Parvalbumin Interneurons of Hippocampus Tune Population Activity at Theta Frequency

SummaryHippocampal theta rhythm arises from a combination of recently described intrinsic theta oscillators and inputs from multiple brain areas. Interneurons expressing the markers parvalbumin (PV) and somatostatin (SOM) are leading candidates to participate in intrinsic rhythm generation and principal cell (PC) coordination in distal CA1 and subiculum. We tested their involvement by optogenetically activating and silencing PV or SOM interneurons in an intact hippocampus preparation that preserves intrinsic connections and oscillates spontaneously at theta frequencies. Despite evidence suggesting that SOM interneurons are crucial for theta, optogenetic manipulation of these interneurons modestly influenced theta rhythm. However, SOM interneurons were able to strongly modulate temporoammonic inputs. In contrast, activation of PV interneurons powerfully controlled PC network and rhythm generation optimally at 8 Hz, while continuously silencing them disrupted theta. Our results thus demonstrate a pivotal role of PV but not SOM interneurons for PC synchronization and the emergence of intrinsic hippocampal theta

Seizure-Like Activities during Head-Up Tilt Test-Induced Syncope

Purpose: Some patients with neurally mediated reflex syncope may be misdiagnosed as epilepsy because myoclonic jerky movements are observed during syncope. The seizure-like activities during the head-up tilt test (HUT) have been rarely reported. The purpose of this study was to assess the characteristics of these seizure-like activities and evaluate whether there are differences in the clinical characteristics and hemodynamic parameters of patients with neurally mediated reflex syncope with and without seizure-like activities during HUT-induced syncope. Materials and Methods: The medical records of 1,383 consecutive patients with a positive HUT were retrospectively reviewed, and 226 patients were included in this study. Results: Of 226 patients, 13 (5.75%) showed seizure-like activities, with 5 of these (2.21%) having multifocal myoclonic jerky movements, 5 (2.21%) having focal seizurelike activity involving one extremity, and 3 (1.33%) having upward deviation of eye ball. Comparison of patients with and without seizure-like activities revealed no significant differences in terms of clinical variables and hemodynamic parameters during HUT. Conclusion: Seizure-like activities occurred occasionally during HUTinduced syncope in patients with neurally mediated reflex syncope. The seizure-like activities during HUT might not be related to the severity of the syncopal episodes or hemodynamic changes during HUT. Key Words: Neurally mediated reflex syncope, seizure-like activities, head-up tilt tes

Design and feasibility testing of a novel group intervention for young women who binge drink in groups

BackgroundYoung women frequently drink alcohol in groups and binge drinking within these natural drinking groups is common. This study describes the design of a theoretically and empirically based group intervention to reduce binge drinking among young women. It also evaluates their engagement with the intervention and the acceptability of the study methods.MethodsFriendship groups of women aged 18–35 years, who had two or more episodes of binge drinking (>6 UK units on one occasion; 48g of alcohol) in the previous 30 days, were recruited from the community. A face-to-face group intervention, based on the Health Action Process Approach, was delivered over three sessions. Components of the intervention were woven around fun activities, such as making alcohol free cocktails. Women were followed up four months after the intervention was delivered. Results The target of 24 groups (comprising 97 women) was recruited. The common pattern of drinking was infrequent, heavy drinking (mean consumption on the heaviest drinking day was UK 18.1 units). Process evaluation revealed that the intervention was delivered with high fidelity and acceptability of the study methods was high. The women engaged positively with intervention components and made group decisions about cutting down. Twenty two groups set goals to reduce their drinking, and these were translated into action plans. Retention of individuals at follow up was 87%.ConclusionsThis study successfully recruited groups of young women whose patterns of drinking place them at high risk of acute harm. This novel approach to delivering an alcohol intervention has potential to reduce binge drinking among young women. The high levels of engagement with key steps in the behavior change process suggests that the group intervention should be tested in a full randomised controlled trial

Patterns of Recurrence after Breast-Conserving Treatment for Early Stage Breast Cancer by Molecular Subtype

