Search

The article discusses adverse events after the Democratic Republic of Congo (DRC) Ministry of Health administered approximately 240,000 doses of yellow fever vaccine to all persons aged ≥9 months during a mass vaccination campaign in Matadi. It is noted that the immunization campaign was to assess completeness and representativeness of passive surveillance data.

Glacial cycles transfer water between continental ice sheets and oceans; they have caused global sea-level (SL) variations up to 100 m during the Pleistocene, at rates of up to 1 cm/yr. These SL variations change the hydrostatic pressure at mid-ocean ridges (MORs), modifying the rate of mantle decompression and the depth at which melting begins beneath the ridge axis. SL variations may therefore induce changes in the flux and composition of magma at MORs, potentially affecting the flux of carbon into the climate system [Huybers and Langmuir 2009]. Published models predict up to 10% variation in carbon emission rates for absolute changes in SL of ~100 m [Burley and Katz, 2015]. However, two major assumptions of those models are (1) that carbon is a passive, incompatible element, and (2) that the perturbations to melting rate do not affect the carbon concentration in the magma. As a result, in the models of Buley and Katz [2015] the perturbations in carbon concentration are only generated at the depth at which the mantle begins to melt and are transported upwards with liquid velocity. The authors predict lags (between a peak in SL and a peak in carbon emissions) of several tens of kyrs. Here, we present 1-D melting-column models in which carbon participates in the thermodynamics of melting, and in which SL variations affect the melting rate throughout the column. We revisit estimates of the impact of SL-changes on magmatism and carbon fluxes at MORs. Our models predict variations in carbon emissions between 1% and 12% for forcing at the periods that dominate the reconstructed SL record of the late Pleistocene. We find that the perturbations to carbon flux near the surface are mainly driven by perturbations to the melting rate. Since these perturbations travel faster than the liquid, we predict lags smaller (<20 kyrs) than those obtained by previous models. [ABSTRACT FROM AUTHOR]

Hylidae are one of the most diverse and widely distributed frog families in the world. The species selected in the present study is representative for the subtropical wetland area of South America. Considering the global decline of amphibian populations, the present contribution is aimed towards the sensitivity of three frog species to a common pollutant, chromium [Cr(VI)]. Toxicity tests were done exposing organisms at two different stages of development (from 24 h embryos to 120 h larvae and from 144 to 240 h tadpoles) using Hyla pulchella, H.nana, and Scinax squalirostris, and measuring mortality and morbidity as end points. Organisms used for testing were obtained from matingpairs collected at a local pond. Assays were done under laboratory standardized conditions with three replications and at least five organisms per replication, using eight dilutions of the toxicant and negative controls. Results of mortality were expressed as 96 h 50% lethalconcentration (LC50). Slope of dose-response plots for the three species were obtained by regression analysis. Comparisons were done by simple linear regression equations. Results from regressionanalysis show that sensitivity of the three species differs significantly (p<0.01). Although the presence of malformations was observed, organisms at earlier stages present a lower sensitivity to chromium. Regarding lethal effects, S. squalirostris is more sensitive (LC50=4.72 mg/L) than the other species (H. nana LC50=10.99 mg/L and H. pulchella LC50=19.67 mg/L) in tests with organisms of the second stage. The present communication contributes to knowledge on the biological effects of Cr(VI) on poorly studied neotropical frog species. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) is the most important human virus transmitted by mosquitos. Dengue pathogenesis is characterized by a large induction of proinflammatory cytokines. This cytokine induction varies among the four DENV serotypes (DENV1 to 4) and poses a challenge for live DENV vaccine design. Here, we identify a viral mechanism to limit NF-κB activation and cytokine secretion by the DENV protein NS5. Using proteomics, we found that NS5 binds and degrades the host protein ERC1 to antagonize NF-κB activation, limit proinflammatory cytokine secretion, and reduce cell migration. We found that ERC1 degradation involves unique properties of the methyltransferase domain of NS5 that are not conserved among the four DENV serotypes. By obtaining chimeric DENV2 and DENV4 viruses, we map the residues in NS5 for ERC1 degradation, and generate recombinant DENVs exchanging serotype properties by single amino acid substitutions. This work uncovers a function of the viral protein NS5 to limit cytokine production, critical to dengue pathogenesis. Importantly, the information provided about the serotype-specific mechanism for counteracting the antiviral response can be applied to improve live attenuated vaccines. [ABSTRACT FROM AUTHOR]

