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951.
Melanie G. Cornejo Titus J. Boggon Thomas Mercher 《The international journal of biochemistry & cell biology》2009,41(12):2376-2379
JAK3 is a non-receptor tyrosine kinase, predominantly expressed in hematopoietic cells and that has been implicated in the signal transduction of the common gamma chain subfamily of cytokine receptors. As a result, JAK3 plays an essential role in hematopoieisis during T cell development. JAK3 inactivating mutations result in immunodeficiency syndromes (SCID) in both humans and mice. Recent data indicate that abnormal activation of JAK3 due to activating mutations is also found in human hematological malignancies, including acute megakaryoblastic leukemia (AMKL) and cutaneous T cell lymphoma (CTCL). After a brief summary of the JAK3 structure and function, we will review the evidence on the emerging role of JAK3 activation in hematological malignancies that warrant further studies to test the relevance of specific inhibition of JAK3 as a therapeutic approach to these challenging clinical entities. 相似文献
952.
953.
Xiaodan Su David M. Lucas Liwen Zhang Hua Xu Vlad Zabrouskov Melanie E. Davis Amy R. Knapp Donn C. Young Philip R. O. Payne Mark R. Parthun Guido Marcucci Michael R. Grever John C. Byrd Michael A. Freitas Dr. 《Proteomics》2009,9(5):1197-1206
The in vitro evaluation of histones and their PTMs has drawn substantial interest in the development of epigenetic therapies. The differential expression of histone isoforms may serve as a potential marker in the classification of diseases affected by chromatin abnormalities. In this study, protein profiling by LC and MS was used to explore differences in histone composition in primary chronic lymphocytic leukemia (CLL) cells. Extensive method validations were performed to determine the experimental variances that would impact histone relative abundance. The resulting data demonstrated that the proposed methodology was suitable for the analysis of histone profiles. In 4 normal individuals and 40 CLL patients, a significant decrease in the relative abundance of histone H2A variants (H2AFL and H2AFA/M*) was observed in primary CLL cells as compared to normal B cells. Protein identities were determined using high mass accuracy MS and shotgun proteomics. 相似文献
954.
Terry Nguyen‐Khuong Melanie Y. White Tzong‐Tyng Hung Shona Seeto Melissa L. Thomas Anna M. Fitzgerald Carlos E. Martucci Sharon Luk Shiu‐Fu Pang Pamela J. Russell Bradley J. Walsh Dr. 《Proteomics》2009,9(7):1883-1892
Bladder cancer (BLCa) is a severe urological cancer of both men and women that commonly recurs and once invasive, is difficult to treat. MINA‐05 (CK Life Sciences Int'l, Hong Kong) is a derivative of complex botanical extracts, shown to reduce cellular proliferation of bladder and prostate carcinomas. We tested the effects of MINA‐05 against human BLCa cell sublines, B8, B8‐RSP‐GCK, B8‐RSP‐LN and C3, from a transitional cell carcinoma, grade IV, to determine the molecular targets of treatment by observing the cellular protein profile. Cells were acclimatised for 48 h then treated for 72 h with concentrations of MINA‐05 reflecting IC50, IC50 and 2×IC50 (n = 3) or with vehicle, (0.5% DMSO). Dose‐dependant changes in protein abundance were detected and characterised using 2‐dimensional electrophoresis and MS. We identified 10 proteins that underwent changes in abundance, pI and/or molecular mass in response to treatment. MINA‐05 was shown to influence proteins across numerous functional classes including cytoskeletal proteins, energy metabolism proteins, protein degradation proteins and tumour suppressors, suggesting a global impact on these cell lines. This study implies that the ability of MINA‐05 to retard cellular proliferation is attributed to its ability to alter cell cycling, metabolism, protein degradation and the cancer cell environment. 相似文献
955.
