Recent Advancement of the Current Aspects of g-C3 N4 for its Photocatalytic Applications in Sustainable Energy System.

Being one of the foremost enticing and intriguing innovations, heterogeneous photocatalysis has also been used to effectively gather, transform, and conserve sustainable sun's radiation for the production of efficient and clean fossil energy as well as a wide range of ecological implications. The generation of solar fuel-based water splitting and CO2 photoreduction is excellent for generating alternative resources and reducing global warming. Developing an inexpensive photocatalyst can effectively split water into hydrogen (H2 ), oxygen (O2 ) sources, and carbon dioxide (CO2 ) into fuel sources, which is a crucial problem in photocatalysis. The metal-free g-C3 N4 photocatalyst has a high solar fuel generation potential. This review covers the most recent advancements in g-C3 N4 preparation, including innovative design concepts and new synthesis methods, and novel ideas for expanding the light absorption of pure g-C3 N4 for photocatalytic application. Similarly, the main issue concerning research and prospects in photocatalysts based g-C3 N4 was also discussed. The current dissertation provides an overview of comprehensive understanding of the exploitation of the extraordinary systemic and characteristics, as well as the fabrication processes and uses of g-C3 N4 .

Azomethine-clubbed thiazoles as human tissue non-specific alkaline phosphatase (h-TNAP) and intestinal alkaline phosphatase (h-IAP) Inhibitors: kinetics and molecular docking studies.

Thiazole derivatives are known inhibitors of alkaline phosphatase, but various side effects have reduced their curative efficacy. Conversely, compounds bearing azomethine linkage display a broad spectrum of biological applications. Therefore, combining the two scaffolds in a single structural unit should result in joint beneficial effects of both. A new series of azomethine-clubbed thiazoles (3a-i) was synthesized and appraised for their inhibitory potential against human tissue non-specific alkaline phosphatase (h-TNAP) and human intestinal alkaline phosphatase (h-IAP). Compounds 3c and 3f were found to be most potent compounds toward h-TNAP with IC50 values of 0.15 ± 0.01 and 0.50 ± 0.01 µM, respectively, whereas 3a and 3f exhibited maximum potency for h-IAP with IC50 value of 2.59 ± 0.04 and 2.56 ± 0.02 µM, respectively. Molecular docking studies were also performed to find the type of binding interaction between potential inhibitor and active sites of enzymes. The enzymes inhibition kinetics studies were carried out to define the mechanism of enzyme inhibition. The current study leads to discovery of some potent inhibitors of alkaline phosphatase that is promising toward identification of compounds with druggable properties.

Deciphering the Effect of Lysine Acetylation on the Misfolding and Aggregation of Human Tau Fragment 171IPAKTPPAPK180 Using Molecular Dynamic Simulation and the Markov State Model.

The formation of neurofibrillary tangles (NFT) with ß-sheet-rich structure caused by abnormal aggregation of misfolded microtubule-associated protein Tau is a hallmark of tauopathies, including Alzheimer's Disease. It has been reported that acetylation, especially K174 located in the proline-rich region, can largely promote Tau aggregation. So far, the mechanism of the abnormal acetylation of Tau that affects its misfolding and aggregation is still unclear. Therefore, revealing the effect of acetylation on Tau aggregation could help elucidate the pathogenic mechanism of tauopathies. In this study, molecular dynamics simulation combined with multiple computational analytical methods were performed to reveal the effect of K174 acetylation on the spontaneous aggregation of Tau peptide 171IPAKTPPAPK180, and the dimerization mechanism as an early stage of the spontaneous aggregation was further specifically analyzed by Markov state model (MSM) analysis. The results showed that both the actual acetylation and the mutation mimicking the acetylated state at K174 induced the aggregation of the studied Tau fragment; however, the effect of actual acetylation on the aggregation was more pronounced. In addition, acetylated K174 plays a major contributing role in forming and stabilizing the antiparallel ß-sheet dimer by forming several hydrogen bonds and side chain van der Waals interactions with residues I171, P172, A173 and T175 of the corresponding chain. In brief, this study uncovered the underlying mechanism of Tau peptide aggregation in response to the lysine K174 acetylation, which can deepen our understanding on the pathogenesis of tauopathies.

