Journals
2018 EN
Kathleen F. O’Rourke · Jennifer M. Axe · Rebecca N. D’Amico
+2 more
Tryptophan synthase is a model system for understanding allosteric regulation within enzyme complexes. Amino acid interaction networks were previously delineated in the isolated alpha subunit (αTS) in the absence of the beta subunit (βTS). The amino acid interaction networks were different between the ligand-free enzyme and the enzyme actively catalyzing turnover. Previous X-ray crystallography studies indicated only minor localized changes when ligands bind αTS, and so, structural changes alone could not explain the changes to the amino acid interaction networks. We hypothesized that the network changes could instead be related to changes in conformational dynamics. As such, we conducted nuclear magnetic resonance relaxation studies on different substrate- and products-bound complexes of αTS. Specifically, we collected 15 N R 2 relaxation dispersion data that reports on microsecond-to-millisecond timescale motion of backbone amide groups. These experiments indicated that there are conformational exchange events throughout αTS. Substrate and product binding change specific motional pathways throughout the enzyme, and these pathways connect the previously identified network residues. These pathways reach the αTS/βTS binding interface, suggesting that the identified dynamic networks may also be important for communication with the βTS subunit.
Journals
2018 EN
Meetu Wadhwa · Garima Chauhan · Koustav Roy
+7 more
Background : Sleep deprivation (SD) plagues modern society due to the professional demands. It prevails in patients with mood and neuroinflammatory disorders. Although growing evidence suggests the improvement in the cognitive performance by psychostimulants during sleep-deprived conditions, the impending involved mechanism is rarely studied. Thus, we hypothesized that mood and inflammatory changes might be due to the glial cells activation induced modulation of the inflammatory cytokines during SD, which could be improved by administering psychostimulants. The present study evaluated the role of caffeine/modafinil on SD-induced behavioral and inflammatory consequences. Methods : Adult male Sprague-Dawley rats were sleep deprived for 48 h using automated SD apparatus. Caffeine (60 mg/kg/day) or modafinil (100 mg/kg/day) were administered orally to rats once every day during SD. Rats were subjected to anxious and depressive behavioral evaluation after SD. Subsequently, blood and brain were collected for biochemical, immunohistochemical and molecular studies. Results : Sleep deprived rats presented an increased number of entries and time spent in closed arms in elevated plus maze test and decreased total distance traveled in the open field (OF) test. Caffeine/modafinil treatment significantly improved these anxious consequences. However, we did not observe substantial changes in immobility and anhedonia in sleep-deprived rats. Caffeine/modafinil significantly down-regulated the pro- and up-regulated the anti-inflammatory cytokine mRNA and protein expression in the hippocampus during SD. Similar outcomes were observed in blood plasma cytokine levels. Caffeine/modafinil treatment significantly decreased the microglial immunoreactivity in DG, CA1 and CA3 regions of the hippocampus during SD, however, no significant increase in immunoreactivity of astrocytes was observed. Sholl analysis signified the improvement in the morphological alterations of astrocytes and microglia after caffeine/modafinil administration during SD. Stereological analysis demonstrated a significant improvement in the number of ionized calcium binding adapter molecule I (Iba-1) positive cells (different states) in different regions of the hippocampus after caffeine or modafinil treatment during SD without showing any significant change in total microglial cell number. Eventually, the correlation analysis displayed a positive relationship between anxiety, pro-inflammatory cytokines and activated microglial cell count during SD. Conclusion : The present study suggests the role of caffeine or modafinil in the amelioration of SD-induced inflammatory response and anxious behavior in rats. Highlights - SD induced mood alterations in rats. - Glial cells activated in association with the changes in the inflammatory cytokines. - Caffeine or modafinil improved the mood and restored inflammatory changes during SD. - SD-induced anxious behavior correlated with the inflammatory consequences.
Journals
2018 EN
Satyam Mukherjee · Ryan Whalen
This paper analyzes court priority queuing behavior by examining the time lapse between when a case enters a court’s docket and when it is ultimately disposed of. Using data from the Supreme courts of the United States, Massachusetts, and Canada we show that each court’s docket features a slow decay with a decreasing tail. This demonstrates that, in each of the courts examined, the vast majority of cases are resolved relatively quickly, while there remains a small number of outlier cases that take an extremely long time to resolve. We discuss the implications for this on legal systems, the study of the law, and future research.
