Novel Josephson effects between multi-gap and single-gap superconductors

Multi-gap superconductors can exhibit qualitatively new phenomena due to existence of multiple order parameters. Repulsive electronic interactions may give rise to a phase difference of $\pi$ between the phases of the order parameters. Collective modes due to the oscillation of the relative phases of these order parameters are also possible. Here we show that both these phenomena are observable in Josephson junctions between a single-gap and a multi-gap superconductor. In particular, a non-monotonic temperature dependence of the Josephson current through the junction reveals the existence of the $\pi$ phase differences in the multi-gap superconductor. This mechanism may be relevant for understanding several experiments on the Josephson junctions with unconventional superconductors. We also discuss how the presence of the collective mode resonantly enhances the DC Josephson current when the voltage across the junction matches the mode frequency. We suggest that our results may apply to MgB$_2$, 2H-NbSe$_2$, spin ladder and bilayer cuprates.Comment: 4 pages, 2 figure

Connexin 36 Expression Regulates Neuronal Differentiation from Neural Progenitor Cells

Background: Gap junction communication has been shown in glial and neuronal cells and it is thought they mediate interand intra-cellular communication. Connexin 36 (Cx36) is expressed extensively in the developing brain, with levels peaking at P14 after which its levels fall and its expression becomes entirely neuronal. These and other data have led to the hypothesis that Cx36 may direct neuronal coupling and neurogenesis during development. Methodology/Principal Findings: To investigate Cx36 function we used a neurosphere model of neuronal cell development and developed lentiviral Cx36 knockdown and overexpression strategies. Cx36 knockdown was confirmed by western blotting, immunocytochemistry and functionally by fluorescence recovery after photobleaching (FRAP). We found that knockdown of Cx36 in neurosphere neuronal precursors significantly reduced neuronal coupling and the number of differentiated neurons. Correspondingly, the lentiviral mediated overexpression of Cx36 significantly increased the number of neurons derived from the transduced neurospheres. The number of oligodendrocytes was also significantly increased following transduction with Cx36 indicating they may support neuronal differentiation. Conclusions/Significance: Our data suggests that astrocytic and neuronal differentiation during development are governed by mechanisms that include the differential expression of Cx36

Search for Matter-Dependent Atmospheric Neutrino Oscillations in Super-Kamiokande

We consider muon neutrino to tau neutrino oscillations in the context of the Mass Varying Neutrino (MaVaN) model, where the neutrino mass can vary depending on the electron density along the flight path of the neutrino. Our analysis assumes a mechanism with dependence only upon the electron density, hence ordinary matter density, of the medium through which the neutrino travels. Fully-contained, partially-contained and upward-going muon atmospheric neutrino data from the Super--Kamiokande detector, taken from the entire SK--I period of 1489 live days, are compared to MaVaN model predictions. We find that, for the case of 2-flavor oscillations, and for the specific models tested, oscillation independent of electron density is favored over density dependence. Assuming maximal mixing, the best-fit case and the density-independent case do not differ significantly.Comment: 6 pages, 1 figur

Cross-regulation of Connexin43 and β-catenin influences differentiation of human neural progenitor cells

Connexin43 (Cx43) is the most widely and abundantly expressed gap junction (GJ) protein and it is strongly associated with the regulation of cell cycle progression. Emerging roles for Cx43 in cell adhesion and migration during neural differentiation have also been recently recognized, and this has emphasized the involvement of Cx43 in different physiological process beyond its role as a GJ protein. In this study, we explore the function of Cx43 in the differentiation of human neural progenitor cells (hNPCs) using viral vectors that mediate the overexpression or knockdown of the protein. Results showed that in the absence of this protein fetal cortex-derived hNPCs differentiated toward a neuronal phenotype at expenses of a glial phenotype. Furthermore, the silencing of Cx43 did not affect hNPC proliferation rate or numbers of apoptotic cells. The increase in the number of neurons was not recapitulated when GJ intercellular communications were pharmacologically blocked, and this suggested that Cx43 was influencing hNPCs differentiation with a GJ-independent effect. In addition, Cx43 knockdown significantly increased β-catenin signaling, which has been shown to regulate the transcription of pro-neuronal genes during embryonic neural development. Our results add further support to the hypothesis that Cx43 protein itself regulates key signaling pathways during development and neurogenesis beyond its role as GJ protein

Olanzapine-Induced Hyperphagia and Weight Gain Associate with Orexigenic Hypothalamic Neuropeptide Signaling without Concomitant AMPK Phosphorylation

The success of antipsychotic drug treatment in patients with schizophrenia is limited by the propensity of these drugs to induce hyperphagia, weight gain and other metabolic disturbances, particularly evident for olanzapine and clozapine. However, the molecular mechanisms involved in antipsychotic-induced hyperphagia remain unclear. Here, we investigate the effect of olanzapine administration on the regulation of hypothalamic mechanisms controlling food intake, namely neuropeptide expression and AMP-activated protein kinase (AMPK) phosphorylation in rats. Our results show that subchronic exposure to olanzapine upregulates neuropeptide Y (NPY) and agouti related protein (AgRP) and downregulates proopiomelanocortin (POMC) in the arcuate nucleus of the hypothalamus (ARC). This effect was evident both in rats fed ad libitum and in pair-fed rats. Of note, despite weight gain and increased expression of orexigenic neuropeptides, subchronic administration of olanzapine decreased AMPK phosphorylation levels. This reduction in AMPK was not observed after acute administration of either olanzapine or clozapine. Overall, our data suggest that olanzapine-induced hyperphagia is mediated through appropriate changes in hypothalamic neuropeptides, and that this effect does not require concomitant AMPK activation. Our data shed new light on the hypothalamic mechanism underlying antipsychotic-induced hyperphagia and weight gain, and provide the basis for alternative targets to control energy balance