Probing the Molecular Mechanism of Rifampin Resistance Caused by the Point Mutations S456L and D441V on Mycobacterium tuberculosis RNA Polymerase through Gaussian Accelerated Molecular Dynamics Simulation.

Rifampin is the first-line antituberculosis drug, with Mycobacterium tuberculosis RNA polymerase as the molecular target. Unfortunately, M. tuberculosis strains that are resistant to rifampin have been identified in clinical settings, which limits its therapeutic effects. In clinical isolates, S531L and D516V (in Escherichia coli) are two common mutated codons in the gene rpoB, corresponding to S456L and D441V in M. tuberculosis However, the resistance mechanism at the molecular level is still elusive. In this work, Gaussian accelerated molecular dynamics simulations were performed to uncover the resistance mechanism of rifampin due to S456L and D441V mutations at the atomic level. The binding free energy analysis revealed that the reduction in the ability of two mutants to bind rifampin is mainly due to a decrease in electrostatic interaction, specifically, a decrease in the energy contribution of the R454 residue. R454 acts as an anchor and forms stable hydrogen bond interaction with rifampin, allowing rifampin to be stably incorporated in the center of the binding pocket. However, the disappearance of the hydrogen bond between R454 and the mutated residues increases the flexibility of the side chain of R454. The conformation of R454 changes, and the hydrogen bond interaction between it and rifampin is disrupted. As result, the rifampin molecule moves to the outside of the pocket, and the binding affinity decreases. Overall, these findings can provide useful information for understanding the drug resistance mechanism of rifampin and also can give theoretical guidance for further design of novel inhibitors to overcome the drug resistance.

The misfolding mechanism of the key fragment R3 of tau protein: a combined molecular dynamics simulation and Markov state model study.

The formation of neurofibrillary tangles (NFT) by abnormal aggregation of misfolded microtubule-associated protein tau is a hallmark of tauopathies, including Alzheimer's disease. However, it remains unclear how tau monomers undergo conformational changes and further lead to the abnormal aggregation. In this work, molecular dynamics simulation combined with the Markov state model (MSM) analysis was used to uncover the misfolding progress and structural characteristics of the key R3 fragment of tau protein at the atomic level. The simulation results show that R3 exists in disordered structures mainly, which is consistent with the experimental results. The MSM analysis identified multiple ß-sheet conformations of R3. The residues involved in the ß-sheet structure formation are mainly located in three regions: PHF6 at the N-terminal, S324 to N327 at the middle of R3, and K331 to G334 at the C-terminal. In addition, the path analysis of the formation of the ß-sheet structure by transition path theory (TPT) revealed that there are multiple paths to form ß-sheet structures from the disordered state, and the timescales are at the millisecond level, indicating that a large number of structural rearrangements occur during the formation of ß-sheet structures. It is interesting to note that S19 is a critical intermediate state for the formation of two target ß-sheet structures, S23 and S4. In S19, three regions of V306 to K311, C322 to G326, and K331 to G334 form a turn structure, the regions that form the ß-sheet structure in target states S23 and S4, indicating that the formation of a turn structure is necessary to form a ß-sheet structure and then the turn structure will eventually transform into the ß-sheet structure through key hydrogen bonding interactions. These findings can provide insights into the kinetics of tau protein misfolding.

Distinctive inhibition of alkaline phosphatase isozymes by thiazol-2-ylidene-benzamide derivatives: Functional insights into their anticancer role.

