382 research outputs found
Cell signalling in survival: Natural compounds and small-molecule inhibitors provide essential insight
Effective response to treatment is still a challenge in the clinical management of many types
of tumors. As result of pharmacological intervention two different fates are observed for
a cancer cell: survival or death. These two cell fates are intimately related to the overall
response to treatment. Survival of a cancer cell to an aggressive treatment usually means
inefficacy of a determined drug and cell death means that the cells were sensitive to the
treatment. In the current literature many types of cell death are suggested. Of equal
importance is the understanding of the mechanisms and signal cascades of survival.
Crosstalk between multiple signal transduction pathways may organize an intricate survival
network with overlapping functions that together provide strong survival signals to a
dying cell. Importantly, these survival signals seem to be on the background of the classic
mechanism of drug resistance which holds true for a lower efficacy of determined class of
molecules or structurally unrelated ones, such as drug efflux, drug uptake, drug metabolism,
DNA repair and impaired drug binding to its target. Importantly, different types of tumors
present different aspects of surviving, as an example the building up of a drug resistant
phenotype in hematological diseases is usually a long term process, resulting in an initial
response to treatment. However, relapses occur after sometime, and not always remission
is achieved with the same therapeutic strategy. The development or acquisition of drug
resistance is a quite remarkable aspect of hematological malignancies. On another hand,
this first response to pharmacological strategies is not really achieved in tumors such as,
pancreatic cancer (PDAC). Less than 10% of pat
On the uniform controllability for a family of non-viscous and viscous Burgers- α systems
In this paper we study the global controllability of families of the so called non-viscous
and viscous Burgers- systems by using boundary and space independent distributed controls. In
these equations, the usual convective velocity of the Burgers equation is replaced by a regularized
velocity, induced by a Helmholtz lter of characteristic wavelength . First, we prove a global exact
controllability result (uniform with respect to ) for the non-viscous Burgers- system, using the return
method and a xed-point argument. Then, the global uniform exact controllability to constant states is
deduced for the viscous equations. To this purpose, we rst prove a local exact controllability property
and, then, we establish a global approximate controllability result for smooth initial and target states
On some geometric inverse problems for nonscalar elliptic systems
In this paper, we consider several geometric inverse problems for linear elliptic systems. We prove
uniqueness and stability results. In particular, we show the way that the observation depends on the perturbations of the domain. In some particular situations, this provides a strategy that could be used to compute
approximations to the solution of the inverse problem. In the proofs, we use techniques related to (local)
Carleman estimates and differentiation with respect to the domain
The effects of inter-crop cultivation Between rows of citrus crop on spreading of Guignardia citricarpa Ascospores and in the citrus black spot occurrence
PAK2 is an effector of TSC1/2 signaling independent of mTOR and a potential therapeutic target for Tuberous Sclerosis Complex
Tuberous sclerosis complex (TSC) is caused by inactivating mutations in either TSC1 or TSC2 and is characterized by uncontrolled mTORC1 activation. Drugs that reduce mTOR activity are only partially successful in the treatment of TSC, suggesting that mTOR-independent pathways play a role in disease development. Here, kinome profiles of wild-type and Tsc2-/- mouse embryonic fibroblasts (MEFs) were generated, revealing a prominent role for PAK2 in signal transduction downstream of TSC1/2. Further investigation showed that the effect of the TSC1/2 complex on PAK2 is mediated through RHEB, but is independent of mTOR and p21RAC. We also demonstrated that PAK2 over-activation is likely responsible for the migratory and cell cycle abnormalities observed in Tsc2-/- MEFs. Finally, we detected high levels of PAK2 activation in giant cells in the brains of TSC patients. These results show that PAK2 is a direct effector of TSC1-TSC2-RHEB signaling and a new target for rational drug therapy in TSC
