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191.
Immune suppression remains a consistent obstacle to successful anti-tumor immune responses. As tumors develop, they create
a microenvironment that not only supports tumor growth and metastasis but also reduces potential adaptive immunity to tumor
antigens. Among the many components of this tumor microenvironment is a population of dendritic cells which exert profound
immune suppressive effects on T cells. In this review, we discuss our recent findings related to these tumor-associated dendritic
cells and how targeting them may serve to generate more durable anti-tumor immune responses. 相似文献
192.
Jay G. Forsythe Sloane L. English Rachel E. Simoneaux Arthur L. Weber 《Origins of life and evolution of the biosphere》2018,48(2):201-211
A one-pot method was developed for the preparation of a series of β-alanine standards of moderate size (2 to ≥12 residues) for studies concerning the prebiotic origins of peptides. The one-pot synthesis involved two sequential reactions: (1) dry-down self-condensation of β-alanine methyl ester, yielding β-alanine peptide methyl ester oligomers, and (2) subsequent hydrolysis of β-alanine peptide methyl ester oligomers, producing a series of β-alanine peptide standards. These standards were then spiked into a model prebiotic product mixture to confirm by HPLC the formation of β-alanine peptides under plausible reaction conditions. The simplicity of this approach suggests it can be used to prepare a variety of β-peptide standards for investigating differences between α- and β-peptides in the context of prebiotic chemistry. 相似文献
193.
Survivin as a target for new anticancer interventions 总被引:66,自引:0,他引:66
Survivin is a member of the inhibitor of apoptosis protein (IAP) family, that has been implicated in both control of cell division and inhibition of apoptosis. Specifically, its anti-apoptotic function seems to be related to the ability to directly or indirectly inhibit caspases. Survivin is selectively expressed in the most common human neoplasms and appears to be involved in tumor cell resistance to some anticancer agents and ionizing radiation. On the basis of these findings survivin has been proposed as an attractive target for new anticancer interventions. Several preclinical studies have demonstrated that down-regulation of survivin expression/function, accomplished through the use of antisense oligonucleotides, dominant negative mutants, ribozymes, small interfering RNAs and cyclin-dependent kinase inhibitors, increased the apoptotic rate, reduced tumor-growth potential and sensitized tumor cells to chemotherapeutic drugs with different action mechanisms and gamma-irradiation in in vitro and in vivo models of different human tumor types. 相似文献
194.
Differential expression analysis for sequence count data 总被引:22,自引:0,他引:22
High-throughput sequencing assays such as RNA-Seq, ChIP-Seq or barcode counting provide quantitative readouts in the form
of count data. To infer differential signal in such data correctly and with good statistical power, estimation of data variability
throughout the dynamic range and a suitable error model are required. We propose a method based on the negative binomial distribution,
with variance and mean linked by local regression and present an implementation, DESeq, as an R/Bioconductor package. 相似文献
195.
Corti A 《Cellular and molecular neurobiology》2010,30(8):1163-1170
Chromogranin A (CgA) is an acidic glycoprotein belonging to a family of regulated secretory proteins stored in the dense core
granules of the adrenal medulla and of many other neuroendocrine cells and neurons. This protein is frequently used as a diagnostic
and prognostic serum marker for a range of neuroendocrine tumors. Circulating CgA is also increased in patients with other
diseases, including subpopulations of patients with non-neuroendocrine tumors, with important prognostic implications. A growing
body of evidence suggests that CgA is more than a diagnostic/prognostic marker for cancer patients. Indeed, results of in
vitro experiments and in vivo studies in animal models suggest that this protein and its fragments can affect several elements
of the tumor microenvironment, including fibroblasts and endothelial cells. In this article, recent findings implicating CgA
as a modulator of the tumor microenvironment and suggesting that abnormal secretion of CgA could play important roles in tumor
progression and response to therapy in cancer patients are reviewed and discussed. 相似文献
196.
