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Leucine-rich repeat protein kinase 2 (LRRK2) is a multi-domain protein encompassing two of biology's most critical molecular switches, a kinase and a GTPase, and mutations in LRRK2 are key players in the pathogenesis of Parkinson's disease (PD). The availability of multiple structures (full-length and truncated) has opened doors to explore intra-domain cross-talk in LRRK2. A helix extending from the WD40 domain and stably docking onto the kinase domain is common in all available structures. This C-terminal (Ct) helix is a hub of phosphorylation and organelle-localization motifs and thus serves as a multi-functional protein : protein interaction module. To examine its intra-domain interactions, we have recombinantly expressed a stable Ct motif (residues 2480-2527) and used peptide arrays to identify specific binding sites. We have identified a potential interaction site between the Ct helix and a loop in the CORB domain (CORB loop) using a combination of Gaussian accelerated molecular dynamics simulations and peptide arrays. This Ct-Motif contains two auto-phosphorylation sites (T2483 and T2524), and T2524 is a 14-3-3 binding site. The Ct helix, CORB loop, and the CORB-kinase linker together form a part of a dynamic 'CAP' that regulates the N-lobe of the kinase domain. We hypothesize that in inactive, full-length LRRK2, the Ct-helix will also mediate interactions with the N-terminal armadillo, ankyrin, and LRR domains (NTDs) and that binding of Rab substrates, PD mutations, or kinase inhibitors will unleash the NTDs., (© 2024 The Author(s).)

In this review article, we systematically investigated the diverse applications of laser technology within the sphere of food processing, encompassing techniques such as laser ablation, microbial inactivation, state-of-the-art food packaging, and non-destructive testing. With a detailed exploration, we assess the utility of laser ablation for the removal of surface contaminants from foodstuffs, while also noting the potential financial and safety implications of its implementation on an industrial scale. Microbial inactivation by laser shows promise for reducing the microbial load on food surfaces, although concerns have been raised about potential damage to the physio-characteristics of some fruits. Laser-based packaging techniques, such as laser perforation and laser transmission welding, offer eco-friendly alternatives to traditional packaging methods and can extend the shelf life of perishable goods. Despite the limitations, laser technology shows great promise in the food industry and has the potential to revolutionize food processing, packaging, and testing. Future research needs to focus on optimizing laser equipment, addressing limitations, and developing mathematical models to enhance the technology's uses.

Blue cone monochromacy (BCM) is a rare X-linked retinal disease characterized by the absence of L- and M-opsin in cone photoreceptors, considered a potential gene therapy candidate. However, most experimental ocular gene therapies utilize subretinal vector injection which would pose a risk to the fragile central retinal structure of BCM patients. Here we describe the use of ADVM-062, a vector optimized for cone-specific expression of human L-opsin and administered using a single intravitreal (IVT) injection. Pharmacological activity of ADVM-062 was established in gerbils, whose cone-rich retina naturally lacks L-opsin. A single IVT administration dose of ADVM-062 effectively transduced gerbil cone photoreceptors and produced a de novo response to long-wavelength stimuli. To identify potential first-in-human doses we evaluated ADVM-062 in non-human primates. Cone-specific expression of ADVM-062 in primates was confirmed using ADVM-062.myc, a vector engineered with the same regulatory elements as ADVM-062. Enumeration of human OPN1LW.myc-positive cones demonstrated that doses ≥3 × 10 10 vg/eye resulted in transduction of 18%-85% of foveal cones. A Good Laboratory Practice (GLP) toxicology study established that IVT administration of ADVM-062 was well tolerated at doses that could potentially achieve clinically meaningful effect, thus supporting the potential of ADVM-062 as a one-time IVT gene therapy for BCM., Competing Interests: Declaration of interests K.H., D.C., J.N., C.D., P.S., K.O.B., M.R., B.S., C.M.G., B.E.R., and R.N.G. are current or previous employees of Adverum Biotechnologies and hold stock grants. J.V.H. is a paid consultant of Adverum Biotechnologies., (Copyright © 2023 Adverum Biotechnologies Inc. Published by Elsevier Inc. All rights reserved.)