In the recent years, the role of alkaline phosphatase (AP) isozymes in the cause of neoplastic diseases such as breast, liver, renal, and bone cancer has been confirmed and, thus they represent a novel target for the discovery of anticancer drugs. In this study different derivatives of thiazol-2-ylidene-benzamide were evaluated for their potential to inhibit alkaline phosphatase (AP) isozymes. Their anticancer potential was assessed using human breast cancer (MCF-7), bone-marrow cancer (K-562), and cervical cancer (HeLa) cell lines in comparison to normal cells from baby hamster kidney BHK-21. The results suggested that in comparison to other derivatives, compounds 2i, 2e, and 2a showed more sensitivity towards human tissue non-specific alkaline phosphatase (h-TNAP). Among these, 2″-chloro-N-(3-(4'-fluorophenyl)-4-methylthiazol-2(3H)-ylidene) benzamide (2e) was found as the most potent and selective inhibitor for h-TNAP with an IC50 value of 0.079 ± 0.002 µM. Moreover, a significant correlation was observed between the enzyme inhibition profile and cytotoxic data. The compounds exhibiting maximum anticancer potential also induced maximum apoptosis in the respective cell lines. Furthermore, the DNA interaction studies exhibited the non-covalent mode of interaction with the herring sperm-DNA. Molecular docking studies also supported the in vitro inhibitory activity of potent compounds. Our findings suggested that potent and selective inhibitors might be useful candidates for the treatment or prevention of those diseases associated with the higher level of AP. Moreover, the study can be useful for the researcher to explore more molecular mechanisms of such derivatives and their analogues with the exact findings.

Synthesis, functionalization and biological activity of arylated derivatives of (+)-estrone.

Various novel arylated estrone derivatives, such as 2-aryl-, 4-aryl- and 2,4-diaryl-estrones, by Suzuki-Miyaura reactions. While the synthesis of 4-arylestrones could be carried out under standard conditions, the synthesis of 2-arylestrones and 2,4-diarylestrones required a thorough optimization of the conditions and it proved to be important to use sterically encumbered biaryl ligands. The best results were obtained by the use of RuPhos. Combination of developed Suzuki coupling reactions with subsequent cyclization reactions afforded more complex hybrid structures, containing dibenzofuran, benzocoumarin and steroid moieties. These derivatives were tested as pancreatic lipase inhibitors and it was found that most of the compounds exhibited inhibition of pancreatic lipase but the maximum inhibitory potential was shown by 4-arylestrones. All of the synthesized derivatives showed inhibitory values in the range of 0.82±0.01-59.7±3.12µM. The biological activity was also rationalized on the bases of docking studies.

Abdominal gunshot wounds-a comparative assessment of severity measures.

BACKGROUND: Penetrating abdominal trauma is a common feature of trauma treated in low- and middle-income countries (LMICs). The penetrating abdominal trauma index (PATI) and the injury severity score (ISS) are severity-measures most often used to gauge injury severity. It remains unclear which measure better accounts for the severity of sustained injuries. This study compares the predictive ability of both injury severity measures in patients presenting to an LMIC in South Asia. METHODS: All isolated gunshot wounds to the abdomen presenting to a university hospital between 2011 and 2012 were included. ISS and PATI were calculated for each case. Primary outcome measures included all-cause mortality and complications. Multivariable analysis adjusting for age, sex, referral status, hypotension, tachycardia, and injury severity measures was performed. The area under the receiver operating characteristic (AUROC) curve were further calculated to compare the respective abilities of ISS and PATI at predicting death and complications. RESULTS: A total of 70 patients were included. The average age on presentation was 34.5 y (±11.4) within a predominantly male (n = 68, 97.1%) cohort. Most gunshot wounds were intentionally inflicted (n = 67, 95.7%). The crude rates of death and complications were 34.3% and 15.7%, respectively. The median ISS was 14 (interquartile range: 11-21), and the median PATI was 16 (interquartile range: 9-26). AUROC analysis revealed that ISS was comparable with PATI at predicting mortality (AUROC [95% confidence interval]: 0.952 [0.902-1.00] versus 0.934 [0.860-1.00]) and complications (AUROC [95% confidence interval]: 0.868 [0.778-0.959] versus 0.895 [0.815-0.975]). CONCLUSIONS: The predictive ability of ISS and PATI severity measures was found to be comparable. The results suggest that both measures can be used to risk-stratify patients with isolated abdominal gunshot wounds in an LMIC.

