An exploratory study into Iraqi refugees\u27 resettlement experience in California\u27s Inland Empire

This study explored the resettlement services and supports given to Iraqi refugees in California\u27s Inland Empire and gave Iraqi refugees an opportunity to voice their opinions and concerns related to resettlement, It also provides guidance for future policies and services offered by resettlement agencies

DETERMINANTS OF COHESIN LOCALIZATION AND FUNCTION IN GENOME ORGANIZATION AND GENE EXPRESSION

The ring-shaped cohesin complex participates in various biological processes including DNA replication and repair, cell cycle progression, gene expression, and three-dimensional organization of the genome. Despite these important roles, little is known regarding the mechanisms that facilitate loading, translocation, and unloading of this complex. The prominent model involves loading of the complex by NIPBL and unloading by WAPL. This model has been challenged, however, by recent reports which provide evidence for previously unappreciated roles of NIPBL and WAPL. For example, NIPBL has been shown to be required for active extrusion of DNA loops by the cohesin complex and some reports provide conflicting evidence on the molecular role of WAPL. Moreover, various recent reports have identified previously unknown binding partners of cohesin. Therefore, additional unrecognized binding partners may exist and affect the localization and/or function of the complex. Finally, new structural evidence suggests that the cohesin ring adopts complex orientations in the nucleus which were not previously identified, which may imply that specific domains of the proteins involved have important roles in the function of the complex or its association with DNA. Utilizing biochemistry, molecular biology, and genomics, this work evaluates the molecular determinants of cohesin localization and function. We introduce a previously unrecognized binding partner of the cohesin complex, WIZ. Loss of WIZ results in genome-wide alterations in cohesin localization and changes in gene expression and genome organization. We demonstrate that WIZ regulates cohesin localization in a manner distinct from the canonical unloader WAPL, and in a manner distinct from its previously identified binding partner G9a. Additional data demonstrate that the cohesin accessory proteins STAG1 and STAG2 have largely redundant roles in the control of cohesin localization but have somewhat unique roles in regulating gene expression. Finally, we analyze the importance of the hinge domain of the cohesin complex by mutating a residue within the SMC1A subunit. We find that disruption of the hinge domain results in genome-wide loss of cohesin binding, widespread changes in gene expression, and loss of enhancer-promoter loops. In all, the work herein advances our understanding of the molecular determinants of cohesin localization and function.Doctor of Philosoph

Genomic Analysis of Demographic History and Ecological Niche Modeling in the Endangered Sumatran Rhinoceros Dicerorhinus sumatrensis

The vertebrate extinction rate over the past century is approximately 22–100 times greater than background extinction rates [1], and large mammals are particularly at risk [2, 3]. Quaternary megafaunal extinctions have been attributed to climate change [4], overexploitation [5], or a combination of the two [6]. Rhinoceroses (Family: Rhinocerotidae) have a rich fossil history replete with iconic examples of climate-induced extinctions [7], but current pressures threaten to eliminate this group entirely. The Sumatran rhinoceros(Dicerorhinus sumatrensis) is among the most imperiled mammals on earth. The 2011 population was estimated at ≤216 wild individuals [8], and currently the species is extirpated, or nearly so, throughout the majority of its former range [8–12]. Understanding demographic history is important in placing current population status into a broader ecological and evolutionary context. Analysis of the Sumatran rhinoceros genome reveals extreme changes in effective population size throughout the Pleistocene. Population expansion during the early to middle Pleistocene was followed by decline. Ecological niche modeling indicated that changing climate most likely played a role in the decline of the Sumatran rhinoceros, as less suitable habitat on an emergent Sundaland corridor isolated Sumatran rhinoceros populations. By the end of the Pleistocene, the Sundaland corridor was submerged, and populations were fragmented and consequently reduced to low Holocene levels from which they would never recover. Past events denuded the Sumatran rhinoceros of genetic diversity through population decline, fragmentation, or some combination of the two and most likely made the species even more susceptible to later exploitation and habitat loss

