Composite Accretion Disk and White Dwarf Photosphere Analyses of the FUSE and HST Observations of EY Cygni

We explore the origin of FUSE and HST STIS far UV spectra of the dwarf nova, EY Cyg, during its quiescence using \emph{combined} high gravity photosphere and accretion disk models as well as model accretion belts. The best-fitting single temperature white dwarf model to the FUSE plus HST STIS spectrum of EY Cygni has T$_{eff} = 24,000$K, log $g = 9.0$, with an Si abundance of 0.1 x solar and C abundance of 0.2 x solar but the distance is only 301 pc. The best-fitting composite model consists of white dwarf with T$_{eff} = 22,000$K, log $g = 9$, plus an accretion belt with T$_{belt} = 36,000$K covering 27% of the white dwarf surface with V$_{belt} sin i = 2000$ km/s. The accretion belt contributes 63% of the FUV light and the cooler white dwarf latitudes contribute 37%. This fit yields a distance of 351 pc which is within 100 pc of our adopted distance of 450 pc. EY Cyg has very weak C {\sc iv} emission and very strong N {\sc v} emission, which is atypical of the majority of dwarf novae in quiescence. We also conducted a morphological study of the surroundings of EY Cyg using direct imaging in narrow nebular filters from ground-based telescopes. We report the possible detection of nebular material^M associated with EY Cygni. Possible origins of the apparently large N {\scv}/C {\sc iv} emission ratio are discussed in the context of nova explosions, contamination of the secondary star and accretion of nova abundance-enriched matter back to the white dwarf via the accretion disk or as a descendant of a precursor binary that survived thermal timescale mass transfer. The scenario involving pollution of the secondary by past novae may be supported by the possible presence of a nova remnant-like nebula around EY Cyg.Comment: To appear in AJ, Oct. 2004. 5 figures, including 2 color ones (2D pictures

Effects of a lifestyle intervention on endothelial function in men on long-term androgen deprivation therapy for prostate cancer

Background: Treatment of prostate cancer with androgen deprivation therapy (ADT) is associated with metabolic changes that have been linked to an increase in cardiovascular risk. Methods: This randomised controlled trial investigated the effects of a 12-week lifestyle intervention that included supervised exercise training and dietary advice on markers of cardiovascular risk in 50 men on long-term ADT recruited to an on-going study investigating the effects of such a lifestyle intervention on quality of life. Participants were randomly allocated to receive the intervention or usual care. Cardiovascular outcomes included endothelial function (flow-mediated dilatation [FMD] of the brachial artery), blood pressure, body composition and serum lipids. Additional outcomes included treadmill walk time and exercise and dietary behaviours. Outcomes were assessed before randomisation [baseline], and 6, 12 and 24 weeks after randomisation. Results: At 12 weeks the difference in mean relative FMD was 2.2% (95% CI 0.1 to 4.3, p = 0.04) with an effect size of 0.60 (95% CI <0.01 to 1.18) favouring the intervention group. Improvements in skeletal muscle mass, treadmill walk time and exercise behaviour also occurred in the intervention group over that duration (p < 0.05). At 24 weeks, only the difference in treadmill walk time was maintained. Conclusion: This study demonstrates that lifestyle changes can improve endothelial function in men on long-term ADT for prostate cancer. The implications for cardiovascular health need further investigation in larger studies over longer duration

Misuse of “Power” and other mechanical terms in sport and exercise science research

In spite of the Système International d’Unitès (SI) that was published in 1960, there continues to be widespread misuse of the terms and nomenclature of mechanics in descriptions of exercise performance. Misuse applies principally to failure to distinguish between mass and weight, velocity and speed, and especially the terms "work" and "power." These terms are incorrectly applied across the spectrum from high-intensity short-duration to long-duration endurance exercise. This review identifies these misapplications and proposes solutions. Solutions include adoption of the term "intensity" in descriptions and categorisations of challenge imposed on an individual as they perform exercise, followed by correct use of SI terms and units appropriate to the specific kind of exercise performed. Such adoption must occur by authors and reviewers of sport and exercise research reports to satisfy the principles and practices of science and for the field to advance

Structure and activity of the Streptococcus pyogenes family GH1 6-phospho β-glycosidase, Spy1599

