114 research outputs found
Variation in Vector Competence for Dengue Viruses Does Not Depend on Mosquito Midgut Binding Affinity
Several factors, such as mosquito and virus genetics and environmental variables, determine the ability of mosquitoes to transmit dengue viruses. In this report, we describe new and important information that in some ways contradicts what is in the literature. Midgut infection barriers have been described as important determinants of virus transmission in mosquitoes but we found that virus binding to these midgut cells does not vary. When we compared binding of 8 different, low passage dengue viruses to mosquito midguts that were dissected out of Aedes aegypti mosquitoes (the main vectors of dengue) from Mexico and Texas, we found that there were no differences. Previously, we (and others) had shown that these same viruses differed significantly in replication and dissemination throughout the rest of the mosquito body, including the salivary glands, and therefore they differed greatly in their potential to be transmitted to humans. Thus, the data presented here are important considerations for future studies of vector competence and in determining strategies for control of dengue viruses in the vector
Hybrid Shell Engineering of Animal Cells for Immune Protections and Regulation of Drug Delivery: Towards the Design of “Artificial Organs”
BACKGROUND: With the progress in medicine, the average human life expectancy is continuously increasing. At the same time, the number of patients who require full organ transplantations is augmenting. Consequently, new strategies for cell transplantation are the subject of great interest. METHODOLOGY/PRINCIPAL FINDINGS: This work reports the design, the synthesis and the characterisation of robust and biocompatible mineralised beads composed of two layers: an alginate-silica composite core and a Ca-alginate layer. The adequate choice of materials was achieved through cytotoxicity LDH release measurement and in vitro inflammatory assay (IL-8) to meet the biocompatibility requirements for medical purpose. The results obtained following this strategy provide a direct proof of the total innocuity of silica and alginate networks for human cells as underscored by the non-activation of immune defenders (THP-1 monocytes). The accessible pore size diameter of the mineralised beads synthesized was estimated between 22 and 30 nm, as required for efficient immuno-isolation without preventing the diffusion of nutrients and metabolites. The model human cells, HepG2, entrapped within these hybrid beads display a high survival rate over more than six weeks according to the measurements of intracellular enzymatic activity, respiration rate, as well as the "de novo" biosynthesis and secretion of albumin out of the beads. CONCLUSIONS/SIGNIFICANCE: The current study shows that active mammalian cells can be protected by a silica-alginate hybrid shell-like system. The functionality of the cell strain can be maintained. Consequently, cells coated with an artificial and a biocompatible mineral shell could respond physiologically within the human body in order to deliver therapeutic agents in a controlled fashion (i.e. insulin), substituting the declining organ functions of the patient
Metal A and Metal B Sites of Nuclear RNA Polymerases Pol IV and Pol V Are Required for siRNA-Dependent DNA Methylation and Gene Silencing
Plants are unique among eukaryotes in having five multi-subunit nuclear RNA polymerases: the ubiquitous RNA polymerases I, II and III plus two plant-specific activities, nuclear RNA polymerases IV and V (previously known as Polymerases IVa and IVb). Pol IV and Pol V are not required for viability but play non-redundant roles in small interfering RNA (siRNA)-mediated pathways, including a pathway that silences retrotransposons and endogenous repeats via siRNA-directed DNA methylation. RNA polymerase activity has not been demonstrated for Polymerases IV or V in vitro, making it unclear whether they are catalytically active enzymes. Their largest and second-largest subunit sequences have diverged considerably from Pol I, II and III in the vicinity of the catalytic center, yet retain the invariant Metal A and Metal B amino acid motifs that bind magnesium ions essential for RNA polymerization. By using site-directed mutagenesis in conjunction with in vivo functional assays, we show that the Metal A and Metal B motifs of Polymerases IV and V are essential for siRNA production, siRNA-directed DNA methylation, retrotransposon silencing, and the punctate nuclear localization patterns typical of both polymerases. Collectively, these data show that the minimal core sequences of polymerase active sites, the Metal A and B sites, are essential for Pol IV and Pol V biological functions, implying that both are catalytically active
The Early Clinical Features of Dengue in Adults: Challenges for Early Clinical Diagnosis
Dengue infection in adults has become increasingly common throughout the world. As most of the clinical features of dengue have been described in children, we undertook a prospective study to determine the early symptoms and signs of dengue in adults. We show here that, overall, dengue cases presented with high rates of symptoms listed in the WHO 1997 or 2009 classification schemes for probable dengue fever thus resulting in high sensitivities of these schemes when applied for early diagnosis. However, symptoms such as myalgia, arthralgia, retro-orbital pain and mucosal bleeding were less frequently reported in older adults. This trend resulted in reduced sensitivity of the WHO classification schemes in older adults even though they showed increased risks of hospitalization and severe dengue. Instead, we suggest that older adults who present with fever and leukopenia should be tested for dengue, even in the absence of other symptoms. This could be useful for early clinical diagnosis in older adults so that they can be monitored and treated for severe dengue, which is especially important when an antiviral drug becomes available
