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991.
992.
Ana-Rita Goncalves Marie-Laurence Moraz Antonella Pasquato Ari Helenius Pierre-Yves Lozach Stefan Kunz 《Journal of virology》2013,87(21):11504-11515
The arenavirus Lassa virus (LASV) causes a severe hemorrhagic fever with high mortality in humans. Antigen-presenting cells, in particular dendritic cells (DCs), are early and preferred targets of LASV, and their productive infection contributes to the virus-induced immunosuppression observed in fatal disease. Here, we characterized the role of the C-type lectin DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN) in LASV entry into primary human DCs using a chimera of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) expressing the LASV glycoprotein (rLCMV-LASVGP). We found that differentiation of human primary monocytes into DCs enhanced virus attachment and entry, concomitant with the upregulation of DC-SIGN. LASV and rLCMV-LASVGP bound to DC-SIGN via mannose sugars located on the N-terminal GP1 subunit of LASVGP. We provide evidence that DC-SIGN serves as an attachment factor for rLCMV-LASVGP in monocyte-derived immature dendritic cells (MDDC) and can accelerate the capture of free virus. However, in contrast to the phlebovirus Uukuniemi virus (UUKV), which uses DC-SIGN as an authentic entry receptor, productive infection with rLCMV-LASVGP was less dependent on DC-SIGN. In contrast to the DC-SIGN-mediated cell entry of UUKV, entry of rLCMV-LASVGP in MDDC was remarkably slow and depended on actin, indicating the use of different endocytotic pathways. In sum, our data reveal that DC-SIGN can facilitate cell entry of LASV in human MDDC but that its role seems distinct from the function as an authentic entry receptor reported for phleboviruses. 相似文献
993.
IL‐1 signaling is critical for expansion but not generation of autoreactive GM‐CSF+ Th17 cells 下载免费PDF全文
Ilgiz A Mufazalov Carsten Schelmbauer Tommy Regen Janina Kuschmann Florian Wanke Laureen A Gabriel Judith Hauptmann Werner Müller Emmanuel Pinteaux Florian C Kurschus Ari Waisman 《The EMBO journal》2017,36(1):102-115
Interleukin‐1 (IL‐1) is implicated in numerous pathologies, including multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE). However, the exact mechanism by which IL‐1 is involved in the generation of pathogenic T cells and in disease development remains largely unknown. We found that following EAE induction, pertussis toxin administration leads to IL‐1 receptor type 1 (IL‐1R1)‐dependent IL‐1β expression by myeloid cells in the draining lymph nodes. This myeloid‐derived IL‐1β did not vitally contribute to the generation and plasticity of Th17 cells, but rather promoted the expansion of a GM‐CSF+ Th17 cell subset, thereby enhancing its encephalitogenic potential. Lack of expansion of GM‐CSF‐producing Th17 cells led to ameliorated disease in mice deficient for IL‐1R1 specifically in T cells. Importantly, pathogenicity of IL‐1R1‐deficient T cells was fully restored by IL‐23 polarization and expansion in vitro. Therefore, our data demonstrate that IL‐1 functions as a mitogenic mediator of encephalitogenic Th17 cells rather than qualitative inducer of their generation. 相似文献
994.
Energy Use and Greenhouse Gas Emissions of Air‐Source Heat Pump and Innovative Ground‐Source Air Heat Pump in a Cold Climate 下载免费PDF全文
Maija K. Mattinen Ari Nissinen Sampsa Hyysalo Jouni K. Juntunen 《Journal of Industrial Ecology》2015,19(1):61-70
This article compares climate impacts of two heat‐pump systems for domestic heating, that is, energy consumption for space heating of a residential building. Using a life cycle approach, the study compared the energy use and greenhouse gas (GHG) emissions of direct electric heating, a conventional air‐source heat pump, and a novel ground‐source air heat pump innovated by a citizen user, to assess whether such user innovation holds benefit. The energy use of the heat pumps was modeled at six temperature intervals based on duration curves of outdoor temperature. Additionally, two heat pump end‐of‐life scenarios were analyzed. Probabilistic uncertainty analysis was applied using a Monte Carlo simulation. The results indicated that, in ideal conditions, that is, assuming perfect air mixing, the conventional air‐source heat pump's emissions were over 40% lower and the ground‐air heat pump's emissions over 70% lower than in the case of direct electric heating. Although proper handling of the refrigerant is important, total leakage from the retirement of the heat‐pump appliance would increase GHG emissions by just 10%. According to the sensitivity analysis, the most influential input parameters are the emission factor related to electricity and the amount of electricity used for heating. 相似文献
995.
996.
Simón E Clotet J Calero F Ramos J Ariño J 《The Journal of biological chemistry》2001,276(32):29740-29747
A screening for multicopy suppressors of the G(1)/S blockage of a conditional sit4 hal3 mutant yielded the NHA1 gene, encoding a Na(+),K(+)/H(+) antiporter, composed of a transmembrane domain and a large carboxyl-terminal tail, which has been related to cation detoxification processes. Expression of either the powerful Saccharomyces cerevisiae Ena1 Na(+)/H(+)-ATPase or the Schizosaccharomyces pombe Sod2 Na(+)/H(+) antiporter, although increasing tolerance to sodium, was unable to mimic the Nha1 function in the cell cycle. Mutation of the conserved Asp residues Asp(266)-Asp(267) selectively abolished Na(+) efflux without modifying K(+) efflux and did not affect the capacity of Nha1 to relieve the G(1) blockage. Mutagenesis analysis revealed that the region near the carboxyl-terminal end of Nha1 comprising residues 800-948 is dispensable for sodium detoxification but necessary for transport of K(+) cations. Therefore, this portion of the protein contains structural elements that selectively modulate Nha1 antiporter functions. This region is also required for Nha1 to function in the cell cycle. However, expression of the closely related Cnh1 antiporter from Candida albicans, which also contains a long carboxyl-terminal extension, although allowing efficient K(+) transport does not relieve cell cycle blockage. This indicates that although the determinants for Nha1-mediated regulation of potassium transport and the cell cycle map very closely in the protein, most probably the function of Nha1 on cell cycle is independent of its ability to extrude potassium cations. 相似文献
997.
