Binary and Millisecond Pulsars at the New Millennium

We review the properties and applications of binary and millisecond pulsars. Our knowledge of these exciting objects has greatly increased in recent years, mainly due to successful surveys which have brought the known pulsar population to over 1300. There are now 56 binary and millisecond pulsars in the Galactic disk and a further 47 in globular clusters. This review is concerned primarily with the results and spin-offs from these surveys which are of particular interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org

The "Persuadable Middle" on Same-Sex Marriage: Formative Research to Build Support among Heterosexual College Students

Same-sex marriage is a controversial policy issue that affects the welfare of gay and lesbian couples throughout the USA. Considerable research examines opinions about same-sex marriage; however, studies have not investigated the covariates of the “persuadable middle”— those individuals who are neutral or unsure about their views. This group of people is often the target of same-sex marriage campaigns, yet they have received no empirical attention.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/89607/1/Woodford et al 2011 Persuadable Middle.pd

Ethical and legal implications of whole genome and whole exome sequencing in African populations

BACKGROUND: Rapid advances in high throughput genomic technologies and next generation sequencing are making medical genomic research more readily accessible and affordable, including the sequencing of patient and control whole genomes and exomes in order to elucidate genetic factors underlying disease. Over the next five years, the Human Heredity and Health in Africa (H3Africa) Initiative, funded by the Wellcome Trust (United Kingdom) and the National Institutes of Health (United States of America), will contribute greatly towards sequencing of numerous African samples for biomedical research. DISCUSSION: Funding agencies and journals often require submission of genomic data from research participants to databases that allow open or controlled data access for all investigators. Access to such genotype-phenotype and pedigree data, however, needs careful control in order to prevent identification of individuals or families. This is particularly the case in Africa, where many researchers and their patients are inexperienced in the ethical issues accompanying whole genome and exome research; and where an historical unidirectional flow of samples and data out of Africa has created a sense of exploitation and distrust. In the current study, we analysed the implications of the anticipated surge of next generation sequencing data in Africa and the subsequent data sharing concepts on the protection of privacy of research subjects. We performed a retrospective analysis of the informed consent process for the continent and the rest-of-the-world and examined relevant legislation, both current and proposed. We investigated the following issues: (i) informed consent, including guidelines for performing culturally-sensitive next generation sequencing research in Africa and availability of suitable informed consent documents; (ii) data security and subject privacy whilst practicing data sharing; (iii) conveying the implications of such concepts to research participants in resource limited settings. SUMMARY: We conclude that, in order to meet the unique requirements of performing next generation sequencing-related research in African populations, novel approaches to the informed consent process are required. This will help to avoid infringement of privacy of individual subjects as well as to ensure that informed consent adheres to acceptable data protection levels with regard to use and transfer of such information

Study protocol: a mixed methods feasibility study for a loaded self-managed exercise programme for patellofemoral pain