Chromium (Cr), one of the hazardous pollutants, exists predominantly as Cr(VI) and Cr(III) in the environment. Cr(VI) is more toxic than Cr(III) due to its high mobility and solubility. Elevated levels of Cr in agricultural soil due to various anthropogenic activities cause Cr accumulation in plants, resulting in a significant reduction in plant yield and quality due to Cr-induced physiological, biochemical and molecular alterations. It can infiltrate the food chain through crop plants and cause harmful effects in humans via biomagnification. Cr(VI) is linked to cancer in humans. Therefore, mitigation strategies are required to remediate Cr-polluted soils and limit its accumulation in plants for safe food production. Recent research on metal and metal oxide nanoparticles (NPs) has shown that they can effectively reduce Cr accumulation and phytotoxicity. The effects of these NPs are influenced by their type and dose, exposure method, plant species and experimental settings. In this review, we present an up-to-date compilation and comprehensive analysis of the existing literature regarding the process of uptake and distribution of Cr and impact and potential mechanisms of metal and metal oxide nanoparticles led mitigation of Cr-induced stress in plants. We have also discussed recent developments, existing research gaps and future research directions in the field of Cr stress mitigation by NPs in plants. Overall, this review can provide valuable insights in reducing Cr accumulation and toxicity using metal and metal oxide nanoparticles, thereby promoting safe and sustainable cultivation of food and phytostabilization of Cr-polluted soil., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: The citrus fruits peel contains a variety of bioactive metabolites that have shown multiple therapeutic effects. However, despite having substantial ethnomedicinal value, citrus peels remained underexplored and regarded as bio-waste. This present study was planned to investigate the effect of a characterized peel extract of Citrus reticulata c.v. (CRE) in pentylenetetrazole (PTZ)-induced kindling and associated cognitive and behavioral impairments in a mouse model. Methods: The kindled animals were treated daily with CRE (100 and 200 mg/kg) and challenged with a sub-effective dose of PTZ every 5th day to record the severity of seizures. In the end, different tests were performed to record behavioral and cognitive performance. Results: CRE-treated kindled animals showed a significant suppression in seizure severity following 20 days of the treatment. In the T-maze test, the extract treatment resulted in a marked increase in the spontaneous alternations, whereas it showed no change in anxiety behavior of kindled animals in the elevated plus-maze test. In both forced swim and tail suspension tests, CRE treatment demonstrated a considerable reduction in immobility time. However, no change in overall locomotion was observed in the open field test among all the groups. An increase in the hippocampal Creb and Bdnf expression and decreased glutamate-to-GABA ratio were observed in the CRE-treated kindled animals. Discussion: The results showed that CRE treatment suppresses epileptic seizures and associated cognitive deficits and depression-like behavior in kindled mice. The gene expression findings supported that the observed protective effects of CRE be due to its interaction with CREB signaling.

LRRK2 is a multi-domain protein with three catalytically inert N-terminal domains (NtDs) and four C-terminal domains, including a kinase and a GTPase domain. LRRK2 mutations are linked to Parkinson's Disease. Recent structures of LRRK2RCKW and a full-length inactive LRRK2 (fl-LRRK2INACT) monomer revealed that the kinase domain drives LRRK2 activation. The LRR domain and also an ordered LRR- COR linker, wrap around the C-lobe of the kinase domain and sterically block the substrate binding surface in fl-LRRK2INACT. Here we focus on the crosstalk between domains. Our biochemical studies of GTPase and kinase activities of fl-LRRK2 and LRRK2RCKW reveal how mutations influence this crosstalk differently depending on the domain borders investigated. Furthermore, we demonstrate that removing the NtDs leads to altered intramolecular regulation. To further investigate the crosstalk, we used Hydrogen-Deuterium exchange Mass Spectrometry (HDX-MS) to characterize the conformation of LRRK2RCKW   and Gaussian Accelerated Molecular Dynamics (GaMD) to create dynamic portraits of fl-LRRK2 and LRRK2RCKW. These models allowed us to investigate the dynamic changes in wild type and mutant LRRK2s. Our data show that the a3ROC helix, the Switch II motif in the ROC domain, and the LRR-ROC linker play crucial roles in mediating local and global conformational changes. We demonstrate how these regions are affected by other domains in fl-LRRK2 and LRRK2RCKW and show how unleashing of the NtDs as well as PD mutations lead to changes in conformation and dynamics of the ROC and kinase domains which ultimately impact kinase and GTPase activities. These allosteric sites are potential therapeutic targets., (Copyright 2023 The Author(s).)

