Structure of the DNA repair helicase XPD.

The XPD helicase (Rad3 in Saccharomyces cerevisiae) is a component of transcription factor IIH (TFIIH), which functions in transcription initiation and Nucleotide Excision Repair in eukaryotes, catalyzing DNA duplex opening localized to the transcription start site or site of DNA damage, respectively. XPD has a 5' to 3' polarity and the helicase activity is dependent on an iron-sulfur cluster binding domain, a feature that is conserved in related helicases such as FancJ. The xpd gene is the target of mutation in patients with xeroderma pigmentosum, trichothiodystrophy, and Cockayne's syndrome, characterized by a wide spectrum of symptoms ranging from cancer susceptibility to neurological and developmental defects. The 2.25 A crystal structure of XPD from the crenarchaeon Sulfolobus tokodaii, presented here together with detailed biochemical analyses, allows a molecular understanding of the structural basis for helicase activity and explains the phenotypes of xpd mutations in humans.

The consequences of increased 4E-BP1 in polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, characterized by cyst formation and growth. Hyperproliferation is a major contributor to cyst growth. At the nexus of regulating proliferation, is 4E-BP1. We demonstrate that ADPKD mouse and rat models, ADPKD patient renal biopsies and PKD1-/- cells exhibited hyperphosphorylated 4E-BP1, a biomarker of increased translation and proliferation. We hypothesized that expression of constitutively active 4E-BP1 constructs (4E-BP1F113A and 4E-BP1R13AF113A) would decrease proliferation and reduce cyst expansion. Utilizing the Pkd1RC/RC mouse, we determined the effect of 4E-BP1F113A on PKD. Unexpectedly, 4E-BP1F113A resulted in increased cyst burden and suppressed apoptosis markers, increased anti-apoptotic Bcl-2 protein and increased mitochondrial proteins. Exogenous 4E-BP1 enhanced proliferation, decreased apoptosis, increased anti-apoptotic Bcl-2 protein, impaired NADPH oxidoreductase activity, increased mitochondrial proteins and increased superoxide production in PKD patient-derived renal epithelial cells. Reduced 4E-BP1 expression suppressed proliferation, restored apoptosis and improved cellular metabolism. These findings provide insight into how cyst-lining cells respond to 4E-BP1.

The effects of dosage and duration of auditory training for older adults with hearing impairment.

This study explored a range of training dosages and durations for a word-based auditory-training procedure for older adults with hearing impairment. Three groups received a different "dose": 2x/week; 3x/week; no training. Fifteen training sessions comprised a "cycle" which was repeated three times for each dosage. Groups that completed training performed significantly better than controls for speech-in-noise materials included in the training regimen, with no significant difference observed between the 2x or 3x/week training groups. Based on these results, as well as prior literature on learning theory, training 2x or 3x/week for 5-15 weeks appears to be sufficient to yield training benefits with this training regimen.

Income and Access to Higher Education: Are High Quality Universities Becoming More or Less Elite? A Longitudinal Case Study of Admissions at UW-Madison.

Has access to selective postsecondary schools expanded or contracted? Evaluating this question has proven a difficult task because data are limited, particularly with regard to family income. We complement previous work and provide a replicable model of institutional analysis. This paper presents a detailed, quantitative assessment of admissions at the University of Wisconsin-Madison, an elite flagship public university-the type that is supposed to offer excellent opportunities to students from all backgrounds. We use an innovative measure of family income to compare applicant, admissions, and enrollment trends for low-income and minority students from 1972 to 2007. The unique aspects of this study include the more reliable measure of income and the ability to look at the full process from applications, admissions, and matriculations (demand and supply), not generally available in national datasets.

Social Support and Psychosocial Well-being Among Low-Income, Adolescent, African American, First-Time Mothers.

AIMS: The aims of this study are to describe for single, low-income, adolescent, African American new mothers how (1) primary sources of social support changed over time, (2) the level of social support (emotional, informational, tangible, and problematic) from these primary sources changed over time, and (3) social support from the primary supporter was associated with mothers' psychosocial well-being (self-esteem and loneliness) over time. DESIGN: A secondary analysis was conducted of data from a previous social support intervention study. SAMPLE: The sample consisted of 35 single, low-income, adolescent (mean [SD] age, 18.3 [1.7] years), African American new mothers. METHODS: Mothers completed social support, self-esteem, and loneliness instruments at 1 and 6 weeks and 3 and 6 months postpartum. RESULTS: Most mothers (64.7%) had changes in their primary social support provider during the first 6 months postpartum. The combination of the adolescent's mother and boyfriend provided the highest level of support, no matter the type, relative to any other source of support. At every time point, positive correlations were found between emotional support and self-esteem and between problematic support and loneliness. CONCLUSION: Single, low-income, African American, adolescent new mothers are at risk for not having a consistent source of support, which may lead to lower self-esteem and greater loneliness. IMPLICATIONS: Clinical nurse specialists could facilitate care guidelines for these new mothers to identify their sources of support at each home visit and advocate for the adolescent's mother and boyfriend to work together to provide support. Bolstering the mothers' natural sources of support can potentially improve self-esteem and reduce loneliness. Improvement in these sources of support could prevent a decline in the mothers' psychosocial well-being. Development and testing support interventions are advocated; findings could guide clinical nurse specialists in addressing these new mothers' needs.

Low-Income, African American, Adolescent Mothers' Depressive Symptoms, Perceived Stress, and Social Support.

The purpose of this descriptive repeated-measures study was to describe depressive symptom patterns and report changes over time in levels of perceived stress and social support depending on patterns of depressive symptoms in single, low-income, African American, adolescent mothers during the initial, 6-month postpartum period. Thirty-five adolescent subjects between the ages of 16 and 22 years old were recruited at health care clinics in two Midwestern cities. Data collections by advanced practice nurses were completed at 1 week, 6 weeks, 3 months, and 6 months postpartum at mothers' homes. Established instruments were used to measure depressive symptoms, perceived stress and social support. Results indicated 63% of adolescent mothers' experienced depressive symptoms sometime during this transition period and 11.4% of these subjects had depressive symptoms at all 4 time points. Depressive symptoms were associated with perceived stress at each time point. Emotional support was inversely associated with depressive symptoms at 2 of the 4 time points. Depressive symptoms and problematic support were significantly related at 3 months and 6 months. Although single, low-income, African American, adolescent mothers are considered a high risk group, some are at even greater risk. This extremely high risk group have depressive symptoms throughout the first 6 months postpartum with the highest level of perceived stress and the most variability in social support relative to groups that were never depressed or were in and out of depression. More studies are needed to understand how to best help these high risk adolescents successfully transition to motherhood.