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21.
Misregulated innate immune signaling and cell death form the basis of much human disease pathogenesis. Inhibitor of apoptosis (IAP) protein family members are frequently overexpressed in cancer and contribute to tumor cell survival, chemo-resistance, disease progression, and poor prognosis. Although best known for their ability to regulate caspases, IAPs also influence ubiquitin (Ub)-dependent pathways that modulate innate immune signaling via activation of nuclear factor κB (NF-κB). Recent research into IAP biology has unearthed unexpected roles for this group of proteins. In addition, the advances in our understanding of the molecular mechanisms that IAPs use to regulate cell death and innate immune responses have provided new insights into disease states and suggested novel intervention strategies. Here we review the functions assigned to those IAP proteins that act at the intersection of cell death regulation and inflammatory signaling.Apoptosis represents a fundamental biological process that relies on the activation of caspases. Inhibitor of apoptosis (IAP) proteins represent a group of negative regulators of both caspases and cell death. Although best known for their ability to regulate caspases and cell death, it is now clear that they function as arbiters of diverse biological processes (Gyrd-Hansen and Meier 2010). Most prominently, IAPs control ubiquitin (Ub)-dependent signaling events that regulate activation of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways that in turn drive expression of genes important for inflammation, immunity, cell migration, and cell survival. IAPs thereby function as E3 Ub ligases, mediating the transfer of Ub from E2s to target substrates. This in turn modulates the signaling process through regulating protein stability as well as via nondegradative means (see below for details). Many of the cellular processes controlled by IAPs are frequently deregulated in cancer and, directly or indirectly, contribute to disease initiation, tumor maintenance, and/or progression, making IAPs obvious targets for anticancer therapy (LaCasse et al. 2008). Accordingly, small pharmacological inhibitors of IAPs, frequently referred to as Smac-mimetics (SM), were developed and are currently undergoing clinical trials for the treatment of cancer (LaCasse et al. 2008). The use of SMs in preclinical tumor models and clinical trials has provided compelling evidence for the therapeutic benefit of IAP inhibition. 相似文献
22.
Eric Allan Wolfgang W. Weisser Markus Fischer Ernst-Detlef Schulze Alexandra Weigelt Christiane Roscher Jussi Baade Romain L. Barnard Holger Beßler Nina Buchmann Anne Ebeling Nico Eisenhauer Christof Engels Alexander J. F. Fergus Gerd Gleixner Marlén Gubsch Stefan Halle Alexandra M. Klein Ilona Kertscher Annely Kuu Markus Lange Xavier Le Roux Sebastian T. Meyer Varvara D. Migunova Alexandru Milcu Pascal A. Niklaus Yvonne Oelmann Esther Pašalić Jana S. Petermann Franck Poly Tanja Rottstock Alexander C. W. Sabais Christoph Scherber Michael Scherer-Lorenzen Stefan Scheu Sibylle Steinbeiss Guido Schwichtenberg Vicky Temperton Teja Tscharntke Winfried Voigt Wolfgang Wilcke Christian Wirth Bernhard Schmid 《Oecologia》2013,173(1):223-237
In order to predict which ecosystem functions are most at risk from biodiversity loss, meta-analyses have generalised results from biodiversity experiments over different sites and ecosystem types. In contrast, comparing the strength of biodiversity effects across a large number of ecosystem processes measured in a single experiment permits more direct comparisons. Here, we present an analysis of 418 separate measures of 38 ecosystem processes. Overall, 45 % of processes were significantly affected by plant species richness, suggesting that, while diversity affects a large number of processes not all respond to biodiversity. We therefore compared the strength of plant diversity effects between different categories of ecosystem processes, grouping processes according to the year of measurement, their biogeochemical cycle, trophic level and compartment (above- or belowground) and according to whether they were measures of biodiversity or other ecosystem processes, biotic or abiotic and static or dynamic. Overall, and for several individual processes, we found that biodiversity effects became stronger over time. Measures of the carbon cycle were also affected more strongly by plant species richness than were the measures associated with the nitrogen cycle. Further, we found greater plant species richness effects on measures of biodiversity than on other processes. The differential effects of plant diversity on the various types of ecosystem processes indicate that future research and political effort should shift from a general debate about whether biodiversity loss impairs ecosystem functions to focussing on the specific functions of interest and ways to preserve them individually or in combination. 相似文献
23.