Background: Statins are lipid-lowering medications that work by blocking rate-limiting enzyme in cholesterol formation. In patients with Chronic periodontitis (CP) and Diabetes mellitus (DM), subgingival delivery of simvastatin (SMV) and rosuvastatin (RSV) have demonstrated to have bone-stimulatory and anti-inflammatory properties. The current study intended to assess and compare the efficacy of sub-gingivally delivered SMV gel and RSV gel as an adjunctive medication to scaling and root planing (SRP) in the management of intrabony defects in CP patients with type 2 DM., Methods: 30 patients with CP and type 2 DM were classified into three treatment groups - SRP + placebo, SRP +1.2% SMV and SRP +1.2% RSV. Clinical parameters: site-specific plaque index, modified sulcus bleeding index (mSBI), pocket probing depth (PPD), and relative attachment level (RAL) were documented at baseline, 3 and 6 months and radiographic parameter: intrabony defect depth (IBD) at baseline and 6 months post-treatment., Results: - LDD of 1.2% SMV and 1.2% RSV demonstrated greater clinical and radiographic improvement than placebo, the improvement being statistically significant for PI, mSBI, and PPD for 1.2% SMV and statistically significant for all clinical and radiological parameters for the 1.2% RSV. 1.2% RSV demonstrated greater IBD fill and RAL gain than 1.2% SMV., Conclusion: - Localized sub-gingival delivery of statins was beneficial in the treatment intrabony defects in patients with CP and well-controlled type 2 DM. IBD fill and RAL gain were higher with 1.2% RSV than with 1.2% SMV., Competing Interests: The authors affirm that there are no conflicts of interest in relation to the current study., (© 2023 The Authors.)

Aims and Objectives: Oral submucous fibrosis is one of the common oral potentially malignant disorders that can result in severe morbidity. Due to its widespread involvement in the oral cavity and high risk of malignant transformation, the diagnosis and treatment of this disease at an early stage is essential to prevent further complications. This research was carried out to review various classification systems of oral submucous fibrosis documented in the literature to date, including their benefits and drawbacks, thus focusing on a need to discover some reliable classification systems., Materials and Methods: An electronic search of the published English literature was performed without publication year limitation in PubMed/Medline, Science Direct, Web of Science, Google Scholar, and Scopus databases using keywords like ('Oral submucous fibrosis' OR 'Oral submucous fibroses'), AND ('Classification' OR 'Grade' OR 'Stage'), AND ('Clinical', OR/ AND 'Histological', OR/AND 'Functional') following PRISMA guidelines. A manual search of all related Dental and Medical journals was also performed. We also checked the reference lists of the relevant articles for any other possible information on the subject., Results: The search strategy revealed 31 relevant articles and it could be appreciated that oral submucous fibrosis has been classified in seven different ways. Each system is enclosed with its own limitations and benefits., Conclusion: From this research, it can be concluded that despite the existence of several classification systems for oral submucous fibrosis, at present, no classification scheme is considered to be reliable that could help in the accurate assessment of the progression of the disease and classifying oral submucous fibrosis still remains a challenging task for clinicians, surgeons, and pathologists. We have postulated a proposed new classification system based on our literature research, but still robust research is needed in this aspect., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of International Society of Preventive and Community Dentistry.)

The ubiquitin-like protein Hub1/UBL-5 associates with proteins non-covalently. Hub1 promotes alternative splicing and splicing of precursor mRNAs with weak introns in yeast and mammalian cells; however, its splicing function has remained elusive in multicellular organisms. Here, we demonstrate the splicing function of Hub1/UBL-5 in the free-living nematode Caenorhabditis elegans. Hub1/UBL-5 binds to the HIND-containing splicing factors Snu66/SART-1 and PRP-38 and associates with other spliceosomal proteins. C. elegans hub1/ubl-5 mutants die at the Larval 3 stage and show splicing defects for selected targets, similar to the mutants in yeast and mammalian cells. UBL-5 complemented growth and splicing defects in Schizosaccharomyces pombe hub1 mutants, confirming its functional conservation. Thus, UBL-5 is important for C. elegans development and plays a conserved pre-mRNA splicing function., (© 2022 Federation of European Biochemical Societies.)