The group A streptococcus Streptococcus pyogenes is the causative agent of a wide spectrum of invasive infections, including necrotizing fasciitis, scarlet fever and toxic shock syndrome. In the context of its carbohydrate chemistry, it is interesting that S. pyogenes (in this work strain M1 GAS SF370) displays a spectrum of oligosaccharide-processing enzymes that are located in close proximity on the genome but that the in vivo function of these proteins remains unknown. These proteins include different sugar transporters (SPy1593 and SPy1595), both GH125 -1,6- and GH38 -1,3-mannosidases (SPy1603 and SPy1604), a GH84 -hexosaminidase (SPy1600) and a putative GH2 -galactosidase (SPy1586), as well as SPy1599, a family GH1 `putative -glucosidase'. Here, the solution of the three-dimensional structure of SPy1599 in a number of crystal forms complicated by unusual crystallographic twinning is reported. The structure is a classical (/)8-barrel, consistent with CAZy family GH1 and other members of the GH-A clan. SPy1599 has been annotated in sequence depositions as a -glucosidase (EC 3.2.1.21), but no such activity could be found; instead, three-dimensional structural overlaps with other enzymes of known function suggested that SPy1599 contains a phosphate-binding pocket in the active site and has possible 6-phospho--glycosidase activity. Subsequent kinetic analysis indeed showed that SPy1599 has 6-phospho--glucosidase (EC 3.2.1.86) activity. These data suggest that SPy1599 is involved in the intracellular degradation of 6-phosphoglycosides, which are likely to originate from import through one of the organism's many phosphoenolpyruvate phosphotransfer systems (PEP-PTSs)

Lower limb joint kinetics during the first stance phase in athletics sprinting: three elite athlete case-studies

This study analysed the first stance phase joint kinetics of three elite sprinters to improve the understanding of technique and investigate how individual differences in technique could influence the resulting levels of performance. Force (1000 Hz) and video (200 Hz) data were collected and resultant moments, power and work at the stance leg metatarsal-phalangeal (MTP), ankle, knee and hip joints were calculated. The MTP and ankle joints both exhibited resultant plantarflexor moments throughout stance. Whilst the ankle joint generated up to four times more energy than it absorbed, the MTP joint was primarily an energy absorber. Knee extensor resultant moments and power were produced throughout the majority of stance, and the best-performing sprinter generated double and four times the amount of knee joint energy compared to the other two sprinters. The hip joint extended throughout stance. Positive hip extensor energy was generated during early stance before energy was absorbed at the hip as the resultant moment became flexor-dominant towards toe-off. The generation of energy at the ankle appears to be of greater importance than in later phases of a sprint, whilst knee joint energy generation may be vital for early acceleration and is potentially facilitated by favourable kinematics at touchdown

Relationships between lower-limb kinematics and block phase performance in a cross section of sprinters

This study investigated lower-limb kinematics to explain the techniques used to achieve high levels of sprint start performance. A cross-sectional design was used to examine relationships between specific technique variables and horizontal external power production during the block phase. Video data were collected (200 Hz) at the training sessions of 16 sprinters who ranged in 100 m personal best times from 9.98 to 11.6 s. Each sprinter performed three 30 m sprints and reliable (all intraclass correlation coefficients, ICC(2,3) ≥ 0.89) lower-limb kinematic data were obtained through manual digitising. The front leg joints extended in a proximal-to-distal pattern for 15 sprinters, and a moderate positive relationship existed between peak front hip angular velocity and block power (r = 0.49, 90% confidence limits = 0.08–0.76). In the rear leg, there was a high positive relationship between relative push duration and block power (r = 0.53, 90% confidence limits = 0.13–0.78). The rear hip appeared to be important; rear hip angle at block exit was highly related to block power (r = 0.60, 90% confidence limits = 0.23–0.82), and there were moderate positive relationships with block power for its range of motion and peak angular velocity (both r = 0.49, 90% confidence limits = 0.08–0.76). As increased block power production was not associated with any negative aspects of technique in the subsequent stance phase, sprinters should be encouraged to maximise extension at both hips during the block phase

The beneficial effect of sulforaphane on platelet responsiveness during caloric load:a single-intake, double-blind, placebo-controlled, crossover trial in healthy participants

