Search for Gravitational Waves from Primordial Black Hole Binary Coalescences in the Galactic Halo

We use data from the second science run of the LIGO gravitational-wave detectors to search for the gravitational waves from primordial black hole (PBH) binary coalescence with component masses in the range 0.2--$1.0 M_\odot$. The analysis requires a signal to be found in the data from both LIGO observatories, according to a set of coincidence criteria. No inspiral signals were found. Assuming a spherical halo with core radius 5 kpc extending to 50 kpc containing non-spinning black holes with masses in the range 0.2--$1.0 M_\odot$, we place an observational upper limit on the rate of PBH coalescence of 63 per year per Milky Way halo (MWH) with 90% confidence.Comment: 7 pages, 4 figures, to be submitted to Phys. Rev.

Determination of quantitative trait loci (QTL) for early maturation in rainbow trout (Oncorhynchus mykiss)

To identify quantitative trait loci (QTL) influencing early maturation (EM) in rainbow trout (Oncorhynchus mykiss), a genome scan was performed using 100 microsatellite loci across 29 linkage groups. Six inter-strain paternal half-sib families using three inter-strain F(1) brothers (approximately 50 progeny in each family) derived from two strains that differ in the propensity for EM were used in the study. Alleles derived from both parental sources were observed to contribute to the expression of EM in the progeny of the brothers. Four genome-wide significant QTL regions (i.e., RT-8, -17, -24, and -30) were observed. EM QTL detected on RT-8 and -24 demonstrated significant and suggestive QTL effects in both male and female progeny. Furthermore, within both male and female full-sib groupings, QTL on RT-8 and -24 were detected in two or more of the five parents used. Significant genome-wide and several strong chromosome-wide QTL for EM localized to different regions in males and females, suggesting some sex-specific control. Namely, QTL detected on RT-13, -15, -21, and -30 were associated with EM only in females, and those on RT-3, -17, and -19 were associated with EM only in males. Within the QTL regions identified, a comparison of syntenic EST markers from the rainbow trout linkage map with the zebrafish (Danio rerio) genome identified several putative candidate genes that may influence EM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10126-008-9098-5) contains supplementary material, which is available to authorized users

Qualitative thematic analysis of consent forms used in cancer genome sequencing

<p>Abstract</p> <p>Background</p> <p>Large-scale whole genome sequencing (WGS) studies promise to revolutionize cancer research by identifying targets for therapy and by discovering molecular biomarkers to aid early diagnosis, to better determine prognosis and to improve treatment response prediction. Such projects raise a number of ethical, legal, and social (ELS) issues that should be considered. In this study, we set out to discover how these issues are being handled across different jurisdictions.</p> <p>Methods</p> <p>We examined informed consent (IC) forms from 30 cancer genome sequencing studies to assess (1) stated purpose of sample collection, (2) scope of consent requested, (3) data sharing protocols (4) privacy protection measures, (5) described risks of participation, (6) subject re-contacting, and (7) protocol for withdrawal.</p> <p>Results</p> <p>There is a high degree of similarity in how cancer researchers engaged in WGS are protecting participant privacy. We observed a strong trend towards both using samples for additional, unspecified research and sharing data with other investigators. IC forms were varied in terms of how they discussed re-contacting participants, returning results and facilitating participant withdrawal. Contrary to expectation, there were no consistent trends that emerged over the eight year period from which forms were collected.</p> <p>Conclusion</p> <p>Examining IC forms from WGS studies elucidates how investigators are handling ELS challenges posed by this research. This information is important for ensuring that while the public benefits of research are maximized, the rights of participants are also being appropriately respected.</p

Comparative mapping of expressed sequence tags containing microsatellites in rainbow trout (Oncorhynchus mykiss)

BACKGROUND: Comparative genomics, through the integration of genetic maps from species of interest with whole genome sequences of other species, will facilitate the identification of genes affecting phenotypes of interest. The development of microsatellite markers from expressed sequence tags will serve to increase marker densities on current salmonid genetic maps and initiate in silico comparative maps with species whose genomes have been fully sequenced. RESULTS: Eighty-nine polymorphic microsatellite markers were generated for rainbow trout of which at least 74 amplify in other salmonids. Fifty-five have been associated with functional annotation and 30 were mapped on existing genetic maps. Homologous sequences were identified for 20 of the EST containing microsatellites to identify comparative assignments within the tetraodon, mouse, and/or human genomes. CONCLUSION: The addition of microsatellite markers constructed from expressed sequence tag data will facilitate the development of high-density genetic maps for rainbow trout and comparative maps with other salmonids and better studied species

Health-Related Quality of Life in Long-Term Survivors of Relapsed Childhood Acute Lymphoblastic Leukemia

