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101.
102.
The pruritic effect of purified bile salts has been tested by applying them to blister bases. All the salts tested were pruritogens, but the dihydroxy salts (especially unconjugated chenodeoxycholate) were more effective than the trihydroxy salts. This may explain the poor correlation between total serum bile salt concentration and pruritus in obstructive jaundice. 相似文献
103.
Solute yields, laboratory dissolution data and both chemical and isotopic markers of rock weathering reactions are used to characterise the biogeochemistry of glacial meltwaters draining a maritime Antarctic glacier. We find that delayed flowpaths through ice-marginal talus and moraine sediments are critical for the acquisition of solute from rock minerals because delayed flowpaths through subglacial sediments are absent beneath this small, cold-based glacier. Here the mechanisms of weathering are similar to those reported in subglacial environments, and include sub-oxic conditions in the early summer and increasingly oxic conditions thereafter. Up to 85% of the NO3 ? and 65% of the SO4 2? are most likely produced by bacterially mediated reactions in these ice marginal sediments. However, reactive pyrite phases are sparse in the host rocks, limiting the export of Fe, SO4 2? and cations that may be removed by weathering once pyrite oxidation has taken place. This means that dissolution of Ca2+ and Na+ from carbonate and silicate minerals dominate, producing moderate cationic denudation yields from Tuva Glacier (163 Σ*meq+ m?2 a?1) compared to a global range of values (94–4,200 Σ*meq+ km?2 a?1). Overall, crustally derived cations represent 42% of the total cationic flux, the rest being accounted for by snowpack sources. 相似文献
104.
Jill S. Heaton Kenneth E. Nussear Todd C. Esque Richard D. Inman Frank M. Davenport Thomas E. Leuteritz Philip A. Medica Nathan W. Strout Paul A. Burgess Lisa Benvenuti 《Biodiversity and Conservation》2008,17(3):575-590
Spatially explicit decision support systems are assuming an increasing role in natural resource and conservation management.
In order for these systems to be successful, however, they must address real-world management problems with input from both
the scientific and management communities. The National Training Center at Fort Irwin, California, has expanded its training
area, encroaching U.S. Fish and Wildlife Service critical habitat set aside for the Mojave desert tortoise (Gopherus agassizii), a federally threatened species. Of all the mitigation measures proposed to offset expansion, the most challenging to implement
was the selection of areas most feasible for tortoise translocation. We developed an objective, open, scientifically defensible
spatially explicit decision support system to evaluate translocation potential within the Western Mojave Recovery Unit for
tortoise populations under imminent threat from military expansion. Using up to a total of 10 biological, anthropogenic, and/or
logistical criteria, seven alternative translocation scenarios were developed. The final translocation model was a consensus
model between the seven scenarios. Within the final model, six potential translocation areas were identified. 相似文献
105.
106.
Joseph D. Trimarco Brook E. Heaton Ryan R. Chaparian Kaitlyn N. Burke Raquel A. Binder Gregory C. Gray Clare M. Smith Vineet D. Menachery Nicholas S. Heaton 《PLoS pathogens》2021,17(5)
Antiviral therapeutics are a front-line defense against virally induced diseases. Because viruses frequently mutate to escape direct inhibition of viral proteins, there is interest in targeting the host proteins that the virus must co-opt to complete its replication cycle. However, a detailed understanding of the interactions between the virus and the host cell is necessary in order to facilitate development of host-directed therapeutics. As a first step, we performed a genome-wide loss of function screen using the alphacoronavirus HCoV-229E to better define the interactions between coronaviruses and host factors. We report the identification and validation of an ER-resident host protein, TMEM41B, as an essential host factor for not only HCoV-229E but also genetically distinct coronaviruses including the pandemic betacoronavirus SARS-CoV-2. We show that the protein is required at an early, but post-receptor engagement, stage of the viral lifecycle. Further, mechanistic studies revealed that although the protein was not enriched at replication complexes, it likely contributes to viral replication complex formation via mobilization of cholesterol and other lipids to facilitate host membrane expansion and curvature. Continued study of TMEM41B and the development of approaches to prevent its function may lead to broad spectrum anti-coronavirus therapeutics. 相似文献
107.
Nicholas S. Heaton Victor H. Leyva-Grado Gene S. Tan Dirk Eggink Rong Hai Peter Palese 《Journal of virology》2013,87(15):8272-8281
Influenza A virus is a major human pathogen responsible for seasonal epidemics as well as pandemic outbreaks. Due to the continuing burden on human health, the need for new tools to study influenza virus pathogenesis as well as to evaluate new therapeutics is paramount. We report the development of a stable, replication-competent luciferase reporter influenza A virus that can be used for in vivo imaging of viral replication. This imaging is noninvasive and allows for the longitudinal monitoring of infection in living animals. We used this tool to characterize novel monoclonal antibodies that bind the conserved stalk domain of the viral hemagglutinin of H1 and H5 subtypes and protect mice from lethal disease. The use of luciferase reporter influenza viruses allows for new mechanistic studies to expand our knowledge of virus-induced disease and provides a new quantitative method to evaluate future antiviral therapies. 相似文献
108.