Dengue virus NS5 protein plays multiple functions in the cytoplasm of infected cells, enabling viral RNA replication and counteracting host antiviral responses. Here, we demonstrate a novel function of NS5 in the nucleus where it interferes with cellular splicing. Using global proteomic analysis of infected cells together with functional studies, we found that NS5 binds spliceosome complexes and modulates endogenous splicing as well as minigene-derived alternative splicing patterns. In particular, we show that NS5 alone, or in the context of viral infection, interacts with core components of the U5 snRNP particle, CD2BP2 and DDX23, alters the inclusion/exclusion ratio of alternative splicing events, and changes mRNA isoform abundance of known antiviral factors. Interestingly, a genome wide transcriptome analysis, using recently developed bioinformatics tools, revealed an increase of intron retention upon dengue virus infection, and viral replication was improved by silencing specific U5 components. Different mechanistic studies indicate that binding of NS5 to the spliceosome reduces the efficiency of pre-mRNA processing, independently of NS5 enzymatic activities. We propose that NS5 binding to U5 snRNP proteins hijacks the splicing machinery resulting in a less restrictive environment for viral replication. [ABSTRACT FROM AUTHOR]

To obtain a comprehensive assessment of metabolite levels from extracts of leukocytes, we have recorded ultrahigh-resolution ¹H-13C HSQC NMR spectra of cell extracts, which exhibit spectral signatures of numerous small molecules. However, conventional acquisition of such spectra is time- consuming and hampers measurements on multiple samples, which would be needed for statistical analysis of metabolite concentrations. Here we show that the measurement time can be dramatically reduced without loss of spectral quality when using nonlinear sampling (NLS) and a new high-fidelity forward maximum- entropy (FM) reconstruction algorithm. This FM reconstruction conserves all measured time-domain data points and guesses the missing data points by an iterative process. This consists of discrete Fourier transformation of the sparse time-domain data set, computation of the spectral entropy, determination of a multidimensional entropy gradient, and calculation of new values for the missing time-domain data points with a conjugate gradient approach. Since this procedure does not alter measured data points, it reproduces signal intensities with high fidelity and does not suffer from a dynamic range problem. As an example we measured a natural abundance ¹H-13C HSQC spectrum of metabolites from granulocyte cell extracts. We show that a high-resolution ¹H-13C HSQC spectrum with 4k complex increments recorded linearly within 3.7 days can be reconstructed from one-seventh of the increments with nearly identical spectral appearance, indistinguishable signal intensities, and comparable or even lower root-mean-square (rms) and peak noise patterns measured in signal-free areas. Thus, this approach allows recording of ultrahigh resolution ¹H- 13C HSQC spectra in a fraction of the time needed for recording linearly sampled spectra. [ABSTRACT FROM AUTHOR]

Background: The use of mycophenolic acid (MPA) in women during pregnancy causes an increase in miscarriages and birth defects with a typical embryopathy profile. Although epidemiological data does not suggest a greater risk among the offspring of male kidney transplant recipients, the European Medicines Agency and The Spanish Agency of Medicines and Medical Devices introduced the recommendation of using contraceptive methods. Methods: We conducted a national retrospective study in 15 Spanish Kidney Transplant Centers to evaluate the frequency of miscarriages and birth defects between the offspring from male kidney transplants recipients. We included 151 males who had fathered 239 offspring, 225 under MPA and 14 without MPA. Results: The results of our study showed an incidence of miscarriages in the MPA group of 9.8%, and of birth defects of 4%. Conclusions: We observed an incidence of miscarriages between the offspring fathered by kidney transplant males under MPA lower than the general population. The incidence of birth defects was similar to the incidence described in other studies and the fact that we did not find the typical embryopathy profile makes it difficult to associate them to the use of MPA. Because of that, we urge the European and Spanish Agencies to reconsider their recommendations for males. [ABSTRACT FROM AUTHOR]

