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431.
Gabriel Bidaux Anne-Sophie Borowiec Natalia Prevarskaya Dmitri Gordienko 《Channels (Austin, Tex.)》2016,10(4):320-331
Recently, we reported the cloning and characterization of short isoform of the icilin-activated cold receptor TRPM8 channel in keratinocytes, dubbed eTRPM8. We demonstrated that eTRPM8 via fine tuning of the endoplasmic reticulum (ER) – mitochondria Ca2+ shuttling regulates mitochondrial ATP and superoxide (O2?-) production and, thereby, mediates control of epidermal homeostasis by mild cold. Here, we provide additional information explaining why eTRPM8 suppression and TRPM8 stimulation both inhibit keratinocyte growth. We also demonstrate that stimulation of eTRPM8 with icilin may give rise to sustained oscillatory responses. Furthermore, we show that ATP-induced cytosolic and mitochondrial Ca2+ responses are attenuated by eTRPM8 suppression. This suggests positive interplay between eTRPM8 and purinergic signaling pathways, what may serve to facilitate the ER-mitochondria Ca2+ shuttling. Finally, we demonstrate that cold (25°C) induces eTRPM8-dependent superoxide-mediated necrosis of keratinocytes. Altogether, these results are in line with our model of eTRPM8-mediated cold-dependent balance between keratinocyte proliferation and differentiation. 相似文献
432.
Porphobilinogen-synthase (PBG-synthase) is an enzyme extensively used as a bioindicator of metals and other oxidizing agents. The objective of this study was to verify the effects of HgCl(2) (5mg/kg/day, s.c.), a metal that mainly affects the nervous and renal systems, on kidney, liver and brain from rats exposed during one of the phases considered critical for development. Mercury decreased PBG-synthase activity from liver, kidney and brain and altered corporal, renal and cerebral weights. The kidney was the most sensitive tissue. It accumulated a large amount of metal and PBG-synthase activity was decreased up to 50%. The second period seemed to be the most sensitive, because in this phase the rats presented alterations in body, brain and kidney weights, and there was also an expressive inhibition in hepatic and renal PBG-synthase activities. In general, large quantities of metal accumulated in the tissues are in agreement with the inhibition verified in these tissues. 相似文献
433.
Identification of binding partners is the crucial first step towards understanding the biological function of a protein. Many protein-protein interactions occur via modular domains that recognize short peptide motifs in their target proteins. Here we describe a chemical/bioinformatics approach for predicting the binding partners of modular domains. The optimal binding motif(s) of a protein domain is identified by screening a combinatorial peptide library. The resulting consensus sequence is used to search protein and genomic databases for potential binding proteins, which are subsequently confirmed (or disproved) by conventional protein binding assays (e.g. pull-down and co-immunoprecipitation). 相似文献
434.
Regulatory T cells prevent CD8 T cell maturation by inhibiting CD4 Th cells at tumor sites 总被引:2,自引:0,他引:2
Chaput N Darrasse-Jèze G Bergot AS Cordier C Ngo-Abdalla S Klatzmann D Azogui O 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(8):4969-4978
Natural regulatory T cells (Tregs) are present in high frequencies among tumor-infiltrating lymphocytes and in draining lymph nodes, supposedly facilitating tumor development. To investigate their role in controlling local immune responses, we analyzed intratumoral T cell accumulation and function in the presence or absence of Tregs. Tumors that grew in normal BALB/c mice injected with the 4T1 tumor cell line were highly infiltrated by Tregs, CD4 and CD8 cells, all having unique characteristics. Most infiltrating Tregs expressed low levels of CD25Rs and Foxp3. They did not proliferate even in the presence of IL-2 but maintained a strong suppressor activity. CD4 T cells were profoundly anergic and CD8 T cell proliferation and cytotoxicity were severely impaired. Depletion of Tregs modified the characteristics of tumor infiltrates. Tumors were initially invaded by activated CD4(+)CD25(-) T cells, which produced IL-2 and IFN-gamma. This was followed by the recruitment of highly cytotoxic CD8(+) T cells at tumor sites leading to tumor rejection. The beneficial effect of Treg depletion in tumor regression was abrogated when CD4 helper cells were also depleted. These findings indicate that the massive infiltration of tumors by Tregs prevents the development of a successful helper response. The Tregs in our model prevent Th cell activation and subsequent development of efficient CD8 T cell activity required for the control of tumor growth. 相似文献
435.
