Open Access
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Item Open Access Muscle cramps? Try pickle juice(2022-12-21) Kolasa, Kathryn M.; Fletcher, MorganItem Open Access Developing Functional Network Connectivity of the Dorsal Anterior Cingulate Cortex Mediates Externalizing Psychopathology in Adolescents with Child Neglect(2021) Boney, Simone; Silveira, Sarita; Tapert, Susan F.; Mishra, JyotiItem Open Access Introduction: Biology and the Idea of Culture(2014) Feder, HelenaThis chapter analyses Frankenstein's dramatization of the costs and consequences of the drive for transcendence in terms of humanist culture's anxieties about human and nonhuman identities in capitalist production. The chapter considers the novel's considerable critical landscape and then its composition history, using a reading of Percy Bysshe Shelley's "Mont Blanc" to open a key moment in Shelley's novel. The oceanic feeling functions as social feeling that extends outwards to both human and nonhuman others. This oceanic or eco-social feeling is, to borrow a use of the term from Mary Mellor, an "immanent" sensibility, a sense of the interconnectedness of the world. Frankenstein moves like an iceberg in chill waters. Structurally, the narrative is surrounded by the Arctic Ocean and, within each concentric narration, a body of water serves as the background for the novel's most dramatic action.Item Open Access Rethinking Multiculturalism: theory and nonhuman cultures(2010) Feder, HelenaItem Open Access Item Open Access Contradiction Is Not Disappointing: An Interview with Michael Hardt(2019-08-19) Feder, HelenaItem Open Access "The Universe is Imaginative": An Interview with David Robertson(2017) Feder, HelenaItem Open Access Science and Social Change: A Conversation with Robert Sapolsky(2019-03-07) Feder, HelenaItem Open Access "Never Waste a Good Crisis": An Interview with Mary Mellor(2018-07-19) Feder, HelenaItem Open Access This Still Present Moment: an Interview with Gary Snyder(2016) Feder, HelenaItem Open Access “The Ingenious Unravelling of Evidence”: Empathy, Extinction, and Wells’s The Croquet Player(2019-09-01) Feder, HelenaWhile we are increasingly challenged to imagine a world without humans, we have also become increasingly attentive to the subject of empathy, in popular culture, the humanities, and the sciences. In The Time Machine (1895), and a number of essays on evolution or extinction, H. G. Wells articulated a speculative evolutionary theory, a vision of nature unencumbered by everyday anthropocentricism. His little-known 1936 novella, The Croquet Player, continues his evolutionary story of humanity by turning to the future’s entanglement with the past and culture’s entanglement with nature. Prescient, Wells’s novella speaks to the parallel phenomena entangled in the strange relation between extinction and empathy.Item Open Access TRANSHUMANISM, FRANKENSTEIN, AND EXTINCTION(2018) Feder, HelenaShelley's novel has been fertile ground for ecocritics over the last two decades. In Ecocriticism and the Idea of Culture (2014, 2016) I wrote about Frankenstein and culture's dialectical horror of nature. As a narrative of failed continuity, Frankenstein also exhibits our fear of culture, its machine determinism, of monstrous production in place of sustainable reproduction. Victor, the isolated, compulsive scientist is not unlike the figure of the lone programmer, coding for the "enhanced" human or cyborg of his uncritical posthuman dreams. Our world and its problems demonstrate that Frankenstein continues to be a prescient novel: before Darwin's theory of evolution, and long before genetic modification and what we call information technology, Shelley imagined the creation of a being as an assemblage of contingent "natureculture" in a bildungsroman that juxtaposes its creator's. While the novel invites us to consider the political promise of the monster (as I've argued elsewhere), it is also a commentary on the dangers of solitude, the dangers of failing to honour the social and ecological contingency, the entanglement, of all things in the pursuit of knowledge.Item Open Access Comparative Genomics and Evolution of Proteins Associated with RNA Polymerase II C-Terminal Domain(2005-11) Guo, Zhenhua; Stiller, John W.The C-terminal domain (CTD) of the largest subunit of RNA polymerase II provides an anchoring point for a wide variety of proteins involved in mRNA synthesis and processing. Most of what is known about CTD-protein interactions comes