Significant research revealed the preocular tear film composition and regulations that remain vital for maintaining Ocular surface functional integrity. Inflammation triggered by many factors is the hallmark of Ocular surface disorders or dry eyes syndrome (DES). The tear deficiencies may lead to ocular surface desiccation, corneal ulceration and/or perforation, higher rates of infectious disease, and the risk of severe visual impairment and blindness. Clinical management remains largely supportive, palliative, and frequent, lifelong use of different lubricating agents. However, few advancements such as punctal plugs, non-steroidal anti-inflammatory drugs, and salivary gland autografts are of limited use. Cell-based therapies, tissue engineering, and regenerative medicine, have recently evolved as long-term cures for many diseases, including ophthalmic diseases. The present article focuses on the different regenerative medicine and reconstruction/bioengineered lacrimal gland formation strategies reported so far, along with their limiting factors and feasibility as an effective cure in future., Competing Interests: Author VS reports grants from SERB during the study: as generated by ICMJE.org. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Singh, Sharma, Vaksh and Chandra.)

Background: Acute pancreatitis (AP) during pregnancy is a rare presentation with an estimated incidence of 1 case per 1000 to 10,000 pregnancies. Severe epigastric and abdominal pain is the earliest and the most common symptom of AP, and adequate pain relief is an integral part of patient management. The aim of our study was to investigate the different pain relief modalities that are used in pregnant women with AP and the efficacy of each method used, in terms of better pain relief and maternal-fetal outcomes., Methods: This was a retrospective observational study over a period of 6 years conducted at a tertiary care hospital. Pregnant women with clinical and biochemical diagnoses of acute pancreatitis were included in the study. Patient's history and clinical and biochemical data were collected from the medical records of the hospital., Results: A total of 12 patients were included in the study, 5 out of 12 patients had gall stones associated with AP, 2 patients had hypertriglyceridemia, and 1 each had preeclampsia and eclampsia. Epidural analgesia at the level of L1-L2 spinal level showed a reduction of VAS scores from 8 or 9 to 1 or 2, indicating excellent pain as compared to t intravenous (i/v) infusion of fentanyl or i/v boluses of injection tramadol, in whom VAS was never reduced below 3. With satisfactory results, labour analgesia and anesthesia for caesarean section was provided via the same catheter in 2 and 3 patients, respectively. Maternal and fetal outcomes were comparable in all the patients., Conclusion: AP in pregnancy, when diagnosed early and managed accordingly, leads to better maternal and fetal outcomes. Epidural analgesia was better than intravenous analgesia in terms of pain management and better recovery of acute pancreatitis patients. In these patients, labour analgesia and anesthesia for caesarean section can be provided through the same catheter, making it a potential novel modality in the treatment of acute pancreatitis in pregnancy., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Sandeepika Dogra et al.)

Tuberculosis (TB) is one of the most widely prevalent infectious diseases that cause significant mortality. Bacillus Calmette-Guérin (BCG), the current TB vaccine used in clinics, shows variable efficacy and has safety concerns for immunocompromised patients. There is a need to develop new and more effective TB vaccines. Outer membrane vesicles (OMVs) are vesicles released by Mycobacteria that contain several lipids and membrane proteins and act as a good source of antigens to prime immune response. However, the use of OMVs as vaccines has been hampered by their heterogeneous size and low stability. Here we report that mycobacterial OMVs can be stabilized by coating over uniform-sized 50 nm gold nanoparticles. The OMV-coated gold nanoparticles (OMV-AuNP) show enhanced uptake and activation of macrophages and dendritic cells. Proteinase K and TLR inhibitor studies demonstrated that the enhanced activation was attributed to proteins present on OMVs and was mediated primarily by TLR2 and TLR4. Mass spectrometry analysis revealed several potential membrane proteins that were common in both free OMVs and OMV-AuNP. Such strategies may open up new avenues and the utilization of novel antigens for developing TB vaccines., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: A paucity of data exists on the role of the interview day in programs and applicants' final rank list. The objective of our study was to investigate the impact interview day has on our programs and our interviewees' final rank list., Methods: For the 2020 appointment year, our program used an Electronic Residency Application System Application Scoring Tool and Interview Scoring Tool to generate the preliminary rank list for our pulmonary and critical care fellowship applicants. The final rank list was decided after interviewers' discussion during the program's rank list meeting. We aimed to correlate the preliminary and final lists. We also surveyed applicants on the importance of interview day in generating their rank list., Results: The final and the preliminary rank lists were strongly correlated (r s (47) = 0.87, P < 0.001). There was a stronger correlation between the final rank and the rank based on the application score (r s (47) = 0.84, P < 0.001) than the rank based on the interview score (r s (47) = 0.64, P < 0.001). For the postinterview survey, 48 applicants were surveyed-20 replied with a response rate of 42% and 18 respondents (90%) rated the interview experience as important or very important in their rank list decisions., Conclusions: The programs rank list correlated more with the candidates' written application than their interview day performance; however, interview experience greatly influenced the applicants' rank lists. In the coronavirus disease 2019 pandemic, in which all interviews are virtual, programs should make diligent efforts to construct virtual interview days, given their importance to applicants in generating their final rank list for the match.

