SecA, a remarkable nanomachine

Biological cells harbor a variety of molecular machines that carry out mechanical work at the nanoscale. One of these nanomachines is the bacterial motor protein SecA which translocates secretory proteins through the protein-conducting membrane channel SecYEG. SecA converts chemically stored energy in the form of ATP into a mechanical force to drive polypeptide transport through SecYEG and across the cytoplasmic membrane. In order to accommodate a translocating polypeptide chain and to release transmembrane segments of membrane proteins into the lipid bilayer, SecYEG needs to open its central channel and the lateral gate. Recent crystal structures provide a detailed insight into the rearrangements required for channel opening. Here, we review our current understanding of the mode of operation of the SecA motor protein in concert with the dynamic SecYEG channel. We conclude with a new model for SecA-mediated protein translocation that unifies previous conflicting data

The DISC (Diabetes in Social Context) Study-evaluation of a culturally sensitive social network intervention for diabetic patients in lower socioeconomic groups: a study protocol

<p>Abstract</p> <p>Background</p> <p>Compared to those in higher socioeconomic groups, diabetic patients in lower socioeconomic groups have less favourable metabolic control and experience more diabetes-related complications. They encounter specific barriers that hinder optimal diabetes self-management, including a lack of social support and other psychosocial mechanisms in their immediate social environments. <it>Powerful Together with Diabetes </it>is a culturally sensitive social network intervention specifically targeted to ethnic Dutch, Moroccan, Turkish, and Surinamese diabetic patients in lower socioeconomic groups. For ten months, patients will participate in peer support groups in which they will share experiences, support each other in maintaining healthy lifestyles, and learn skills to resist social pressure. At the same time, their significant others will also receive an intervention, aimed at maximizing support for and minimizing the negative social influences on diabetes self-management. This study aims to test the effectiveness of <it>Powerful Together with Diabetes</it>.</p> <p>Methods/Design</p> <p>We will use a quasi-experimental design with an intervention group (Group 1) and two comparison groups (Groups 2 and 3), N = 128 in each group. Group 1 will receive <it>Powerful Together with Diabetes</it>. Group 2 will receive <it>Know your Sugar</it>, a six-week group intervention that does not focus on the participants' social environments. Group 3 receives standard care only. Participants in Groups 1 and 2 will be interviewed and physically examined at baseline, 3, 10, and 16 months. We will compare their haemoglobin A1C levels with the haemoglobin A1C levels of Group 3. Main outcome measures are haemoglobin A1C, diabetes-related quality of life, diabetes self-management, health-related, and intermediate outcome measures. We will conduct a process evaluation and a qualitative study to gain more insights into the intervention fidelity, feasibility, and changes in the psychosocial mechanism in the participants' immediate social environments.</p> <p>Discussion</p> <p>With this study, we will assess the feasibility and effectiveness of a culturally sensitive social network intervention for lower socioeconomic groups. Furthermore, we will study how to enable these patients to optimally manage their diabetes. This trial is registered in the Dutch Trial Register: NTR1886</p

Co- and post-translational translocation through the protein-conducting channel:analogous mechanisms at work?

Many proteins are translocated across, or integrated into, membranes. Both functions are fulfilled by the 'translocon/translocase', which contains a membrane-embedded proteinconducting channel (PCC) and associated soluble factors that drive translocation and insertion reactions using nucleotide triphosphates as fuel. This perspective focuses on reinterpreting existing experimental data in light of a recently proposed PCC model comprising a front-to-front dimer of SecY or Sec61 heterotrimeric complexes. In this new framework, we propose (i) a revised model for SRP-SR-mediated docking of the ribosome-nascent polypeptide to the PCC; (ii) that the dynamic interplay between protein substrate, soluble factors and PCC controls the opening and closing of a transmembrane channel across, and/or a lateral gate into, the membrane; and (iii) that co-and post-translational translocation, involving the ribosome and SecA, respectively, not only converge at the PCC but also use analogous mechanisms for coordinating protein translocation

Recruiting Chinese Americans into cancer screening intervention trials: Strategies and outcomes

BACKGROUND: Cancer is the leading cause of death among Asian Americans. While Asian Americans are the fastest growing minority population in the United States, they are under-represented in cancer research and report poor adherence to cancer screening guidelines. PURPOSE: This study utilized data from two large randomized intervention trials to evaluate strategies to recruit first-generation Chinese American immigrants from community settings and Chinese American physician practices. Findings will inform effective strategies for promoting Asian American participation in cancer control research. METHODS: Chinese Americans who were nonadherent to annual mammography screening guidelines (Study 1 with 664 immigrant women >age 40) and to colorectal cancer screening guidelines (Study 2 with 455 immigrants >age 50) were enrolled from the greater Washington DC, New York City (NYC), and Philadelphia (PA) areas. Both studies trained bilingual staff to enroll Chinese-speaking participants with the aid of linguistically appropriate fliers and brochures to obtain consent. Study 1 adopted community approaches and worked with community organizations to enroll participants. Study 2 randomly selected potential participants through 24 Chinese American primary care physician offices, and mailed letters from physicians to enroll patients, followed by telephone calls from research staff. The success of recruitment approaches was assessed by yield rates based on number of participants approached, ineligible, and consented. RESULTS: Most participants (70%) of Study 1 were enrolled through in-person community approaches (e.g, Chinese schools, stores, health fairs, and personal networks). The final yield of specific venues differed widely (6% to 100%) due to various proportions of ineligible subjects (2% to 64%) and refusals (0% to 92%). The Study 2 recruitment approach (physician letter followed by telephone calls) had different outcomes in two geographic areas, partially due to differences in demographic characteristics in the DC and NYC/PA areas. The community approaches enrolled more recent immigrants and uninsured Chinese Americans than the physician and telephone call approach (p<.001). Enrollment cost is provided to inform future research studies. LIMITATIONS: Our recruitment outcomes might not be generalizable to all Chinese Americans or other Asian American populations because they may vary by study protocols (e.g., length of trials), target populations (i.e., eligibility criteria), and available resources. CONCLUSIONS: Use of multiple culturally relevant strategies (e.g., building trusting relationships through face-to-face enrollment, use of bilingual and bicultural staff, use of a physician letter, and employing linguistically appropriate materials) was crucial for successfully recruiting a large number of Chinese Americans in community and clinical settings. Our data demonstrates that substantial effort is required for recruitment; studies need to budget for this effort to ensure the inclusion of Asian Americans in health research