Postcopulatory sexual selection

The female reproductive tract is where competition between the sperm of different males takes place, aided and abetted by the female herself. Intense postcopulatory sexual selection fosters inter-sexual conflict and drives rapid evolutionary change to generate a startling diversity of morphological, behavioural and physiological adaptations. We identify three main issues that should be resolved to advance our understanding of postcopulatory sexual selection. We need to determine the genetic basis of different male fertility traits and female traits that mediate sperm selection; identify the genes or genomic regions that control these traits; and establish the coevolutionary trajectory of sexes

Heparin based prophylaxis to prevent venous thromboembolic events and death in patients with cancer - a subgroup analysis of CERTIFY

<p>Abstract</p> <p>Background</p> <p>Patients with cancer have an increased risk of VTE. We compared VTE rates and bleeding complications in 1) cancer patients receiving LMWH or UFH and 2) patients with or without cancer.</p> <p>Methods</p> <p>Acutely-ill, non-surgical patients ≥70 years with (n = 274) or without cancer (n = 2,965) received certoparin 3,000 UaXa o.d. or UFH 5,000 IU t.i.d. for 8-20 days.</p> <p>Results</p> <p>1) Thromboembolic events in cancer patients (proximal DVT, symptomatic non-fatal PE and VTE-related death) occurred at 4.50% with certoparin and 6.03% with UFH (OR 0.73; 95% CI 0.23-2.39). Major bleeding was comparable and minor bleedings (0.75 vs. 5.67%) were nominally less frequent. 7.5% of certoparin and 12.8% of UFH treated patients experienced serious adverse events. 2) Thromboembolic event rates were comparable in patients with or without cancer (5.29 vs. 4.13%) as were bleeding complications. All cause death was increased in cancer (OR 2.68; 95%CI 1.22-5.86). 10.2% of patients with and 5.81% of those without cancer experienced serious adverse events (OR 1.85; 95% CI 1.21-2.81).</p> <p>Conclusions</p> <p>Certoparin 3,000 UaXa o.d. and 5,000 IU UFH t.i.d. were equally effective and safe with respect to bleeding complications in patients with cancer. There were no statistically significant differences in the risk of thromboembolic events in patients with or without cancer receiving adequate anticoagulation.</p> <p>Trial Registration</p> <p>clinicaltrials.gov, <a href="http://www.clinicaltrials.gov/ct2/show/NCT00451412">NCT00451412</a></p

Effect of eplerenone on parathyroid hormone levels in patients with primary hyperparathyroidism: a randomized, double-blind, placebo-controlled trial

<p>Abstract</p> <p>Background</p> <p>Increasing evidence suggests the bidirectional interplay between parathyroid hormone and aldosterone as an important mechanism behind the increased risk of cardiovascular damage and bone disease observed in primary hyperparathyroidism. Our primary object is to assess the efficacy of the mineralocorticoid receptor-blocker eplerenone to reduce parathyroid hormone secretion in patients with parathyroid hormone excess.</p> <p>Methods/design</p> <p>Overall, 110 adult male and female patients with primary hyperparathyroidism will be randomly assigned to eplerenone (25 mg once daily for 4 weeks and 4 weeks with 50 mg once daily after dose titration] or placebo, over eight weeks. Each participant will undergo detailed clinical assessment, including anthropometric evaluation, 24-h ambulatory arterial blood pressure monitoring, echocardiography, kidney function and detailed laboratory determination of biomarkers of bone metabolism and cardiovascular disease.</p> <p>The study comprises the following exploratory endpoints: mean change from baseline to week eight in (1) parathyroid hormone(1–84) as the primary endpoint and (2) 24-h systolic and diastolic ambulatory blood pressure levels, NT-pro-BNP, biomarkers of bone metabolism, 24-h urinary protein/albumin excretion and echocardiographic parameters reflecting systolic and diastolic function as well as cardiac dimensions, as secondary endpoints.</p> <p>Discussion</p> <p>In view of the reciprocal interaction between aldosterone and parathyroid hormone and the potentially ensuing target organ damage, the EPATH trial is designed to determine whether eplerenone, compared to placebo, will effectively impact on parathyroid hormone secretion and improve cardiovascular, renal and bone health in patients with primary hyperparathyroidism.</p> <p>Trial registration</p> <p>ISRCTN33941607</p

