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The neurotrophins, a family of related polypeptide growth factors including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3 and NT-4/5 promote the survival and differentiation of distinctive sets of embryonic neurons. Here we define a new functional role for neurotrophins, as autocrine or local paracrine mediators(More)
Complex spatial heterogeneity of ecological systems is difficult to capture and interpret using global models alone. For this reason, recent attention has been paid to local spatial modeling techniques. We used one local modeling approach, geographically weighted regression (GWR), to investigate the effects of local spatial heterogeneity on multivariate(More)
Using the Illumina 450K array and a stringent statistical analysis with age and gender correction, we report genome-wide differences in DNA methylation between pathology-free regions derived from human multiple sclerosis-affected and control brains. Differences were subtle, but widespread and reproducible in an independent validation cohort. The(More)
Cholecystokinin (CCK), released by lipid in the intestine, initiates satiety by acting at cholecystokinin type 1 receptors (CCK(1)Rs) located on vagal afferent nerve terminals located in the wall of the gastrointestinal tract. In the present study, we determined the role of the CCK(1)R in the short term effects of a high fat diet on daily food intake and(More)
Aging hematopoietic stem cells (HSCs) exhibit defective lineage specification that is thought to be central to increased incidence of myeloid malignancies and compromised immune competence in the elderly. Mechanisms underlying these age-related defects remain largely unknown. We show that the deacetylase Sirtuin (SIRT)1 is required for homeostatic HSC(More)
Vertebrate kidney development involves a series of complex interactions between the ureteric bud and undifferentiated mesenchyme resulting in the production of the nephron unit. These interactions are thought to be dependent on a variety of locally derived soluble factors, including peptide growth factors and their receptors. We have extensively analyzed(More)
Food intake is controlled by peripheral signals from the gastrointestinal tract and adipocytes, which are integrated within the central nervous system. There is evidence that signals from the GI tract are modulated by long term changes in diet, possibly leading to hyperphagia and increased body weight. We tested the hypothesis that diet-induced obese-prone(More)
Aptamers are single-stranded synthetic DNA- or RNA-based oligonucleotides that fold into various shapes to bind to a specific target, which includes proteins, metals, and molecules. Aptamers have high affinity and high specificity that are comparable to that of antibodies. They are obtained using iterative method, called (Systematic Evolution of Ligands by(More)
We present a new system for automated localization and quantification of the expression of protein biomarkers in immunofluorescence (IF) microscopic images. The system includes a novel method for discriminating the biomarker signal from background, where signal may be the expression of any of the many biomarkers or counterstains used in IF. The method is(More)
Morphological and architectural characteristics of primary tissue compartments, such as epithelial nuclei (EN) and cytoplasm, provide important cues for cancer diagnosis, prognosis, and therapeutic response prediction. We propose two feature sets for the robust quantification of these characteristics in multiplex immunofluorescence (IF) microscopy images of(More)