Genetic and environmental variation in condition, cutaneous immunity, and haematocrit in house wrens

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Life-history studies of wild bird populations often focus on the relationship between an individual's condition and its capacity to mount an immune response, as measured by a commonly-employed assay of cutaneous immunity, the PHA skin test. In addition, haematocrit, the packed cell volume in relation to total blood volume, is often measured as an indicator of physiological performance. A multi-year study of a wild population of house wrens has recently revealed that those exhibiting the highest condition and strongest PHA responses as nestlings are most likely to be recruited to the breeding population and to breed through two years of age; in contrast, intermediate haematocrit values result in the highest recruitment to the population. Selection theory would predict, therefore, that most of the underlying genetic variation in these traits should be exhausted resulting in low heritability, although such traits may also exhibit low heritability because of increased residual variance. Here, we examine the genetic and environmental variation in condition, cutaneous immunity, and haematocrit using an animal model based on a pedigree of approximately 2,800 house wrens. RESULTS: Environmental effects played a paramount role in shaping the expression of the fitness-related traits measured in this wild population, but two of them, condition and haematocrit, retained significant heritable variation. Condition was also positively correlated with both the PHA response and haematocrit, but in the absence of any significant genetic correlations, it appears that this covariance arises through parallel effects of the environment acting on this suite of traits. CONCLUSIONS: The maintenance of genetic variation in different measures of condition appears to be a pervasive feature of wild bird populations, in contradiction of conventional selection theory. A major challenge in future studies will be to explain how such variation persists in the face of the directional selection acting on condition in house wrens and other species.We thank the 2004–2006 Wren Crews for field assistance and the ParkLands Foundation (Merwin Preserve) and the Sears and Butler families for the use of their properties. Financial support was provided by NSF grants GK12-0086354, IBN-0316580, IOS-0718140 and IOS-1118160; NIH grant R15HD076308-01; a visiting professorship from the Leverhulme Trust (SKS); the School of Biological Sciences, Illinois State University; a BBSRC David Phillips Research Fellowship (AJW); and student-research grants from the Beta Lambda Chapter of the Phi Sigma Biological Sciences Honor Society (AMF)

Psychological determinants of whole-body endurance performance

Background: No literature reviews have systematically identified and evaluated research on the psychological determinants of endurance performance, and sport psychology performance-enhancement guidelines for endurance sports are not founded on a systematic appraisal of endurance-specific research. Objective: A systematic literature review was conducted to identify practical psychological interventions that improve endurance performance and to identify additional psychological factors that affect endurance performance. Additional objectives were to evaluate the research practices of included studies, to suggest theoretical and applied implications, and to guide future research. Methods: Electronic databases, forward-citation searches, and manual searches of reference lists were used to locate relevant studies. Peer-reviewed studies were included when they chose an experimental or quasi-experimental research design, a psychological manipulation, endurance performance as the dependent variable, and athletes or physically-active, healthy adults as participants. Results: Consistent support was found for using imagery, self-talk, and goal setting to improve endurance performance, but it is unclear whether learning multiple psychological skills is more beneficial than learning one psychological skill. The results also demonstrated that mental fatigue undermines endurance performance, and verbal encouragement and head-to-head competition can have a beneficial effect. Interventions that influenced perception of effort consistently affected endurance performance. Conclusions: Psychological skills training could benefit an endurance athlete. Researchers are encouraged to compare different practical psychological interventions, to examine the effects of these interventions for athletes in competition, and to include a placebo control condition or an alternative control treatment. Researchers are also encouraged to explore additional psychological factors that could have a negative effect on endurance performance. Future research should include psychological mediating variables and moderating variables. Implications for theoretical explanations of endurance performance and evidence-based practice are described

Assessment of the proliferative, apoptotic and cellular renovation indices of the human mammary epithelium during the follicular and luteal phases of the menstrual cycle

Introduction During the menstrual cycle, the mammary gland goes through sequential waves of proliferation and apoptosis. in mammary epithelial cells, hormonal and non-hormonal factors regulate apoptosis. To determine the cyclical effects of gonadal steroids on breast homeostasis, we evaluated the apoptotic index ( AI) determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling ( TUNEL) staining in human mammary epithelial cells during the spontaneous menstrual cycle and correlated it with cellular proliferation as determined by the expression of Ki-67 during the same period.Methods Normal breast tissue samples were obtained from 42 randomly selected patients in the proliferative ( n = 21) and luteal ( n = 21) phases. Menstrual cycle phase characterization was based on the date of the last and subsequent menses, and on progesterone serum levels obtained at the time of biopsy.Results the proliferation index ( PI), defined as the number of Ki-67-positive nuclei per 1,000 epithelial cells, was significantly larger in the luteal phase (30.46) than in the follicular phase (13.45; P = 0.0033). the AI was defined as the number of TUNEL-positive cells per 1,000 epithelial cells. the average AI values in both phases of the menstrual cycle were not statistically significant ( P = 0.21). However, the cell renewal index ( CRI = PI/AI) was significantly higher in the luteal phase ( P = 0.033). A significant cyclical variation of PI, AI and CRI was observed. PI and AI peaks occurred on about the 24th day of the menstrual cycle, whereas the CRI reached higher values on the 28th day.Conclusions We conclude that proliferative activity is dependent mainly on hormonal fluctuations, whereas apoptotic activity is probably regulated by hormonal and non-hormonal factors.Universidade Federal de São Paulo, Dept Gyneol, Mastol Div, São Paulo, BrazilStanford Univ, Sch Med, Dept Neurosurg, Stanford, CA 94305 USAAPC Pathol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Gyneol, Mastol Div, São Paulo, BrazilWeb of Scienc