Near complete aortic transection and its successful repair using a novel cardiopulmonary bypass technique.

The case of a 38-year old female, victim of a road traffic accident who presented with a near complete aortic transection is presented. An emergent repair employing cardiopulmonary bypass was attempted in the operating room. Anticipating a high-risk of compromise to cerebral perfusion from air micro-emboli, the bypass was attempted with an innovative approach involving the successful cannulation of the pulmonary artery and descending aorta. The patient survived and was found to be doing well on subsequent post-operative visits.

Identification of Aggregation Mechanism of Acetylated PHF6* and PHF6 Tau Peptides Based on Molecular Dynamics Simulations and Markov State Modeling.

The microtubule-associated protein tau (MAPT) has a critical role in the development and preservation of the nervous system. However, tau's dysfunction and accumulation in the human brain can lead to several neurodegenerative diseases, such as Alzheimer's disease, Down's syndrome, and frontotemporal dementia. The microtubule binding (MTB) domain plays a significant, important role in determining the tau's pathophysiology, as the core of paired helical filaments PHF6* (275VQIINK280) and PHF6 (306VQIVYK311) of R2 and R3 repeat units, respectively, are formed in this region, which promotes tau aggregation. Post-translational modifications, and in particular lysine acetylation at K280 of PHF6* and K311 of PHF6, have been previously established to promote tau misfolding and aggregation. However, the exact aggregation mechanism is not known. In this study, we established an atomic-level nucleation-extension mechanism of the separated aggregation of acetylated PHF6* and PHF6 hexapeptides, respectively, of tau. We show that the acetylation of the lysine residues promotes the formation of ß-sheet enriched high-ordered oligomers. The Markov state model analysis of ac-PHF6* and ac-PHF6 aggregation revealed the formation of an antiparallel dimer nucleus which could be extended from both sides in a parallel manner to form mixed-oriented and high-ordered oligomers. Our study describes the detailed mechanism for acetylation-driven tau aggregation, which provides valuable insights into the effect of post-translation modification in altering the pathophysiology of tau hexapeptides.

ETSNet: A deep neural network for EEG-based temporal-spatial pattern recognition in psychiatric disorder and emotional distress classification.

The use of EEG for evaluating and diagnosing neurological abnormalities related to psychiatric diseases and identifying human emotions has been improved by deep learning advancements. This research aims to categorize individuals with schizophrenia (SZ), their biological relatives (REL), and healthy controls (HC) using resting EEG brain source signal data defined by regions of interest (ROIs). The proposed solution is a deep neural network for the cortical source signals of the ROIs, incorporating a Squeeze-and-Excitation Block and multiple CNNs designed for eyes-open and closed resting states. The model, called EEG Temporal Spatial Network (ETSNet), has two variants: ETSNets and ETSNetf. Two evaluations were conducted to show the effectiveness of the proposed model. The average accuracy for the classification of SZ, REL, and HC using EEG resting data was 99.57% (ETSNetf), and the average accuracy for the classification of eyes-open (EO) and eyes-closed (EC) resting states was 93.15% (ETSNets). An ablation study was also conducted using two public datasets for intellectual and developmental disorders and emotional states, showing improved classification accuracy compared to advanced EEG classification algorithms when using ETSNets.

Design and synthesis of adamantane-1-carbonyl thiourea derivatives as potent and selective inhibitors of h-P2X4 and h-P2X7 receptors: An Emerging therapeutic tool for treatment of inflammation and neurological disorders.

P2X receptors are potential therapeutic targets for the treatment of various neurodegenerative disorders, pain, inflammation, hypertension, and cancer. Adamantane ring has been reported to exhibit significant inhibitory potential towards P2X receptors, especially for P2X7R. We have utilized uniqueness of adamantane moiety in our synthesized compounds and introduced various substitutions that enhanced the potency as well as selectivity for P2XR subtypes. Among synthesized derivatives, 4n and 5b were found to be most potent and selective inhibitors for h-P2X4R and h-P2X7R, respectively. 4n was found to be highly selective for h-P2X4R with IC50 ± SEM = 0.04 ± 0.01 µM, that is 22 times more potent than BX-430, a standard selective inhibitor of h-P2X4R. 5b has IC50 ± SEM of 0.073 ± 0.04 µM, which is comparable with the known antagonists of h-P2X7R. 4n and 5b were studied for mode of inhibition of P2XRs and both were found to be negative allosteric modulators. In silico studies were also conducted to find the type of interactions as well as mode of inhibition.

