New Structural and Functional Contexts of the Dx[DN]xDG Linear Motif: Insights into Evolution of Calcium-Binding Proteins

Binding of calcium ions (Ca2+) to proteins can have profound effects on their structure and function. Common roles of calcium binding include structure stabilization and regulation of activity. It is known that diverse families – EF-hands being one of at least twelve – use a Dx[DN]xDG linear motif to bind calcium in near-identical fashion. Here, four novel structural contexts for the motif are described. Existing experimental data for one of them, a thermophilic archaeal subtilisin, demonstrate for the first time a role for Dx[DN]xDG-bound calcium in protein folding. An integrin-like embedding of the motif in the blade of a β-propeller fold – here named the calcium blade – is discovered in structures of bacterial and fungal proteins. Furthermore, sensitive database searches suggest a common origin for the calcium blade in β-propeller structures of different sizes and a pan-kingdom distribution of these proteins. Factors favouring the multiple convergent evolution of the motif appear to include its general Asp-richness, the regular spacing of the Asp residues and the fact that change of Asp into Gly and vice versa can occur though a single nucleotide change. Among the known structural contexts for the Dx[DN]xDG motif, only the calcium blade and the EF-hand are currently found intracellularly in large numbers, perhaps because the higher extracellular concentration of Ca2+ allows for easier fixing of newly evolved motifs that have acquired useful functions. The analysis presented here will inform ongoing efforts toward prediction of similar calcium-binding motifs from sequence information alone

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Activation of persons living with HIV for treatment, the great study Health behavior, health promotion and society

Background: Patient empowerment represents a potent tool for addressing racial, ethnic and socioeconomic disparities in health care, particularly for chronic conditions such as HIV infection that require active patient engagement. This multimodal intervention, developed in concert with HIV patients and clinicians, aims to provide HIV patients with the knowledge, skills, attitudes and tools to become more activated patients. Methods/design: Randomized controlled trial of a multimodal intervention designed to activate persons living with HIV. The intervention includes four components: 1) use of a web-enabled hand-held device (Apple iPod Touch) loaded with a Personal Health Record (ePHR) customized for HIV patients; 2) six 90-minute group-based training sessions in use of the device, internet and the ePHR; 3) a pre-visit coaching session; and 4) clinician education regarding how they can support activated patients. Outcome measures include pre- post changes in patient activation measure score (primary outcome), eHealth literacy, patient involvement in decision-making and care, medication adherence, preventive care, and HIV Viral Load. Discussion: We hypothesize that participants receiving the intervention will show greater improvement in empowerment and the intervention will reduce disparities in study outcomes. Disparities in these measures will be smaller than those in the usual care group. Findings have implications for activating persons living with HIV and for other marginalized groups living with chronic illness. Trial registration: ClinicalTrials.gov Identifier: NCT02165735, 6/13/2014

Values and options in cancer care (VOICE): study design and rationale for a patient-centered communication and decision-making intervention for physicians, patients with advanced cancer, and their caregivers

Abstract Background Communication about prognosis and treatment choices is essential for informed decision making in advanced cancer. This article describes an investigation designed to facilitate communication and decision making among oncologists, patients with advanced cancer, and their caregivers. Methods/design The Values and Options in Cancer Care (VOICE) Study is a National Cancer Institute sponsored randomized controlled trial conducted in the Rochester/Buffalo, NY and Sacramento, CA regions. A total of 40 oncologists, approximately 400 patients with advanced cancer, and their family/friend caregivers (one per patient, when available) are expected to enroll in the study. Drawing upon ecological theory, the intervention uses a two-pronged approach: oncologists complete a multifaceted tailored educational intervention involving standardized patient instructors (SPIs), and patients and caregivers complete a coaching intervention to facilitate prioritizing and discussing questions and concerns. Follow-up data will be collected approximately quarterly for up to three years. Discussion The intervention is hypothesized to enhance patient-centered communication, quality of care, and patient outcomes. Analyses will examine the effects of the intervention on key elements of physician-patient-caregiver communication (primary outcomes), the physician-patient relationship, shared understanding of prognosis, patient well-being, and health service utilization (secondary outcomes). Trial registration Clinical Trials Identifier: NCT0148562