Present study identified WM (T1) and DCH-177(T2) as cadmium (Cd) tolerant and GCH2 (S1) and GCH4 (S2) as Cd-sensitive genotypes of castor. Cd treatment (500 μM) led to a significant decline in leaf and root biomass, photosynthetic rate (Pn), stomatal conductance (C), transpiration rate (E), water use efficiency (WUE), photosynthetic pigments content, and altered chlorophyll fluorescence in S1 and S2 genotypes but no significant changes were detected in the T1 and T2 genotypes. The content of H 2 O 2 and malondialdehyde (MDA; stable end product of lipid peroxidation) increased significantly in S1 and S2 castor plants treated with 500 μM Cd, whereas no significant alteration was observed in T1 and T2 in comparison to their respective controls. In general, Cd tolerance is associated with its reduced accumulation. However, no significant difference in Cd accumulation in roots and leaves of S1 genotype was observed compared to T1 genotype. Significant enhancement in the concentration of redox-active metal copper (Cu) was observed in roots and leaves of 500 μM Cd-treated S1 plants but not in T1 plants. Overall, our results suggest that enhanced content of Cu, H 2 O 2 , and MDA and reduced photosynthetic parameters might be the cause of Cd sensitivity observed in the S1 genotype., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Inhalable microparticle-based drug delivery platforms are being investigated extensively for Tuberculosis (TB) treatment as they offer efficient deposition in lungs and improved pharmacokinetics of the encapsulated cargo. However, the effect of physical parameters of microcarriers on interaction with Mycobacterium tuberculosis (Mtb) infected mammalian cells is underexplored. In this study, we report that Mtb-infected macrophages are highly phagocytic and microparticle surface charge plays a major role in particle internalization by infected cells. Microparticles of different sizes (0.5-2 μm) were internalized in large numbers by Mtb-infected THP-1 macrophages and murine primary Bone Marrow Derived Macrophages in vitro. Drastic improvement in particle uptake was observed with cationic particles in vitro and in mice lungs. Rapid uptake of rifampicin-loaded cationic microparticles allowed high intracellular accumulation of the drug and led to enhanced anti-bacterial function when compared to non-modified rifampicin-loaded microparticles. Cytocompatibility assay and histological analysis in vivo confirmed that the formulations were safe and did not elicit any adverse reaction. Additionally, pulmonary delivery of cationic particles in mice resulted in two-fold higher uptake in resident alveolar macrophages compared to non-modified particles. This study provides a framework for future design of drug carriers to improve delivery of anti-TB drugs inside Mtb-infected cells., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Anthropogenic activities, geological processes, and biogenic sources have led to the enhanced concentration of arsenic (As), a toxic metalloid in water and soil. Non-edible, economically important plants can be employed for safe As phytoremediation in addition to generating extra income. However, these plants may get affected by stressful local environmental conditions. Native plant species are adapted to local environmental conditions and hence overcome this problem. Native non-edible economic plant species which show high As tolerance and accumulation are promising candidate for safe, efficient, and economically beneficial phytoremediation of As-contaminated sites. The current review discusses the potential of native economic plant species that can be used in As phytoremediation programme. However, since their phytoremediation potential is moderate, possible strategies for increasing As  olerance and accumulation, especially genetic modification, have been discussed in detail. Knowledge gained from the review can be used for the development of As tolerance and accumulation in non-edible economic native plants., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Intracellular pathogens reside in specialised compartments within the host cells restricting the access of antibiotics. Insufficient intracellular delivery of antibiotics along with several other resistance mechanisms weaken the efficacy of current therapies. An alternative to antibiotic therapy could be bacteriophage (phage) therapy. Although phage therapy has been in practice for a century against various bacterial infections, the efficacy of phages against intracellular bacteria is still being explored. In this review, we will discuss the advancement and challenges in phage therapy, particularly against intracellular bacterial pathogens. Finally, we will highlight the uptake mechanisms and approaches to overcome the challenges to phage therapy against intracellular bacteria.

