Magnetic resonance imaging correlates of neuro-axonal pathology in the MS spinal cord.

In people with multiple sclerosis (MS), the spinal cord is the structure most commonly affected by clinically detectable pathology at presentation, and a key part of the central nervous system involved in chronic disease deterioration. Indices, such as the spinal cord cross-sectional area at the level C2 have been developed as tools to predict future disability, and-by inference-axonal loss. However, this and other histo-pathological correlates of spinal cord magnetic resonance imaging (MRI) changes in MS remain incompletely understood. In recent years, there has been a surge of interest in developing quantitative MRI tools to measure specific tissue features, including axonal density, myelin content, neurite density, and orientation, among others, with an emphasis on the spinal cord. Quantitative MRI techniques including T1 and T2 , magnetization transfer and a number of diffusion-derived indices have all been applied to MS spinal cord. Particularly diffusion-based MRI techniques combined with microscopic resolution achievable using high magnetic field scanners enable a new level of anatomical detail and quantification of indices that are clinically meaningful.Barts Charity (grants # 468/1506 & G‐001109

Hierarchically coupled ultradian oscillators generating robust circadian rhythms

Ensembles of mutually coupled ultradian cellular oscillators have been proposed by a number of authors to explain the generation of circadian rhythms in mammals. Most mathematical models using many coupled oscillators predict that the output period should vary as the square root of the number of participating units, thus being inconsistent with the well-established experimental result that ablation of substantial parts of the suprachiasmatic nuclei (SCN), the main circadian pacemaker in mammals, does not eliminate the overt circadian functions, which show no changes in the phases or periods of the rhythms. From these observations, we have developed a theoretical model that exhibits the robustness of the circadian clock to changes in the number of cells in the SCN, and that is readily adaptable to include the successful features of other known models of circadian regulation, such as the phase response curves and light resetting of the phase

Effect of plyometric training on handspring vault performance and functional power in youth female gymnasts

This study aimed to determine the effect of plyometric training (PT) when added to habitual gymnastic training (HT) on handspring vault (HV) performance variables. Twenty youth female competitive gymnasts (Age: 12.5 ± 1.67 y) volunteered to participate and were randomly assigned to two independent groups. The experimental plyometric training group (PTG) undertook a six-week plyometric program, involving two additional 45 min PT sessions a week, alongside their HT, while the control group (CG) performed regular HT only. Videography was used (120 Hz) in the sagittal plane to record both groups performing three HVs for both the baseline and post-intervention trials. Furthermore, participants completed a countermovement jump test (CMJ) to assess the effect of PT on functional power. Through the use of Quintic biomechanics software, significant improvements (P < 0.05) were found for the PTG for run-up velocity, take-off velocity, hurdle to board distance, board contact time, table contact time and post-flight time and CMJ height. However, there were no significant improvements on pre-flight time, shoulder angle or hip angle on the vault for the PTG. The CG demonstrated no improvement for all HV measures. A sport-specific PT intervention improved handspring vault performance measures and functional power when added to the habitual training of youth female gymnasts. The additional two hours plyometric training seemingly improved the power generating capacity of movement-specific musculature, which consequently improved aspects of vaulting performance. Future research is required to examine the whether the improvements are as a consequence of the additional volume of sprinting and jumping activities, as a result of the specific PT method or a combination of these factors

A Direct Measurement of Hard Two-Photon Exchange with Electrons and Positrons at CLAS12

One of the most surprising discoveries made at Jefferson Lab has been the discrepancy in the determinations of the proton's form factor ratio $\mu_p G_E^p/G_M^p$ between unpolarized cross section measurements and the polarization transfer technique. Over two decades later, the discrepancy not only persists but has been confirmed at higher momentum transfers now accessible in the 12-GeV era. The leading hypothesis for the cause of this discrepancy, a non-negligible contribution from hard two-photon exchange, has neither been conclusively proven or disproven. This state of uncertainty not only clouds our knowledge of one-dimensional nucleon structure but also poses a major concern for our field's efforts to map out the three-dimensional nuclear structure. A better understanding of multi-photon exchange over a wide phase space is needed. We propose making comprehensive measurements of two-photon exchange over a wide range in momentum transfer and scattering angle using the CLAS12 detector. Specifically, we will measure the ratio of positron-proton to electron-proton elastic scattering cross sections, using the proposed positron beam upgrade for CEBAF. The experiment will use 2.2, 4.4, and 6.6 GeV lepton beams incident on the standard CLAS12 unpolarized hydrogen target. Data will be collected by the CLAS12 detector in its standard configuration, except for a modified trigger to allow the recording of events with beam leptons scattered into the CLAS12 central detector. The sign of the beam charge, as well as the polarity of the CLAS12 solenoid and toroid, will be reversed several times in order to suppress systematics associated with local detector efficiency and time-dependent detector performance. The proposed high-precision determination of two-photon effects will be...Comment: Experimental Proposal E12+23-008 submitted to Jefferson Lab PAC 51, 34 pages, 18 figure

Trends over 5 Decades in U.S. Occupation-Related Physical Activity and Their Associations with Obesity

