Housing Cost Burden and Maternal Stress among Very Low Income Mothers

As the affordable housing shortage proliferates, more American households struggle with high housing cost burdens. Grounded in Belsky’s (1984) parenting stress framework, we use a weighted low-income sample from the Fragile Families and Child Wellbeing Study of mothers who rent their homes (N=388) to investigate a relationship between housing cost burden, or paying a substantial portion of income toward housing, and higher rates of reported maternal stress. Findings of the linear regression indicate that younger mothers and those paying 30% or more of their income each month toward rent have higher reported maternal stress scores. These findings are discussed with attention to practice and policy implications

Coping, productive time use, and negative mood among adults with severe mental illness: A daily diary study

Most studies on coping among persons with severe mental illness have relied on retrospective self-report methods; a limitation of this methodology is susceptibility to recall bias. The purpose of the present investigation was to expand the current understanding of the impact of coping among persons with severe mental illness by examining coping strategies, mood, and social functioning (operationalized as productive time use) using a daily process design. Twenty-seven adults diagnosed with severe mental illness completed baseline clinical interviews and up to 20 days of nightly telephone interviews addressing coping and daily life. A total of 198 coping efforts were reported for 387 days. Mixed-effects regression analyses examined the association between type of daily coping strategy (problem-centered, neutral, or avoidant) and both daily proportion of time participants spent in productive activity and daily negative mood, controlling for demographic and clinical variables. The results indicated that productive time use was significantly lower on days when avoidant strategies were used, in contrast with days when problem-centered strategies and neutral strategies were used. There was no significant main effect of coping on negative mood, although there was a trend in the expected direction. Findings support the hypothesis that the types of coping strategies adults with severe mental illness use are related to better social functioning on a daily level

C-C Chemokine Receptor 5 on Pulmonary Mesenchymal Cells Promotes Experimental Metastasis via the Induction of Erythroid Differentiation Regulator 1

C-C Chemokine receptor five knockout (Ccr5-/-) mice develop fewer experimental pulmonary metastases than wild type (WT) mice. This phenomenon was explored by applying gene-expression profiling to the lungs of mice with these metastases. Consequently, Erythroid Differentiation Regulator 1 (Erdr1) was identified as upregulated in the WT mice. Though commonly associated with bone marrow stroma, Erdr1 was differentially expressed in WT pulmonary mesenchymal cells (PMCs) and murine embryonic fibroblasts (MEFs). Moreover, the Ccr5 ligand Ccl4 increased its expression by 3.36 ± 0.14 fold. Ccr5 signaling was dependent on the Map2k but not the Pi3k pathway since treatment with U0126 inhibited upregulation of Erdr1 but treatment with LY294002 increased the expression by 3.44 ± 0.92 fold (p < 0.05). Erdr1's effect on B16-F10 melanoma metastasis was verified by the adoptive transfer of WT MEFs into Ccr5-/- mice. In this model, MEFs that had been transduced with Erdr1 shRNA lowered metastasis by 33% compared to control transduced MEFs. The relevance of ERDR1 on human disease was assessed by co-culturing chronic lymphocytic leukemia (CLL) cells with M2-10B4 stromal cells that had been transfected with shRNA or control plasmids. After 96 hours of co-culture, the cell counts were higher with control cell lines compared with Erdr1 knockdown lines (OR 1.88 ± 0.27, 2.52 ± 0.66 respectively). This increase was associated with a decrease in apoptotic cells (OR 0.69 ± 0.18, 0.58 ± 0.12 respectively)

Domainâ specific impairment in cognitive control among remitted youth with a history of major depression

AimImpairment in neuropsychological functioning is common in major depressive disorder (MDD), but it is not clear to what degree these deficits are related to risk (e.g. trait), scar, burden or state effects of MDD. The objective of this study was to use neuropsychological measures, with factor scores in verbal fluency, processing speed, attention, setâ shifting and cognitive control in a unique population of young, remitted, unmedicated, early course individuals with a history of MDD in hopes of identifying putative trait markers of MDD.MethodsYouth aged 18â 23 in remission from MDD (rMDD; n = 62) and healthy controls (HC; n = 43) were assessed with neuropsychological tests at two time points. These were from four domains of executive functioning, consistent with previous literature as impaired in MDD: verbal fluency and processing speed, conceptual reasoning and setâ shifting, processing speed with interference resolution, and cognitive control.ResultsrMDD youth performed comparably to HCs on verbal fluency and processing speed, processing speed with interference resolution, and conceptual reasoning and setâ shifting, reliably over time. Individuals with rMDD demonstrated relative decrements in cognitive control at Time 1, with greater stability than HC participants.ConclusionMDD may be characterized by regulatory difficulties that do not pertain specifically to active mood state or fluctuations in symptoms. Deficient cognitive control may represent a trait vulnerability or early course scar of MDD that may prove a viable target for secondary prevention or early remediation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138407/1/eip12253_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138407/2/eip12253.pd

Monte Carlo investigation of the effect of blood volume and oxygen saturation on optical path in reflectance pulse oximetry