from animal and yeast models. The consensus sequence and repetitive structure of the CTD is conserved strongly across a wide range of organisms, implying that the same is true of many of its known functions. In some eukaryotic groups, however, the CTD has been allowed to degenerate, suggesting a comparable lack of essential protein interactions. To date, there has been no comprehensive examination of CTD-related proteins across the eukaryotic domain to determine which of its identified functions are correlated with strong stabilizing selection on CTD structure. Here we report a comparative investigation of genes encoding 50 CTD-associated proteins, identifying putative homologs from 12 completed or nearly completed eukaryotic genomes. The presence of a canonical CTD generally is correlated with the apparent presence and conservation of its known protein partners; however, no clear set of interactions emerges that is invariably linked to conservation of the CTD. General rates of evolution, phylogenetic patterns, and the conservation of modeled tertiary structure of capping enzyme guanylyltransferase (Cgt1) indicate a pattern of coevolution of components of a transcription factory organized around the CTD, presumably driven by common functional constraints. These constraints complicate efforts to determine orthologous gene relationships and can mislead phylogenetic and informatic algorithms.Item Open Access Comparative Study of the Roles of AhpC and KatE as Respiratory Antioxidants in Brucella abortus 2308(2010-10) Steele, Kendra H.; Baumgartner, John; Wright Valderas, Michelle; Roop II, R. MartinBrucella strains are exposed to potentially toxic levels of H2O2 both as a consequence of their aerobic metabolism and through the respiratory burst of host phagocytes. To evaluate the relative contributions of the sole catalase KatE and the peroxiredoxin AhpC produced by these strains in defense against H2O2-mediated toxicity, isogenic katE, ahpC, and katE ahpC mutants were constructed and the phenotypic properties of these mutants compared with those of the virulent parental strain B. abortus 2308. The results of these studies indicate that AhpC is the primary detoxifier of endogenous H2O2 generated by aerobic metabolism. KatE, on the other hand, plays a major role in scavenging exogenous and supraphysiologic levels of H2O2, although this enzyme can play a supporting role in the detoxification of H2O2 of endogenous origin if AhpC is absent. B. abortus ahpC and katE mutants exhibit wild-type virulence in C57BL/6 and BALB/c mice, but the B. abortus ahpC katE double mutant is extremely attenuated, and this attenuation is not relieved in derivatives of C57BL/6 mice that lack NADPH oxidase (cybb) or inducible nitric oxide synthase (Nos2) activity. These experimental findings indicate that the generation of endogenous H2O2 represents a relevant environmental stress that B. abortus 2308 must deal with during its residence in the host and that AhpC and KatE perform compensatory roles in detoxifying this metabolic H2O2. Brucella abortus, a facultative intracellular pathogen, causes abortion and infertility in cattle. Humans can also be infected by ingesting contaminated dairy products, through inhalation of infectious aerosols, or via direct contact with an infected fetus (43). Human brucellosis causes flu-like symptoms with a relapsing fever, and this debilitating disease can persist for months or years without appropriate treatment. Although human brucellosis remains a significant zoonotic disease worldwide (47) and a potential bioterrorism threat (70), there is currently no vaccine to prevent human infection, and antibiotic treatment of these infections remains problematic (2). Prolonged survival and replication in host macrophages play a critical role in the virulence of the Brucella spp. (34, 57). Experimental evidence indicates that reactive oxygen species (ROS) such as superoxide (O2−) and hydrogen peroxide (H2O2) are important components of the brucellacidal activity of these phagocytes (31). Because the brucellae rely on respiratory metabolism for their energy production (52), these bacteria must also deal with endogenous ROS generated as a by-product of aerobic metabolism (27). Several enzymes that directly detoxify O2− and H2O2 have been identified in Brucella. SodC is a periplasmic Cu-Zn superoxide dismutase (6), and phenotypic evaluation of an isogenic sodC mutant indicates that this enzyme protects B. abortus 2308 from O2− generated