Characterization of a single genomic locus encoding the clustered protocadherin receptor diversity in Xenopus tropicalis

Clustered protocadherins (cPcdhs) constitute the largest subgroup of the cadherin superfamily (Hulpiau & van Roy, 2009) and in mammals are grouped into clusters of alpha-, beta- and gamma-types. Tens of tandemly-arranged paralogous Pcdh genes of the protocadherin clusters generate a substantial diversity of receptor isoforms. cPcdhs are known to have important roles in neuronal development and genetic alterations of cPcdhs have been found to be associated with several neurological diseases. Here, we present a first characterization of cPcdhs in Xenopus tropicalis (X. tropicalis). We determined and annotated all cPcdh isoforms revealing that they are present in a single chromosomal locus. We validated a total of 96 isoforms, which we show are organized in three distinct clusters. The X. tropicalis cPcdh locus is composed of one alpha- and two distinct gamma-protocadherin clusters (pcdh-gamma1 and pcdh-gamma2). Bioinformatics analyses assisted by genomic BAC clone sequencing showed that the X. tropicalis alpha- and gamma-protocadherins are conserved at the cluster level, but unlike mammals, X. tropicalis does not contain a beta-protocadherin cluster. In contrast, the number of gamma-protocadherin isoforms has expanded possibly due to lineage-specific gene duplications. Interestingly, the number of X. tropicalis alpha-protocadherins is identical between X. tropicalis and mouse. Moreover, we find highly conserved as well as novel promoter elements potentially involved in regulating the cluster-specific expression of clustered protocadherin isoforms. This study provides important information for the understanding of the evolutionary history of cPcdh genes and future mechanistic studies. It provides an annotated X. tropicalis cPcdh genomic map and a first molecular characterization essential for functional and comparative studies

Evaluating outcomes from an integrated health service for older patients

Background: Hospital-associated disability is the loss of the ability to complete one activity of daily living (ADL), with this decline occurring between the onset of acute illness and discharge from the hospital. Approximately 30% of patients who are >70 years old and admitted to hospitals are discharged with an ADL disability. Comprehensive geriatric assessment (CGA) models use a multidimensional, interdisciplinary process of diagnosis and treatment with the goal of improving outcomes and decreasing lengths of stay. Methods: A retrospective clinical audit of Ipswich Hospital’s medical records included patients for random selection who were >75 years of age and had an acute admission to the Older Person Evaluation Review and Assessment (OPERA) or general medicine (GM) service from July 2012 to December 2012. Data were collected for the entire admission period on length of stay, comorbidities, allied health visits, functional ability, and delirium and dementia at admission. Results: Of the 267 patients evaluated, 133 were admitted to the OPERA service, and 134 were admitted to the GM service. Patients admitted to the OPERA service were significantly more ill than patients admitted to the GM service as measured by the Charlson Comorbidity Index scores (6.53 - 1.83 vs 6.02 - 1.96, respectively, P¼0.02), Katz Index of Independence in ADL scores (3.77 - 2.22 vs 4.72 - 2.00, respectively,

Regulation of Drosophila Brain Wiring by Neuropil Interactions via a Slit-Robo-RPTP Signaling Complex

The axonal wiring molecule Slit and its Round-About (Robo) receptors are conserved regulators of nerve cord patterning. Robo receptors also contribute to wiring brain circuits. Whether molecular mechanisms regulating these signals are modified to fit more complex brain wiring processes is unclear. We investigated the role of Slit and Robo receptors in wiring Drosophila higher-order brain circuits and identified differences in the cellular and molecular mechanisms of Robo/Slit function. First, we find that signaling by Robo receptors in the brain is regulated by the Receptor Protein Tyrosine Phosphatase RPTP69d. RPTP69d increases membrane availability of Robo3 without affecting its phosphorylation state. Second, we detect no midline localization of Slit during brain development. Instead, Slit is enriched in the mushroom body, a neuronal structure covering large areas of the brain. Thus, a divergent molecular mechanism regulates neuronal circuit wiring in the Drosophila brain, partly in response to signals from the mushroom body