24.
Vlastimil Hart Tomá? Ku?ta Pavel Němec Veronika Bláhová Milo? Je?ek Petra Nováková Sabine Begall Jaroslav ?erveny Vladimír Hanzal Erich Pascal Malkemper Kamil ?típek Christiane Vole Hynek Burda 《PloS one》2012,7(12)
While magnetoreception in birds has been studied intensively, the literature on magnetoreception in bony fish, and particularly in non-migratory fish, is quite scarce. We examined alignment of common carps (Cyprinus carpio) at traditional Christmas sale in the Czech Republic. The sample comprised measurements of the directional bearings in 14,537 individual fish, distributed among 80 large circular plastic tubs, at 25 localities in the Czech Republic, during 817 sampling sessions, on seven subsequent days in December 2011. We found that carps displayed a statistically highly significant spontaneous preference to align their bodies along the North-South axis. In the absence of any other common orientation cues which could explain this directional preference, we attribute the alignment of the fish to the geomagnetic field lines. It is apparent that the display of magnetic alignment is a simple experimental paradigm of great heuristic potential. 相似文献
25.
Ngo Y Benhamou Y Thibault V Ingiliz P Munteanu M Lebray P Thabut D Morra R Messous D Charlotte F Imbert-Bismut F Bonnefont-Rousselot D Rousselot-Bonnefont D Moussalli J Ratziu V Poynard T 《PloS one》2008,3(7):e2573
Background
The combination of transaminases (ALT), biopsy, HBeAg and viral load have classically defined the inactive status of carriers of chronic hepatitis B. The use of FibroTest (FT) and ActiTest (AT), biomarkers of fibrosis and necroinflammatory activity, has been previously validated as alternatives to biopsy. We compared the 4-year prognostic value of combining FT-AT and viral load for a better definition of the inactive carrier status.Methods and Findings
1,300 consecutive CHB patients who had been prospectively followed since 2001 were pre-included. The main endpoint was the absence of liver-related complications, transplantation or death. We used the manufacturers'' definitions of normal FT (< = 0.27), normal AT (< = 0.29) and 3 standard classes for viral load. The adjustment factors were age, sex, HBeAg, ethnic origin, alcohol consumption, HIV-Delta-HCV co-infections and treatment.Results
1,074 patients with baseline FT-AT and viral load were included: 41 years old, 47% African, 27% Asian, 26% Caucasian. At 4 years follow-up, 50 complications occurred (survival without complications 93.4%), 36 deaths occurred (survival 95.0%), including 27 related to HBV (survival 96.1%). The prognostic value of FT was higher than those of viral load or ALT when compared using area under the ROC curves [0.89 (95%CI 0.84–0.93) vs 0.64 (0.55–0.71) vs 0.53 (0.46–0.60) all P<0.001], survival curves and multivariate Cox model [regression coefficient 5.2 (3.5–6.9; P<0.001) vs 0.53 (0.15–0.92; P = 0.007) vs −0.001 (−0.003−0.000;P = 0.052)] respectively. A new definition of inactive carriers was proposed with an algorithm combining “zero” scores for FT-AT (F0 and A0) and viral load classes. This new algorithm provides a 100% negative predictive value for the prediction of liver related complications or death. Among the 275 patients with the classic definition of inactive carrier, 62 (23%) had fibrosis presumed with FT, and 3 died or had complications at 4 year.Conclusion
In patients with chronic hepatitis B, a combination of FibroTest-ActiTest and viral load testing accurately defined the prognosis and the inactive carrier status. 相似文献26.
27.