by the oxidative burst of host macrophages (22). Brucella strains also produce a single monofunctional catalase that is a structural homolog of Escherichia coli KatE. Although this protein does not possess a standard export signal sequence (63) or a predicted twin arginine transport signal sequence (data not shown), cell fractionation studies with the appropriate controls indicate that this protein resides in the periplasmic compartment (63). B. abortus and Brucella melitensis katE mutants exhibit increased sensitivity to H2O2 compared to their parental strains in in vitro assays (21, 33). A B. melitensis katE mutant retains its virulence in experimentally infected goats (21), and B. abortus katE mutants display wild-type virulence in the mouse model (59). These experimental findings suggest that KatE does not play an indispensable role in protecting the brucellae from oxidative killing by host phagocytes. A gene (BAB1_0591) encoding a Mn superoxide dismutase (SodA) has also been identified in B. abortus 2308. SodA activity increases in a B. abortus sodC mutant, suggesting that SodA works in concert with SodC to protect B. abortus 2308 from oxidative damage (65), but the precise role that SodA plays in resistance to oxidative stress in this bacterium remains to be determined experimentally. The genes designated BAB2_0531 and BAB2_0532 in the B. abortus 2308 genome sequence are predicted to encode the components of an alkyl hydroperoxide reductase complex (AhpC and AhpD, respectively). Peroxiredoxins of the AhpC family detoxify H2O2, organic peroxides, and peroxynitrite (ONOO−) (9, 48). AhpD and AhpF are peroxiredoxin reductases that use reducing equivalents generated by cellular metabolism to restore the enzymatic activity of AhpC (10, 49). Studies performed with multiple bacterial species indicate that the AhpCD and AhpCF complexes serve as important antioxidants (4, 8, 11, 15, 16, 36, 37, 41, 44, 55, 66), and indeed, work in E. coli suggests that AhpC is the major scavenger of H2O2 generated in the cytoplasm of this bacterium as a by-product of aerobic metabolism (61). AhpC has also been shown to play a role in the virulence of several bacterial pathogens, including Helicobacter pylori (45), Mycobacterium bovis (72), and Staphylococcus aureus (15) but does not appear to be required for the virulence of Salmonella enterica serovar Typhimurium (68), Mycobacterium tuberculosis (64), Legionella pneumophila (51), or Porphyromonas gingivalis (32) in experimental models. In this report, we present evidence that AhpC is the primary antioxidant used by B. abortus 2308 to detoxify endogenous H2O2 generated by respiratory metabolism during routine aerobic cultivation. KatE, on the other hand, plays a major role in scavenging exogenous and supraphysiologic levels of H2O2, although this enzyme can play a supporting role in the detoxification of H2O2 of endogenous origin if AhpC is absent. Interestingly, AhpC and KatE appear to play complementary roles in protecting B. abortus 2308 from H2O2 of metabolic origin during residence in mice, and the presence of either AhpC or KatE alone is sufficient to allow this strain to maintain a chronic infection.Item Open Access Comparative impacts of two major hurricane seasons on the Neuse River and western Pamlico Sound ecosystems(2004-06-22) Corbett, D. Reide (David Reide), 1971-Ecosystem-level impacts of two hurricane seasons were compared several years after the storms in the largest lagoonal estuary in the U.S., the Albemarle–Pamlico Estuarine System. A segmented linear regression flow model was developed to compare mass-water transport and nutrient loadings to a major artery, the Neuse River Estuary (NRE), and to estimate mean annual versus storm-related volume delivery to the NRE and Pamlico Sound. Significantly less water volume was delivered by Hurricane Fran (1996), but massive fish kills occurred in association with severe dissolved oxygen deficits and high contaminant loadings (total nitrogen, total phosphorus, suspended solids, and fecal bacteria). The high water volume of the second hurricane season (Hurricanes Dennis, Floyd, and Irene in 1999) delivered generally comparable but more dilute contaminant loads, and no major fish kills were reported. There were no discernable long-term adverse impacts on water quality. Populations of undesirable organisms, such as toxic dinoflagellates, were displaced down-estuary to habitats less conducive for growth. The response of fisheries was