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131.
Yogesh K. Gupta Yasin F. Dagdas Ana-Lilia Martinez-Rocha Michael J. Kershaw George R. Littlejohn Lauren S. Ryder Jan Sklenar Frank Menke Nicholas J. Talbot 《The Plant cell》2015,27(11):3277-3289
Magnaporthe oryzae is the causal agent of rice blast disease, the most devastating disease of cultivated rice (Oryza sativa) and a continuing threat to global food security. To cause disease, the fungus elaborates a specialized infection cell called an appressorium, which breaches the cuticle of the rice leaf, allowing the fungus entry to plant tissue. Here, we show that the exocyst complex localizes to the tips of growing hyphae during vegetative growth, ahead of the Spitzenkörper, and is required for polarized exocytosis. However, during infection-related development, the exocyst specifically assembles in the appressorium at the point of plant infection. The exocyst components Sec3, Sec5, Sec6, Sec8, and Sec15, and exocyst complex proteins Exo70 and Exo84 localize specifically in a ring formation at the appressorium pore. Targeted gene deletion, or conditional mutation, of genes encoding exocyst components leads to impaired plant infection. We demonstrate that organization of the exocyst complex at the appressorium pore is a septin-dependent process, which also requires regulated synthesis of reactive oxygen species by the NoxR-dependent Nox2 NADPH oxidase complex. We conclude that septin-mediated assembly of the exocyst is necessary for appressorium repolarization and host cell invasion. 相似文献
132.
Saul Jaime-Figueroa Javier De Vicente Johannes Hermann Alam Jahangir Sue Jin Andreas Kuglstatter Stephen M. Lynch John Menke Linghao Niu Vaishali Patel Ada Shao Michael Soth Minh Diem Vu Calvin Yee 《Bioorganic & medicinal chemistry letters》2013,23(9):2522-2526
We report the discovery of a novel series of ATP-competitive Janus kinase 3 (JAK3) inhibitors based on the 5H-pyrrolo[2,3-b]pyrazine scaffold. The initial leads in this series, compounds 1a and 1h, showed promising potencies, but a lack of selectivity against other isoforms in the JAK family. Computational and crystallographic analysis suggested that the phenyl ether moiety possessed a favorable vector to achieve selectivity. Exploration of this vector resulted in the identification of 12b and 12d, as potent JAK3 inhibitors, demonstrating improved JAK family and kinase selectivity. 相似文献
133.
The structure of pseudorabies virus (PRV) capsids isolated from the nucleus of infected cells and from PRV virions was determined by cryo-electron microscopy (cryo-EM) and compared to herpes simplex virus type 1 (HSV-1) capsids. PRV capsid structures closely resemble those of HSV-1, including distribution of the capsid vertex specific component (CVSC) of HSV-1, which is a heterodimer of the pUL17 and pUL25 proteins. Occupancy of CVSC on all PRV capsids is near 100%, compared to ~ 50% reported for HSV-1 C-capsids and 25% or less that we measure for HSV-1 A- and B-capsids. A PRV mutant lacking pUL25 does not produce C-capsids and lacks visible CVSC density in the cryo-EM-based reconstruction. A reconstruction of PRV capsids in which green fluorescent protein was fused within the N-terminus of pUL25 confirmed previous studies with a similar HSV-1 capsid mutant localizing pUL25 to the CVSC density region that is distal to the penton. However, comparison of the CVSC density in a 9-Å-resolution PRV C-capsid map with the available crystal structure of HSV-1 pUL25 failed to find a satisfactory fit, suggesting either a different fold for PRV pUL25 or a capsid-bound conformation for pUL25 that does not match the X-ray model determined from protein crystallized in solution. The PRV capsid imaged within virions closely resembles C-capsids with the addition of weak but significant density shrouding the pentons that we attribute to tegument proteins. Our results demonstrate significant structure conservation between the PRV and HSV capsids. 相似文献
134.
Werner Schönfeld Karl-Heinz Menke Reinhild Schönfeld Kurt R.H. Repke 《Biochemical and biophysical research communications》1984,119(1):423-430
Cibacron Blue F3GA (Cb) effectively and reversibly inhibits the activity of (Na,K)-ATPase. Its inhibitory effect does not occur through occupation of the ouabain binding site, but presumably results from Cb-occupation of one catalytic site not competitively attracting ATP. Cb also inhibits ouabain binding to (Na,K)-ATPase. Its inhibitory effect is competitively antagonized by ATP proving accomodation of Cb in the ATP binding site. - If one admits Cb as a suitable analytical tool for the detection of a supersecondary structure folding pattern, the findings suggest that the ATP binding site is lined by β-pleated sheets flanked by α-helices thus providing an environment that funnels ATP to the catalytic site. 相似文献
135.
NORMAN SARTORIUS WOLFGANG GAEBEL HELEN‐ROSE CLEVELAND HEATHER STUART TSUYOSHI AKIYAMA JULIO ARBOLEDA‐FLÓREZ ANJA E. BAUMANN OYE GUREJE MIGUEL R. JORGE MARIANNE KASTRUP YURIKO SUZUKI ALLAN TASMAN 《World psychiatry》2010,9(3):131-144
In 2009 the WPA President established a Task Force that was to examine
available evidence about the stigmatization of psychiatry and psychiatrists
and to make recommendations about action that national psychiatric societies
and psychiatrists as professionals could do to reduce or prevent the stigmatization
of their discipline as well as to prevent its nefarious consequences. This
paper presents a summary of the Task Force’s findings and recommendations.
