Identification of sex hormone-binding globulin in the human hypothalamus

Gonadal steroids are known to influence hypothalamic functions through both genomic and non-genomic pathways. Sex hormone-binding globulin ( SHBG) may act by a non-genomic mechanism independent of classical steroid receptors. Here we describe the immunocytochemical mapping of SHBG-containing neurons and nerve fibers in the human hypothalamus and infundibulum. Mass spectrometry and Western blot analysis were also used to characterize the biochemical characteristics of SHBG in the hypothalamus and cerebrospinal fluid (CSF) of humans. SHBG-immunoreactive neurons were observed in the supraoptic nucleus, the suprachiasmatic nucleus, the bed nucleus of the stria terminalis, paraventricular nucleus, arcuate nucleus, the perifornical region and the medial preoptic area in human brains. There were SHBG-immunoreactive axons in the median eminence and the infundibulum. A partial colocalization with oxytocin could be observed in the posterior pituitary lobe in consecutive semithin sections. We also found strong immunoreactivity for SHBG in epithelial cells of the choroid plexus and in a portion of the ependymal cells lining the third ventricle. Mass spectrometry showed that affinity-purified SHBG from the hypothalamus and choroid plexus is structurally similar to the SHBG identified in the CSF. The multiple localizations of SHBG suggest neurohypophyseal and neuroendocrine functions. The biochemical data suggest that CSF SHBG is of brain rather than blood origin. Copyright (c) 2005 S. Karger AG, Base

Dual-task costs while walking increase in old age for some, but not for other tasks: an experimental study of healthy young and elderly persons

<p>Abstract</p> <p>Background</p> <p>It has been suggested in the past that the ability to walk while concurrently engaging in a second task deteriorates in old age, and that this deficit is related to the high incidence of falls in the elderly. However, previous studies provided inconsistent findings about the existence of such an age-related dual-task deficit (ARD). In an effort to explain this inconsistency, we explored whether ARD while walking emerges for some, but not for other types of task.</p> <p>Methods</p> <p>Healthy young and elderly subjects were tested under five different combinations of a walking and a non-walking task. The results were analysed jointly with those of a previous study from our lab, such that a total of 13 task combinations were evaluated. For each task combination and subject, we calculated the mean dual-task costs across both constituent tasks, and quantified ARD as the difference between those costs in elderly and in young subjects.</p> <p>Results</p> <p>An analysis of covariance yielded no significant effects of obstacle presence and overall task difficulty on ARD, but a highly significant effect of visual demand: non-walking tasks which required ongoing visual observation led to ARD of more than 8%, while those without such requirements led to near-zero ARD. We therefore concluded that the visual demand of the non-walking task is critical for the emergence of ARD while walking.</p> <p>Conclusion</p> <p>Combinations of walking and concurrent visual observation, which are common in everyday life, may contribute towards disturbed gait and falls during daily activities in old age. Prevention and rehabilitation programs for seniors should therefore include training of such combinations.</p

MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors

There is increasing evidence that oncogenic transformation modifies the metabolic program of cells. A common alteration is the upregulation of glycolysis, and efforts to target glycolytic enzymes for anticancer therapy are under way. Here, we performed a genome-wide haploid genetic screen to identify resistance mechanisms to 3-bromopyruvate (3-BrPA), a drug candidate that inhibits glycolysis in a poorly understood fashion. We identified the SLC16A1 gene product, MCT1, as the main determinant of 3-BrPA sensitivity. MCT1 is necessary and sufficient for 3-BrPA uptake by cancer cells. Additionally, SLC16A1 mRNA levels are the best predictor of 3-BrPA sensitivity and are most elevated in glycolytic cancer cells. Furthermore, forced MCT1 expression in 3-BrPA–resistant cancer cells sensitizes tumor xenografts to 3-BrPA treatment in vivo. Our results identify a potential biomarker for 3-BrPA sensitivity and provide proof of concept that the selectivity of cancer-expressed transporters can be exploited for delivering toxic molecules to tumors.National Institutes of Health (U.S.) (NIH CA103866)Jane Coffin Childs Memorial Fund for Medical Research (Fellowship)National Science Foundation (U.S.) (Fellowship)Howard Hughes Medical Institute (Investigator

Hydrology Affects Environmental and Spatial Structuring of Microalgal Metacommunities in Tropical Pacific Coast Wetlands

The alternating climate between wet and dry periods has important effects on the hydrology and therefore on niche-based processes of water bodies in tropical areas. Additionally, assemblages of microorganism can show spatial patterns, in the form of a distance decay relationship due to their size or life form. We aimed to test spatial and environmental effects, modulated by a seasonal flooding climatic pattern, on the distribution of microalgae in 30 wetlands of a tropical dry forest region: the Pacific coast of Costa Rica and Nicaragua. Three surveys were conducted corresponding to the beginning, the highest peak, and the end of the hydrological year during the wet season, and species abundance and composition of planktonic and benthic microalgae was determined. Variation partitioning analysis (as explained by spatial distance or environmental factors) was applied to each seasonal dataset by means of partial redundancy analysis. Our results show that microalgal assemblages were structured by spatial and environmental factors depending on the hydrological period of the year. At the onset of hydroperiod and during flooding, neutral effects dominated community dynamics, but niche-based local effects resulted in more structured algal communities at the final periods of desiccating water bodies. Results suggest that climatemediated effects on hydrology can influence the relative role of spatial and environmental factors on metacommunities of microalgae. Such variability needs to be accounted in order to describe accurately community dynamics in tropical coastal wetlands.Agencia Española de Cooperación y Desarrollo/[A1024073/09]/AECID/EspañaAgencia Española de Cooperación y Desarrollo/[A/031019/10]/AECID/EspañaAgencia Española de Cooperación y Desarrollo/[C/032994/10]/AECID/EspañaAgencia Española de Cooperación y Desarrollo/[A3/ 036594/11]/AECID/EspañaUniversidad de Costa Rica/[741-B1-517]/UCR/Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)UCR::Vicerrectoría de Docencia::Salud::Facultad de Microbiologí