PrimPol is required for replicative tolerance of G quadruplexes in vertebrate cells

G quadruplexes (G4s) can present potent blocks to DNA replication. Accurate and timely replication of G4s in vertebrates requires multiple specialized DNA helicases and polymerases to prevent genetic and epigenetic instability. Here we report that PrimPol, a recently described primase-polymerase (PrimPol), plays a crucial role in the bypass of leading strand G4 structures. While PrimPol is unable to directly replicate G4s, it can bind and reprime downstream of these structures. Disruption of either the catalytic activity or zinc-finger of PrimPol results in extreme G4-dependent epigenetic instability at the BU-1 locus in avian DT40 cells, indicative of extensive uncoupling of the replicative helicase and polymerase. Together, these observations implicate PrimPol in promoting restart of DNA synthesis downstream of, but closely coupled to, G4 replication impediments

Measurement of the cross-section ratio 3H(d,γ)5He/3H(d,α)n at 100 keV

The cross-section ratio for 3H(d,γ)5He relative to 3H(d,α)n has been measured at an effective deuteron bombarding energy of 100 keV with a NaI pair spectrometer and a tritiated-titanium target. The ratio was determined to be (1.2±0.3)×10^-4 by comparing the spectra and count rates for 3H(d,γ)5He and 3H(d,α)n with 2H(3He,γ)5Li and 2H(3He,α)1H

Pregnancy in the female athlete - Part 1: antenatal

As female participation in sport and exercise continues to increase, there is a strong likelihood that a strength and conditioning (S&C) coach will work with a pregnant athlete. High profile athletes such as Serena Williams and Dame Jessica Ennis-Hill have shown recently that it is not uncommon for female athletes to become mothers during their careers, rather than after they have retired. However, historically pregnancy was perceived as time spent away from sport and being active was wrongly associated with a high, unreasonable risk to the unborn foetus. The challenge for the S&C coach working with pregnant athletes is navigating the wide range of global recommendations that are often aimed at active or inactive individuals, but not at elite athletes. It is fundamental that any coach working with pregnant athletes is knowledgeable about the physiological and anatomical changes that occur throughout the trimesters, the nutritional demands of pregnancy, and its effect on weight management in order to appropriately facilitate athlete and foetal health during the antenatal period. Therefore, the aim of this initial review is to summarise current literature and provide key insights that promote best practice for practitioners working with pregnant athletes. The use of ‘women’ throughout this paper will refer to the general population and ‘sportswomen’ to the athletic population. ‘Antenatal’ refers to a pregnant woman before childbirth and the term ‘postnatal’ means after childbirth, something which will be covered in part 2 of this review series

The effects of oral contraceptives on exercise performance in women: a systematic review and meta-analysis

Background: Oral contraceptive pills (OCPs) are double agents, which downregulate endogenous concentrations of oestradiol and progesterone whilst simultaneously providing daily supplementation of exogenous oestrogen and progestin during the OCP-taking days. This altered hormonal milieu differs significantly from that of eumenorrheic women and might impact exercise performance, due to changes in ovarian hormone-mediated physiological processes. Objective: To explore the effects of OCPs on exercise performance in women and to provide evidence-based performance recommendations to users. Methods: This review complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A between-group analysis was performed, wherein performance of OCP users was compared with naturally menstruating women, and a within-group analysis was conducted, wherein performance during OCP consumption was compared with OCP withdrawal. For the between-group analysis, women were phase matched in two ways: (1) OCP withdrawal versus the early follicular phase of the menstrual cycle and (2) OCP consumption versus all phases of the menstrual cycle except for the early follicular phase. Study quality was assessed using a modified Downs and Black Checklist and a strategy based on the recommendations of the Grading of Recommendations Assessment Development and Evaluation working group. All meta-analyses were conducted within a Bayesian framework to facilitate probabilistic interpretations. Results: 42 studies and 590 participants were included. Most studies (83%) were graded as moderate, low or very low quality, with 17% achieving high quality. For the between-group meta-analysis comparing OCP users with naturally menstruating women, posterior estimates of the pooled effect were used to calculate the probability of at least a small effect (d ≥ 0.2). Across the two between-group comparison methods, the probability of a small effect on performance favouring habitual OCP users was effectually zero (p < 0.001). In contrast, the probability of a small effect on performance favouring naturally menstruating women was moderate under comparison method (1) (d ≥ 0.2; p = 0.40) and small under comparison method (2) (d ≥ 0.2; p = 0.19). Relatively large between-study variance was identified for both between-group comparisons (0.5 = 0.16 [95% credible interval (CrI) 0.01-0.44] and 0.5 = 0.22 [95% CrI 0.06-0.45]). For the within-group analysis comparing OCP consumption with withdrawal, posterior estimates of the pooled effect size identified almost zero probability of a small effect on performance in either direction (d ≥ 0.2; p ≤ 0.001). Conclusions: OCP use might result in slightly inferior exercise performance on average when compared to naturally menstruating women, although any group-level effect is most likely to be trivial. Practically, as effects tended to be trivial and variable across studies, the current evidence does not warrant general guidance on OCP use compared with non-use. Therefore, when exercise performance is a priority, an individualised approach might be more appropriate. The analysis also indicated that exercise performance was consistent across the OCP cycle

