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

Upgrade of the Glasgow photon tagging spectrometer for Mainz MAMI-C

The Glasgow photon tagging spectrometer at Mainz has been upgraded so that it can be used with the 1500 MeV electron beam now available from the Mainz microtron MAMI-C. The changes made and the resulting properties of the spectrometer are discussed.Comment: 20 pages, 12 figure

Out of the Orient: Post-Tethyan transoceanic and trans-Arabian routes fostered the spread of Baorini skippers in the Afrotropics

The origin of taxa presenting a disjunct distribution between Africa and Asia has puzzled biogeographers for more than a century. This biogeographic pattern has been hypothesized to be the result of transoceanic long-distance dispersal, Oligocene dispersal through forested corridors, Miocene dispersal through the Arabian Peninsula or passive dispersal on the rifting Indian plate. However, it has often been difficult to pinpoint the mechanisms at play. We investigate biotic exchange between the Afrotropics and the Oriental region during the Cenozoic, a period in which geological changes altered landmass connectivity. We use Baorini skippers (Lepidoptera, Hesperiidae) as a model, a widespread clade of butterflies in the Old World tropics with a disjunct distribution between the Afrotropics and the Oriental region. We use anchored phylogenomics to infer a robust evolutionary tree for Baorini skippers and estimate divergence times and ancestral ranges to test biogeographic hypotheses. Our phylogenomic tree recovers strongly supported relationships for Baorini skippers and clarifies the systematics of the tribe. Dating analyses suggest that these butterflies originated in the Oriental region, Greater Sunda Islands, and the Philippines in the early Miocene c. 23 Ma. Baorini skippers dispersed from the Oriental region towards Africa at least five times in the past 20 Ma. These butterflies colonized the Afrotropics primarily through trans-Arabian geodispersal after the closure of the Tethyan seaway in the mid-Miocene. Range expansion from the Oriental region towards the African continent probably occurred via the Gomphotherium land bridge through the Arabian Peninsula. Alternative scenarios invoking long-distance dispersal and vicariance are not supported. The Miocene climate change and biome shift from forested areas to grasslands possibly facilitated geodispersal in this clade of butterflies.Directorate for Biological Sciences. Grant Numbers: DEB‐1541500, DEB‐1541560.Peer reviewe

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

Geodetic model of the 2016 Central Italy earthquake sequence inferred from InSAR and GPS data

We investigate a large geodetic data set of interferometric synthetic aperture radar (InSAR)and GPS measurements to determine the source parameters for the three main shocks of the 2016Central Italy earthquake sequence on 24 August and 26 and 30 October (Mw6.1, 5.9, and 6.5,respectively). Our preferred model is consistent with the activation of four main coseismic asperitiesbelonging to the SW dipping normal fault system associated with the Mount Gorzano-Mount Vettore-Mount Bove alignment. Additional slip, equivalent to aMw~ 6.1–6.2 earthquake, on a secondary (1) NEdipping antithetic fault and/or (2) on a WNW dipping low-angle fault in the hanging wall of the mainsystem is required to better reproduce the complex deformation pattern associated with the greatestseismic event (theMw6.5 earthquake). The recognition of ancillary faults involved in the sequencesuggests a complex interaction in the activated crustal volume between the main normal faults and thesecondary structures and a partitioning of strain releas

Asperities and barriers on the seismogenic zone in North Chile: state-of-the-art after the 2007 Mw 7.7 Tocopilla earthquake inferred by GPS and InSAR data

