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941.
942.
Trivedi PJ Patel PS Brahmbhatt MM Patel BP Gajjar SB Dalal EN Shukla SN Shah PM Bakshi SR 《Indian journal of human genetics》2009,15(3):137-139
We report here two cases of trisomy 13 in acute myeloid leukemia M1 subtype. short-term unstimulated bone marrow and peripheral blood lymphocyte culture showed 47, XY, +13 in all metaphase plates and trisomy 13 was confirmed with whole chromosome paint probes. Trisomy 13 in AML-M1 is a rare numerical abnormality. This is the first Indian report of sole trisomy 13 in AML-M1. Here, we present two cases of elder male patients, which may constitute a distinct subtype. 相似文献
943.
944.
Manish B. Shah Cheryl Ingram‐Smith Leroy L. Cooper Jun Qu Yu Meng Kerry S. Smith Andrew M. Gulick 《Proteins》2009,77(3):685-698
The acyl‐AMP forming family of adenylating enzymes catalyze two‐step reactions to activate a carboxylate with the chemical energy derived from ATP hydrolysis. X‐ray crystal structures have been determined for multiple members of this family and, together with biochemical studies, provide insights into the active site and catalytic mechanisms used by these enzymes. These studies have shown that the enzymes use a domain rotation of 140° to reconfigure a single active site to catalyze the two partial reactions. We present here the crystal structure of a new medium chain acyl‐CoA synthetase from Methanosarcina acetivorans. The binding pocket for the three substrates is analyzed, with many conserved residues present in the AMP binding pocket. The CoA binding pocket is compared to the pockets of both acetyl‐CoA synthetase and 4‐chlorobenzoate:CoA ligase. Most interestingly, the acyl‐binding pocket of the new structure is compared with other acyl‐ and aryl‐CoA synthetases. A comparison of the acyl‐binding pocket of the acyl‐CoA synthetase from M. acetivorans with other structures identifies a shallow pocket that is used to bind the medium chain carboxylates. These insights emphasize the high sequence and structural diversity among this family in the area of the acyl‐binding pocket. Proteins 2009. © 2009 Wiley‐Liss, Inc. 相似文献
945.
F.A. Shah M.A. Ansari J. Watkins Z. Phelps J. Cross T.M. Butt 《Biocontrol Science and Technology》2009,19(7):743-753
The influence of 15 commercially available fungicides on the germination, growth and virulence of Metarhizium anisopliae, Beauveria bassiana, Isaria fumosorosea, and Lecanillium longisporum was evaluated. The influence of the fungicides on conidial germination was dependant on the fungicide type and dose. Most fungicides retarded conidial germination of all the fungi tested at 10× and at the recommended rate of application, however, their toxicity declined at lower concentrations. Most of the fungicides inhibited mycelial growth of B. bassiana, whereas L. longisporum growth was unaffected. Only two and eight fungicides influenced mycelial growth of I. fumosorosea and M. anisopliae, respectively. None of the fungicides influenced the virulence of B. bassiana and L. longisporum, however, tolylfluanid and azoxystrobin reduced the virulence of M. anisopliae and I. fumosorosea, respectively. These studies clearly show that certain fungicides have the potential to inhibit germination of entomopathogenic fungi in vitro but appear to have little or no effect on their virulence against target insects. 相似文献
946.
David A. Ellis Julie K. Blazel Chinh V. Tran Frank Ruebsam Douglas E. Murphy Lian-Sheng Li Jingjing Zhao Yuefen Zhou Helen M. McGuire Alan X. Xiang Stephen E. Webber Qiang Zhao Qing Han Charles R. Kissinger Matthew Lardy Alberto Gobbi Richard E. Showalter Amit M. Shah Mei Tsan Rupal A. Patel Leo Kirkovsky 《Bioorganic & medicinal chemistry letters》2009,19(21):6047-6052
The discovery of 5,5′- and 6,6′-dialkyl-5,6-dihydro-1H-pyridin-2-ones as potent inhibitors of the HCV RNA-dependent RNA polymerase (NS5B) is described. Several of these agents also display potent antiviral activity in cell culture experiments (EC50 <0.10 μM). In vitro DMPK data for selected compounds as well as crystal structures of representative inhibitors complexed with the NS5B protein are also disclosed. 相似文献
947.