Melanie Ann Sacco Kamila Koropacka Eric Grenier Marianne J. Jaubert Alexandra Blanchard Aska Goverse Geert Smant Peter Moffett 《PLoS pathogens》2009,5(8)
Plant NB-LRR proteins confer robust protection against microbes and metazoan
parasites by recognizing pathogen-derived avirulence (Avr) proteins that are
delivered to the host cytoplasm. Microbial Avr proteins usually function as
virulence factors in compatible interactions; however, little is known about the
types of metazoan proteins recognized by NB-LRR proteins and their relationship
with virulence. In this report, we demonstrate that the secreted protein RBP-1
from the potato cyst nematode Globodera pallida elicits defense
responses, including cell death typical of a hypersensitive response (HR),
through the NB-LRR protein Gpa2. Gp-Rbp-1 variants from
G. pallida populations both virulent and avirulent to
Gpa2 demonstrated a high degree of polymorphism, with
positive selection detected at numerous sites. All Gp-RBP-1
protein variants from an avirulent population were recognized by Gpa2, whereas
virulent populations possessed Gp-RBP-1 protein variants both
recognized and non-recognized by Gpa2. Recognition of Gp-RBP-1
by Gpa2 correlated to a single amino acid polymorphism at position 187 in the
Gp-RBP-1 SPRY domain. Gp-RBP-1 expressed
from Potato virus X elicited Gpa2-mediated defenses that required Ran
GTPase-activating protein 2 (RanGAP2), a protein known to interact with the Gpa2
N terminus. Tethering RanGAP2 and Gp-RBP-1 variants via fusion
proteins resulted in an enhancement of Gpa2-mediated responses. However,
activation of Gpa2 was still dependent on the recognition specificity conferred
by amino acid 187 and the Gpa2 LRR domain. These results suggest a two-tiered
process wherein RanGAP2 mediates an initial interaction with pathogen-delivered
Gp-RBP-1 proteins but where the Gpa2 LRR determines which
of these interactions will be productive. 相似文献
956.
Dominik Schüßler Marina B. Blanco Nicola K. Guthrie Gabriele M. Sgarlata Melanie Dammhahn Refaly Ernest Mamy Rina Evasoa Alida Hasiniaina Daniel Hending Fabien Jan Barbara le Pors Alex Miller Gillian Olivieri Ando N. Rakotonanahary Solofomalala Jacques Rakotondranary Romule Rakotondravony Tantely Ralantoharijaona Veronarindra Ramananjato Blanchard Randrianambinina Nancia N. Raoelinjanakolona Emilienne Rasoazanabary Rodin M. Rasoloarison David W. Rasolofoson Solofonirina Rasoloharijaona Emmanuel Rasolondraibe Sam Hyde Roberts Helena Teixeira Tobias van Elst Steig E. Johnson Jörg U. Ganzhorn Lounès Chikhi Peter M. Kappeler Edward E. Louis Jr. Jordi Salmona Ute Radespiel 《American journal of physical anthropology》2024,183(1):60-78
957.
Himpsl SD Pearson MM Arewång CJ Nusca TD Sherman DH Mobley HL 《Molecular microbiology》2010,78(1):138-157
Proteus mirabilis causes complicated urinary tract infections (UTIs). While the urinary tract is an iron-limiting environment, iron acquisition remains poorly characterized for this uropathogen. Microarray analysis of P. mirabilis HI4320 cultured under iron limitation identified 45 significantly upregulated genes (P ≤ 0.05) that represent 21 putative iron-regulated systems. Two gene clusters, PMI0229-0239 and PMI2596-2605, encode putative siderophore systems. PMI0229-0239 encodes a non-ribosomal peptide synthetase-independent siderophore system for producing a novel siderophore, proteobactin. PMI2596-2605 are contained within the high-pathogenicity island, originally described in Yersinia pestis, and encodes proteins with apparent homology and organization to those involved in yersiniabactin production and uptake. Cross-feeding and biochemical analysis shows that P. mirabilis is unable to utilize or produce yersiniabactin, suggesting that this yersiniabactin-related locus is functionally distinct. Only disruption of both systems resulted in an in vitro iron-chelating defect; demonstrating production and iron-chelating activity for both siderophores. These findings clearly show that proteobactin and the yersiniabactin-related siderophore function as iron acquisition systems. Despite the activity of both siderophores, only mutants lacking the yersiniabactin-related siderophore have reduced fitness in vivo. The fitness requirement for the yersiniabactin-related siderophore during UTI shows, for the first time, the importance of siderophore production in vivo for P. mirabilis. 相似文献
958.
