Modulation and regulation of canonical transient receptor potential 3 (TRPC3) channels

Canonical transient receptor potential 3 (TRPC3) channel is a non-selective cation permeable channel that plays an essential role in calcium signalling. TRPC3 is highly expressed in the brain and also found in endocrine tissues and smooth muscle cells. The channel is activated directly by binding of diacylglycerol downstream of G-protein coupled receptor activation. In addition, TRPC3 is regulated by endogenous factors including Ca2+ ions, other endogenous lipids, and interacting proteins. The molecular and structural mechanisms underlying activation and regulation of TRPC3 are incompletely understood. Recently, several high-resolution cryogenic electron microscopy structures of TRPC3 and the closely related channel TRPC6 have been resolved in different functional states and in the presence of modulators, coupled with mutagenesis studies and electrophysiological characterisation. Here, we review the recent literature which has advanced our understanding of the complex mechanisms underlying modulation of TRPC3 by both endogenous and exogenous factors. TRPC3 plays an important role in Ca2+ homeostasis and entry into cells throughout the body, and both pathological variants and downstream dysregulation of TRPC3 channels have been associated with a number of diseases. As such, TRPC3 may be a valuable therapeutic target, and understanding its regulatory mechanisms will aid future development of pharmacological modulators of the channel

Gestational age at delivery and special educational need: retrospective cohort study of 407,503 schoolchildren

<STRONG>Background</STRONG> Previous studies have demonstrated an association between preterm delivery and increased risk of special educational need (SEN). The aim of our study was to examine the risk of SEN across the full range of gestation. <STRONG>Methods and Findings</STRONG> We conducted a population-based, retrospective study by linking school census data on the 407,503 eligible school-aged children resident in 19 Scottish Local Authority areas (total population 3.8 million) to their routine birth data. SEN was recorded in 17,784 (4.9%) children; 1,565 (8.4%) of those born preterm and 16,219 (4.7%) of those born at term. The risk of SEN increased across the whole range of gestation from 40 to 24 wk: 37–39 wk adjusted odds ratio (OR) 1.16, 95% confidence interval (CI) 1.12–1.20; 33–36 wk adjusted OR 1.53, 95% CI 1.43–1.63; 28–32 wk adjusted OR 2.66, 95% CI 2.38–2.97; 24–27 wk adjusted OR 6.92, 95% CI 5.58–8.58. There was no interaction between elective versus spontaneous delivery. Overall, gestation at delivery accounted for 10% of the adjusted population attributable fraction of SEN. Because of their high frequency, early term deliveries (37–39 wk) accounted for 5.5% of cases of SEN compared with preterm deliveries (<37 wk), which accounted for only 3.6% of cases. <STRONG>Conclusions</STRONG> Gestation at delivery had a strong, dose-dependent relationship with SEN that was apparent across the whole range of gestation. Because early term delivery is more common than preterm delivery, the former accounts for a higher percentage of SEN cases. Our findings have important implications for clinical practice in relation to the timing of elective delivery

The cost of promiscuity: sexual transmission of Nosema microsporidian parasites in polyandrous honey bees

Multiple mating (and insemination) by females with different males, polyandry, is widespread across animals, due to material and/or genetic benefits for females. It reaches particularly high levels in some social insects, in which queens can produce significantly fitter colonies by being polyandrous. It is therefore a paradox that two thirds of eusocial hymenopteran insects appear to be exclusively monandrous, in spite of the fitness benefits that polyandry could provide. One possible cost of polyandry could be sexually transmitted parasites, but evidence for these in social insects is extremely limited. Here we show that two different species of Nosema microsporidian parasites can transmit sexually in the honey bee Apis mellifera. Honey bee males that are infected by the parasite have Nosema spores in their semen, and queens artificially inseminated with either Nosema spores or the semen of Nosema-infected males became infected by the parasite. The emergent and more virulent N. ceranae achieved much higher rates of infection following insemination than did N. apis. The results provide the first quantitative evidence of a sexually transmitted disease (STD) in social insects, indicating that STDs may represent a potential cost of polyandry in social insects

