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Proteins from Crenarchaeal organisms exhibit remarkable thermal stability. The aromatic amino acids in Cren7, a Crenarchaeal protein, regulate protein stability and further modulate DNA binding and its compaction. Specific aromatic amino acids were mutated, and using spectroscopic and theoretical approaches, we have examined the structure, DNA binding affinity, and DNA bending ability of mutants. and compared with wild-type (WT) Cren7. The reverse titration profiles were analysed by a noncooperativeMcGhee-von Hippel model to estimate affinity constant (Ka) and site size (n) associated with binding to the DNA. Biolayer interferometry (BLI) measurements showed that the binding affinity decreased at higher salt concentrations. For theoretical analysis of extent of DNA bending, radius of gyration and bending angle were compared for WT and mutants. Time evolution of order parameters based on translational and rotational motion of tryptophan residue (W26) was used for qualitative detection of stacking interactions between W26 of Cren7 and DNA nucleobases. It was observed that orientation of W26 in F41A favored formation of a new lone pair-lone pair interaction between DNA and Cren7. Consequently, in thermostable proteins, the aromatic residues at the terminus maintain structural stability, whereas the residues at the core optimize the degree of DNA bending and compaction.

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Hybrid nanocomposites, which comprise organic and inorganic materials, have gained increasing attention in applications for enhanced sensing response to both reducing and oxidation gases. In this study, a novel nanocomposite is synthesized using chemical polymerization by reinforcing Ag/Cu nanoparticles with different concentrations doped into the polyaniline matrix. This hybrid nanocomposite is used as a sensing platform for ammonia detection with different concentrations (ppm). The homogeneous distribution of Ag/Cu nanoparticles onto the PANI matrix provides a smooth and dense surface area, further accelerating the transmission of electrons. The synergistic effect of the PANI@Ag/Cu matrix is responsible for the outstanding conductivity, compatibility, and catalytic ability of the proposed gas sensor. The structure, morphology, and surface composition of as-synthesized samples were examined using X-ray diffraction, field emission scanning electron microscopy, ultraviolet-visible spectroscopy, energy dispersive spectroscopy, thermogravimetric analysis, and Fourier transform infrared spectroscopy. The results indicated that the resistive sensor based on the PANI@Ag/Cu3 hybrid nanocomposite exhibited the highest response toward ammonia at room temperature, with a response value of 86% to a concentration of 300 ppm. We also investigated the sensing properties of volatile organic compounds, including carbon dioxide, carbon monoxide, ethanol and hydrogen sulphide. Characterization and gas sensing measurements exhibited protonation and deprotonation of the PANI@Ag/Cu heterojunction, which contributes to the ammonia sensing mechanism. Overall, the obtained findings demonstrated that the PANI@Ag/Cu hybrid nanocomposite is a promising material for gas sensing applications in environmental monitoring.

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Dengue fever is a mosquito-borne viral illness that affects over 100 nations around the world, including Africa, America, the Eastern Mediterranean, Southeast Asia, and the Western Pacific. Those who get infected by virus for the second time are at greater risk of having persistent dengue symptoms. Dengue fever has yet to be treated with a long-lasting vaccination or medication. Because of their ease of use, mosquito repellents have become popular as a dengue prevention technique. However, this has resulted in environmental degradation and harm, as well as bioaccumulation and biomagnification of hazardous residues in the ecosystem. Synthetic pesticides have caused a plethora of serious problems that were not foreseen when they were originally introduced. The harm caused by the allopathic medications/synthetic pesticides/chemical mosquito repellents has paved the door to employment of eco-friendly/green approaches in order to reduce dengue cases while protecting the integrity of the nearby environment too. Since the cases of dengue have become rampant these days, hence, starting the medication obtained from green approaches as soon as the disease is detected is advisable. In the present paper, we recommend environmentally friendly dengue management strategies, which, when combined with a reasonable number of vector control approaches, may help to avoid the dengue havoc as well as help in maintaining the integrity of the ecosystem.

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The molecular association of proteins with nucleic acids leading to the formation of macromolecular complexes is a crucial step in several biological processes. Stabilization of these complexes involves electrostatic interactions between ion pairs (salt bridges) of nucleic acid phosphates and protein side chains. The crenarchaeal DNA binding protein, Cren7 plays a key role in the regulation of chromosomal structure and gene expression in eukaryotic extremophiles. However, the molecular contacts that occur at the interface of protein-DNA complexes and their contribution to the electrostatic interaction have not been fully elucidated. This work presents a quantitative description of the mechanism of the electrostatic interaction between the protein and DNA. We have identified a few residues located at the Cren7-DNA interface that could potentially be responsible for the interaction. Structural studies using circular dichroism indicate mutation of these surface residues minimally affect their structure and stability. The binding affinity of these mutants for the DNA duplexes was examined from reverse titration, biolayer interferometry, and fluorescence anisotropy measurements with calf thymus DNA, polynucleotides, and small DNA oligonucleotides. The resulting kinetic parameters highlight a difference in electrostatic interactions potentials exhibited by residues positioned at different locations of the protein-DNA interface. Computational studies attribute this difference to their surrounding atmosphere and energetic stabilization parameters. The biophysical approach described here can be extended for other proteins that play a crucial role in DNA bending and compaction, to properly evaluate the role of specific residues on the mechanisms of DNA binding.