AM-UNet: automated mini 3D end-to-end U-net based network for brain claustrum segmentation.

Recent advances in deep learning (DL) have provided promising solutions to medical image segmentation. Among existing segmentation approaches, the U-Net-based methods have been used widely. However, very few U-Net-based studies have been conducted on automatic segmentation of the human brain claustrum (CL). The CL segmentation is challenging due to its thin, sheet-like structure, heterogeneity of its image modalities and formats, imperfect labels, and data imbalance. We propose an automatic optimized U-Net-based 3D segmentation model, called AM-UNet, designed as an end-to-end process of the pre and post-process techniques and a U-Net model for CL segmentation. It is a lightweight and scalable solution which has achieved the state-of-the-art accuracy for automatic CL segmentation on 3D magnetic resonance images (MRI). On the T1/T2 combined MRI CL dataset, AM-UNet has obtained excellent results, including Dice, Intersection over Union (IoU), and Intraclass Correlation Coefficient (ICC) scores of 82%, 70%, and 90%, respectively. We have conducted the comparative evaluation of AM-UNet with other pre-existing models for segmentation on the MRI CL dataset. As a result, medical experts confirmed the superiority of the proposed AM-UNet model for automatic CL segmentation. The source code and model of the AM-UNet project is publicly available on GitHub: https://github.com/AhmedAlbishri/AM-UNET.

Synthesis, Carbonic Anhydrase II/IX/XII Inhibition, DFT, and Molecular Docking Studies of Hydrazide-Sulfonamide Hybrids of 4-Methylsalicyl- and Acyl-Substituted Hydrazide.

Carbonic anhydrases (CAs and EC 4.2.1.1) are the Zn2+ containing enzymes which catalyze the reversible hydration of CO2 to carbonate and proton. If they are not functioning properly, it would lead towards many diseases including tumor. Synthesis of hydrazide-sulfonamide hybrids (19-36) was carried out by the reaction of aryl (10-11) and acyl (12-13) hydrazides with substituted sulfonyl chloride (14-18). Final product formation was confirmed by FT-IR, NMR, and EI-MS. Density functional theory (DFT) calculations were performed on all the synthesized compounds to get the ground-state geometries and compute NMR properties. NMR computations were in excellent agreement with the experimental NMR data. All the synthesized hydrazide-sulfonamide hybrids were in vitro evaluated against CA II, CA IX, and CA XII isozymes for their carbonic anhydrase inhibition activities. Among the entire series, only compounds 22, 32, and 36 were highly selective inhibitors of hCA IX and did not inhibit hCA XII. To investigate the binding affinity of these compounds, molecular docking studies of compounds 32 and 36 were carried out against both hCA IX and hCA XII. By using BioSolveIT's SeeSAR software, further studies to provide visual clues to binding affinity indicate that the structural elements that are responsible for this were also studied. The binding of these compounds with hCA IX was highly favorable (as expected) and in agreement with the experimental data.

Development, Molecular Docking, and In Silico ADME Evaluation of Selective ALR2 Inhibitors for the Treatment of Diabetic Complications via Suppression of the Polyol Pathway.