Silicon-based spin and charge quantum computation

Silicon-based quantum-computer architectures have attracted attention because of their promise for scalability and their potential for synergetically utilizing the available resources associated with the existing Si technology infrastructure. Electronic and nuclear spins of shallow donors (e.g. phosphorus) in Si are ideal candidates for qubits in such proposals due to the relatively long spin coherence times. For these spin qubits, donor electron charge manipulation by external gates is a key ingredient for control and read-out of single-qubit operations, while shallow donor exchange gates are frequently invoked to perform two-qubit operations. More recently, charge qubits based on tunnel coupling in P$_2^+$ substitutional molecular ions in Si have also been proposed. We discuss the feasibility of the building blocks involved in shallow donor quantum computation in silicon, taking into account the peculiarities of silicon electronic structure, in particular the six degenerate states at the conduction band edge. We show that quantum interference among these states does not significantly affect operations involving a single donor, but leads to fast oscillations in electron exchange coupling and on tunnel-coupling strength when the donor pair relative position is changed on a lattice-parameter scale. These studies illustrate the considerable potential as well as the tremendous challenges posed by donor spin and charge as candidates for qubits in silicon.Comment: Review paper (invited) - to appear in Annals of the Brazilian Academy of Science

Prevalence and Determinants of Obesity among Primary School Children in Dar es Salaam, Tanzania.

Childhood obesity has increased dramatically and has become a public health concern worldwide. Childhood obesity is likely to persist through adulthood and may lead to early onset of NCDs. However, there is paucity of data on obesity among primary school children in Tanzania. This study assessed the prevalence and determinants of obesity among primary school children in Dar es Salaam. A cross sectional study was conducted among school age children in randomly selected schools in Dar es Salaam. Anthropometric and blood pressure measurements were taken using standard procedures. Body Mass Index (BMI) was calculated as weight in kilograms divided by the square of height in meters (kg/m2). Child obesity was defined as BMI at or above 95th percentile for age and sex. Socio-demographic characteristics of children were determined using a structured questionnaire. Logistic regression was used to determine association between independent variables with obesity among primary school children in Dar es Salaam. A total of 446 children were included in the analysis. The mean age of the participants was 11.1±2.0 years and 53.1% were girls. The mean BMI, SBP and DBP were 16.6±4.0 kg/m2, 103.9±10.3mmHg and 65.6±8.2mmHg respectively. The overall prevalence of child obesity was 5.2% and was higher among girls (6.3%) compared to boys (3.8%). Obese children had significantly higher mean values for age (p=0.042), systolic and diastolic blood pressures (all p<0.001). Most obese children were from households with fewer children (p=0.019) and residing in urban areas (p=0.002). Controlling for other variables, age above 10 years (AOR=3.3, 95% CI=1.5-7.2), female sex (AOR=2.6, 95% CI=1.4-4.9), urban residence (AOR=2.5, 95% CI=1.2-5.3) and having money to spend at school (AOR=2.6, 95% CI=1.4-4.8) were significantly associated with child obesity. The prevalence of childhood obesity in this population was found to be low. However, children from urban schools and girls were proportionately more obese compared to their counterparts. Primary preventive measures for childhood obesity should start early in childhood and address socioeconomic factors of parents contributing to childhood obesity

Robotic milking technologies and renegotiating situated ethical relationships on UK dairy farms

Robotic or automatic milking systems (AMS) are novel technologies that take over the labor of dairy farming and reduce the need for human-animal interactions. Because robotic milking involves the replacement of 'conventional' twice-a-day milking managed by people with a system that supposedly allows cows the freedom to be milked automatically whenever they choose, some claim robotic milking has health and welfare benefits for cows, increases productivity, and has lifestyle advantages for dairy farmers. This paper examines how established ethical relations on dairy farms are unsettled by the intervention of a radically different technology such as AMS. The renegotiation of ethical relationships is thus an important dimension of how the actors involved are re-assembled around a new technology. The paper draws on in-depth research on UK dairy farms comparing those using conventional milking technologies with those using AMS. We explore the situated ethical relations that are negotiated in practice, focusing on the contingent and complex nature of human-animal-technology interactions. We show that ethical relations are situated and emergent, and that as the identities, roles, and subjectivities of humans and animals are unsettled through the intervention of a new technology, the ethical relations also shift. © 2013 Springer Science+Business Media Dordrecht

