Partners in Conflict: The Politics of Gender, Sexuality, and Labor in The Chilean Agrarian Reform, 1950-1973, by Heidi Tinsman

Histor

A follow-up study of girls who graduated from the vocational school at Worcester, Massachusetts, during the years 1937-1947

Thesis (M.A.)--Boston University, 1949. This item was digitized by the Internet Archive

A realist process evaluation of Enhanced Triple P for Baby and Mellow Bumps, within a Trial of Healthy Relationship Initiatives for the Very Early years (THRIVE): study protocol for a randomized controlled trial

Background: THRIVE is a three-arm randomised controlled trial (RCT) that aims to evaluate whether antenatal and early postnatal interventions, Enhanced Triple B for Baby (ETPB) plus care as usual (CAU) or Mellow Bumps (MB) plus CAU (versus CAU alone), can: 1) improve the mental health and well-being of pregnant women with complex health and social care needs; 2) improve mother-infant bonding and interaction; 3) reduce child maltreatment; and 4) improve child language acquisition. This paper focuses on THRIVE’s realist process evaluation, which is carefully monitoring what is happening in the RCT. Methods: Realistic evaluation provides the theoretical rationale for the process evaluation. We question: 1) how faithfully are MB and ETPB implemented? 2) What are the mechanisms by which they work, if they do, and who do they work for and how? 3) What contextual factors are necessary for the programmes to function, or might prevent them functioning? The mixed-methods design includes quantitative measures, which are pre- and post-training/intervention questionnaires for facilitators and mothers-to-be, and post-session evaluation forms. Qualitative data collection methods include participant observation of facilitator training and the delivery of a series of antenatal sessions in selected intervention groups (n = 3 for ETPB and n = 3 for MB), semi-structured interviews with facilitators, pregnant women, partners, and referring facilitators, and telephone interviews examining the content of the postnatal components of ETPB and MB. Discussion: The findings of this process evaluation will help researchers and decision makers interpret the outcomes of THRIVE. It will provide a greater understanding of: how the interventions work (if they do); the extent and quality of their implementation; contextual factors facilitating and constraining intervention functioning; variations in response within and between subgroups of vulnerable parents; and benefits or unintended consequences of either intervention. Few studies to date have published detailed research protocols illustrating how realist process evaluation is designed and conducted as an integral part of a randomised controlled trial

Navigating later life transitions: An evaluation of emotional and psychological interventions

Transitions in later life, for instance retiring from paid work, changing career, ending or starting a relationship, can have a major impact on people’s lives and their wellbeing. Recognising a gap in preventative support for transitions such as these, the Calouste Gulbenkian Foundation (CGF; UK Branch) has funded a number of projects that provide group-based psychological and emotional support as part of its Transitions in Later Life (TiLL) programme. CGF and the Centre for Ageing Better partnered on the evaluation of two of these courses — Working Longer and Living Life to the Full, a two-day course run by Cheshire and Wirral Partnership NHS Foundation Trust (CWP) and Changing Gears, a three-day course run by Age & Opportunity in Dublin, Ireland. The aim of the evaluation was to find out what impact the courses had on individual attributes that would help people be better prepared for later life transitions; what changes people make as a result of the courses; and what practice, resources or processes in the organisations are important in ensuring their implementation and efficacy

A genome-wide study replicates linkage of 3p22-24 to extreme longevity in humans and identifies possible additional loci

Journal ArticleBackground: Although there is abundant evidence that human longevity is heritable, efforts to map loci responsible for variation in human lifespan have had limited success. Methodology/Principal Findings: We identified individuals from a large multigenerational population database (the Utah Population Database) who exhibited high levels of both familial longevity and individual longevity. This selection identified 325 related ‘‘affected individuals'', defined as those in the top quartile for both excess longevity (EL = observed lifespan - expected lifespan) and familial excess longevity (FEL = weighted average EL across all relatives). A whole-genome scan for genetic linkage was performed on this sample using a panel of 1100 microsatellite markers. A strongly suggestive peak (Z = 4.2, Monte Carlo-adjusted p-value 0.09) was observed in the vicinity of D3S3547 on chromosome 3p24.1, at a point nearly identical to that reported recently by an independent team of researchers from Harvard Medical School (HMS) [1]. Meta-analysis of linkage scores on 3p from the two studies produced a minimum nominal p-value of 1.00561029 at 55 cM. Other potentially noteworthy peaks in our data occur on 18q23-24, 8q23, and 17q21. Meta-analysis results from combined UPDB and HMS data yielded additional support, but not formal replication, for linkage on 8q, 9q, and 17q. Conclusions/Significance: Corroboration of the linkage of exceptional longevity to 3p22-24 greatly strengthens the case that genes in this region affect variation in longevity and suggest, therefore, an important role in the regulation of human lifespan. Future efforts should include intensive study of the 3p22-24 region

Genetic structure of the Utah Mormons: comparison of results based on RFLPs, blood groups, migration matrices, isonymy, and pedigrees

