2,995 research outputs found

    Neuronalis összeköttetések a szomatoszenzoros kérgi área 3b és área 1 kézreprezentációs területén főemlősökben | Neuronal connections within the hand representation in areas 3b and 1 of the somatosensory cortex in primates

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    Absztrakt Bevezetés: A szomatoszenzoros kérgi área 3b és 1 közti szoros funkcionális kapcsolatot reciprok neuronalis összeköttetések biztosítják, jelezve, hogy a tapintási észlelés meghatározó módon függ a két área interakciójától. Célkitűzés: Jelen vizsgálat célja e neuronkörök megismerése volt a distalis ujjbegy-reprezentáció szintjén. Módszer: Az áreán belüli és áreák közötti összeköttetések vizsgálatához fiziológiai térképezéssel kombinált pályajelölést alkalmaztunk mókusmajmokban (Saimiri sciureus). Eredmények: A szerzők kimutatták, hogy a két área közötti reciprok összeköttetések az azonos ujjbegy reprezentációját preferálják. Ezzel szemben az áreán belüli kapcsolatok horizontális eloszlása igazolja a fiziológiai megfigyeléseket, amelyek erős kapcsolatot mutattak a szomszédos ujjbegyek reprezentációi között. Érdekes, hogy az injektált kérgi reprezentáció lokális bemeneti területe, amely a két áreában különbözik, egyforma méretű bőrfelületet reprezentál. Következtetések: Eredményeikből azt a következtetést lehet levonni, hogy áreán belül a lokális, horizontális kapcsolatok az ujjak közötti információ integrálásában, az áreák közötti, ujjbegy-reprezentációra lokalizálódó kapcsolatok pedig a kézmozgás során a stimulusok lokalizációjában játszhatnak szerepet. Orv. Hetil., 2016, 157(33), 1320–1325. | Abstract Introduction: The close functional relationship between areas 3b and 1 of the somatosensory cortex is based on their reciprocal connections indicating that tactile sensation depends on the interaction of these two areas. Aim: The aim of the authors was to explore this neuronal circuit at the level of the distal finger pad representation. Method: The study was made by bidirectional tract tracing aided by neurophysiological mapping in squirrel monkeys (Saimiri sciureus). Results: Inter-areal connections between the two areas preferred the homologues representations. However, intra-areal connections were formed between the neighboring finger pad representations supporting the physiological observations. Interestingly, the size of the local input area of the injected cortical micro-region, which differed in the two areas, represented the same skin area. Conclusions: The authors propose that intra-areal connections are important in integrating information across fingers, while inter-areal connections are important in maintaining input localization during hand movement. Orv. Hetil., 2016, 157(33), 1320–1325

    Where do women and men in Britain obtain contraception? Findings from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3).

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    INTRODUCTION: To estimate the prevalence of use of different sources of contraceptive supplies in Britain and its variation by key demographic and behavioural characteristics. METHODS: Cross-sectional probability sample survey of women and men aged 16-74 years, resident in Britain, interviewed between 2010 and 2012. Analyses reported here were of 4571 women and 3142 men aged 16-44 years who reported having vaginal sex in the past year. Those relying exclusively on sterilisation (including hysterectomy) were excluded. Sources of contraceptive supplies were categorised as: general practice, community clinic, retail and other. Prevalence of use of these sources was estimated, and associated factors examined. RESULTS: Some 87.0% of women and 73.8% of men accessed at least one source of contraceptive supplies in the previous year. Most women (59.1%) used general practice and most men (54.6%) used retail outlets. Community clinics were less commonly used, by 23.0% of women and 21.3% of men, but these users were younger and at greater sexual health risk. These associations were also observed among the 27.3% of women and 30.6% of men who used more than one source category (general practice, community clinic or retail) for contraceptive supplies. CONCLUSIONS: People in Britain use a variety of sources to obtain contraceptive supplies and some sources are more commonly used by those more vulnerable to poorer sexual health. Our findings suggest that national policy changes to increase access to contraceptive methods have had an effect on the diversity of services used

    Where do women and men in Britain obtain contraception? Findings from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3).