BACKGROUND: Relapses occur in about 20% of children with acute lymphoblastic leukemia (ALL). Approximately one-third of these children can be cured. Their risk for late effects is high because of intensified treatment, but their health-related quality of life (HRQOL) was largely unmeasured. Our aim was to compare HRQOL of ALL survivors with the general population, and of relapsed with non-relapsed ALL survivors. METHODOLOGY/PRINCIPAL FINDINGS: As part of the Swiss Childhood Cancer Survivor Study (SCCSS) we sent a questionnaire to all ALL survivors in Switzerland who had been diagnosed between 1976-2003 at age <16 years, survived ≥5 years, and were currently aged ≥16 years. HRQOL was assessed with the Short Form-36 (SF-36), which measures four aspects of physical health and four aspects of mental health. A score of 50 corresponded to the mean of a healthy reference population. We analyzed data from 457 ALL survivors (response: 79%). Sixty-one survivors had suffered a relapse. Compared to the general population, ALL survivors reported similar or higher HRQOL scores on all scales. Survivors with a relapse scored lower in general health perceptions (51.6) compared to those without (55.8;p=0.005), but after adjusting for self-reported late effects, this difference disappeared. CONCLUSION/SIGNIFICANCE: Compared to population norms, ALL survivors reported good HRQOL, even after a relapse. However, relapsed ALL survivors reported poorer general health than non-relapsed. Therefore, we encourage specialists to screen for poor general health in survivors after a relapse and, when appropriate, specifically seek and treat underlying late effects. This will help to improve patients' HRQOL

Choline transporter gene variation is associated with attention-deficit hyperactivity disorder

The neurotransmitter acetylcholine (ACh) plays a critical role in brain circuits mediating motor control, attention, learning and memory. Cholinergic dysfunction is associated with multiple brain disorders including Alzheimer’s Disease, addiction, schizophrenia and Attention-Deficit Hyperactivity Disorder (ADHD). The presynaptic choline transporter (CHT, SLC5A7) is the major, rate-limiting determinant of ACh production in the brain and periphery and is consequently upregulated during tasks that require sustained attention. Given the contribution of central cholinergic circuits to the control of movement and attention, we hypothesized that functional CHT gene variants might impact risk for ADHD. We performed a case-control study, followed by family-based association tests on a separate cohort, of two purportedly functional CHT polymorphisms (coding variant Ile89Val (rs1013940) and a genomic SNP 3’ of the CHT gene (rs333229), affording both a replication sample and opportunities to reduce potential population stratification biases. Initial genotyping of pediatric ADHD subjects for two purportedly functional CHT alleles revealed a 2–3 fold elevation of the Val89 allele (n = 100; P = 0.02) relative to healthy controls, as well as a significant decrease of the 3’SNP minor allele in Caucasian male subjects (n = 60; P = 0.004). In family based association tests, we found significant overtransmission of the Val89 variant to children with a Combined subtype diagnosis (OR = 3.16; P = 0.01), with an increased Odds Ratio for a haplotype comprising both minor alleles. These studies show evidence of cholinergic deficits in ADHD, particularly for subjects with the Combined subtype, and, if replicated, may encourage further consideration of cholinergic agonist therapy in the disorder

Age-Dependent Targeting of Protein Phosphatase 1 to Ca2+/Calmodulin-Dependent Protein Kinase II by Spinophilin in Mouse Striatum

Mechanisms underlying age-dependent changes of dendritic spines on striatal medium spiny neurons are poorly understood. Spinophilin is an F-actin- and protein phosphatase 1 (PP1)-binding protein that targets PP1 to multiple downstream effectors to modulate dendritic spine morphology and function. We found that calcium/calmodulin-dependent protein kinase II (CaMKII) directly and indirectly associates with N- and C-terminal domains of spinophilin, but F-actin can displace CaMKII from the N-terminal domain. Spinophilin co-localizes PP1 with CaMKII on the F-actin cytoskeleton in heterologous cells, and spinophilin co-localizes with synaptic CaMKII in neuronal cultures. Thr286 autophosphorylation enhances the binding of CaMKII to spinophilin in vitro and in vivo. Although there is no change in total levels of Thr286 autophosphorylation, maturation from postnatal day 21 into adulthood robustly enhances the levels of CaMKII that co-immunoprecipitate with spinophilin from mouse striatal extracts. Moreover, N- and C-terminal domain fragments of spinophilin bind more CaMKII from adult vs. postnatal day 21 striatal lysates. Total levels of other proteins that interact with C-terminal domains of spinophilin decrease during maturation, perhaps reducing competition for CaMKII binding to the C-terminal domain. In contrast, total levels of α-internexin and binding of α-internexin to the spinophilin N-terminal domain increases with maturation, perhaps bridging an indirect interaction with CaMKII. Moreover, there is an increase in the levels of myosin Va, α-internexin, spinophilin, and PP1 in striatal CaMKII immune complexes isolated from adult and aged mice compared to those from postnatal day 21. These changes in spinophilin/CaMKII interactomes may contribute to changes in striatal dendritic spine density, morphology, and function during normal postnatal maturation and aging