Circular Single-Stranded Synthetic DNA Delivery Vectors for MicroRNA

Single-stranded (ss) circular oligodeoxynucleotides were previously found to undergo rolling circle transcription (RCT) by phage and bacterial RNA polymerases (RNAPs) into tandemly repetitive RNA multimers. Here, we redesign them to encode minimal primary miRNA mimics, with the long term aim of intracellular transcription followed by RNA processing and maturation via endogenous pathways. We describe an improved method for circularizing ss synthetic DNA for RCT by using a recently described thermostable RNA ligase, which does not require a splint oligonucleotide to juxtapose the ligating ends. In vitro transcription of four templates demonstrates that the secondary structure inherent in miRNA-encoding vectors does not impair their RCT by RNAPs previously shown to carry out RCT. A typical primary-miRNA rolling circle transcript was accurately processed by a human Drosha immunoprecipitate, indicating that if human RNAPs prove to be capable of RCT, the resulting transcripts should enter the endogenous miRNA processing pathway in human cells. Circular oligonucleotides are therefore candidate vectors for small RNA delivery in human cells, which express RNAPs related to those tested here

Red Is Not a Proxy Signal for Female Genitalia in Humans

Red is a colour that induces physiological and psychological effects in humans, affecting competitive and sporting success, signalling and enhancing male social dominance. The colour is also associated with increased sexual attractiveness, such that women associated with red objects or contexts are regarded as more desirable. It has been proposed that human males have a biological predisposition towards the colour red such that it is ‘sexually salient’. This hypothesis argues that women use the colour red to announce impending ovulation and sexual proceptivity, with this functioning as a proxy signal for genital colour, and that men show increased attraction in consequence. In the first test of this hypothesis, we show that contrary to the hypothesis, heterosexual men did not prefer redder female genitalia and, by extension, that red is not a proxy signal for genital colour. We found a relative preference for pinker genital images with redder genitalia rated significantly less sexually attractive. This effect was independent of raters' prior sexual experience and variation in female genital morphology. Our results refute the hypothesis that men's attraction to red is linked to an implied relationship to genital colour and women's signalling of fertility and sexual proceptivity

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Evaluating the impact of MEDLINE filters on evidence retrieval: study protocol

<p>Abstract</p> <p>Background</p> <p>Rather than searching the entire MEDLINE database, clinicians can perform searches on a filtered set of articles where relevant information is more likely to be found. Members of our team previously developed two types of MEDLINE filters. The 'methods' filters help identify clinical research of high methodological merit. The 'content' filters help identify articles in the discipline of renal medicine. We will now test the utility of these filters for physician MEDLINE searching.</p> <p>Hypothesis</p> <p>When a physician searches MEDLINE, we hypothesize the use of filters will increase the number of relevant articles retrieved (increase 'recall,' also called sensitivity) and decrease the number of non-relevant articles retrieved (increase 'precision,' also called positive predictive value), compared to the performance of a physician's search unaided by filters.</p> <p>Methods</p> <p>We will survey a random sample of 100 nephrologists in Canada to obtain the MEDLINE search that they would first perform themselves for a focused clinical question. Each question we provide to a nephrologist will be based on the topic of a recently published, well-conducted systematic review. We will examine the performance of a physician's unaided MEDLINE search. We will then apply a total of eight filter combinations to the search (filters used in isolation or in combination). We will calculate the recall and precision of each search. The filter combinations that most improve on unaided physician searches will be identified and characterized.</p> <p>Discussion</p> <p>If these filters improve search performance, physicians will be able to search MEDLINE for renal evidence more effectively, in less time, and with less frustration. Additionally, our methodology can be used as a proof of concept for the evaluation of search filters in other disciplines.</p

An analysis of the utilisation of chemoprophylaxis against Pneumocystis jirovecii pneumonia in patients with malignancy receiving corticosteroid therapy at a cancer hospital

Pneumocystis jirovecii pneumonia (PCP) is associated with high mortality in immunocompromised patients without human immunodeficiency virus infection. However, chemoprophylaxis is highly effective. In patients with solid tumours or haematologic malignancy, several risk factors for developing PCP have been identified, predominantly corticosteroid therapy. The aims of this study were to identify the potentially preventable cases of PCP in patients receiving corticosteroid therapy at a tertiary care cancer centre and to estimate the frequency of utilisation of chemoprophylaxis in these patients. Two retrospective reviews were performed. Over a 10-year period, 14 cases of PCP were identified: no cases were attributable to failed chemoprophylaxis, drug allergy or intolerance. During a 6-month period, 73 patients received high-dose corticosteroid therapy (⩾25 mg prednisolone or ⩾4 mg dexamethasone daily) for ⩾4 weeks. Of these, 22 (30%) had haematologic malignancy, and 51 (70%) had solid tumours. Fewer patients with solid tumours received prophylaxis compared to patients with haematologic malignancy (3.9 vs 63.6%, P<0.0001). Guidelines for PCP chemoprophylaxis in patients with haematologic malignancy or solid tumours who receive corticosteroid therapy are proposed. Successful primary prevention of PCP in this population will require a multifaceted approach targeting the suboptimal prescribing patterns for chemoprophylaxis