Journal ArticleThe genetic structure of the Utah Mormon population is examined using 25 blood group and 47 RFLP alleles obtained from 442 subjects living in 8 geographic subdivisions. Nei's Gst was 0.013 (p 0.4) for the blood group data, showing that only 1% of the genetic variance in this population can be attributed to subdivision effects. A comparison of intersubdivision distance matrices based on blood groups, RFLPs, migration matrices, isonymy, and pedigrees shows that genetic distances have relatively low and nonsignificant correlations with the other three types of data

Redox Signaling in Eukaryotic DNA Replication and Repair

DNA-mediated charge transport chemistry (DNA CT) offers an intriguing regulatory mechanism in biology, as it is long-range, rapid, and sensitive to mismatches and perturbations to base stacking. DNA-processing enzymes in all three domains of life moreover have been shown to contain [4Fe4S] clusters, commonly redox cofactors. Bacterial [4Fe4S] repair proteins have been shown to signal one another using long-range DNA-mediated charge transport (DNA CT), facilitating the redistribution to damaged genomic DNA in cells. The role of metabolically expensive, [4Fe4S] cluster cofactors in eukaryotic systems, however, was less clear than in prokaryotes. Here we examine the chemical role of the [4Fe4S] cluster in eukaryotic DNA primase and the human base excision repair glycosylase, MUTYH. The primase cluster functions as a redox switch regulating DNA binding and redox signaling activity in humans and yeast. Yeast moreover require the primase redox switch for viability. Human MUTYH, a bifunctional glycosylase which repairs oxidative DNA lesions, performs DNA-mediated redox signaling, similarly to the bacterial homologue MutY. The MUTYH mutation which destabilizes the [4Fe4S] cluster during redox signaling, C306W, promotes degradation and loss of activity, associated with hereditary colorectal cancer. To assess the redox role of the human primase [4Fe4S] cluster, we perform anaerobic DNA electrochemistry on the [4Fe4S] domain of human primase (p58C), which independently binds DNA. On DNA-modified Au electrodes, we compare the redox activity of electrochemically oxidized and electrochemically reduced p58C. Oxidized [4Fe4S]3+ p58C is electrochemically active, and reduced [4Fe4S]2+ p58C state is redox-inert. This redox-driven switch is electrochemically reversible, and is mediated by a triad of conserved tyrosines between the DNA binding interface and [4Fe4S] cluster. Mutation of residues Y309, Y345, and Y347 to phenylalanine causes attenuation of redox switching on DNA. Single-atom mutations in the redox pathway moreover compromise initiation and truncation of primer synthesis but do not affect RNA polymerase activity. We find that primase truncation is gated by DNA CT in vitro; a single mismatch in the nascent primer abrogates truncation of primase products. As primase is tethered to DNA polymerase α, a putative [4Fe4S] enzyme to which primase hands off the RNA-primed template, we propose that DNA-mediated signaling between primase and polymerase α chemically regulates this handoff during the first steps of replication. Eukaryotic primase must bind both DNA and nucleotide triphosphates (NTPs) in order to convert to active form. Using DNA electrochemistry we show that p58C, and full-length DNA primase, display a robust, semi-reversible NTP-dependent signal on DNA, centered near 150mV vs. NHE. This signal is dependent on the tyrosine redox pathway. The presence of reversible redox activity at a physiological potential when primase is bound to DNA and NTPs suggests that reversible redox switching from the [4Fe4S]2+ to the [4Fe4S]3+ state is important for the activity of primase during replication. The cluster serves as a redox switch governing DNA binding in yeast primase, just as in human primase. Mutation of tyrosines 395 and 397 in yeast primase moreover, alters the same electron transfer chemistry as the mutation of their orthologues, Y345 and Y347, respectively, alters in human primase. Although these tyrosines are arranged differently in the yeast and human proteins, they perform the same reaction to affect the switch. The single-atom Y395F mutation causes some sensitivity to chemically induced oxidative stress in yeast, and single-residue mutation Y397L confers lethality in yeast cells. A constellation of tyrosines for protein-DNA electron transfer mediates the redox switch in eukaryotic primases, regulates the affinity for RNA-primed DNA template, and is required for primase function in vivo. We finally characterize a novel mutation in the [4Fe4S] human base excision repair protein, MUTYH, which destabilizes the cluster environment and has pathogenic consequences. The MUTYH C306W mutation alters one of the cysteines coordinating the cluster to tryptophan. This mutation moreover is associated with hereditary colorectal cancer and causes defective DNA binding and enzymatic activity. We perform DNA electrochemistry on WT MUTYH, as well as C306W and two cancer-associated mutants, Y197C and G396D, which have an unaltered cluster environment. MUTYH variants participate in redox signaling, but C306W is destabilized upon oxidation from the [4Fe4S]2+ to the [4Fe4S]3+ state during signaling on DNA, leading to degradation to a [3Fe4S]+ cluster and loss of DNA binding and activity. A [4Fe4S] human DNA repair enzyme performs redox signaling on DNA; dysregulation of this signaling activity is linked to tumorigenesis.</p