Human neuronal stargazin-like proteins, γ_2, γ_3 and γ_4; an investigation of their specific localization in human brain and their influence on Ca_V2.1 voltage-dependent calcium channels expressed in Xenopus oocytes

Background: Stargazin (γ2) and the closely related γ3, and γ4 transmembrane proteins are part of a family of proteins that may act as both neuronal voltage-dependent calcium channel (VDCC) γ subunits and transmembrane α-amino-3-hydroxy-5-methyl-4-isoxazoleproponinc (AMPA) receptor regulatory proteins (TARPs). In this investigation, we examined the distribution patterns of the stargazin-like proteins γ2, γ3, and γ4 in the human central nervous system (CNS). In addition, we investigated whether human γ2 or γ4 could modulate the electrophysiological properties of a neuronal VDCC complex transiently expressed in Xenopus oocytes. Results: The mRNA encoding human γ2 is highly expressed in cerebellum, cerebral cortex, hippocampus and thalamus, whereas γ3 is abundant in cerebral cortex and amygdala and γ4 in the basal ganglia. Immunohistochemical analysis of the cerebellum determined that both γ2 and γ4 are present in the molecular layer, particularly in Purkinje cell bodies and dendrites, but have an inverse expression pattern to one another in the dentate cerebellar nucleus. They are also detected in the interneurons of the granule cell layer though only γ2 is clearly detected in granule cells. The hippocampus stains for γ2 and γ4 throughout the layers of the every CA region and the dentate gyrus, whilst γ3 appears to be localized particularly to the pyramidal and granule cell bodies. When co-expressed in Xenopus oocytes with a CaV2.1/β4 VDCC complex, either in the absence or presence of an α2δ2 subunit, neither γ2 nor γ4 significantly modulated the VDCC peak current amplitude, voltage-dependence of activation or voltage-dependence of steady-state inactivation. Conclusion: The human γ2, γ3 and γ4 stargazin-like proteins are detected only in the CNS and display differential distributions among brain regions and several cell types in found in the cerebellum and hippocampus. These distribution patterns closely resemble those reported by other laboratories for the rodent orthologues of each protein. Whilst the fact that neither γ2 nor γ4 modulated the properties of a VDCC complex with which they could associate in vivo in Purkinje cells adds weight to the hypothesis that the principal role of these proteins is not as auxiliary subunits of VDCCs, it does not exclude the possibility that they play another role in VDCC function

How Do We Come to Know? Exploring Maple Syrup Production and Climate Change in Near North Ontario

This paper reports on a pilot project exploring the impacts of climate change on maple syrup production in understudied near north, Ontario spaces. Maple syrup is produced by settler, Métis and First Nations communities for commercial distribution and as part of a mixed subsistence economy. The focus on maple syrup is opportune, since syrup production and sugar maple trees (Acer saccharum) are extremely susceptible to climate change and the biophysical and social impacts of climate change on maple syrup production in the near north of Ontario have yet to be understood. Given that the process of developing research is under-reported and that this project has had the opportunity to undertake a funded development process, this paper describes and assesses our process of ‘coming to know’, which has been guided by the following objectives: 1) to undertake an exploratory investigation of the nature of available data about long-term syrup production and climate change in both settler and Indigenous communities, 2) to include and valorize marginalized Indigenous voices and ecologies, 3) to focus on collecting climate change data from understudied near north spaces, 4) to assess the availability and quality of ecological and quantitative data in order to enhance locally-relevant understandings of climate change, and 5) to work towards the development of a cross-cultural and transdisciplinary methodological framework within which to accomplish the first four objectives. We approach these objectives across disciplinary boundaries and cultural perspectives, and with growing relationships with community partners. We describe the rich sources of information found through the pilot study and discuss highlights of our on-going process of developing our research project

Stability of freely falling granular streams

A freely falling stream of weakly cohesive granular particles is modeled and analysed with help of event driven simulations and continuum hydrodynamics. The former show a breakup of the stream into droplets, whose size is measured as a function of cohesive energy. Extensional flow is an exact solution of the one-dimensional Navier-Stokes equation, corresponding to a strain rate, decaying like 1/t from its initial value, gammaDot0. Expanding around this basic state, we show that the flow is stable for short times (gammaDot0 * t << 1), whereas for long times (gammaDot0 * t >> 1) perturbations of all wavelength grow. The growthrate of a given wavelength depends on the instant of time when the fluctuation occurs, so that the observable patterns can vary considerably.Comment: 4 page, 5 figures. Submitted to PRL. Supplementary material: see http://wwwuser.gwdg.de/~sulrich/research/#Publication

From Giving Birth to Paid Labor: The Effects of Adult Education for Prime-Aged Mothers

Women without work after childbirth are at risk of losing their connection to the labor market. However, they may participate in adult education programs. We analyze the effect of this on the duration to work and on the wage rate, by applying conditional difference-in-differences approaches. We use Swedish matched longitudinal register data sets covering the full population. The Swedish adult education program is unprecedented in its size, and enrollment is universally available at virtually no cost. We focus on low-skilled women who have recently given birth. We take account of program accessibility, selection issues, course heterogeneity, the income received during adult education, parental leave, and child care fees. To understand the enrollment decision from the mothers' point of view, we use the estimates to calibrate a job search model.evaluation of adult education, job search model, female labor supply, wages, participation, unemployment, schooling, conditional difference-in-differences