Despite the clinical importance of pulse oximetry, the precise nature of the interaction of light with tissue, which underlies the technique, is not yet fully understood. The limitations of the method with regard toits accuracy inconditions of compromised perfusion and/or low blood oxygen saturations are well documented but have only partly been resolved. Results from a static monolayer Monte Carlo modelof optical path and reflectance attwo wavelengths most commonly usedinpulse-oximetry (660 and 940 nm) through skin tissue, containing different volume fractions of blood witharange of oxygen saturations, are presented. Results exhibited differences in mean optical path (MOP) between the two wavelengths, with differences generally increasing with increasing tissue oxygen saturation and decreasing blood volume.As anexample, inatypical sensor configuration, the MOP of red light traveling through skin containing 7.5% blood volume fraction with mean oxygen saturationof60% was 58% higher than that for infrared. The results presented should contribute to further understandingofthe effectofphysiological conditions suchasanemia, ischemia and hypoxemia on the accuracy of pulse oximetry readings

Upregulation of the cell-cycle regulator RGC-32 in Epstein-Barr virus-immortalized cells

Epstein-Barr virus (EBV) is implicated in the pathogenesis of multiple human tumours of lymphoid and epithelial origin. The virus infects and immortalizes B cells establishing a persistent latent infection characterized by varying patterns of EBV latent gene expression (latency 0, I, II and III). The CDK1 activator, Response Gene to Complement-32 (RGC-32, C13ORF15), is overexpressed in colon, breast and ovarian cancer tissues and we have detected selective high-level RGC-32 protein expression in EBV-immortalized latency III cells. Significantly, we show that overexpression of RGC-32 in B cells is sufficient to disrupt G2 cell-cycle arrest consistent with activation of CDK1, implicating RGC-32 in the EBV transformation process. Surprisingly, RGC-32 mRNA is expressed at high levels in latency I Burkitt's lymphoma (BL) cells and in some EBV-negative BL cell-lines, although RGC-32 protein expression is not detectable. We show that RGC-32 mRNA expression is elevated in latency I cells due to transcriptional activation by high levels of the differentially expressed RUNX1c transcription factor. We found that proteosomal degradation or blocked cytoplasmic export of the RGC-32 message were not responsible for the lack of RGC-32 protein expression in latency I cells. Significantly, analysis of the ribosomal association of the RGC-32 mRNA in latency I and latency III cells revealed that RGC-32 transcripts were associated with multiple ribosomes in both cell-types implicating post-initiation translational repression mechanisms in the block to RGC-32 protein production in latency I cells. In summary, our results are the first to demonstrate RGC-32 protein upregulation in cells transformed by a human tumour virus and to identify post-initiation translational mechanisms as an expression control point for this key cell-cycle regulator

Disruption of CTCF-YY1-dependent looping of the human papillomavirus genome activates differentiation-induced viral oncogene transcription.

The complex life cycle of oncogenic human papillomavirus (HPV) initiates in undifferentiated basal epithelial keratinocytes where expression of the E6 and E7 oncogenes is restricted. Upon epithelial differentiation, E6/E7 transcription is increased through unknown mechanisms to drive cellular proliferation required to support virus replication. We report that the chromatin-organising CCCTC-binding factor (CTCF) promotes the formation of a chromatin loop in the HPV genome that epigenetically represses viral enhancer activity controlling E6/E7 expression. CTCF-dependent looping is dependent on the expression of the CTCF-associated Yin Yang 1 (YY1) transcription factor and polycomb repressor complex (PRC) recruitment, resulting in trimethylation of histone H3 at lysine 27. We show that viral oncogene up-regulation during cellular differentiation results from YY1 down-regulation, disruption of viral genome looping, and a loss of epigenetic repression of viral enhancer activity. Our data therefore reveal a key role for CTCF-YY1-dependent looping in the HPV life cycle and identify a regulatory mechanism that could be disrupted in HPV carcinogenesis

RNA polymerase II stalling promotes nucleosome occlusion and pTEFb recruitment to drive immortalization by Epstein-Barr virus

Epstein-Barr virus (EBV) immortalizes resting B-cells and is a key etiologic agent in the development of numerous cancers. The essential EBV-encoded protein EBNA 2 activates the viral C promoter (Cp) producing a message of ~120 kb that is differentially spliced to encode all EBNAs required for immortalization. We have previously shown that EBNA 2-activated transcription is dependent on the activity of the RNA polymerase II (pol II) C-terminal domain (CTD) kinase pTEFb (CDK9/cyclin T1). We now demonstrate that Cp, in contrast to two shorter EBNA 2-activated viral genes (LMP 1 and 2A), displays high levels of promoter-proximally stalled pol II despite being constitutively active. Consistent with pol II stalling, we detect considerable pausing complex (NELF/DSIF) association with Cp. Significantly, we observe substantial Cp-specific pTEFb recruitment that stimulates high-level pol II CTD serine 2 phosphorylation at distal regions (up to +75 kb), promoting elongation. We reveal that Cp-specific pol II accumulation is directed by DNA sequences unfavourable for nucleosome assembly that increase TBP access and pol II recruitment. Stalled pol II then maintains Cp nucleosome depletion. Our data indicate that pTEFb is recruited to Cp by the bromodomain protein Brd4, with polymerase stalling facilitating stable association of pTEFb. The Brd4 inhibitor JQ1 and the pTEFb inhibitors DRB and Flavopiridol significantly reduce Cp, but not LMP1 transcript production indicating that Brd4 and pTEFb are required for Cp transcription. Taken together our data indicate that pol II stalling at Cp promotes transcription of essential immortalizing genes during EBV infection by (i) preventing promoter-proximal nucleosome assembly and ii) necessitating the recruitment of pTEFb thereby maintaining serine 2 CTD phosphorylation at distal regions