species-dependent: there was no apparent impact of the hurricanes on commercial landings of bivalve molluscs or shrimp. In contrast, interacting effects of hurricane floodwaters in 1999 and intensive fishing pressure led to striking reductions in blue crabs. Overall, the data support the premise that, in shallow estuaries frequently disturbed by hurricanes, there can be relatively rapid recovery in water quality and biota, and benefit from the scouring activity of these storms.Item Open Access Comparative evaluation of two severe acute respiratory syndrome (SARS) vaccine candidates in mice challenged with SARS coronavirus(2006-03-01) Roper, Rachel L.Two different severe acute respiratory syndrome (SARS) vaccine strategies were evaluated for theirability to protect against live SARS coronavirus (CoV) challenge in a murine model of infection.A whole killed (inactivated byb-propiolactone) SARS-CoV vaccine and a combination of twoadenovirus-based vectors, one expressing the nucleocapsid (N) and the other expressing the spike(S) protein (collectively designated Ad S/N), were evaluated for the induction of serum neutralizingantibodies and cellular immune responses and their ability to protect against pulmonary SARS-CoVreplication. The whole killed virus (WKV) vaccine given subcutaneously to 129S6/SvEv micewas more effective than the Ad S/N vaccine administered either intranasally or intramuscularlyin inhibiting SARS-CoV replication in the murine respiratory tract. This protective ability of theWKV vaccine correlated with the induction of high serum neutralizing-antibody titres, but not withcellular immune responses as measured by gamma interferon secretion by mouse splenocytes.Titres of serum neutralizing antibodies induced by the Ad S/N vaccine administered intranasallyor intramuscularly were significantly lower than those induced by the WKV vaccine. However,Ad S/N administered intranasally, but not intramuscularly, significantly limited SARS-CoVreplication in the lungs. Among the vaccine groups, SARS-CoV-specific IgA was found only in thesera of mice immunized intranasally with Ad S/N, suggesting that mucosal immunity may play arole in protection for the intranasal Ad S/N delivery system. Finally, the sera of vaccinated micecontained antibodies to S, further suggesting a role for this protein in conferring protective immunityagainst SARS-CoV infectionItem Open Access Comparative DNA Analysis of Solid Tumors by Flow Cytometric and Image Analyses of Touch Imprints and Flow Cell Suspensions(1992-09-01) Elsheikh, Tarik M.; Silverman, Jan F.; Mccool, Janet W.; Riley, Roger S.Comparative DNA analysis by flow cytometric (FCM) and image analyses (IA) has shown a high concordance rate. When present, discordance has been attributed to the presence of aneuploid cell populations detected only by IA, yet missed by FCM. This phenomenon has been explained by loss of aneuploid cells during FCM cell processing, differences in sampling area, or misinterpretation of the DNA histograms. To determine which factors are responsible for the discordance between IA and FCM, 82 fresh solid tumors from various sites were examined. Flow cytometric analysis was performed on cell suspensions isolated from the tumors, whereas IA was performed on touch imprints (IAT) and on cytosmears of the same cell suspension used for FCM (IAF). Comparison between IAT and IAF (IAT/IAF) assessed cell processing and sampling area differences, whereas IAF/FCM comparison assessed differences in apparatus and methodology as possible contributing factors to discordance. Furthermore, DNA histograms of IAT, IAF, and FCM were analyzed in the discordant cases to determine whether the discordance was due primarily to different cell populations detected (true discordance) or due to differences in histogram interpretation of the same cell populations (false discordance). IAT/IAF and IAF/FCM concordance rates (90% and 88%) were not significantly different from that of IAT/FCM (87%). False discordance accounted for most of the discordant cases in IAT/FCM comparison (six cases, 67%), whereas true discordance was seen in three cases. In all three truly discordant cases, the DNAaneuploid cell populations detected only by IAT yet missed by FCM were also detected by IAF. This study demonstrates that discordance between IA and FCM is probably not due to cell loss during FCM cell processing or sampling area differences, but may be due to differences in assessing DNA ploidy in the interpretation of IA