The Spectacular Ionized Interstellar Medium of NGC55

We present deep Halpha+[NII], [SII] (6716,6731A) and [OII] (3726,3729A) images of the highly inclined, actively star--forming SBm galaxy NGC 55, located in the nearby Sculptor Group. Due to its proximity, NGC 55 provides a unique opportunity to study the disk--halo interface in a late--type galaxy with unprecedented spatial resolution. Our images reveal a spectacular variety of ionized gas features, ranging from giant HII region complexes, to supergiant filamentary and shell features, to patches of very faint diffuse emission. Many of these features protrude well above the plane of the galaxy, including a very faint fragmented shell of emission which is visible at 2.6 kpc above the disk. We identify candidate `chimneys' extending out of the disk, which could be the conduits into the halo for hot gas around disk star-forming regions, and could also provide low-density paths for the passage of UV photons from the disk to the halo. Several of the identified chimneys are `capped' with clumps of ionized gas, one of which, located at 1.5 kpc above the disk plane, appears to be the site of recent star formation. Emission--line ratios ([OII]/Halpha+[NII], [SII]/Halpha+[NII]) constrain the ionization mechanism of the gas, and our images allow the first measurement of [OII]/Halpha+[NII] in extra-planar diffuse ionized gas. The diffuse gas is characterized by emission--line ratios which are enhanced on average by a factor of two compared to those of bright HII regions. Each line ratio increases in value smoothly from the cores of HII regions, through the haloes of HII regions, into the diffuse ionized gas. Such a continuous trend is predicted by models in which the diffuse gas is ionized by photons produced by massive stars in HII regions.Comment: 19 pages, including 4 figures, plus 2 external tables. Accepted for publication in the Astronomical Journal. Compressed, postscript versions of the plates are available at ftp://skysrv.pha.jhu.edu/ferguson

An investigation of the breadth of neutralising antibody response in cats naturally infected with feline immunodeficiency virus

Neutralising antibodies (NAbs) are believed to comprise an essential component of the protective immune response induced by vaccines against FIV and HIV infections. However, relatively little is known about the role of NAbs in controlling FIV infection and subsequent disease progression. Here we present studies examining the neutralisation of HIV-luciferase pseudotypes bearing homologous and heterologous FIV Envs (n=278) by sequential plasma samples collected at 6 month intervals from naturally infected cats (n=38) over a period of 18 months. We evaluated the breadth of the NAb response against non-recombinant homologous and heterologous clade A and clade B viral variants as well as recombinants and assessed the results, testing for evidence of an association between the potency of the NAb response and the duration of infection, CD4 T lymphocyte numbers, health status and survival times of the infected cats. Neutralisation profiles varied significantly between FIV infected cats and strong autologous neutralisation, assessed using luciferase based in vitro assays, did not correlate with the clinical outcome. No association was observed between strong NAb responses and either improved health status or increased survival time of infected animals, implying that other protective mechanisms are likely to be involved. Similarly, no correlation was observed between the development of autologous NAbs and the duration of infection. Furthermore, cross-neutralising antibodies were evident in only a small proportion (13%) of cats

Rapid evolution of the env gene leader sequence in cats naturally infected with feline immunodeficiency virus (FIV)

Analysing the evolution of FIV on the intra-host level is important, in order to address whether the diversity and composition of viral quasispecies affects disease progression.&lt;p&gt;&lt;/p&gt; We examined the intra-host diversity and the evolutionary rates of the entire env and structural fragments of the env sequences obtained from sequential blood samples in 43 naturally infected domestic cats that displayed different clinical outcomes. We observed in the majority of cats that FIV env showed very low levels of intra-host diversity. We estimated that env evolved at the rate of 1.16 x 10-3 substitutions per site per year and demonstrated that recombinant sequences evolved faster than non-recombinant sequences. It was evident that the V3-V5 fragment of FIV env displayed higher evolutionary rates in healthy cats than in those with terminal illness. Our study provided the first evidence that the leader sequence of env, rather than the V3-V5 sequence, had the highest intra-host diversity and the highest evolutionary rate of all env fragments, consistent with this region being under a strong selective pressure for genetic variation.&lt;p&gt;&lt;/p&gt; Overall, FIV env displayed relatively low intra-host diversity and evolved slowly in naturally infected cats. The maximal evolutionary rate was observed in the leader sequence of env. Although genetic stability is not necessarily a prerequisite for clinical stability, the higher genetic stability of FIV compared to HIV might explain why many naturally infected cats do not progress to AIDS rapidly.&lt;p&gt;&lt;/p&gt

Solid fuel use and cooking practices as a major risk factor for ALRI mortality among African children

Background: Almost half of global child deaths due to acute lower respiratory infections (ALRIs) occur in sub-Saharan Africa, where three-quarters of the population cook with solid fuels. This study aims to quantify the impact of fuel type and cooking practices on childhood ALRI mortality in Africa, and to explore implications for public health interventions. Methods: Early-release World Health Survey data for the year 2003 were pooled for 16 African countries. Among 32 620 children born during the last 10 years, 1455 (4.46%) were reported to have died prior to their fifth birthday. Survival analysis was used to examine the impact of different cooking-related parameters on ALRI mortality, defined as cough accompanied by rapid breathing or chest indrawing based on maternal recall of symptoms prior to death. Results: Solid fuel use increases the risk of ALRI mortality with an adjusted hazard ratio of 2.35 (95% CI 1.22 to 4.52); this association grows stronger with increasing outcome specificity. Differences between households burning solid fuels on a well-ventilated stove and households relying on cleaner fuels are limited. In contrast, cooking with solid fuels in the absence of a chimney or hood is associated with an adjusted hazard ratio of 2.68 (1.38 to 5.23). Outdoor cooking is less harmful than indoor cooking but, overall, stove ventilation emerges as a more significant determinant of ALRI mortality. Conclusions: This study shows substantial differences in ALRI mortality risk among African children in relation to cooking practices, and suggests that stove ventilation may be an important means of reducing indoor air pollution