Noise-assisted spike propagation in myelinated neurons

We consider noise-assisted spike propagation in myelinated axons within a multi-compartment stochastic Hodgkin-Huxley model. The noise originates from a finite number of ion channels in each node of Ranvier. For the subthreshold internodal electric coupling, we show that (i) intrinsic noise removes the sharply defined threshold for spike propagation from node to node, and (ii) there exists an optimum number of ion channels which allows for the most efficient signal propagation and it corresponds to the actual physiological values.Comment: 8 pages, 12 figures, accepted for publication in Phys. Rev.

Endocytosis restricts Arabidopsis KNOLLE syntaxin to the cell division plane during late cytokinesis

Cytokinesis represents the final stage of eukaryotic cell division during which the cytoplasm becomes partitioned between daughter cells. The process differs to some extent between animal and plant cells, but proteins of the syntaxin family mediate membrane fusion in the plane of cell division in diverse organisms. How syntaxin localization is kept in check remains elusive. Here, we report that localization of the Arabidopsis KNOLLE syntaxin in the plane of cell division is maintained by sterol-dependent endocytosis involving a clathrin- and DYNAMIN-RELATED PROTEIN1A-dependent mechanism. On genetic or pharmacological interference with endocytosis, KNOLLE mis-localizes to lateral plasma membranes after cell-plate fusion. Fluorescence-loss-in-photo-bleaching and fluorescence-recovery-after-photo-bleaching experiments reveal lateral diffusion of GFP-KNOLLE from the plane of division to lateral membranes. In an endocytosis-defective sterol biosynthesis mutant displaying lateral KNOLLE diffusion, KNOLLE secretory trafficking remains unaffected. Thus, restriction of lateral diffusion by endocytosis may serve to maintain specificity of syntaxin localization during late cytokinesis

Tobacco control environment: cross-sectional survey of policy implementation, social unacceptability, knowledge of tobacco health harms and relationship to quit ratio in 17 low-income, middle-income and high-income countries

OBJECTIVES: This study examines in a cross-sectional study ‘the tobacco control environment’ including tobacco policy implementation and its association with quit ratio. SETTING: 545 communities from 17 high-income, upper-middle, low-middle and low-income countries (HIC, UMIC, LMIC, LIC) involved in the Environmental Profile of a Community’s Health (EPOCH) study from 2009 to 2014. PARTICIPANTS: Community audits and surveys of adults (35–70 years, n=12 953). PRIMARY AND SECONDARY OUTCOME MEASURES: Summary scores of tobacco policy implementation (cost and availability of cigarettes, tobacco advertising, antismoking signage), social unacceptability and knowledge were associated with quit ratios (former vs ever smokers) using multilevel logistic regression models. RESULTS: Average tobacco control policy score was greater in communities from HIC. Overall 56.1% (306/ 545) of communities had >2 outlets selling cigarettes and in 28.6% (154/539) there was access to cheap cigarettes (<5cents/cigarette) (3.2% (3/93) in HIC, 0% UMIC, 52.6% (90/171) LMIC and 40.4% (61/151) in LIC). Effective bans (no tobacco advertisements) were in 63.0% (341/541) of communities (81.7% HIC, 52.8% UMIC, 65.1% LMIC and 57.6% LIC). In 70.4% (379/538) of communities, >80% of participants disapproved youth smoking (95.7% HIC, 57.6% UMIC, 76.3% LMIC and 58.9% LIC). The average knowledge score was >80% in 48.4% of communities (94.6% HIC, 53.6% UMIC, 31.8% LMIC and 35.1% LIC). Summary scores of policy implementation, social unacceptability and knowledge were positively and significantly associated with quit ratio and the associations varied by gender, for example,communities in the highest quintile of the combined scores had 5.0 times the quit ratio in men (Odds ratio (OR) 5 0, 95% CI 3.4 to 7.4) and 4.1 times the quit ratio in women (OR 4.1, 95% CI 2.4 to 7.1). CONCLUSIONS: This study suggests that more focus is needed on ensuring the tobacco control policy is actually implemented, particularly in LMICs. The gender-related differences in associations of policy, social unacceptability and knowledge suggest that different strategies to promoting quitting may need to be implemented in men compared to women.IS

Environmental Profile of a Community\u27s Health (EPOCH): An Instrument to Measure Environmental Determinants of Cardiovascular Health in Five Countries

