Velocity and processivity of helicase unwinding of double-stranded nucleic acids

Helicases are molecular motors which unwind double-stranded nucleic acids (dsNA) in cells. Many helicases move with directional bias on single-stranded (ss) nucleic acids, and couple their directional translocation to strand separation. A model of the coupling between translocation and unwinding uses an interaction potential to represent passive and active helicase mechanisms. A passive helicase must wait for thermal fluctuations to open dsNA base pairs before it can advance and inhibit NA closing. An active helicase directly destabilizes dsNA base pairs, accelerating the opening rate. Here we extend this model to include helicase unbinding from the nucleic-acid strand. The helicase processivity depends on the form of the interaction potential. A passive helicase has a mean attachment time which does not change between ss translocation and ds unwinding, while an active helicase in general shows a decrease in attachment time during unwinding relative to ss translocation. In addition, we describe how helicase unwinding velocity and processivity vary if the base-pair binding free energy is changed.Comment: To appear in special issue on molecular motors, Journal of Physics - Condensed Matte

Proposal for a Performance Dashboard for the Monitoringof Water and Sewage Service Companies (WaSCs)

The water and sewage industry provides an essential service to the community, but it is characterized by natural monopoly tendencies of service suppliers. In this framework, it is very important to assist regulators with a small set of critical indicators (performance dashboard) for the evaluation and monitoring of the service provided by Water and Sewage Companies (WaSCs). The paper originates from the analysis of situation of Piemonte (Italy), where each regional and local body adopts a proprietary Performance Measurement System (PMS). In order to improve the coordination of information flow and to support the definition of common service standards, a methodology to merge existing PMSs and define a unique shared reference system is proposed. The Kaplan and Norton's Balanced Scorecard (BSC) is adopted as the reference model of this approach. BSC is widely recognized to be an exhaustive and balanced framework in describing the performances of an organization and ensures that all the operational aspects of WaSCs are adequately monitored. The output of the proposed procedure is a general performance dashboard for the monitoring of WaSCs. The dashboard is shown and some remarks about indicators properties are developed. In particular, this analysis highlights some common pitfalls originated by a ‘rushed' aggregation of several performance indicators. Description is supported by several example

Diurnal cortisol and obesity in adolescents with and without Down syndrome

BackgroundThe prevalence of obesity in adolescents with Down syndrome (DS) far exceeds that in the general population. Cortisol, an adrenal hormone, can be obesogenic when dysregulated. However, the diurnal patterns of this hormone have not been examined among individuals with DS. Variations in adiposity may also mediate cortisol regulation. This study sought to examine diurnal cortisol patterns in adolescents with DS as well as associations between cortisol function and obesity.MethodA total of 32 adolescents, including 16 with DS and 16 controls with typical development (TD) of similar sex, age and Tanner pubertal stage (P > 0.05), participated in this preliminary study. Participants completed a dual‐energy X‐ray absorptiometry scan to measure body composition and collected saliva samples for cortisol measurements in the morning, afternoon and night. Linear mixed models with random intercepts and repeated measures were used to examine the daily trajectory of log‐transformed cortisol concentrations between adolescents with and without DS. A second model examined the interaction between DS and presence of elevated body fatness.ResultsAdolescents with DS had higher morning cortisol concentrations (intercept = 0.37 μg/dL), but this was not significantly different than in TD (0.35 μg/dL, P = 0.16). Cortisol significantly declined across hours (b = −0.026 μg/dL/h, P  0.05; d = 0.30).ConclusionsThis study is the first to examine diurnal cortisol in DS but is limited in sample size. These preliminary findings suggest that diurnal cortisol patterns are not significantly different between adolescents with DS and TD and that cortisol levels are not associated with adiposity in this population. Despite these non‐significant differences, youth with DS continue to be an ‘at‐risk’ population for paediatric obesity in need of clinical intervention.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151976/1/jir12682_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151976/2/jir12682.pd

Genetic and Antigenic Analysis of the First A/New Caledonia/20/99-like H1N1 Influenza Isolates Reported in the Americas

