visual light-curves spanning 34 years of observations as well as occultation data. The shape model of Pallas derived here reproduces well both the projected shape of Pallas on the sky and light-curve behavior at all the epochs considered. We resolved the pole ambiguity and found the spin-vector coordinates to be within 5 deg. of [long, lat] = [30 deg., -16 deg.] in the ECJ2000.0 reference frame, indicating a high obliquity of ~84 deg., leading to high seasonal contrast. The best triaxial-ellipsoid fit returns radii of a=275 km, b= 258 km, and c= 238 km. From the mass of Pallas determined by gravitational perturbation on other minor bodies [(1.2 +/- 0.3) x 10-10 Solar Masses], we derive a density of 3.4 +/- 0.9 g.cm-3 significantly different from the density of C-type (1) Ceres of 2.2 +/- 0.1 g.cm-3. Considering the spectral similarities of Pallas and Ceres at visible and near-infrared wavelengths, this may point to fundamental differences in the interior composition or structure of these two bodies. We define a planetocentric longitude system for Pallas, following IAU guidelines. We also present the first albedo maps of Pallas covering ~80% of the surface in K-band. These maps reveal features with diameters in the 70-180 km range and an albedo contrast of about 6% wrt the mean surface albedo.Comment: 16 pages, 8 figures, 6 table

SARS-CoV-2 Spike Protein Is Capable of Inducing Cell–Cell Fusions Independent from Its Receptor ACE2 and This Activity Can Be Impaired by Furin Inhibitors or a Subset of Monoclonal Antibodies

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was responsible for the COVID-19 pandemic, efficiently spreads cell-to-cell through mechanisms facilitated by its membrane glycoprotein spike. We established a dual split protein (DSP) assay based on the complementation of GFP and luciferase to quantify the fusogenic activity of the SARS-CoV-2 spike protein. We provide several lines of evidence that the spike protein of SARS-CoV-2, but not SARS-CoV-1, induced cell–cell fusion even in the absence of its receptor, angiotensin-converting enzyme 2 (ACE2). This poorly described ACE2-independent cell fusion activity of the spike protein was strictly dependent on the proteasomal cleavage of the spike by furin while TMPRSS2 was dispensable. Previous and current variants of concern (VOCs) differed significantly in their fusogenicity. The Delta spike was extremely potent compared to Alpha, Beta, Gamma and Kappa, while the Omicron spike was almost devoid of receptor-independent fusion activity. Nonetheless, for all analyzed variants, cell fusion was dependent on furin cleavage and could be pharmacologically inhibited with CMK. Mapping studies revealed that amino acids 652-1273 conferred the ACE2-independent fusion activity of the spike. Unexpectedly, residues proximal to the furin cleavage site were not of major relevance, whereas residue 655 critically regulated fusion. Finally, we found that the spike’s fusion activity in the absence of ACE2 could be inhibited by antibodies directed against its N-terminal domain (NTD) but not by antibodies targeting its receptor-binding domain (RBD). In conclusion, our BSL-1-compatible DSP assay allowed us to screen for inhibitors or antibodies that interfere with the spike’s fusogenic activity and may therefore contribute to both rational vaccine design and development of novel treatment options against SARS-CoV-2.</jats:p