Conductive and Kinetic Properties of Connexin45 Hemichannels Expressed in Transfected HeLa Cells

Human HeLa cells transfected with mouse connexin Cx45 were used to examine the conductive and kinetic properties of Cx45 hemichannels. The experiments were carried out on single cells using a voltage-clamp method. Lowering the [Ca2+]o revealed an extra current. Its sensitivity to extracellular Ca2+ and gap junction channel blockers (18α-glycyrrhetinic acid, palmitoleic acid, heptanol), and its absence in non-transfected HeLa cells suggested that it is carried by Cx45 hemichannels. The conductive and kinetic properties of this current, I hc, were determined adopting a biphasic pulse protocol. I hc activated at positive V m and deactivated partially at negative V m. The analysis of the instantaneous I hc yielded a linear function g hc,inst = f(V m) with a hint of a negative slope (g hc,inst: instantaneous conductance). The analysis of the steady-state I hc revealed a sigmoidal function g hc,ss = f(V m) best described with the Boltzmann equation: V m,0 = −1.08mV, g hc,min = 0.08 (g hc,ss: steady-state conductance; V m, 0:V m at which g hc,ss is half-maximally activated; g hc,min: minimal conductance; major charge carriers: K+ and Cl−). The g hc was minimal at negative V m and maximal at positive V m. This suggests that Cx45 connexons integrated in gap junction channels are gating with negative voltage. I hc deactivated exponentially with time, giving rise to single time constants, τd. The function τd = f(V m) was exponential and increased with positive V m (τd = 7.6s at V m = 0mV). The activation of I hc followed the sum of two exponentials giving rise to the time constants, τa1 and τa2. The function τa1 = f(V m) and τa2 = f(V m) were bell-shaped and yielded a maximum of ≅ 0.6s at V m ≅ −20mV and ≅ 4.9s at V m ≅ 15mV, respectively. Neither τa1 = f(V m) nor τa2 = f(V m) coincided with τd = f(V m). These findings conflict with the notion that activation and deactivation follow a simple reversible reaction scheme governed by first-order voltage-dependent processe

Geometric realizations of curvature models by manifolds with constant scalar curvature

We show any Riemannian curvature model can be geometrically realized by a manifold with constant scalar curvature. We also show that any pseudo-Hermitian curvature model, para-Hermitian curvature model, hyper-pseudo-Hermitian curvature model, or hyper-para-Hermitian curvature model can be realized by a manifold with constant scalar and *-scalar curvature

Bias in the journal impact factor

The ISI journal impact factor (JIF) is based on a sample that may represent half the whole-of-life citations to some journals, but a small fraction (<10%) of the citations accruing to other journals. This disproportionate sampling means that the JIF provides a misleading indication of the true impact of journals, biased in favour of journals that have a rapid rather than a prolonged impact. Many journals exhibit a consistent pattern of citation accrual from year to year, so it may be possible to adjust the JIF to provide a more reliable indication of a journal's impact.Comment: 9 pages, 8 figures; one reference correcte

Conceptions and expectations of research collaboration in the European social sciences: Research policies, institutional contexts and the autonomy of the scientific field

This paper investigates the interactions between policy drivers and academic practice in international research collaboration. It draws on the case of the Open Research Area (ORA), a funding scheme in the social sciences across four national research agencies, seeking to boost collaboration by supporting “integrated” projects. The paper discusses the scheme’s governance and its place within the European policy space before turning to awarded researchers’ perceptions of its originality and impact on their project’s emergence and development. Drawing on Bourdieu’s field theory, we analyse the scheme’s capacity to challenge researchers’ habitual collaborative practice as well as the hierarchical foundations of the social science field. We relate the discourses of researchers, located in France, Germany, the Netherlands and the United Kingdom, to such structural dimensions of the academic profession as, disciplinary cultures, institutional environments and national performance management of research careers. The paper argues that the ORA introduces novel mechanisms of power sharing and answerability in social sciences research capable of unsettling the autonomy of the scientific field. This analysis offers a new perspective on the often unquestioned superiority of the model of international collaboration induced by schemes such as ORA

Implementing a 48 h EWTD-compliant rota for junior doctors in the UK does not compromise patients’ safety : assessor-blind pilot comparison

