Functional trait plasticity diverges between sexes in African cichlids: A contribution toward ecological sexual dimorphism?

Phenotypic plasticity enables development to produce multiple phenotypes in response to environmental conditions. Plasticity driven variation has been suggested to play a key role in adaptive divergence, and plasticity itself can evolve. However, the interaction of plasticity with the multiple levels involved with adaptive divergence is less understood. For example, sexual dimorphism can contribute adaptive variation through ecological sexual dimorphism (ESD), but the contribution of plasticity to this phenomenon is unknown. Therefore, to determine the potential contribution of plasticity to ESD, we used the adaptive radiation of Malawi cichlids. Two mouthbrooding species (Labeotropheus fuelleborni and Tropheops "Red Cheek") with differences in foraging tactics underwent foraging experiments using benthic and limnetic treatments while accounting for sex. Plasticity in craniofacial shape and three functionally important traits were measured. Plasticity was shown, but without any sex-based differences in shape. However, for mechanical advantage traits of the mandible sex by diet interactions were found. This suggests that ESD, may be influenced by phenotypic plasticity that diverges between sexes. Given the involvement of the mandible in parental care in cichlids this may indicate that sexual divergence in plasticity may trade-off against maternal care tactics

Oxygen supplementation facilitating successful prosthetic fitting and rehabilitation of a patient with severe chronic obstructive pulmonary disease following trans-tibial amputation: a case report

Abstract Introduction Dysvascular amputations are increasingly performed in patients with underlying cardiac and pulmonary disorders. A limb prosthesis is rarely offered to patients with severe chronic obstructive pulmonary disease because of their inability to achieve the high energy expenditure required for prosthetic ambulation. We describe a case of successful prosthetic fitting and rehabilitation of a patient with severe chronic obstructive pulmonary disease with the aid of oxygen supplementation. Case presentation A 67-year-old aboriginal woman with severe chronic obstructive pulmonary disease and hypercapnic respiratory failure underwent right trans-tibial (below the knee) amputation for severe foot gangrene. An aggressive rehabilitation program of conditioning exercises and gait training utilizing oxygen therapy was initiated. She was custom-fitted with a right trans-tibial prosthesis. A rehabilitation program improved her strength, endurance and stump contracture, and she was able to walk for short distances with the prosthesis. The motion analysis studies showed a cadence of 73.5 steps per minute, a velocity of 0.29 meters per second and no difference in right and left step time and step length. Conclusion This case report illustrates that patients with significant severe chronic obstructive pulmonary disease can be successfully fitted with limb prostheses and undergo rehabilitation using supplemental oxygen along with optimization of their underlying comorbidities. Despite the paucity of published information in this area, prosthesis fitting and rehabilitation should be considered in patients who have undergone amputation and have severe chronic obstructive disease.</p

Identification of Two Independent Risk Factors for Lupus within the MHC in United Kingdom Families

The association of the major histocompatibility complex (MHC) with SLE is well established yet the causal variants arising from this region remain to be identified, largely due to inadequate study design and the strong linkage disequilibrium demonstrated by genes across this locus. The majority of studies thus far have identified strong association with classical class II alleles, in particular HLA-DRB1*0301 and HLA-DRB1*1501. Additional associations have been reported with class III alleles; specifically, complement C4 null alleles and a tumor necrosis factor promoter SNP (TNF-308G/A). However, the relative effects of these class II and class III variants have not been determined. We have thus used a family-based approach to map association signals across the MHC class II and class III regions in a cohort of 314 complete United Kingdom Caucasian SLE trios by typing tagging SNPs together with classical typing of the HLA-DRB1 locus. Using TDT and conditional regression analyses, we have demonstrated the presence of two distinct and independent association signals in SLE: HLA-DRB1*0301 (nominal p = 4.9 × 10−8, permuted p < 0.0001, OR = 2.3) and the T allele of SNP rs419788 (nominal p = 4.3 × 10−8, permuted p < 0.0001, OR = 2.0) in intron 6 of the class III region gene SKIV2L. Assessment of genotypic risk demonstrates a likely dominant model of inheritance for HLA-DRB1*0301, while rs419788-T confers susceptibility in an additive manner. Furthermore, by comparing transmitted and untransmitted parental chromosomes, we have delimited our class II signal to a 180 kb region encompassing the alleles HLA-DRB1*0301-HLA-DQA1*0501-HLA-DQB1*0201 alone. Our class III signal importantly excludes independent association at the TNF promoter polymorphism, TNF-308G/A, in our SLE cohort and provides a potentially novel locus for future genetic and functional studies