Background The environment in which people live is known to be important in influencing diet, physical activity, smoking, psychosocial and other risk factors for cardiovascular (CV) disease. However no instrument exists that evaluates communities for these multiple environmental factors and is suitable for use across different communities, regions and countries. This report describes the design and reliability of an instrument to measure environmental determinants of CV risk factors. Method/Principal Findings The Environmental Profile of Community Health (EPOCH) instrument comprises two parts: (I) an assessment of the physical environment, and (II) an interviewer-administered questionnaire to collect residents\u27 perceptions of their community. We examined the inter-rater reliability amongst 3 observers from each region of the direct observation component of the instrument (EPOCH I) in 93 rural and urban communities in 5 countries (Canada, Colombia, Brazil, China and India). Data collection using the EPOCH instrument was feasible in all communities. Reliability of the instrument was excellent (Intraclass Correlation Coefficient - ICC&gt;0.75) for 24 of 38 items and fair to good (ICC 0.4–0.75) for 14 of 38 items. Conclusion This report shows data collection with the EPOCH instrument is feasible and direct observation of community measures reliable. The EPOCH instrument will enable further research on environmental determinants of health for population studies from a broad range of settings

A prospective, single-arm, open-label, non-randomized, phase IIa trial of a nonavalent prophylactic HPV vaccine to assess immunogenicity of a prime and deferred-booster dosing schedule among 9-11 year-old girls and boys - clinical protocol

Background Human papillomavirus (HPV) vaccines are indicated for the prevention of cancers and genital warts caused by vaccine-covered HPV types. Although the standard regimen requires a two or three-dose vaccine series, there is emerging data suggesting that a single dose of the bivalent or quadrivalent HPV vaccine generates persistently positive antibody titers. No similar data is yet available for the nonavalent HPV vaccine, currently the only HPV vaccine available in the United States. The overall objective of our study is to assess the stability and kinetics of antibody titers for 24months following a single dose of the nonavalent HPV vaccine among preteen girls and boys. Methods This is a prospective, single-arm, open-label, non-randomized, Phase IIa trial among 9-11year-old girls and boys to determine the immunogenicity after a single dose of the nonavalent HPV vaccine (GARDASIL (R) 9) over 24months, with a deferred booster dose at 24months and an optional booster at 30months after the first dose. Participants provide blood specimens at 6, 12, 18, 24, and 30months after the first dose. Serologic geometric mean titers (GMT) of the nine vaccine types (HPV 16/18/ 6/11/31/33/45/52/58) will be measured at each time point. The primary objective is to determine the stability of type-specific serologic GMT of HPV16 and HPV18 between the 6- vs. 12-month, 12- vs. 18-month, and 18- vs. 24-month visits. Secondary objectives are to determine the stability of type-specific serologic GMT of the other HPV types (HPV 6/11/31/33/45/52/58) between the visits and to assess safety and reactogenicity after each vaccine dose. Discussion Single dose HPV vaccination could simplify the logistics and reduce costs of HPV vaccination in the US and across the world. This study will contribute important immunogenicity data on the stability and kinetics of type-specific antibody titers and inform feasibility of the single dose HPV vaccination paradigm.National Cancer Institute [HHSN26100009, CA023074]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Proline provides site-specific flexibility for in vivo collagen.

Fibrillar collagens have mechanical and biological roles, providing tissues with both tensile strength and cell binding sites which allow molecular interactions with cell-surface receptors such as integrins. A key question is: how do collagens allow tissue flexibility whilst maintaining well-defined ligand binding sites? Here we show that proline residues in collagen glycine-proline-hydroxyproline (Gly-Pro-Hyp) triplets provide local conformational flexibility, which in turn confers well-defined, low energy molecular compression-extension and bending, by employing two-dimensional 13C-13C correlation NMR spectroscopy on 13C-labelled intact ex vivo bone and in vitro osteoblast extracellular matrix. We also find that the positions of Gly-Pro-Hyp triplets are highly conserved between animal species, and are spatially clustered in the currently-accepted model of molecular ordering in collagen type I fibrils. We propose that the Gly-Pro-Hyp triplets in fibrillar collagens provide fibril "expansion joints" to maintain molecular ordering within the fibril, thereby preserving the structural integrity of ligand binding sites.BBSRC, EPSRC, Raymond and Beverly Sackler Fund for Physics of Medicine, Wellcome Trust, ER

Outcomes in patients with gunshot wounds to the brain.