Ecosystem properties and microbial community changes in primary succession on a glacier forefront 总被引:13,自引:0,他引:13
We studied microbial community composition in a primary successional chronosequence on the forefront of Lyman Glacier, Washington,
United States. We sampled microbial communities in soil from nonvegetated areas and under the canopies of mycorrhizal and
nonmycorrhizal plants from 20- to 80-year-old zones along the successional gradient. Three independent measures of microbial
biomass were used: substrate-induced respiration (SIR), phospholipid fatty acid (PLFA) analysis, and direct microscopic counts.
All methods indicated that biomass increased over successional time in the nonvegetated soil. PLFA analysis indicated that
the microbial biomass was greater under the plant canopies than in the nonvegetated soils; the microbial community composition
was clearly different between these two types of soils. Over the successional gradient, the microbial community shifted from
bacterial-dominated to fungal-dominated. Microbial respiration increased while specific activity (respiration per unit biomass)
decreased in nonvegetated soils over the successional gradient. We proposed and evaluated new parameters for estimating the
C use efficiency of the soil microbial community: “Max” indicates the maximal respiration rate and “Acc” the total C released
from the sample after a standard amount of substrate is added. These, as well as the corresponding specific activities (calculated
as Max and Acc per unit biomass), decreased sharply over the successional gradient. Our study suggests that during the early
stages of succession the microbial community cannot incorporate all the added substrate into its biomass, but rapidly increases
its respiration. The later-stage microbial community cannot reach as high a rate of respiration per unit biomass but remains
in an “energy-saving state,” accumulating C to its biomass.
Received: 4 June 1998 / Accepted: 11 January 1999 相似文献
998.
Rousso-Noori L Knobler H Levy-Apter E Kuperman Y Neufeld-Cohen A Keshet Y Akepati VR Klinghoffer RA Chen A Elson A 《Cell metabolism》2011,13(5):562-572
Molecular-level understanding of body weight control is essential for combating obesity. We show that female mice lacking tyrosine phosphatase epsilon (RPTPe) are protected from weight gain induced by high-fat food, ovariectomy, or old age and exhibit increased whole-body energy expenditure and decreased adiposity. RPTPe-deficient mice, in particular males, exhibit improved glucose homeostasis. Female nonobese RPTPe-deficient mice are leptin hypersensitive and exhibit reduced circulating leptin concentrations, suggesting that RPTPe inhibits hypothalamic leptin signaling in vivo. Leptin hypersensitivity persists in aged, ovariectomized, and high-fat-fed RPTPe-deficient mice, indicating that RPTPe helps establish obesity-associated leptin resistance. RPTPe associates with and dephosphorylates JAK2, thereby downregulating leptin receptor signaling. Leptin stimulation induces phosphorylation of hypothalamic RPTPe at its C-terminal Y695, which drives RPTPe to downregulate JAK2. RPTPe is therefore an inhibitor of hypothalamic leptin signaling in vivo, and provides controlled negative-feedback regulation of this pathway following its activation. 相似文献
999.
Expression of Cell Cycle-Related Genes During Neuronal Apoptosis: Is there a Distinct Pattern? 总被引:5,自引:0,他引:5
Shirvan Anat Ziv Ilan Zilkha-Falb Rina Machlyn Tatyana Barzilai Ari Melamed Eldad 《Neurochemical research》1998,23(5):767-777
An emerging hypothesis considers the process of neuronal apoptosis as a consequence of unscheduled and unsynchronized induction of cell cycle mediators. Induction of several cell cycle genes precedes neuronal apoptosis and may be involved in determination of cell fate. We have now characterized changes in expression of cell cycle genes during apoptosis induced by oxidative stress in chick post-mitotic sympathetic neurons. Induction of cyclin B occurred prior to the commitment of neurons to both dopamine- and peroxide-triggered apoptosis. Both the neuronal death and the rise in cyclin B were inhibited by antioxidant treatment, suggesting a functional role for cyclin B induction during neuronal apoptosis. Induction of the cyclin dependent kinase CDK5 protein coincided with the time point when neurons were irreversibly committed to die. Expression of other cell cycle mediators such as cyclin D1 and the cyclin dependent kinases CDC2 and CDK2 was undetected and not induced by exposure to oxidative stress. Comparative analysis of the profile of cell cycle mediators induced during neuronal apoptosis of different neuronal cell populations revealed no distinct pattern of events. There are no cell cycle stage-specific mediators that are ultimately stimulated during neuronal apoptosis, suggesting that multiple pathways of re-activating the dormant cell-cycle, converge to determine entry into apoptosis. Nevertheless, the existence of some cell cycle mediators, that were not reported so far to be induced in post mitotic neurons during oxidative stress, substantiate them as part of the strong differentiating forces. 相似文献
1000.
The E3 ubiquitin ligase activity of arabidopsis PLANT U-BOX17 and its functional tobacco homolog ACRE276 are required for cell death and defense 总被引:10,自引:0,他引:10 下载免费PDF全文
Yang CW González-Lamothe R Ewan RA Rowland O Yoshioka H Shenton M Ye H O'Donnell E Jones JD Sadanandom A 《The Plant cell》2006,18(4):1084-1098