Levin Simon A. Anderies John M. Adger Neil Barrett Scott Bennett Elena M. Cardenas Juan Camilo Carpenter Stephen R. Crpin Anne-Sophie Ehrlich Paul Fischer Joern Folke Carl Kautsky Nils Kling Catherine Nyborg Karine Polasky Stephen Scheffer Marten Segerson Kathleen Shogren Jason van den Bergh Jeroen Walker Brian Weber Elke U. Wilen James 《Ecosystems》2022,25(3):697-711
Ecosystems - The increasing frequency of extreme events, exogenous and endogenous, poses challenges for our societies. The current pandemic is a case in point; but "once-in-a-century"... 相似文献
436.
Agnes Rouaud Olivier Hanon Anne-Sophie Boureau Guillaume Gilles Chapelet Laure de Decker 《PloS one》2015,10(3)
Background
Given the prevalence of non-valvular atrial fibrillation in the geriatric population, thromboembolic prevention by means of vitamin K antagonists (VKA) is one of the most frequent daily concerns of practitioners. The effectiveness and safety of treatment with VKA correlates directly with maximizing the time in therapeutic range, with an International Normalized Ratio (INR) of 2.0-3.0. The older population concentrates many of factors known to influence INR rate, particularly concomitant medications and concurrent medical conditions, also defined as comorbidities.Objective
Determine whether a high burden on comorbidities, defined by a Charlson Comorbidity Index (CCI) of 3 or greater, is associated a lower quality of INR control.Study-Design
Cross-sectional study.Settings
French geriatric care units nationwide.Participants
2164 patients aged 80 and over and treated with vitamin K antagonists.Measurements
Comorbidities were assessed using the Charlson Comorbidity Index (CCI). The recorded data included age, sex, falls, kidney failure, hemorrhagic event, VKA treatment duration, and the number and type of concomitant medications. Quality of INR control, defined as time in therapeutic range (TTR), was assessed using the Rosendaal method.Results
487 patients were identified the low-quality control of INR group. On multivariate logistic regression analysis, low-quality control of INR was independently associated with a CCI ≥3 (OR = 1.487; 95% CI [1.15; 1.91]). The other variables associated with low-quality control of INR were: hemorrhagic event (OR = 3.151; 95% CI [1.64; 6.07]), hospitalization (OR = 1.614, 95% CI [1.21; 2.14]).Conclusion
An elevated CCI score (≥3) was associated with low-quality control of INR in elderly patients treated with VKA. Further research is needed to corroborate this finding. 相似文献437.
Roula Tahtouh Anne-Sophie Azzi Nada Alaaeddine Soulaima Chamat Hasnaa Bouharoun-Tayoun Layal Wardi Issam Raad Riad Sarkis Najibe Abou Antoun George Hilal 《PloS one》2015,10(3)
Alpha-fetoprotein (AFP) is a diagnostic marker for hepatocellular carcinoma (HCC). A direct relationship between poor prognosis and the concentration of serum AFP has been observed. Telomerase, an enzyme that stabilizes the telomere length, is expressed by 90% of HCC. The aim of this study was to investigate the effect of telomerase inhibition on AFP secretion and the involvement of the PI3K/Akt/mTOR signaling pathway. Proliferation and viability tests were performed using tetrazolium salt. Apoptosis was determined through the Annexin V assay using flow cytometry. The concentrations of AFP were measured using ELISA kits. The AFP mRNA expression was evaluated using RT-PCR, and cell migration was evaluated using a Boyden chamber assay. The in vivo effect of costunolide on AFP production was tested in NSG mice. Telomerase inhibition by costunolide and BIBR 1532 at 5 and 10 μM decreased AFP mRNA expression and protein secretion by HepG2/C3A cells. The same pattern was obtained with cells treated with hTERT siRNA. This treatment exhibited no apoptotic effect. The AFP mRNA expression and protein secretion by PLC/PRF/5 was decreased after treatment with BIBR1532 at 10 μM. In contrast, no effect was obtained for PLC/PRF/5 cells treated with costunolide at 5 or 10 μM. Inhibition of the PI3K/Akt/mTOR signaling pathway decreased the AFP concentration. In contrast, the MAPK/ERK pathway appeared to not be involved in HepG2/C3A cells, whereas ERK inhibition decreased the AFP concentration in PLC/PRF/5 cells. Modulation of the AFP concentration was also obtained after the inhibition or activation of PKC. Costunolide (30 mg/kg) significantly decreased the AFP serum concentration of NSG mice bearing HepG2/C3A cells. Both the inhibition of telomerase and the inhibition of the PI3K/Akt/mTOR signaling pathway decreased the AFP production of HepG2/C3A and PLC/PRF/5 cells, suggesting a relationship between telomerase and AFP expression through the PI3K/Akt/mTOR pathway 相似文献
438.
