Biosynthesis of 3-thia-α-amino acids on a carrier peptide.

A subset of natural products, such as polyketides and nonribosomal peptides, is biosynthesized while tethered to a carrier peptide via a thioester linkage. Recently, we reported that the biosyntheses of 3-thiaglutamate and ammosamide, single amino acid-derived natural products, employ a very different type of carrier peptide to which the biosynthetic intermediates are bound via an amide linkage. During their biosyntheses, a peptide aminoacyl-transfer ribonucleic acid (tRNA) ligase (PEARL) first loads an amino acid to the C terminus of the carrier peptide for subsequent modification by other enzymes. Proteolytic removal of the modified C-terminal amino acid yields the mature product. We termed natural products that are biosynthesized using such pathways pearlins. To investigate the diversity of pearlins, in this study we experimentally characterized another PEARL-encoding biosynthetic gene cluster (BGC) from Tistrella mobilis (tmo). The enzymes encoded in the tmo BGC transformed cysteine into 3-thiahomoleucine both in vitro and in Escherichia coli. During this process, a cobalamin-dependent radical S-adenosylmethionine (SAM) enzyme catalyzes C-isopropylation. This work illustrates that the biosynthesis of amino acid-derived natural products on a carrier peptide is a widespread strategy in nature and expands the spectrum of thiahemiaminal analogs of amino acids that may serve a broader, currently unknown function.

The cumulation of ill health and low agency in socially excluded city dwellers in the Netherlands: how to better identify high-risk/high-need population segments with public health survey data.

BACKGROUND: Population segmentation and risk stratification are important strategies for allocating resources in public health, health care and social care. Social exclusion, which is defined as the cumulation of disadvantages in social, economic, cultural and political domains, is associated with an increased risk of health problems, low agency, and as a consequence, a higher need for health and social care. The aim of this study is to test social exclusion against traditional social stratifiers to identify high-risk/high-need population segments. METHODS: We used data from 33,285 adults from the 2016 Public Health Monitor of four major cities in the Netherlands. To identify at-risk populations for cardiovascular risk, cancer, low self-rated health, anxiety and depression symptoms, and low personal control, we compared relative risks (RR) and population attributable fractions (PAF) for social exclusion, which was measured with the Social Exclusion Index for Health Surveys (SEI-HS), and four traditional social stratifiers, namely, education, income, labour market position and migration background. RESULTS: The analyses showed significant associations of social exclusion with all the health indicators and personal control. Particular strong RRs were found for anxiety and depression symptoms (7.95) and low personal control (6.36), with corresponding PAFs of 42 and 35%, respectively. Social exclusion was significantly better at identifying population segments with high anxiety and depression symptoms and low personal control than were the four traditional stratifiers, while the two approaches were similar at identifying other health problems. The combination of social exclusion with a low labour market position (19.5% of the adult population) captured 67% of the prevalence of anxiety and depression symptoms and 60% of the prevalence of low personal control, as well as substantial proportions of the other health indicators. CONCLUSIONS: This study shows that the SEI-HS is a powerful tool for identifying high-risk/high-need population segments in which not only ill health is concentrated, as is the case with traditional social stratifiers, but also a high prevalence of anxiety and depression symptoms and low personal control are present, in addition to an accumulation of social problems. These findings have implications for health care practice, public health and social interventions in large cities.

Sense of mastery differences between working-age Swedish- and Finnish-speaking Finns: a population-based study.

AIM: To examine the probability of a high sense of mastery in a population-representative sample of working-age people and to study the differences in mastery between Finnish-speaking and Swedish-speaking Finns in particular. METHODS: The data originates from the Western Finland Mental Health Surveys (2008-2014). Associations between sense of mastery and language groups were analyzed with logistic regressions. RESULTS: Swedish-speaking Finns have a higher sense of mastery and the association is mediated by social support. Moreover, a difference in a high sense of mastery is found between Swedish- and Finnish-speaking married women that are outside the labor market. CONCLUSIONS: Our findings imply that Finnish-speaking women that are outside the labor market, e.g. on maternity leave or taking care of the household, should be recognized in health and social care services as a group that can benefit from additional support.

Caregiver stressors and depressive symptoms among older husbands and wives in the United States.

Framed by Pearlin's Stress Process Model, this study prospectively examines the effects of primary stress factors reflecting the duration, amount, and type of care on the depressive symptoms of spousal caregivers over a2-year period, and whether the effects of stressors differ between husbands and wives. Data are from the 2004 and 2006 waves of the Health and Retirement Study and we included community-dwelling respondents providing activities of daily life (ADL) and/or instrumental activities of daily life (IADL) help to their spouses/partners (N = 774). Results from multivariate regression models indicate that none of the primary stressors were associated with depressive symptoms. However, wives providing only personal care had significantly more depressive symptoms than wives providing only instrumental care, while husbands providing different types of care showed no such differences. To illuminate strategies for reducing the higher distress experienced by wife caregivers engaged in personal care assistance, further studies are needed incorporating couples' relational dynamics and gendered experiences in personal care.

Does becoming an ADL spousal caregiver increase the caregiver's depressive symptoms?

This study investigated whether transitioning into the role of activities of daily living (ADL) spousal caregiver is associated with increased depressive symptoms for older husbands and wives among a sample of coresiding community-dwelling older couples. Using data from the Health and Retirement Study, we estimated a two-level linear model to examine the association between change in caregiver status and respondents' depressive symptoms at follow-up, controlling for other factors identified in Pearlin's stress process model (PSPM). Results indicate that both husbands and wives who become ADL caregivers have more follow-up depressive symptoms than noncaregivers. Furthermore, wives continuing as caregivers have more follow-up depressive symptoms than wives who do not provide care. Finally, the physical health of the spousal caregiver is related to depressive symptoms at follow-up. We conclude with policy and practice implications of these three main findings.