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The social gradient in health – that individuals with lower SES have worse health than those with higher SES– is welldocumented using self-reports of health in more developed countries. Less is known about the relationship between SES and health biomarkers among older adults residing in less developed countries. We use data from the ChineseLongitudinal Healthy Longevity Survey (CLHLS) longevity areas sub-sample to examine the social gradient in healthamong rural young-old and oldest-old adults (N=2,121). Our health indicators include individual biomarkers, metabolic syndrome, and self-reports of health. We found a largely positive relationship between SES and health. SES was more consistently associated with individual biomarkers among the oldest-old than the young-old, providing evidence for cumulative disadvantage. We discuss the implications of our findings for older adults who have lived through different social, economic, and health regimes.

Jennifer Harrison Elder,1 Consuelo Maun Kreider,2 Susan N Brasher,3 Margaret Ansell4 1Department of Family and Community Health Nursing Science, 2Department of Occupational Therapy, University of Florida, Gainesville, FL, 3Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, 4Health Science Center Libraries, University of Florida, Gainesville, FL, USA Abstract: Autism spectrum disorder (ASD) refers to a lifelong condition that usually appears in late infancy or early childhood, and is characterized by social and communication deficits that impede optimal functioning. Despite widespread research and greater public awareness, ASD has an unclear etiology and no known cure, making it difficult to acquire accurate and timely diagnoses. In addition, once an ASD diagnosis is made, parents find it challenging to navigate the healthcare system and determine which interventions are most effective and appropriate for their child. A growing body of evidence supports the value of early diagnosis and treatment with evidence-based interventions, which can significantly improve the quality of life of individuals with ASD as well as of their carers and families. Particularly noteworthy are early interventions that occur in natural surroundings and can be modified to address age-related goals throughout the lifespan. Therefore, the purpose of this review is to: 1) provide readers with a brief background related to ASD; 2) describe commonly used screening instruments and tools for early diagnosis; 3) describe early interventions that have empirical support; and 4) discuss how the parent–child and family relationships can be affected through this process. This information can provide professionals with information they can use to assist families who make critical and potentially life-changing decisions for children with ASD. Keywords: autism spectrum disorder, ASD, early diagnosis, early intervention, parent–child relationship

Growth factor receptor-binding protein-2 (Grb2) plays a key role in signal transduction initiated by Bcr/Abl oncoproteins and growth factors, functioning as an adaptor protein through its Src homology 2 and 3 (SH2 and SH3) domains. We found that Grb2 was tyrosine-phosphorylated in cells expressing BCR/ABL and in A431 cells stimulated with epidermal growth factor (EGF). Phosphorylation of Grb2 by Bcr/Abl or EGF receptor reduced its SH3-dependent binding to Sos in vivo, but not its SH2-dependent binding to Bcr/Abl. Tyr209 within the C-terminal SH3 domain of Grb2 was identified as one of the tyrosine phosphorylation sites, and phosphorylation of Tyr209 abolished the binding of the SH3 domain to a proline-rich Sos peptide in vitro. In vivo expression of a Grb2 mutant where Tyr209 was changed to phenylalanine enhanced BCR/ABL-induced ERK activation and fibroblast transformation, and potentiated and prolonged Grb2-mediated activation of Ras, mitogen-activated protein kinase and c-Jun N-terminal kinase in response to EGF stimulation. These results suggest that tyrosine phosphorylation of Grb2 is a novel mechanism of down-regulation of tyrosine kinase signaling.

The catalytic activity of the c-Abl tyrosine kinase is tightly regulated by its Src homology 3 (SH3) domain through a complex mechanism that may involve intramolecular binding to Pro242 in the linker region between the SH2 and catalytic domains as well as interactions with a trans-inhibitor. We analysed the effect of mutation or replacement of SH3 on c-Abl tyrosine kinase activity and transformation. Random mutagenesis of SH3 identified several novel point mutations that dysregulated c-Abl kinase activity in vivo, but the RT loop was insensitive to mutational activation. Activating SH3 mutations abolished binding of proline-rich SH3 ligands in vitro, while mutations at Ser140 in the connector between the SH3 and SH2 domains activated Abl kinase activity in vivo and in vitro but did not impair SH3 ligand-binding. Abl was regulated efficiently when its SH3 domain was replaced with a heterologous SH3 from c-Src that binds a different spectrum of proline-rich ligands, but not by substitution of a modular WW domain with similar ligand-binding specificity. These results suggest that the SH3 domain regulates Abl principally by binding to the atypical intramolecular ligand Pro242 rather than a canonical PxxP ligand. Coordination between the SH3 and SH2 domains mediated by the connector region may be required for regulation of Abl even in the absence of SH2 ligand binding.

