Mechanism of Mg 2+ -accompanied product release in sugar nucleotidyltransferases

The nucleotidyl transfer reaction, catalyzed by sugar nucleotidyltransferases (SNTs), is assisted by two active site Mg 2+ ions. While studying this reaction using X-ray crystallography, we captured snapshots of the pyrophosphate (product) as it exits along a pocket. Surprisingly, one of the active site Mg 2+ ions remains coordinated to the exiting pyrophosphate. This hints at the participation of Mg 2+ in the process of product release, besides its role in catalyzing nucleotidyl transfer. These observations are further supported by enhanced sampling molecular dynamics simulations. Free energy computations suggest that the product release is likely to be rate limiting in SNTs, and the origin of the high free energy barrier for product release could be traced back to the “slow” conformational change of an Arg residue at the exit end of the pocket. These results establish a dual role for Mg 2+, and propose a general mechanism of product release during the nucleotidyl transfer by SNTs

Influence of Mo on the Fe:Mo:C nano-catalyst thermodynamics for single-walled carbon nanotube growth

We explore the role of Mo in Fe:Mo nanocatalyst thermodynamics for low-temperature chemical vapor deposition growth of single walled carbon nanotubes (SWCNTs). By using the size-pressure approximation and ab initio modeling, we prove that for both Fe-rich (~80% Fe or more) and Mo-rich (~50% Mo or more) Fe:Mo clusters, the presence of carbon in the cluster causes nucleation of Mo2C. This enhances the activity of the particle since it releases Fe, which is initially bound in a stable Fe:Mo phase, so that it can catalyze SWCNT growth. Furthermore, the presence of small concentrations of Mo reduce the lower size limit of low-temperature steady-state growth from ~0.58nm for pure Fe particles to ~0.52nm. Our ab initio-thermodynamic modeling explains experimental results and establishes a new direction to search for better catalysts.Comment: 7 pages, 3 figures. submitte

Theoretical study of the thermal behavior of free and alumina-supported Fe-C nanoparticles

The thermal behavior of free and alumina-supported iron-carbon nanoparticles is investigated via molecular dynamics simulations, in which the effect of the substrate is treated with a simple Morse potential fitted to ab initio data. We observe that the presence of the substrate raises the melting temperature of medium and large $Fe_{1-x}C_x$ nanoparticles ($x$ = 0-0.16, $N$ = 80-1000, non- magic numbers) by 40-60 K; it also plays an important role in defining the ground state of smaller Fe nanoparticles ($N$ = 50-80). The main focus of our study is the investigation of Fe-C phase diagrams as a function of the nanoparticle size. We find that as the cluster size decreases in the 1.1-1.6-nm-diameter range the eutectic point shifts significantly not only toward lower temperatures, as expected from the Gibbs-Thomson law, but also toward lower concentrations of C. The strong dependence of the maximum C solubility on the Fe-C cluster size may have important implications for the catalytic growth of carbon nanotubes by chemical vapor deposition.Comment: 13 pages, 11 figures, higher quality figures can be seen in article 9 at http://alpha.mems.duke.edu/wahyu

A critical assessment of technical advances in pharmaceutical removal from wastewater – A critical review

Use of pharmaceutical products has seen a tremendous increase in the recent decades. It has been observed that more than thirty million tons of pharmaceuticals are consumed worldwide. The used pharmaceutical products are not completely metabolized in human and animal body. Therefore, they are excreted to the environment and remain there as persistent organic chemicals. These compounds emerge as toxic contaminants in water and affect the human metabolism directly or indirectly. This literature review is an endeavour to understand the origin, applications and current advancement in the removal of pharmaceuticals from the environment. It discusses about the pharmaceuticals used in medical applications such diagnosis and disease treatment. In addition, it discusses about the recent approaches applied in pharmaceutical removal including microbial fuel cells, biofiltration, and bio nanotechnology approaches. Moreover, the challenges associated with pharmaceutical removal are presented considering biological and environmental factors. The review suggest the potential recommendations on pharmaceutical removal.The corresponding author Prof. Vinay Kumar is thankful to all the co-authors for their collaborative efforts in writing this paper. This work was supported by Department of Community Medicine, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, India.Peer reviewe

Genomic Testing in Localized Prostate Cancer Can Identify Subsets of African Americans With Aggressive Disease

