174 research outputs found

    Using scent to lift customers' moods

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    Faced with tougher and tougher online competition, traditional retailers are scrambling to find ways to exploit the advantages of realworld sales that e-commerce vendors can’t easily duplicate, such as taste and feel – and smell. Strong scents brighten attitudes and open wallets, and a recent study shows that the right scent at the right intensity can increase sales by nearly a third

    Mutant IDH1 Differently Affects Redox State and Metabolism in Glial Cells of Normal and Tumor Origin

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    IDH1R132H (isocitrate dehydrogenase 1) mutations play a key role in the development of low-grade gliomas. IDH1wt converts isocitrate to α-ketoglutarate while reducing nicotinamide adenine dinucleotide phosphate (NADP+), whereas IDH1R132H uses α-ketoglutarate and NADPH to generate the oncometabolite 2-hydroxyglutarate (2-HG). While the effects of 2-HG have been the subject of intense research, the 2-HG independent effects of IDH1R132H are still ambiguous. The present study demonstrates that IDH1R132H expression but not 2-HG alone leads to significantly decreased tricarboxylic acid (TCA) cycle metabolites, reduced proliferation, and enhanced sensitivity to irradiation in both glioblastoma cells and astrocytes in vitro. Glioblastoma cells, but not astrocytes, showed decreased NADPH and NAD+ levels upon IDH1R132H transduction. However, in astrocytes IDH1R132H led to elevated expression of the NAD-synthesizing enzyme nicotinamide phosphoribosyltransferase (NAMPT). These effects were not 2-HG mediated. This suggests that IDH1R132H cells utilize NAD+ to restore NADP pools, which only astrocytes could compensate via induction of NAMPT. We found that the expression of NAMPT is lower in patient-derived IDH1-mutant glioma cells and xenografts compared to IDH1-wildtype models. The Cancer Genome Atlas (TCGA) data analysis confirmed lower NAMPT expression in IDH1-mutant versus IDH1-wildtype gliomas. We show that the IDH1 mutation directly affects the energy homeostasis and redox state in a cell-type dependent manner. Targeting the impairments in metabolism and redox state might open up new avenues for treating IDH1-mutant gliomas.publishedVersio

    A Comparison of Two Motion Sensors for the Assessment of Free-Living Physical Activity of Adolescents

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    This study assessed and compared the daily step counts recorded by two different motion sensors in order to estimate the free-living physical activity of 135 adolescent girls. Each girl concurrently wore a Yamax pedometer and an ActiGraph accelerometer (criterion measure) every day for seven consecutive days. The convergent validity of the pedometer can be considered intermediate when used to measure the step counts in free-living physical activity; but should be considered with caution when used to classify participants’ step counts into corresponding physical activity categories because of a likelihood of ‘erroneous’ classification in comparison with the accelerometer

    THE IMPACT OF DIETARY PROTEIN OR AMINO ACID SUPPLEMENTATION ON MUSCLE MASS AND STRENGTH IN ELDERLY PEOPLE: INDIVIDUAL PARTICIPANT DATA AND META-ANALYSIS OF RCT’S

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    Objectives Increasing protein or amino acid intake has been promoted as a promising strategy to increase muscle mass and strength in elderly people, however, long-term intervention studies show inconsistent findings. Therefore, we aim to determine the impact of protein or amino acid supplementation compared to placebo on muscle mass and strength in older adults by combining the results from published trials in a metaanalysis and pooled individual participant data analysis. Design We searched Medline and Cochrane databases and performed a meta-analysis on eight available trials on the effect of protein or amino acid supplementation on muscle mass and strength in older adults. Furthermore, we pooled individual data of six of these randomized double-blind placebo-controlled trials. The main outcomes were change in lean body mass and change in muscle strength for both the meta-analysis and the pooled analysis. Results The meta-analysis of eight studies (n=557) showed no significant positive effects of protein or amino acid supplementation on lean body mass (mean difference: 0.014 kg: 95% CI -0.152; 0.18), leg press strength (mean difference: 2.26 kg: 95% CI -0.56; 5.08), leg extension strength (mean difference: 0.75 kg: 95% CI: -1.96, 3.47) or handgrip strength (mean difference: -0.002 kg: 95% CI -0.182; 0.179). Likewise, the pooled analysis showed no significant difference between protein and placebo treatment on lean body mass (n=412: p=0.78), leg press strength (n=121: p=0.50), leg extension strength (n=121: p=0.16) and handgrip strength (n=318: p=0.37). Conclusions There is currently no evidence to suggest that protein or amino acid supplementation without concomitant nutritional or exercise interventions increases muscle mass or strength in predominantly healthy elderly people

