Glycosylation restores survival of chilled blood platelets     

Hoffmeister KM  Josefsson EC  Isaac NA  Clausen H  Hartwig JH  Stossel TP 《Science (New York, N.Y.)》2003,301(5639):1531-1534

Cooling of blood platelets clusters the von Willebrand factor receptor complex. Macrophage alphaMbeta2 integrins bind to the GPIbalpha subunit of the clustered complex, resulting in rapid clearance of transfused, cooled platelets. This precludes refrigeration of platelets for transfusion, but the current practice of room temperature storage has major drawbacks. We document that alphaMbeta2 is a lectin that recognizes exposed beta-N-acetylglucosamine residues of N-linked glycans on GPIbalpha. Enzymatic galactosylation of chilled platelets blocks alphaMbeta2 recognition, prolonging the circulation of functional cooled platelets. Platelet-associated galactosyltransferase produces efficient galactosylation when uridine diphosphate-galactose is added, affording a potentially simple method for storing platelets in the cold.  相似文献   

Dietary restriction in long-lived dwarf flies     

Clancy DJ  Gems D  Hafen E  Leevers SJ  Partridge L 《Science (New York, N.Y.)》2002,296(5566):319

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Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice     

Okkenhaug K  Bilancio A  Farjot G  Priddle H  Sancho S  Peskett E  Pearce W  Meek SE  Salpekar A  Waterfield MD  Smith AJ  Vanhaesebroeck B 《Science (New York, N.Y.)》2002,297(5583):1031-1034

Class IA phosphoinositide 3-kinases (PI3Ks) are a family of p85/p110 heterodimeric lipid kinases that generate second messenger signals downstream of tyrosine kinases, thereby controlling cell metabolism, growth, proliferation, differentiation, motility, and survival. Mammals express three class IA catalytic subunits: p110alpha, p110beta, and p110delta. It is unclear to what extent these p110 isoforms have overlapping or distinct biological roles. Mice expressing a catalytically inactive form of p110delta (p110delta(D910A)) were generated by gene targeting. Antigen receptor signaling in B and T cells was impaired and immune responses in vivo were attenuated in p110delta mutant mice. They also developed inflammatory bowel disease. These results reveal a selective role for p110delta in immunity.  相似文献   

The ecological context of life history evolution     

Partridge L  Harvey PH 《Science (New York, N.Y.)》1988,241(4872):1449-1455

There is now a good theoretical understanding of life history evolution, and detailed explicit optimality models have been constructed. These present a challenge for empirical work examining some of the assumptions, such as the extent and mechanisms of the costs of growth and reproduction. In addition, there is an obvious need for comparative tests of the models. These tests, properly applied, may be particularly informative because they can deal with multiple independent variables, including ecological variables, and can reveal broad trends against a background of constraints on optima and the rate of evolutionary approach to them. Life histories are the probabilities of survival and the rates of reproduction at each age in the life-span. Reproduction is costly, so that fertility at all ages cannot simultaneously be maximized by natural selection. Allocation of reproductive effort has evolved in response to the demographic impact of different environments but is constrained by genetic variance and evolutionary history.  相似文献   

Comment on "Brain IRS2 signaling coordinates life span and nutrient homeostasis"     

Selman C  Lingard S  Gems D  Partridge L  Withers DJ 《Science (New York, N.Y.)》2008,320(5879):1012; author reply 1012

Taguchi et al. (Reports, 20 July 2007, p. 369) reported that mice heterozygous for a null mutation in insulin receptor substrate-2 (Irs2) display a 17% increase in median life span. However, using the same mouse model, we find no evidence for life-span extension and suggest that the findings of Taguchi et al. were due to atypical life-span profiles in their study animals.  相似文献   

Supernova shock breakout from a red supergiant     

Schawinski K  Justham S  Wolf C  Podsiadlowski P  Sullivan M  Steenbrugge KC  Bell T  Röser HJ  Walker ES  Astier P  Balam D  Balland C  Carlberg R  Conley A  Fouchez D  Guy J  Hardin D  Hook I  Howell DA  Pain R  Perrett K  Pritchet C  Regnault N  Yi SK 《Science (New York, N.Y.)》2008,321(5886):223-226

Massive stars undergo a violent death when the supply of nuclear fuel in their cores is exhausted, resulting in a catastrophic "core-collapse" supernova. Such events are usually only detected at least a few days after the star has exploded. Observations of the supernova SNLS-04D2dc with the Galaxy Evolution Explorer space telescope reveal a radiative precursor from the supernova shock before the shock reached the surface of the star and show the initial expansion of the star at the beginning of the explosion. Theoretical models of the ultraviolet light curve confirm that the progenitor was a red supergiant, as expected for this type of supernova. These observations provide a way to probe the physics of core-collapse supernovae and the internal structures of their progenitor stars.  相似文献   

Direct isolation of satellite cells for skeletal muscle regeneration   总被引：6，自引：0，他引：6  