Threshold effect of foreign direct investment on environmental degradation

The aim of this paper is to investigate the threshold effect of foreign direct investment (FDI) on environmental degradation. In empirical analysis, FDI and environmental degradation are jointly determined under the given threshold variable and other exogenous variables. Using carbon dioxide (CO2) emissions per capita as a proxy for environmental degradation, the results show that increasing FDI worsens CO2 emissions after a threshold level of corruption has been reached. Our results demonstrate that increasing FDI will increase CO2 emissions when the degree of corruptibility is relatively high. The study suggests that further FDI and improved environmental quality are competing rather than compatible objectives in high-corruption countries and are compatible rather than competing objectives in low-corruption countries. Higher trade liberalization in low-corruption countries could contribute to negative environmental consequences because of the increased output or economic activity which results from increased trade. The robustness estimation confirms the evidence that pollution and economic development increase together up to a certain income level, after which the trend reverses.info:eu-repo/semantics/publishedVersio

MEF2A regulates mGluR-dependent AMPA receptor trafficking independently of Arc/Arg3.1

© 2018 The Author(s). Differential trafficking of AMPA receptors (AMPARs) to and from the postsynaptic membrane is a key determinant of the strength of excitatory neurotransmission, and is thought to underlie learning and memory. The transcription factor MEF2 is a negative regulator of memory in vivo, in part by regulating trafficking of the AMPAR subunit GluA2, but the molecular mechanisms behind this have not been established. Here we show, via knockdown of endogenous MEF2A in primary neuronal culture, that MEF2A is specifically required for Group I metabotropic glutamate receptor (mGluR)-mediated GluA2 internalisation, but does not regulate AMPAR expression or trafficking under basal conditions. Furthermore, this process occurs independently of changes in expression of Arc/Arg3.1, a previously characterised MEF2 transcriptional target and mediator of mGluR-dependent long-term depression. These data demonstrate a novel MEF2A-dependent mechanism for the regulation of activity-dependent AMPAR trafficking

Early star-forming galaxies and the reionization of the Universe

Star forming galaxies represent a valuable tracer of cosmic history. Recent observational progress with Hubble Space Telescope has led to the discovery and study of the earliest-known galaxies corresponding to a period when the Universe was only ~800 million years old. Intense ultraviolet radiation from these early galaxies probably induced a major event in cosmic history: the reionization of intergalactic hydrogen. New techniques are being developed to understand the properties of these most distant galaxies and determine their influence on the evolution of the universe.Comment: Review article appearing in Nature. This posting reflects a submitted version of the review formatted by the authors, in accordance with Nature publication policies. For the official, published version of the review, please see http://www.nature.com/nature/archive/index.htm

Childhood socioeconomic position and objectively measured physical capability levels in adulthood: a systematic review and meta-analysis

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Grip strength, walking speed, chair rising and standing balance time are objective measures of physical capability that characterise current health and predict survival in older populations. Socioeconomic position (SEP) in childhood may influence the peak level of physical capability achieved in early adulthood, thereby affecting levels in later adulthood. We have undertaken a systematic review with meta-analyses to test the hypothesis that adverse childhood SEP is associated with lower levels of objectively measured physical capability in adulthood.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods and Findings:&lt;/b&gt; Relevant studies published by May 2010 were identified through literature searches using EMBASE and MEDLINE. Unpublished results were obtained from study investigators. Results were provided by all study investigators in a standard format and pooled using random-effects meta-analyses. 19 studies were included in the review. Total sample sizes in meta-analyses ranged from N = 17,215 for chair rise time to N = 1,061,855 for grip strength. Although heterogeneity was detected, there was consistent evidence in age adjusted models that lower childhood SEP was associated with modest reductions in physical capability levels in adulthood: comparing the lowest with the highest childhood SEP there was a reduction in grip strength of 0.13 standard deviations (95% CI: 0.06, 0.21), a reduction in mean walking speed of 0.07 m/s (0.05, 0.10), an increase in mean chair rise time of 6% (4%, 8%) and an odds ratio of an inability to balance for 5s of 1.26 (1.02, 1.55). Adjustment for the potential mediating factors, adult SEP and body size attenuated associations greatly. However, despite this attenuation, for walking speed and chair rise time, there was still evidence of moderate associations.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Policies targeting socioeconomic inequalities in childhood may have additional benefits in promoting the maintenance of independence in later life.&lt;/p&gt