scholarly journals Protonation of Glutamate 208 Induces the Release of Agmatine in an Outward-facing Conformation of an Arginine/Agmatine Antiporter

2011 ◽  
Vol 286 (22) ◽  
pp. 19693-19701 ◽  
Author(s):  
Elia Zomot ◽  
Ivet Bahar
Keyword(s):  
Binding Pocket ◽  
Substrate Binding Pocket ◽  
Time Resolved ◽  
Extracellular Region ◽  
Acidic Conditions ◽  
Using Data ◽  
Dynamics Simulations ◽  
The Impact ◽  
First Time

Virulent enteric pathogens have developed several systems that maintain intracellular pH to survive extreme acidic conditions. One such mechanism is the exchange of arginine (Arg+) from the extracellular region with its intracellular decarboxylated form, agmatine (Agm2+). The net result of this process is the export of a virtual proton from the cytoplasm per antiport cycle. Crystal structures of the arginine/agmatine antiporter from Escherichia coli, AdiC, have been recently resolved in both the apo and Arg+-bound outward-facing conformations, which permit us to assess for the first time the time-resolved mechanisms of interactions that enable the specific antiporter functionality of AdiC. Using data from ∼1 μs of molecular dynamics simulations, we show that the protonation of Glu-208 selectively causes the dissociation and release of Agm2+, but not Arg+, to the cell exterior. The impact of Glu-208 protonation is transmitted to the substrate binding pocket via the reorientation of Ile-205 carbonyl group at the irregular portion of transmembrane (TM) helix 6. This effect, which takes place only in the subunits where Agm2+ is released, invites attention to the functional role of the unwound portion of TM helices (TM6 Trp-202–Glu-208 in AdiC) in facilitating substrate translocation, reminiscent of the behavior observed in structurally similar Na+-coupled transporters.

Relationship between big five personality model and abusive supervision

2019 ◽  
Vol 12 (2) ◽  
Author(s):  
Bibi Tahira ◽  
Naveed Saif ◽  
Muhammad Haroon ◽  
Sadaqat Ali
Keyword(s):  
Big Five ◽  
Abusive Supervision ◽  
State Universities ◽  
Big Five Personality ◽  
Big Five Model ◽  
The Impact ◽  
First Time ◽  
Supervisor Behavior ◽  
Moderating Role

The current study tries to understand the diverse nature of relationship between personality Big Five Model (PBFM) and student's perception of abusive supervision in higher education institutions of Khyber Pakhtoonkhwa Pakistan. Data was collected in dyads i.e. (supervisors were asked to rate their personality attributes while student were asked to rate the supervisor behavior) through adopted construct. For this purpose, data was collected from three government state universities and one Private Sector University. The focus was on MS/M.Phill and PhD student and their supervisors of the mentioned universities. After measuring normality and validity regression analysis was conducted to assess the impact of supervisor personality characteristics that leads to abusive supervision. Findings indicate interestingly that except agreeableness other four attributes of (PBFM) are play their role for abusive supervision. The results are novel in the nature as for the first time Neuroticism, openness to experience, extraversion and conscientiousness are held responsible for the abusive supervision. The study did not explore the demographic characteristics, and moderating role of organizational culture, justice and interpersonal deviances to understand the strength of relationship in more detail way. Keywords: Personality big five model, abusive supervision, HEIs

scholarly journals Phenotypic Susceptibility to Bevirimat in Isolates from HIV-1-Infected Patients without Prior Exposure to Bevirimat

2010 ◽  
Vol 54 (6) ◽  
pp. 2345-2353 ◽  
Author(s):  
Nicolas A. Margot ◽  
Craig S. Gibbs ◽  
Michael D. Miller
Keyword(s):  
Recombinant Viruses ◽  
Gag Polyprotein ◽  
New Class ◽  
Major Mutation ◽  
Hiv Drugs ◽  
The Impact ◽  
First Time ◽  
Hiv 1

ABSTRACT Bevirimat (BVM) is the first of a new class of anti-HIV drugs with a novel mode of action known as maturation inhibitors. BVM inhibits the last cleavage of the Gag polyprotein by HIV-1 protease, leading to the accumulation of the p25 capsid-small peptide 1 (SP1) intermediate and resulting in noninfectious HIV-1 virions. Early clinical studies of BVM showed that over 50% of the patients treated with BVM did not respond to treatment. We investigated the impact of prior antiretroviral (ARV) treatment and/or natural genetic diversity on BVM susceptibility by conducting in vitro phenotypic analyses of viruses made from patient samples. We generated 31 recombinant viruses containing the entire gag and protease genes from 31 plasma samples from HIV-1-infected patients with (n = 21) or without (n = 10) prior ARV experience. We found that 58% of the patient isolates tested had a >10-fold reduced susceptibility to BVM, regardless of the patient's ARV experience or the level of isolate resistance to protease inhibitors. Analysis of mutants with site-directed mutations confirmed the role of the V370A SP1 polymorphism (SP1-V7A) in resistance to BVM. Furthermore, we demonstrated for the first time that a capsid polymorphism, V362I (CA protein-V230I), is also a major mutation conferring resistance to BVM. In contrast, none of the previously defined resistance-conferring mutations in Gag selected in vitro (H358Y, L363M, L363F, A364V, A366V, or A366T) were found to occur among the viruses that we analyzed. Our results should be helpful in the design of diagnostics for prediction of the potential benefit of BVM treatment in HIV-1-infected patients.