Arsenic (As) is a toxic environmental pollutant. Growing Ricinus communis (castor) on As-contaminated land has the advantage that in addition to revegetation of contaminated land, it can produce bioenergy. To date, As tolerance mechanisms of this plant are not fully understood. In our previous study, we screened tolerant and sensitive genotypes of castor and reported higher total As concentration, enhanced reactive oxygen species (ROS) generation, and oxidative stress in sensitive genotypes of castor GCH 2 and GCH 4 in comparison to tolerant genotypes WM and DCH 177. In the present study, we compared the activity, isoenzyme profile, and gene expression of ROS-scavenging enzymes, proline content, and expression of nicotianamine synthase genes (RcNAS1, RcNAS2, and RcNAS3) in As-tolerant and As-sensitive genotypes of castor. SOD and GPX activity increased significantly in roots of tolerant genotype WM but remained the same or decreased in sensitive genotype GCH 2 and GCH 4 at 200 μM arsenate [As(V)] treatment indicating their important role in As tolerance in castor. CAT activity and proline content increased in sensitive genotypes but remained the same in tolerant genotypes due to As(V) treatment. APX activity showed no significant change in roots and leaves of both tolerant and sensitive genotypes. NAS genes (RcNAS1, RcNAS2, and RcNAS3) encode enzymes that catalyze trimerization of S-adenosylmethionine to form nicotianamine and are critical for metal chelation and heavy metal tolerance. Differential responses of RcNAS1, RcNAS2, and RcNAS3 genes in WM and GCH 2 due to As(V) treatment suggest their role in As(V) tolerance.

Objective: We sought to evaluate the impact of pulmonary embolism (PE) response teams (PERTs) on all consecutive patients with PE., Background: Multidisciplinary PERTs have been promoted for the management and treatment of (PE); however, the impact of PERTs on clinical outcomes has not been prospectively evaluated., Methods: We prospectively studied 220 patients with computed tomography (CT)-confirmed PE between January, 2019 and August, 2019. Baseline characteristics, as well as medical, interventional, and operational care, were captured. The total population was divided into 2 groups, ie, those with PERT activation and those without PERT activation. PERT activation was left at the discretion of the primary team. Our primary outcome was 90-day composite endpoint (rate of readmission, major bleeds, and mortality). Using 2:1 propensity-matched and multivariable-adjusted Cox proportional hazard analyses, we examined the impact of PERT activation on primary outcome, treatment approach, and length of stay., Results: Of the total 220 patients, PERT was activated in 47 (21.4%). The PERT cohort, as compared with the non-PERT cohort, was more likely to present with dyspnea, syncope, lower systolic blood pressure, higher heart rate, higher respiratory rate, lower oxygen saturation, higher troponin levels, and higher right ventricular to left ventricular ratio. PERT activation was associated with increased use of advanced therapies (36.2% vs 1.2%; P<.001) and catheter-directed inventions (25.5% vs 0.6%; P<.001). In multivariable-adjusted analysis of propensity-matched cohorts, PERT activation was associated with lower 90-day outcomes (hazard ratio, 0.40; 95% confidence interval, 0.21-0.75; P<.01)., Conclusion: At our institution, PERT had a clinically significant impact on therapeutic strategies and 90-day outcomes in patients with PE.