Diabetic complications are associated with overexpression of aldose reductase, an enzyme that catalyzes the first step of the polyol pathway. Osmotic stress in the hyperglycemic state is linked with the intracellular accumulation of sorbitol along with the depletion of NADPH and eventually leads to oxidative stress via formation of reactive oxygen species and advanced glycation end products (AGEs). These kinds of mechanisms cause the development of various diabetic complications including neuropathy, nephropathy, retinopathy, and atherosclerotic plaque formation. Various aldose reductase inhibitors have been developed to date for the treatment of diabetic complications, but all have failed in different stages of clinical trials due to toxicity and poor pharmacokinetic profiles. This toxicity is rooted in a nonselective inhibition of both ALR2 and ALR1, homologous enzymes involved in the metabolism of toxic aldehydes such as methylglyoxal and 3-oxyglucosazone. In the present study, we developed a series of thiosemicarbazone derivatives as selective inhibitors of ALR2 with both antioxidant and antiglycation potential. Among the synthesized compounds, 3c exhibited strong and selective inhibition of ALR2 (IC50 1.42 µM) along with good antioxidant and antiglycative properties. The binding mode of 3c was assessed through molecular docking and cluster analysis via MD simulations, while in silico ADME evaluation studies predicted the compounds' druglike properties. Therefore, we report 3c as a drug candidate with promising antioxidant and antiglycative properties that may be useful for the treatment of diabetic complications through selective inhibition of ALR2.

Development and exploration of novel substituted thiosemicarbazones as inhibitors of aldose reductase via in vitro analysis and computational study.

The role of aldose reductase (ALR2) in causing diabetic complications is well-studied, with overactivity of ALR2 in the hyperglycemic state leading to an accumulation of intracellular sorbitol, depletion of cytoplasmic NADPH and oxidative stress and causing a variety of different conditions including retinopathy, nephropathy, neuropathy and cardiovascular disorders. While previous efforts have sought to develop inhibitors of this enzyme in order to combat diabetic complications, non-selective inhibition of both ALR2 and the homologous enzyme aldehyde reductase (ALR1) has led to poor toxicity profiles, with no drugs targeting ALR2 currently approved for therapeutic use in the Western world. In the current study, we have synthesized a series of N-substituted thiosemicarbazones with added phenolic moieties, of which compound 3m displayed strong and selective ALR2 inhibitory activity in vitro (IC50 1.18 µM) as well as promising antioxidant activity (75.95% free radical scavenging activity). The target binding modes of 3m were studied via molecular docking studies and stable interactions with ALR2 were inferred through molecular dynamics simulations. We thus report the N-substituted thiosemicarbazones as promising drug candidates for selective inhibition of ALR2 and possible treatment of diabetic complications.

Synthesis of Sulfonamide Tethered (Hetero)aryl ethylidenes as Potential Inhibitors of P2X Receptors: A Promising Way for the Treatment of Pain and Inflammation.

P2X receptors have the ability to regulate various physiological functions like neurotransmission, inflammatory responses, and pain sensation. Such physiological properties make these receptors a new target for the treatment of pain and inflammation. Several antagonists of P2X receptors have been studied for the treatment of neuropathic pain and neurodegenerative disorders but potency and selectivity are the major issues with these known inhibitors. Sulfonamide derivatives were reported to be potent inhibitors of P2X receptors. In this study, sulfonamide carrying precursor hydrazide was synthesized by a facile method that was subsequently condensed with methyl (hetero)arylketones to obtain a series of new (hetero)aryl ethylidenes. These compounds were screened for inhibitory potential against h-P2X2, h-P2X4, h-P2X5, and h-P2X7 receptors to find their potency and selectivity. Computational studies were performed to confirm the mode of inhibition as well as type of interaction between ligand and target site. In calcium signaling experiments, compound 6h was found to be the most potent and selective inhibitor of h-P2X2 and h-P2X7 receptors with IC50 ± standard error of the mean (SEM) values of 0.32 ± 0.01 and 1.10 ± 0.21 µM, respectively. Compounds 6a and 6c exhibited selective inhibition for h-P2X7 receptor, whereas 6e, 7a, and 7b expressed selective inhibitions toward h-P2X2 receptor that were comparable to the positive control suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS).

Genetic behavior of controlling area under disease progress curve for stripe rust (Puccinia striiformis f. sp. tritici) in two wheat (Triticum aestivum) crosses.

Genetic effects on controlling resistance to stripe rust (Puccinia striiformis f. sp. tritici Eriksson)were determined in two wheat crosses, Bakhtawar-92 (B-92) x Frontana and Inqilab-91 x Fakhre Sarhad using area under the disease progress curve (AUDPC) as a measure of stripe rust resistance. The resistant and susceptible parents involved in developing genetic populations were identified by initial assessment of 45 wheat accessions for stripe rust reaction. Mixed inheritance model was applied to the data analysis of six basic populations (P(1), F(1), P(2), B(1), B(2), and F(2)) in the crosses. The results indicated that AUDPC in cross 1 was controlled by two major genes with additive-dominance epistatic effect plus polygenes with additive-dominance-epistatic effects (model E) whereas, in the case of cross 2, it was under the control of two major genes with additive-dominance epistatic effect plus additive-dominant polygenes (model E-1). Additive effect was predominant over all other types of genetic effects, suggesting that the delay in selection for resistance until maximum favorable genes are accumulated in the individuals is desired. The tendency of backcrosses toward their respective pollen donor parents indicated the control of resistance through nuclear genes rather than the cytoplasmic factors. Occurrence of resistant as well as susceptible transgressive segregates (though very few in F(2) for each cross) indicated the presence of favorable as well as some adverse genes for resistance to stripe rust in the parents. The major gene heritability was higher than that of the polygene in B(1), B(2), and F(2) for the crosses. The major gene as well as the polygene heritability was 48.99 to 87.12% and 2.26 to 36.80% for the two crosses, respectively. The highest phenotypic variations in AUDPC (2,504.10 to 5,833.14) for segregating progenies (B(1), B(2), and F(2)) represent that the character was highly influenced by the environment. The experimental results of the two crosses indicate that resistance to stripe rust is under control of two major genes in association with several polygene rather than cytoplasmic inheritance.

Knowledge rather than language proficiency affects achievement scores in interactive objectively structured performance evaluation.

BACKGROUND: A common belief is that language proficiency might have affected the outcome scores of the Oral Structured Performance Evaluation (OSPE) especially at the interactive stations. The objective of this study was to explore this postulation. METHODS: The subject of Behavioural Sciences was examined for the first time as a component of undergraduate medical curriculum in 2nd Professional Medical Examinations in 2007. Equal weightage was given to written and OSPE components in the examination. The OSPE scores in the interactive component of all (1457) candidates were compared with their written scores in the subject of Behavioural Sciences as well as their Higher Secondary School Certificate (HSSC) scores in the subject of English using Multiple Linear Regression Analysis in SPSS v.12. RESULTS: Overall as well as in the Public Medical Colleges, relative to each other, knowledge of the subject as indicated by marks obtained in the written component of the examination exerted a positive and statistically significant (p < 0.05), and command over language as indicated by marks obtained in the HSSC examination exerted a small positive but statistically insignificant (p = 0.231 and 0.639 respectively) influence on the performance of students in the interactive OSPE component. In the private medical colleges command over language exerted a small negative but statistically insignificant (p = 0.936) influence on the performance of students in the interactive OSPE component of the examination. CONCLUSION: Command over the subject content is the best indicator of achievement in OSPE.

Molecular dynamic simulations reveal structural insights into substrate and inhibitor binding modes and functionality of Ecto-Nucleoside Triphosphate Diphosphohydrolases.

Ecto-nucleotidase enzymes catalyze the hydrolysis of extracellular nucleotides to their respective nucleosides. Herein, we place the focus on the elucidation of structural features of the cell surface located ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDase1-3 and 8). The physiological role of these isozymes is crucially important as they control purinergic signaling by modulating the extracellular availability of nucleotides. Since, crystal or NMR structure of the human isozymes are not available - structures have been obtained by homology modeling. Refinement of the homology models with poor stereo-chemical quality is of utmost importance in order to derive reliable structures for subsequent studies. Therefore, the resultant models obtained by homology modelling were refined by running molecular dynamic simulation. Binding mode analysis of standard substrates and of competitive inhibitor was conducted to highlight important regions of the active site involved in hydrolysis of the substrates and possible mechanism of inhibition.