181 research outputs found
Detection of viral antigen, IgM and IgG antibodies in cerebrospinal fluid of Chikungunya patients with neurological complications
BACKGROUND: During Chikungunya virus (CHIKV) epidemic in Nagpur, India, we identified some suspected Chikungunya patients with neurological complications. Early and cost-effective diagnosis of these patients remains problematic despite many new advanced diagnostic methods. A reliable diagnostic test, which could be performed in any standard pathology laboratory, would help to obtain definitive early diagnosis of CHIKV patients with neurological complications. In our laboratory, in-house ELISA protocol for viral antigen, immunoglobulin M (IgM) and IgG detection has been developed and assessed for the diagnosis of CHIKV patients with neurological complications. METHOD: Cerebrospinal fluid samples of forty-six patients who developed neurological symptoms within two months of CHIKV infections along with control subjects were included in the study and were analyzed for the presence of antigens and of IgM and IgG using an ELISA protocol. RESULTS: The ELISA method for antigen detection yielded 80% sensitivity and 87% specificity for the diagnosis of CHIKV patients with neurological complications. The sensitivity for detection of IgM 48% or IgG 63% was significantly lower than the antigen assay (80%). CONCLUSION: The detection of viral antigen in CSF of CHIKV patients with neurological complications by ELISA method gave a more reliable diagnosis than antibodies detection that can be used to develop an immunodiagnostic assay with increased sensitivity and specificity
Design of the strut braced wing aircraft in the agile collaborative MDO framework
The paper describes the deployment of the AGILE Development Framework to investigate the Strut Braced Wing aircraft configuration. The design process consists of a multilevel multidisciplinary architecture, progressing from the initial conceptual synthesis to the physics based analysis. All the main disciplinary domains, including on board system design and cost assessment, are accounted for in the assembled workflow. Due to the specific characteristics of the Strut Braced Wing configuration, the aeroelastic analysis is the main focus of the study and it is addressed at both high and low fidelity levels. The integration of the engine-wing system is also included in the design process. All the design competences, which are hosted at the different partners, communicate via CPACS (Common Parametric Aircraft Configuration Schema) data schema. All the results generated, including the multidisciplinary design process itself, will be published and made available as part of the AGILE Overall Aircraft Design database
Psychedelics and schizophrenia: Distinct alterations to Bayesian inference
Schizophrenia and states induced by certain psychotomimetic drugs may share some physiological and phenomenological properties, but they differ in fundamental ways: one is a crippling chronic mental disease, while the others are temporary, pharmacologically-induced states presently being explored as treatments for mental illnesses. Building towards a deeper understanding of these different alterations of normal consciousness, here we compare the changes in neural dynamics induced by LSD and ketamine (in healthy volunteers) against those associated with schizophrenia, as observed in resting-state M/EEG recordings. While both conditions exhibit increased neural signal diversity, our findings reveal that this is accompanied by an increased transfer entropy from the front to the back of the brain in schizophrenia, versus an overall reduction under the two drugs. Furthermore, we show that these effects can be reproduced via different alterations of standard Bayesian inference applied on a computational model based on the predictive processing framework. In particular, the effects observed under the drugs are modelled as a reduction of the precision of the priors, while the effects of schizophrenia correspond to an increased precision of sensory information. These findings shed new light on the similarities and differences between schizophrenia and two psychotomimetic drug states, and have potential implications for the study of consciousness and future mental health treatments
Assessment of immune response to repeat stimulation with BCG vaccine using in vitro PBMC model
Global Trends in the Use of Insecticides to Control Vector-Borne Diseases
Background: Data on insecticide use for vector control are essential for guiding pesticide management systems on judicious and appropriate use, resistance management, and reduction of risks to human health and the environment
Investigation of Immune Biomarkers Using Subcutaneous Model of M. tuberculosis Infection in BALB/c Mice: A Preliminary Report
Evaluation and screening of vaccines against tuberculosis
depends on development of proper cost effective disease
models along with identification of different immune markers
that can be used as surrogate endpoints of protection in preclinical
and clinical studies. The objective of the present
study was therefore evaluation of subcutaneous model of
M.tuberculosis infection along with investigation of different
immune biomarkers of tuberculosis infection in BALB/c
mice. Groups of mice were infected subcutaneously with two
different doses : high (2Γ106
CFU) and low doses (2Γ102