'Countries in the Air': Travel and Geomodernism in Louis MacNeice's BBC Features

In the middle stretch of his twenty-two-year BBC career, the poet and producer Louis MacNeice earned a reputation as one of the ‘undisputed masters of creative sound broadcasting’, a reputation derived, in part, from a huge range of radio features that were founded upon his journeys abroad. Through close examination of some of his most significant overseas soundscapes – including Portrait of Rome (1947) and Portrait of Delhi (1948) – this article will consider the role and function of travel in shaping MacNeice’s engagement with the radio feature as a modernist form at a particular transcultural moment when Britain moved through the end of the Second World War and the eventual disintegration of its empire

Predictors of dizziness in older persons: a 10-year prospective cohort study in the community

BACKGROUND: The current diagnosis-oriented approach of dizziness does not suit older patients. Often, it is difficult to identify a single underlying cause, and when a diagnosis is made, therapeutic options may be limited. Identification of predictors of dizziness may provide new leads for the management of dizziness in older patients. The aim of the present study was to investigate long-term predictors of regular dizziness in older persons. METHODS: Population-based cohort study of 1,379 community-dwelling participants, aged ≥60 years, from the Longitudinal Aging Study Amsterdam (LASA). Regular dizziness was ascertained during face-to-face medical interviews during 7- and 10-year follow-up. We investigated 26 predictors at baseline from six domains: socio-demographic, medical history, medication, psychological, sensory, and balance/gait. We performed multivariate logistic regression analyses with presence of regular dizziness at 7- and 10-year follow-up as dependent variables. We assessed the performance of the models by calculating calibration and discrimination. RESULTS: Predictors of regular dizziness at 7-year follow-up were living alone, history of dizziness, history of osteo/rheumatoid arthritis, use of nitrates, presence of anxiety or depression, impaired vision, and impaired function of lower extremities. Predictors of regular dizziness at 10-year follow-up were history of dizziness and impaired function of lower extremities. Both models showed good calibration (Hosmer-Lemeshow P value of 0.36 and 0.31, respectively) and acceptable discrimination (adjusted AUC after bootstrapping of 0.77 and 0.71). CONCLUSIONS: Dizziness in older age was predicted by multiple factors. A multifactorial approach, targeting potentially modifiable predictors (e.g., physical exercise for impaired function of lower extremities), may add to the current diagnosis-oriented approach. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2318-14-133) contains supplementary material, which is available to authorized users

Trophoblast organoids as a model for maternal-fetal interactions during human placentation.

The placenta is the extraembryonic organ that supports the fetus during intrauterine life. Although placental dysfunction results in major disorders of pregnancy with immediate and lifelong consequences for the mother and child, our knowledge of the human placenta is limited owing to a lack of functional experimental models1. After implantation, the trophectoderm of the blastocyst rapidly proliferates and generates the trophoblast, the unique cell type of the placenta. In vivo, proliferative villous cytotrophoblast cells differentiate into two main sub-populations: syncytiotrophoblast, the multinucleated epithelium of the villi responsible for nutrient exchange and hormone production, and extravillous trophoblast cells, which anchor the placenta to the maternal decidua and transform the maternal spiral arteries2. Here we describe the generation of long-term, genetically stable organoid cultures of trophoblast that can differentiate into both syncytiotrophoblast and extravillous trophoblast. We used human leukocyte antigen (HLA) typing to confirm that the organoids were derived from the fetus, and verified their identities against four trophoblast-specific criteria3. The cultures organize into villous-like structures, and we detected the secretion of placental-specific peptides and hormones, including human chorionic gonadotropin (hCG), growth differentiation factor 15 (GDF15) and pregnancy-specific glycoprotein (PSG) by mass spectrometry. The organoids also differentiate into HLA-G+ extravillous trophoblast cells, which vigorously invade in three-dimensional cultures. Analysis of the methylome reveals that the organoids closely resemble normal first trimester placentas. This organoid model will be transformative for studying human placental development and for investigating trophoblast interactions with the local and systemic maternal environment.Centre for Trophoblast Reearch Royal Society Dorothy Hodgkin Fellowship Marie Curie Intra-European Fellowshi

