1,191 research outputs found
Quantitative and qualitative analysis on the legislative production relating to healthcare in passage in the National Congress in the years 2007 and 2008
Management of lithiasis in pelvic kidney through laparoscopy-guided percutaneous transperitoneal nephrolithotripsy
Promoção do autocuidado de idosos para o envelhecer saudável: aplicação da teoria de nola pender
Targeting BTK for the treatment of FLT3-ITD mutated acute myeloid leukemia
Approximately 20% of patients with acute myeloid leukaemia (AML) have a mutation in FMS-like-tyrosine-kinase-3 (FLT3). FLT3 is a trans-membrane receptor with a tyrosine kinase domain which, when activated, initiates a cascade of phosphorylated proteins including the SRC family of kinases. Recently our group and others have shown that pharmacologic inhibition and genetic knockdown of Bruton's tyrosine kinase (BTK) blocks AML blast proliferation, leukaemic cell adhesion to bone marrow stromal cells as well as migration of AML blasts. The anti-proliferative effects of BTK inhibition in human AML are mediated via inhibition of downstream NF-κB pro-survival signalling however the upstream drivers of BTK activation in human AML have yet to be fully characterised. Here we place the FLT3-ITD upstream of BTK in AML and show that the BTK inhibitor ibrutinib inhibits the survival and proliferation of FLT3-ITD primary AML blasts and AML cell lines. Furthermore ibrutinib inhibits the activation of downstream kinases including MAPK, AKT and STAT5. In addition we show that BTK RNAi inhibits proliferation of FLT3-ITD AML cells. Finally we report that ibrutinib reverses the cyto-protective role of BMSC on FLT3-ITD AML survival. These results argue for the evaluation of ibrutinib in patients with FLT3-ITD mutated AML
Utilização da tomografia computadorizada para o diagnóstico da articulação temporomandibular
Tratamento fisioterapêutico vascular para a doença venosa crônica: artigo de revisão
Social interaction, noise and antibiotic-mediated switches in the intestinal microbiota
The intestinal microbiota plays important roles in digestion and resistance
against entero-pathogens. As with other ecosystems, its species composition is
resilient against small disturbances but strong perturbations such as
antibiotics can affect the consortium dramatically. Antibiotic cessation does
not necessarily restore pre-treatment conditions and disturbed microbiota are
often susceptible to pathogen invasion. Here we propose a mathematical model to
explain how antibiotic-mediated switches in the microbiota composition can
result from simple social interactions between antibiotic-tolerant and
antibiotic-sensitive bacterial groups. We build a two-species (e.g. two
functional-groups) model and identify regions of domination by
antibiotic-sensitive or antibiotic-tolerant bacteria, as well as a region of
multistability where domination by either group is possible. Using a new
framework that we derived from statistical physics, we calculate the duration
of each microbiota composition state. This is shown to depend on the balance
between random fluctuations in the bacterial densities and the strength of
microbial interactions. The singular value decomposition of recent metagenomic
data confirms our assumption of grouping microbes as antibiotic-tolerant or
antibiotic-sensitive in response to a single antibiotic. Our methodology can be
extended to multiple bacterial groups and thus it provides an ecological
formalism to help interpret the present surge in microbiome data.Comment: 20 pages, 5 figures accepted for publication in Plos Comp Bio.
Supplementary video and information availabl
The C-terminal region of Trypanosoma cruzi MASPs is antigenic and secreted via exovesicles.
Trypanosoma cruzi is the etiological agent of Chagas disease, a neglected and emerging tropical disease, endemic to South America and present in non-endemic regions due to human migration. The MASP multigene family is specific to T. cruzi, accounting for 6% of the parasite's genome and plays a key role in immune evasion. A common feature of MASPs is the presence of two conserved regions: an N-terminal region codifying for signal peptide and a C-terminal (C-term) region, which potentially acts as GPI-addition signal peptide. Our aim was the analysis of the presence of an immune response against the MASP C-term region. We found that this region is highly conserved, released via exovesicles (EVs) and has an associated immune response as revealed by epitope affinity mapping, IFA and inhibition of the complement lysis assays. We also demonstrate the presence of a fast IgM response in Balb/c mice infected with T. cruzi. Our results reveal the presence of non-canonical secreted peptides in EVs, which can subsequently be exposed to the immune system with a potential role in evading immune system targets in the parasite
Fast assessment of mineral constituents in grass by inductively coupled plasma optical emission spectrometry
- …