Caffeine Consumption Prevents Diabetes-Induced Memory Impairment and Synaptotoxicity in the Hippocampus of NONcZNO10/LTJ Mice

Diabetic conditions are associated with modified brain function, namely with cognitive deficits, through largely undetermined processes. More than understanding the underlying mechanism, it is important to devise novel strategies to alleviate diabetes-induced cognitive deficits. Caffeine (a mixed antagonist of adenosine A1 and A2A receptors) emerges as a promising candidate since caffeine consumption reduces the risk of diabetes and effectively prevents memory deficits caused by different noxious stimuli. Thus, we took advantage of a novel animal model of type 2 diabetes to investigate the behavioural, neurochemical and morphological modifications present in the hippocampus and tested if caffeine consumption might prevent these changes. We used a model closely mimicking the human type 2 diabetes condition, NONcNZO10/LtJ mice, which become diabetic at 7–11 months when kept under an 11% fat diet. Caffeine (1 g/l) was applied in the drinking water from 7 months onwards. Diabetic mice displayed a decreased spontaneous alternation in the Y-maze accompanied by a decreased density of nerve terminal markers (synaptophysin, SNAP25), mainly glutamatergic (vesicular glutamate transporters), and increased astrogliosis (GFAP immunoreactivity) compared to their wild type littermates kept under the same diet. Furthermore, diabetic mice displayed up-regulated A2A receptors and down-regulated A1 receptors in the hippocampus. Caffeine consumption restored memory performance and abrogated the diabetes-induced loss of nerve terminals and astrogliosis. These results provide the first evidence that type 2 diabetic mice display a loss of nerve terminal markers and astrogliosis, which is associated with memory impairment; furthermore, caffeine consumption prevents synaptic dysfunction and astrogliosis as well as memory impairment in type 2 diabetes

The Genome of Ganderma lucidum Provide Insights into Triterpense Biosynthesis and Wood Degradation

BACKGROUND: Ganoderma lucidum (Reishi or Ling Zhi) is one of the most famous Traditional Chinese Medicines and has been widely used in the treatment of various human diseases in Asia countries. It is also a fungus with strong wood degradation ability with potential in bioenergy production. However, genes, pathways and mechanisms of these functions are still unknown. METHODOLOGY/PRINCIPAL FINDINGS: The genome of G. lucidum was sequenced and assembled into a 39.9 megabases (Mb) draft genome, which encoded 12,080 protein-coding genes and ∼83% of them were similar to public sequences. We performed comprehensive annotation for G. lucidum genes and made comparisons with genes in other fungi genomes. Genes in the biosynthesis of the main G. lucidum active ingredients, ganoderic acids (GAs), were characterized. Among the GAs synthases, we identified a fusion gene, the N and C terminal of which are homologous to two different enzymes. Moreover, the fusion gene was only found in basidiomycetes. As a white rot fungus with wood degradation ability, abundant carbohydrate-active enzymes and ligninolytic enzymes were identified in the G. lucidum genome and were compared with other fungi. CONCLUSIONS/SIGNIFICANCE: The genome sequence and well annotation of G. lucidum will provide new insights in function analyses including its medicinal mechanism. The characterization of genes in the triterpene biosynthesis and wood degradation will facilitate bio-engineering research in the production of its active ingredients and bioenergy

Development of estimates of dietary nitrates, nitrites, and nitrosamines for use with the short willet food frequency questionnaire

<p>Abstract</p> <p>Background</p> <p>Studies have suggested that nitrates, nitrites, and nitrosamines have an etiologic role in adverse pregnancy outcomes and chronic diseases such as cancer. Although an extensive body of literature exists on estimates of these compounds in foods, the extant data varies in quality, quantified estimates, and relevance.</p> <p>Methods</p> <p>We developed estimates of nitrates, nitrites, and nitrosamines for food items listed in the Short Willet Food Frequency Questionnaire (WFFQ) as adapted for use in the National Birth Defects Prevention Study. Multiple reference databases were searched for published literature reflecting nitrate, nitrite, and nitrosamine values in foods. Relevant published literature was reviewed; only publications reporting results for items listed on the WFFQ were selected for inclusion. The references selected were prioritized according to relevance to the U.S. population.</p> <p>Results</p> <p>Based on our estimates, vegetable products contain the highest levels of nitrate, contributing as much as 189 mg/serving. Meat and bean products contain the highest levels of nitrites with values up to 1.84 mg/serving. Alcohol, meat and dairy products contain the highest values of nitrosamines with a maximum value of 0.531 μg/serving. The estimates of dietary nitrates, nitrites, and nitrosamines generated in this study are based on the published values currently available.</p> <p>Conclusion</p> <p>To our knowledge, these are the only estimates specifically designed for use with the adapted WFFQ and generated to represent food items available to the U.S. population. The estimates provided may be useful in other research studies, specifically in those exploring the relation between exposure to these compounds in foods and adverse health outcomes.</p

