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41.
Castellano JM Batrynchuk J Dolbeare K Verma V Mann A Skoblenick KJ Johnson RL Mishra RK 《Peptides》2007,28(10):2009-2015
Two melanocyte-stimulating hormone release inhibiting factor-1 (MIF-1) also known as L-prolyl-L-leucyl-glycinamide (PLG) peptidomimetic analogs, 3(R)-[[[2(S)-pyrrolidinyl]carbonyl]-amino]-3-(butyl)-2-oxo-1-pyrrolidineacetamide trifluoroacetate (A) and 3(R)-[[[2(S)-pyrrolidinyl]carbonyl]amino]-3-(benzyl)-2-oxo-1-pyrrolidineacetamide trifluoroacetate (B), were evaluated for their ability to modulate dopaminergic activity by measuring apomorphine-induced rotations in 6-hydroxydopamine (6-OHDA)-lesioned rats, and haloperidol (HP)-induced vacuous chewing movements (VCMs) in rats; animal models of Parkinson's disease (PD) and human tardive dyskinesia (TD), respectively. In the 6-OHDA model, both analogs were found to potentiate the contralateral rotational behavior induced by apomorphine dose-dependently and with approximately the same potency. Furthermore, each analog was able to significantly attenuate HP-induced VCMs with almost equal efficacy. The potency and efficacy of these analogs were significantly greater than their parent compound, PLG. These results suggest that both analogs can modulate dopaminergic activity in vivo, likely by the same mechanisms recruited by PLG previously reported. 相似文献
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Although it is now possible to fold peptides and miniproteins in molecular dynamics simulations, it is well appreciated that force fields are not all transferable to different proteins. Here, we investigate the influence of the protein force field and the solvent model on the folding energy landscape of a prototypical two‐state folder, the GB1 hairpin. We use extensive replica‐exchange molecular dynamics simulations to characterize the free‐energy surface as a function of temperature. Most of these force fields appear similar at a global level, giving a fraction folded at 300 K between 0.2 and 0.8 in all cases, which is a difference in stability of 2.8 kT, and are generally consistent with experimental data at this temperature. The most significant differences appear in the unfolded state, where there are different residual secondary structures which are populated, and the overall dimensions of the unfolded states, which in most of the force fields are too collapsed relative to experimental Förster Resonance Energy Transfer (FRET) data. Proteins 2011. © 2010 Wiley‐Liss, Inc. 相似文献
45.
Migraine is a neurovascular disorder, and hence, any alteration in vascular endothelial function by either the endothelin system or the apolipoproteins may contribute to its pathophysiology. Thus, we investigated the role of EDNRA -231 G>A and APOE HhaI polymorphism for a possible association with migraine. Genotyping of 613 subjects consisting of 217 migraine subjects, 217 healthy controls (HC), and 179 subjects with tension-type headache was performed using the standard PCR-RFLP method. Data were analyzed by taking the Bonferroni-corrected p-values into account. We found significant difference in the frequency of EDNRA AA genotype between migraine subjects when compared with HC (p-value?=?0.005; OR?=?2.542; confidence interval [CI]?=?1.329-4.863). A similar trend was shown by female migraine subjects at genotype and allele levels. The association of EDNRA -231 G>A polymorphism with migraine fit a recessive model (migraine vs. HC, p-value?=?0.002; OR?=?1.917; CI?=?2.268-2.898). Female migraineurs without aura (MO) followed a similar trend. In the case of APOE HhaI polymorphism, E3E4 and E2E3 genotypes conferred risk when taken together in case of migraine versus HC (p-value?=?0.005; OR?=?2.715; CI?=?1.342-5.490) and migraine with aura (MA) versus HC (p-value?=?0.004; OR?=?3.422; CI?=?7.992). The risk was also seen after stratification on the basis of gender in female migraineurs (total migraine and MA). The interaction of EDNRA and APOE genotypes did not show further significance. The AA genotype and A allele of EDNRA -231 G>A polymorphism conferred risk for total migraine and MO. In APOE HhaI polymorphism, E3E4 and E2E3 conferred risk when taken together in total migraine and MA. 相似文献
46.
The expression of cathepsin L, a lysosomal protease, is known to be elevated in cancer and other pathologies. Multiple splice variants of human cathepsin L with variable 5'UTRs exist, which encode for the same protein. Previously we have observed that variant hCATL A (bearing the longest 5'UTR) was translated in vitro with significantly lower efficiency than variant hCATL AIII (bearing the shortest 5'UTR). Contrary to these findings, results of the present study reveal that in cancer cells, hCATL A mRNA exhibits higher translatability in spite of having lower stability than AIII. This is the first report demonstrating a highly contrasting trend in translation efficiencies of hCATL variants in rabbit reticulocytes and live cells. Expression from chimeric mRNAs containing 5'UTRs of A or AIII upstream to luciferase reporter cDNA established the A UTR to be the sole determinant for this effect. Transient transfections of bicistronic plasmids and mRNAs confirmed the presence of a functional Internal Ribosome Entry Site in this UTR. Our data suggest that differential stability and translation initiation modes mediated by the 5'UTRs of human cathepsin L variants are involved in regulating its expression. 相似文献
47.