Purpose: To evaluate the long-term safety of vascular endothelial growth factor (VEGF) suppression with sustained aflibercept expression after a single intravitreal injection (IVI) of ADVM-022, an anti-VEGF gene therapy, in non-human primates (NHPs)., Methods: Non-human primates received bilateral IVI of ADVM-022, a gene therapy vector encoding aflibercept, a standard of care for the treatment of VEGF-based retinal disease. Aflibercept levels from ocular fluids and tissues were measured. Ocular inflammation was assessed by slit lamp biomicroscopy and fundoscopy. The integrity of the retinal structure was analyzed by optical coherence tomography and blue light fundus autofluorescence and electroretinography was performed to determine retinal function. Histologic evaluation of the retina was performed at the longest time point measured (2.5 years after injection)., Results: Sustained expression of aflibercept was noted out to the last time point evaluated. Mild to moderate inflammatory responses were observed, which trended toward spontaneous resolution without anti-inflammatory treatment. No abnormalities in retinal structure or function were observed, as measured by optical coherence tomography and electroretinography, respectively. RPE integrity was maintained throughout the study; no histologic abnormalities were observed 2.5 years after ADVM-022 IVI., Conclusions: In non-human primates, long-term, sustained aflibercept expression and the resulting continuous VEGF suppression by a single IVI of ADVM-022, appears to be safe, with no measurable adverse effects on normal retinal structure and function evaluated out to 2.5 years., Translational Relevance: Together with the results from previous ADVM-022 preclinical studies, these data support the evaluation of this gene therapy candidate in clinical trials as a potential durable treatment for various VEGF-mediated ophthalmic disorders., Competing Interests: Disclosure: S. Kiss, Adverum (C, R), Novartis (C, F), Optos (C, F), Genentech/Roche (C, F), Regeneron (C, F), Regenx Bio (R), Fortress Bio (R); K. Oresic Bender (E); R.N. Grishanin (E); K.M. Hanna (E); J.D. Nieves (E); P. Sharma (E); A.T. Nguyen (E); R.J. Rosario, None; J.S. Greengard (E); C.M. Gelfman (E); M. Gasmi (S), (Copyright 2021 The Authors.)

Background: The use of scaling, root planing, antimicrobials, or antibiotics in the treatment of Chronic Periodontitis have proven beneficial in the past. The reduction in inflammatory markers and significant resolve in the clinical signs and symptoms and microbial loads evinced by a number of studies are a clear corroboration of the fact, but certain restraints utilizing these methods call for more effective ways of treating the disease. Later, lasers or photodynamic dyes used with the lasers like methylene blue or toluidine blue O have also not proven much efficacy and need further research. Hence the present pilot study is a step forward in this direction as it helps analyse the microbiological and clinical effects of indocyanine green antimicrobial photodynamic therapy an as adjunct to the non-surgical periodontal therapy in treating chronic periodontitis patients., Materials and Methods: 30 patients diagnosed with generalized chronic periodontitis were treated with scaling and root planing alone - control sites; and indocyanine green antimicrobial photodynamic therapy in addition to scaling and root planing - experimental sites. 810 ​nm low level Gallium Aluminium Arsenide diode laser was used to activate the dye in the periodontal pockets of the experimental sites. Clinical parameters i.e. gingival index, plaque index, sulcus bleeding index, probing pocket depth and relative attachment level; and microbiological parameter i.e. the total viable anaerobic count were recorded at the inception and at 3- and 6-months post therapy., Results: Experimental sites showed significantly greater amelioration in all inquired clinical parameters and microbiological parameter at the end of 3- and 6-months of therapy., Conclusion: While the gold standard scaling and root planing remains, clinicians may also contemplate using the indocyanine green mediated antimicrobial photodynamic therapy as an adjunct to it. Also, it is a safer, cost effective, less arduous, and patient friendly means of treating the disease., (© 2020 Craniofacial Research Foundation. Published by Elsevier B.V. All rights reserved.)

We demonstrate the novel spiroannulation of exo -imines with 1,3-dipoles, for the first time, leading to 3D spirocycles with a secondary amine (NH) in the spiro-ring. The synthetic method described herein allows access to these previously unexplored heterospirocyclic cores that have application in the discovery of functional molecules for medicinal and materials science. This was demonstrated by discovering an unprecedented class of heterospirocycles with antimalarial activity against the human protozoan P. falciparum .