Spatial Variation among Lakes within Landscapes: Ecological Organization along Lake Chains 总被引:6,自引:0,他引:6
Patricia A. Soranno Katherine E. Webster Joan L. Riera Timothy K. Kratz Jill S. Baron Paul A. Bukaveckas George W. Kling David S. White Nel Caine Richard C. Lathrop Peter R. Leavitt 《Ecosystems》1999,2(5):395-410
Although limnologists have long been interested in regional patterns in lake attributes, only recently have they considered
lakes connected and organized across the landscape, rather than as spatially independent entities. Here we explore the spatial
organization of lake districts through the concept of landscape position, a concept that considers lakes longitudinally along
gradients of geomorphology and hydrology. We analyzed long-term chemical and biological data from nine lake chains (lakes
in a series connected through surface or groundwater flow) from seven lake districts of diverse hydrologic and geomorphic
settings across North America. Spatial patterns in lake variables driven by landscape position were surprisingly common across
lake districts and across a wide range of variables. On the other hand, temporal patterns of lake variables, quantified using
synchrony, the degree to which pairs of lakes exhibit similar dynamics through time, related to landscape position only for
lake chains with lake water residence times that spanned a wide range and were generally long (close to or greater than 1
year). Highest synchrony of lakes within a lake chain occurred when lakes had short water residence times. Our results from
both the spatial and temporal analyses suggest that certain features of the landscape position concept are robust enough to
span a wide range of seemingly disparate lake types. The strong spatial patterns observed in this analysis, and some unexplained
patterns, suggest the need to further study these scales and to continue to view lake ecosystems spatially, longitudinally,
and broadly across the landscape. 相似文献
439.
At reproductive onset the marine green alga Acetabularia acetabulum (L.) P.C. Silva redirects growth from vertical elongation of the axis of the plant to lateral expansion of a disk-shaped
reproductive structure, the “cap.” We used amputation to synchronize cap initiation and to facilitate investigation of the
light requirements during amputation-induced cap initiation. Following amputation of a nascent cap, most plants initiate one
whorl of vegetative hairs and then a cap. Both hair and cap initiation required photosynthesis, as indicated by studies with
3-(3′,4′-dichlorophenyl)-1, 1-dimethylurea, but did not require the nucleus. Amputation-induced hair initiation occurred in
red light, but 10 min of blue light given in a background of red light significantly increased hair initiation, supporting
previous studies that hair initiation is a blue-light-triggered photomorphogenic event. Amputation-induced cap initiation
also occurred in red light, but daily 10-min flashes of blue light given in a background of red light did not significantly
enhance cap initiation. We also examined the light requirements of intact plants at each phase of development. In the absence
of blue light, juveniles and adults with ≤13.7 ± 4.3 whorls of hairs arrested in development and failed to initiate caps.
In contrast, very late adults with ≥13.7 ± 4.3 whorls of hairs initiated caps in the absence of blue light, suggesting that
there is a point in late adult development beyond which cap initiation does not require blue light. Several plausible interpretations
of the role of light and the nucleus in the regulation of reproductive onset are discussed to try to reconcile these data
with those in the literature.
Received: 18 March 1999 / Accepted: 13 May 1999 相似文献
440.
S Endres M Wilke H Frank P Kn?ll M Kratz M Windler A Wilke 《Biomedizinische Technik》2005,50(12):408-412
The objective of this study was to evaluate the bone ingrowth of a new vacuum plasma sprayed titanium surface (vps-ti) in comparison to cs-titanium implants in a g?ttinger minipig model. Fifteen g?ttinger minipigs each received the two implants, vacuum plasma sprayed titanium with a porosity of 50% and a pore size of 200 microm (vps-ti) and an implant with a similar porosity but a different pore size 500 microm (cs-ti), at the proximal femur metaphysis by press-fit technique. The pigs were euthanized at three different postsurgical periods: 4, 8 and 12 weeks. Each femur was harvested and qualitative (macroscopic and microscopic) and quantitative (histomorphometric) histological analysis was done on histological slides. The results indicated that there was a difference in bone ingrowth between the two implants, whereas the bone ingrowth of vps-ti was superior to cs-ti after 4 and 8 weeks healing time. 12 weeks post implantationem no statistiscal difference was evident. The pore size of 200 microm seemed superior to a pore size of 500 microm. Whether or not these effects lead to a better mechanical stability remains unanswered. 相似文献