Amblyopia and quality of life: a systematic review

Background/Aims Amblyopia is a common condition which can affect up to 5% of the general population. The health-related quality of life (HRQoL) implications of amblyopia and/or its treatment have been explored in the literature. Methods A systematic literature search was undertaken (16th-30th January 2007) to identify the HRQoL implications of amblyopia and/or its treatment. Results A total of 25 papers were included in the literature review. The HRQoL implications of amblyopia related specifically to amblyopia treatment, rather than the condition itself. These included the impact upon family life; social interactions; difficulties undertaking daily activities; and feelings and behaviour. The identified studies adopted a number of methodologies. The study populations included; children with the condition; parents of children with amblyopia; and adults who had undertaken amblyopia treatment as a child. Some studies developed their own measures of HRQoL, and others determined HRQoL through proxy measures. Conclusions The reported findings of the HRQoL implications are of importance when considering the management of cases of amblyopia. Further research is required to assess the immediate and long-term effects of amblyopia and/or its treatment upon HRQoL using a more standardised approach

Aging and the Environment: A Research Framework

The rapid growth in the number of older Americans has many implications for public health, including the need to better understand the risks posed to older adults by environmental exposures. Biologic capacity declines with normal aging; this may be exacerbated in individuals with pre-existing health conditions. This decline can result in compromised pharmacokinetic and pharmacodynamic responses to environmental exposures encountered in daily activities. In recognition of this issue, the U.S. Environmental Protection Agency (EPA) is developing a research agenda on the environment and older adults. The U.S. EPA proposes to apply an environmental public health paradigm to better understand the relationships between external pollution sources → human exposures → internal dose → early biologic effect → adverse health effects for older adults. The initial challenge will be using information about aging-related changes in exposure, pharmacokinetic, and pharmacodynamic factors to identify susceptible subgroups within the diverse population of older adults. These changes may interact with specific diseases of aging or medications used to treat these conditions. Constructs such as “frailty” may help to capture some of the diversity in the older adult population. Data are needed regarding a) behavior/activity patterns and exposure to the pollutants in the microenvironments of older adults; b) changes in absorption, distribution, metabolism, and excretion with aging; c) alterations in reserve capacity that alter the body’s ability to compensate for the effects of environmental exposures; and d) strategies for effective communication of risk and risk reduction methods to older individuals and communities. This article summarizes the U.S. EPA’s development of a framework to address and prioritize the exposure, health effects, and risk communications concerns for the U.S. EPA’s evolving research program on older adults as a susceptible subpopulation

Age-related differences in integrin expression in peripheral blood lymphocytes

Alpha integrins play an important role in cell to cell and cell to extra-cellular matrix interactions required for an effective T-lymphocyte-mediated immune response, however little is known about age related differences in expression of alpha integrins on T-cells in humans. We here measured alpha-4 (α4) integrin (CD49d) expression on T-lymphocytes via peripheral blood sampling, comparing parameters between cohorts of young and old adults. No age-related differences were found for the absolute numbers of T-cells, although the percentage of CD4+ T-cells in older adults was significantly greater and the percentage of CD8+ T-cells lower than in younger cohorts. Percentage and absolute numbers of CD3+ T-cells co-expressing CD49d were significantly lower in older adults compared to younger cohorts, and the percentage of gated CD4+ and CD8+ cells that co-labelled positively for CD49d was also reduced in this group. There were no age-related differences in circulating levels of cytokines (Type I interferons) that are known to regulate cell surface integrin expression. Reduced expression of alpha integrins on T-cells may be an early indicator of the loss of homeostatic control that occurs with ageing, contributing to diminished effector T-cell responses during senescence

Preoperative acute inflammatory markers as predictors for postoperative complications in primary total knee arthroplasty

Background: C-reactive protein (CRP) has been suggested as an independent risk factor for cardiovascular pathology in the nonsurgical setting. While postoperative CRP and erythrocyte sedimentation rate (ESR) have an established role in aiding the diagnosis of periprosthetic joint infections, some authors suggest a link between preoperative CRP and postoperative complications in patients undergoing total joint arthroplasty. Methods: We conducted a retrospective cohort study of 351 patients who underwent unilateral primary total knee arthroplasty by a single surgeon during a 28-month period (January 2013 through April 2015). Patient medical records were reviewed for the following complications occurring within 90 days postoperatively: myocardial infarction, arrhythmia, pulmonary embolism, wound infection, acute renal failure, and reoperation. Results: We found no statistically significant link between postoperative complications and preoperative CRP levels (P=0.5005) or ESR levels (P=0.1610). Conclusion: The results of this study do not support the routine inclusion of CRP and ESR analysis as part of the preoperative evaluation for elective total knee arthroplasty