Background and aims: As our understanding of platelet activation in response to infections and/or inflammatory conditions is growing, it is becoming clearer that safe, yet efficacious, platelet-targeted phytochemicals could improve public health beyond the field of cardiovascular diseases. The phytonutrient sulforaphane shows promise for clinical use due to its effect on inflammatory pathways, favorable pharmacokinetic profile, and high bioavailability. The potential of sulforaphane to improve platelet functionality in impaired metabolic processes has however hardly been studied in humans. This study investigated the effects of broccoli sprout consumption, as a source of sulforaphane, on urinary 11-dehydro-thromboxane B2 (TXB2), a stable thromboxane metabolite used to monitor eicosanoid biosynthesis and response to antithrombotic therapy, in healthy participants exposed to caloric overload. Methods: In this double-blind, placebo-controlled, crossover trial 12 healthy participants were administered 16g of broccoli sprouts, or pea sprouts (placebo) followed by the standardized high-caloric drink PhenFlex given to challenge healthy homeostasis. Urine samples were collected during the study visits and analyzed for 11-dehydro-TXB2, sulforaphane and its metabolites. Genotyping was performed using Illumina GSA v3.0 DTCBooster. Results: Administration of broccoli sprouts before the caloric load reduced urinary 11-dehydro-TXB2 levels by 50% (p = 0.018). The amount of sulforaphane excreted in the urine during the study visits correlated negatively with 11-dehydro-TXB2 (rs = −0.377, p = 0.025). Participants carrying the polymorphic variant NAD(P)H dehydrogenase quinone 1 (NQO1*2) showed decreased excretion of sulforaphane (p = 0.035). Conclusion: Sulforaphane was shown to be effective in targeting platelet responsiveness after a single intake. Our results indicate an inverse causal relationship between sulforaphane and 11-dehydro-TXB2, which is unaffected by the concomitant intake of the metabolic challenge. 11-Dehydro-TXB2 shows promise as a non-invasive, sensitive, and suitable biomarker to investigate the effects of phytonutrients on platelet aggregation within hours. Clinical trial registration: [https://clinicaltrials.gov/], identifier [NCT05146804].</p

Combined effects of genotype and childhood adversity shape variability of DNA methylation across age

Lasting effects of adversity, such as exposure to childhood adversity (CA) on disease risk, may be embedded via epigenetic mechanisms but findings from human studies investigating the main effects of such exposure on epigenetic measures, including DNA methylation (DNAm), are inconsistent. Studies in perinatal tissues indicate that variability of DNAm at birth is best explained by the joint effects of genotype and prenatal environment. Here, we extend these analyses to postnatal stressors. We investigated the contribution of CA, cis genotype (G), and their additive (G+CA) and interactive (GxCA) effects to DNAm variability in blood or saliva from five independent cohorts with a total sample size of 1074 ranging in age from childhood to late adulthood. Of these, 541 were exposed to CA, which was assessed retrospectively using self-reports or verified through social services and registries. For the majority of sites (over 50%) in the adult cohorts, variability in DNAm was best explained by G+CA or GxCA but almost never by CA alone. Across ages and tissues, 1672 DNAm sites showed consistency of the best model in all five cohorts, with GxCA interactions explaining most variance. The consistent GxCA sites mapped to genes enriched in brain-specific transcripts and Gene Ontology terms related to development and synaptic function. Interaction of CA with genotypes showed the strongest contribution to DNAm variability, with stable effects across cohorts in functionally relevant genes. This underscores the importance of including genotype in studies investigating the impact of environmental factors on epigenetic marks.Peer reviewe

Report of Seminar on Law and Medicine

Reports from the UK/CLE Seminar on Law and Medicine held May 26-28, 1976

Forskolin-induced Organoid Swelling is Associated with Long-term CF Disease Progression

RATIONALE: Cystic fibrosis (CF) is a monogenic life-shortening disease associated with highly variable individual disease progression which is difficult to predict. Here we assessed the association of forskolin-induced swelling (FIS) of patient-derived organoids (PDO) with long-term CF disease progression in multiple organs and compared FIS with the golden standard biomarker sweat chloride concentration (SCC). METHODS: We retrieved 9-year longitudinal clinical data from the Dutch CF Registry of 173 people with mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Individual CFTR function was defined by FIS, measured as the relative size increase of intestinal organoids after stimulation with 0.8 µM forskolin, quantified as area under the curve (AUC). We used linear mixed effect models and multivariable logistic regression to estimate the association of FIS with long-term FEV1pp decline and development of pancreatic insufficiency, CF-related liver disease and diabetes. Within these models, FIS was compared with SCC. RESULTS: FIS was strongly associated with longitudinal changes of lung function, with an estimated difference in annual FEV1pp decline of 0.32% (95%CI: 0.11%-0.54%; p=0.004) per 1000-points change in AUC. Moreover, increasing FIS levels were associated with lower odds of developing pancreatic insufficiency (adjusted OR: 0.18, 95%CI: 0.07-0.46, p<0.001), CF-related liver disease (adjusted OR: 0.18, 95%CI: 0.06-0.54, p=0.002) and diabetes (adjusted OR: 0.34, 95%CI: 0.12-0.97, p=0.044). These associations were absent for SCC. CONCLUSION: This study exemplifies the prognostic value of a PDO-based biomarker within a clinical setting, which is especially important for people carrying rare CFTR mutations with unclear clinical consequences