Evolution of geminiviruses and their satellites 总被引:1,自引:0,他引:1
Muhammad Shah Nawaz-ul-Rehman 《FEBS letters》2009,583(12):1825-113
Geminiviruses and their satellites have circular single stranded DNA genomes, infecting many crops and weeds across the globe. To successfully invade new hosts, break host resistance, move virus particles within and between plants, geminiviruses and their satellites have evolved a coordinated network of protein interactions, showing a possible evolutionary path. Humans have played an important role in the last century to promote the emergence of many geminivirus diseases, thereby impacting their evolution. The greatest molecular diversity of geminiviruses and their satellites resides in Southeast Asia revealing a possible center of origin. This minireview leads us to a possible general grand scheme of their evolution. 相似文献
948.
Short duplexes between the U3 small nucleolar RNA and the precursor ribosomal RNA must form quickly and with high yield to satisfy the high demand for ribosome synthesis in rapidly growing eukaryotic cells. These interactions, designated the U3-ETS (external transcribed spacer) and U3-18S duplexes, are essential to initiate the processing of small subunit ribosomal RNA. Previously, we showed that duplexes corresponding to those in Saccharomyces cerevisiae are only observed in vitro after addition of one of two proteins: Imp3p or Imp4p. Here, we used fluorescence-based and other in vitro assays to determine whether these proteins possess RNA chaperone activities and to assess whether these activities are sufficient to satisfy the duplex yield and rate requirements expected in vivo. Assembly of both proteins with the U3 small nucleolar RNA into a chaperone complex destabilizes a U3 stem structure, apparently to expose its 18S base-pairing site. As a result, the chaperone complex accelerates formation of the U3-18S duplex from an undetectable rate to one comparable with the intrinsic rate observed for hybridizing short duplexes. The chaperone complex also stabilizes the U3-ETS duplex by 2.7 kcal/mol. These chaperone activities provide high U3-ETS duplex yield and rapid U3-18S duplex formation over a broad concentration range to help ensure that the U3-precursor ribosomal RNA interactions limit neither ribosome biogenesis nor rapid cell growth. The thermodynamic and kinetic framework used is general and thus suitable for investigating the mechanism of action of other RNA chaperones. 相似文献
949.
Girish V. Shah Anbalagan Muralidharan Mitan Gokulgandhi Kamal Soan Shibu Thomas 《The Journal of biological chemistry》2009,284(2):1018-1030
Calcitonin, a neuroendocrine peptide, and its receptor are localized in the
basal epithelium of benign prostate but in the secretory epithelium of
malignant prostates. The abundance of calcitonin and calcitonin receptor mRNA
displays positive correlation with the Gleason grade of primary prostate
cancers. Moreover, calcitonin increases tumorigenicity and invasiveness of
multiple prostate cancer cell lines by cyclic AMP-dependent protein
kinase-mediated actions. These actions include increased secretion of matrix
metalloproteinases and urokinase-type plasminogen activator and an increase in
prostate cancer cell invasion. Activation of calcitonin-calcitonin receptor
autocrine loop in prostate cancer cell lines led to the loss of cell-cell
adhesion, destabilization of tight and adherens junctions, and internalization
of key integral membrane proteins. In addition, the activation of
calcitonin-calcitonin receptor axis induced epithelial-mesenchymal transition
of prostate cancer cells as characterized by cadherin switch and the
expression of the mesenchymal marker, vimentin. The activated calcitonin
receptor phosphorylated glycogen synthase kinase-3, a key regulator of
cytosolic β-catenin degradation within the WNT signaling pathway. This
resulted in the accumulation of intracellular β-catenin, its
translocation in the nucleus, and transactivation of β-catenin-responsive
genes. These results for the first time identify actions of
calcitonin-calcitonin receptor axis on prostate cancer cells that lead to the
destabilization of cell-cell junctions, epithelial-to-mesenchymal transition,
and activation of WNT/β-catenin signaling. The results also suggest that
cyclic AMP-dependent protein kinase plays a key role in calcitonin
receptor-induced destabilization of cell-cell junctions and activation of
WNT-β-catenin signaling.Prostate cancer
(PC)2 is the most
commonly diagnosed cancer and the second leading cause of cancer deaths in men
in the United States (1,
2). Although androgen ablation
therapy is effective in men with advanced disease for some time, the disease
subsequently progresses to the androgen-independent stage. The population of
prostate cells expressing neuroendocrine factors such as calcitonin (CT) also
increases during this progression
(3–5).