Montarras D  Morgan J  Collins C  Relaix F  Zaffran S  Cumano A  Partridge T  Buckingham M 《Science (New York, N.Y.)》2005,309(5743):2064-2067

Muscle satellite cells contribute to muscle regeneration. We have used a Pax3(GFP/+) mouse line to directly isolate (Pax3)(green fluorescent protein)-expressing muscle satellite cells, by flow cytometry from adult skeletal muscles, as a homogeneous population of small, nongranular, Pax7+, CD34+, CD45-, Sca1- cells. The flow cytometry parameters thus established enabled us to isolate satellite cells from wild-type muscles. Such cells, grafted into muscles of mdx nu/nu mice, contributed both to fiber repair and to the muscle satellite cell compartment. Expansion of these cells in culture before engraftment reduced their regenerative capacity.  相似文献   

A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis     

Andries K  Verhasselt P  Guillemont J  Göhlmann HW  Neefs JM  Winkler H  Van Gestel J  Timmerman P  Zhu M  Lee E  Williams P  de Chaffoy D  Huitric E  Hoffner S  Cambau E  Truffot-Pernot C  Lounis N  Jarlier V 《Science (New York, N.Y.)》2005,307(5707):223-227

The incidence of tuberculosis has been increasing substantially on a worldwide basis over the past decade, but no tuberculosis-specific drugs have been discovered in 40 years. We identified a diarylquinoline, R207910, that potently inhibits both drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro (minimum inhibitory concentration 0.06 mug/ml). In mice, R207910 exceeded the bactericidal activities of isoniazid and rifampin by at least 1 log unit. Substitution of drugs included in the World Health Organization's first-line tuberculosis treatment regimen (rifampin, isoniazid, and pyrazinamide) with R207910 accelerated bactericidal activity, leading to complete culture conversion after 2 months of treatment in some combinations. A single dose of R207910 inhibited mycobacterial growth for 1 week. Plasma levels associated with efficacy in mice were well tolerated in healthy human volunteers. Mutants selected in vitro suggest that the drug targets the proton pump of adenosine triphosphate (ATP) synthase.  相似文献   

The structure of an open form of an E. coli mechanosensitive channel at 3.45 A resolution     

Wang W  Black SS  Edwards MD  Miller S  Morrison EL  Bartlett W  Dong C  Naismith JH  Booth IR 《Science (New York, N.Y.)》2008,321(5893):1179-1183

How ion channels are gated to regulate ion flux in and out of cells is the subject of intense interest. The Escherichia coli mechanosensitive channel, MscS, opens to allow rapid ion efflux, relieving the turgor pressure that would otherwise destroy the cell. We present a 3.45 angstrom-resolution structure for the MscS channel in an open conformation. This structure has a pore diameter of approximately 13 angstroms created by substantial rotational rearrangement of the three transmembrane helices. The structure suggests a molecular mechanism that underlies MscS gating and its decay of conductivity during prolonged activation. Support for this mechanism is provided by single-channel analysis of mutants with altered gating characteristics.  相似文献   

Oxidative burst and phagocytic activity of phagocytes in canine parvoviral enteritis     

Kelly du Preez  Yolandi Rautenbach  Emma H. Hooijberg  Amelia Goddard 《Journal of veterinary diagnostic investigation》2021,33(5):884

Canine parvoviral enteritis (CPE) is a severe disease characterized by systemic inflammation and immunosuppression. The function of circulating phagocytes (neutrophils and monocytes) in affected dogs has not been fully investigated. We characterized the functional capacity of canine phagocytes in CPE by determining their oxidative burst and phagocytic activities using flow cytometry. Blood was collected from 28 dogs with CPE and 11 healthy, age-matched, control dogs. Oxidative burst activity was assessed by stimulating phagocytes with opsonized Escherichia coli or phorbol 12-myristate 13-acetate (PMA) and measuring the percentage of phagocytes producing reactive oxygen species and the magnitude of this production. Phagocytosis was measured by incubating phagocytes with opsonized E. coli and measuring the percentage of phagocytes containing E. coli and the number of bacteria per cell. Complete blood counts and serum C-reactive protein (CRP) concentrations were also determined. Serum CRP concentration was negatively and positively correlated with segmented and band neutrophil concentrations, respectively. Overall, no differences in phagocyte function were found between dogs with CPE and healthy control dogs. However, infected dogs with neutropenia or circulating band neutrophils had decreased PMA-stimulated oxidative burst activity compared to healthy controls. Additionally, CPE dogs with neutropenia or circulating band neutrophils had decreased PMA- and E. coli–stimulated oxidative burst activity and decreased phagocytosis of E. coli compared to CPE dogs without neutropenia or band neutrophils. We conclude that phagocytes have decreased oxidative burst and phagocytic activity in neutropenic CPE dogs and in CPE dogs with circulating band neutrophils.  相似文献