Background: There are currently no field data about the effect of implementing European Working Time Directive (EWTD)-compliant rotas in a medical setting. Surveys of doctors’ subjective opinions on shift work have not provided reliable objective data with which to evaluate its efficacy. Aim: We therefore studied the effects on patient's safety and doctors’ work-sleep patterns of implementing an EWTD-compliant 48 h work week in a single-blind intervention study carried out over a 12-week period at the University Hospitals Coventry & Warwickshire NHS Trust. We hypothesized that medical error rates would be reduced following the new rota. Methods: Nineteen junior doctors, nine studied while working an intervention schedule of <48 h per week and 10 studied while working traditional weeks of <56 h scheduled hours in medical wards. Work hours and sleep duration were recorded daily. Rate of medical errors (per 1000 patient-days), identified using an established active surveillance methodology, were compared for the Intervention and Traditional wards. Two senior physicians blinded to rota independently rated all suspected errors. Results: Average scheduled work hours were significantly lower on the intervention schedule [43.2 (SD 7.7) (range 26.0–60.0) vs. 52.4 (11.2) (30.0–77.0) h/week; P < 0.001], and there was a non-significant trend for increased total sleep time per day [7.26 (0.36) vs. 6.75 (0.40) h; P = 0.095]. During a total of 4782 patient-days involving 481 admissions, 32.7% fewer total medical errors occurred during the intervention than during the traditional rota (27.6 vs. 41.0 per 1000 patient-days, P = 0.006), including 82.6% fewer intercepted potential adverse events (1.2 vs. 6.9 per 1000 patient-days, P = 0.002) and 31.4% fewer non-intercepted potential adverse events (16.6 vs. 24.2 per 1000 patient-days, P = 0.067). Doctors reported worse educational opportunities on the intervention rota. Conclusions: Whilst concerns remain regarding reduced educational opportunities, our study supports the hypothesis that a 48 h work week coupled with targeted efforts to improve sleep hygiene improves patient safety

Screening for Chronic Conditions Using a Patient Internet Portal: Recruitment for an Internet-based Primary Care Intervention

Background: Patient Internet portals have created new opportunities for assessment and management of chronic conditions. Objective: To conduct an online screening survey for a study recruitment using a secure patient Internet portal to identify primary care patients with untreated depression, chronic pain, or mobility difficulty before nonurgent office visits. Design: Internet-based screening survey for a randomized trial. Participants: Patients who were registered portal users who had scheduled primary care appointments. Approach: Electronic study invitations via the portal were sent to 4,047 patients with scheduled visits to 34 primary care physicians participating in the study. After clicking on a link in the study invitation, patients were consecutively shown the study description, consent form, and lastly, the screening survey to determine final eligibility for study participation. Results: Of the 2,113 (52%) patients who opened the study invitation, 1,001 consented online to join the study and 981 (98%) of these completed the screening survey. Of the respondents, 319 (33%) screened positive for 1 or more of the 3 conditions. Conclusions: The online screening survey conducted through the patient portal was effective in identifying patients with chronic conditions in advance of scheduled primary care visits for participation in an intervention study

UK science press officers, professional vision and the generation of expectations

Science press officers can play an integral role in helping promote expectations and hype about biomedical research. Using this as a starting point, this article draws on interviews with 10 UK-based science press officers, which explored how they view their role as science reporters and as generators of expectations. Using Goodwin’s notion of ‘professional vision’, we argue that science press officers have a specific professional vision that shapes how they produce biomedical press releases, engage in promotion of biomedical research and make sense of hype. We discuss how these insights can contribute to the sociology of expectations, as well as inform responsible science communication.This project was funded by the Wellcome Trust (Wellcome Trust Biomedical Strategic Award 086034)

Changes in intracellular ion activities induced by adrenaline in human and rat skeletal muscle

To study the stimulating effect of adrenaline (ADR) on active Na+/K+ transport we used double-barrelled ion-sensitive micro-electrodes to measure the activities of extracellular K+ (aKe) and intracellular Na+ (aNai) in isolated preparations of rat soleus muscle, normal human intercostal muscle and one case of hyperkalemic periodic paralysis (h.p.p.). In these preparations bath-application of ADR (10−6 M) resulted in a membrane hyperpolarization and transient decreasesaKe andaNai which could be blocked by ouabain (3×10−4 M). In the h.p.p. muslce a continuous rise ofaNai induced by elevation ofaKe to 5.2 mM could be stopped by ADR. In addition, the intracellular K+ activity (aKi), the free intracellular Ca2+ concentration (pCai) and intracellular pH (pHi) were monitored in rat soleus muscle. During ADRaKi increased, pHi remained constant and intracellular Ca2+ apparently decreased. In conclusion, our data show that ADR primarily stimulates the Na+/K+ pump in mammalian skeletal muscle. This stimulating action is not impaired in the h.p.p. muscle