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    INTRODUCTION: To estimate the prevalence of use of different sources of contraceptive supplies in Britain and its variation by key demographic and behavioural characteristics. METHODS: Cross-sectional probability sample survey of women and men aged 16-74 years, resident in Britain, interviewed between 2010 and 2012. Analyses reported here were of 4571 women and 3142 men aged 16-44 years who reported having vaginal sex in the past year. Those relying exclusively on sterilisation (including hysterectomy) were excluded. Sources of contraceptive supplies were categorised as: general practice, community clinic, retail and other. Prevalence of use of these sources was estimated, and associated factors examined. RESULTS: Some 87.0% of women and 73.8% of men accessed at least one source of contraceptive supplies in the previous year. Most women (59.1%) used general practice and most men (54.6%) used retail outlets. Community clinics were less commonly used, by 23.0% of women and 21.3% of men, but these users were younger and at greater sexual health risk. These associations were also observed among the 27.3% of women and 30.6% of men who used more than one source category (general practice, community clinic or retail) for contraceptive supplies. CONCLUSIONS: People in Britain use a variety of sources to obtain contraceptive supplies and some sources are more commonly used by those more vulnerable to poorer sexual health. Our findings suggest that national policy changes to increase access to contraceptive methods have had an effect on the diversity of services used

    Elevated circulating amyloid concentrations in obesity and diabetes promote vascular dysfunction

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    Diabetes, obesity and Alzheimer’s disease (AD) are associated with vascular complications and impaired nitric oxide (NO) production. Furthermore, increased β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), APP and β-amyloid (Aβ) are linked with vascular disease development and raised BACE1 and Aβ accompany hyperglycemia and hyperlipidemia. However, the causal relationship between obesity and diabetes, raised Aβ and vascular dysfunction is unclear. We report that diet-induced obesity (DIO) in mice raised plasma and vascular Aβ42 that correlated with decreased NO bioavailability, endothelial dysfunction and raised blood pressure. Genetic or pharmacological reduction of BACE1 activity and Aβ42 prevented and reversed, respectively, these outcomes. In contrast, expression of human mutant APP in mice or Aβ42 infusion into control diet-fed mice to mimic obese levels impaired NO production, vascular relaxation and raised blood pressure. In humans, raised plasma Aβ42 correlated with diabetes and endothelial dysfunction. Mechanistically, higher Aβ42 reduced endothelial NO synthase (eNOS), cyclic GMP and protein kinase G (PKG) activity independently of diet whereas endothelin-1 was increased by diet and Aβ42. Lowering Aβ42 reversed the DIO deficit in the eNOS-cGMP-PKG pathway and decreased endothelin-1. Our findings suggest that BACE1 inhibitors may have therapeutic value in the treatment of vascular disease associated with diabetes

    Structure and morphology of light-reflecting synthetic and biogenic polymorphs of isoxanthopterin: A comparison

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    Until recently it was thought that the only optical function of pteridines in biology was to act as light-absorbing pigments, but a recent report by some of us revealed that crystalline isoxanthopterin is a reflector in the eyes of decapod crustaceans. Here, we report the formation of crystalline isoxanthopterin synthetically from the polar dimethyl sulfoxide solvent, with X-ray diffraction analysis revealing a crystal structure different from that of biogenic isoxanthopterin. The structure of the new polymorph was determined in two independent ways. In one approach, it was generated and optimized using first-principles calculations, followed by comparison of simulation and experiment for high-resolution powder X-ray diffraction (PXRD) and electron diffraction. In the other approach, the structure was obtained definitively from PXRD data using a direct-space genetic algorithm for structure solution followed by Rietveld refinement. The synthetic structure is different from its biogenic counterpart, especially in having a nonplanar criss-cross H-bonded arrangement. We also rationalized the morphology of the crystals and the effect of the DMSO thereon, via a comparison between observed and theoretical growth morphologies. In addition, we calculated the optical properties of the synthetic structure and found its two dominant refractive indices to be somewhat lower than those of its biogenic counterpart, but still as high as those of reflecting guanine crystals. Synthetic isoxanthopterin therefore emerges as a promising candidate for incorporation in artificial optical systems

