1,064 research outputs found

    Extraction and Quantification of Atrazine

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    Undergraduate Basi

    EVOLUTION OF THE KINETICS AND DYNAMICS OF HEME-CREVICE LOOP REGULATING CHEMISTRY IN HUMAN CYTOCHROME C

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    Cytochrome c, cytc, is a metalloprotein that plays primary roles in electron transport and intrinsic apoptotic pathways. Much of the chemistry that cytc is involved with is regulated by a highly conserved region known as the heme crevice loop, consisting of residues 70-85. Only three of these residues (those at positions 81, 83 and 85) are not universally conserved within the evolutionary timeline. Here I look to elucidate possible evolutionary roles for several of the key residues known to be important in regulating heme chemistry of cytc. I first address the role that lysine 72 plays in cytc folding and chemistry. Here I provide evidence that K72 alters the alkaline conformational transition of cytc. Trimethylated lysine 72, tmK72, was previously investigated and shows similar trends in peroxidase activity (McClelland et al 2013). Lastly I address I81 which is not only within the heme crevice loop and not universally conserved, but is also a hydrophobic surface residue. Here I make a Hu I81A variant, mutating to the alanine seen in yeast cytc. Our hypothesis was that this mutation would show a destabilization of the heme crevice loop region when monitoring the charge transfer band (695 nm), and more importantly observing an increase in peroxidase activity when monitoring for tetraguaiacol (470 nm) in our enzymatic assay. This signifies this mutation could have evolved to lock down that heme crevice loop in order to decrease peroxidase activity when intrinsic apoptosis pathways evolved in mammals. pH titration data showed a decrease in stability of the alkaline conformational transition in our I81A variant when compared to Hu WT. When looking at peroxidase activity we see a significant increase in kcat(s-1) values of I81A compared to Hu WT. The Hu I81A indeed shows what we would expect of a mutation which evolved to decrease peroxidase activity. Analysis of pH jump data in the Soret region of cytc shows that there is an effect on lysine 73 or 79 bound alkaline ligands (unable to be determined) by a decrease in amplitude, however there is no effect on the lysine 72 bound alkaline ligand

    You Got the Job, Now What?: An Evaluation of the New Employee Orientation Program at the University of Montana

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    When new members begin their employment with an organization, they make a transition from being an outsider to an insider. A significant moment arranged by the organization to facilitate socialization is the New Employee Orientation (NEO). This evaluation examines NEO in relation to the encounter stage of the socialization process. Focusing on what and how information is provided during the NEO program at the University of Montana (UM), this evaluation is based on research of the informational components of Klein and Weaver (2000) and the socialization tactics from Van Maanen and Schein (1979). General conclusions regarding NEO and socialization as well as recommendations for improvement are presented for the benefit of the Human Resource Services office at UM

    Geographies of Inequality: Urban Renewal and the Race, Gender, and Class of Post-Katrina New Orleans

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    In this paper, we address pressing questions on the perpetuation of race, gender, and class inequalities in ongoing restoration practices shaping the New New Orleans. We unpack federal and local efforts to rebuild and revitalize the city over the last ten years and map the geography of New Orleans at the neighborhood level both before and after the storm. We discuss how mismanaged resources, corrupt profit-taking, conflicts of interest for the stakeholders, and socially unconscious design conditioned a fiscally irresponsible and non-inclusive recovery. These efforts have pushed out already marginalized populations, resulted in the gentrification of historically African American neighborhoods, and ultimately maintained complex social inequalities

    The HB22.7 Anti-CD22 monoclonal antibody enhances bortezomib-mediated lymphomacidal activity in a sequence dependent manner

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    Most non-Hodgkin's lymphomas (NHL) initially respond to chemotherapy, but relapse is common and treatment is often limited by chemotherapy-related toxicity. Bortezomib, is a highly selective proteasome inhibitor with anti-NHL activity; it is currently FDA approved for second-line treatment of mantle cell lymphoma (MCL). Bortezomib exerts its activity in part through the generation of reactive oxygen species (ROS) and also by the induction of apoptosis

    Radiation measurements in the new tandem accelerator FEL

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    The measurements of both spontaneous and stimulated emissions of radiation in the newly configured Israeli EA-FEL are made for the first time. The radiation at the W-band was measured and characterized. The results match the predictions of our earlier theoretical modeling and calculations.Comment: 4 pages, 3 figures, FEL 2003 Conference repor