scholarly journals Entrepreneurial intention of engineering students: the role of motivations and barriers

2021 ◽  
Vol 5 (2) ◽  
pp. first
Author(s):  
Bich Huy Hai Bui ◽  
Minh Tien Pham
Keyword(s):  
Engineering Students ◽  
Positive Impact ◽  
Entrepreneurial Intention ◽  
Statistical Regression ◽  
Internal Factors ◽  
University Of Technology ◽  
Entrepreneurial Motivations ◽  
Using Data ◽  
The Impact

The purpose of this study is to explore perceptions of entrepreneurial motivations and barriers and to assess their influence on the entrepreneurial intention of engineering students. Using data of 350 respondents who are students at HCMC University of Technology, VNU-HCM, the study identifies the key motives and barriers towards entrepreneurship. The data are then subjected to statistical regression in order to identify causal relationships between the motivations, barriers, and entrepreneurial intention. The results indicate that creativity, independence, and economic motivation have a positive impact on entrepreneurial intention and that the most important motivator for the entrepreneurial intention of engineering students is creativity. On the contrary, lack of knowledge is the only barrier (an internal barrier) that impedes the students' intention of entrepreneurship. These results imply that the students' entrepreneurial intention is more affected by internal factors (for both motivations and barriers) than external factors. In terms of the relative power of the effects of motives and barriers on students' entrepreneurial intention, the results suggest that the impact of motivations is generally more powerful than that of barriers. The findings have important implications for educators and policymakers.

Reflections from the field (mountain, cityscape and park): walking for management development and links to being-in-the world, belonging and “Ba”

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Arthur F. Turner ◽  
Gareth Edwards ◽  
Catherine Latham ◽  
Harriet Shortt
Keyword(s):  
Leadership Development ◽  
Management Development ◽  
Learning And Development ◽  
Content Type ◽  
Personal Story ◽  
The World ◽  
Effective Use ◽  
The Impact ◽  
First Time

PurposeThe purpose of this paper, based on reflections from practice, is to shed light on the realities of using walking as a tool for learning and development. This is done through an initial analysis of longitudinal reflective data spanning seven years and connecting these reflections to the concepts: being-in-the-world, belonging and Ba.Design/methodology/approachThis research takes a practice based phenomenological and reflective approach. The value of this approach is to seek a new understanding, through three distinct conceptual frames, of the effective use of walking within management development.FindingsThe findings connect three conceptual approaches of being-in-the-world, belonging and “Ba” to the practicalities of delivery, thus encouraging practitioners and designers to deeply reflect on the role of walking in management development.Research limitations/implicationsA limitation is that this is largely a personal story exploring the impact of an intuitively developed set of interventions. Despite this, the paper represents a unique and deep interpretation of walking as a mechanism for management development.Practical implicationsThe paper concludes with three recommendations to practitioners wanting to use walking in management development programmes. These are: facilitators need to be familiar with their surroundings; they should look for spaces and places where participants can connect and build relationships; and organisers and sponsors need to recognise how walking not only consolidates knowledge but can help create knowledge too.Originality/valueThis is a unique, seven-year longitudinal study that broadens the theoretical focus of walking as a mechanism for management and leadership development that combines the theoretical lenses of being-in-the-world, belonging and “Ba”, the authors believe, for the first time in research on management development.

scholarly journals Specialization and Performance: Evidence from NCAA 4 × 400 m Relay Times

Economies ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 96
Author(s):  
Candon Johnson ◽  
Robert Schultz ◽  
Joshua C. Hall
Keyword(s):  
Performance Measure ◽  
Division I ◽  
Division Iii ◽  
Overall Performance ◽  
The Difference ◽  
And Performance ◽  
Using Data ◽  
The Impact ◽  
Better Than

This paper investigates the impact of having open 400 meter (400 m) runners on NCAA relay teams. Using data from 2012–2016 containing the top 100 4 × 400 m in each NCAA Division relay times for each year, it is found that more 400 m specialists lead to an increase in the overall performance of the team, measured by a decrease in relay times. The effect is examined across Division I–III NCAA track teams. The results are consistent across each division. We view this as a test of the role of specialization on performance. Using runners who specialize in 400 m races should increase overall team performance as long as specialization does not lead to an inefficient allocation of team human capital. An additional performance measure is used examining the difference between projected and actual relay times. Divisions I and II are found to perform better than projected with an increase in 400 m runners, but there is no effect found in Division III.

