Deportation Under Obama and Trump: A Contrasting Examination of Immigration Legislation and Their Real and Perceived Impact Under Different Administrations

This thesis explores deportation in modern America. With an initial examination of the immigration laws passed in the 1980 and 90s which resulted in the advent of mass deportation, this paper then explore regional responses to a lack of congressional immigration reform and the subsequent federal response. Focusing on the Obama administration and the first year of the Trump Presidency this paper explores the actions and impact that these men have on some of the country’s most vulnerable residents

DNA mismatch repair-dependent responses to the food-borne carcinogen 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the mouse

The DNA mismatch repair (MMR) pathway maintains genomic stability and reduces cancer risk (colorectal and other internal cancers) by correcting polymerase errors and activating cell cycle checkpoints and apoptosis in response to DNA damage. Few studies have examined the influence of commonly encountered environmental mutagens/carcinogens on the etiology of MMR-deficient cancers. 2-Amino-1-methyl-6- phenylimidazo [4,5-bJ pyridine (PhIP) is a cooked-meat mutagen implicated in human colorectal carcinogenesis. To determine whether PhIP represents a cancer risk to individuals with MMR-deficiency, I examined the effect of Mlh1-deficiency on PhIP-induced mutagenesis, turnorigenesis, and cell-turnover responses in mice following exposure to eight intraperitoneal (i.p.) injections of 50 mg/kg PhIP. Mlh1⁻/⁻ mice were hypermutable by PhIP in colon and small intestine (as measured using transgene shuttle vectors), demonstrating specific increases in mutations not typically associated with PhIP. In contrast, G/C to T/A transversions, the "signature PhIP mutation" were similarly induced in Mlh1⁻/⁻ and wild-type mice. In cancer studies, Mlh1⁻/⁻ mice showed heightened susceptibility to induction of colonic aberrant crypt foci (a biomarker for colon carcinogenesis), whereas adenomas of the small intestine and colon were not induced. Cell-turnover responses in Mlh1⁺/⁺ and Mlh1⁻/⁻ mouse colon were evaluated following multiple i.p. injections or a single i.p. injection of 50 mg/kg PhIP. These responses were compared to a single i.p. injection of 80 mg/kg 1 ,2-dimethylhydrazine (DMH). Colonic apoptosis in response to PhIP increased, shifted to predominately the stem cell compartment of colon crypts, and was partially Mlh1-dependent. This response was also rapid, occurring at 8 h after treatment and diminishing by 16 h. Similar effects were observed in DMH-exposed animals. The apoptotic response to PhIP was greater after multiple exposures compared to a single exposure. PhIP-exposure did not notably alter cell proliferation, whereas proliferation was consistently reduced in DMH-treated mice. These results suggest that loss of Mlh1 alters homeostatic functions of the colonic crypt that may contribute to suppression of the mutagenic effects of PhIP. These data are consistent with the hypothesis that PhIP exposure increases mutagenesis and carcinogenesis in Mlh1⁻/⁻ mice, and support further evaluation of the risk that consumption of heterocyclic amines may impart to MMR-deficient individuals

Combined gene dosage requirement for SWI/SNF catalytic subunits during early mammalian development

Mammalian SWI/SNF complexes utilize either BRG1 or BRM as alternative catalytic subunits with DNA-dependent ATPase activity to remodel chromatin. Although the two proteins are 75% identical, broadly expressed, and have similar biochemical activities in vitro, BRG1 is essential for mouse embryonic development, while BRM is dispensable. To investigate whether BRG1 and BRM have overlapping functions during mouse embryogenesis, we performed double-heterozygous intercrosses using constitutive null mutations previously created by gene targeting. The progeny of these crosses had a distribution of genotypes that was significantly skewed relative to their combined gene dosage. This was most pronounced at the top and bottom of the gene dosage hierarchy with a 1.5-fold overrepresentation of Brg1+/+;Brm+/+ mice and a corresponding 1.6-fold underrepresentation of Brg1+/−;Brm−/− mice. To account for the underrepresentation of Brg1+/−;Brm−/− mice, timed matings and blastocyst outgrowth assays demonstrated that ~50% of these embryos failed to develop beyond the peri-implantation stage. These results challenge the idea that BRG1 is the exclusive catalytic subunit of SWI/SNF complexes in ES cells and suggest that BRM also interacts with the pluripotency transcription factors to facilitate self-renewal of the inner cell mass. In contrast to implantation, the Brm genotype did not influence an exencephaly phenotype that arises because of Brg1 haploinsufficiency during neural tube closure and that results in peri-natal lethality. Taken together, these results support the idea that BRG1 and BRM have overlapping functions for certain developmental processes but not others during embryogenesis

