The unique N-terminal sequence of the BKCa channel α-subunit determines its modulation by β-subunits

Large conductance voltage- and Ca2+-activated K+ (BKCa) channels are essential regulators of membrane excitability in a wide variety of cells and tissues. An important mechanism of modulation of BKCa channel activity is its association with auxiliary subunits. In smooth muscle cells, the most predominant regulatory subunit of BKCa channels is the β1-subunit. We have previously described that BKCa channels with distinctive N-terminal ends (starting with the amino acid sequence MDAL, MSSN or MANG) are differentially modulated by the β1-subunit, but not by the β2. Here we extended our studies to understand how the distinct N-terminal regions differentially modulate channel activity by β-subunits. We recorded inside-out single-channel currents from HEK293T cells co-expressing the BKCa containing three N-terminal sequences with two β1-β2 chimeric constructs containing the extracellular loop of β1 or β2, and the transmembrane and cytoplasmic domains of β2 or β1, respectively. Both β chimeric constructs induced leftward shifts of voltage-activation curves of channels starting with MANG and MDAL, in the presence of 10 or 100 μM intracellular Ca2+. However, MSSN showed no shift of the voltage-activation, at the same Ca2+ concentrations. The presence of the extracellular loop of β1 in the chimera resembled results seen with the full β1 subunit, suggesting that the extracellular region of β1 might be responsible for the lack of modulation observed in MSSN. We further studied a poly-serine stretch present in the N-terminal region of MSSN and observed that the voltage-activation curves of BKCa channels either containing or lacking this poly-serine stretch were leftward shifted by β1-subunit in a similar way. Overall, our results provide further insights into the mechanism of modulation of the different N-terminal regions of the BKCa channel by β-subunits and highlight the extension of this region of the channel as a form of modulation of channel activity

The Relationship of Grit and Social Media Addiction for College Students

This quantitative study explored the relationship between grit and social media. Researchers have noted a significant increase in the use of social media among college students that often results in negative outcomes, both personally and academically. Previous studies have shown that grit is a trait that negatively relates to various types of addictive behavior. However, little is known about the correlation between grit and social media addiction specifically. The purpose of this study was to determine the relationship between grit and social media addiction. This study collected data from the student populations of three private colleges and followed a correlational design. The sample of 158 participants were enrolled in on-campus or online courses and responded to an online survey through Survey Monkey. Participants provided basic demographic information and completed the 8-item Grit-S scale and 6-item Bergen Social Media Addiction Scale. The researcher analyzed this data to determine the strength of the correlation between these variables using the Pearson correlation. The result of this study revealed a significant negative correlation between the variables. This research will benefit school administrators, parents, and policymakers seeking to be successful in their academic endeavors. Future researchers can expand on these findings by exploring this correlation among other populations as well as conducting longitudinal studies that could establish if those who are at risk of addictions develop them later in life

Deaf and hearing children's picture naming Impact of age of acquisition and language modality on representational gesture

Stefanini, Bello, Caselli, Iverson, & Volterra (2009) reported that Italian 24-36 month old children use a high proportion of representational gestures to accompany their spoken responses when labelling pictures. The two studies reported here used the same naming task with (1) typically developing 24-46-month-old hearing children acquiring English and (2) 24-63-month-old deaf children of deaf and hearing parents acquiring British Sign Language (BSL) and spoken English. In Study 1 children scored within the range of correct spoken responses previously reported, but produced very few representational gestures. However, when they did gesture, they expressed the same action meanings as reported in previous research. The action bias was also observed in deaf children of hearing parents in Study 2, who labelled pictures with signs, spoken words and gestures. The deaf group with deaf parents used BSL almost exclusively with few additional gestures. The function of representational gestures in spoken and signed vocabulary development is considered in relation to differences between native and non-native sign language acquisition

Do people with intellectual disabilities understand their prescription medication? A scoping review

