Type II phosphoinositide 5-phosphatases have unique sensitivities towards fatty acid composition and head group phosphorylation

AbstractThe catalytic properties of the type II phosphoinositide 5-phosphatases of Lowe's oculocerebrorenal syndrome, INPP5B, Synaptojanin1, Synaptojanin2 and SKIP were analysed with respect to their substrate specificity and enzymological properties. Our data reveal that all phosphatases have unique substrate specificities as judged by their corresponding KM and VMax values. They also possessed an exclusive sensitivity towards fatty acid composition, head group phosphorylation and micellar presentation. Thus, the biological function of these enzymes will not just be determined by their corresponding regulatory domains, but will be distinctly influenced by their catalytic properties as well. This suggests that the phosphatase domains fulfil a unique catalytic function that cannot be fully compensated by other phosphatases

ASD and the Future: “The Times They Are A Changin’”

Today’s generation of autistic people at the precipice of transitioning into adulthood face great opportunity as well as great struggles ahead of them. This workshop will present grassroots personal and professional efforts to develop responsive educational, vocational, and social programs that lead to quality transitions to college, work opportunities, entrepreneurship possibilities, and daily living/relationship success. Neurodiverse, strengths-based orientations with be discussed with respect to developing identities from personal, familial, cultural, and community perspectives. Professional and parent panel members will join Dr. Mitchell from Foundations Behavioral Health, The Center for Autism, and Ruttenberg Autism Center

Staurosporine Induces a Sequential Program of Mouse Keratinocyte Terminal Differentiation through Activation of PKC Isozymes

Staurosporine (stsp) induces assembly of cornified envelopes in mouse keratinocyte cultures. To clarify whether this effect is the consequence of a coordinated differentiation program similar to that observed in epidermis, we assessed the expression of multiple differentiation-specific markers in stsp-treated keratinocytes. In medium containing 0.05mM Ca2+ in which the basal cell phenotype is normally maintained, stsp induced dose-dependent increases in keratin 1, epidermal and keratinocyte transglutaminases, SPR-1, loricrin, and profilaggrin mRNA. Based on nuclear run-on analysis, stsp-mediated marker expression was found to be due at least in part to increased transcription. Since protein kinase C (PKC) activation is required for keratinocyte differentiation, we tested whether stsp influenced this signaling pathway. Stsp induced the translocation of multiple PKC isoforms from the cytosol to membrane and/or cytoskeletal fractions, inducing isozyme downregulation within 24h. Moreover, AP-1 DNA binding activity was elevated in stsp-treated keratinocytes, consistent with the notion that this agent influences keratinocyte-specific gene expression via the PKC pathway. Stsp-mediated marker expression was inhibited by the PKC inhibitor GF 109203X. In cells pre-treated with bryostatin 1 to selectively down-modulate specific PKC isoforms, stsp-induced loricrin, filaggrin, and SPR-1 expression was suppressed when PKC α, ϵ, and/or δ were downregulated, suggesting that these isozymes may be necessary for marker expression in response to this agent. Thus, in addition to its effects on cornified envelope assembly, stsp induces a coordinate program of differentiation-specific keratinocyte gene expression that is mediated at least in part by the PKC signaling pathway

Implications of Visual Social Access on the Welfare and Behavior of Shelter Dogs

Animal shelter environments have many stressful factors that impact the welfare of shelter dogs, such as lack of predictability and control, and social isolation. Social isolation has been found to increase abnormal behavior and lead to poorer adoption outcomes. Providing visual access to shelter dogs is a relatively easy environmental modification that increases social opportunities and allows for more predictability and control over the environment, potentially improving welfare. To investigate the impact of visual access on the behavior of dogs, we used a within-subject design, conducting 5-min focal observations four times weekly before, during, and after visual access was provided by partially removing a barrier between crates at a suburban dog shelter. Our preliminary analysis of 17 subjects using non-parametric Friedman’s Tests (alpha = .05) found no significant difference between phases in regard to anxiety behaviors (χ2 (2) = .50, p = .78), frustration behaviors (χ2 (2) = .51, p = .77), time spent in the front of the crate (χ2 (2) = 4.50, p = .11), self-directed behaviors (χ2 (2) = 1.86, p = .40), resting behaviors (χ2 (2) = 4.59, p = .10), or vocalizations (χ2 (2) = 4.59, p = .10). The absence of an increase in vocalizations during visual access may encourage shelters to implement this change. However, the lack of a decrease in anxiety or frustration behaviors may indicate that visual access alone is insufficient for providing welfare benefits and that shelters should prioritize increasing social contact in dogs through playgroups or group housing