Polymerase chain reaction (PCR), followed by restriction digestion is universally used for molecular diagnosis of spinal muscular atrophy (SMA). In the present study, we have used a modified strategy based on amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) to develop a rapid and reliable method for mutation detection and prenatal diagnosis in SMA patients. The telomeric (SMN1) and centromeric (SMN2) copies of exon 7 of the survival motor neuron (SMN) gene were amplified by ARMS-PCR, using primers specific to SMN1 and SMN2 nucleotide sequence with the exonic mismatch G (for SMN1) and A (for SMN2) at the 3' end. The PCR products were analyzed on agarose gels. All the patients who had homozygous deletion of exon 7 of SMN1 gene by conventional PCR-restriction fragment length polymorphism (PCR-RFLP) method showed the same deletion status by ARMS-PCR. This procedure showed a 100% concordance between PCR-RFLP and ARMS-PCR methods for the detection of SMN1/SMN2 status in patients with SMA. An artifact due to incomplete digestion is not a problem while using ARMS-PCR. The modified protocol is specific, rapid and highly reliable for use in prenatal diagnosis as well. 相似文献
48.
Puckett JL Liu J Bhalla V Kravetz D Krinsky ML Hassanein T Mittal RK 《American journal of physiology. Gastrointestinal and liver physiology》2005,288(5):G914-G919
We report our experience with an ultrasound system to measure esophageal varix pressure in an in vitro model. The ultrasound system consists of a 12.5 MHz frequency intraluminal ultrasound probe, a water infusion catheter, and a manometry catheter, all contained within a nondistensible latex bag. Esophagi and external jugular veins were harvested from five pigs. The vein and ultrasound system were placed inside the esophagus. One end of the vein was connected to a water reservoir to modulate its pressure; the other end was connected in two different ways to simulate hydrodynamic and hydrostatic flow conditions. The bag was inflated with water until vein occlusion was discernible on the ultrasound images. The influences of vein pressure, vein cross-sectional area and esophageal elasticity on the ultrasound measurement of vein pressure were assessed. A total of 108 trials were performed at nine different vein pressures. Complete vein occlusion occurred when the bag pressure was slightly greater (1.4 +/- 0.7 mmHg) than the vein pressure. For a vein pressure of 25 mmHg, the average occlusion and opening pressures were 27 +/- 0.2 and 25.7 +/- 0.3 mmHg, respectively (P < .05) suggesting that the vein opening pressure on the ultrasound images is more accurate than the vein closing pressure. In conclusion, the ultrasound technique can accurately measure intravariceal pressure in vitro. The bag pressure at the point of vein reopening is the best determinant of the vein pressure. 相似文献
49.
Wang J Shaner N Mittal B Zhou Q Chen J Sanger JM Sanger JW 《Cell motility and the cytoskeleton》2005,61(1):34-48
During myofibril formation, Z-bodies, small complexes of alpha-actinin and associated proteins, grow in size, fuse and align to produce Z-bands. To determine if there were changes in protein dynamics during the assembly process, Fluorescence Recovery after Photobleaching was used to measure the exchange of Z-body and Z-band proteins with cytoplasmic pools in cultures of quail myotubes. Myotubes were transfected with plasmids encoding Yellow, Green, or Cyan Fluorescent Protein linked to the Z-band proteins: actin, alpha-actinin, cypher, FATZ, myotilin, and telethonin. Each Z-band protein showed a characteristic recovery rate and mobility. All except telethonin were localized in both Z-bodies and Z-bands. Proteins that were present both early in development in Z-bodies and later in Z-bands had faster exchange rates in Z-bodies. These results suggest that during myofibrillogenesis, molecular interactions develop between the Z-band proteins that decrease their mobility and increase the stability of the Z-bands. A truncated construct of alpha-actinin, which localized in Z-bands in myotubes and exhibited a very low rate of exchange, led to disruption of myofibrils, suggesting the importance of dynamic, intact alpha-actinin molecules for the formation and maintenance of Z-bands. Our experiments reveal the Z-band to be a much more dynamic structure than its appearance in electron micrographs of cross-striated muscle cells might suggest. 相似文献
50.
Chintamani Jai Parakash Singh Mahesh K Mittal Sunita Saxena Anju Bansal Ashima Bhatia Pranjal Kulshreshtha 《World journal of surgical oncology》2005,3(1):1-9