CFU) of M.tuberculosis and immune markers including humoral
and cellular markers were evaluated 30 days post
M.tuberculosis infections. Based on results, we found that
high dose of subcutaneous infection produced chronic disease
with significant (p<0.001) production of immune markers
of infection like IFNΞ³, heat shock antigens (65, 71) and
antibody titres against panel of M.tuberculosis antigens
(ESAT-6, CFP-10, Ag85B, 45kDa, GroES, Hsp-16) all of
which correlated with high bacterial burden in lungs and
spleen. To conclude high dose of subcutaneous infection produces
chronic TB infection in mice and can be used as convenient
alternative to aerosol models in resource limited
settings. Moreover assessment of immune markers namely
mycobacterial antigens and antibodies can provide us valuable
insights on modulation of immune response post
infection. However further investigations along with optimization
of study protocols are needed to justify the outcome
of present study and establish such markers as surrogate
endpoints of vaccine protection in preclinical and clinical
studies in futur
Resistance of Foxp3+ Regulatory T Cells to Nur77-Induced Apoptosis Promotes Allograft Survival
The NR4A nuclear receptor family member Nur77 (NR4A1) promotes thymocyte apoptosis during negative selection of autoreactive thymocytes, but may also function in mature extrathymic T cells. We studied the effects of over-expression of Nur77 on the apoptosis of murine peripheral T cells, including thymic-derived Foxp3+ regulatory (Treg) cells. Overexpression of Nur77 in the T cell lineage decreased numbers of peripheral CD4 and CD8 T cells by βΌ80% compared to wild-type (WT) mice. However, the proportions of Treg cells were markedly increased in the thymus (61% of CD4+Foxp3+ singly positive thymocytes vs. 8% in WT) and secondary lymphoid organs (40β50% of CD4+Foxp3+ T cells vs. 7β8% in WT) of Nur77 transgenic (Nur77Tg) mice, and immunoprecipitation studies showed Nur77 was associated with a recently identified HDAC7/Foxp3 transcriptional complex. Upon activation through the T cell receptor in vitro or in vivo, Nur77Tg T cells showed only marginally decreased proliferation but significantly increased apoptosis. Fully allogeneic cardiac grafts transplanted to Nur77Tg mice survived long-term with well-preserved structure, and recipient splenocytes showed markedly enhanced apoptosis and greatly reduced anti-donor recall responses. Allografts in Nur77Tg recipients had significantly increased expression of multiple Treg-associated genes, including Foxp3, Foxp1, Tip60 and HDAC9. Allograft rejection was restored by CD25 monoclonal antibody therapy, indicating that allograft acceptance was dependent upon Treg function in Nur77Tg recipients. These data show that compared to conventional CD4 and CD8 T cells, Foxp3+ Tregs are relatively resistant to Nur77-mediated apoptosis, and that tipping the balance between the numbers of Tregs and responder T cells in the early period post-transplantation can determine the fate of the allograft. Hence, induced expression of Nur77 might be a novel means to achieve long-term allograft survival
The N-terminus of FILIA Forms an Atypical KH Domain with a Unique Extension Involved in Interaction with RNA
FILIA is a member of the recently identified oocyte/embryo expressed gene family in eutherian mammals, which is characterized by containing an N-terminal atypical KH domain. Here we report the structure of the N-terminal fragment of FILIA (FILIA-N), which represents the first reported three-dimensional structure of a KH domain in the oocyte/embryo expressed gene family of proteins. The structure of FILIA-N revealed a unique N-terminal extension beyond the canonical KH region, which plays important roles in interaction with RNA. By co-incubation with the lysates of mice ovaries, FILIA and FILIA-N could sequester specific RNA components, supporting the critical roles of FILIA in regulation of RNA transcripts during mouse oogenesis and early embryogenesis
HDAC Inhibition Decreases the Expression of EGFR in Colorectal Cancer Cells
Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase which
promotes cell proliferation and survival, is abnormally overexpressed in
numerous tumors of epithelial origin, including colorectal cancer (CRC). EGFR
monoclonal antibodies have been shown to increase the median survival and are
approved for the treatment of colorectal cancer. Histone deacetylases (HDACs),
frequently overexpressed in colorectal cancer and several malignancies, are
another attractive targets for cancer therapy. Several inhibitors of HDACs
(HDACi) are developed and exhibit powerful antitumor abilities. In this study,
human colorectal cancer cells treated with HDACi exhibited reduced EGFR
expression, thereby disturbed EGF-induced ERK and Akt phosphorylation. HDACi
also decreased the expression of SGLT1, an active glucose transporter found to
be stabilized by EGFR, and suppressed the glucose uptake of cancer cells. HDACi
suppressed the transcription of EGFR and class I HDACs were proved to be
involved in this event. Chromatin immunoprecipitation analysis showed that HDACi
caused the dissociation of SP1, HDAC3 and CBP from EGFR promoter. Our data
suggested that HDACi could serve as a single agent to block both EGFR and HDAC,
and may bring more benefits to the development of CRC therapy
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