#6 - Implications of Visual Social Access on the Welfare and Behavior of Shelter Dogs

Given the large number of dogs housed in animal shelters each year, it is important to consider how the shelter environment impacts dog welfare. The shelter environment is stressful due to factors such as excessive noise, lack of predictability and control, and social isolation. Social isolation in shelter dogs has been found to increase abnormal behavior and aggression and lead to poorer adoption outcomes. While social housing is ideal, it requires resources not available to all shelters. Providing visual access to other dogs is a relatively easy environmental modification that increases social opportunities and allows for more predictability and control over the environment, potentially improving welfare. To investigate the impact of visual access on the behavior of dogs, we used a within-subject design, conducting 5-min focal observations four times weekly before, during, and after visual access was provided by partially removing a barrier between crates at a suburban dog shelter. Our preliminary analysis of 17 subjects using non-parametric Friedman’s Tests (alpha = .05) found no significant difference between phases in regard to anxiety behaviors (χ2 (2) = .50, p = .78), frustration behaviors (χ2 (2) = .51, p = .77), time spent in the front of the crate (χ2 (2) = 4.50, p = .11), self-directed behaviors (χ2 (2) = 1.86, p = .40), resting behaviors (χ2 (2) = 4.59, p = .10), or vocalizations (χ2 (2) = 4.59, p= .10). The absence of an increase in vocalizations during visual access may encourage shelters to implement this change. However, the lack of a decrease in anxiety or frustration behaviors may indicate that visual access alone is insufficient for providing welfare benefits and that shelters should prioritize increasing social contact in dogs through playgroups or group housing. Keywords: shelter dog, animal welfare, barking, social housing, visual access, social contact, anxiety, environmental predictability, choic

Femoral Artery Atherosclerosis Is Associated With Physical Function Across the Spectrum of the Ankle-Brachial Index: The San Diego Population Study.

BackgroundThe ankle-brachial index (ABI) is inadequate to detect early-stage atherosclerotic disease, when interventions to prevent functional decline may be the most effective. We determined associations of femoral artery atherosclerosis with physical functioning, across the spectrum of the ABI, and within the normal ABI range.Methods and resultsIn 2007-2011, 1103 multiethnic men and women participated in the San Diego Population Study, and completed all components of the summary performance score. Using Doppler ultrasound, superficial and common femoral intima media thickness and plaques were ascertained. Logistic regression was used to assess associations of femoral atherosclerosis with the summary performance score and its individual components. Models were adjusted for demographics, lifestyle factors, comorbidities, lipids, and kidney function. In adjusted models, among participants with a normal-range ABI (1.00-1.30), the highest tertile of superficial intima media thickness was associated with lower odds of a perfect summary performance score of 12 (odds ratio=0.56 [0.36, 0.87], P=0.009), and lower odds of a 4-m walk score of 4 (0.34 [0.16, 0.73], P=0.006) and chair rise score of 4 (0.56 [0.34, 0.94], P=0.03). Plaque presence (0.53 [0.29, 0.99], P=0.04) and greater total plaque burden (0.61 [0.43, 0.87], P=0.006) were associated with worse 4-m walk performance in the normal-range ABI group. Higher superficial intima media thickness was associated with lower summary performance score in all individuals (P=0.02).ConclusionsFindings suggest that use of femoral artery atherosclerosis measures may be effective in individuals with a normal-range ABI, especially, for example, those with diabetes mellitus or a family history of peripheral artery disease, when detection can lead to earlier intervention to prevent functional declines and improve quality of life