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At present, food security is a matter of debate of global magnitude and fulfilling the feeding requirement of > 8 billion human populations by 2030 is one of the major concerns of the globe. Aquaculture plays a significant role to meet the global food requirement. Shrimp species such as Litopenaeus vannamei, Penaeus monodon, and Macrobrachium rosenbergii are among the most popular food commodities worldwide. As per Global Outlook for Aquaculture Leadership survey, disease outbreaks have been a matter of concern from the past many decades regarding the shrimp aquaculture production. Among the past disease outbreaks, white spot disease caused by the white spot syndrome virus is considered to be one of the most devastating ones that caused colossal losses to the shrimp industry. Since the virus is highly contagious, it spreads gregariously among the shrimp population; hence, practicing proper sanitization practices is crucial in order to have disease-free shrimps. Additionally, in order to control the disease, antibiotics were used that further leads to bioaccumulation and biomagnification of antibiotics in several food webs. The bioaccumulation of the toxic residues in the food webs further adversely affected human too. Recently, immunostimulants/antivirals were used as an alternative to antibiotics. They were found to enhance the immune system of shrimps in eco-friendly manner. In context to this, the present paper presents a critical review on the immunostimulants available from plants, animals, and chemicals against WSSV in shrimps. Looking into this scenario, maintaining proper sanitation procedures in conjunction with the employment of immunostimulants may be a viable approach for preserving shrimp aquaculture across the globe.

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White Spot disease is a devastating disease of shrimps caused by White Spot Syndrome Virus in multifarious shrimp species. At present there is no absolute medication to suppress the disease hence, there is an urgent need for development of drug against the virus. Molecular interaction between viral envelope protein VP28 and shrimp receptor protein especially chitins play a pivotal role in ingression of WSSV. In the present study, we have tried to shed light on structural aspects of lectin protein in Marsupenaeus japonicus (MjsvCL). A structural insight to the CTLD-domain of MjsvCL has facilitated the understanding of the binding mechanism between the two proteins that is responsible for entry of WSSV into shrimps. Further, incorporation of molecular dynamics simulation and MMPBSA studies revealed the affinity of binding and certain hotspot residues, which are critical for association of both the proteins. For the first time we have proposed that these amino acids are quintessential for formation of VP28-MjsvCL complex and play crucial role in entry of WSSV into shrimps. Targeting the interaction between VP28 and CTLD of MjsvCL may possibly serve as a potential drug target. The current study provides information for better understanding the interaction between VP28 and MjsvCL that could be a plausible site for future inhibitors against WSSV in shrimps.Communicated by Ramaswamy H. Sarma.

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Host-parasite relationships can be best understood at the level of protein-protein interaction between host and pathogen. Such interactions are instrumental in understanding the important stages of life cycle of pathogen such as adsorption of the pathogen on host surface followed by effective entry of pathogen into the host body, movement of the pathogen across the host cytoplasm to reach the host nucleus and replication of the pathogen within the host. White Spot Disease (WSD) is a havoc for shrimps and till date no effective treatment is available against the disease. Moreover information regarding the mechanism of entry of White Spot Syndrome Virus (WSSV) into shrimps, as well as knowledge about the protein interactions occurring between WSSV and shrimp during viral entry are still at very meagre stage. A cumulative and critically assessed information on various viral-shrimp interactions occurring during viral entry can help to understand the exact pathway of entry of WSSV into the shrimp which in turn can be used to device drugs that can stop the entry of virus into the host. In this context, we highlight various WSSV and shrimp proteins that play role in the entry mechanism along with the description of the interaction between host and pathogen proteins.

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White spot disease is a devastating disease of shrimp Penaeus monodon in which the shrimp receptor protein PmRab7 interacts with viral envelop protein VP28 to form PmRab7-VP28 complex, which causes initiation of the disease. The molecular mechanism implicated in the disease, the dynamic behavior of proteins as well as interaction between both the biological counterparts that crafts a micro-environment feasible for entry of virus into the shrimp is still unknown. In the present study, we applied molecular modeling (MM), molecular dynamics (MD) and docking to compute surface mapping of infective amino acid residues between interacting proteins. Our result showed that α-helix of PmRab7 (encompassing Ser74, Ile143, Thr184, Arg53, Asn144, Thr184, Arg53, Arg79) interacts with ß-sheets of VP28 (containing Ser74, Ile143, Thr184, Arg53, Asn144, Thr184, Arg53, Arg79) and Arg69-Ser74, Val75-Ile143, Leu73-Ile143, Arg79-Asn144, Ala198-Ala182 bonds contributed in the formation of PmRab7-VP28 complex. Further studies on the amino acid residues and bonds may open new possibilities for preventing PmRab7-VP28 complex formation, thus reducing chances of WSD. The quantitative predictions provide a scope for experimental testing in future as well as endow with a straightforward evidence to comprehend cellular mechanisms underlying the disease.

