A transient homotypic interaction model for the influenza A virus NS1 protein effector domain

Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open') in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins

Efficacy and safety of an antiviral Iota-Carrageenan nasal spray: a randomized, double-blind, placebo-controlled exploratory study in volunteers with early symptoms of the common cold

Background: The common cold, the most prevalent contagious viral disease in humans still lacks a safe and effective antiviral treatment. Iota-Carrageenan is broadly active against respiratory viruses in-vitro and has an excellent safety profile. This study investigated the efficacy and safety of an Iota-Carrageenan nasal spray in patients with common cold symptoms. Methods: In a randomized, double-blind, placebo-controlled exploratory trial, 35 human subjects suffering from early symptoms of common cold received Iota-Carrageenan (0.12%) in a saline solution three times daily for 4 days, compared to placebo. Results: Administration of Iota-Carrageenan nasal spray reduced the symptoms of common cold (p = 0.046) and the viral load in nasal lavages (p = 0.009) in patients with early symptoms of common cold. Pro-inflammatory mediators FGF-2, Fractalkine, GRO, G-CSF, IL-8, IL-1α, IP-10, IL-10, and IFN-α2 were reduced in the Iota-Carrageenan group. Conclusions: Iota-Carrageenan nasal spray appears to be a promising treatment for safe and effective treatment of early symptoms of common cold. Larger trials are indicated to confirm the results

Beyond climate envelopes: effects of weather on regional population trends in butterflies

Although the effects of climate change on biodiversity are increasingly evident by the shifts in species ranges across taxonomical groups, the underlying mechanisms affecting individual species are still poorly understood. The power of climate envelopes to predict future ranges has been seriously questioned in recent studies. Amongst others, an improved understanding of the effects of current weather on population trends is required. We analysed the relation between butterfly abundance and the weather experienced during the life cycle for successive years using data collected within the framework of the Dutch Butterfly Monitoring Scheme for 40 species over a 15-year period and corresponding climate data. Both average and extreme temperature and precipitation events were identified, and multiple regression was applied to explain annual changes in population indices. Significant weather effects were obtained for 39 species, with the most frequent effects associated with temperature. However, positive density-dependence suggested climatic independent trends in at least 12 species. Validation of the short-term predictions revealed a good potential for climate-based predictions of population trends in 20 species. Nevertheless, data from the warm and dry year of 2003 indicate that negative effects of climatic extremes are generally underestimated for habitat specialists in drought-susceptible habitats, whereas generalists remain unaffected. Further climatic warming is expected to influence the trends of 13 species, leading to an improvement for nine species, but a continued decline in the majority of species. Expectations from climate envelope models overestimate the positive effects of climate change in northwestern Europe. Our results underline the challenge to include population trends in predicting range shifts in response to climate change

Psychiatric disorders and clinical correlates of suicidal patients admitted to a psychiatric hospital in Tokyo

<p>Abstract</p> <p>Background</p> <p>Patients admitted to a psychiatric hospital with suicidal behavior (SB) are considered to be especially at high risk of suicide. However, the number of studies that have addressed this patient population remains insufficient compared to that of studies on suicidal patients in emergency or medical settings. The purpose of this study is to seek features of a sample of newly admitted suicidal psychiatric patients in a metropolitan area of Japan.</p> <p>Method</p> <p>155 suicidal patients consecutively admitted to a large psychiatric center during a 20-month period, admission styles of whom were mostly involuntary, were assessed using Structured Clinical Interviews for DSM-IV Axis I and II Disorders (SCID-I CV and SCID-II) and SB-related psychiatric measures. Associations of the psychiatric diagnoses and SB-related characteristics with gender and age were examined.</p> <p>Results</p> <p>The common DSM-IV axis I diagnoses were affective disorders 62%, anxiety disorders 56% and substance-related disorders 38%. 56% of the subjects were diagnosed as having borderline PD, and 87% of them, at least one type of personality disorder (PD). SB methods used prior to admission were self-cutting 41%, overdosing 32%, self-strangulation 15%, jumping from a height 12% and attempting traffic death 10%, the first two of which were frequent among young females. The median (range) of the total number of SBs in the lifetime history was 7 (1-141). Severity of depressive symptomatology, suicidal intent and other symptoms, proportions of the subjects who reported SB-preceding life events and life problems, and childhood and adolescent abuse were comparable to those of the previous studies conducted in medical or emergency service settings. Gender and age-relevant life-problems and life events were identified.</p> <p>Conclusions</p> <p>Features of the studied sample were the high prevalence of affective disorders, anxiety disorders and borderline PD, a variety of SB methods used prior to admission and frequent SB repetition in the lifetime history. Gender and age appeared to have an influence on SB method selection and SB-preceding processes. The findings have important implications for assessment and treatment of psychiatric suicidal patients.</p