BACKGROUND: The true causes of the obesity epidemic are not well understood and there are few longitudinal population-based data published examining this issue. The objective of this analysis was to examine trends in occupational physical activity during the past 5 decades and explore how these trends relate to concurrent changes in body weight in the U.S. METHODOLOGY/PRINCIPAL FINDINGS: Analysis of energy expenditure for occupations in U.S. private industry since 1960 using data from the U.S. Bureau of Labor Statistics. Mean body weight was derived from the U.S. National Health and Nutrition Examination Surveys (NHANES). In the early 1960's almost half the jobs in private industry in the U.S. required at least moderate intensity physical activity whereas now less than 20% demand this level of energy expenditure. Since 1960 the estimated mean daily energy expenditure due to work related physical activity has dropped by more than 100 calories in both women and men. Energy balance model predicted weights based on change in occupation-related daily energy expenditure since 1960 for each NHANES examination period closely matched the actual change in weight for 40-50 year old men and women. For example from 1960-62 to 2003-06 we estimated that the occupation-related daily energy expenditure decreased by 142 calories in men. Given a baseline weight of 76.9 kg in 1960-02, we estimated that a 142 calories reduction would result in an increase in mean weight to 89.7 kg, which closely matched the mean NHANES weight of 91.8 kg in 2003-06. The results were similar for women. CONCLUSION: Over the last 50 years in the U.S. we estimate that daily occupation-related energy expenditure has decreased by more than 100 calories, and this reduction in energy expenditure accounts for a significant portion of the increase in mean U.S. body weights for women and men

Resistance to ursodeoxycholic acid-induced growth arrest can also result in resistance to deoxycholic acid-induced apoptosis and increased tumorgenicity

BACKGROUND: There is a large body of evidence which suggests that bile acids increase the risk of colon cancer and act as tumor promoters, however, the mechanism(s) of bile acids mediated tumorigenesis is not clear. Previously we showed that deoxycholic acid (DCA), a tumorogenic bile acid, and ursodeoxycholic acid (UDCA), a putative chemopreventive agent, exhibited distinct biological effects, yet appeared to act on some of the same signaling molecules. The present study was carried out to determine whether there is overlap in signaling pathways activated by tumorogenic bile acid DCA and chemopreventive bile acid UDCA. METHODS: To determine whether there was an overlap in activation of signaling pathways by DCA and UDCA, we mutagenized HCT116 cells and then isolated cell lines resistant to UDCA induced growth arrest. These lines were then tested for their response to DCA induced apoptosis. RESULTS: We found that a majority of the cell lines resistant to UDCA-induced growth arrest were also resistant to DCA-induced apoptosis, implying an overlap in DCA and UDCA mediated signaling. Moreover, the cell lines which were the most resistant to DCA-induced apoptosis also exhibited a greater capacity for anchorage independent growth. CONCLUSION: We conclude that UDCA and DCA have overlapping signaling activities and that disregulation of these pathways can lead to a more advanced neoplastic phenotype

A Methodological Framework for the Reconstruction of Contiguous Regions of Ancestral Genomes and Its Application to Mammalian Genomes

The reconstruction of ancestral genome architectures and gene orders from homologies between extant species is a long-standing problem, considered by both cytogeneticists and bioinformaticians. A comparison of the two approaches was recently investigated and discussed in a series of papers, sometimes with diverging points of view regarding the performance of these two approaches. We describe a general methodological framework for reconstructing ancestral genome segments from conserved syntenies in extant genomes. We show that this problem, from a computational point of view, is naturally related to physical mapping of chromosomes and benefits from using combinatorial tools developed in this scope. We develop this framework into a new reconstruction method considering conserved gene clusters with similar gene content, mimicking principles used in most cytogenetic studies, although on a different kind of data. We implement and apply it to datasets of mammalian genomes. We perform intensive theoretical and experimental comparisons with other bioinformatics methods for ancestral genome segments reconstruction. We show that the method that we propose is stable and reliable: it gives convergent results using several kinds of data at different levels of resolution, and all predicted ancestral regions are well supported. The results come eventually very close to cytogenetics studies. It suggests that the comparison of methods for ancestral genome reconstruction should include the algorithmic aspects of the methods as well as the disciplinary differences in data aquisition

Family planning among people living with HIV in post-conflict Northern Uganda: A mixed methods study

<p>Abstract</p> <p>Background</p> <p>Northern Uganda experienced severe civil conflict for over 20 years and is also a region of high HIV prevalence. This study examined knowledge of, access to, and factors associated with use of family planning services among people living with HIV (PLHIV) in this region.</p> <p>Methods</p> <p>Between February and May 2009, a total of 476 HIV clinic attendees from three health facilities in Gulu, Northern Uganda, were interviewed using a structured questionnaire. Semi-structured interviews were conducted with another 26 participants. Factors associated with use of family planning methods were examined using logistic regression methods, while qualitative data was analyzed within a social-ecological framework using thematic analysis.</p> <p>Results</p> <p>There was a high level of knowledge about family planning methods among the PLHIV surveyed (96%). However, there were a significantly higher proportion of males (52%) than females (25%) who reported using contraception. Factors significantly associated with the use of contraception were having ever gone to school [adjusted odds ratio (AOR) = 4.32, 95% confidence interval (CI): 1.33-14.07; p = .015], discussion of family planning with a health worker (AOR = 2.08, 95% CI: 1.01-4.27; p = .046), or with one's spouse (AOR = 5.13, 95% CI: 2.35-11.16; p = .000), not attending the Catholic-run clinic (AOR = 3.67, 95% CI: 1.79-7.54; p = .000), and spouses' non-desire for children (AOR = 2.19, 95% CI: 1.10-4.36; p = .025). Qualitative data revealed six major factors influencing contraception use among PLHIV in Gulu including personal and structural barriers to contraceptive use, perceptions of family planning, decision making, covert use of family planning methods and targeting of women for family planning services.</p> <p>Conclusions</p> <p>Multilevel, context-specific health interventions including an integration of family planning services into HIV clinics could help overcome some of the individual and structural barriers to accessing family planning services among PLHIV in Gulu. The integration also has the potential to reduce HIV incidence in this post-conflict region.</p