Changing environments and genetic variation: natural variation in inbreeding does not compromise short-term physiological responses

Selfing plant lineages are surprisingly widespread and successful in a broad range of environments, despite showing reduced genetic diversity, which is predicted to reduce their long-term evolutionary potential. However, appropriate short-term plastic responses to new environmental conditions might not require high levels of standing genetic variation. In this study, we tested whether mating system variation among populations, and associated changes in genetic variability, affected short-term responses to environmental challenges. We compared relative fitness and metabolome profiles of naturally outbreeding (genetically diverse) and inbreeding (genetically depauperate) populations of a perennial plant, Arabidopsis lyrata, under constant growth chamber conditions and an outdoor common garden environment outside its native range. We found no effect of inbreeding on survival, flowering phenology or short-term physiological responses. Specifically, naturally occurring inbreeding had no significant effects on the plasticity of metabolome profiles, using either multivariate approaches or analysis of variation in individual metabolites, with inbreeding populations showing similar physiological responses to outbreeding populations over time in both growing environments. We conclude that low genetic diversity in naturally inbred populations may not always compromise fitness or short-term physiological capacity to respond to environmental change, which could help to explain the global success of selfing mating strategies

Changing environments and genetic variation: natural variation in inbreeding does not compromise short-term physiological responses

Selfing plant lineages are surprisingly widespread and successful in a broad range of environments, despite showing reduced genetic diversity, which is predicted to reduce their long-term evolutionary potential. However, appropriate short-term plastic responses to new environmental conditions might not require high levels of standing genetic variation. In this study, we tested whether mating system variation among populations, and associated changes in genetic variability, affected short-term responses to environmental challenges. We compared relative fitness and metabolome profiles of naturally outbreeding (genetically diverse) and inbreeding (genetically depauperate) populations of a perennial plant, Arabidopsis lyrata, under constant growth chamber conditions and an outdoor common garden environment outside its native range. We found no effect of inbreeding on survival, flowering phenology or short-term physiological responses. Specifically, naturally occurring inbreeding had no significant effects on the plasticity of metabolome profiles, using either multivariate approaches or analysis of variation in individual metabolites, with inbreeding populations showing similar physiological responses to outbreeding populations over time in both growing environments. We conclude that low genetic diversity in naturally inbred populations may not always compromise fitness or short-term physiological capacity to respond to environmental change, which could help to explain the global success of selfing mating strategies

Emergency Department Discharge Instructions: Lessons Learned through Developing New Patient Education Materials

Our multidisciplinary team developed a new set of discharge instructions for five common emergency department diagnoses using recommended tools for creating literacy-appropriate and patient-centered education materials. We found that the recommended tools for document creation were essential in constructing the new instructions. However, while the tools were necessary, they were not sufficient. This paper describes the insights gained and lessons learned in this document creation process

Loss of α2-6 sialylation promotes the transformation of synovial fibroblasts into a pro-inflammatory phenotype in arthritis

In healthy joints, synovial fibroblasts (SFs) provide the microenvironment required to mediate homeostasis, but these cells adopt a pathological function in rheumatoid arthritis (RA). Carbohydrates (glycans) on cell surfaces are fundamental regulators of the interactions between stromal and immune cells, but little is known about the role of the SF glycome in joint inflammation. Here we study stromal guided pathophysiology by mapping SFs glycosylation pathways. Combining transcriptomic and glycomic analysis, we show that transformation of fibroblasts into pro-inflammatory cells is associated with glycan remodeling, a process that involves TNF-dependent inhibition of the glycosyltransferase ST6Gal1 and α2-6 sialylation. SF sialylation correlates with distinct functional subsets in murine experimental arthritis and remission stages in human RA. We propose that pro-inflammatory cytokines remodel the SF-glycome, converting the synovium into an under-sialylated and highly pro-inflammatory microenvironment. These results highlight the importance of glycosylation in stromal immunology and joint inflammation

Sedentary time in older men and women: an international consensus statement and research priorities