The Impact of AIS Usage on AIS Effectiveness Among Jordanian SMEs: A Multi-group Analysis of the Role of Firm Size

2020 ◽  
pp. 097215092096507
Author(s):  
Abdalwali Lutfi ◽  
Manaf Al-Okaily ◽  
Adi Alsyouf ◽  
Abdallah Alsaad ◽  
Abdallah Taamneh
Keyword(s):  
Firm Size ◽  
Group Analysis ◽  
Research Model ◽  
Accounting Information System ◽  
Resource Based View ◽  
It Usage ◽  
Using Data ◽  
The Impact ◽  
Self Administered Questionnaire

In this research, we look at the antecedents of accounting information system (AIS) usage and their impact on the effectiveness of AIS. Therefore, drawing upon the resource-based view (RBV) and the technology–organization–environment (TOE) framework, we propose an integrated model to investigate the precursors and impacts of AIS utilization among Jordanian small and medium-sized enterprises (SMEs). The model so proposed incorporates the usage of AIS and its performance aspects into one framework. The current research utilized a self-administered questionnaire survey to collect data. Using data drawn from 186 respondents, the research model was verified empirically in the context of Jordanian SMEs. The findings revealed that compatibility, competitive pressure, organizational readiness, the commitment of the owners/managers and government supports have exerted a significant influence on the usage of AIS. In addition, the results demonstrated that AIS usage significantly influenced the effectiveness of AIS. In addition, firm size moderated the effect of AIS usage on AIS effectiveness. The findings of the current study afford insights as to how firms might garner improved usage of an AIS to gain better firm performance and provide contributions to the small but developing stream of research examining both antecedents and impacts of IS/IT usage.

scholarly journals Role of Ureolytic Activity in Bacillus cereus Nitrogen Metabolism and Acid Survival

2008 ◽  
Vol 74 (8) ◽  
pp. 2370-2378 ◽  
Author(s):  
Maarten Mols ◽  
Tjakko Abee
Keyword(s):  
Bacillus Cereus ◽  
Nitrogen Source ◽  
Nitrogen Metabolism ◽  
Acid Stress ◽  
Main Role ◽  
Strain Atcc ◽  
Acid Shock ◽  
Acidic Conditions ◽  
The Impact

ABSTRACT The presence and activities of urease genes were investigated in 49 clinical, food, and environmental Bacillus cereus isolates. Ten strains were shown to have urease genes, with eight of these strains showing growth on urea as the sole nitrogen source. Two of the urease-positive strains, including the sequenced strain ATCC 10987, could not use urea for growth, despite their capacities to produce active urease. These observations can be explained by the inability of the two strains to use ammonium as a nitrogen source. The impact of urea hydrolysis on acid stress resistance was subsequently assessed among the ureolytic B. cereus strains. However, none of the strains displayed increased fitness under acidic conditions or showed enhanced acid shock survival in the presence of urea. Expression analysis of urease genes in B. cereus ATCC 10987 revealed a low level of expression of these genes and a lack of pH-, nitrogen-, urea-, oxygen-, and growth phase-dependent modulation of mRNA transcription. This is in agreement with the low urease activity observed in strain ATCC 10987 and the other nine strains tested. Although a role for B. cereus ureolytic activity in acid survival cannot be excluded, its main role appears to be in nitrogen metabolism, where ammonium may be provided to the cells in nitrogen-limited, urea-containing environments.

scholarly journals Structural Basis of Enantioselective Inhibition of Cyclooxygenase-1 by S-α-Substituted Indomethacin Ethanolamides

2007 ◽  
Vol 282 (38) ◽  
pp. 28096-28105 ◽  
Author(s):  
Christine A. Harman ◽  
Melissa V. Turman ◽  
Kevin R. Kozak ◽  
Lawrence J. Marnett ◽  
William L. Smith ◽  
...  
Keyword(s):  
Binding Pocket ◽  
Drug Binding ◽  
Structural Basis ◽  
Cyclooxygenase 1 ◽  
Cox 2 ◽  
The Impact ◽  
First Time ◽  
Side Pocket ◽  
Cox 1 ◽  
Equal Efficacy

