Unfolded states under folding conditions accommodate sequence-specific conformational preferences with random coil-like dimensions

Proteins are marginally stable molecules that fluctuate between folded and unfolded states. Here, we provide a high-resolution description of unfolded states under refolding conditions for the N-terminal domain of the L9 protein (NTL9). We use a combination of time-resolved Förster resonance energy transfer (FRET) based on multiple pairs of minimally perturbing labels, time-resolved small-angle X-ray scattering (SAXS), all-atom simulations, and polymer theory. Upon dilution from high denaturant, the unfolded state undergoes rapid contraction. Although this contraction occurs before the folding transition, the unfolded state remains considerably more expanded than the folded state and accommodates a range of local and nonlocal contacts, including secondary structures and native and nonnative interactions. Paradoxically, despite discernible sequence-specific conformational preferences, the ensemble-averaged properties of unfolded states are consistent with those of canonical random coils, namely polymers in indifferent (theta) solvents. These findings are concordant with theoretical predictions based on coarse-grained models and inferences drawn from single-molecule experiments regarding the sequence-specific scaling behavior of unfolded proteins under folding conditions

An Internet-based self-help intervention for people with HIV and depressive symptoms: study protocol for a randomized controlled trial

BACKGROUND: Many people living with HIV suffer from depressive symptoms. In a previous pilot study, self-help cognitive behavioral therapy (in booklet format) was found to be effective in treating depressive symptoms in people with HIV. We developed an online self-help program in Dutch and English (based on the booklet) for people with HIV and depressive symptoms. Besides the main question regarding the effectiveness of the program aimed at lowering depressive symptoms, sub-questions will focus on the moderators of treatment success (for which patients is the program especially beneficial?) and the mechanisms of change underlying the treatment outcome (which mediators affect the outcome of treatment?). In this paper, the protocol of the study will be described. METHODS/DESIGN: The effectiveness of the program will be investigated by comparing the intervention group with a waiting list-control group in a randomized controlled design, by including a pretest and three post-tests. The self-help program contains four main components: activation, relaxation, changing maladaptive cognitions, and goal attainment. Participants with mild to moderate depressive symptoms will work on the program for 6 to 10 weeks, during which a coach will provide motivational support by telephone once a week. Participants in the control condition will receive weekly minimal support from a coach for 8 weeks, and after the second post-test, they can gain access to the self-help program. Depressive symptoms and possible mediators (e.g., activation, cognitive coping, self-efficacy, and goal adjustment) will be assessed by self-report three times during the intervention/waiting period and at the pretest and first post-test. DISCUSSION: The proposed study aims to evaluate the effectiveness of an online self-help intervention for people with HIV and depressive symptoms. If the intervention is shown to be effective, the program will be implemented. Consequently, many patients with HIV could be reached, and their psychological care may be improved. TRIAL REGISTRATION: Netherlands Trial Register: NTR5407 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1292-6) contains supplementary material, which is available to authorized users

Adversity and syndemic production among men participating in the multicenter AIDS cohort study: A life-course approach

Objectives. We tested a theory of syndemic production among men who have sex with men (MSM) using data from a large cohort study. Methods. Participants were 1551 men from the Multicenter AIDS Cohort Study enrolled at 4 study sites: Baltimore, Maryland-Washington, DC; Chicago, Illinois; Los Angeles, California; and Pittsburgh, Pennsylvania. Participants who attended semiannual visits from April 1, 2008, to March 31, 2009, completed an additional survey that captured data about events throughout their life course thought to be related to syndemic production. Results. Using multivariate analysis, we found that the majority of life-course predictor variables (e.g., victimization, internalized homophobia) were significantly associated with both the syndemic condition and the component psychosocial health outcomes (depressive symptoms, stress, stimulant use, sexual compulsivity, intimate partner violence). A nested negative binomial analysis showed that the overall life course significantly explained variability in the syndemic outcomes (χ2 = 247.94; P < .001; df = 22). Conclusions. We identified life-course events and conditions related to syndemic production that may help to inform innovative interventions that will effectively disentangle interconnecting health problems and promote health among MSM. Copyright © 2012 by the American Public Health Association®

High-Resolution Mass Spectrometry to Identify and Quantify Acetylation Protein Targets.