© 2019 The Authors. Journal of Applied Research in Intellectual Disabilities Published by John Wiley & Sons Ltd.Background: People with intellectual disabilities are more likely to experience poor health than the general population and are frequently prescribed multiple medications. Therefore, it is important that people with intellectual disabilities understand their medication and potential adverse effects. Method: A scoping review explored people with intellectual disabilities' knowledge of prescription medications, their risks and how medication understanding can be improved. Results: Ten journal articles were included. People with intellectual disabilities often lacked understanding of their medication, including its name, purpose and when and how to take it. Participants were often confused or unaware of adverse effects associated with their medication. Information was sometimes explained to carers rather than people with intellectual disabilities. Some interventions and accessible information helped to improve knowledge in people with intellectual disabilities. Conclusion: There is a need for accessible and tailored information about medication to be discussed with people with intellectual disabilities in order to meet legal and best practice standards.Peer reviewe

Generalised Elliptic Functions

We consider multiply periodic functions, sometimes called Abelian functions, defined with respect to the period matrices associated with classes of algebraic curves. We realise them as generalisations of the Weierstras P-function using two different approaches. These functions arise naturally as solutions to some of the important equations of mathematical physics and their differential equations, addition formulae, and applications have all been recent topics of study. The first approach discussed sees the functions defined as logarithmic derivatives of the sigma-function, a modified Riemann theta-function. We can make use of known properties of the sigma function to derive power series expansions and in turn the properties mentioned above. This approach has been extended to a wide range of non hyperelliptic and higher genus curves and an overview of recent results is given. The second approach defines the functions algebraically, after first modifying the curve into its equivariant form. This approach allows the use of representation theory to derive a range of results at lower computational cost. We discuss the development of this theory for hyperelliptic curves and how it may be extended in the future.Comment: 16 page

Na+-leak channel, non-selective (NALCN) regulates myometrial excitability and facilitates successful parturition

Background/Aims: Uterine contractility is controlled by electrical signals generated by myometrial smooth muscle cells. Because aberrant electrical signaling may cause inefficient uterine contractions and poor reproductive outcomes, there is great interest in defining the ion channels that regulate uterine excitability. In human myometrium, the Na+ leak channel, non-selective (NALCN) contributes to a gadolinium-sensitive, Na+-dependent leak current. The aim of this study was to determine the role of NALCN in regulating uterine excitability and examine its involvement in parturition. Methods: Wildtype C57BL/6J mice underwent timed-mating and NALCN uterine expression was measured at several time points across pregnancy including pregnancy days 7, 10, 14, 18 and 19. Sharp electrode current clamp was used to measure uterine excitability at these same time points. To determine NALCN’s contribution to myometrial excitability and pregnancy outcomes, we created smooth-muscle-specific NALCN knockout mice by crossing NALCNfx/fx mice with myosin heavy chain Cre (MHCCreeGFP) mice. Parturition outcomes were assessed by observation via surveillance video recording cre control, flox control, smNALCN+/-, and smNALCN-/- mice. Myometrial excitability was compared between pregnancy day 19 flox controls and smNALCN-/- mice. Results: We found that in the mouse uterus, NALCN protein levels were high early in pregnancy, decreased in mid and late pregnancy, and then increased in labor and postpartum. Sharp electrode current clamp recordings of mouse longitudinal myometrial samples from pregnancy days 7, 10, 14, 18, and 19 revealed day-dependent increases in burst duration and interval and decreases in spike density. NALCN smooth muscle knockout mice had reduced myometrial excitability exemplified by shortened action potential bursts, and an increased rate of abnormal labor, including prolonged and dysfunctional labor. Conclusions: Together, our findings demonstrate that the Na+ conducting channel NALCN contributes to the myometrial action potential waveform and is important for successful labor outcomes

Reviewing research evidence and the case of participation in sport and physical recreation by black and minority ethnic communities

The paper addresses the implications of using the process of systematic review in the many areas of leisure where there is a dearth of material that would be admitted into conventional Cochrane Reviews. This raises important questions about what constitutes legitimate knowledge, questions that are of critical import not just to leisure scholars, but to the formulation of policy. The search for certainty in an area that lacks conceptual consensus results in an epistemological imperialism that takes a geocentric form. While clearly, there is a need for good research design whatever the style of research, we contend that the wholesale rejection of insightful research is profligate and foolhardy. A mechanism has to be found to capitalise on good quality research of whatever form. In that search, we draw upon our experience of conducting a review of the material available on participation in sport and physical recreation by people from Black and minority ethnic groups. The paper concludes with a proposal for a more productive review process that makes better use of the full panoply of good quality research available. © 2012 © 2012 Taylor & Francis