At this stage, the disease is metastatic and chemoresistant. Present evidence
suggests that cancer metastasis is usually preceded by the disruption of
normal cell-cell adhesion and the loss of integrity of the primary tumor site
(6,
7). This process may include
several genetic, molecular, and morphological changes characterized by
epithelial-to-mesenchymal transition (EMT)
(8–10).
The EMT is characterized by the loss of cell polarity, altered cell-cell and
cell-matrix adhesion, and acquisition of migratory, mesenchymal phenotype.
Other reported changes include down-regulation of E-cadherin, induction of
N-cadherin, release of β-catenin from junctional complexes, and its
translocation to the nucleus
(11–13).
However, the precise molecular mechanisms associated with this process are
obscure.Several growth factors, including hepatocyte growth factor, transforming
growth factor-β, vascular endothelial growth factor, and epidermal growth
factor, have been reported to induce EMT in tumor cell lines
(14–16).
We have shown that the expression of CT and its G protein-coupled receptor
(CTR) is remarkably higher in advanced PCs, and the CT-CTR autocrine axis is a
potent stimulator of PC cell tumorigenicity, invasion, and metastasis
(4,
17–19).
Although CT-stimulated increase in the motility and invasion of PC cells may
be mediated by CT-stimulated secretion of matrix metalloproteinases and
urokinase-type plasminogen activator, the precise molecular mechanisms
preceding these CTR actions remain to be elucidated
(18,
20). We tested the hypothesis
that CT induces biochemical and morphological changes associated with EMT to
increase the invasiveness of PC cells.Our results indicate that activation of the CT-CTR autocrine axis in
prostate cancer cells induced several changes associated with EMT such as
remodeling of tight and adherens junctions, cadherin switching, and activation
of WNT/β-catenin signaling. In contrast, the silencing of the CT-CTR axis
reversed this process. Moreover, cyclic AMP-dependent protein kinase (PKA)
plays a key role in this CT-CTR-mediated process. This is the first study
demonstrating the action of prostate CTR on junctional complexes and
WNT/β-catenin signaling of PC cell lines. 相似文献
950.
The canola industry generates more than $11 billion of yearly income to the Canadian economy. One problem of meal quality
is the dark polyphenolic pigments that accumulate in the seed coat. Seed coat-specific promoters are a pre-requisite to regulate
the genes involved in seed coat development and metabolism. The β-glucuronidase (GUS) reporter gene was used to test an Arabidopsis promoter in developing and mature seeds of canola (Brassica napus). The promoter tested is the regulatory region of the laccase gene (AtLAC15) from Arabidopsis thaliana. The AtLAC15 promoter::GUS construct was inserted into canola double haploid line DH12075 using Agrobacterium-mediated transformation. Southern blot analysis using a 536 bp GUS probe showed variation among the transformed plants in
the T-DNA copy numbers and the position of the insertion in their genomes. Histochemical assay of the GUS enzyme in different
tissues (roots, leaves, stem, pollen grains, flowers, siliques, embryos and seed coats) showed ascending GUS activity only
in the seed coat from 10 days after pollination (DAP) to the fully mature stage (35 DAP). GUS stain was observed in the mucilage
cell layer, in the outer integument layer of the seed coat but not in the inner integument. The AtLAC15 promoter exhibited a specificity and expression level that is useful as a seed coat-specific promoter for canola. 相似文献