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991.
Riad Schulz Thomas Emmrich Heidi Lemmerhirt Ulrike Leffler Kristin Sydow Carsten Hirt Thomas Kiefer Andreas Link Patrick J. Bednarski 《Bioorganic & medicinal chemistry letters》2012,22(21):6712-6715
Cancer cells isolated from two patients with malignant non-Hodgkin B-cell lymphomas that became resistant to chemotherapy during clinical treatment were made ?fourfold resistant in culture to anticancer drugs, that is cisplatin, etoposide, methotrexate and bortezomib. Because most resistant lines showed significantly increased expression of the anti-oxidative enzyme glutathione peroxidase 1 (GPx1), GPx1 was investigated as a target for inhibitor development. Virtual screening of a library of diverse structures by docking them to the active site of the X-ray crystal structure of bovine GPx1 uncovered compounds that might block the enzyme. An enzyme assay confirmed an acylhydrazone heterocycle (3) with GPx inhibitory activity. Combinations of 3 with the anticancer drugs listed above led to reversal of resistance in the lymphoma cell lines. 相似文献
992.
993.
Rautengarten C Ebert B Ouellet M Nafisi M Baidoo EE Benke P Stranne M Mukhopadhyay A Keasling JD Sakuragi Y Scheller HV 《Plant physiology》2012,158(2):654-665
The cuticle is a complex aliphatic polymeric layer connected to the cell wall and covers surfaces of all aerial plant organs. The cuticle prevents nonstomatal water loss, regulates gas exchange, and acts as a barrier against pathogen infection. The cuticle is synthesized by epidermal cells and predominantly consists of an aliphatic polymer matrix (cutin) and intracuticular and epicuticular waxes. Cutin monomers are primarily C(16) and C(18) unsubstituted, ω-hydroxy, and α,ω-dicarboxylic fatty acids. Phenolics such as ferulate and p-coumarate esters also contribute to a minor extent to the cutin polymer. Here, we present the characterization of a novel acyl-coenzyme A (CoA)-dependent acyl-transferase that is encoded by a gene designated Deficient in Cutin Ferulate (DCF). The DCF protein is responsible for the feruloylation of ω-hydroxy fatty acids incorporated into the cutin polymer of aerial Arabidopsis (Arabidopsis thaliana) organs. The enzyme specifically transfers hydroxycinnamic acids using ω-hydroxy fatty acids as acyl acceptors and hydroxycinnamoyl-CoAs, preferentially feruloyl-CoA and sinapoyl-CoA, as acyl donors in vitro. Arabidopsis mutant lines carrying DCF loss-of-function alleles are devoid of rosette leaf cutin ferulate and exhibit a 50% reduction in ferulic acid content in stem insoluble residues. DCF is specifically expressed in the epidermis throughout all green Arabidopsis organs. The DCF protein localizes to the cytosol, suggesting that the feruloylation of cutin monomers takes place in the cytoplasm. 相似文献
994.
Schwandt T Schumak B Gielen GH Jüngerkes F Schmidbauer P Klocke K Staratschek-Jox A van Rooijen N Kraal G Ludwig-Portugall I Franken L Wehner S Kalff JC Weber O Kirschning C Coch C Kalinke U Wenzel J Kurts C Zawatzky R Holzmann B Layland L Schultze JL Burgdorf S den Haan JM Knolle PA Limmer A 《The EMBO journal》2012,31(1):201-213
Early during Gram-negative sepsis, excessive release of pro-inflammatory cytokines can cause septic shock that is often followed by a state of immune paralysis characterized by the failure to mount adaptive immunity towards secondary microbial infections. Especially, the early mechanisms responsible for such immune hypo-responsiveness are unclear. Here, we show that TLR4 is the key immune sensing receptor to initiate paralysis of T-cell immunity after bacterial sepsis. Downstream of TLR4, signalling through TRIF but not MyD88 impaired the development of specific T-cell immunity against secondary infections. We identified type I interferon (IFN) released from splenic macrophages as the critical factor causing T-cell immune paralysis. Early during sepsis, type I IFN acted selectively on dendritic cells (DCs) by impairing antigen presentation and secretion of pro-inflammatory cytokines. Our results reveal a novel immune regulatory role for type I IFN in the initiation of septic immune paralysis, which is distinct from its well-known immune stimulatory effects. Moreover, we identify potential molecular targets for therapeutic intervention to overcome impairment of T-cell immunity after sepsis. 相似文献
995.
996.
Anders Mosbech Kasper L. Johansen Nikolaj I. Bech Peter Lyngs Ann M. A. Harding Carsten Egevang Richard A. Phillips Jerome Fort 《Polar Biology》2012,35(2):305-311
Seabirds are important components in marine ecosystems. However, knowledge of their ecology and spatial distribution during
the non-breeding season is poor. More investigations during this critical period are required urgently, as marine environments
are expected to be profoundly affected by climate change and human activities, with both direct and indirect consequences
for marine top predators. Here, we studied the distribution of little auks (Alle alle), one of the most abundant seabird species worldwide. We found that after the breeding season, birds from East Greenland
quickly travelled north-east to stay for several weeks within a restricted area in the Greenland Sea. Activity patterns indicated
that flying behaviour was much reduced during this period, suggesting that this is the primary moulting region for little
auks. Birds then performed a southerly migration to overwinter off Newfoundland. These preliminary results provide important
information for the conservation of this species and emphasise the need for further studies at a larger spatial scale. 相似文献
997.
