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211.
Helpers in primitively eusocial and cooperatively breeding animal societies forfeit their own reproduction to rear the offspring of a queen or breeding pair, but may eventually attain breeding status themselves. Kin selection provides a widely accepted theoretical framework for understanding these societies, but differences in genetic relatedness do not explain a universal societal feature: the huge variation between individuals in helping effort. An alternative explanation for this variation lies in a fundamental trade-off faced by helpers: by working harder, they increase the indirect component of their fitness, but simultaneously decrease their own future survival and fecundity. Here, we show that individuals work less hard when they stand to lose more future fitness through working. We experimentally manipulated two components of future fitness in social queues of hover wasps (Stenogastrinae): a helper's chance of inheriting an egg-laying position, and the workforce available to rear her offspring should she inherit. After each manipulation, helpers increased or decreased their effort as appropriate to the change in expected future fitness that they experienced. Although helping provides significant indirect fitness benefits for hover wasps, our study shows that variation in the costs associated with helping is the major determinant of helping effort. 相似文献
212.
P Dutta G Courties Y Wei F Leuschner R Gorbatov CS Robbins Y Iwamoto B Thompson AL Carlson T Heidt MD Majmudar F Lasitschka M Etzrodt P Waterman MT Waring AT Chicoine AM van der Laan HW Niessen JJ Piek BB Rubin J Butany JR Stone HA Katus SA Murphy DA Morrow MS Sabatine C Vinegoni MA Moskowitz MJ Pittet P Libby CP Lin FK Swirski R Weissleder M Nahrendorf 《Nature》2012,487(7407):325-329
During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaques in the arterial wall and cause their rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons. Here we show that the systemic response to ischaemic injury aggravates chronic atherosclerosis. After myocardial infarction or stroke, Apoe-/- mice developed larger atherosclerotic lesions with a more advanced morphology. This disease acceleration persisted over many weeks and was associated with markedly increased monocyte recruitment. Seeking the source of surplus monocytes in plaques, we found that myocardial infarction liberated haematopoietic stem and progenitor cells from bone marrow niches via sympathetic nervous system signalling. The progenitors then seeded the spleen, yielding a sustained boost in monocyte production. These observations provide new mechanistic insight into atherogenesis and provide a novel therapeutic opportunity to mitigate disease progression. 相似文献
213.
Dieter Adam Andreas Linkermann 《Cellular and molecular life sciences : CMLS》2016,73(11-12):2123-2124
214.
Recent advances in catalysis have made the incorporation of fluorine into complex organic molecules easier than ever before, but selective, general and practical fluorination reactions remain sought after. Fluorination of molecules often imparts desirable properties, such as metabolic and thermal stability, and fluorinated molecules are therefore frequently used as pharmaceuticals or materials. But the formation of carbon-fluorine bonds in complex molecules is a significant challenge. Here we discuss reactions to make organofluorides that have emerged within the past few years and which exemplify how to overcome some of the intricate challenges associated with fluorination. 相似文献
215.
216.
Frezza C Zheng L Folger O Rajagopalan KN MacKenzie ED Jerby L Micaroni M Chaneton B Adam J Hedley A Kalna G Tomlinson IP Pollard PJ Watson DG Deberardinis RJ Shlomi T Ruppin E Gottlieb E 《Nature》2011,477(7363):225-228
Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid cycle (TCA cycle) that catalyses the hydration of fumarate into malate. Germline mutations of FH are responsible for hereditary leiomyomatosis and renal-cell cancer (HLRCC). It has previously been demonstrated that the absence of FH leads to the accumulation of fumarate, which activates hypoxia-inducible factors (HIFs) at normal oxygen tensions. However, so far no mechanism that explains the ability of cells to survive without a functional TCA cycle has been provided. Here we use newly characterized genetically modified kidney mouse cells in which Fh1 has been deleted, and apply a newly developed computer model of the metabolism of these cells to predict and experimentally validate a linear metabolic pathway beginning with glutamine uptake and ending with bilirubin excretion from Fh1-deficient cells. This pathway, which involves the biosynthesis and degradation of haem, enables Fh1-deficient cells to use the accumulated TCA cycle metabolites and permits partial mitochondrial NADH production. We predicted and confirmed that targeting this pathway would render Fh1-deficient cells non-viable, while sparing wild-type Fh1-containing cells. This work goes beyond identifying a metabolic pathway that is induced in Fh1-deficient cells to demonstrate that inhibition of haem oxygenation is synthetically lethal when combined with Fh1 deficiency, providing a new potential target for treating HLRCC patients. 相似文献
217.
