Novel venom gene discovery in the platypus

Background: To date, few peptides in the complex mixture of platypus venom have been identified and sequenced, in part due to the limited amounts of platypus venom available to study. We have constructed and sequenced a cDNA library from an active platypus venom gland to identify the remaining components.Results: We identified 83 novel putative platypus venom genes from 13 toxin families, which are homologous to known toxins from a wide range of vertebrates (fish, reptiles, insectivores) and invertebrates (spiders, sea anemones, starfish). A number of these are expressed in tissues other than the venom gland, and at least three of these families (those with homology to toxins from distant invertebrates) may play non-toxin roles. Thus, further functional testing is required to confirm venom activity. However, the presence of similar putative toxins in such widely divergent species provides further evidence for the hypothesis that there are certain protein families that are selected preferentially during evolution to become venom peptides. We have also used homology with known proteins to speculate on the contributions of each venom component to the symptoms of platypus envenomation.Conclusions: This study represents a step towards fully characterizing the first mammal venom transcriptome. We have found similarities between putative platypus toxins and those of a number of unrelated species, providing insight into the evolution of mammalian venom

Examining the Role of Narrative Performance Appraisal Comments on Performance

Despite their prevalence in performance appraisal systems and purported importance in theory, narrative performance appraisal comments have been rarely examined. This study aimed to contribute to the literature by developing and testing a theory of quality narrative feedback. The author argues that managerial feedback that is both directive (i.e., lengthy, specific, and includes goals) and motivational (i.e., positive and high in interactional justice) would be related to year-lagged performance. Negative and positive emotions are also proposed as mediators of this relationship. Performance appraisal comments were coded for a sample of 1,019 clinical nurses. The structural equations modeling results provided preliminary evidence that feedback favorability and interactional justice demonstrated significant direct and indirect (through positive and negative emotion) effects on year-lagged employee performance. © 2013 Copyright Taylor and Francis Group, LLC

Attitudes Toward Disability: The Relationship Between Attitudes Toward Disability and Frequency of Interaction with People with Disabilities (PWD)

The social and medical models of disability are sets of underlying assumptions explaining people's beliefs about the causes and implications of disability. The medical model is the predominant model in the United States that is associated with the belief that disability is an undesirable status that needs to be cured (Darling & Heckert, 2010). This model focuses on the diagnosis, treatment and curative efforts related to disability. The social model is preferred by disability activists and researchers which focuses on society’s involvement in disability, such as stigmatization, discrimination and the interpersonal barriers that are features of one’s disability. The social model suggests that society disables individuals and is the cause of impairment (Olkin, 2003). Allport’s contact hypothesis states that increased contact with people with disabilities (PWD) will reduce prejudice through relationship building and social connection (Allport, 1954). Pettigrew’s Intergroup Contact Theory, similar to Allport’s contact hypothesis, argues that essential conditions must be met in order to reduce feelings of prejudice. These conditions are: learning about the outgroup, changing behavior, generating affective ties, and ingroup reappraisal (Pettigrew, 1998). Based on these theories, increased interaction with PWD should result in more favorable attitudes about PWD. We further propose that contact may serve to alter disability model orientation, which in turn may affect attitudes. This is the first large-scale study that examines how disability models influence the relationship between contact and attitudes toward PWD. It was hypothesized that participants with more frequent interactions with PWD would have more favorable attitudes towards disability. This would be mediated by models of disability. Participants of the study were undergraduate students enrolled in a required university course, with a majority of them being in their first year. The survey consisted of the Attitudes Toward Disabled Persons scale, a single item assessing frequency of contact with PWD, and the Darling (2013) social and medical model scales, and was distributed to a total of 1,506 students. Supporting our hypothesis, the medical and social models partially mediated the relationship between contact and attitudes towards disability. Medical model compared to social model was more strongly associated with contact and attitudes. This suggests that contact with PWD can help decrease medical model beliefs in general, but is less effective at promoting social model beliefs. Implications of this study might suggest that more frequent contact with PWD on college campuses could be possible by hiring more educators who disclose their disability or accommodate to more people with disabilities as students. As for future directions of this study, an expansion beyond college students could provide insight into different demographics and their attitudes toward disability, and could also reveal the potential influence of cohort effects. Future studies may also want to further assess to what degree attitudes and perceptions about PWD change when certain conditions are met, such as those mentioned in Pettigrew’s Intergroup Contact Theory

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

Development and Validation of a Symptom-Based Activity Index for Adults With Eosinophilic Esophagitis

Standardized instruments are needed to assess the activity of eosinophilic esophagitis (EoE), to provide endpoints for clinical trials and observational studies. We aimed to develop and validate a patient-reported outcome (PRO) instrument and score, based on items that could account for variations in patients’ assessments of disease severity. We also evaluated relationships between patients’ assessment of disease severity and EoE-associated endoscopic, histologic, and laboratory findings