Forest-based climate change mitigation and adaptation in Europe

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Stimulation of Lateral Septum CRF2 Receptors Promotes Anorexia and Stress-Like Behaviors: Functional Homology to CRF1 Receptors in Basolateral Amygdala

The corticotropin-releasing factor (CRF) system is the primary central mediator of stress-like states, coordinating behavioral, endocrine, and autonomic responses to stress. Although induction of anorexia is a well documented effect of CRF receptor agonist administration, the central sites and behavioral processes underlying this phenomenon are poorly understood. The present studies addressed this question by examining the neuroanatomical, behavioral, and pharmacological mechanisms mediating decreases in feeding produced by the CR

Building on the past, shaping the future: The environmental mutagenesis and genomics society

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97167/1/em21765.pd

Contribution of the land sector to a 1.5 °C world

Acknowledgements The analysis in this study was guided by the valuable feedback and recommendations of expert consultations and interviews, and we extend our gratitude to all those individuals who contributed to our research and analysis: Jeff Atkins (Virginia Commonwealth University), Jonah Busch (Earth Innovation Institute), Peter Ellis (The Nature Conservancy), Jason Funk (Center for Carbon Removal), Trisha Gopalakrishna (The Nature Conservancy), Alan Kroeger (Climate Focus), Bernice Lee (Chatham House), Donna Lee (Climate and Land Use Alliance), Simon Lewis (University College London), Guy Lomax (The Nature Conservancy), Dann Mitchell (University of Bristol), Raoni Rajão (University of Minas Gerais), Joeri Rogelj (IIASA), Carl-Friedrich Schleussner (Climate Analytics), Paul West (University of Minnesota), Graham Wynne (Prince of Wales International Sustainability Unit), Ana Yang (Children’s Investment Fund Foundation) and Dan Zarin (Climate and Land Use Alliance). A special thank you to Esther Chak and Mary-Jo Valentino (Imaginary Office) for designing the figures in this study. This work was generously supported by the Children’s Investment Fund Foundation and the authors’ institutions and funding sources.Peer reviewedPostprin

Cell cycle stage-specific roles of Rad18 in tolerance and repair of oxidative DNA damage

The E3 ubiquitin ligase Rad18 mediates tolerance of replication fork-stalling bulky DNA lesions, but whether Rad18 mediates tolerance of bulky DNA lesions acquired outside S-phase is unclear. Using synchronized cultures of primary human cells, we defined cell cycle stage-specific contributions of Rad18 to genome maintenance in response to ultraviolet C (UVC) and H2O2-induced DNA damage. UVC and H2O2 treatments both induced Rad18-mediated proliferating cell nuclear antigen mono-ubiquitination during G0, G1 and S-phase. Rad18 was important for repressing H2O2-induced (but not ultraviolet-induced) double strand break (DSB) accumulation and ATM S1981 phosphorylation only during G1, indicating a specific role for Rad18 in processing of oxidative DNA lesions outside S-phase. However, H2O2-induced DSB formation in Rad18-depleted G1 cells was not associated with increased genotoxin sensitivity, indicating that back-up DSB repair mechanisms compensate for Rad18 deficiency. Indeed, in DNA LigIV-deficient cells Rad18-depletion conferred H2O2-sensitivity, demonstrating functional redundancy between Rad18 and non-homologous end joining for tolerance of oxidative DNA damage acquired during G1. In contrast with G1-synchronized cultures, S-phase cells were H2O2-sensitive following Rad18-depletion. We conclude that although Rad18 pathway activation by oxidative lesions is not restricted to S-phase, Rad18-mediated trans-lesion synthesis by Polη is dispensable for damage-tolerance in G1 (because of back-up non-homologous end joining-mediated DSB repair), yet Rad18 is necessary for damage tolerance during S-phase