The Mw 7.7 2007 November 14 earthquake had an epicentre located close to the city of Tocopilla, at the southern end of a known seismic gap in North Chile. Through modelling of Global Positioning System (GPS) and radar interferometry (InSAR) data, we show that this event ruptured the deeper part of the seismogenic interface (30–50 km) and did not reach the surface. The earthquake initiated at the hypocentre and was arrested ~150 km south, beneath the Mejillones Peninsula, an area already identified as an important structural barrier between two segments of the Peru–Chile subduction zone. Our preferred models for the Tocopilla main shock show slip concentrated in two main asperities, consistent with previous inversions of seismological data. Slip appears to have propagated towards relatively shallow depths at its southern extremity, under the Mejillones Peninsula. Our analysis of post-seismic deformation suggests that small but still significant post-seismic slip occurred within the first 10 d after the main shock, and that it was mostly concentrated at the southern end of the rupture. The post-seismic deformation occurring in this period represents ~12–19 per cent of the coseismic deformation, of which ~30–55 per cent has been released aseismically. Post-seismic slip appears to concentrate within regions that exhibit low coseismic slip, suggesting that the afterslip distribution during the first month of the post-seismic interval complements the coseismic slip. The 2007 Tocopilla earthquake released only ~2.5 per cent of the moment deficit accumulated on the interface during the past 130 yr and may be regarded as a possible precursor of a larger subduction earthquake rupturing partially or completely the 500-km-long North Chile seismic gap

'Motivate': the effect of a Football in the Community delivered weight loss programme on over 35-year old men and women's cardiovascular risk factors

The purpose of this study was to examine whether an innovative, inclusive and integrated 12-week exercise, behaviour change and nutrition advice-based weight management programme could significantly improve the cardiovascular risk factors of overweight and obese men and women over the age of 35. One hundred and ninety-four men and 98 women (mean age = 52.28 ± 9.74 and 51.19 ± 9.04) attending a community-based intervention delivered by Notts County Football in the Community over one year, took part in the study. Height (m), weight (kg), fitness (meters covered during a 6 min walk) and waist circumference (cm) were measured at weeks 1 and 12 as part of the intervention. Changes in body weight, waist circumference and fitness for men and women were measured by a 2-way repeated measures ANOVA, with significance set to p < 0.05.Weight, waist circumference and fitness significantly improved over time in both men (4.96 kg, 6.29 cm, 70.22 m; p < 0.05) and women (4.26 kg, 5.90 cm, 35.29 m; p < 0.05). The results demonstrated that the FITC lead weight loss intervention was successful in significantly improving cardiovascular risk factors in both men and women. In particular, the weight loss reductions achieved were comparable to those seen in similar, more costly men-only programmes. This is the first study to demonstrate the efficacy of such an intervention in an inclusive, mixed gender programme and more specifically, in women

Olfaction: anatomy, physiology and behavior

The anatomy, physiology and function of the olfactory system are reviewed, as are the normal effects of olfactory stimulation. It is speculated that olfaction may have important but unobtrusive effects on human behavior

Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility

We recently reported that a sequence variant in the cell-cycle-checkpoint kinase CHEK2 (CHEK2 1100delC) is a low-penetrance breast cancer-susceptibility allele in noncarriers of BRCA1 or BRCA2 mutations. To investigate whether other CHEK2 variants confer susceptibility to breast cancer, we screened the full CHEK2 coding sequence in BRCA1/2-negative breast cancer cases from 89 pedigrees with three or more cases of breast cancer. We identified one novel germline variant, R117G, in two separate families. To evaluate the possible association of R117G and two germline variants repo

Physical and functional interactions between human mitochondrial single-stranded DNA-binding protein and tumour suppressor p53

Single-stranded DNA-binding proteins (SSB) form a class of proteins that bind preferentially single-stranded DNA with high affinity. They are involved in DNA metabolism in all organisms and serve a vital role in replication, recombination and repair of DNA. In this report, we identify human mitochondrial SSB (HmtSSB) as a novel protein-binding partner of tumour suppressor p53, in mitochondria. It binds to the transactivation domain (residues 1–61) of p53 via an extended binding interface, with dissociation constant of 12.7 (± 0.7) μM. Unlike most binding partners reported to date, HmtSSB interacts with both TAD1 (residues 1–40) and TAD2 (residues 41–61) subdomains of p53. HmtSSB enhances intrinsic 3′-5′ exonuclease activity of p53, particularly in hydrolysing 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) present at 3′-end of DNA. Taken together, our data suggest that p53 is involved in DNA repair within mitochondria during oxidative stress. In addition, we characterize HmtSSB binding to ssDNA and p53 N-terminal domain using various biophysical measurements and we propose binding models for both