Short Term Development and Fate of MGE-Like Neural Progenitor Cells in Jaundiced and Non-Jaundiced Rat Brain

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Neonatal hyperbilirubinemia targets specific brain regions and can lead to kernicterus. One of the most debilitating symptoms of kernicterus is dystonia, which results from bilirubin toxicity to the globus pallidus (GP). Stem cell transplantation into the GP to replace lost neurons and restore basal ganglia circuits function is a potential therapeutic strategy to treat dystonia in kernicterus. In this study we transplanted human medial ganglionic eminence (MGE)-like neural progenitor cells (NPCs) that we differentiated into a primarily gamma-aminobutyric acid (GABA)ergic phenotype, into the GP of non-immunosuppressed jaundiced (jj) and non-jaundiced (Nj) rats. We assessed the survival and development of graft cells at three time-points post-transplantation. While grafted MGE-like NPCs survived and generated abundant fibers in both jj and Nj brains, NPC survival was greater in the jj brain. These results were consistent with our previous finding that excitatory spinal interneuron-like NPCs exhibited a higher survival rate in the jj brain than in the Nj brain. Our findings further support our hypothesis that slightly elevated bilirubin levels in the jj brain served as an antioxidant and immunosuppressant to protect the transplanted cells. We also identified graft fibers growing toward brain regions that receive projections from the GP, as well as host fibers extending toward the graft. These promising findings suggest that MGE-like NPCs may have the capacity to restore the circuits connecting GP and other nuclei.NIH Center of Biomedical Research Excellence program project P20 GM104936Children's Mercy HospitalRonald D. Deffenbaugh FoundationKansas Intellectual and Developmental Disabilities Research Center HD09021

In search of a pan-European culture: European values, beliefs and models of selfhood in global perspective

What, if any, are the common cultural characteristics that distinguish European societies and groups when viewed against a backdrop of global cultural variation? We sought to identify any shared features of European cultures through secondary multilevel analyses of two large datasets that together provided measures of cultural values, beliefs and models of selfhood from samples in all inhabited continents. Although heterogeneous in many respects—including the value dimension of autonomy versus embeddedness—European samples shared two distinctive features: a decontextualized representation of personhood and a cultural model of selfhood emphasizing difference from others. Compared to samples from other regions, European samples on average also emphasized egalitarianism and harmony values, commitment to others in their models of selfhood, and an immutable concept of personhood, but not uniformly so. We interpret these findings in relation to a Durkheimian model of individualism

Aerobiology over Antarctica – a new initiative for atmospheric ecology

The role of aerial dispersal in shaping patterns of biodiversity remains poorly understood, mainly due to a lack of coordinated efforts in gathering data at appropriate temporal and spatial scales. It has been long known that the rate of dispersal to an ecosystem can significantly influence ecosystem dynamics, and that aerial transport has been identified as an important source of biological input to remote locations. With the considerable effort devoted in recent decades to understanding atmospheric circulation in the south-polar region, a unique opportunity has emerged to investigate the atmospheric ecology of Antarctica, from regional to continental scales. This concept note identifies key questions in Antarctic microbial biogeography and the need for standardized sampling and analysis protocols to address such questions. A consortium of polar aerobiologists is established to bring together researchers with a common interest in the airborne dispersion of microbes and other propagules in the Antarctic, with opportunities for comparative studies in the Arctic

Neutrino Propagation in a Strongly Magnetized Medium

We derive general expressions at the one-loop level for the coefficients of the covariant structure of the neutrino self-energy in the presence of a constant magnetic field. The neutrino energy spectrum and index of refraction are obtained for neutral and charged media in the strong-field limit ($M_{W}\gg \sqrt{B}\gg m_{e},T,\mu ,| \mathbf{p}|$) using the lowest Landau level approximation. The results found within the lowest Landau level approximation are numerically validated, summing in all Landau levels, for strong $B\gg T^{2}$ and weakly-strong $B \gtrsim T^{2}$ fields. The neutrino energy in leading order of the Fermi coupling constant is expressed as the sum of three terms: a kinetic-energy term, a term of interaction between the magnetic field and an induced neutrino magnetic moment, and a rest-energy term. The leading radiative correction to the kinetic-energy term depends linearly on the magnetic field strength and is independent of the chemical potential. The other two terms are only present in a charged medium. For strong and weakly-strong fields, it is found that the field-dependent correction to the neutrino energy in a neutral medium is much larger than the thermal one. Possible applications to cosmology and astrophysics are considered.Comment: 23 pages, 4 figures. Corrected misprints in reference

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al

Solution structure of a repeated unit of the ABA-1 nematode polyprotein allergen of ascaris reveals a novel fold and two discrete lipid-binding sites

Parasitic nematode worms cause serious health problems in humans and other animals. They can induce allergic-type immune responses, which can be harmful but may at the same time protect against the infections. Allergens are proteins that trigger allergic reactions and these parasites produce a type that is confined to nematodes, the nematode polyprotein allergens (NPAs). These are synthesized as large precursor proteins comprising repeating units of similar amino acid sequence that are subsequently cleaved into multiple copies of the allergen protein. NPAs bind small lipids such as fatty acids and retinol (Vitamin A) and probably transport these sensitive and insoluble compounds between the tissues of the worms. Nematodes cannot synthesize these lipids, so NPAs may also be crucial for extracting nutrients from their hosts. They may also be involved in altering immune responses by controlling the lipids by which the immune and inflammatory cells communicate. We describe the molecular structure of one unit of an NPA, the well-known ABA-1 allergen of Ascaris and find its structure to be of a type not previously found for lipid-binding proteins, and we describe the unusual sites where lipids bind within this structur

Eight common genetic variants associated with serum dheas levels suggest a key role in ageing mechanisms

Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands-yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15×10-36), SULT2A1 (rs2637125; p = 2.61×10-19), ARPC1A (rs740160; p = 1.56×10-16), TRIM4 (rs17277546; p = 4.50×10-11), BMF (rs7181230; p = 5.44×10-11), HHEX (rs2497306; p = 4.64×10-9), BCL2L11 (rs6738028; p = 1.72×10-8), and CYP2C9 (rs2185570; p = 2.29×10-8). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS

Nation-level moderators of the extent to which self-efficacy and relationship harmony predict students’ depression and life satisfaction: evidence from ten cultures

Previous two-nation comparisons have provided evidence that self-efficacy may be a protective factor against depression in individualist cultures, whereas relationship harmony may be a stronger protective factor in collectivist cultures. However, wider sampling and more specific measures of cultural difference are required to test these conclusions. Student ratings of depression and life satisfaction were surveyed in 10 samples drawn from nine nations. Culture-level individualism positively moderated the relationship of self-efficacy to low depression. However, culture-level collectivism negatively moderated the linkage of relationship harmony to depression. To better understand these effects, four separate nation-level predictors derived from dimensions of self-construal were employed. Effects of self-efficacy were strongest where cultural models of selfhood emphasized self-direction (vs. receptiveness to influence); effects of relationship harmony were strongest where cultural models of selfhood emphasized dependence on others (vs. self-reliance). These results illustrate the value of unpackaging the diffusely defined concept of individualism-collectivism