Sedentary time is a modifiable determinant of poor health, and in older adults, reducing sedentary time may be an important first step in adopting and maintaining a more active lifestyle. The primary purpose of this consensus statement is to provide an integrated perspective on current knowledge and expert opinion pertaining to sedentary behaviour in older adults on the topics of measurement, associations with health outcomes, and interventions. A secondary yet equally important purpose is to suggest priorities for future research and knowledge translation based on gaps identified. A five-step Delphi consensus process was used. Experts in the area of sedentary behaviour and older adults (n=15) participated in three surveys, an in-person consensus meeting, and a validation process. The surveys specifically probed measurement, health outcomes, interventions, and research priorities. The meeting was informed by a literature review and conference symposium, and it was used to create statements on each of the areas addressed in this document. Knowledge users (n=3) also participated in the consensus meeting. Statements were then sent to the experts for validation. It was agreed that self-report tools need to be developed for understanding the context in which sedentary time is accumulated. For health outcomes, it was agreed that the focus of sedentary time research in older adults needs to include geriatric-relevant health outcomes, that there is insufficient evidence to quantify the dose-response relationship, that there is a lack of evidence on sedentary time from older adults in assisted facilities, and that evidence on the association between sedentary time and sleep is lacking. For interventions, research is needed to assess the impact that reducing sedentary time, or breaking up prolonged bouts of sedentary time has on geriatric-relevant health outcomes. Research priorities listed for each of these areas should be considered by researchers and funding agencies

The continuum of fetal alcohol spectrum disorders in a community in South Africa: Prevalence and characteristics in a fifth sample

The prevalence and characteristics of the continuum of diagnoses within fetal alcohol spectrum disorders (FASD) were researched in a fifth sample in a South African community

Breastfeeding and maternal alcohol use: Prevalence and effects on child outcomes and fetal alcohol spectrum disorders

Determine any effects that maternal alcohol consumption during the breastfeeding period has on child outcomes

Clinical heterogeneity can hamper the diagnosis of patients with ZAP70 deficiency

One of the severe combined immunodeficiencies (SCIDs), which is caused by a genetic defect in the signal transduction pathways involved in T-cell activation, is the ZAP70 deficiency. Mutations in ZAP70 lead to both abnormal thymic development and defective T-cell receptor (TCR) signaling of peripheral T-cells. In contrast to the lymphopenia in most SCID patients, ZAP70-deficient patients have lymphocytosis, despite the selective absence of CD8+ T-cells. The clinical presentation is usually before 2 years of age with typical findings of SCID. Here, we present three new ZAP70-deficient patients who vary in their clinical presentation. One of the ZAP70-deficient patients presented as a classical SCID, the second patient presented as a healthy looking wheezy infant, whereas the third patient came to clinical attention for the eczematous skin lesions simulating atopic dermatitis with eosinophilia and elevated immunoglobulin E (IgE), similar to the Omenn syndrome. This study illustrates that awareness of the clinical heterogeneity of ZAP70 deficiency is of utmost importance for making a fast and accurate diagnosis, which will contribute to the improvement of the adequate treatment of this severe immunodeficiency

UBVRI Light Curves of 44 Type Ia Supernovae

We present UBVRI photometry of 44 type-Ia supernovae (SN Ia) observed from 1997 to 2001 as part of a continuing monitoring campaign at the Fred Lawrence Whipple Observatory of the Harvard-Smithsonian Center for Astrophysics. The data set comprises 2190 observations and is the largest homogeneously observed and reduced sample of SN Ia to date, nearly doubling the number of well-observed, nearby SN Ia with published multicolor CCD light curves. The large sample of U-band photometry is a unique addition, with important connections to SN Ia observed at high redshift. The decline rate of SN Ia U-band light curves correlates well with the decline rate in other bands, as does the U-B color at maximum light. However, the U-band peak magnitudes show an increased dispersion relative to other bands even after accounting for extinction and decline rate, amounting to an additional ~40% intrinsic scatter compared to B-band.Comment: 84 authors, 71 pages, 51 tables, 10 figures. Accepted for publication in the Astronomical Journal. Version with high-res figures and electronic data at http://astron.berkeley.edu/~saurabh/cfa2snIa

Cardiovascular Outcomes and the Physical and Chemical Properties of Metal Ions Found in Particulate Matter Air Pollution: a QICAR Study

Background: This paper presents an application of quantitative ion character–activity relationships (QICAR) to estimate associations of human cardiovascular (CV) diseases (CVDs) with a set of metal ion properties commonly observed in ambient air pollutants. QICAR has previously been used to predict ecotoxicity of inorganic metal ions based on ion properties