University ranking systems are being implemented with the aim of assessing and comparing higher education institutions at a global level. Despite their being increasingly used, rankings are often strongly criticized for their social and economic implications, as well as for limitations in their technical implementation. One of these limitations is that they do not consider the specific characteristics of online education. This study used a participatory approach to define a set of criteria and indicators suitable to reflect the specific nature of distance education. This endeavour will help evaluate and rank online higher education institutions more appropriately than in current practice, where indicators are devised for traditional universities. To this end, several stakeholders and informants were involved in a Delphi study in an attempt to reach the broader higher education institutions (HEI) community. According to the study participants, apart from students’ achievements and general quantitative measures of HEI performance, which are quite common in traditional ranking systems, teaching and student learning experience turned out to be the most important criteria. Student support, teacher support, technological infrastructure, research and organization were deemed middle ground criteria, while sustainability and reputation were regarded as the least important criteria.

Using the specific Abl tyrosine kinase inhibitor STI 571, we purified unphosphorylated murine type IV c-Abl and measured the kinetic parameters of c-Abl tyrosine kinase activity in a solution with a peptide-based assay. Unphosphorylated c-Abl exhibited substantial peptide kinase activity with K(m) of 204 microm and V(max) of 33 pmol min(-1). Contrary to previous observations using immune complex kinase assays, we found that a transforming c-Abl mutant with a Src homology 3 domain point mutation (P131L) had significantly (about 6-fold) higher intrinsic kinase activity than wild-type c-Abl (K(m) = 91 microm, V(max) = 112 pmol min(-1)). Autophosphorylation stimulated the activity of wild-type c-Abl about 18-fold and c-Abl P131L about 3.6-fold, resulting in highly active kinases with similar catalytic rates. The autophosphorylation rate was dependent on Abl protein concentration consistent with an intermolecular reaction. A tyrosine to phenylalanine mutation (Y412F) at the c-Abl residue homologous to the c-Src catalytic domain autophosphorylation site impaired the activation of wild-type c-Abl by 90% but reduced activation of c-Abl P131L by only 45%. Mutation of a tyrosine (Tyr-245) in the linker region between the Src homology 2 and catalytic domains that is conserved among the Abl family inhibited the autophosphorylation-induced activation of wild-type c-Abl by 50%, whereas the c-Abl Y245F/Y412F double mutant was minimally activated by autophosphorylation. These results support a model where c-Abl is inhibited in part through an intramolecular Src homology 3-linker interaction and stimulated to full catalytic activity by sequential phosphorylation at Tyr-412 and Tyr-245.

In 1993, writing about their years of feminist collaboration, Carey Kaplan and Ellen Cronan Rose explained that while they sometimes found such endeavors challenging, ultimately they were "exhilarating, consoling, and precious" (559). In the years since then, those working in women and gender studies have continued to advocate for collaboration in the academy, calling for interdisciplinary studies and team teaching. In this essay, the authors (a literature specialist, a sociologist, and a historian) discuss their experiences with feminist interdisciplinary collaboration, reflecting on team teaching Introduction to Women's Studies since 2012. After laying out the philosophical and theoretical background for their pedagogy (feminism, collaboration, and interdisciplinarity), they discuss the theme that unites their research and teaching interests across discipline boundaries and provides an organizing principle for their course: "Gender, Confinement, and Freedom." The authors then show how the course culminates in two collaborative and memorable experiences. The first, a class visit to the Maryland Correction Institution for Women, connects what they have been talking about in the classroom to the world outside the classroom. The second, an end-of-course discussion of and writing project on Harriet Jacobs's 1861 "Incidents in the Life of a Slave Girl," serves to tie the entire semester together. In the next section, the authors assess the class based on three criteria: critical understanding of the course theme, implementation of an interdisciplinary perspective, and awareness of implications beyond academia. In the conclusion, the authors reflect on what they learned and discuss ideas for changes moving forward. Ultimately, they show that although they succeeded on the first two criteria, they have more work to do if they want to fulfill the promise and potential of feminist pedagogy.

Currently, the administration of surfactant to preterm infants with respiratory distress syndrome (RDS) mainly relies on intratracheal instillation; however, there is increasing evidence of aerosolized surfactant being an effective non-invasive strategy. We present a historical narrative spanning sixty years of development of aerosolization systems. We also offer an overview of the pertinent mechanisms needed to create and manage the ideal aerosolization system, with a focus on delivery, distribution, deposition, and dispersion in the context of the human lung. More studies are needed to optimize treatment with aerosolized surfactants, including determination of ideal dosages, nebulizer types, non-invasive interfaces, and breath synchronization. However, the field is rapidly evolving, and widespread clinical use may be achieved in the near future.

Despite the advent of effective, curative treatments for hepatitis C virus (HCV), a preventative vaccine remains essential for the global elimination of HCV. It is now clear that the induction of broadly neutralising antibodies (bNAbs) is essential for the rational design of such a vaccine. This review details the current understanding of epitopes on the HCV envelope, characterising the potency, breadth and immunodominance of antibodies induced against these epitopes, as well as describing the interactions between B-cell receptors and HCV infection, with a particular focus on bNAb heavy and light chain variable gene usage. Additionally, we consider the importance of a public repertoire for antibodies against HCV, compiling current knowledge and suggesting that further research in this area may be critical to the rational design of an effective HCV vaccine.