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Diabetes mellitus, an epidemic metabolic disorders characterized by high blood glucose level associated with various macrovascular and microvascular complications, is one of the main causes of human suffering across the globe. Researchers around the world mainly focused on insulin, insulin analogues, oral hypoglycemic agents and various other complementary and alternate medicines to control the blood glucose levels in diabetes. The present review summarizes the disorders associated with elevation of blood glucose level, biochemical & endocrinological aspects and the current strategies to control. The emphasis has been laid in particular on the new potential biological targets and the possible treatment as well as the current ongoing research status on new generation hypoglycemic agents.

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Oseltamivir (has known by its brand name 'Tamiflu') is a prodrug, requiring ester hydrolysis for conversion to the active form, Oseltamivir carboxylate. Oseltamivir was the first orally active neuraminidase inhibitor commercially developed by US based Gilead Sciences and is currently marketed by F. Hoffmann-La Roche (Roche). Oseltamivir is an antiviral drug which works by blocking the function of the viral neuraminidase protein. US FDA approved Oseltamivir for prophylaxis of uncomplicated influenza A and B. Currently, Oseltamivir is the only first line defense drug available for the treatment of Swine Flu. Orally Oseltamivir is well tolerated and effective in treatment of influenza in adolescents and adults, including the elderly and patients with chronic cardiac and/or respiratory disease. Many of the pharmaceutical companies targeted Oseltamivir as a block buster molecule. In present review, we have tried to cover chemistry, mode of binding, total synthesis, current patent status, adverse effect and clinical status of Oseltamivir giving emphasis on medicinal chemistry aspect.

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Rheumatoid arthritis (RA) is mainly an auto-immune disease characterized by inflammation in joints. 1 in 50 people develop RA at some stage and at any age. This review summarizes the etiology, pathophysiology, risk factor, and treatment related to RA. The emphasis has been laid in particular on the new potential biological targets and the possible treatment as well as the current ongoing research status on RA.

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STUDY OBJECTIVE: To examine the spectrum of sleep disorders in patients with chronic traumatic brain injury (TBI) and determine if the severity of sleep disorder is related to severity of chronic TBI. METHODS: Patients who underwent evaluation for sleep disorder/s following a TBI were included in this retrospective analysis. Sixty adult patients with TBI (age 20-69 yr; 38 M and 22 F), who presented with sleep-related complaints 3 months to 2 years following TBI, were studied. None had sleep complaints prior to the TBI. Orophrayngeal, chin, and TMJ examinations were considered benign. The severity of injury was assessed by the Global Assessment of Functioning (GAF) scale. Polysomnograms (PSGs) were performed on 54 patients (90%), 28 of whom underwent multiple sleep latency tests (MSLTs) because they scored >11 on the Epworth Sleepiness Scale (ESS). The Beck Depression Inventory (BDI) scale was administered if there was sleep maintenance insomnia, and the Hamilton Anxiety Scale (HAS) was administered if there was sleep onset insomnia. RESULTS: The TBI severity was mild in 40%, moderate in 20%, and severe in 40%. The Epworth Sleepiness Scale (ESS) score was elevated (>11) in 52%. Hypersomnia was the presenting complaint in 50%, mostly due to sleep apnea, narcolepsy, and periodic limb movement disorder (PLMD). Insomnia was the presenting complaint in 25%, half with sleep maintenance insomnia and high BDI scores, and the remainder with sleep onset insomnia and high HAS scores. Parasomnia was the presenting complaint in 25%; the most frequent parasomnia was REM behavior disorder (RBD). GAF scores were significantly correlated (p < 0.05) with some of the measures of sleep disruption (stage 1, sleep efficiency, and wake during sleep), but not with others (wake before sleep, stage-shifts, PLMI, PLMA and AHI) on the PSG. Fifty-three percent (15/28) had a mean sleep onset latency <5 minutes, and 32% (9/28), also had two or more sleep onset rapid eye movement periods (SOREMPs) on the MSLT. CONCLUSION: The results of this study demonstrate that a full spectrum of common sleep disorders occurs in patients with chronic TBI. The severity of chronic TBI as measured by GAF scores is correlated with some of the measures of sleep disruption but not others, indicating a complex and multifactorial pathogenesis.

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