Melanie Falb Irene Amata Frank Gabel Bernd Simon Teresa Carlomagno 《Nucleic acids research》2010,38(18):6274-6285
K-turn motifs are universal RNA structural elements providing a binding platform for proteins in several cellular contexts. Their characteristic is a sharp kink in the phosphate backbone that puts the two helical stems of the protein-bound RNA at an angle of 60°. However, to date no high-resolution structure of a naked K-turn motif is available. Here, we present the first structural investigation at atomic resolution of an unbound K-turn RNA (the spliceosomal U4-Kt RNA) by a combination of NMR and small-angle neutron scattering data. With this study, we wish to address the question whether the K-turn structural motif assumes the sharply kinked conformation in the absence of protein binders and divalent cations. Previous studies have addressed this question by fluorescence resonance energy transfer, biochemical assays and molecular dynamics simulations, suggesting that the K-turn RNAs exist in equilibrium between a kinked conformation, which is competent for protein binding, and a more extended conformation, with the population distribution depending on the concentration of divalent cations. Our data shows that the U4-Kt RNA predominantly assumes the more extended conformation in the absence of proteins and divalent cations. The internal loop region is well structured but adopts a different conformation from the one observed in complex with proteins. Our data suggests that the K-turn consensus sequence does not per se code for the kinked conformation; instead the sharp backbone kink requires to be stabilized by protein binders. 相似文献
959.
Manuela Nowotny Jennifer Hummel Melanie Weber Doreen Möckel Manfred Kössl 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2010,196(12):939-945
Bushcrickets have a tonotopically organised hearing organ, the so-called crista acustica, in the tibia of the forelegs. This organ responds to a frequency range of about 5–80 kHz and lies behind the anterior tympanum
on top of a trachea branch. We analyzed the sound-induced vibration pattern of the anterior tympanum, using a Laser-Doppler-Vibrometer
Scanning microscope system, in order to identify frequency-dependent amplitude and phase of displacement. The vibration pattern
evoked by a frequency sweep (4–79 kHz) showed an amplitude maximum which would correspond to the resonance frequency of an
open tube system. At higher frequencies of about 30 kHz a difference in the amplitude and phase response between the distal
and the proximal part of the tympanum was detected. The inner plate of the tympanum starts to wobble at this frequency. This
higher mode in the motion pattern is not explained by purely acoustic characteristics of the tracheal space below the tympanum
but may depend on the mechanical impedance of the tympanum plate. In accordance with a previous hypothesis, the tympanum moves
over the whole tested frequency range in the dorso-ventral direction like a hinged flap with the largest displacement in its
ventral part and no higher modes of vibration. 相似文献
960.
Ontogenetic change in the visual acuity of Seriola lalandi larvae was measured using both behavioural and anatomical techniques. Visual acuity improved over early development (day
4 to day 7 post-hatch), although for all three larval ages examined estimates of anatomical acuity were consistently lower
(higher acuity) than estimates of behavioural acuity. At hatching the eyes of larval kingfish were characterized by an undifferentiated
retina surrounding a spherical lens, by day 4 post-hatch the eyes appeared to be functional, the retina was fully pigmented
and the optic nerve had made contact with the optic tectum. Analysis of prey search behaviour indicated that larvae employ
a saltatory type search behaviour in which brief stationary periods are interspersed with repositioning movements. The mean
reactive angle increased between day 4 and day 7 post-hatch indicating that the horizontal visual field was expanding with
development, thereby increasing the search area of larvae. Pre-strike distances of early larvae were substantially less than
one body length, being constantly around a 1/3 of a body length for all larval ages examined. 相似文献