The Task Force reviewed the literature concerning the image of psychiatry
and psychiatrists in the media and the opinions about psychiatry and psychiatrists
of the general public, of students of medicine, of health professionals other
than psychiatrists and of persons with mental illness and their families.
It also reviewed the evidence about the interventions that have been undertaken
to combat stigma and consequent discrimination and made a series of recommendations
to the national psychiatric societies and to individual psychiatrists. The
Task Force laid emphasis on the formulation of best practices of psychiatry
and their application in health services and on the revision of curricula
for the training of health personnel. It also recommended that national psychiatric
societies establish links with other professional associations, with organizations
of patients and their relatives and with the media in order to approach the
problems of stigma on a broad front. The Task Force also underlined the role
that psychiatrists can play in the prevention of stigmatization of psychiatry,
stressing the need to develop a respectful relationship with patients, to
strictly observe ethical rules in the practice of psychiatry and to maintain
professional competence. 相似文献
136.
137.
Mithoe SC Boersema PJ Berke L Snel B Heck AJ Menke FL 《Journal of proteome research》2012,11(1):438-448
Tyrosine (Tyr) phosphorylation plays an essential role in signaling in animal systems. However, a few studies have also reported Tyr phosphorylation in plants, but the relative contribution of tyrosine phosphorylation to plant signal transduction has remained an open question. We present an approach to selectively measure and quantify Tyr phosphorylation in plant cells, which can also be applied to whole plants. We combined a (15)N stable isotope metabolic labeling strategy with an immuno-affinity purification using phospho-tyrosine (pY) specific antibodies. This single enrichment strategy was sufficient to reproducibly identify and quantify pY containing peptides from total plant cell extract in a single LC-MS/MS run. We succeeded in identifying 149 unique pY peptides originating from 135 proteins, including a large set of different protein kinases and several receptor-like kinases. We used flagellin perception by Arabidopsis cells, a model system for pathogen triggered immune (PTI) signaling, to test our approach. We reproducibly quantified 23 pY peptides in 2 inversely labeled biological replicates identifying 11 differentially phosphorylated proteins. These include a set of 3 well-characterized flagellin responsive MAP kinases and 4 novel MAP kinases. With this targeted approach, we elucidate a new level of complexity in flagellin-induced MAP kinase activation. 相似文献
138.
Iwata Y Boström EA Menke J Rabacal WA Morel L Wada T Kelley VR 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(9):4568-4580
CSF-1, required for macrophage (M?) survival, proliferation, and activation, is upregulated in the tubular epithelial cells (TECs) during kidney inflammation. CSF-1 mediates M?-dependent destruction in lupus-susceptible mice with nephritis and, paradoxically, M?-dependent renal repair in lupus-resistant mice after transient ischemia/reperfusion injury (I/R). We now report that I/R leads to defective renal repair, nonresolving inflammation, and, in turn, early-onset lupus nephritis in preclinical MRL/MpJ-Faslpr/Fas(lpr) mice (MRL-Fas(lpr) mice). Moreover, defective renal repair is not unique to MRL-Fas(lpr) mice, as flawed healing is a feature of other lupus-susceptible mice (Sle 123) and MRL mice without the Fas(lpr) mutation. Increasing CSF-1 hastens renal healing after I/R in lupus-resistant mice but hinders healing, exacerbates nonresolving inflammation, and triggers more severe early-onset lupus nephritis in MRL-Fas(lpr) mice. Probing further, the time-related balance of M1 "destroyer" M? shifts toward the M2 "healer" phenotype in lupus-resistant mice after I/R, but M1 M? continue to dominate in MRL-Fas(lpr) mice. Moreover, hypoxic TECs release mediators, including CSF-1, that are responsible for stimulating the expansion of M1 M? inherently poised to destroy the kidney in MRL-Fas(lpr) mice. In conclusion, I/R induces CSF-1 in injured TECs that expands aberrant M? (M1 phenotype), mediating defective renal repair and nonresolving inflammation, and thereby hastens the onset of lupus nephritis. 相似文献
139.
140.
Climatic drivers of hemispheric asymmetry in global patterns of ant species richness 总被引:2,自引:0,他引:2
Robert R. Dunn Donat Agosti Alan N. Andersen Xavier Arnan Carsten A. Bruhl Xim Cerdá Aaron M. Ellison Brian L. Fisher Matthew C. Fitzpatrick Heloise Gibb Nicholas J. Gotelli Aaron D. Gove Benoit Guenard Milan Janda Michael Kaspari Edward J. Laurent Jean-Philippe Lessard John T. Longino Jonathan D. Majer Sean B. Menke Terrence P. McGlynn Catherine L. Parr Stacy M. Philpott Martin Pfeiffer Javier Retana rew V. Suarez Heraldo L. Vasconcelos Michael D. Weiser Nathan J. Sanders 《Ecology letters》2009,12(4):324-333
Although many taxa show a latitudinal gradient in richness, the relationship between latitude and species richness is often asymmetrical between the northern and southern hemispheres. Here we examine the latitudinal pattern of species richness across 1003 local ant assemblages. We find latitudinal asymmetry, with southern hemisphere sites being more diverse than northern hemisphere sites. Most of this asymmetry could be explained statistically by differences in contemporary climate. Local ant species richness was positively associated with temperature, but negatively (although weakly) associated with temperature range and precipitation. After contemporary climate was accounted for, a modest difference in diversity between hemispheres persisted, suggesting that factors other than contemporary climate contributed to the hemispherical asymmetry. The most parsimonious explanation for this remaining asymmetry is that greater climate change since the Eocene in the northern than in the southern hemisphere has led to more extinctions in the northern hemisphere with consequent effects on local ant species richness. 相似文献