    The Case for a Muon Collider Higgs Factory

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    We propose the construction of a compact Muon Collider Higgs Factory. Such a machine can produce up to \sim 14,000 at 8\times 10^{31} cm^-2 sec^-1 clean Higgs events per year, enabling the most precise possible measurement of the mass, width and Higgs-Yukawa coupling constants.Comment: Supporting letter for the document: "Muon Collider Higgs Factory for Smowmass 2013", A White Paper submitted to the 2013 U.S. Community Summer Study of the Division of Particles and Fields of the American Physical Society, Y. Alexahin, et. al, FERMILAB-CONF-13-245-T (July, 2013

    Novel approaches to analysis of the North Star Ambulatory Assessment (NSAA) in Duchenne muscular dystrophy (DMD): Observations from a phase 2 trial

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    Introduction: The North Star Ambulatory Assessment (NSAA) tool is a key instrument for measuring clinical outcomes in patients with Duchenne muscular dystrophy (DMD). To gain a better understanding of the longitudinal utility of the NSAA, we evaluated NSAA data from a phase II trial of 120 patients with DMD treated with domagrozumab or placebo. Methods: The NSAA exploratory analyses included assessment of individual skills gained/lost, total skills gained/lost, cumulative loss of function, and the impact of transient loss of function due to a temporary disability on NSAA total score (temporary zero score). Results: There was no significant difference in the total number of NSAA skills gained (mean 1.41 and 1.04, respectively; p = 0.3314) or lost (3.90 vs. 5.0; p = 0.0998) between domagrozumab- vs. placebo-treated patients at week 49. However, domagrozumab-treated patients were less likely to lose the ability to perform a NSAA item (hazard ratio 0.80, 95% confidence interval [CI]: 0.65–0.98, p = 0.029) over 48-weeks vs. placebo-treated patients. When temporary zero scores were changed to “not obtainable” (8 values from 7 patients), domagrozumab-treated patients scored higher on the NSAA total score versus placebo-treated patients (difference at week 49: 2.0, 95% CI: 0.1–3.9, p = 0.0359). Conclusions: These exploratory analyses reveal additional approaches to interpreting the NSAA data beyond just change in NSAA total score. These observations also highlight the importance of reporting items as “not obtainable” for a patient with a temporary/transient physical disability that impacts their ability to perform the NSAA test

    c-Rel is required for the development of thymic Foxp3+ CD4 regulatory T cells

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    During thymopoiesis, a unique program of gene expression promotes the development of CD4 regulatory T (T reg) cells. Although Foxp3 maintains a pattern of gene expression necessary for T reg cell function, other transcription factors are emerging as important determinants of T reg cell development. We show that the NF-κB transcription factor c-Rel is highly expressed in thymic T reg cells and that in c-rel−/− mice, thymic T reg cell numbers are markedly reduced as a result of a T cell–intrinsic defect that is manifest during thymocyte development. Although c-Rel is not essential for TGF-β conversion of peripheral CD4+CD25− T cells into CD4+Foxp3+ cells, it is required for optimal homeostatic expansion of peripheral T reg cells. Despite a lower number of peripheral T reg cells in c-rel−/− mice, the residual peripheral c-rel−/− T reg cells express normal levels of Foxp3, display a pattern of cell surface markers and gene expression similar to those of wild-type T reg cells, and effectively suppress effector T cell function in culture and in vivo. Collectively, our results indicate that c-Rel is important for both the thymic development and peripheral homeostatic proliferation of T reg cells
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