Rhamnolipids, produced by Pseudomonas aeruginosa, represent an important group of biosurfactants having various industrial, environmental, and medical applications. Current
methods for rhamnolipid quantification involve the use of strong hazardous acids/chemicals, indirect measurement of the concentration
of sugar moiety, or require the availability of expensive equipment (HPLC-MS). A safer, easier method that measures the whole
rhamnolipid molecules would significantly enhance strain selection, metabolic engineering, and process development for economical
rhamnolipid production. A semi-quantitative method was reported earlier to differentiate between the rhamnolipid-producing
and non-producing strains using agar plates containing methylene blue and cetyl trimethylammonium bromide (CTAB). In this
study, a rapid and simple method for rhamnolipid analysis was developed by systematically investigating the complexation of
rhamnolipids and methylene blue, with and without the presence of CTAB. The method relies on measuring the absorbance (at
638 nm) of the rhamnolipid−methylene blue complex that partitions into the chloroform phase. With P. aeruginosa fermentation samples, the applicability of this method was verified by comparison of the analysis results with those obtained
from the commonly used anthrone reaction technique. 相似文献
197.
Gloria Alvarez-Sola Iker Uriarte Maria U. Latasa Maddalen Jimenez Marina Barcena-Varela Eva Santamaría Raquel Urtasun Carlos Rodriguez-Ortigosa Jesús Prieto Pedro Berraondo Maite G. Fernandez-Barrena Carmen Berasain Matías A. Avila 《生物化学与生物物理学报:疾病的分子基础》2018,1864(4):1326-1334
The liver has an extraordinary regenerative capacity rapidly triggered upon injury or resection. This response is intrinsically adjusted in its initiation and termination, a property termed the “hepatostat”. Several molecules have been involved in liver regeneration, and among them bile acids may play a central role. Intrahepatic levels of bile acids rapidly increase after resection. Through the activation of farnesoid X receptor (FXR), bile acids regulate their hepatic metabolism and also promote hepatocellular proliferation. FXR is also expressed in enterocytes, where bile acids stimulate the expression of fibroblast growth factor 15/19 (FGF15/19), which is released to the portal blood. Through the activation of FGFR4 on hepatocytes FGF15/19 regulates bile acids synthesis and finely tunes liver regeneration as part of the “hepatostat”. Here we review the experimental evidences supporting the relevance of the FXR-FGF15/19-FGFR4 axis in liver regeneration and discuss potential therapeutic applications of FGF15/19 in the prevention of liver failure. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen. 相似文献
198.
199.
Vanessa B. Fortes Júlio César Bicca-Marques 《International journal of primatology》2008,29(3):717-722
We located 4 brown howlers (1 adult male, 2 adult females, and 1 juvenile male) showing abnormally lighter pelage in 3 social
groups comprising 5, 6, and 9 individuals in a 20 ha-forest fragment in the State of Rio Grande do Sul, Brazil. Two additional
groups composed only of normally colored individuals also live in the fragment, which is isolated from nearby fragments by
267–1009 m. They were the only brown howlers with abnormal pelage color out of a total of 386 individuals belonging to 67
groups in 21 fragments in the 5876-ha study area. The isolation of the forest fragment, its high howler density (2.2 individuals⁄ha),
and large group size (8.8 ± 2.4 individuals) may decrease the likelihood of successful immigration into the population, leading
to an increased probability of inbreeding that may facilitate the expression of rare alleles. 相似文献
200.
Random network models have been a popular tool for investigating cortical network dynamics. On the scale of roughly a cubic millimeter of cortex, containing about 100,000 neurons, cortical anatomy suggests a more realistic architecture. In this locally connected random network, the connection probability decreases in a Gaussian fashion with the distance between neurons. Here we present three main results from a simulation study of the activity dynamics in such networks. First, for a broad range of parameters these dynamics exhibit a stationary state of asynchronous network activity with irregular single-neuron spiking. This state can be used as a realistic model of ongoing network activity. Parametric dependence of this state and the nature of the network dynamics in other regimes are described. Second, a synchronous excitatory stimulus to a fraction of the neurons results in a strong activity response that easily dominates the network dynamics. And third, due to that activity response an embedding of a divergent-convergent feed-forward subnetwork (as in synfire chains) does not naturally lead to a stable propagation of synchronous activity in the subnetwork; this is in contrast to our earlier findings in isolated subnetworks of that type. Possible mechanisms for stabilizing the interplay of volleys of synchronous spikes and network dynamics by specific learning rules or generalizations of the subnetworks are discussed. 相似文献