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161.
162.
Design of cyclic and d‐amino acids containing peptidomimetics for inhibition of protein‐protein interactions of HER2‐HER3
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Sandeep Pallerla Himgauri Naik Sitanshu Singh Ted Gauthier Rushikesh Sable Seetharama D. Jois 《Journal of peptide science》2018,24(2)
HER2 receptors are surface proteins belonging to the epidermal growth factor family of receptors. Their numbers are elevated in breast, lung, and ovarian cancers. HER2‐positive cancers are aggressive, have higher mortality rate, and have a poor prognosis. We have designed peptidomimetics that bind to HER2 and block the HER2‐mediated dimerization of epidermal growth factor family of receptors. Among these, a symmetrical cyclic peptidomimetic (compound 18 ) exhibited antiproliferative activity in HER2‐overexpressing lung cancer cell lines with IC50 values in the nanomolar concentration range. To improve the stability of the peptidomimetic, d ‐amino acids were introduced into the peptidomimetic, and several analogs of compound 18 were designed. Among the analogs of compound 18 , compound 32 , a cyclic, d ‐amino acid‐containing peptidomimetic, was found to have an IC50 value in the nanomolar range in HER2‐overexpressing cancer cell lines. The antiproliferative activity of compound 32 was also measured by using a 3D cell culture model that mimics the in vivo conditions. The binding of compound 32 to the HER2 protein was studied by surface plasmon resonance. In vitro stability studies indicated that compound 32 was stable in serum for 48 hours and intact peptide was detectable in vivo for 12 hours. Results from our studies indicated that 1 of the d ‐amino acid analogs of 18 , compound 32 , binds to the HER2 extracellular domain, inhibiting the phosphorylation of kinase of HER2. 相似文献
163.
Jagurti Jadhav Sruba Dutta Sandeep Kale 《Preparative biochemistry & biotechnology》2018,48(3):234-241
Glycolipids are one of the major classes of biosurfactants in which the rhamnolipids are best studied. The present work investigates the optimization of inoculum age and batch time for maximizing the yield of rhamnolipid from Pseudomonas aeruginosa (MTCC 2453). The yield and titer of rhamnolipids were maximum in the fermentation batch with an inoculum age of 24?hr. Batch time studies were performed on biomass production, rhamnolipid production, and sunflower oil utilization. The maximum yield of rhamnolipid was achieved at 96?hr when the culture cells were in the late exponential/early stationary phase. At optimum substrate concentration, maximum yield of 10.8?g/L was achieved. Further, downstream processing of crude rhamnolipid from broth using organic solvent extraction and subsequent purification using adsorption chromatography was done. In this study, chromatographic method was developed for purification of rhamnolipid by adsorption phenomena with more than 88.7% purity and 86.5% recovery. The present study provides new perspective on concepts involving separation by adsorption. Further antimicrobial properties and surfactant properties were studied for rhamnolipid production. 相似文献
164.
Sandeep Shewale 《Preparative biochemistry & biotechnology》2018,48(4):312-320
The objective of this work is to put forth the optimization and kinetics of total phenolic compounds extraction from Azadirachta indica leaves in a stirred batch extraction. Various experiential extraction parameters have been studied for maximum extraction of the total phenolic compounds. The maximum yield of total phenolic compounds was found to be 10.80?mg?g?1 of dried neem powder under the optimized conditions. The extraction kinetics behavior followed first-order kinetics with diffusion coefficient ranged from 1.8?×?10?12 to 3.2?×?10?12?m2 s?1 for all sets. Activation energy (Ea) value for the extraction of the total phenolic compounds was found to be 22.87?kJ?mol?1. The kinetic expression model developed by Spiro and Siddique showed a good agreement with the experimental outcomes. The obtained results can be used to scale up the operations for industrial purposes. 相似文献
165.