We have previously shown that the small metal-binding proteins CusF3H+ and SmbP can be used as fusion proteins for the expression and purification of recombinant proteins in Escherichia coli. Because of their small size, both around 10 kDa, they are suitable for the production of peptides to avoid meager yields after the final purification step of tag removal. Bin1b is a beta-defensin found in the epididymis of rats that has shown to have antimicrobial activity. Previous methodologies used to express this antimicrobial peptide in E. coli involve the expression of the peptide as inclusion bodies followed by in vitro refolding or the supplementation of the proteins necessary for proper folding of the peptide in the cytoplasm via a second plasmid. Here, we developed a methodology that forgoes these approaches and instead uses the fusion proteins CusF3H+ or SmbP and the E. coli strain SHuffle to obtain a soluble recombinant protein that contains the mature Bin1b peptide. The recombinant protein is purified using IMAC chromatography and is subsequently cleaved with enterokinase to separate the fusion protein from Bin1b. The purified peptide displays antimicrobial activity against E. coli, as previously shown. Furthermore, we also tested its antimicrobial activity against the Gram-positive bacteria Staphylococcus aureus and found that Bin1b is also capable of inhibiting the growth of this bacterium. In conclusion, we developed a practical methodology for the expression and purification of the bioactive Bin1b peptide in E. coli using the fusion proteins CusF3H+ and SmbP. This approach could be further applied for the production of more biologically active peptides. • The Bin1b peptide expressed in E. coli SHuffle tagged with the proteins CusF3H+ or SmbP yields a soluble polypeptide. • Bin1b contains disulfide bonds without the need for in vitro refolding or accessory plasmids. • The recombinant Bin1b peptide exhibits antimicrobial activity against Gram-positive and Gram-negative bacteria. [ABSTRACT FROM AUTHOR]

Skin glands in amphibians are either distributed throughout the skin or aggregated in multiglandular structures such as the parotoids typical of most species of Bufonidae. Although many early divergent and derived bufonids lack a discrete parotoid in the postorbital–supratympanic (PoSt) region, they have a great macroscopic diversity in the skin morphology of this region. To understand the origin and evolution of this diversity, in particular of the parotoids, we describe the histomorphology of the skin of the PoSt and dorsal regions in 17 species of bufonids, with or without external evident parotoid, and compare it with previously published descriptions. The survey results in 27 characters that were optimized on a phylogenetic hypothesis of Bufonidae. Our results reveal that the PoSt region has a noteworthy morphological diversity of types of glands, spatial organization and differences in the secretion products. Some morphological characters represent putative synapomorphies of internal clades of Bufonidae and are related to the progressive differentiation towards defined structures (macroglands, parotoids). These morphological results, along with published information on the toxicity of the skin secretions and defensive behaviours in some representative species, allow us to infer possible relationships between these features. [ABSTRACT FROM AUTHOR]