Identifying a Window of Vulnerability during Fetal Development in a Maternal Iron Restriction Model

It is well acknowledged from observations in humans that iron deficiency during pregnancy can be associated with a number of developmental problems in the newborn and developing child. Due to the obvious limitations of human studies, the stage during gestation at which maternal iron deficiency causes an apparent impairment in the offspring remains elusive. In order to begin to understand the time window(s) during pregnancy that is/are especially susceptible to suboptimal iron levels, which may result in negative effects on the development of the fetus, we developed a rat model in which we were able to manipulate and monitor the dietary iron intake during specific stages of pregnancy and analyzed the developing fetuses. We established four different dietary-feeding protocols that were designed to render the fetuses iron deficient at different gestational stages. Based on a functional analysis that employed Auditory Brainstem Response measurements, we found that maternal iron restriction initiated prior to conception and during the first trimester were associated with profound changes in the developing fetus compared to iron restriction initiated later in pregnancy. We also showed that the presence of iron deficiency anemia, low body weight, and changes in core body temperature were not defining factors in the establishment of neural impairment in the rodent offspring

Protecting an ecosystem service: approaches to understanding and mitigating threats to wild insect pollinators

Insect pollination constitutes an ecosystem service of global importance, providing significant economic and aesthetic benefits as well as cultural value to human society, alongside vital ecological processes in terrestrial ecosystems. It is therefore important to understand how insect pollinator populations and communities respond to rapidly changing environments if we are to maintain healthy and effective pollinator services. This paper considers the importance of conserving pollinator diversity to maintain a suite of functional traits to provide a diverse set of pollinator services. We explore how we can better understand and mitigate the factors that threaten insect pollinator richness, placing our discussion within the context of populations in predominantly agricultural landscapes in addition to urban environments. We highlight a selection of important evidence gaps, with a number of complementary research steps that can be taken to better understand: i) the stability of pollinator communities in different landscapes in order to provide diverse pollinator services; ii) how we can study the drivers of population change to mitigate the effects and support stable sources of pollinator services; and, iii) how we can manage habitats in complex landscapes to support insect pollinators and provide sustainable pollinator services for the future. We advocate a collaborative effort to gain higher quality abundance data to understand the stability of pollinator populations and predict future trends. In addition, for effective mitigation strategies to be adopted, researchers need to conduct rigorous field-testing of outcomes under different landscape settings, acknowledge the needs of end-users when developing research proposals and consider effective methods of knowledge transfer to ensure effective uptake of actions

Automatic Detection of User Abilities through the SmartAbility Framework

This paper presents a proposed smartphone application for the unique SmartAbility Framework that supports interaction with technology for people with reduced physical ability, through focusing on the actions that they can perform independently. The Framework is a culmination of knowledge obtained through previously conducted technology feasibility trials and controlled usability evaluations involving the user community. The Framework is an example of ability-based design that focuses on the abilities of users instead of their disabilities. The paper includes a summary of Versions 1 and 2 of the Framework, including the results of a two-phased validation approach, conducted at the UK Mobility Roadshow and via a focus group of domain experts. A holistic model developed by adapting the House of Quality (HoQ) matrix of the Quality Function Deployment (QFD) approach is also described. A systematic literature review of sensor technologies built into smart devices establishes the capabilities of sensors in the Android and iOS operating systems. The review defines a set of inclusion and exclusion criteria, as well as search terms used to elicit literature from online repositories. The key contribution is the mapping of ability-based sensor technologies onto the Framework, to enable the future implementation of a smartphone application. Through the exploitation of the SmartAbility application, the Framework will increase technology amongst people with reduced physical ability and provide a promotional tool for assistive technology manufacturers

Evidence for Hitchhiking of Deleterious Mutations within the Human Genome

Deleterious mutations present a significant obstacle to adaptive evolution. Deleterious mutations can inhibit the spread of linked adaptive mutations through a population; conversely, adaptive substitutions can increase the frequency of linked deleterious mutations and even result in their fixation. To assess the impact of adaptive mutations on linked deleterious mutations, we examined the distribution of deleterious and neutral amino acid polymorphism in the human genome. Within genomic regions that show evidence of recent hitchhiking, we find fewer neutral but a similar number of deleterious SNPs compared to other genomic regions. The higher ratio of deleterious to neutral SNPs is consistent with simulated hitchhiking events and implies that positive selection eliminates some deleterious alleles and increases the frequency of others. The distribution of disease-associated alleles is also altered in hitchhiking regions. Disease alleles within hitchhiking regions have been associated with auto-immune disorders, metabolic diseases, cancers, and mental disorders. Our results suggest that positive selection has had a significant impact on deleterious polymorphism and may be partly responsible for the high frequency of certain human disease alleles