The dynamic nature of protein posttranslational modification (PTM) allows cells to rapidly respond to changes in their environment, such as nutrition, stress, or signaling. Lysine residues are targets for several types of modifications, including methylation, ubiquitination, and various acylation groups, especially acetylation. Currently, one of the best methods for identification and quantification of protein acetylation is immunoaffinity enrichment in combination with high-resolution mass spectrometry. As we are using a relatively novel and comprehensive mass spectrometric approach, data-independent acquisition (DIA), this protocol provides high-throughput, accurate, and reproducible label-free PTM quantification. Here we describe detailed protocols to process relatively small amounts of mouse liver tissue that integrate isolation of proteins, proteolytic digestion into peptides, immunoaffinity enrichment of acetylated peptides, identification of acetylation sites, and comprehensive quantification of relative abundance changes for thousands of identified lysine acetylation sites

Columnar aerosol optical and radiative properties according to season and air mass transport pattern over East Asia

The column-integrated optical and radiative properties of aerosols in the downwind area of East Asia were investigated based on sun/sky radiometer measurements performed from February 2004 to June 2005 at Gwangju (35.23A degrees N, 126.84A degrees E) and Anmyeon (36.54A degrees N, 126.33A degrees E), Korea. The observed aerosol data were analyzed for differences among three seasons: spring (March-May), summer (June-August), and autumn/winter (September-February). The data were also categorized into five types depending on the air mass origin in arriving in the measurement sites: (a) from a northerly direction in spring (S-N), (b) from a westerly direction in spring (S-W), (c) cases with a low ngstrom exponent (<0.8) in spring (dust), (d) from a northerly direction in autumn/winter (AW(N)), and (e) from a westerly direction during other seasons (AW(W)). The highest ngstrom exponents (alpha) at Gwangju and Anmyeon were 1.43 A +/- 0.30 and 1.49 A +/- 0.20, respectively, observed in summer. The lowest column-mean single-scattering albedo (omega) at 440 nm observed at Gwangju and Anmyeon were 0.89 A +/- 0.02 and 0.88 A +/- 0.02, respectively, during a period marked by the advection of dust from the Asian continent. The highest omega values at Gwangju and Anmyeon were 0.95 A +/- 0.02 and 0.96 A +/- 0.02, respectively, observed in summer. Variations in the aerosol radiative-forcing efficiency (beta) were related to the conditions of the air mass origin. The forcing efficiency in summer was -131.7 and -125.6 W m(-2) at the surface in Gwangju and Anmyeon, respectively. These values are lower than those under the atmospheric conditions of spring and autumn/winter. The highest forcing efficiencies in autumn/winter were -214.3 and -255.9 W m(-2) at the surface in Gwangju and Anmyeon, respectively, when the air mass was transported from westerly directions.Peer reviewe

Suicidal Ideation, Resilience, and Healthcare Implications for Newly Diagnosed HIV-Positive Men Who Have Sex with Men in China: A Qualitative Study

Globally, suicidal ideation and behavior have been widely reported among people living with human immunodeficiency virus (HIV). Knowledge gaps exist regarding the longer life and resilience-related experiences of people living with HIV (PLWH). Specifically, there is a dearth of data about the interaction of perceived risk and resilient factors resulting in a wide spectrum of intentional suicidal ideation outcomes in a Chinese cultural context. This qualitative research drew from a larger ethnographic study of newly diagnosed HIV-positive men who have sex with men (MSM) in Mainland China. Interviews were conducted with 31 MSM within 6 months of diagnosis of HIV infection. Initial suicidal ideation was commonly reported with participants subsequently feeling more resilient to these thoughts through gaining a greater understanding of their prognosis and treatment. Post-HIV diagnosis, some participants reported forming new relationships and receiving increased support from their partners, friends, peers, families, and community-based organizations. At follow-up, these participants generally reported suicidal ideation had declined. However, participants who continued to express suicidal ideation perceived extended pressure from their families’ expectations for them to engage in heterosexual marriages and parenthood. Furthermore, these men reported ongoing hardships in their daily life, unemployment, lack of social support, and isolation. Among this Mainland Chinese cohort of HIV-positive MSM, suicidal ideation may be a transient phenomenon experienced initially following HIV diagnosis that resolves with increased and specific familial, social, and service-based support. It is crucial to identify the causes of stress and social suffering associated with HIV diagnosis in order to reduce suicidal ideation. In China, action is needed to develop routine mental health screening and to increase services that support PLWH. Important services mechanism to accomplish this are promoting resilience through intentional activities as well as continued public health campaigns to reduce stigma toward HIV-positive MSM