Introduction:Gunshot wounds to the brain (GSWB) confer high lethality and uncertain recovery. It is unclear which patients benefit from aggressive resuscitation, and furthermore whether patients with GSWB undergoing cardiopulmonary resuscitation (CPR) have potential for survival or organ donation. Therefore, we sought to determine the rates of survival and organ donation, as well as identify factors associated with both outcomes in patients with GSWB undergoing CPR. Methods:We performed a retrospective, multicenter study at 25 US trauma centers including dates between June 1, 2011 and December 31, 2017. Patients were included if they suffered isolated GSWB and required CPR at a referring hospital, in the field, or in the trauma resuscitation room. Patients were excluded for significant torso or extremity injuries, or if pregnant. Binomial regression models were used to determine predictors of survival/organ donation. Results:825 patients met study criteria; the majority were male (87.6%) with a mean age of 36.5 years. Most (67%) underwent CPR in the field and 2.1% (n=17) survived to discharge. Of the non-survivors, 17.5% (n=141) were considered eligible donors, with a donation rate of 58.9% (n=83) in this group. Regression models found several predictors of survival. Hormone replacement was predictive of both survival and organ donation. Conclusion:We found that GSWB requiring CPR during trauma resuscitation was associated with a 2.1% survival rate and overall organ donation rate of 10.3%. Several factors appear to be favorably associated with survival, although predictions are uncertain due to the low number of survivors in this patient population. Hormone replacement was predictive of both survival and organ donation. These results are a starting point for determining appropriate treatment algorithms for this devastating clinical condition. Level of evidence:Level II

Environmental Profile of a Community's Health (EPOCH): An Instrument to Measure Environmental Determinants of Cardiovascular Health in Five Countries

BACKGROUND: The environment in which people live is known to be important in influencing diet, physical activity, smoking, psychosocial and other risk factors for cardiovascular (CV) disease. However no instrument exists that evaluates communities for these multiple environmental factors and is suitable for use across different communities, regions and countries. This report describes the design and reliability of an instrument to measure environmental determinants of CV risk factors. METHOD/PRINCIPAL FINDINGS: THE ENVIRONMENTAL PROFILE OF COMMUNITY HEALTH (EPOCH) INSTRUMENT COMPRISES TWO PARTS: (I) an assessment of the physical environment, and (II) an interviewer-administered questionnaire to collect residents' perceptions of their community. We examined the inter-rater reliability amongst 3 observers from each region of the direct observation component of the instrument (EPOCH I) in 93 rural and urban communities in 5 countries (Canada, Colombia, Brazil, China and India). Data collection using the EPOCH instrument was feasible in all communities. Reliability of the instrument was excellent (Intraclass Correlation Coefficient--ICC>0.75) for 24 of 38 items and fair to good (ICC 0.4-0.75) for 14 of 38 items. CONCLUSION: This report shows data collection with the EPOCH instrument is feasible and direct observation of community measures reliable. The EPOCH instrument will enable further research on environmental determinants of health for population studies from a broad range of settings

Degenerate Rotating Black Holes, Chiral CFTs and Fermi Surfaces I - Analytic Results for Quasinormal Modes

In this work we discuss charged rotating black holes in $AdS_5 \times S^5$ that degenerate to extremal black holes with zero entropy. These black holes have scaling properties between charge and angular momentum similar to those of Fermi surface operators in a subsector of $\mathcal{N}=4$ SYM. We add a massless uncharged scalar to the five dimensional supergravity theory, such that it still forms a consistent truncation of the type IIB ten dimensional supergravity and analyze its quasinormal modes. Separating the equation of motion to a radial and angular part, we proceed to solve the radial equation using the asymptotic matching expansion method applied to a Heun equation with two nearby singularities. We use the continued fraction method for the angular Heun equation and obtain numerical results for the quasinormal modes. In the case of the supersymmetric black hole we present some analytic results for the decay rates of the scalar perturbations. The spectrum of quasinormal modes obtained is similar to that of a chiral 1+1 CFT, which is consistent with the conjectured field-theoretic dual. In addition, some of the modes can be found analytically.Comment: 41 pages, 1 figure, LaTeX; v2: typos corrected, references adde