Pascal Vallotton Antoine M. van Oijen Cynthia B. Whitchurch Vladimir Gelfand Leslie Yeo Georgios Tsiavaliaris Stephanie Heinrich Elisa Dultz Karsten Weis David Grünwald 《Traffic (Copenhagen, Denmark)》2017,18(12):840-852
Object tracking is an instrumental tool supporting studies of cellular trafficking. There are three challenges in object tracking: the identification of targets; the precise determination of their position and boundaries; and the assembly of correct trajectories. This last challenge is particularly relevant when dealing with densely populated images with low signal‐to‐noise ratios—conditions that are often encountered in applications such as organelle tracking, virus particle tracking or single‐molecule imaging. We have developed a set of methods that can handle a wide variety of signal complexities. They are compiled into a free software package called Diatrack. Here we review its main features and utility in a range of applications, providing a survey of the dynamic imaging field together with recommendations for effective use. The performance of our framework is shown to compare favorably to a wide selection of custom‐developed algorithms, whether in terms of localization precision, processing speed or correctness of tracks. 相似文献
28.
The neo-vascularization of the host site is crucial for the primary fixation and the long-term stability of the bone-implant interface. Our aim was to investigate the progression of endothelial cell population in the first weeks of healing. We proposed a theoretical reactive model to study the role of initial conditions, random motility, haptotaxis and chemotaxis in interactions with fibronectin factors and transforming angiogenic factors. The application of governing equations concerned a canine experimental implant and numerical experiments based upon statistical designs of experiments supported the discussion. We found that chemotaxis due to transforming angiogenic factors was attracting endothelial cells present into the host bone. Haptotaxis conditioned by fibronectin factors favored cells adhesion to the host bone. The combination of diffusive and reactive effects nourished the wave front migration of endothelial cells from the host bone towards the implant. Angiogenesis goes together with new-formed bone formation in clinics, so the similarity of distribution patterns of mineralized tissue observed in-vivo and the spatio-temporal concentration of endothelial cells predicted by the model, tended to support the reliability of our theoretical approach. 相似文献
29.
Pascal Fournier Christian Maizeret David Jimenez Jean-Pierre Chusseau Stéphane Aulagnier François Spitz 《Acta theriologica》2007,52(1):1-12
The European minkMustela lutreola Linnaeus, 1761 and the European polecatMustela putorius Linnaeus, 1758 are related species sympatric in southwestern France. The European mink is rapidly disappearing whereas the
polecat maintains good populations. Seasonal habitat use of both species was compared in the Landes de Gascogne region to
identify if some vulnerability factors of the European mink were associated with habitats occupied by this mustelid. Potential
habitats were mapped using a satellite picture and 12 main types of habitats were defined. Animal locations were recorded
by radiotracking 9 European mink and 14 polecats from March 1996 to August 1999. Resting animals were located by triangulation,
and, when possible, resting places were described. Animals in activity were tracked by continuous monitoring. Data collected
revealed a strong preference of European mink for flooded habitats, particularly open marshes, flooded woodlands and moorlands.
They seldom left the corridor of the riparian forest and their resting places were mainly in flooded environments, above ground
(under herbs or bushes) or in cavities between tree roots. European polecats were less tightly linked to wetlands. Most of
their locations were in the pine forests outside the valleys and their resting places were mainly in burrows. The strong specialisation
of European mink in aquatic habitats is probably one of the main reasons for its decline because wetlands suffer drastic damages
throughout all of its range. Maintaining adequate water levels is crucial for satisfying habitat requirements of mink. 相似文献
30.
ElFihry Raouia Elmessaoudi-Idrissi Mohcine Jadid Fatima-Zahra Zaidane Imane Chihab Hajar Tahiri Mohamed Kabine Mostafa Badre Wafaa Chemin Isabelle Marchio Agnes Pineau Pascal Ezzikouri Sayeh Benjelloun Soumaya 《中国病毒学》2020,35(5):566-574
Virologica Sinica - Hepatitis C virus (HCV) is still one of the main causes of liver disease worldwide. Metabolic disorders, including non-alcoholic fatty liver disease (NAFLD), induced by HCV have... 相似文献