From February through May of 1999, 13 cases of Influenza A virus (FLUAV), type H1N1 were reported at a Department of Defense influenza surveillance sentinel site in Lima, Peru. Genetic and antigenic analysis by hemagglutination inhibition and direct nucleotide sequencing of the HA1 region of the hemagglutinin gene were performed on two isolates, A/Peru/1641/99 and A/Peru/1798/99. Both isolates were distinct from the Bayern/7/95-like viruses circulating in the Americas and closely related to a Beijing/262/95-like variant, A/New Caledonia/20/99. With the exception of travel-related cases, the detection of these isolates represents the first appearance of New Caledonia/20/99-like viruses in the Americas. Since the characterization of these Peru isolates, a number of New Caledonia/20/99-like viruses have been reported worldwide. For the 2000/01 and 2001/02 influenza seasons, the World Health Organization (WHO) has recommended the inclusion of A/New Caledonia/20/99 as the H1N1 vaccine component for both the southern and northern hemispheres

Hydrolysis of N -Alkyl Sulfamates and the Catalytic Efficiency of an S–N Cleaving Sulfamidase

The final step in the degradation of heparin sulfate involves the enzymatic hydrolysis of its 2-sulfamido groups. To evaluate the power of the corresponding sulfamidases as catalysts, we examined the reaction of N-neopentyl sulfamate at elevated temperatures and found it to undergo specific acid catalyzed hydrolysis even at alkaline pH. A rate constant of 10−16 s−1 was calculated using the Eyring equation for water attack on the N-protonated species at pH 7, 25 °C. As a model for the pH neutral reaction, a rate constant for hydroxide attack on (CH3)3CCH2N+H2SO3− at pH 7, 25 °C was calculated to be 10−19 s−1. The corresponding rate enhancement (kcat/knon) produced by the N-sulfamidase of F. heparinum is approximately 1016-fold, which is somewhat larger than those generated by most hydrolytic enzymes but considerably smaller than those generated by S-O cleaving sulfatases

Consistency of Mycobacterium tuberculosis-Specific Interferon-Gamma Responses in HIV-1-Infected Women during Pregnancy and Postpartum

Background. We determined the consistency of positive interferon-gamma (IFN-γ) release assays (IGRAs) to detect latent TB infection (LTBI) over one-year postpartum in HIV-1-infected women. Methods. Women with positive IGRAs during pregnancy had four 3-monthly postpartum IGRAs. Postpartum change in magnitude of IFN-γ response was determined using linear mixed models. Results. Among 18 women with positive pregnancy IGRA, 15 (83%) had a subsequent positive IGRA; 9 (50%) were always positive, 3 (17%) were always negative, and 6 (33%) fluctuated between positive and negative IGRAs. Women with pregnancy IGRA IFN-γ>8 spot forming cells (SFCs)/well were more likely to have consistent postpartum IGRA response (odds ratio: 10.0; 95% confidence interval (CI): 0.9–117.0). Change in IFN-γ response over postpartum was 10.2 SFCs/well (95% CI: −1.5–21.8 SFCs/well). Conclusion. Pregnancy positive IGRAs were often maintained postpartum with increased consistency in women with higher baseline responses. There were modest increases in magnitude of IGRA responses postpartum

A five year longitudinal study investigating the prevalence of childhood obesity: comparison of BMI and waist circumference.

Objective: The purpose of this study was to examine the prevalence of obesity over time in the same individuals comparing body mass index (BMI), waist circumference (WC) and waist to height ratio (WHtR). Study design: Five year longitudinal repeated measures study (2005–2010). Children were aged 11–12 (Y7) years at baseline and measurements were repeated at age 13–14 (Y9) years and 15–16 (Y11) years. Methods: WC and BMI measurements were carried out by the same person over the five years and raw values were expressed as standard deviation scores (sBMI and sWC) against the growth reference used for British children. Results: Mean sWC measurements were higher than mean sBMI measurements for both sexes and at all assessment occasions and sWC measurements were consistently high in girls compared to boys. Y7 sWC = 0.792 [95% confidence interval (CI) 0.675–0.908], Y9 sWC = 0.818 (95%CI 0.709–0.928), Y11 sWC = 0.943 (95%CI 0.827–1.06) for boys; Y7 sWC = 0.843 (0.697–0.989), Y9 sWC = 1.52 (95%CI 1.38–0.67), Y11 sWC = 1.89 (95%CI 1.79–2.04) for girls. Y7 sBMI = 0.445 (95%CI 0.315–0.575), Y9 sBMI = 0.314 (95%CI 0.189–0.438), Y11 sBMI = 0.196 (95%CI 0.054–0.337) for boys; Y7 sBMI = 0.353 (0.227–0.479), Y9 sBMI = 0.343 (95%CI 0.208–0.478), Y11 sBMI = 0.256 (95%CI 0.102–0.409) for girls. The estimated prevalence of obesity defined by BMI decreased in boys (18%, 12% and 10% in Y 7, 9 and 11 respectively) and girls (14%, 15% and 11% in Y 7, 9 and 11). In contrast, the prevalence estimated by WC increased sharply (boys; 13%, 19% and 23%; girls, 20%, 46% and 60%). Conclusion: Central adiposity, measured by WC is increasing alongside a stabilization in BMI. Children appear to be getting fatter and the additional adiposity is being stored centrally which is not detected by BMI. These substantial increases in WC are a serious concern, especially in girls