BACKGROUND: Personalized genomic classifiers have transformed the management of prostate cancer (PCa) by identifying the most aggressive subsets of PCa. Nevertheless, the performance of genomic classifiers to risk classify African American men is thus far lacking in a prospective setting. METHODS: This is a prospective study of the Decipher genomic classifier for National Comprehensive Cancer Network low- and intermediate-risk PCa. Study-eligible non-African American men were matched to African American men. Diagnostic biopsy specimens were processed to estimate Decipher scores. Samples accrued in NCT02723734, a prospective study, were interrogated to determine the genomic risk of reclassification (GrR) between conventional clinical risk classifiers and the Decipher score. RESULTS: The final analysis included a clinically balanced cohort of 226 patients with complete genomic information (113 African American men and 113 non-African American men). A higher proportion of African American men with National Comprehensive Cancer Network-classified low-risk (18.2%) and favorable intermediate-risk (37.8%) PCa had a higher Decipher score than non-African American men. Self-identified African American men were twice more likely than non-African American men to experience GrR (relative risk [RR] = 2.23, 95% confidence interval [CI] = 1.02 to 4.90; P = .04). In an ancestry-determined race model, we consistently validated a higher risk of reclassification in African American men (RR = 5.26, 95% CI = 1.66 to 16.63; P = .004). Race-stratified analysis of GrR vs non-GrR tumors also revealed molecular differences in these tumor subtypes. CONCLUSIONS: Integration of genomic classifiers with clinically based risk classification can help identify the subset of African American men with localized PCa who harbor high genomic risk of early metastatic disease. It is vital to identify and appropriately risk stratify the subset of African American men with aggressive disease who may benefit from more targeted interventions

Profile of Multi Drug Resistant Tuberculosis patients: A Study at Drug Resistant Tuberculosis Centre in Kumaun Region, Uttarakhand

Background: Drug Resistant Tuberculosis (DR-TB) has frequently been encountered in India, and its presence has been known virtually from the time anti-TB drugs were introduced for the treatment of Tuberculosis. Multi Drug Resistant Tuberculosis (MDR-TB) is a man-made phenomenon and has become a formidable challenge to effective Tuberculosis control in India. Objectives: To study the Socio-demographic and Clinical profile of Multi Drug Resistant Tuberculosis (MDR-TB) patients presenting to Drug Resistant Tuberculosis (DR-TB) Centre at Govt. Medical College, Haldwani in the Kumaun region, Uttarakhand. Methodology:  This study is a Record based study, where in service data available at Drug Resistant Tuberculosis (DR-TB) Centre at Govt. Medical College, Haldwani in the Kumaun region, Uttarakhand, was accessed and analyzed. Inclusion criteria included all patients with diagnosis of Multi Drug Resistant Tuberculosis (MDR-TB) presenting to the centre from 1st April 2015 to 31st December 2015. Results: The present study showed that younger age group particularly males were more affected with MDR-TB. Under-nutrition was quite prevalent among the MDR-TB patients. 56.7% cases were addicted to alcohol and 54.3% cases were addicted to smoking. 85.8% patients took treatment for TB and 44.1% not completed their treatment. Relapse of previous anti-tuberculosis treatment was found to be the major contributor in MDR-TB suspect cases. Prevalence of XDR-TB was also found to be low. Conclusion: The findings of the study emphasize the importance of studying the socio-demographic factors and baseline clinical characteristics in different MDR-TB patient categories to timely modify and strengthen the national programs

An analysis of work-family conflict resolution in the IT industry for employee sustainability

Work-Family Conflict is the concept that has become very prevalent in these uncertain times of pandemic and in these new working styles and setups. The study aimed to understand the response of IT employees to work-family conflicts faced by them during the Covid-19 pandemic giving insights about employee sustainability. It sought to investigate the relationship between the work-family conflicts they experienced and the organisational structure of their workplaces. A descriptive study was conducted using convenience sampling and a total of 132 complete responses were used as the sample data to perform the analysis. IT employees face a considerable amount of work-family conflict. There is a significant difference between work-family conflict faced by IT employees in different working setups, so it becomes important to manage work and family in a situation of remote working during an unprecedented time of the pandemic. For the resolution of work-family conflict, IT employees deal with this conflict differently in different family setups. In the coming times of Hybrid working, it becomes all the more important to understand how employees are resolving this work-family conflict and what additional steps can be taken to further alleviate the situation leading to employee sustainability in the long run