Introduction multiple conditions in later life (multi-morbidity) is a major challenge for health and care systems worldwide, is of particular relevance for older people, but has not (until recently) received high priority as a topic for research. We have identified the top 10 research priorities from the perspective of older people, their carers, and health and social care professionals using the methods of a James Lind Alliance Priority Setting Partnership. Methods in total, 354 participants (162 older people and carers, 192 health professionals) completed a survey and 15 older people and carers were interviewed to produce 96 'unanswered questions'. These were further refined by survey and interviews to a shortlist of 21 topics, and a mix of people aged 80+ living with three or more conditions, carers and health and social care providers to prioritised the top 10. Results the key priorities were about the prevention of social isolation, the promotion of independence and physical and emotional well-being. In addition to these broad topics, the process also identified detailed priorities including the role of exercise therapy, the importance of falls (particularly fear of falling), the recognition and management of frailty and Comprehensive Geriatric Assessment. Conclusion these topics provide a unique perspective on research priorities on multiple conditions in later life and complement existing UK and International recommendations about the optimisation of health and social care systems to deliver essential holistic models of care and the prevention and treatment of multiple co-existing conditions. [ABSTRACT FROM AUTHOR]

We present analogue models simulating the subduction of an oceanic lithosphere beneath an overriding plate advancing at variable rates. The convergence velocity is imposed by lateral boundary conditions in this experimental set. We analyze the geometry of the slab and the deformation of the overriding plate. Experiments confirm the strong correlation between the absolute velocity of the overriding plate on the one hand, the geometry of the subducting plate and the deformation of the overriding plate on the other hand. Following an instantaneous change in kinematic boundary conditions, the subduction system progressively shifts to a new steady-state regime. Models suggest that the adjustment time necessary to shift from the previous to the new equilibrium is independent of the imposed upper plate velocity. Transient stage lasts ∼ 12.5 ± 6 m.y. for the shallow slab dip (100–150-km depth), ∼ 29.2 ± 10 m.y. for the deeper slab dip (300–350-km depth), and ∼ 2.2 ± 2 m.y. for the upper plate deformation. The analysis of present-day subduction zones and their evolution through the last 20 m.y suggests an adjustment time of ∼15 m.y. for shallow slab dip and ∼20 m.y. for deep slab dip in Nature. Since only few subduction zones have shown a constant upper plate velocity over the last 15 m.y., it suggests that most of them are in a transient stage at present-day. [ABSTRACT FROM AUTHOR]

Dengue is a mosquito-borne virus that has become a major public health concern worldwide in recent years. However, the current treatment for dengue disease is only supportive therapy, and no specific antivirals are available to control the infections. Therefore, the need for safe and effective antiviral drugs against this virus is of utmost importance. Entry of the dengue virus (DENV) into a host cell is mediated by its major envelope protein, E . The crystal structure of the E protein reveals a hydrophobic pocket occupied by the detergent n -octyl-β- d -glucoside (β-OG) lying at a hinge region between domains I and II, which is important for the low-pH-triggered conformational rearrangement required for fusion. Thus, the E protein is an attractive target for the development of antiviral agents. In this work, we performed prospective docking-based virtual screening to identify small molecules that likely bind to the β-OG binding site. Twenty-three structurally different compounds were identified and two of them had an EC 50 value in the low micromolar range. In particular, compound 2 (EC 50 = 3.1 μM) showed marked antiviral activity with a good therapeutic index. Molecular dynamics simulations were used in an attempt to characterize the interaction of 2 with protein E , thus paving the way for future ligand optimization endeavors. These studies highlight the possibility of using a new class of DENV inhibitors against dengue. [ABSTRACT FROM AUTHOR]

This study performed in South-Eastern Benin aims to correlate the regional subterranean aquatic fauna, still poorly unknown, with the main physico-chemical characteristics of well-water used by human populations. Two kinds of descriptors are used. Physico-chemical analyses of water and faunistic sampling were consequently performed for one year at 15 stations. Multivariate analyses show different groups of stations depending on the kind of descriptor. Thus it appears that, in the Pobè region, the water quality, very variable from one station to another, is certainly not the main determinant of the well-water fauna distribution. Among the subterranean crustaceans, species belonging to genera Allocyclops and Metastenasellus have never been described before. These results are a contribution to the knowledge of the regional biodiversity and suggest that this biodiversity can be used as an indicator for better protection of regional groundwater. [ABSTRACT FROM AUTHOR]