218.
Genome sequencing reveals insights into physiology and longevity of the naked mole rat 总被引:1,自引:0,他引:1
Kim EB Fang X Fushan AA Huang Z Lobanov AV Han L Marino SM Sun X Turanov AA Yang P Yim SH Zhao X Kasaikina MV Stoletzki N Peng C Polak P Xiong Z Kiezun A Zhu Y Chen Y Kryukov GV Zhang Q Peshkin L Yang L Bronson RT Buffenstein R Wang B Han C Li Q Chen L Zhao W Sunyaev SR Park TJ Zhang G Wang J Gladyshev VN 《Nature》2011,479(7372):223-227
219.
Nanofabrication strategies are becoming increasingly expensive and equipment-intensive, and consequently less accessible to researchers. As an alternative, scanning probe lithography has become a popular means of preparing nanoscale structures, in part owing to its relatively low cost and high resolution, and a registration accuracy that exceeds most existing technologies. However, increasing the throughput of cantilever-based scanning probe systems while maintaining their resolution and registration advantages has from the outset been a significant challenge. Even with impressive recent advances in cantilever array design, such arrays tend to be highly specialized for a given application, expensive, and often difficult to implement. It is therefore difficult to imagine commercially viable production methods based on scanning probe systems that rely on conventional cantilevers. Here we describe a low-cost and scalable cantilever-free tip-based nanopatterning method that uses an array of hard silicon tips mounted onto an elastomeric backing. This method-which we term hard-tip, soft-spring lithography-overcomes the throughput problems of cantilever-based scanning probe systems and the resolution limits imposed by the use of elastomeric stamps and tips: it is capable of delivering materials or energy to a surface to create arbitrary patterns of features with sub-50-nm resolution over centimetre-scale areas. We argue that hard-tip, soft-spring lithography is a versatile nanolithography strategy that should be widely adopted by academic and industrial researchers for rapid prototyping applications. 相似文献
220.
Vinod Sundaramoorthy Adam K. Walker Justin Yerbury Kai Ying Soo Manal A. Farg Vy Hoang Rafaa Zeineddine Damian Spencer Julie D. Atkin 《Cellular and molecular life sciences : CMLS》2013,70(21):4181-4195
Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly progressing neurodegenerative disorder and the majority of ALS is sporadic, where misfolding and aggregation of Cu/Zn-superoxide dismutase (SOD1) is a feature shared with familial mutant-SOD1 cases. ALS is characterized by progressive neurospatial spread of pathology among motor neurons, and recently the transfer of extracellular, aggregated mutant SOD1 between cells was demonstrated in culture. However, there is currently no evidence that uptake of SOD1 into cells initiates neurodegenerative pathways reminiscent of ALS pathology. Similarly, whilst dysfunction to the ER–Golgi compartments is increasingly implicated in the pathogenesis of both sporadic and familial ALS, it remains unclear whether misfolded, wildtype SOD1 triggers ER–Golgi dysfunction. In this study we show that both extracellular, native wildtype and mutant SOD1 are taken up by macropinocytosis into neuronal cells. Hence uptake does not depend on SOD1 mutation or misfolding. We also demonstrate that purified mutant SOD1 added exogenously to neuronal cells inhibits protein transport between the ER–Golgi apparatus, leading to Golgi fragmentation, induction of ER stress and apoptotic cell death. Furthermore, we show that extracellular, aggregated, wildtype SOD1 also induces ER–Golgi pathology similar to mutant SOD1, leading to apoptotic cell death. Hence extracellular misfolded wildtype or mutant SOD1 induce dysfunction to ER–Golgi compartments characteristic of ALS in neuronal cells, implicating extracellular SOD1 in the spread of pathology among motor neurons in both sporadic and familial ALS. 相似文献