Madhuram Khandelwal Vivek Anand Sandeep Appunni Amlesh Seth Prabhjot Singh Sandeep Mathur Alpana Sharma 《Molecular and cellular biochemistry》2018,439(1-2):105-115
During the past decade, microRNAs have continuously been suggested as a promising therapeutic tool due to their beneficial effects, such as their multi-targets and multi-functions in pathologic conditions. As a pathologic phenotype is generally regulated by multiple signaling pathways, in this study we identified a microRNA regulating multiple target genes within cardiac hypertrophic signaling pathways. microRNA-133a is known to play a crucial role in cardiac hypertrophy. However, the role of microRNA-133a, which may regulate several signaling pathways in norepinephrine-induced cardiac hypertrophy via multi-targeting, has not been investigated. In the current study, we showed that microRNA-133a can protect cardiomyocyte hypertrophy against norepinephrine stimulation in neonatal rat ventricular cardiomyocytes via new targets, PKCδ and Gq, all of which are related to downstream signaling pathways of the α1-adrenergic receptor. Taken together, these results suggest the advantages of the therapeutic use of microRNAs as an effective potential drug regulating multiple signaling pathways under pathologic conditions. 相似文献
166.
Transient Arrest of Germinal Vesicle Breakdown Improved In Vitro Development Potential of Buffalo (Bubalus Bubalis) Oocytes
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167.
William J. Meurer Brigid Rowell Devin Brown Alexander Tsodikov Angela Fagerlin Steven A. Telian Laura Damschroder Lawrence C. An Lewis B. Morgenstern Laura Loudermilk Sandeep Vijan Kevin A. Kerber 《Trials》2018,19(1):697
Background
Benign paroxysmal positional vertigo (BPPV) is the most common peripheral vestibular disorder, and accounts for 8% of individuals with moderate or severe dizziness. BPPV patients experience substantial inconveniences and disabilities during symptomatic periods. BPPV therapeutic processes – the Dix-Hallpike Test (DHT) and the Canalith Repositioning Maneuver (CRM) – have an evidence base that is at the clinical practice guideline level. The most commonly used CRM is the modified Epley maneuver. The DHT is the gold standard test for BPPV and the CRM is supported by numerous randomized controlled trials and systematic reviews. Despite this, BPPV care processes are underutilized.Methods/design
This is a stepped-wedge, randomized clinical trial of a multi-faceted educational and care-process-based intervention designed to improve the guideline-concordant care of patients with BPPV presenting to the emergency department (ED) with dizziness. The unit of randomization and target of intervention is the hospital. After an initial observation period, the six hospitals will undergo the intervention in five waves (two closely integrated hospitals will be paired). The order will be randomized. The primary endpoint is measured at the individual patient level, and is the presence of documentation of either the Dix-Hallpike Test or CRM. The secondary endpoints are referral to a health care provider qualified to treat dizziness for CRM and 90-day stroke rates following an ED dizziness visit. Formative evaluations are also performed to monitor and identify potential and actual influences on the progress and effectiveness of the implementation efforts.Discussion
If this study safely increases documentation of the DHT/CRM, this will be an important step in implementing the use of these evidenced-based processes of care. Positive results will support conducting larger-scale follow-up studies that assess patient outcomes. The data collection also enables evaluation of potential and actual influences on the progress and effectiveness of the implementation efforts.Trial registration
ClinicalTrials.gov, ID: NCT02809599. The record was first available to the public on 22 June 2016 prior to the enrollment of the first patients in October 2016.168.
