Individual differences in striatum activity to food commercials predict weight gain in adolescents

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109559/1/oby20882.pd

The Hyaluronan Receptor for Endocytosis (HARE) Activates NF-κB-mediated Gene Expression in Response to 40–400-kDa, but Not Smaller or Larger, Hyaluronans

Background: HARE mediates systemic clearance of hyaluronan (HA), which turns over continuously in tissues. Results: HARE uptake of 40–400-kDa, but not larger or smaller, HA stimulated NF-κB activation. Conclusion: HA-HARE signal complexes activate NF-κB and gene transcription only with optimally sized HA. Significance: HARE responsiveness to a narrow size range ofHAdegradation products may be a sensing system to detect tissue ECM stress

The Hyaluronan Receptor for Endocytosis (HARE) Activates NF-κB-mediated Gene Expression in Response to 40–400-kDa, but Not Smaller or Larger, Hyaluronans

Background: HARE mediates systemic clearance of hyaluronan (HA), which turns over continuously in tissues. Results: HARE uptake of 40–400-kDa, but not larger or smaller, HA stimulated NF-κB activation. Conclusion: HA-HARE signal complexes activate NF-κB and gene transcription only with optimally sized HA. Significance: HARE responsiveness to a narrow size range ofHAdegradation products may be a sensing system to detect tissue ECM stress

Nanoconnectomic upper bound on the variability of synaptic plasticity

Information in a computer is quantified by the number of bits that can be stored and recovered. An important question about the brain is how much information can be stored at a synapse through synaptic plasticity, which depends on the history of probabilistic synaptic activity. The strong correlation between size and efficacy of a synapse allowed us to estimate the variability of synaptic plasticity. In an EM reconstruction of hippocampal neuropil we found single axons making two or more synaptic contacts onto the same dendrites, having shared histories of presynaptic and postsynaptic activity. The spine heads and neck diameters, but not neck lengths, of these pairs were nearly identical in size. We found that there is a minimum of 26 distinguishable synaptic strengths, corresponding to storing 4.7 bits of information at each synapse. Because of stochastic variability of synaptic activation the observed precision requires averaging activity over several minutes

Mapping pneumonia research: a systematic analysis of UK investments and published outputs 1997–2013

BackgroundThe burden of pneumonia continues to be substantial, particularly among the poorest in global society. We describe here the trends for UK pneumonia R&D investment and published outputs, and correlate with 2013 global mortality.MethodsData related to awards to UK institutions for pneumonia research from 1997 to 2013 were systematically sourced and categorised by disease area and type of science. Investment was compared to mortality figures in 2010 and 2013 for pneumonia, tuberculosis and influenza. Investment was also compared to publication data.ResultsOf all infectious disease research between 2011 and 2013 (£917.0 million), £28.8 million (3.1%) was for pneumonia. This was an absolute and proportionate increase from previous time periods. Translational pneumonia research (33.3%) received increased funding compared with 1997–2010 where funding was almost entirely preclinical (87.5%, here 30.9%), but high-burden areas such as paediatrics, elderly care and antimicrobial resistance received little investment. Annual investment remains volatile; publication temporal trends show a consistent increase. When comparing investment to global burden with a novel ‘investment by mortality observed’ metric, tuberculosis (£48.36) and influenza (£484.21) receive relatively more funding than pneumonia (£43.08), despite investment for pneumonia greatly increasing in 2013 compared to 2010 (£7.39). Limitations include a lack of private sector data and the need for careful interpretation of the comparisons with burden, plus categorisation is subjective.ConclusionsThere has been a welcome increase for pneumonia funding awarded to UK institutions in 2011–2013 compared with 1997–2010, along with increases for more translational research. Published outputs relating to pneumonia rose steadily from 1997 to 2013. Investment relative to mortality for pneumonia has increased, but it remains low compared to other respiratory infections and clear inequities remain. Analyses that measure investments in pneumonia can provide an insight into funding trends and research gaps.Research in contextPneumonia continues to be a high-burden illness around the globe. This paper shows that although research funding is increasing in the UK (between 1997 and 2013), it remains poorly funded compared to other important respiratory infectious diseases such as tuberculosis and influenza. Publications about pneumonia have been steadily increasing over time, indicating continuing academic and clinical interest in the topic. Though global mortality of pneumonia is declining, it should still be an area of high priority for funders, policymakers and researchers

Whole exome sequencing and molecular modeling of a missense variant in TNFAIP3 that segregates with disease in a family with chronic urticaria and angioedema

Chronic urticaria is a common condition characterized by recurrent hives lasting several weeks or months and is usually idiopathic. Approximately half of the individuals with chronic urticaria will present with episodes of angioedema that can be severe and debilitating. In this report, we describe a 47-year-old Hispanic male who presented initially for an evaluation of chronic hives following hospitalization due to hive-induced anaphylaxis. The individual had a history significant for urticaria and angioedema beginning in his early 30s. Interestingly, both the individual’s 41-year-old sister and 12-year-old daughter were also affected with chronic urticaria and severe angioedema. Whole exome sequencing of the proband and several family members revealed a heterozygous variant of uncertain significance in exon 2 of TNFAIP3, denoted as c.65G>A (p.R22Q), in all affected members. Variants in TNFAIP3 have been associated with multiple autoimmune diseases, susceptibility to allergy and asthma, and periodic fever syndromes, suggesting that this variant could potentially play a role in disease