Composition and Hierarchical Organisation of a Spider Silk

Albeit silks are fairly well understood on a molecular level, their hierarchical organisation and the full complexity of constituents in the spun fibre remain poorly defined. Here we link morphological defined structural elements in dragline silk of Nephila clavipes to their biochemical composition and physicochemical properties. Five layers of different make-ups could be distinguished. Of these only the two core layers contained the known silk proteins, but all can vitally contribute to the mechanical performance or properties of the silk fibre. Understanding the composite nature of silk and its supra-molecular organisation will open avenues in the production of high performance fibres based on artificially spun silk material

Salt restriction in kidney disease—a missed therapeutic opportunity?

The importance of salt restriction in the treatment of patients with renal disease has remained highly controversial. In the following we marshal the current evidence that salt plays a definite role in the genesis of hypertension and target organ damage, point to practical problems of salt restriction, and report on novel pathomechanisms of how salt affects blood pressure and causes target organ damage

The role of complement in ocular pathology

Functionally active complement system and complement regulatory proteins are present in the normal human and rodent eye. Complement activation and its regulation by ocular complement regulatory proteins contribute to the pathology of various ocular diseases including keratitis, uveitis and age-related macular degeneration. Furthermore, a strong relationship between age-related macular degeneration and polymorphism in the genes of certain complement components/complement regulatory proteins is now well established. Recombinant forms of the naturally occurring complement regulatory proteins have been exploited in the animal models for treatment of these ocular diseases. It is hoped that in the future recombinant complement regulatory proteins will be used as novel therapeutic agents in the clinic for the treatment of keratitis, uveitis, and age-related macular degeneration

The restorative role of annexin A1 at the blood–brain barrier

Annexin A1 is a potent anti-inflammatory molecule that has been extensively studied in the peripheral immune system, but has not as yet been exploited as a therapeutic target/agent. In the last decade, we have undertaken the study of this molecule in the central nervous system (CNS), focusing particularly on the primary interface between the peripheral body and CNS: the blood–brain barrier. In this review, we provide an overview of the role of this molecule in the brain, with a particular emphasis on its functions in the endothelium of the blood–brain barrier, and the protective actions the molecule may exert in neuroinflammatory, neurovascular and metabolic disease. We focus on the possible new therapeutic avenues opened up by an increased understanding of the role of annexin A1 in the CNS vasculature, and its potential for repairing blood–brain barrier damage in disease and aging

Lessons from mouse chimaera experiments with a reiterated transgene marker:revised marker criteria and a review of chimaera markers

Recent reports of a new generation of ubiquitous transgenic chimaera markers prompted us to consider the criteria used to evaluate new chimaera markers and develop more objective assessment methods. To investigate this experimentally we used several series of fetal and adult chimaeras, carrying an older, multi-copy transgenic marker. We used two additional independent markers and objective, quantitative criteria for cell selection and cell mixing to investigate quantitative and spatial aspects of developmental neutrality. We also suggest how the quantitative analysis we used could be simplified for future use with other markers. As a result, we recommend a five-step procedure for investigators to evaluate new chimaera markers based partly on criteria proposed previously but with a greater emphasis on examining the developmental neutrality of prospective new markers. These five steps comprise (1) review of published information, (2) evaluation of marker detection, (3) genetic crosses to check for effects on viability and growth, (4) comparisons of chimaeras with and without the marker and (5) analysis of chimaeras with both cell populations labelled. Finally, we review a number of different chimaera markers and evaluate them using the extended set of criteria. These comparisons indicate that, although the new generation of ubiquitous fluorescent markers are the best of those currently available and fulfil most of the criteria required of a chimaera marker, further work is required to determine whether they are developmentally neutral. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11248-015-9883-7) contains supplementary material, which is available to authorized users