Simultaneous disruption of two DNA polymerases, Polη and Polζ, in Avian DT40 cells unmasks the role of Polη in cellular response to various DNA lesions

Replicative DNA polymerases are frequently stalled by DNA lesions. The resulting replication blockage is released by homologous recombination (HR) and translesion DNA synthesis (TLS). TLS employs specialized TLS polymerases to bypass DNA lesions. We provide striking in vivo evidence of the cooperation between DNA polymerase η, which is mutated in the variant form of the cancer predisposition disorder xeroderma pigmentosum (XP-V), and DNA polymerase ζ by generating POLη−/−/POLζ−/− cells from the chicken DT40 cell line. POLζ−/− cells are hypersensitive to a very wide range of DNA damaging agents, whereas XP-V cells exhibit moderate sensitivity to ultraviolet light (UV) only in the presence of caffeine treatment and exhibit no significant sensitivity to any other damaging agents. It is therefore widely believed that Polη plays a very specific role in cellular tolerance to UV-induced DNA damage. The evidence we present challenges this assumption. The phenotypic analysis of POLη−/−/POLζ−/− cells shows that, unexpectedly, the loss of Polη significantly rescued all mutant phenotypes of POLζ−/− cells and results in the restoration of the DNA damage tolerance by a backup pathway including HR. Taken together, Polη contributes to a much wide range of TLS events than had been predicted by the phenotype of XP-V cells

Effects of low energy availability on bone health in endurance athletes and high-impact exercise as a potential countermeasure: a narrative review

Endurance athletes expend large amounts of energy in prolonged high-intensity exercise and, due to the weight-sensitive nature of most endurance sports, often practice periods of dietary restriction. The Female Athlete Triad and Relative Energy Deficiency in Sport models consider endurance athletes at high-risk for suffering from low energy availability and associated health complications, including an increased chance of bone stress injury. Several studies have examined the effects of low energy availability on various parameters of bone structure and markers of bone (re)modelling; however, there are differences in findings and research methods and critical summaries are lacking. It is difficult for athletes to reduce energy expenditure or increase energy intake (to restore energy availability) in an environment where performance is a priority. Development of an alternative tool to help protect bone health would be beneficial. High-impact exercise can be highly osteogenic and energy efficient; however, at present, it is rarely utilized to promote bone health in endurance athletes. Therefore, with a view to reducing the prevalence of bone stress injury, the objectives of this review are to evaluate the effects of low energy availability on bone health in endurance athletes and explore whether a high-impact exercise intervention may help to prevent those effects from occurring

New young planetary nebulae in IPHAS

Original article can be found at: http://www.aanda.org/ Copyright The European Southern Observatory. DOI: 10.1051/0004-6361/200811575Aims. We search for very small-diameter galactic planetary nebulae (PNe) representing the earliest phases of PN evolution. The IPHAS catalogue of H-emitting stars provides a useful basis for this study since all sources present in this catalogue must be of small angular diameter. Methods. The PN candidates are selected based on their location in two colour-colour diagrams: IPHAS (r' - H) vs. (r' - i'), and 2MASS (J - H) vs. (H - ). Spectroscopic follow-up was carried out on a sample of candidates to confirm their nature. Results. We present a total of 83 PN candidates. We were able to obtain spectra or find the classification from the literature for 35 candidates. Five of these objects are likely to be new PNe, including one large bipolar PN discovered serendipitously close to an emission-line star. PN distances deduced from extinction-distance relations based on IPHAS field-star photometry are presented for the first time. These yield distance estimates for our objects in the range 2 kpc and 6 kpc. From the data in hand, we conclude that four of the discovered objects are probably young PNe.Peer reviewe

Managing female athlete health : Auditing the representation of female versus male participants among research in supplements to manage diagnosed micronutrient issues

Micronutrient deficiencies and sub-optimal intakes among female athletes are a concern and are commonly prevented or treated with medical supplements. However, it is unclear how well women have been considered in the research underpinning current supplementation practices. We conducted an audit of the literature supporting the use of calcium, iron, and vitamin D. Of the 299 studies, including 25,171 participants, the majority (71%) of participants were women. Studies with exclusively female cohorts (37%) were also more prevalent than those examining males in isolation (31%). However, study designs considering divergent responses between sexes were sparse, accounting for 7% of the literature. Moreover, despite the abundance of female participants, the quality and quantity of the literature specific to female athletes was poor. Just 32% of studies including women defined menstrual status, while none implemented best-practice methodologies regarding ovarian hormonal control. Additionally, only 10% of studies included highly trained female athletes. Investigations of calcium supplementation were particularly lacking, with just two studies conducted in highly trained women. New research should focus on high-quality investigations specific to female athletes, alongside evaluating sex-based differences in the response to calcium, iron, and vitamin D, thus ensuring the specific needs of women have been considered in current protocols involving medical supplements

Bayesian Processing for the Detection of Radioactive Contraband from Uncertain Measurements

With the increase in terrorist activities throughout the world, the need to develop techniques capable of detecting radioactive contraband in a timely manner is a critical requirement. The development of Bayesian processors for the detection of contraband stems from the fact that the posterior distribution is clearly multimodal eliminating the usual Gaussian-based processors. The development of a sequential bootstrap processor for this problem is discussed and shown how it is capable of providing an enhanced signal for eventual detection