Physical and Chemical Properties of Cloud Droplet Residuals and Aerosol Particles During the Arctic Ocean 2018 Expedition

Detailed knowledge of the physical and chemical properties and sources of particles that form clouds is especially important in pristine areas like the Arctic, where particle concentrations are often low and observations are sparse. Here, we present in situ cloud and aerosol measurements from the central Arctic Ocean in August–September 2018 combined with air parcel source analysis. We provide direct experimental evidence that Aitken mode particles (particles with diameters ≲70 nm) significantly contribute to cloud condensation nuclei (CCN) or cloud droplet residuals, especially after the freeze-up of the sea ice in the transition toward fall. These Aitken mode particles were associated with air that spent more time over the pack ice, while size distributions dominated by accumulation mode particles (particles with diameters ≳70 nm) showed a stronger contribution of oceanic air and slightly different source regions. This was accompanied by changes in the average chemical composition of the accumulation mode aerosol with an increased relative contribution of organic material toward fall. Addition of aerosol mass due to aqueous-phase chemistry during in-cloud processing was probably small over the pack ice given the fact that we observed very similar particle size distributions in both the whole-air and cloud droplet residual data. These aerosol–cloud interaction observations provide valuable insight into the origin and physical and chemical properties of CCN over the pristine central Arctic Ocean

Pepsinogen A, pepsinogen C, and gastrin as markers of atrophic chronic gastritis in European dyspeptics

Serum levels of pepsinogen and gastrin are parameters that can be used as biomarkers for gastric mucosa. The aim of this study was to validate these serum biomarkers, that is pepsinogen A (PGA), pepsinogen C (PGC), PGA/PGC ratio, and gastrin, as screening tests for precancerous lesions: atrophic chronic gastritis (ACG) or Helicobacter pylori-related corpus-predominant or multifocal atrophy. The study population was comprised of a subsample of 284 patients from the 451 included in the Eurohepygast cohort, between 1995 and 1997. The concentrations of PGA, PGC, and gastrin were measured by radioimmunoassays. Histological diagnosis was the gold standard. Cut-off points were calculated using receiving operator characteristics (ROC) curves. Factors linked to variation of biomarkers were identified using multivariate linear regression. The mean of each biomarker in the sample was: PGA, 77.4 μg l−1; PGC, 13.2 μg l−1; PGA/PGC, 6.7; and gastrin, 62.4 ng l−1. For ACG patients, the areas under the PGA, PGC, PGA/PGC, and gastrin ROC curves were 0.55, 0.62, 0.73, and 0.58, respectively. The best cut-off point for PGA/PGC was 5.6, with sensitivity 65% and specificity 77.9%. For H. pylori-related corpus-predominant or multifocal atrophy, the areas under the respective ROC curves were 0.57, 0.67, 0.84, and 0.69. The best cut-off point for PGA/PGC was 4.7, with sensitivity 77.1% and specificity 87.4%. The results suggested that only the PGA/PGC ratio can be considered as a biomarker for precancerous lesions of the stomach, and may be useful as a screening test

Detection of multiple respiratory pathogens during primary respiratory infection: nasal swab versus nasopharyngeal aspirate using real-time polymerase chain reaction

In this study, we present the multiple detection of respiratory viruses in infants during primary respiratory illness, investigate the sensitivity of nasal swabs and nasopharyngeal aspirates, and assess whether patient characteristics and viral load played a role in the sensitivity. Healthy infants were included at signs of first respiratory tract infection. Paired nasopharyngeal aspirates and nasal swabs were collected. Real-time polymerase chain reaction (PCR) was carried out for 11 respiratory pathogens. Paired nasopharyngeal aspirates and nasal swabs were collected in 98 infants. Rhinovirus (n = 67) and respiratory syncytial virus (n = 39) were the most frequently detected. Co-infection occurred in 48% (n = 45) of the infants. The sensitivity of the nasal swab was lower than the nasopharyngeal aspirate, in particular, for respiratory syncytial virus (51% vs. 100%) and rhinovirus (75% vs. 97%). The sensitivity of the nasal swab was strongly determined by the cycle threshold (CT) value (p < 0.001). The sensitivity of the swab for respiratory syncytial virus, but not rhinovirus, was 100% in children with severe symptoms (score ≥11). It is concluded that, for community-based studies and surveillance purposes, the nasal swab can be used, though the sensitivity is lower than the aspirate, in particular, for the detection of mild cases of respiratory syncytial virus (RSV) infection

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO