An active immune surveillance and a range of barriers to infection allow the host to effectively eliminate microbial pathogens. However, pathogens may use diverse strategies to subdue such host ...defences. For instance, one such mechanism is the use of leucine-rich repeat (LRR) proteins by pathogens (microbial) to cause infection. In this study, we aimed at identifying novel virulence factor(s) in Leishmania donovani, based on the possibility of lateral gene transfers of bacterial virulence factor(s) to L. donovani.
Rigorous homology searching protocols including Hidden Markov Model (HMM) and BLASTp based searches were employed to detect remote but significant similarities between L. donovani proteins and bacterial virulence factors.
We found that some L. donovani proteins are similar to internalin-A (Inl-A) protein of Listeria monocytogenes, a surface LRR protein that helps mediate host cell invasion by interacting with E-cadherin on the cell membrane. However, to date, no such invasion mechanism has been reported in Leishmania donovani, the causative agent of visceral leishmaniasis. Moreover, a comparative LRR motif analysis of L. donovani Inl-A-like proteins against the Inl-A protein of L. monocytogenes revealed existence of characteristic consensus LRR regions, suggesting a reliable evolutionary relationship between them. Further, through rigorous three dimensional (3D) modeling of L. donovani Inl-A-like proteins and subsequent molecular docking studies we suggest the probability of human E-cadherin binding with the L. donovani Inl-A-like proteins.
We have identified three potential candidates (UniProt ID: E9B7L9, E9BMT7 and E9BUL5) of Inl-A-like LRR containing proteins in L. donovani with the help of systematic whole genome sequence analysis. Thus, herein we propose the existence of a novel class of Inl-A-like virulence factor proteins in L. donovani and other Leishmania species based on sequence similarity, phylogenetic analysis and molecular modelling studies in L. donovani.
We present spectrograph design details and initial radial velocity results from the PRL optical fiber-fed high-resolution cross-dispersed echelle spectrograph (PARAS), which has recently been ...commissioned at the Mount Abu 1.2 m telescope in India. Data obtained as part of the postcommissioning tests with PARAS show velocity precision better than 2 m s-1 over a period of several months on bright RV standard stars. For observations of σ Dra, we report 1.7 m s-1 precision for a period of 7 months, and for HD 9407, we report 2.1 m s-1 over a period of 2 months. PARAS is capable of single-shot spectral coverage of 3800-9500 Å at a resolution of ∼67,000. The RV results were obtained between 3800 and 6900 Å using simultaneous wavelength calibration with a thorium-argon (ThAr) hollow cathode lamp. The spectrograph is maintained under stable conditions of temperature with a precision of 0.01-0.02° C (rms) at 25.55° C and is enclosed in a vacuum vessel at pressure of 0.1 ± 0.03 mbar. The blaze peak efficiency of the spectrograph between 5000 and 6500 Å, including the detector, is ∼30%; it is ∼25% with the fiber transmission. The total efficiency, including spectrograph, fiber transmission, focal ratio degradation (FRD), and telescope (with 81% reflectivity) is ∼7% in the same wavelength region on a clear night with good seeing conditions. The stable point-spread function (PSF), environmental control, existence of a simultaneous calibration fiber, and availability of observing time make PARAS attractive for a variety of exoplanetary and stellar astrophysics projects. Future plans include testing of octagonal fibers for further scrambling of light and extensive calibration over the entire wavelength range up to 9500 Å using thorium-neon (ThNe) or uranium-neon (UNe) spectral lamps. Thus, we demonstrate how such highly stabilized instruments, even on small aperture telescopes, can contribute significantly to the ongoing radial velocity searches for low-mass planets around bright stars.
We present here the information on the design and performance of the recently commissioned 2.5-meter telescope at the PRL Mount Abu Observatory, located at Gurushikhar, Mount Abu, India. The ...telescope has been successfully installed at the site, and the Site Acceptance Test (SAT) was completed in October 2022. It is a highly advanced telescope in India, featuring the Ritchey-Chrétien optical configuration with primary mirror active optics, tip-tilt on sideport, and wave front correction sensors. Along with the telescope, its two first light instruments namely Faint Object Camera (FOC) and PARAS-2 were also integrated and attached with it in the June 2022. FOC is a camera that uses a 4096 X 4112 pixels detector SDSS type filters with enhanced transmission and known as u’, g’, r’, i’, z’. It has a limiting magnitude of 21 mag for 10 minutes exposure in the r’-band. The other first light instrument, PARAS-2, is a state-of-the-art high-resolution fiber-fed spectrograph operating in the 380-690 nm wave-band, aimed to unveil the super-Earth like worlds. The spectrograph works at a resolution of ∼107,000, making it the highest-resolution spectrograph in Asia to date, It is employed in an ultra-stable temperature and pressure environment, at 22.5 ± 0.001 ◦C and 0.005 ± 0.0005 mbar, respectively. Initial calibration tests of the spectrograph using a Uranium Argon Hollow Cathode Lamp (UAr HCL) have yielded intrinsic instrumental RV stability down to 30 cm s−1.
Introduction: Atopic dermatitis (AD) is a chronic, inflammatory skin disorder that significantly impairs life quality and mostly affects children. Although classical approaches of treatment have been ...effective in mitigating the symptoms of AD, novel remedial measures based on a better understanding of immunopathogenesis are needed to target the underlying etiology. Aims and Objectives: Probiotics improve the intestinal micro environment and restore the balance of immune responses, thereby, emerging as a novel therapeutic option in the management of AD. Taking into account the updated information available, this review aims to discuss the beneficial effects of probiotics on gut microbiota, their role in strengthening the epidermal barrier and immunological responses, and hence their clinical usage in AD. Results: Classically, AD has been understood as a complex interplay between genetic susceptibility, barrier dysfunction, immune dysregulation, and exogenous factors. Current research has demonstrated that AD is associated with changes in both skin and gut microflora. The “gut-skin” axis hypothesis and the interaction between them have been demonstrated in research. Patients with AD have demonstrated gut dysbiosis, which leads to immune dysregulation and can serve as a potential trigger for AD. Probiotics, by their ability to put right gut dysbiosis, have demonstrated modest efficacy in reducing disease activity in clinical studies. Conclusion: Although multiple randomized controlled trials and meta-analyses have demonstrated the utility of probiotics as adjuvant therapy in the management of AD, the need of the hour is to develop precise guidelines pertaining to their usage in AD.
Using a model of wealth distribution where traders are characterized by quenched random saving propensities and trade among themselves by bipartite transactions, we mimic the enhanced rates of ...trading of the rich by introducing the preferential selection rule using a pair of continuously tunable parameters. The bipartite trading defines a growing trade network of traders linked by their mutual trade relationships. With the preferential selection rule this network appears to be highly heterogeneous characterized by the scale-free nodal degree and the link weight distributions and presents signatures of nontrivial strength-degree correlations. With detailed numerical simulations and using finite-size scaling analysis we present evidence that the associated critical exponents are continuous functions of the tuning parameters. However the wealth distribution has been observed to follow the well-known Pareto law robustly for all positive values of the tuning parameters.
•Tautomerisation pathways in (Z)-4-(hydroxymethylene) isochroman -1,3-dione are identified in S0 and S1.•Several conformers are distinguished for both tautomers.•The variation of reaction force and ...force constants are studied and transition region is characterized.•Maximum Hardness Principle and Minimum Electrophilicity Principles are studied both in S0 and S1.
(Z)-4-(hydroxymethylene) isochroman-1,3-dione (HIC) and 3-hydroxy-1-oxoisochroman-4-carbaldehyde (HOC) exhibits a number of conformers. Out of these, we are primarily interested on the one showing tautomerisation between them through the migration of H atom. The tautomerisation reactions are theoretically characterized by DFT and ab-initio calculations in S0 and by CIS and TDDFT calculations in S1. All the computational techniques confirm the HIC to be the most stable conformer as well as tautomer in S0. In S1 state, TDDFT computations hint at HOC and CIS indicates HIC as the minimum with an energy difference of 1-2 kcal/mole between the tautomers. All the conformers/configurations and the transition state structures are identified and respective potential energy curves connecting these structures are drawn in S0. IRC calculations in S0 and S1 show the evolution from HIC to HOC form and vice versa through the transition state. The energy difference between the tautomers is less in S1 indicating larger probability of intramolecular proton transfer in S1 than in S0. The vibrational signatures are identified and all the modes are assigned in S0. Electron distribution in HOMO and LUMO are calculated and interpreted for both the forms. The energy and hardness profiles are opposite to each other, verifying the principle of maximum hardness for all the structures in S0. The minimum electrophilicity principle is followed by the transition state structure only in S0, while both the principles are obeyed in S1. The electron density difference plots indicate the transfer of charges on excitation.
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•Monohydrates of THIQ are analyzed through PES and NBO studies.•A new structure TEW1a is found to be the most stable conformer in S0 in M062-X, ωB97X-D, MP2 and CCSD methods.•Potential energy ...surfaces yield eleven monohydrates in S0.•The behavior of two OH bonds of water are thoroughly analyzed.•“Free” OH bond show important characteristics.
The global minima in the potential energy surface of 1, 2, 3, 4-tetrahydroisoquinoline (THIQ):(H2O) prefer the twisted equatorial orientation of the NH group. It is characterized by a strong OH⋅⋅⋅N and a weak O-H⋅⋅⋅π hydrogen bonds. The computations at the ab initio level and DFT methods with M06–2X and ωB97X-D functionals generated consistent results. The monohydrate with the axial orientation of NH having a single OH⋅⋅⋅N bond in the twisted configuration of THIQ is higher by 240 ± 40 cm−1. The N⋅⋅⋅H bond length is smaller in the latter. All the clusters are located in the potential energy surface of THIQ :(H2O) drawn with the variation of the dihedral angles of the saturated ring of THIQ. Various kinds of hydrogen bonds are observed. Binding energy of each structure is computed incorporating BSSE corrections. Interestingly, the largest of them correspond to a conformer of THIQ, where it was a transition state in the bare molecule. The vibrational analysis of the clusters indicates the reassignment of a number of bands in the observed IR spectra. The red-shifts observed in the different stretching modes of water in the two lowest energy clusters are suitably explained. This is further verified from NBO computations. The changes in s-character, NBO energies and OH bond lengths with the variation of hydrogen bond distances clearly signify the dominant nature of hyperconjugation mechanism. The natures of each OH bonds of water are investigated thoroughly. The bond which is not taking part in hydrogen bonding shows some apparently unexpected behaviors. HOMO and LUMO plots and their energy differences are employed to qualitatively explain the experimental results observed earlier. Changes in Molecular Electrostatic Potentials (MEP) on cluster formation are explained and confirm our computations. Maximum hardness principle (MHP) is followed by the most stable monohydrate only. Hardness values display a certain arrangement depending on the type of hydrogen bonding sites. We suggest further experiments to confirm our key observations.
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•Tautomerisation pathways in (Z)−4-(hydroxypropyl) isochroman-1, 3‑dione are identified.•Several conformers are identified for both tautomers.•The role of substituents in the tautomerisation process ...in AICs is explored.•Maximum hardness principle and minimum electrophilicity principles are studied extensively.•Crystal structure data and FT-IR spectra corroborate our computational results.
This article thoroughly probes the interconnectivity between all the conformations/configurations and the tautomerisation pathway in (Z)-4-(hydroxypropyl) isochroman-1, 3‑dione (PIC) both in S0 and S1 states. The crystal structure data corroborates our computational results done with DFT and MP2 methods utilizing various basis sets. The tautomers are separated by 2.5 ± 0.3 kcal/mole in S0. The comparison of potential energy curves of close analogues shows that the inertia of the substituted functional groups (here C2H5) plays a significant role in the proton transfer process. Intrinsic Reaction Coordinate (IRC) and frequency computations locate the transitions states (TS) in S0.The transition region in the tautomerisation pathway is clearly marked with the evaluation of reaction force and force constants. The excited state computations with CIS and TDDFT methods show some inconsistency regarding the relative energies of the tautomers. Maximum hardness principle (MHP) and minimum electrophilicity principle (MEP) are applied in this case. The frontier molecular orbitals in both the tautomers confirms the S0→S1 transition as π-π* in nature. The plot of the difference in electron densities between S0 and S1 states in both the tautomers hint at the photophysical processes occurring on excitation. The vibrational signatures are detected and characteristic spectral lines and their relative intensities are discussed. The strong C = O stretching vibration appearing at 1740 cm−1 in the observed FT-IR spectra is computed to be at 1757 cm−1 confirming our assertion of PIC as a minimum energy tautomer.
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•Tautomerisation pathways in (Z)-4-(hydroxyethyl) isochroman-1, 3-dione are identified.•Several conformers and transition states are identified for both tautomers.•The variation of ...reaction force and force constants are studied and transition region is characterized.•Maximum Hardness Principle and Minimum Electrophilicity Principles are studied extensively.
The saturated and unsaturated rings in the tautomers of (Z)-4-(hydroxyethyl) isochroman-1, 3-dione (EIC) and 4-acetyl-3-hydroxyisochroman-1-one (AOC) are found to be nonplanar. All the DFT and ab-initio computational methods with various basis sets identify EIC as the global minimum in S0. IRC and frequency computations locate the transition states (TS). AOC and TS are located about 3.5 ± 0.5 kcal/mole and 4.5 ± 0.8 kcal/mole higher in energy than EIC. The transition region is clearly marked with the evaluation of reaction force and force constants. CIS and TDDFT computations show inconsistent results. MHP is obeyed by the EIC tautomer, while MEP is obeyed by the TS structure. Frontier molecular orbitals confirms the S0 → S1 transition as π-π* in nature. The vibrational signatures in the tautomers corresponding to CO stretching modes and ring modes are identified. The earlier observed 1740 cm-1C = O stretching mode is computed to appear at 1763 cm−1 in EIC.
Background:
Dhat syndrome is a culture-bound syndrome of the Indian subcontinent. Traditional and cultural teachings through generations, and myths and misconceptions about sex are its principal ...contributing factors. Although prevalent, there is scarcity in studies on Dhat syndrome, particularly from Bengal.
Aims and objectives:
1. To study the phenomenology of Dhat syndrome in men attending the out patients department (OPD).
2. To study the comorbid sexual and psychiatric disorders associated with Dhat syndrome.
Methodology:
This was a cross-sectional observational study conducted in the psychiatric OPD in a tertiary care medical college hospital in West Bengal. The duration of the study was 18 months. 122 patients were included in this study that fulfilled the inclusion and exclusion criteria. The diagnosis of Dhat syndrome was made as per International Classification of Diseases, Tenth Revision, diagnostic criteria for research (DCR) criteria. A semi-structured pro forma was used to obtain sociodemographic variables along with numerous physical and sexual symptoms. Mini International Neuropsychiatric Interview was applied for psychiatric comorbidities. Data were analyzed using Statistical Package for Social Studies 17 by SPSS Inc., Chicago.
Results:
122 patients met the inclusion and exclusion criteria. Majority of patients were among age group of 20 to 30 years (60.7%). 56.6% were from the Muslim community and 43.4% were from the Hindu community. 54.1% population was unmarried and 39.3% were newly married. Routes of passage were night falls in 62.3% patients, and 52.5% patients pointed toward passage through urine. Many patients reported passage of semen more than one route. All patients (100%) complained about generalized weakness and thinning of semen. 66.4% had generalized body ache, 55.7% complain about headache, 60.7% decreased body glow, 50% had loss of appetite, 98.4% had decreased self-confidence, sleep disturbance was reported in 34.3% patients, 58.2% reported that their penis was becoming smaller, and 49.2% patients reported decreased sexual capability. The most common comorbid condition was sexual dysfunction (39.3%) followed by depressive disorders (27.9%). Premature ejaculation was found in 54.17% patients and erectile dysfunction in 33.33%.
Conclusion:
Dhat syndrome is a common culture-bound syndrome in Bengal. It is widespread in the Muslim community also. The importance of exploration of sexual comorbidities in Dhat syndrome is very much needed.
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