RNA Polymerase II CTD phosphatase Rtr1 fine-tunes transcription termination

RNA Polymerase II (RNAPII) transcription termination is regulated by the phosphorylation status of the C-terminal domain (CTD). The phosphatase Rtr1 has been shown to regulate serine 5 phosphorylation on the CTD; however, its role in the regulation of RNAPII termination has not been explored. As a consequence of RTR1 deletion, interactions within the termination machinery and between the termination machinery and RNAPII were altered as quantified by Disruption-Compensation (DisCo) network analysis. Of note, interactions between RNAPII and the cleavage factor IA (CF1A) subunit Pcf11 were reduced in rtr1Δ, whereas interactions with the CTD and RNA-binding termination factor Nrd1 were increased. Globally, rtr1Δ leads to decreases in numerous noncoding RNAs that are linked to the Nrd1, Nab3 and Sen1 (NNS) -dependent RNAPII termination pathway. Genome-wide analysis of RNAPII and Nrd1 occupancy suggests that loss of RTR1 leads to increased termination at noncoding genes. Additionally, premature RNAPII termination increases globally at protein-coding genes with a decrease in RNAPII occupancy occurring just after the peak of Nrd1 recruitment during early elongation. The effects of rtr1Δ on RNA expression levels were lost following deletion of the exosome subunit Rrp6, which works with the NNS complex to rapidly degrade a number of noncoding RNAs following termination. Overall, these data suggest that Rtr1 restricts the NNS-dependent termination pathway in WT cells to prevent premature termination of mRNAs and ncRNAs. Rtr1 facilitates low-level elongation of noncoding transcripts that impact RNAPII interference thereby shaping the transcriptome

Trends in misdemeanor arrest rates in New York.

John Jay College of Criminal Justice is pleased to publish this report documenting patterns in misdemeanor arrests in New York City (and, to a lesser extent, in New York State) over the past three decades. This report presents trends in the types of misdemeanors for which New Yorkers have been arrested; analyzes these data by the age, gender, and race/ethnicity of those receiving this enforcement attention; examines shifts in misdemeanor arrest activity by police precincts; displays changes in the issuance of Desk Appearance Tickets over time; and traces these misdemeanor arrests to the initial court disposition at arraignment. (from Introduction, p. 8) Report downloaded from: https://datacollaborativeforjustice.org/publication/trends-in-misdemeanor-arrests-in-new-york Table of Contents Acknowledgements -- List of figures -- Introduction -- Goals of the Project -- About the data presented in this publication -- Overall trends : felony arrests and misdemeanor arrests -- Overall trends by gender -- Overall trends by age -- Overall trends by race/ethnicity -- Overall trends by charge types --Overall trends by disposition types -- Ovrall trends by sentence types -- A closer look at New York City -- Desk appearance tickets -- Arrests by precincts from 1993 to 2013 -- Conclusion -- Appendix A: Charge codes, frequency, and categories from 1980 to 2013 for New York State -- Appendix B: Rates of misdemeanor arrests for females in New York City by age -- Appendix C: Number of misdemeanor arrests in New York City by precincts from 1993 to 2003. Link to the report in the John Jay College Library Catalog

Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.

We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10-7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants

Common Sense Recommendations for the Application of Tax Law to Digital Assets

In response to the Joint Committee on Taxation’s July 2023 request for comments on application of various Internal Revenue Code sections on digital assets, we propose a consistent set of rules to apply current law to digital assets. We highlight that the underlying economics and characteristics of transactions should be the primary concern for the application of rules and the valuation of digital assets. We believe any digital asset rules should (1) treat classes of digital assets with unique characteristics differently based on their economics, (2) minimize incentives for users to engage in tax-motivated structuring of transactions, and (3) allow the Internal Revenue Service authority to react to and regulate new classes of digital assets as they are created. We do not believe that the unique features of digital assets are a challenge to applying current law or warrant special tax preferred treatment

Geographic Variations in Retention in Care among HIV-Infected Adults in the United States

ObjectiveTo understand geographic variations in clinical retention, a central component of the HIV care continuum and key to improving individual- and population-level HIV outcomes.DesignWe evaluated retention by US region in a retrospective observational study.MethodsAdults receiving care from 2000–2010 in 12 clinical cohorts of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) contributed data. Individuals were assigned to Centers for Disease Control and Prevention (CDC)-defined regions by residential data (10 cohorts) and clinic location as proxy (2 cohorts). Retention was ≥2 primary HIV outpatient visits within a calendar year, >90 days apart. Trends and regional differences were analyzed using modified Poisson regression with clustering, adjusting for time in care, age, sex, race/ethnicity, and HIV risk, and stratified by baseline CD4+ count.ResultsAmong 78,993 adults with 444,212 person-years of follow-up, median time in care was 7 years (Interquartile Range: 4–9). Retention increased from 2000 to 2010: from 73% (5,000/6,875) to 85% (7,189/8,462) in the Northeast, 75% (1,778/2,356) to 87% (1,630/1,880) in the Midwest, 68% (8,451/12,417) to 80% (9,892/12,304) in the South, and 68% (5,147/7,520) to 72% (6,401/8,895) in the West. In adjusted analyses, retention improved over time in all regions (p<0.01, trend), although the average percent retained lagged in the West and South vs. the Northeast (p<0.01).ConclusionsIn our population, retention improved, though regional differences persisted even after adjusting for demographic and HIV risk factors. These data demonstrate regional differences in the US which may affect patient care, despite national care recommendations