Neighborhood Environment and Falls Among Community-Dwelling Older Adults

Background: Falls present a major challenge to active aging, but the relationship between neighborhood factors and falls is poorly understood. This study examined the relationship between fall events and neighborhood factors, including neighborhood social cohesion (sense of belonging, trust, friendliness, and helpfulness) and physical environment (vandalism/graffiti, rubbish, vacant/deserted houses, and perceived safety walking home at night). Methods: Data were analyzed from 9259 participants over four biennial waves (2006–2012) of the Health and Retirement Study (HRS), a nationally representative sample of adults aged 65 and older in the United States. Results: In models adjusting for demographic and health-related covariates, a one-unit increase in neighborhood social cohesion was associated with 4% lower odds of experiencing a single fall (odds ratio (OR): 0.96, 95% confidence interval (CI): 0.93–0.99) and 6% lower odds of experiencing multiple falls (OR: 0.94, 95% CI: 0.90–0.98). A one-unit increase in the physical environment scale was associated with 4% lower odds of experiencing a single fall (OR: 0.96, 95% CI: 0.93–0.99) and with 5% lower odds of experiencing multiple falls (OR: 0.95, 95% CI: 0.91–1.00) in adjusted models. Conclusions: The physical and social neighborhood environment may affect fall risk among community-dwelling older adults. Findings support the ongoing need for evidence-based fall prevention programming in community and clinical settings

Superficial simplicity of the 2010 El Mayor–Cucapah earthquake of Baja California in Mexico

The geometry of faults is usually thought to be more complicated at the surface than at depth and to control the initiation, propagation and arrest of seismic ruptures. The fault system that runs from southern California into Mexico is a simple strike-slip boundary: the west side of California and Mexico moves northwards with respect to the east. However, the M_w 7.2 2010 El Mayor–Cucapah earthquake on this fault system produced a pattern of seismic waves that indicates a far more complex source than slip on a planar strike-slip fault. Here we use geodetic, remote-sensing and seismological data to reconstruct the fault geometry and history of slip during this earthquake. We find that the earthquake produced a straight 120-km-long fault trace that cut through the Cucapah mountain range and across the Colorado River delta. However, at depth, the fault is made up of two different segments connected by a small extensional fault. Both segments strike N130° E, but dip in opposite directions. The earthquake was initiated on the connecting extensional fault and 15 s later ruptured the two main segments with dominantly strike-slip motion. We show that complexities in the fault geometry at depth explain well the complex pattern of radiated seismic waves. We conclude that the location and detailed characteristics of the earthquake could not have been anticipated on the basis of observations of surface geology alone

Relationship between psychological and biological factors and physical activity and exercise behaviour in Filipino students

The aim of the present study was threefold. Firstly, it investigated whether a general measure or specific measure of motivational orientation was better in describing the relationship between motivation and exercise behaviour. Secondly, it examined the relationship between the four most popular indirect methods of body composition assessment and physical activity and exercise patterns. Thirdly, the interaction between motivation and body composition on physical activity and exercise behaviour was explored in a sample of 275 Filipino male and female students. Males were found to have higher levels of exercise whereas females had higher levels of physical activity. Furthermore, general self-motivation together with body weight and percentage body fat were found to be the best predictor of exercise behaviour whereas the tension/pressure subscale of the ‘Intrinsic Motivation Inventory’ (IMI) was the best predictor of levels of physical activity. However, significant gender differences were observed. That is, for the males only self-motivation and for the females only body weight and BMI predicted exercise behaviour. Also, tension/pressure predicted physical activity levels for the females but not the males. No inverse relationship was found between the four body composition measures and exercise and physical activity behaviour. The results support the notion that the psychobiological approach might be particularly relevant for high intensity exercise situations but also highlights some important gender differences. Finally, the results of this study emphasise the need for more cross-cultural research