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Ketan Patel

Publications and source records attributed to Ketan Patel.

43 records · Page 3Linked to original sources

Combinatorial use of mRNA and two-dimensional electrophoresis expression data to choose relevant features for mass spectrometric identification.

It is only recently that quantitative studies of differential proteome analysis (DPA) have become possible. In this paper the issues involved in quantitative DPA are discussed and novel tools to select features for identification by mass spectrometry (MS) are described. The problem of comparing two sets of gels on a global level is explored as well as how to find specific protein features that differentiate two sets of two-dimensional electrophoresis gels. The concept of a 'virtual' gel, derived from gene expression data, is introduced. The virtual gel enables the co-analysis of data from gene and protein expression. We discuss the value of such an approach, and consider what new information can be gained by using gene and protein expression together. These tools are illustrated by analysis of data from tandem gene and protein expression experiments. Features that are highlighted by the above methods are putative candidates for MS identification. Tools are described that integrate the process of feature selection, cutting, and MS analysis.

Breast↗

Evidence that nitric oxide regulates cell-cycle progression in the developing chick neuroepithelium.

In all developing epithelia, the nuclei continually migrate between the apical and basal sides of the cell during the cell cycle, with S phase occurring basally and mitosis occurring apically. The purpose and mechanism of this nuclear migration are unknown. Here, we show that nitric oxide (NO) is endogenously produced in the developing chicken neural tube, where it apparently regulates cell-cycle progression. We provide evidence that high NO levels promote entry into S phase basally, whereas low levels of NO facilitate entry into mitosis apically.

Animals↗

Titin-cap associates with, and regulates secretion of, Myostatin.

Myostatin, a secreted growth factor, is a key negative regulator of skeletal muscle growth. To identify modifiers of Myostatin function, we screened for Myostatin interacting proteins. Using a yeast two-hybrid screen, we identified Titin-cap (T-cap) protein as interacting with Myostatin. T-cap is a sarcomeric protein that binds to the N-terminal domain of Titin and is a substrate of the titin kinase. Mammalian two-hybrid studies, in vitro binding assays and protein truncations in the yeast two-hybrid system verified the specific interaction between processed mature Myostatin and full-length T-cap. Analysis of protein-protein interaction using surface plasmon resonance (Biacore, Uppsala, Sweden) kinetics revealed a high affinity between Myostatin and T-cap with a KD of 40 nM. When T-cap was stably overexpressed in C(2)C(12) myoblasts, the rate of cell proliferation was significantly increased. Western analyses showed that production and processing of Myostatin were not altered in cells overexpressing T-cap, but an increase in the retention of mature Myostatin indicated that T-cap may block Myostatin secretion. Bioassay for Myostatin confirmed that conditioned media from myoblasts overexpressing T-cap contained lower levels of Myostatin. Given that Myostatin negatively regulates myoblast proliferation, the increase in proliferation observed in myoblasts overexpressing T-cap could thus be due to reduced Myostatin secretion. These results suggest that T-cap, by interacting with Myostatin, controls Myostatin secretion in myogenic precursor cells without affecting the processing step of precursor Myostatin.

Animals↗

BMPs induce dermal markers and ectopic feather tracts.

Bone morphogenetic protein (BMP) signaling is known to be involved in multiple inductive events during embryogenesis including the development of amniote skin. Here, we demonstrate that early application of BMP-2 to the lateral trunk of chick embryos induces the formation of dense dermis, which is competent to participate in feather development. We show that BMPs induce the dermis markers Msx-1 and cDermo-1 and lead to dermal proliferation, to expression of beta-catenin, and eventually to the formation of ectopic feather tracts in originally featherless regions of chick skin. Moreover, we present a detailed analysis of cDermo-1 expression during early feather development. The data implicate that cDermo-1 is located downstream of BMP in a signaling pathway that leads to condensation of dermal cells. The roles of BMP and cDermo-1 during development of dermis and feather primordia are discussed.

Animals↗

Muscle development genes: their relevance in neuromuscular disorders.

Myogenesis is a complex cascade of events that involves the specification and differentiation of muscle precursor cells or myoblasts, their fusion to form primary and secondary myotubes and subsequent maturation into muscle fibres. In addition, the development of axial muscle requires the migration of muscle precursor cells. These events are under strict genetic control. The contribution of individual genes to this process has been highlighted both by the phenotype of mice with targeted inactivation of individual myogenic regulatory factors and by rare human disorders in which the involvement of these genes has been demonstrated. The inactivation of known myogenic regulatory genes is associated with abnormal regulation of skeletal muscle differentiation and has an effect on regeneration but does not cause progressive muscle weakness or wasting. This review summarises recent developments in this field and will be of particular relevance to those interested in neuromuscular disorders. We also examine the possibility that some rare human conditions associated with abnormal muscle formation may be due to genetic defects in one of the myogenic regulatory genes.

Animals↗

The effect of therapeutic irradiation on LactoSorb absorbable copolymer.

Bioabsorbable implants continue to gain popularity in providing temporary internal fixation due to their many advantages over metallic internal fixation. Coincident with the presence of internal fixation devices, it may be necessary to use radiotherapy to treat tumors. While metal implants can alter the distribution of the radiotherapy beam, bioabsorbable polymer implants are, essentially, tissue equivalent. This ionizing irradiation, in sufficiently high dose, can affect polymers through chain scission and cross-linking and accelerate the hydrolysis of absorbable polymers. However, little is known about the effects of therapeutic doses on such materials. This study exposed LactoSorb (Biomet, Inc., Warsaw, IN) absorbable copolymer to doses of x-ray irradiation in a clinically relevant manner, in vitro, with individual doses of 2 Gy administered five days per week for up to eight weeks, yielding a total cumulative dose of up to 80 Gy. Specimens were tested both mechanically and for inherent viscosity. Overall, the LactoSorb specimens withstood exposure to the irradiation exceedingly well, providing empirical evidence of the suitability of this material for temporary internal fixation when subsequent radiotherapy in the region is probable.

Absorbable Implants↗