    Choledochocele: an unusual form of choledochal cyst

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    Choledochocele, or type III choledochal cyst, is a rare anomaly. Two children with choledochocele, both younger than any previously reported patient, were recently cared for at the University of Michigan Medical Center and prompted a literature review of this subject. Since 1974, 40 cases of choledochocele have been reported with enough clinical information for critical review. Ten of these patients were 21 years of age or younger. Presenting symptoms were not specific for choledochocele; they were generally interpreted to result from other biliary or gastrointestinal disorders that are more common for each age group. In pediatric patients the most frequent signs and symptoms of choledochocele were abdominal pain (70%), nausea and/or vomiting (60%), jaundice (30%), and acute pancreatitis (30%). While two-thirds of adult patients with choledochocele had undergone prior cholecystectomy (with stones rarely found), this was observed only once in children. Obstructive symptoms led to evaluation of the stomach and duodenum with either barium upper GI series or endoscopy in all children. These demonstrated an extrinsic mass effect in 90% of the patients. Endoscopic retrograde cholangiopancreatography identified a choledochocele in all cases in which the study was successfully executed. Intravenous cholangiography was sensitive in children, but less so in the adult patients reviewed. Other imaging efforts (computerized tomography, ultrasound, radionuclide scanning) were less dependable. Transduodenal marsupialization is the treatment of choice for patients of all ages and was provided in both of these newly reported children.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47183/1/383_2004_Article_BF00179633.pd

    Executive Functioning in Daily Life in Parkinson's Disease: Initiative, Planning and Multi-Task Performance

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    Impairments in executive functioning are frequently observed in Parkinson's disease (PD). However, executive functioning needed in daily life is difficult to measure. Considering this difficulty the Cognitive Effort Test (CET) was recently developed. In this multi-task test the goals are specified but participants are free in their approach. This study applies the CET in PD patients and investigates whether initiative, planning and multi-tasking are associated with aspects of executive functions and psychomotor speed. Thirty-six PD patients with a mild to moderate disease severity and thirty-four healthy participants were included in this study. PD patients planned and demonstrated more sequential task execution, which was associated with a decreased psychomotor speed. Furthermore, patients with a moderate PD planned to execute fewer tasks at the same time than patients with a mild PD. No differences were found between these groups for multi-tasking. In conclusion, PD patients planned and executed the tasks of the CET sequentially rather than in parallel presumably reflecting a compensation strategy for a decreased psychomotor speed. Furthermore, patients with moderate PD appeared to take their impairments into consideration when planning how to engage the tasks of the test. This compensation could not be detected in patients with mild PD

    Molecular Signatures of Prostate Stem Cells Reveal Novel Signaling Pathways and Provide Insights into Prostate Cancer

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    BACKGROUND:The global gene expression profiles of adult and fetal murine prostate stem cells were determined to define common and unique regulators whose misexpression might play a role in the development of prostate cancer. METHODOLOGY/PRINCIPAL FINDINGS:A distinctive core of transcriptional regulators common to both fetal and adult primitive prostate cells was identified as well as molecules that are exclusive to each population. Elements common to fetal and adult prostate stem cells include expression profiles of Wnt, Shh and other pathways identified in stem cells of other organs, signatures of the aryl-hydrocarbon receptor, and up-regulation of components of the aldehyde dehydrogenase/retinoic acid receptor axis. There is also a significant lipid metabolism signature, marked by overexpression of lipid metabolizing enzymes and the presence of the binding motif for Srebp1. The fetal stem cell population, characterized by more rapid proliferation and self-renewal, expresses regulators of the cell cycle, such as E2f, Nfy, Tead2 and Ap2, at elevated levels, while adult stem cells show a signature in which TGF-beta has a prominent role. Finally, comparison of the signatures of primitive prostate cells with previously described profiles of human prostate tumors identified stem cell molecules and pathways with deregulated expression in prostate tumors including chromatin modifiers and the oncogene, Erg. CONCLUSIONS/SIGNIFICANCE:Our data indicate that adult prostate stem or progenitor cells may acquire characteristics of self-renewing primitive fetal prostate cells during oncogenesis and suggest that aberrant activation of components of prostate stem cell pathways may contribute to the development of prostate tumors

    Activity-Dependent Bulk Synaptic Vesicle Endocytosis-A Fast, High Capacity Membrane Retrieval Mechanism

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    Central nerve terminals are placed under considerable stress during intense stimulation due to large numbers of synaptic vesicles (SVs) fusing with the plasma membrane. Classical clathrin-dependent SV endocytosis cannot correct for the large increase in nerve terminal surface area in the short term, due to its slow kinetics and low capacity. During such intense stimulation an additional SV retrieval pathway is recruited called bulk endocytosis. Recent studies have shown that bulk endocytosis fulfils all of the physiological requirements to remedy the acute changes in nerve terminal surface area to allow the nerve terminal to continue to function. This review will summarise the recent developments in the field that characterise the physiology of bulk endocytosis which show that it is a fast, activity-dependent and high capacity mechanism that is essential for the function of central nerve terminals
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