Purpose: To study clinical features and patterns of recurrence after breast-conserving treatment (BCT) for three molecular subtypes of early stage breast cancer. Methods: The sample studied included 596 patients with T1-2N0-1 breast cancer who received BCT. Three groups were defined by receptor status. Luminal: estrogen receptor (ER) or progesterone receptor (PR) positive; triple negative (TN): ER, PR, and epidermal growth factor receptor-2 (HER2) receptor negative; and HER2 overexpressing: ER and PR negative but HER2 receptor positive. Results: The number of patients in each group was 408 (68.5%), 105 (17.6%), and 83 (13.9%), respectively. The median follow-up period was 79 months. The TN and HER2 subtypes occurred in younger patients (p=0.0007) and had higher nuclear grade and poorer histologic grade (p<0.0001 and 0.0071, respectively). During the follow-up period, locoregional recurrence was detected as th

Erratum: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls.

This corrects the article DOI: 10.1038/sdata.2017.179

Landscape-level controls on dissolved carbon flux from diverse catchments of the circumboreal

Author Posting. © American Geophysical Union, 2012. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 26 (2012): GB0E02, doi:10.1029/2012GB004299.While much of the dissolved organic carbon (DOC) within rivers is destined for mineralization to CO2, a substantial fraction of riverine bicarbonate (HCO3−) flux represents a CO2 sink, as a result of weathering processes that sequester CO2 as HCO3−. We explored landscape-level controls on DOC and HCO3− flux in subcatchments of the boreal, with a specific focus on the effect of permafrost on riverine dissolved C flux. To do this, we undertook a multivariate analysis that partitioned the variance attributable to known, key regulators of dissolved C flux (runoff, lithology, and vegetation) prior to examining the effect of permafrost, using riverine biogeochemistry data from a suite of subcatchments drawn from the Mackenzie, Yukon, East, and West Siberian regions of the circumboreal. Across the diverse catchments that we study, controls on HCO3− flux were near-universal: runoff and an increased carbonate rock contribution to weathering (assessed as riverwater Ca:Na) increased HCO3− yields, while increasing permafrost extent was associated with decreases in HCO3−. In contrast, permafrost had contrasting and region-specific effects on DOC yield, even after the variation caused by other key drivers of its flux had been accounted for. We used ionic ratios and SO4 yields to calculate the potential range of CO2 sequestered via weathering across these boreal subcatchments, and show that decreasing permafrost extent is associated with increases in weathering-mediated CO2 fixation across broad spatial scales, an effect that could counterbalance some of the organic C mineralization that is predicted with declining permafrost.Funding for this work was provided through NSF-OPP-0229302 and NSF-OPP-0732985. Additional support to S.E.T. was provided by an NSERC Postdoctoral Fellowship.2013-02-2

Epigenetic and Transcriptional Variability Shape Phenotypic Plasticity.

Epigenetic and transcriptional variability contribute to the vast diversity of cellular and organismal phenotypes and are key in human health and disease. In this review, we describe different types, sources, and determinants of epigenetic and transcriptional variability, enabling cells and organisms to adapt and evolve to a changing environment. We highlight the latest research and hypotheses on how chromatin structure and the epigenome influence gene expression variability. Further, we provide an overview of challenges in the analysis of biological variability. An improved understanding of the molecular mechanisms underlying epigenetic and transcriptional variability, at both the intra- and inter-individual level, provides great opportunity for disease prevention, better therapeutic approaches, and personalized medicine

The Met oncogene and basal-like breast cancer: another culprit to watch out for?

Recent findings suggest the involvement of the MET oncogene, encoding the tyrosine kinase receptor for hepatocyte growth factor, in the onset and progression of basal-like breast carcinoma. The expression profiles of basal-like tumors - but not those of other breast cancer subtypes - are enriched for gene sets that are coordinately over-represented in transcriptional signatures regulated by Met. Consistently, tissue microarray analyses have revealed that Met immunoreactivity is much higher in basal-like cases of human breast cancer than in other tumor types. Finally, mouse models expressing mutationally activated forms of Met develop a high incidence of mammary tumors, some of which exhibit basal characteristics. The present review summarizes current knowledge on the role and activity of Met in basal-like breast cancer, with a special emphasis on the correlation between this tumor subtype and the cellular hierarchy of the normal mammary gland