The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey : baryon acoustic oscillations in the Data Releases 10 and 11 Galaxy samples

We present a one per cent measurement of the cosmic distance scale from the detections of the baryon acoustic oscillations (BAO) in the clustering of galaxies from the Baryon Oscillation Spectroscopic Survey, which is part of the Sloan Digital Sky Survey III. Our results come from the Data Release 11 (DR11) sample, containing nearly one million galaxies and covering approximately 8500 square degrees and the redshift range 0.2 < z < 0.7. We also compare these results with those from the publicly released DR9 and DR10 samples. Assuming a concordance Λ cold dark matter (ΛCDM) cosmological model, the DR11 sample covers a volume of 13 Gpc3 and is the largest region of the Universe ever surveyed at this density. We measure the correlation function and power spectrum, including density-field reconstruction of the BAO feature. The acoustic features are detected at a significance of over 7σ in both the correlation function and power spectrum. Fitting for the position of the acoustic features measures the distance relative to the sound horizon at the drag epoch, rd, which has a value of rd,fid = 149.28 Mpc in our fiducial cosmology. We find DV = (1264 ± 25 Mpc)(rd/rd,fid) at z = 0.32 and DV = (2056 ± 20 Mpc)(rd/rd,fid) at z = 0.57. At 1.0 per cent, this latter measure is the most precise distance constraint ever obtained from a galaxy survey. Separating the clustering along and transverse to the line of sight yields measurements at z = 0.57 of DA = (1421 ± 20 Mpc)(rd/rd,fid) and H = (96.8 ± 3.4 km s−1 Mpc−1)(rd,fid/rd). Our measurements of the distance scale are in good agreement with previous BAO measurements and with the predictions from cosmic microwave background data for a spatially flat CDM model with a cosmological constant.Publisher PDFPeer reviewe

Separation of intra-S checkpoint protein contributions to DNA replication fork protection and genomic stability in normal human fibroblasts

The ATR-dependent intra-S checkpoint protects DNA replication forks undergoing replication stress. The checkpoint is enforced by ATR-dependent phosphorylation of CHK1, which is mediated by the TIMELESS-TIPIN complex and CLASPIN. Although loss of checkpoint proteins is associated with spontaneous chromosomal instability, few studies have examined the contribution of these proteins to unchallenged DNA metabolism in human cells that have not undergone carcinogenesis or crisis. Furthermore, the TIMELESS-TIPIN complex and CLASPIN may promote replication fork protection independently of CHK1 activation. Normal human fibroblasts (NHF) were depleted of ATR, CHK1, TIMELESS, TIPIN or CLASPIN and chromosomal aberrations, DNA synthesis, activation of the DNA damage response (DDR) and clonogenic survival were evaluated. This work demonstrates in NHF lines from two individuals that ATR and CHK1 promote chromosomal stability by different mechanisms that depletion of CHK1 produces phenotypes that resemble more closely the depletion of TIPIN or CLASPIN than the depletion of ATR, and that TIMELESS has a distinct contribution to suppression of chromosomal instability that is independent of its heterodimeric partner, TIPIN. Therefore, ATR, CHK1, TIMELESS-TIPIN and CLASPIN have functions for preservation of intrinsic chromosomal stability that are separate from their cooperation for activation of the intra-S checkpoint response to experimentally induced replication stress. These data reveal a complex and coordinated program of genome maintenance enforced by proteins known for their intra-S checkpoint function