Up-regulated expression of LAMP2 and autophagy activity during neuroendocrine differentiation of prostate cancer LNCaP cells

Neuroendocrine (NE) prostate cancer (PCa) is a highly aggressive subtype of prostate cancer associated with resistance to androgen ablation therapy. In this study, we used LNCaP prostate cancer cells cultured in a serum-free medium for 6 days as a NE model of prostate cancer. Serum deprivation increased the expression of NE markers such as neuron-specific enolase (NSE) and βIII tubulin (βIII tub) and decreased the expression of the androgen receptor protein in LNCaP cells. Using cDNA microarrays, we compared gene expression profiles of NE cells and non-differentiated LNCaP cells. We identified up-regulation of 155 genes, among them LAMP2, a lysosomal membrane protein involved in lysosomal stability and autophagy. We then confirmed up-regulation of LAMP2 in NE cells by qRT-PCR, Western blot and confocal microscopy assays, showing that mRNA up-regulation correlated with increased levels of LAMP2 protein. Subsequently, we determined autophagy activity in NE cells by assessing the protein levels of SQSTM/p62 and LC3 by Western blot and LC3 and Atg5 mRNAs content by qRT-PCR. The decreased levels of SQSTM/p62 was accompanied by an enhanced expression of LC3 and ATG5, suggesting activation of autophagy in NE cells. Blockage of autophagy with 1μM AKT inhibitor IV, or by silencing Beclin 1 and Atg5, prevented NE cell differentiation, as revealed by decreased levels of the NE markers. In addition, AKT inhibitor IV as well as Beclin1 and Atg5 kwockdown attenuated LAMP2 expression in NE cells. On the other hand, LAMP2 knockdown by siRNA led to a marked blockage of autophagy, prevention of NE differentiation and decrease of cell survival. Taken together, these results suggest that LAMP2 overexpression assists NE differentiation of LNCaP cells induced by serum deprivation and facilitates autophagy activity in order to attain the NE phenotype and cell survival. LAMP2 could thus be a potential biomarker and potential target for NE prostate cancer

Changes in Body Weight and Psychotropic Drugs: A Systematic Synthesis of the Literature

<div><h3>Introduction</h3><p>Psychotropic medication use is associated with weight gain. While there are studies and reviews comparing weight gain for psychotropics within some classes, clinicians frequently use drugs from different classes to treat psychiatric disorders.</p> <h3>Objective</h3><p>To undertake a systematic review of all classes of psychotropics to provide an all encompassing evidence-based tool that would allow clinicians to determine the risks of weight gain in making both intra-class and interclass choices of psychotropics.</p> <h3>Methodology and Results</h3><p>We developed a novel hierarchical search strategy that made use of systematic reviews that were already available. When such evidence was not available we went on to evaluate randomly controlled trials, followed by cohort and other clinical trials, narrative reviews, and, where necessary, clinical opinion and anecdotal evidence. The data from the publication with the highest level of evidence based on our hierarchical classification was presented. Recommendations from an expert panel supplemented the evidence used to rank these drugs within their respective classes. Approximately 9500 articles were identified in our literature search of which 666 citations were retrieved. We were able to rank most of the psychotropics based on the available evidence and recommendations from subject matter experts. There were few discrepancies between published evidence and the expert panel in ranking these drugs.</p> <h3>Conclusion</h3><p>Potential for weight gain is an important consideration in choice of any psychotropic. This tool will help clinicians select psychotropics on a case-by-case basis in order to minimize the impact of weight gain when making both intra-class and interclass choices.</p> </div

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014–2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V