Feasibility and acceptability of electronic symptom surveillance with clinician feedback using the Patient-Reported Outcomes version of Common Terminology Criteria for Adverse Events (PRO-CTCAE) in Danish prostate cancer patients

Abstract Background The aim was to examine the feasibility, acceptability and clinical utility of electronic symptom surveillance with clinician feedback using a subset of items drawn from the Patient-Reported Outcomes version of Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a cancer treatment setting. Methods Danish-speaking men with castration-resistant metastatic prostate cancer receiving treatment at the Department of Oncology, Rigshospitalet, Copenhagen between March 9, 2015 and June 8, 2015 were invited to participate (n = 63 eligible). Participants completed the PRO-CTCAE questionnaire on tablet computers using AmbuFlex software at each treatment visit in the outpatient clinic. In total, 22 symptomatic toxicities (41 PRO-CTCAE items), corresponding to the symptomatic adverse-events profile associated with the regimens commonly used for prostate cancer treatment (Docetaxel, Cabazitaxel, Abiraterone, Alpharadin), were selected. Participants’ PRO-CTCAE responses were presented graphically to their treating oncologists via an AmbuFlex dashboard, for real-time use to enhance the patient-clinician dialogue that occurs during the consultation prior to each treatment cycle. Technical and clinical barriers and acceptability were evaluated through semi-structured interviews with both patients and oncologists. Patients receiving active treatment at the end of the study period completed an evaluation questionnaire. Results Fifty-four out of sixty-three (86%) eligible patients were enrolled. The PRO-CTCAE questionnaire was completed a total of 168 times by 54 participants (median number per patient was 3, range 1–5). Eight surveys were missed, resulting in a compliance rate of 97%. At the end of the study period, 35 patients (65%) were still receiving active treatment and completed the evaluation questionnaire. Patients reported that their PRO-CTCAE responses served as a communication tool. Oncologists stated that the availability of the PRO-CTCAE self-reports during the consultation improved patient-clinician communication about side effects. Conclusion Electronic capture of symptomatic toxicities using PRO-CTCAE and the submission of self-reports to clinicians prior to consultation were feasible among metastatic prostate cancer patients receiving chemotherapy in an outpatient setting, and this procedure was acceptable to both patients and clinicians. Continued research, including a cluster-randomized trial, will evaluate the effects of submitting patients’ PRO-CTCAE results to clinicians prior to consultation on the quality of side-effects management and resultant clinical outcomes

Framing Scientific Analyses for Risk Management of Environmental Hazards by Communities: Case Studies with Seafood Safety Issues

Risk management provides a context for addressing environmental health hazards. Critical to this approach is the identification of key opportunities for participation. We applied a framework based on the National Research Council’s (NRC) analytic–deliberative risk management dialogue model that illustrates two main iterative processes: informing and framing. The informing process involves conveying information from analyses of risk issues, often scientific, to all parties so they can participate in deliberation. In the framing process, ideas and concerns from stakeholder deliberations help determine what and how scientific analyses will be carried out. There are few activities through which affected parties can convey their ideas from deliberative processes for framing scientific analyses. The absence of participation results in one-way communication. The analytic–deliberative dialogue, as envisioned by the NRC and promoted by the National Institute of Environmental Health Sciences (NIEHS), underscores the importance of two-way communication. In this article we present case studies of three groups—an Asian and Pacific Islander community coalition and two Native American Tribes—active in framing scientific analyses of health risks related to contaminated seafood. Contacts with these organizations were established or enhanced through a regional NIEHS town meeting. The reasons for concern, participation, approaches, and funding sources were different for each group. Benefits from their activities include increased community involvement and ownership, better focusing of analytical processes, and improved accuracy and appropriateness of risk management. These examples present a spectrum of options for increasing community involvement in framing analyses and highlight the need for increased support of such activities