    Loss of murine Paneth cell function alters the immature intestinal microbiome and mimics changes seen in neonatal necrotizing enterocolitis

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    Necrotizing enterocolitis (NEC) remains the leading cause of gastrointestinal morbidity and mortality in premature infants. Human and animal studies suggest a role for Paneth cells in NEC pathogenesis. Paneth cells play critical roles in host-microbial interactions and epithelial homeostasis. The ramifications of eliminating Paneth cell function on the immature host-microbial axis remains incomplete. Paneth cell function was depleted in the immature murine intestine using chemical and genetic models, which resulted in intestinal injury consistent with NEC. Paneth cell depletion was confirmed using histology, electron microscopy, flow cytometry, and real time RT-PCR. Cecal samples were analyzed at various time points to determine the effects of Paneth cell depletion with and without Klebsiella gavage on the microbiome. Deficient Paneth cell function induced significant compositional changes in the cecal microbiome with a significant increase in Enterobacteriacae species. Further, the bloom of Enterobacteriaceae species that occurs is phenotypically similar to what is seen in human NEC. This further strengthens our understanding of the importance of Paneth cells to intestinal homeostasis in the immature intestine

    Mycobacterium tuberculosis MycP1 Protease Plays a Dual Role in Regulation of ESX-1 Secretion and Virulence

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    SummaryMycobacterium tuberculosis uses the ESX-1 secretion system to deliver virulence proteins during infection of host cells. Here we report a mechanism of posttranscriptional control of ESX-1 mediated by MycP1, a M. tuberculosis serine protease. We show that MycP1 is required for ESX-1 secretion but that, unexpectedly, genetic inactivation of MycP1 protease activity increases secretion of ESX-1 substrates. We demonstrate that EspB, an ESX-1 substrate required for secretion, is a target of MycP1 in vitro and in vivo. During macrophage infection, an inactive MycP1 protease mutant causes hyperactivation of ESX-1-stimulated innate signaling pathways. MycP1 is required for growth in mice during acute infection, while loss of its protease activity leads to attenuated virulence during chronic infection. As the key ESX-1 substrates ESAT-6 and CFP-10 are highly immunogenic, fine-tuning of their secretion by MycP1 may balance virulence and immune detection and be essential for successful maintenance of long-term M. tuberculosis infection

    Cellular and clinical impact of Haploinsufficiency for genes involved in ATR signaling

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    Ataxia telangiectasia and Rad3-related (ATR) protein, a kinase that regulates a DNA damage-response pathway, is mutated in ATR-Seckel syndrome (ATR-SS), a disorder characterized by severe microcephaly and growth delay. Impaired ATR signaling is also observed in cell lines from additional disorders characterized by microcephaly and growth delay, including non-ATR-SS, Nijmegen breakage syndrome, and MCPH1 (microcephaly, primary autosomal recessive, 1)-dependent primary microcephaly. Here, we examined ATR-pathway function in cell lines from three haploinsufficient contiguous gene-deletion disorders--a subset of blepharophimosis-ptosis-epicanthus inversus syndrome, Miller-Dieker lissencephaly syndrome, and Williams-Beuren syndrome--in which the deleted region encompasses ATR, RPA1, and RFC2, respectively. These three genes function in ATR signaling. Cell lines from these disorders displayed an impaired ATR-dependent DNA damage response. Thus, we describe ATR signaling as a pathway unusually sensitive to haploinsufficiency and identify three further human disorders displaying a defective ATR-dependent DNA damage response. The striking correlation of ATR-pathway dysfunction with the presence of microcephaly and growth delay strongly suggests a causal relationship

    Lexical Diversity, Lexical Sophistication, and Predictability for Speech in Multiple Listening Conditions

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    When talkers anticipate that a listener may have difficulty understanding their speech, they adopt a speaking style typically described as “clear speech.” This speaking style includes a variety of acoustic modifications and has perceptual benefits for listeners. In the present study, we examine whether clear speaking styles also include modulation of lexical items selected and produced during naturalistic conversations. Our results demonstrate that talkers do, indeed, modulate their lexical selection, as measured by a variety of lexical diversity and lexical sophistication indices. Further, the results demonstrate that clear speech is not a monolithic construct. Talkers modulate their speech differently depending on the communication situation. We suggest that clear speech should be conceptualized as a set of speaking styles, in which talkers take the listener and communication situation into consideration
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