Evolução anual da qualidade do leite cru refrigerado processado em uma indústria de Minas Gerais
C9ORF72 patient-derived endothelial cells drive blood-brain barrier disruption and contribute to neurotoxicity
The blood-brain barrier (BBB) serves as a highly intricate and dynamic interface connecting the brain and the bloodstream, playing a vital role in maintaining brain homeostasis. BBB dysfunction has been associated with multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS); however, the role of the BBB in neurodegeneration is understudied. We developed an ALS patient-derived model of the BBB by using cells derived from 5 patient donors carrying C9ORF72 mutations. Brain microvascular endothelial-like cells (BMEC-like cells) derived from C9ORF72-ALS patients showed altered gene expression, compromised barrier integrity, and increased P-glycoprotein transporter activity. In addition, mitochondrial metabolic tests demonstrated that C9ORF72-ALS BMECs display a significant decrease in basal glycolysis accompanied by increased basal and ATP-linked respiration. Moreover, our study reveals that C9-ALS derived astrocytes can further affect BMECs function and affect the expression of the glucose transporter Glut-1. Finally, C9ORF72 patient-derived BMECs form leaky barriers through a cell-autonomous mechanism and have neurotoxic properties towards motor neurons
Building The Sugarcane Genome For Biotechnology And Identifying Evolutionary Trends
Background: Sugarcane is the source of sugar in all tropical and subtropical countries and is becoming increasingly important for bio-based fuels. However, its large (10 Gb), polyploid, complex genome has hindered genome based breeding efforts. Here we release the largest and most diverse set of sugarcane genome sequences to date, as part of an on-going initiative to provide a sugarcane genomic information resource, with the ultimate goal of producing a gold standard genome.Results: Three hundred and seventeen chiefly euchromatic BACs were sequenced. A reference set of one thousand four hundred manually-annotated protein-coding genes was generated. A small RNA collection and a RNA-seq library were used to explore expression patterns and the sRNA landscape. In the sucrose and starch metabolism pathway, 16 non-redundant enzyme-encoding genes were identified. One of the sucrose pathway genes, sucrose-6-phosphate phosphohydrolase, is duplicated in sugarcane and sorghum, but not in rice and maize. A diversity analysis of the s6pp duplication region revealed haplotype-structured sequence composition. Examination of hom(e)ologous loci indicate both sequence structural and sRNA landscape variation. A synteny analysis shows that the sugarcane genome has expanded relative to the sorghum genome, largely due to the presence of transposable elements and uncharacterized intergenic and intronic sequences.Conclusion: This release of sugarcane genomic sequences will advance our understanding of sugarcane genetics and contribute to the development of molecular tools for breeding purposes and gene discovery. © 2014 de Setta et al.; licensee BioMed Central Ltd.151European Commission: Agriculture and Rural Development: Sugar http://ec.europa.eu/agriculture/sugar/index_en.htmKellogg, E.A., Evolutionary history of the grasses (2001) Plant Physiol, 125, pp. 1198-1205Grivet, L., Arruda, P., Sugarcane genomics: depicting the complex genome of an important tropical crop (2001) Curr Opin Plant Biol, 5, pp. 122-127Piperidis, G., Piperidis, N., D'Hont, A., Molecular cytogenetic investigation of chromosome composition and transmission in sugarcane (2010) Mol Genet Genomics, 284, pp. 65-73D'Hont, A., 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Mortality among patients with non-affective functional psychoses in a metropolitan area of South-Eastern Brazil
Evidence of Color Coherence Effects in W+jets Events from ppbar Collisions at sqrt(s) = 1.8 TeV
We report the results of a study of color coherence effects in ppbar
collisions based on data collected by the D0 detector during the 1994-1995 run
of the Fermilab Tevatron Collider, at a center of mass energy sqrt(s) = 1.8
TeV. Initial-to-final state color interference effects are studied by examining
particle distribution patterns in events with a W boson and at least one jet.
The data are compared to Monte Carlo simulations with different color coherence
implementations and to an analytic modified-leading-logarithm perturbative
calculation based on the local parton-hadron duality hypothesis.Comment: 13 pages, 6 figures. Submitted to Physics Letters
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