Journals
2018 EN
Sunil Kumar Sahu · Ping Zheng · Nan Yao
Rice ( Oryza sativa ) is the leading source of nutrition for more than half of the world’s population, and by far it is the most important commercial food crop. But, its growth and production are significantly hampered by the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo) which causes leaf blight disease. Earlier studies have reported the antibacterial ability of FDA-approved niclosamide drug against Xoo. However, the underlying mechanism by which niclosamide blocks the growth of Xoo remained elusive. In the present study, by employing the microbiological, microscopical, molecular, bioinformatics and analytical tools we found that niclosamide can directly inhibit the growth of the Xoo by hampering the biofilm formation and the production of xanthomonadin and exopolysaccharide substances (EPS) required for relentless growth and virulence of Xoo. Interestingly, niclosamide was found to specifically suppress the growth of Xoo without affecting other bacteria like Escherichia coli . Our electron microscopic observations disclosed that niclosamide disrupts the membrane permeability of Xoo and causes the release of intracellular components. Similarly, the molecular docking analysis disclosed the molecular interaction of niclosamide with the biofilm, virulence and quorum sensing related proteins, which was further substantiated by relative gene expression analysis where niclosamide was found to significantly downregulate the expression of these key regulatory genes. In addition, considerable changes in chemical structures were detected by Fourier Transform Infrared Spectroscopy (FTIR) in response to niclosamide treatment. Overall, our findings advocate the utilization of niclosamide as a safe and potent alternative antibacterial compound to control bacterial blight disease in rice.
Journals
2018 EN
Sandeep Sharma · Ranabir Sahu · Sudhir Navathe
+5 more
Spot blotch, caused by the hemibiotropic fungus Bipolaris sorokiniana , is amongst the most damaging diseases of wheat. Still, natural variation in expression of biochemical traits that determine field resistance to spot blotch in wheat remain unaddressed. To understand how genotypic variations relate to metabolite profiles of the components of defense-signaling and the plant performance, as well as to discover novel sources of resistance against spot blotch, we have conducted field studies using 968 wheat genotypes at 5 geographical locations in South-Asia in 2 years. 46 genotypes were identified as resistant. Further, in independent confirmatory trials in subsequent 3 years, over 5 geographical locations, we re-characterized 55 genotypes for their resistance (above 46 along with Yangmai#6, a well characterized resistant genotype, and eight susceptible genotypes). We next determined time-dependent spot blotch-induced metabolite profiles of components of defense-signaling as well as levels of enzymatic components of defense pathway (such as salicylic acid (SA), phenolic acids, and redox components), and derived co-variation patterns with respect to resistance in these 55 genotypes. Spot blotch-induced SA accumulation was negatively correlated to disease progression. Amongst phenolic acids, syringic acid was most strongly inversely correlated to disease progression, indicating a defensive function, which was independently confirmed. Thus, exploring natural variation proved extremely useful in determining traits influencing phenotypic plasticity and adaptation to complex environments. Further, by overcoming environmental heterogeneity, our study identifies germplasm and biochemical traits that are deployable for spot blotch resistance in wheat along South-Asia.
Journals
2018 EN
Rakesh Sahu · Narendra S. Chaudhari
In Mobile Ad-hoc networks (MANET), power conservation and utilization is an acute problem and has received significant attention from academics and industry in recent years. Nodes in MANET function on battery power, which is a rare and limited energy resource. Hence, its conservation and utilization should be done judiciously for the effective functioning of the network. In this paper, a novel protocol namely Energy Reduction Multipath Routing Protocol for MANET using Recoil Technique (AOMDV-ER) is proposed, which conserves the energy along with optimal network lifetime, routing overhead, packet delivery ratio and throughput. It performs better than any other AODV based algorithms, as in AOMDV-ER the nodes transmit packets to their destination smartly by using a varying recoil off time technique based on their geographical location. This concept reduces the number of transmissions, which results in the improvement of network lifetime. In addition, the local level route maintenance reduces the additional routing overhead. Lastly, the prediction based link lifetime of each node is estimated which helps in reducing the packet loss in the network. This protocol has three subparts: an optimal route discovery algorithm amalgamation with the residual energy and distance mechanism; a coordinated recoiled nodes algorithm which eliminates the number of transmissions in order to reduces the data redundancy, traffic redundant, routing overhead, end to end delay and enhance the network lifetime; and a last link reckoning and route maintenance algorithm to improve the packet delivery ratio and link stability in the network. The experimental results show that the AOMDV-ER protocol save at least 16% energy consumption, 12% reduction in routing overhead, significant achievement in network lifetime and packet delivery ratio than Ad hoc on demand multipath distance vector routing protocol (AOMDV), Ad hoc on demand multipath distance vector routing protocol life maximization (AOMR-LM) and Source routing-based multicast protocol (SRMP) algorithms. Hence, the AOMDV-ER algorithm performs better than these recently developed algorithms.