Emerging therapies for severe asthma

Many patients with asthma have poorly controlled symptoms, and particularly for those with severe disease, there is a clear need for improved treatments. Two recent therapies licensed for use in asthma are omalizumab, a humanized monoclonal antibody that binds circulating IgE antibody, and bronchial thermoplasty, which involves the delivery of radio frequency energy to the airways to reduce airway smooth muscle mass. In addition, there are new therapies under development for asthma that have good potential to reach the clinic in the next five years. These include biological agents targeting pro-inflammatory cytokines such as interleukin-5 and interleukin-13, inhaled ultra long-acting β2-agonists and once daily inhaled corticosteroids. In addition, drugs that block components of the arachidonic acid pathway that targets neutrophilic asthma and CRTH2 receptor antagonists that inhibit the proinflammatory actions of prostaglandin D2 may become available. We review the recent progress made in developing viable therapies for severe asthma and briefly discuss the idea that development of novel therapies for asthma is likely to increasingly involve the assessment of genotypic and/or phenotypic factors

Profiling of Differentially Expressed Genes Using Suppression Subtractive Hybridization in an Equine Model of Chronic Asthma

Background :\ud Gene expression analyses are used to investigate signaling pathways involved in diseases. In asthma, they have been primarily derived from the analysis of bronchial biopsies harvested from mild to moderate asthmatic subjects and controls. Due to ethical considerations, there is currently limited information on the transcriptome profile of the peripheral lung tissues in asthma.\ud \ud Objective :\ud To identify genes contributing to chronic inflammation and remodeling in the peripheral lung tissue of horses with heaves, a naturally occurring asthma-like condition.\ud \ud Methods :\ud Eleven adult horses (6 heaves-affected and 5 controls) were studied while horses with heaves were in clinical remission (Pasture), and during disease exacerbation induced by a 30-day natural antigen challenge during stabling (Challenge). Large peripheral lung biopsies were obtained by thoracoscopy at both time points. Using suppression subtractive hybridization (SSH), lung cDNAs of controls (Pasture and Challenge) and asymptomatic heaves-affected horses (Pasture) were subtracted from cDNAs of horses with heaves in clinical exacerbation (Challenge). The differential expression of selected genes of interest was confirmed using quantitative PCR assay.\ud \ud Results :\ud Horses with heaves, but not controls, developed airway obstruction when challenged. Nine hundred and fifty cDNA clones isolated from the subtracted library were screened by dot blot array and 224 of those showing the most marked expression differences were sequenced. The gene expression pattern was confirmed by quantitative PCR in 15 of 22 selected genes. Novel genes and genes with an already defined function in asthma were identified in the subtracted cDNA library. Genes of particular interest associated with asthmatic airway inflammation and remodeling included those related to PPP3CB/NFAT, RhoA, and LTB4/GPR44 signaling pathways.\ud \ud Conclusions :\ud Pathways representing new possible targets for anti-inflammatory and anti-remodeling therapies for asthma were identified. The findings of genes previously associated with asthma validate this equine model for gene expression studies

The BELFRAIL (BFC80+) study: a population-based prospective cohort study of the very elderly in Belgium

In coming decades the proportion of very elderly people living in the Western world will dramatically increase. This forthcoming "grey epidemic" will lead to an explosion of chronic diseases. In order to anticipate booming health care expenditures and to assure that social security is funded in the future, research focusing on the relationship between chronic diseases, frailty and disability is needed. The general aim of the BELFRAIL cohort study (BFC80+) is to study the dynamic interaction between health, frailty and disability in a multi-system approach focusing on cardiac dysfunction and chronic heart failure, lung function, sarcopenia, renal insufficiency and immunosenescence