Helices on Interdomain Interface Couple Catalysis in the ATPPase Domain with Allostery in Plasmodium falciparum GMP Synthetase.

GMP synthetase catalyses the conversion of XMP to GMP through a series of reactions that include hydrolysis of Gln to generate ammonia in the glutamine amidotransferase (GATase) domain, activation of XMP to adenyl-XMP intermediate in the ATP pyrophosphatase (ATPPase) domain and reaction of ammonia with the intermediate to generate GMP. The functioning of GMP synthetases entails bidirectional domain crosstalk, which leads to allosteric activation of the GATase domain, synchronization of catalytic events and tunnelling of ammonia. Herein, we have taken recourse to the analysis of structures of GMP synthetases, site-directed mutagenesis and steady-state and transient kinetics on the Plasmodium falciparum enzyme to decipher the molecular basis of catalysis in the ATPPase domain and domain crosstalk. Our results suggest an arrangement at the interdomain interface, of helices with residues that play roles in ATPPase catalysis as well as domain crosstalk enabling the coupling of ATPPase catalysis with GATase activation. Overall, the study enhances our understanding of GMP synthetases, which are drug targets in many infectious pathogens.

First Principle Study of Temperature-Dependent Magnetoresistance and Spin Filtration Effect in WS2 Nanoribbon.

An applicable use of density functional theory (DFT) along with nonequilibrium Green's function (NEGF) is done for exploring the temperature-dependent spin electron transport nature in a ferromagnetic tungsten disulfide (WS2) nanoribbon. To demonstrate the effect of temperature on spin filtration and spin Seebeck effect, we evaluated vital parameters such as spin-polarized current and spin filtration efficiency. Spin filtration efficiency of around ∼95% is obtained in the high-temperature difference range. The high temperature (TL) of the left electrode in comparison to the high temperature (TR) of the right electrode results in higher and lower spin filtration efficiency in parallel magnetization (PM) and antiparallel magnetization (APM), respectively. Transmission spectrum plots at equilibrium are also calculated in PM and APM to justify the temperature-dependent spin transport behavior in the WS2 nanoribbon. Giant thermal magnetoresistance around 1.934 × 103% is achieved. The temperature-dependent negative differential resistance behavior of the current plot has been observed. Huge value of thermal magnetoresistance (MR) and excellent spin filtration obtained for WS2 nanoribbon suggests the potential application of this material in spin caloritronic devices.

Investigation of the structural, electronic, and optical properties of Mn-doped CsPbCl3: theory and experiment.

Wide energy gap inorganic halide perovskites have become emerging candidates for potential applications in modern optoelectronics devices. However, to date, these semiconducting compounds have not been explored theoretically to a significant extent. Herein, we performed ab initio computations to explain the structural, electronic and optical behaviour of inorganic CsPbCl3 and Mn-doped CsPbCl3 nanocrystals (NCs). We also synthesized these NCs and further validated our experimental results with density functional theory (DFT) calculations. The results provide insight into the effect of Mn doping on the important properties of CsPbCl3 NCs such as their lattice parameter, electronic band structure, density of states, dielectric constant, absorption coefficient and refractive index. After geometry optimization using the Limited-memory Broyden-Fletcher-Goldfarb-Shanno (LBFGS) algorithm, a reduction in the lattice parameter from 5.605 Å to 5.574 Å was observed after doping Mn in the CsPbCl3 NCs, which is in good agreement with the calculated results from the X-ray diffraction (XRD) pattern (5.610 Å to 5.580 Å) and high-resolution transmission electron microscopy (HRTEM) images (5.603 Å to 5.575 Å). The incorporation of Mn in CsPbCl3 was observed in the electronic band structure in the form of additional states present in the energy gap and an increment in the band gap of the CsPbCl3 NCs. This result is consistent with the photoluminescence (PL) plot, which showed dual color emission in the case of the Mn-doped CsPbCl3, which is attributed to the Mn2+ d-band to d-band transition. The partial density of states (PDOS) of the Mn-doped CsPbCl3 NCs clearly indicates the contribution of the Mn 3d orbitals to the upper valence band and conduction band together with the contribution of the Pb 6p and Cl 3p orbitals. Moreover, a blue-shift phenomenon was observed from the dielectric constant and absorption coefficient spectra, which is due to the incorporation of Mn in CsPbCl3. Also, a significant peak was observed in the absorption coefficient and dielectric constant spectra around 2.08 eV, which is in good agreement with the PL plot. This DFT study with experimental observation provides a way to investigate this type of compound and to tailor its interesting characteristics through doping.