histograms and/or dilution of aneuploid cells by normal diploid cells in FCM.Item Open Access Compactifications of convergens spaces(1979) Kent, D.C.; Richardson, G.D.This paper summarizes most of the results to date on convergence space compactifications, and establishes necessary and sufficient conditions for the existence of largest and smallest compactifications subject to various conditions imposed upon the compactifications.Item Open Access Compact operators and nest representations of limit algebras(2007-01-04) Katsoulis, Elias; Peters, Justin R.In this paper we study the nest representations $ \rho: \mathcal{A} \longrightarrow \operatorname{Alg} \mathcal{N}$ of a strongly maximal TAF algebra $ \mathcal{A}$, whose ranges contain non-zero compact operators. We introduce a particular class of such representations, the essential nest representations, and we show that their kernels coincide with the completely meet irreducible ideals. From this we deduce that there exist enough contractive nest representations, with non-zero compact operators in their range, to separate the points in $ \mathcal{A}$. Using nest representation theory, we also give a coordinate-free description of the fundamental groupoid for strongly maximal TAF algebras. For an arbitrary nest representation $ \rho: \mathcal{A} \longrightarrow \operatorname{Alg} \mathcal{N}$, we show that the presence of non-zero compact operators in the range of $ \rho$ implies that $ \mathcal{N}$ is similar to a completely atomic nest. If, in addition, $ \rho (\mathcal{A} )$ is closed, then every compact operator in $ \rho (\mathcal{A} )$ can be approximated by sums of rank one operators $ \rho (\mathcal{A} )$. In the case of $ \mathbb{N}$-ordered nest representations, we show that $ \rho ( \mathcal{A})$ contains finite rank operators iff $ \ker \rho $ fails to be a prime ideal.Item Open Access Combined effects of aberrant MEK1 activity and BCL2 overexpression on relieving the cytokine dependency of human and murine hematopoietic cells(2000-06-06) Blalock, WL; Moye, PW; Chang, Fumin; Pearce, M; LS, Steelman; McMahon, M; McCubrey, JAThe MEK1 oncoprotein plays a critical role in Ras/Raf/ MEK/MAPK-mediated transmission of mitogenic signals from cell surface receptors to the nucleus. In order to examine this pathway's role in leukemic transformation, a conditionally active (β-estradiol-inducible) form of the MEK1 protein was created by ligating a cDNA encoding an N-terminal truncated form of MEK1 to the hormone-binding domain of the estrogen receptor (ER). We introduced this chimeric ΔMEK1:ER oncoprotein into cytokine-dependent human TF-1 and murine FDC-P1 hematopoietic cell lines. Two different types of cells were recovered after drug selection in medium containing either cytokine or β-estradiol: (1) cells that expressed the ΔMEK1:ER oncoprotein but remained cytokine-dependent and (2) MEK1-responsive cells that grew in response to ΔMEK1:ER activation. Cytokine-dependent cells were recovered 102 to 104 times more frequently than MEK1-responsive cells depending upon the particular cell line. To determine whether BCL2 overexpression could synergize with the ΔMEK1:ER oncoprotein in relieving cytokine dependence, the cytokine-dependent ΔMEK1:ER-expressing cells were infected with a BCL2-containing retrovirus, and the frequency of MEK1-responsive cells determined. BCL2 overexpression, by itself, did not relieve cytokine dependency of the parental cells, however, it did increase the frequency at which MEK1-responsive cells were recovered approximately 10-fold. ΔMEK1:ER+BCL2 cells remained viable for at least 3 days after estradiol deprivation, whereas viability was readily lost upon withdrawal of β-estradiol in the MEK1-responsive cells which lacked BCL2 overexpression. The MAP kinases, ERK1 and ERK2 were activated in response to ΔMEK1:ER stimulation in both ΔMEK1:ER and ΔMEK1:ER+BCL2 cells. As compared to the cytokine-dependent ΔMEK1:ER and BCL2 infected cells, MEK1-responsive BCL2 infected cells expressed higher levels of BCL2. While both MEK1-responsive ΔMEK1:ER and ΔMEK1:ER+BCL2 infected cells expressed cDNAs encoding the autocrine cytokine GM-CSF, more GM-CSF cDNAs and bioactivity were detected in the MEK1-responsive ΔMEK1:ER+BCL2 cells than in the MEK1-responsive cells lacking BCL2 or cytokine-dependent cells. These conditionally transformed cells will be useful in furthering our understanding of the roles MEK1 and BCL2 play in the prevention of apoptosis in hematopoietic cells.