Background: Patellofemoral pain (PFP) is one of the most common forms of knee pain in adults under the age of 40, with a prevalence of 23% in the general population. The long-term prognosis is poor, with only one third of people pain-free 1 year after diagnosis. The biomedical model of pain in relation to persistent PFP has recently been called into question. It has been suggested that interventions for chronic musculoskeletal conditions should consider alternative mechanisms of action, beyond muscles and joints. Modern treatment therapies should consider desensitising strategies, with exercises that target movements and activities patients find fearful and painful. High-quality research on exercise prescription in relation to pain mechanisms, not directed at specific tissue pathology, and dose response clearly warrants further investigation. Our primary aim is to establish the feasibility and acceptability of conducting a definitive RCT which will evaluate the clinical and cost-effectiveness of a loaded self-managed exercise programme for people with patellofemoral pain. Method: This is a single-centred, multiphase, sequential, mixed-methods trial that will evaluate the feasibility of running a definitive large-scale randomised controlled trial of a loaded self-managed exercise programme versus usual physiotherapy. Initially, 8–10 participants with a minimum 3-month history of PFP will be recruited from an NHS physiotherapy waiting list and interviewed. Participants will be invited to discuss perceived barriers and facilitators to exercise engagement, and the meaning and impact of PFP. Then, 60 participants will be recruited in the same manner for the main phase of the feasibility trial. A web-based service will randomise patients to a loaded self-managed exercise programme or usual physiotherapy. The loaded self-managed exercise programme is aimed at addressing lower limb knee and hip weakness and is positioned within a framework of reducing fear/avoidance with an emphasis on self-management. Baseline assessment will include demographic data, average pain within the last week (VAS), fear avoidance behaviours, catastrophising, self-efficacy, sport and leisure activity participation, and general quality of life. Follow-up will be 3 and 6 months. The analysis will focus on descriptive statistics and confidence intervals. The qualitative components will follow a thematic analysis approach. Discussion: This study will evaluate the feasibility of running a definitive large-scale trial on patients with patellofemoral pain, within the NHS in the UK. We will identify strengths and weaknesses of the proposed protocol and the utility and characteristics of the outcome measures. The results from this study will inform the design of a multicentre trial

A Conserved Function of C. elegans CASY-1 Calsyntenin in Associative Learning

BACKGROUND: Whole-genome association studies in humans have enabled the unbiased discovery of new genes associated with human memory performance. However, such studies do not allow for a functional or causal testing of newly identified candidate genes. Since polymorphisms in Calsyntenin 2 (CLSTN2) showed a significant association with episodic memory performance in humans, we tested the C. elegans CLSTN2 ortholog CASY-1 for possible functions in the associative behavior of C. elegans. METHODOLOGY/PRINCIPAL FINDINGS: Using three different associative learning paradigms and functional rescue experiments, we show that CASY-1 plays an important role during associative learning in C. elegans. Furthermore, neuronal expression of human CLSTN2 in C. elegans rescues the learning defects of casy-1 mutants. Finally, genetic interaction studies and neuron-specific expression experiments suggest that CASY-1 may regulate AMPA-like GLR-1 glutamate receptor signaling. CONCLUSION/SIGNIFICANCE: Our experiments demonstrate a remarkable conservation of the molecular function of Calsyntenins between nematodes and humans and point at a role of C. elegans casy-1 in regulating a glutamate receptor signaling pathway

Predation and infanticide influence ideal free choice by a parrot occupying heterogeneous tropical habitats

The ideal free distribution (IFD) predicts that organisms will disperse to sites that maximize their fitness based on availability of resources. Habitat heterogeneity underlies resource variation and influences spatial variation in demography and the distribution of populations. We relate nest site productivity at multiple scales measured over a decade to habitat quality in a box-nesting population of Forpus passerinus (green-rumped parrotlets) in Venezuela to examine critical IFD assumptions. Variation in reproductive success at the local population and neighborhood scales had a much larger influence on productivity (fledglings per nest box per year) than nest site or female identity. Habitat features were reliable cues of nest site quality. Nest sites with less vegetative cover produced greater numbers of fledglings than sites with more cover. However, there was also a competitive cost to nesting in high-quality, low-vegetative cover nest boxes, as these sites experienced the most infanticide events. In the lowland local population, water depth and cover surrounding nest sites were related with F. passerinus productivity. Low vegetative cover and deeper water were associated with lower predation rates, suggesting that predation could be a primary factor driving habitat selection patterns. Parrotlets also demonstrated directional dispersal. Pairs that changed nest sites were more likely to disperse from poor-quality nest sites to high-quality nest sites rather than vice versa, and juveniles were more likely to disperse to, or remain in, the more productive of the two local populations. Parrotlets exhibited three characteristics fundamental to the IFD: habitat heterogeneity within and between local populations, reliable habitat cues to productivity, and active dispersal to sites of higher fitness