Whole Exome Sequencing and Molecular Modeling of a Missense Variant in TNFAIP3

Chronic urticaria is a common condition characterized by recurrent hives lasting several weeks or months and is usually idiopathic. Approximately half of the individuals with chronic urticaria will present with episodes of angioedema that can be severe and debilitating. In this report, we describe a 47-year-old Hispanic male who presented initially for an evaluation of chronic hives following hospitalization due to hive-induced anaphylaxis. The individual had a history significant for urticaria and angioedema beginning in his early 30s. Interestingly, both the individual’s 41-year-old sister and 12-year-old daughter were also affected with chronic urticaria and severe angioedema. Whole exome sequencing of the proband and several family members revealed a heterozygous variant of uncertain significance in exon 2 of TNFAIP3, denoted as c.65G>A (p.R22Q), in all affected members. Variants in TNFAIP3 have been associated with multiple autoimmune diseases, susceptibility to allergy and asthma, and periodic fever syndromes, suggesting that this variant could potentially play a role in disease

Chronic and episodic stress predict physical symptom bother following breast cancer diagnosis.

Breast cancer patients often experience adverse physical side effects of medical treatments. According to the biobehavioral model of cancer stress and disease, life stress during diagnosis and treatment may negatively influence the trajectory of women's physical health-related adjustment to breast cancer. This longitudinal study examined chronic and episodic stress as predictors of bothersome physical symptoms during the year after breast cancer diagnosis. Women diagnosed with breast cancer in the previous 4 months (N = 460) completed a life stress interview for contextual assessment of chronic and episodic stress severity at study entry and 9 months later. Physical symptom bother (e.g., pain, fatigue) was measured at study entry, every 6 weeks through 6 months, and at nine and 12 months. In multilevel structural equation modeling (MSEM) analyses, both chronic stress and episodic stress occurring shortly after diagnosis predicted greater physical symptom bother over the study period. Episodic stress reported to have occurred prior to diagnosis did not predict symptom bother in MSEM analyses, and the interaction between chronic and episodic stress on symptom bother was not significant. Results suggest that ongoing chronic stress and episodic stress occurring shortly after breast cancer diagnosis are important predictors of bothersome symptoms during and after cancer treatment. Screening for chronic stress and recent stressful life events in the months following diagnosis may help to identify breast cancer patients at risk for persistent and bothersome physical symptoms. Interventions to prevent or ameliorate treatment-related physical symptoms may confer added benefit by addressing ongoing non-cancer-related stress in women's lives

Reduction of Stabilin-2 Contributes to a Protection Against AtherosclerosisStabilin

We have previously identified a novel atherosclerosis quantitative trait locus (QTL), Arch atherosclerosis 5 (Aath5), on mouse chromosome 10 by three-way QTL analyses between Apoe−/− mice on a DBA/2J, 129S6 and C57BL/6J background. The DBA/2J haplotype at the Aath5 locus was associated with smaller plaque size. One of the candidate genes underlying Aath5 was Stabilin-2 (Stab2), which encodes a clearance receptor for hyaluronan (HA) predominantly expressed in liver sinusoidal endothelial cells (LSECs). However, the role of Stab2 in atherosclerosis is unknown. A congenic line of Apoe−/− mice carrying Aath5 covering the Stab2DBA allele on a background of 129S6 confirmed the small reductions of atherosclerotic plaque development. To further determine whether Stab2 is an underlying gene for Aath5, we generated Stab2−/−Apoe−/− mice on a C57BL/6J background. When fed with a Western diet for 8 weeks, Stab2−/−Apoe−/− males developed approximately 30% smaller plaques than Stab2+/+Apoe−/− mice. HA was accumulated in circulation but not in major organs in the Stab2 deficient mice. STAB2-binding molecules that are involved in atherosclerosis, including acLDL, apoptotic cells, heparin and vWF were not likely the direct cause of the protection in the Stab2−/−Apoe−/− males. These data indicate that reduction of Stab2 is protective against atherosclerotic plaque development, and that Stab2 is a contributing gene underlying Aath5, although its effect is small. To test whether non-synonymous amino acid changes unique to DBA/2J affect the function of STAB2 protein, we made HEK293 cell lines expressing STAB2129 or STAB2DBA proteins, as well as STAB2129 proteins carrying each of five DBA-unique replacements that have been predicted to be deleterious. These mutant cells were capable of internalizing 125I -HA and DiI-acLDL similarly to the control cells. These results indicate that the amino acid changes unique to DBA/2J are not affecting the function of STAB2 protein, and support our previous observation that the reduced transcription of Stab2 in the liver sinusoid as a consequence of the insertion of a viral-derived sequence, intracisternal A particle, is the primary contributor to the athero-protection conferred by the DBA/2J allele