Multidisciplinary Digital Publishing Institute
Journals
2018 EN
Mahesh Suresh Patil · Satyam Panchal · Namwon Kim
+1 more
Temperature control of the lithium-ion pouch cells is crucial for smooth operation, longevity and enhanced safety in the battery-operated electric vehicles. Investigating the thermal behavior of lithium-ion pouch cells and optimizing the cooling performance are required to accomplish better performance, long life, and enhanced safety. In the present study, the cooling performance characteristics of 20 Ah lithium-ion pouch cell with cold plates along both surfaces are investigated by varying the inlet coolant mass flow rates and the inlet coolant temperatures. The inlet coolant mass flow rate is varied from 0.000833 kg/s to 0.003333 kg/s, and the inlet coolant temperature is varied from 5 °C to 35 °C. In addition, the effects of the cold plate geometry parameter on cooling performance of 20 Ah lithium-ion pouch cell are studied by varying the number of the channels from 4 to 10. The maximum temperature and difference between the maximum and the minimum temperatures are considered as important criteria for cooling performance evaluation of the 20 Ah lithium-ion pouch cell with cold plates along both surfaces. The cooling energy efficiency parameter ( β ) and the pressure drop for 20 Ah lithium-ion pouch cell with cold plates along both surfaces are also reported. The study shows that enhanced cooling energy efficiency is accompanied with low inlet coolant temperature, low inlet coolant mass flow rate, and a high number of the cooling channels. As a result, the temperature distribution, the pressure drop, and the cooling energy efficiency parameter ( β ) of the 20 Ah lithium-ion pouch cell with cold plates along both surfaces are provided, and could be applied for optimizing the cooling performances of the thermal management system for lithium-ion batteries in electric vehicles.
Multidisciplinary Digital Publishing Institute
Journals
2018 EN
Eric J. Romer · Anita Thyagarajan · Smita Krishnamurthy
+5 more
Platelet-activating factor-receptor (PAF-R) agonists are pleiotropic lipid factors that influence multiple biological processes, including the induction and resolution of inflammation as well as immunosuppression. PAF-R agonists have been shown to modulate tumorigenesis and/or tumor growth in various skin cancer models by suppressing either cutaneous inflammation and/or anti-tumoral adaptive immunity. We have previously shown that a chronic systemic PAF-R agonist administration of mice enhances the growth of subcutaneously implanted melanoma tumors. Conversely, chronic topical applications of a PAF-R agonist suppressed non-melanoma skin cancer (NMSC) in a topical chemical carcinogenesis model (dimethylbenz[a]anthracene/phorbol 12-myristate 13-acetate (DMBA/PMA)) in-part via anti-inflammatory effects. These results indicate that the context of PAF-R agonist exposure via either chronic cutaneous or systemic administration, result in seemingly disparate effects on tumor promotion. To further dissect the contextual role of PAF-R agonism on tumorigenesis, we chronically administered systemic PAF-R agonist, carbamoyl-PAF (CPAF) to mice under a cutaneous chemical carcinogenesis protocol, recently characterized to initiate both NMSC and melanocytic nevus formation that can progress to malignant melanoma. Our results showed that while systemic CPAF did not modulate melanocytic nevus formation, it enhanced the growth of NMSC tumors.
Multidisciplinary Digital Publishing Institute
Journals
2018 EN
Anita Thyagarajan · Sayali M. Kadam · Langni Liu
+4 more
Studies, including ours, have shown that pro-oxidative stressors, such as chemotherapeutic agents, generate oxidized lipids with agonistic platelet-activating factor (PAF) activity. Importantly, recent reports have implicated that these PAF-agonists are transported extracellularly via microvesicle particles (MVPs). While the role of PAF-receptor (PAF-R) has been implicated in mediating chemotherapy effects, its significance in chemotherapy-mediated MVP release in pancreatic cancer has not been studied. The current studies determined the functional significance of PAF-R in gemcitabine chemotherapy-mediated MVP release in human pancreatic cancer cells. Using PAF-R-expressing (PANC-1) and PAF-R-deficient (Hs766T) cells, we demonstrate that gemcitabine induces MVP release in a PAF-R-dependent manner. Blocking of PAF-R via PAF-R antagonist or inhibition of MVP generation via inhibitor of acid sphingomyelinase (aSMase) enzyme, significantly attenuated gemcitabine-mediated MVP release from PANC-1 cells, however, exerted no effects in Hs766T cells. Notably, MVPs from gemcitabine-treated PANC-1 cells, contained a measurable amount of PAF-agonists. Mechanistically, pretreatment with ERK1/2 or p38 inhibitors significantly abrogated gemcitabine-mediated MVP release, indicating the involvement of mitogen-activated protein kinase (MAPK) pathway in PAF-R-dependent gemcitabine-mediated MVP release. These findings demonstrate the significance of PAF-R in gemcitabine-mediated MVP release, as well as the rationale of evaluating PAF-R targeting agents with gemcitabine against pancreatic cancer.
Multidisciplinary Digital Publishing Institute
Journals
2018 EN
D. R. Sahu · Ravi P. Agarwal · Vipin Kumar Singh
In this paper, we design a new third order Newton-like method and establish its convergence theory for finding the approximate solutions of nonlinear operator equations in the setting of Banach spaces. First, we discuss the convergence analysis of our third order Newton-like method under the ω -continuity condition. Then we apply our approach to solve nonlinear fixed point problems and Fredholm integral equations, where the first derivative of an involved operator does not necessarily satisfy the Holder and Lipschitz continuity conditions. Several numerical examples are given, which compare the applicability of our convergence theory with the ones in the literature.
Multidisciplinary Digital Publishing Institute