Marieta Barrow Heaton Kendra Siler‐Marsiglio Michael Paiva Alexandra Kotler Jonathan Rogozinski Stacey Kubovec Mary Coursen Vladimir Madorsky 《Developmental neurobiology》2013,73(2):127-141
These studies investigated interactions taking place at the mitochondrial membrane in neonatal rat cerebellum following ethanol exposure and focused on interactions between proapoptotic Bax and proteins of the permeability transition pore (PTP), voltage‐dependent anion channel (VDAC) and adenine nucleotide translocator (ANT) of the outer and inner mitochondrial membranes, respectively. Cultured cerebellar granule cells were used to assess the role of these interactions in ethanol neurotoxicity. Analyses were made at the age of maximal cerebellar ethanol vulnerability (P4), compared to the later age of relative resistance (P7), to determine whether differential ethanol sensitivity was mirrored by differences in these molecular interactions. We found that, following ethanol exposure, Bax proapoptotic associations with both VDAC and ANT were increased, particularly at the age of greater ethanol sensitivity, and these interactions were sustained at this age for at least 2 h postexposure. Since Bax:VDAC interactions disrupt protective VDAC interactions with mitochondrial hexokinase (HXK), we also assessed VDAC:HXK associations following ethanol treatment and found such interactions were altered by ethanol treatment, but only at 2 h postexposure and only in the P4, ethanol‐sensitive cerebellum. Ethanol neurotoxicity in cultured neuronal preparations was abolished by pharmacological inhibition of both VDAC and ANT interactions with Bax but not by a Bax channel blocker. Therefore, we conclude that, at this age, within the constraints of our experimental model, a primary mode of Bax‐induced initiation of the apoptosis cascade following ethanol insult involves interactions with proteins of the PTP complex and not channel formation independent of PTP constituents. © 2012 Wiley Periodicals, Inc. Develop Neurobiol, 2013 相似文献
109.
Soil carbon increased by twice the amount of biochar carbon applied after 6 years: Field evidence of negative priming 总被引:1,自引:0,他引:1
Humberto Blanco‐Canqui David A. Laird Emily A. Heaton Samuel Rathke Bharat Sharma Acharya 《Global Change Biology Bioenergy》2020,12(4):240-251
Applying biochar to agricultural soils has been proposed as a means of sequestering carbon (C) while simultaneously enhancing soil health and agricultural sustainability. However, our understanding of the long‐term effects of biochar and annual versus perennial cropping systems and their interactions on soil properties under field conditions is limited. We quantified changes in soil C concentration and stocks, and other soil properties 6 years after biochar applications to corn (Zea mays L.) and dedicated bioenergy crops on a Midwestern US soil. Treatments were as follows: no‐till continuous corn, Liberty switchgrass (Panicum virgatum L.), and low‐diversity prairie grasses, 45% big bluestem (Andropogon gerardii), 45% Indiangrass (Sorghastrum nutans), and 10% sideoats grama (Bouteloua curtipendula), as main plots, and wood biochar (9.3 Mg/ha with 63% total C) and no biochar applications as subplots. Biochar‐amended plots accumulated more C (14.07 Mg soil C/ha vs. 2.25 Mg soil C/ha) than non‐biochar‐amended plots in the 0–30 cm soil depth but other soil properties were not significantly affected by the biochar amendments. The total increase in C stocks in the biochar‐amended plots was nearly twice (14.07 Mg soil C/ha) the amount of C added with biochar 6 years earlier (7.25 Mg biochar C/ha), suggesting a negative priming effect of biochar on formation and/or mineralization of native soil organic C. Dedicated bioenergy crops increased soil C concentration by 79% and improved both aggregation and plant available water in the 0–5 cm soil depth. Biochar did not interact with the cropping systems. Overall, biochar has the potential to increase soil C stocks both directly and through negative priming, but, in this study, it had limited effects on other soil properties after 6 years. 相似文献
110.
The current model of hepatitis C virus (HCV) production involves the assembly of virions on or near the surface of lipid droplets, envelopment at the ER in association with components of VLDL synthesis, and egress via the secretory pathway. However, the cellular requirements for and a mechanistic understanding of HCV secretion are incomplete at best. We combined an RNA interference (RNAi) analysis of host factors for infectious HCV secretion with the development of live cell imaging of HCV core trafficking to gain a detailed understanding of HCV egress. RNAi studies identified multiple components of the secretory pathway, including ER to Golgi trafficking, lipid and protein kinases that regulate budding from the trans-Golgi network (TGN), VAMP1 vesicles and adaptor proteins, and the recycling endosome. Our results support a model wherein HCV is infectious upon envelopment at the ER and exits the cell via the secretory pathway. We next constructed infectious HCV with a tetracysteine (TC) tag insertion in core (TC-core) to monitor the dynamics of HCV core trafficking in association with its cellular cofactors. In order to isolate core protein movements associated with infectious HCV secretion, only trafficking events that required the essential HCV assembly factor NS2 were quantified. TC-core traffics to the cell periphery along microtubules and this movement can be inhibited by nocodazole. Sub-populations of TC-core localize to the Golgi and co-traffic with components of the recycling endosome. Silencing of the recycling endosome component Rab11a results in the accumulation of HCV core at the Golgi. The majority of dynamic core traffics in association with apolipoprotein E (ApoE) and VAMP1 vesicles. This study identifies many new host cofactors of HCV egress, while presenting dynamic studies of HCV core trafficking in infected cells. 相似文献