Replication Factor C Complexes Play Unique Pro- and Anti-Establishment Roles in Sister Chromatid Cohesion

Recent studies have lead to a rapid expansion of sister chromatid cohesion pathways. Of particular interest is the growth in classifications of anti-establishment factors—now including those that are cohesin-associated (Rad61/WAPL and Pds5) or DNA replication fork-associated (Elg1-RFC). In this study, we show that the two classes of anti-establishment complexes are indistinguishable when challenged both genetically and functionally. These findings suggest that both classes function in a singular pathway that is centered on Ctf7/Eco1 (herein termed Ctf7) regulation. The anti-establishment activity of Elg1-RFC complex is particular intriguing given that an alternate Ctf18-RFC complex exhibits robust pro-establishment activity. Here, we provide several lines of evidence, including the use of Ctf7 bypass suppressors, indicating that these activities are not simply antagonistic. Moreover, the results suggest that Ctf18-RFC is capable of promoting sister chromatid pairing reactions independent of Ctf7. The combination of these studies suggest a new model of sister chromatid pairing regulation

Antibodies against CD20 or B-Cell Receptor Induce Similar Transcription Patterns in Human Lymphoma Cell Lines

BACKGROUND: CD20 is a cell surface protein exclusively expressed on B cells. It is a clinically validated target for Non-Hodgkin's lymphomas (NHL) and autoimmune diseases. The B cell receptor (BCR) plays an important role for development and proliferation of pre-B and B cells. Physical interaction of CD20 with BCR and components of the BCR signaling cascade has been reported but the consequences are not fully understood. METHODOLOGY: In this study we employed antibodies against CD20 and against the BCR to trigger the respective signaling. These antibodies induced very similar expression patterns of up- and down-regulated genes in NHL cell lines indicating that CD20 may play a role in BCR signaling and vice versa. Two of the genes that were rapidly and transiently induced by both stimuli are CCL3 and CCL4. 4 hours after stimulation the concentration of these chemokines in culture medium reaches a maximum. Spleen tyrosine kinase Syk is a cytoplasmic tyrosine kinase and a key component of BCR signaling. Both siRNA mediated silencing of Syk and inhibition by selective small molecule inhibitors impaired CCL3/CCL4 protein induction after treatment with either anti-CD20 or anti-BCR antibodies. CONCLUSION: Our results suggest that treatment with anti-CD20 antibodies triggers at least partially a BCR activation-like response in NHL cell lines

Phenology of Scramble Polygyny in a Wild Population of Chrysolemid Beetles: The Opportunity for and the Strength of Sexual Selection

Recent debate has highlighted the importance of estimating both the strength of sexual selection on phenotypic traits, and the opportunity for sexual selection. We describe seasonal fluctuations in mating dynamics of Leptinotarsa undecimlineata (Coleoptera: Chrysomelidae). We compared several estimates of the opportunity for, and the strength of, sexual selection and male precopulatory competition over the reproductive season. First, using a null model, we suggest that the ratio between observed values of the opportunity for sexual selections and their expected value under random mating results in unbiased estimates of the actual nonrandom mating behavior of the population. Second, we found that estimates for the whole reproductive season often misrepresent the actual value at any given time period. Third, mating differentials on male size and mobility, frequency of male fighting and three estimates of the opportunity for sexual selection provide contrasting but complementary information. More intense sexual selection associated to male mobility, but not to male size, was observed in periods with high opportunity for sexual selection and high frequency of male fights. Fourth, based on parameters of spatial and temporal aggregation of female receptivity, we describe the mating system of L. undecimlineata as a scramble mating polygyny in which the opportunity for sexual selection varies widely throughout the season, but the strength of sexual selection on male size remains fairly weak, while male mobility inversely covaries with mating success. We suggest that different estimates for the opportunity for, and intensity of, sexual selection should be applied in order to discriminate how different behavioral and demographic factors shape the reproductive dynamic of populations