Woody plant diversity in relation to environmental factors in a seasonally dry tropical forest landscape
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Handanakere S. Dattaraja Sandeep Pulla Hebbalalu S. Suresh Mavinakoppa S. Nagaraja Chilakunda A. Srinivasa Murthy Raman Sukumar 《植被学杂志》2018,29(4):704-714
Questions
Water availability is known to be a first‐order driver of plant diversity; yet water also affects fire regimes and soil fertility, which, in turn, affect plant diversity. We examined how precipitation, fire and soil properties jointly determine woody plant diversity. Specifically, we asked how woody plant diversity varies along a sharp precipitation gradient (about 600–1,800 mm mean annual precipitation [MAP ]within a ~45‐km distance) exhibiting considerable variation in long‐term fire burn frequency and soil fertility, in a southern Indian seasonally dry tropical forest (SDTF ) landscape.Location
Mudumalai, Western Ghats, India.Methods
Woody plants ≥1‐cm DBH were enumerated in 19 1‐ha permanent plots spanning a range of tropical vegetation types from dry thorn forest, through dry and moist deciduous forest to semi‐evergreen forest. Burn frequencies were derived from annual fire maps. Six measures of surface soil properties – total exchangeable bases (Ca + Mg + K), organic carbon (OC ), total N, pH , plant available P and micronutrients (Fe + Cu + Zn + Mn) were used in the analyses. Five measures of diversity – species richness, Shannon diversity, the rarefied/extrapolated versions of these two measures, and Fisher's α – were modelled as functions of MAP , annual fire burn frequency and the principal components of soil properties.Results
Most soil nutrients and OC increased with MAP , except in the wettest sites. Woody productivity increased with MAP , while fire frequency was highest at intermediate values of MAP . Woody plant diversity increased with MAP but decreased with increasing fire frequency, resulting in two local diversity maxima along the MAP gradient – in the semi‐evergreen and dry thorn forest – separated by a low‐diversity central region in dry deciduous forest where fire frequency was highest. Soil variables were, on the whole, less strongly correlated with diversity than MAP .Conclusions
Although woody plant diversity in this landscape, representative of regional SDTF s, is primarily limited by water availability, our study emphasizes the role of fire as a potentially important second‐order driver that acts to reduce diversity in this landscape.169.
Predicting soils and environmental impacts associated with switchgrass for bioenergy production: a DAYCENT modeling approach
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Liming Lai Sandeep Kumar Solomon M. Folle Vance N. Owens 《Global Change Biology Bioenergy》2018,10(4):287-302
Switchgrass (Panicum virgatum L.) production has the potential to improve soils and the environment. However, little is known about the long‐term future assessment of soil and environmental impacts associated with switchgrass production. In this study, soil organic carbon (SOC), soil nitrate (), water‐filled pore space (WFPS), carbon dioxide (CO2) and nitrous oxide (N2O) fluxes, and biomass yield from switchgrass field were predicted using DAYCENT models for 2016 through 2050. Measured data for model calibration and validation at this study site managed with nitrogen fertilization rates (N rates) (low, 0 kg N ha?1; medium, 56 kg N ha?1; and high, 112 kg N ha?1) and landscape positions (shoulder and footslope) for switchgrass production were collected from the previously published studies. Modeling results showed that the N fertilization can enhance SOC and soil NO3?, but increase soil N2O and CO2 fluxes. In this study, medium N fertilization was the optimum rate for enhancing switchgrass yield and reducing negative impact on the environment. Footslope position can be beneficial for improving SOC, , and yield, but contribute higher greenhouse gas (GHG) emissions compared to those of the shoulder. An increase in temperature and decrease in precipitation (climate scenarios) may reduce soil , WFPS, and N2O flux. Switchgrass production can improve and maintain SOC and , and reduce N2O and CO2 fluxes over the predicted years. These findings indicate that switchgrass could be a sustainable bioenergy crop on marginally yielding lands for improving soils without significant negative impacts on the environment in the long run. 相似文献
170.
Mohammed A. Khedr Melendhran Pillay Sandeep Chandrashekharappa Deepak Chopra Bandar E. Aldhubiab Mahesh Attimarad 《Journal of biomolecular structure & dynamics》2018,36(8):2163-2178
A series of trisubstituted indolizine analogues has been designed as a result of a fragment-based approach to target the inhibition of mycobacterial enoyl-acyl carrier protein reductase. Anti-tuberculosis (TB) screening of the characterized compounds by a resazurin microplate assay method revealed that ethyl group at second position of indolizine nucleus exhibited activity against susceptible and multidrug-resistant strains of Mycobacterium tuberculosis at concentration of 5.5 and 11.3 μg/mL, respectively. A molecular docking study was also conducted to evaluate the stability of the active compounds, and compound with ethyl substitution at second position of indolizine nucleus showed the highest free binding energy of ΔG ?24.11 (kcal/mol), a low clash score of 3.04, and high lipo score of ?13.33. Indolizine analog with ethyl substitution at second position demonstrated Molecular Mechanics/Generalized Born Surface Area (?23.85 kcal/mol). Two molecular dynamics studies were computed (100 ps and 50 ns) to calculate the relationship between the potential and kinetic energies of the active anti-TB compound with time and temperature. The discovery of this lead may have a positive impact on anti-TB drug discovery. 相似文献