Resveratrol increases BRCA1 and BRCA2 mRNA expression in breast tumour cell lines
International audienceThe phytochemical resveratrol, found in grapes, berries and peanuts, has been found to possess cancer chemopreventive effects by inhibiting diverse cellular events associated with tumour initiation, promotion and progression. Resveratrol is also a phyto-oestrogen, binds to and activates oestrogen receptors that regulate the transcription of oestrogen-responsive target genes such as the breast cancer susceptibility genes BRCA1 and BRCA2. We investigated the effects of resveratrol on BRCA1 and BRCA2 expression in human breast cancer cell lines (MCF7, HBL 100 and MDA-MB 231) using quantitative real-time RT-PCR, and by perfusion chromatography of the proteins. All cell lines were treated with 30 microM resveratrol. The expressions of BRCA1 and BRCA2 mRNAs were increased although no change in the expression of the proteins were found. These data indicate that resveratrol at 30 micro M can increase expression of genes involved in the aggressiveness of human breast tumour cell lines
Serotype-Specific Differences in the Risk of Dengue Hemorrhagic Fever: An Analysis of Data Collected in Bangkok, Thailand from 1994 to 2006
The four dengue viruses (DENV) represent the most common human arbovirus infections in the world and are currently a challenging problem, particularly in the tropical and subtropical regions of Asia and the Americas. Infection with DENV may produce symptoms of varying severity. While access to care, appropriate interventions, host genetic factors, and previous exposure to DENV are all known to affect the outcome of the infection, it is not entirely understood why some individuals develop more severe disease. It has been hypothesized that the four dengue serotypes differ in disease severity and clinical manifestations. This analysis assessed whether there were significant differences in severity of disease caused by the dengue serotypes in a pediatric population in Thailand. We found significant and non-significant correlations between dengue serotype 2 infection and more severe dengue disease. We also found that individual serotypes varied in disease severity between study years, perhaps supporting the hypothesis that the particular sequences of primary and secondary DENV infections influence disease severity
Clinical and Virological Factors Influencing the Performance of a NS1 Antigen-Capture Assay and Potential Use as a Marker of Dengue Disease Severity
Dengue is the most prevalent arthropod-borne disease in tropical regions. The clinical manifestation may vary from asymptomatic to potentially fatal dengue shock syndrome. Early laboratory confirmation of dengue diagnosis is essential since many symptoms are not specific. Dengue non-structural protein 1 (NS1) may be used in simple antigen-capture ELISA for early detection of dengue virus infection. Our result demonstrated that the Platelia NS1 antigen detection kit had a quite low overall sensitivity. However, sensitivity rises significantly when used in combination with MAC-ELISA. When taking into account the various forms of dengue infection, the NS1 antigen detection was found relatively high in patients sampled during the first 3 days of fever onset, in patients with primary infection, DENV-1 infection, with high level of viremia and in mild form of dengue fever. In asymptomatically infected individuals, RT-PCR assay has proved to be more sensitive than NS1 antigen detection. Moreover, the NS1 antigen level correlated significantly with high viremia and low level of NS1 antigen was associated with more severe disease
Morphological brain differences between adult stutterers and non-stutterers
BACKGROUND: The neurophysiological and neuroanatomical foundations of persistent developmental stuttering (PDS) are still a matter of dispute. A main argument is that stutterers show atypical anatomical asymmetries of speech-relevant brain areas, which possibly affect speech fluency. The major aim of this study was to determine whether adults with PDS have anomalous anatomy in cortical speech-language areas. METHODS: Adults with PDS (n = 10) and controls (n = 10) matched for age, sex, hand preference, and education were studied using high-resolution MRI scans. Using a new variant of the voxel-based morphometry technique (augmented VBM) the brains of stutterers and non-stutterers were compared with respect to white matter (WM) and grey matter (GM) differences. RESULTS: We found increased WM volumes in a right-hemispheric network comprising the superior temporal gyrus (including the planum temporale), the inferior frontal gyrus (including the pars triangularis), the precentral gyrus in the vicinity of the face and mouth representation, and the anterior middle frontal gyrus. In addition, we detected a leftward WM asymmetry in the auditory cortex in non-stutterers, while stutterers showed symmetric WM volumes. CONCLUSIONS: These results provide strong evidence that adults with PDS have anomalous anatomy not only in perisylvian speech and language areas but also in prefrontal and sensorimotor areas. Whether this atypical asymmetry of WM is the cause or the consequence of stuttering is still an unanswered question
Activated peripheral lymphocytes with increased expression of cell adhesion molecules and cytotoxic markers are associated with dengue fever disease
Trauma Systems Therapy in Residential Settings: Improving Emotion Regulation and the Social Environment of Traumatized Children and Youth in Congregate Care
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