Military Sexual Trauma and Obesity Among Women Veterans.

BACKGROUND/OBJECTIVE: Posttraumatic stress disorder (PTSD), the experience of military sexual trauma (MST) that may contribute to PTSD, and obesity are three issues that complicate care for our population of new veterans. Our aim was to analyze the association of MST and diagnosed PTSD with obesity among female veterans. MATERIALS AND METHODS: Women 20-103 years old using the Veterans Health Administration (VA) in fiscal year 2014 (October 2013-September 2014) with diagnosis and body-mass data were identified in administrative databases (213,985 of 404,183 women). MST was defined by use of an MST clinic or positive MST screen, PTSD by International Classification of Diseases, Ninth Revision (ICD-9) diagnosis code (309.81), and weight categories from body-mass index. RESULTS: The unadjusted chi-square of MST by obesity showed a modest association: 52% MST-affected versus 46% non-MST women were obese. MST status was associated with PTSD (50% MST vs. 15% non-MST women). A multivariable model of obesity adjusting for clinical and demographic covariates estimated a 9% increased risk of obesity from MST (adjusted risk ratio [RR] = 1.09). Younger age, African American race, and chronic disease such as hypertension and dyslipidemia correlated with obesity. Adding PTSD to the model did not affect the association with MST: RR (MST) = 1.09, RR (PTSD) = 1.00 (not significant). CONCLUSIONS: This study showed association of MST with obesity in female veterans, independent of PTSD. Weight-gain in patients with trauma may add psychological or medical risk to the burden of disease shouldered by female veterans with MST. Primary care clinicians may need to consider integrating mental health into care of patients with suspected history of trauma especially sexual trauma.

Preventative care for patients with inflammatory bowel disease in the Veterans Health Administration.

Patients with inflammatory bowel disease (IBD) have underlying immune dysregulation. Immunosuppressive medications put them at risk of infection. This study assessed rates of recommended vaccinations and preventative screening in patients with IBD.Nationwide data on patients diagnosed with IBD in the Veterans Health Administration (VHA) October 2004 to September 2014 were extracted. Variation in vaccination, screenings, and risk of death by demographic factors (age group, gender) were estimated in bivariate and multivariable analyses.During the 10-year study period, 62,002 patients were treated for IBD. Nonmelanoma skin cancer was found in 2.6%, and these patients more commonly accessed dermatology clinic (22.5% vs 15.2%; chi-square = 66.6; df = 1; P < 0.0001). In total, 15% received DEXA scans, especially women (34.7% vs 13.2% men; chi-square = 1415.5; df = 1; P < 0.0001). Eye manifestations were noted in 38.3% yet only 31% were referred to ophthalmology. Abnormal Pap smears were found for 15% of women <65 (compared to 5% among normal patient populations); 34% had no record of Pap smear in VHA data. Vaccination rates were modest: pneumococcal 39%; TDAP 23%; hepatitis B 3%; varicella and PPD <0.5%. In an adjusted logistic regression model, 5-year mortality was lower among those using primary care prior to IBD diagnosis (odds ratio [OR] = 0.61; 95% CI 0.55-0.68).Despite the current IBD guidelines, vaccination and preventative screening rates were unacceptably low among patients diagnosed with IBD. Interventions such as education and increased awareness may be needed to improve these rates.