Schradin C Lindholm AK Johannesen J Schoepf I Yuen CH König B Pillay N 《Molecular ecology》2012,21(3):541-553
Environmental change poses challenges to many organisms. The resilience of a species to such change depends on its ability to respond adaptively. Social flexibility is such an adaptive response, whereby individuals of both sexes change their reproductive tactics facultatively in response to fluctuating environmental conditions, leading to changes in the social system. Social flexibility focuses on individual flexibility, and provides a unique opportunity to study both the ultimate and proximate causes of sociality by comparing between solitary and group-living individuals of the same population: why do animals form groups and how is group-living regulated by the environment and the neuro-endocrine system? These key questions have been studied for the past ten years in the striped mouse Rhabdomys pumilio. High population density favours philopatry and group-living, while reproductive competition favours dispersal and solitary-living. Studies of genetic parentage reveal that relative fitness of alternative reproductive tactics depends on the prevailing environment. Tactics have different fitness under constrained ecological conditions, when competitive ability is important. Under conditions with relaxed ecological constraints, alternative tactics can yield equal fitness. Both male and female striped mice display alternative reproductive tactics based on a single strategy, i.e. all individuals follow the same decision rules. These changes are regulated by endocrine mechanisms. Social flexibility is regarded as an adaptation to unpredictably changing environments, selecting for high phenotypic flexibility based on a broad reaction norm, not on genetic polymorphism for specific tactics. 相似文献
998.
Cadena CD Kozak KH Gómez JP Parra JL McCain CM Bowie RC Carnaval AC Moritz C Rahbek C Roberts TE Sanders NJ Schneider CJ VanDerWal J Zamudio KR Graham CH 《Proceedings. Biological sciences / The Royal Society》2012,279(1726):194-201
Many biodiversity hotspots are located in montane regions, especially in the tropics. A possible explanation for this pattern is that the narrow thermal tolerances of tropical species and greater climatic stratification of tropical mountains create more opportunities for climate-associated parapatric or allopatric speciation in the tropics relative to the temperate zone. However, it is unclear whether a general relationship exists among latitude, climatic zonation and the ecology of speciation. Recent taxon-specific studies obtained different results regarding the role of climate in speciation in tropical versus temperate areas. Here, we quantify overlap in the climatic distributions of 93 pairs of sister species of mammals, birds, amphibians and reptiles restricted to either the New World tropics or to the Northern temperate zone. We show that elevational ranges of tropical- and temperate-zone species do not differ from one another, yet the temperature range experienced by species in the temperate zone is greater than for those in the tropics. Moreover, tropical sister species tend to exhibit greater similarity in their climatic distributions than temperate sister species. This pattern suggests that evolutionary conservatism in the thermal niches of tropical taxa, coupled with the greater thermal zonation of tropical mountains, may result in increased opportunities for allopatric isolation, speciation and the accumulation of species in tropical montane regions. Our study exemplifies the power of combining phylogenetic and spatial datasets of global climatic variation to explore evolutionary (rather than purely ecological) explanations for the high biodiversity of tropical montane regions. 相似文献
999.
De Dreu CK Greer LL Handgraaf MJ Shalvi S Van Kleef GA 《Proceedings. Biological sciences / The Royal Society》2012,279(1731):1150-1154
In intergroup competition and conflict, humans benefit from coalitions with strong partners who help them to protect their in-group and prevail over competing out-groups. Here, we link oxytocin, a neuropeptide produced in the hypothalamus, to ally selection in intergroup competition. In a double-blind placebo-controlled experiment, males self-administered oxytocin or placebo, and made selection decisions about six high-threat and six low-threat targets as potential allies in intergroup competition. Males given oxytocin rather than placebo viewed high-threat targets as more useful allies and more frequently selected them into their team than low-threat targets. 相似文献
1000.
Tøttrup AP Klaassen RH Strandberg R Thorup K Kristensen MW Jørgensen PS Fox J Afanasyev V Rahbek C Alerstam T 《Proceedings. Biological sciences / The Royal Society》2012,279(1730):1008-1016
The small size of the billions of migrating songbirds commuting between temperate breeding sites and the tropics has long prevented the study of the largest part of their annual cycle outside the breeding grounds. Using light-level loggers (geolocators), we recorded the entire annual migratory cycle of the red-backed shrike Lanius collurio, a trans-equatorial Eurasian-African passerine migrant. We tested differences between autumn and spring migration for nine individuals. Duration of migration between breeding and winter sites was significantly longer in autumn (average 96 days) when compared with spring (63 days). This difference was explained by much longer staging periods during autumn (71 days) than spring (9 days). Between staging periods, the birds travelled faster during autumn (356 km d(-1)) than during spring (233 km d(-1)). All birds made a protracted stop (53 days) in Sahelian sub-Sahara on southbound migration. The birds performed a distinct loop migration (22 000 km) where spring distance, including a detour across the Arabian Peninsula, exceeded the autumn distance by 22 per cent. Geographical scatter between routes was particularly narrow in spring, with navigational convergence towards the crossing point from Africa to the Arabian Peninsula. Temporal variation between individuals was relatively constant, while different individuals tended to be consistently early or late at different departure/arrival occasions during the annual cycle. These results demonstrate the existence of fundamentally different spatio-temporal migration strategies used by the birds during autumn and spring migration, and that songbirds may rely on distinct staging areas for completion of their annual cycle, suggesting more sophisticated endogenous control mechanisms than merely clock-and-compass guidance among terrestrial solitary migrants. After a century with metal-ringing, year-round tracking of long-distance migratory songbirds promises further insights into bird migration. 相似文献