The modification of the nonselective nonsteroidal anti-inflammatory drug, indomethacin, by amidation presents a promising strategy for designing novel cyclooxygenase (COX)-2-selective inhibitors. A series of α-substituted indomethacin ethanolamides, which exist as R/S-enantiomeric pairs, provides a means to study the impact of stereochemistry on COX inhibition. Comparative studies revealed that the R- and S-enantiomers of the α-substituted analogs inhibit COX-2 with almost equal efficacy, whereas COX-1 is selectively inhibited by the S-enantiomers. Mutagenesis studies have not been able to identify residues that manifest the enantioselectivity in COX-1. In an effort to understand the structural impact of chirality on COX-1 selectivity, the crystal structures of ovine COX-1 in complexes with an enantiomeric pair of these indomethacin ethanolamides were determined at resolutions between 2.75 and 2.85Å. These structures reveal unique, enantiomer-selective interactions within the COX-1 side pocket region that stabilize drug binding and account for the chiral selectivity observed with the (S)-α-substituted indomethacin ethanolamides. Kinetic analysis of binding demonstrates that both inhibitors bind quickly utilizing a two-step mechanism. However, the second binding step is readily reversible for the R-enantiomer, whereas for the S-enantiomer, it is not. These studies establish for the first time the structural and kinetic basis of high affinity binding of a neutral inhibitor to COX-1 and demonstrate that the side pocket of COX-1, previously thought to be sterically inaccessible, can serve as a binding pocket for inhibitor association.

scholarly journals Chronic opioid pretreatment potentiates the sensitization of fear learning by trauma

2019 ◽  
Vol 45 (3) ◽  
pp. 482-490 ◽  
Author(s):  
Zachary T. Pennington ◽  
Jeremy M. Trott ◽  
Abha K. Rajbhandari ◽  
Kevin Li ◽  
Wendy M. Walwyn ◽  
...  
Keyword(s):  
Basolateral Amygdala ◽  
Traumatic Event ◽  
Fear Learning ◽  
Opioid Use ◽  
Physical Injuries ◽  
Opioid Administration ◽  
The Impact ◽  
First Time ◽  
Considerable Period

AbstractDespite the large comorbidity between PTSD and opioid use disorders, as well as the common treatment of physical injuries resulting from trauma with opioids, the ability of opioid treatments to subsequently modify PTSD-related behavior has not been well studied. Using the stress-enhanced fear learning (SEFL) model for PTSD, we characterized the impact of chronic opioid regimens on the sensitization of fear learning seen following traumatic stress in mice. We demonstrate for the first time that chronic opioid pretreatment is able to robustly augment associative fear learning. Highlighting aversive learning as the cognitive process mediating this behavioral outcome, these changes were observed after a considerable period of drug cessation, generalized to learning about multiple aversive stimuli, were not due to changes in stimulus sensitivity or basal anxiety, and correlated with a marker of synaptic plasticity within the basolateral amygdala. Additionally, these changes were not observed when opioids were given after the traumatic event. Moreover, we found that neither reducing the frequency of opioid administration nor bidirectional manipulation of acute withdrawal impacted the subsequent enhancement in fear learning seen. Given the fundamental role of associative fear learning in the generation and progression of PTSD, these findings are of direct translational relevance to the comorbidity between opioid dependence and PTSD, and they are also pertinent to the use of opioids for treating pain resulting from traumas involving physical injuries.

The Role of Sex and Age on Pre-drinking: An Exploratory International Comparison of 27 Countries

2019 ◽  
Vol 54 (4) ◽  
pp. 378-385 ◽  
Author(s):  
Jason Ferris ◽  
Cheneal Puljević ◽  
Florian Labhart ◽  
Adam Winstock ◽  
Emmanuel Kuntsche
Keyword(s):  
Multilevel Models ◽  
The United States ◽  
Drinking Behaviour ◽  
Single Model ◽  
Policy Makers ◽  
Worldwide Phenomenon ◽  
Using Data ◽  
The Impact ◽  
Multivariate Multilevel Models

Abstract Aims This exploratory study aims to model the impact of sex and age on the percentage of pre-drinking in 27 countries, presenting a single model of pre-drinking behaviour for all countries and then comparing the role of sex and age on pre-drinking behaviour between countries. Methods Using data from the Global Drug Survey, the percentages of pre-drinkers were estimated for 27 countries from 64,485 respondents. Bivariate and multivariate multilevel models were used to investigate and compare the percentage of pre-drinking by sex (male and female) and age (16–35 years) between countries. Results The estimated percentage of pre-drinkers per country ranged from 17.8% (Greece) to 85.6% (Ireland). The influence of sex and age on pre-drinking showed large variation between the 27 countries. With the exception of Canada and Denmark, higher percentages of males engaged in pre-drinking compared to females, at all ages. While we noted a decline in pre-drinking probability among respondents in all countries after 21 years of age, after the age of 30 this probability remained constant in some countries, or even increased in Brazil, Canada, England, Ireland, New Zealand and the United States. Conclusions Pre-drinking is a worldwide phenomenon, but varies substantially by sex and age between countries. These variations suggest that policy-makers would benefit from increased understanding of the particularities of pre-drinking in their own country to efficiently target harmful pre-drinking behaviours.

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