Antibiotic resistance continues to be a major global health risk with an increase in multi-drug resistant infections seen across nearly all bacterial diseases. Mycobacterial infections such as Tuberculosis (TB) and Non-Tuberculosis infections have seen a significant increase in the incidence of multi-drug resistant and extensively drug-resistant infections. With this increase in drug-resistant Mycobacteria, mycobacteriophage therapy offers a promising alternative. However, a comprehensive study on the infection dynamics of mycobacteriophage against their host bacteria and the evolution of bacteriophage (phage) resistance in the bacteria remains elusive. We aim to study the infection dynamics of a phage cocktail against Mycobacteria under various pathophysiological conditions such as low pH, low growth rate and hypoxia. We show that mycobacteriophages are effective against M. smegmatis under various conditions and the phage cocktail prevents emergence of resistance for long durations. Although the phages are able to amplify after infection, the initial multiplicity of infection plays an important role in reducing the bacterial growth and prolonging efficacy. Mycobacteriophages are effective against antibiotic-resistant strains of Mycobacterium and show synergy with antibiotics such as rifampicin and isoniazid. Finally, we also show that mycobacteriophages are efficient against M. tuberculosis both under lag and log phase for several weeks. These findings have important implications for developing phage therapy for Mycobacterium., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Kalapala, Sharma and Agarwal.)

Protein kinases and GTPases are the two major molecular switches that regulate much of biology, and both of these domains are embedded within the large multi-domain Leucine-Rich Repeat Kinase 2 (LRRK2). Mutations in LRRK2 are the most common cause of familial Parkinson's disease (PD) and are also implicated in Crohn's disease. The recent Cryo-Electron Microscopy (Cryo-EM) structure of the four C-terminal domains [ROC COR KIN WD40 (RCKW)] of LRRK2 includes both of the catalytic domains. Although the important allosteric N-terminal domains are missing in the Cryo-EM structure this structure allows us to not only explore the conserved features of the kinase domain, which is trapped in an inactive and open conformation but also to observe the direct allosteric cross-talk between the two domains. To define the unique features of the kinase domain and to better understand the dynamic switch mechanism that allows LRRK2 to toggle between its inactive and active conformations, we have compared the LRRK2 kinase domain to Src, BRaf, and PKA. We also compare and contrast the two canonical glycine-rich loop motifs in LRRK2 that anchor the nucleotide: the G-Loop in protein kinases that anchors ATP and the P-Loop in GTPases that anchors GTP. The RCKW structure also provides a template for the cross-talk between the kinase and GTPase domains and brings new mechanistic insights into the physiological function of LRRK2 and how the kinase domain, along with key phosphorylation sites, can serve as an allosteric hub for mediating conformational changes., (Copyright © 2020 Taylor, Kaila-Sharma, Weng, Aoto, Schmidt, Knapp, Mathea and Herberg.)

Different doses of gamma Irradiation (0 Gy, 10 Gy, 60 Gy, 100 Gy and 200 Gy) were evaluated as potential treatment to extend the storage period and maintain the quality attributes of onion bulbs (cv. Punjab Noraya ) at ambient temperature for a period of 144 days. It was observed that storage parameters such as physiological loss in weight, sprouting percentage, rotting percentage and quality traits like total soluble solids, firmness, color parameters, ascorbic acid and pyruvic acid varied significantly ( p  < 0.05) during storage period with respect to doses of irradiation. No rotting and sprouting were observed upto 24 days and 84 days, respectively in both gamma irradiated and un-irradiated bulbs. At 5 months of storage, the physiological loss in weight varied from 28.5 to 63.6% in all treatments. Physiological weight loss and rotting percentage were higher in the untreated (control) as well as bulbs radiated @ 10 Gy and 200 Gy. Firmness was better retained in the bulbs irradiated with gamma rays @ 120 Gy bulbs upto 84 days of storage. However, no clear-cut pattern for colour changes (L, a, b values) was observed with respect to the irradiation doses. TSS in bulbs decreased upto 36 days of storage and thereafter increased upto 48th day of storage irrespective of the dose of gamma irradiation. Ascorbic acid content of bulbs decreases significantly in all the irradiation treatments during storage but pyruvic acid initially increased, then decreased and again increased at the end of the storage period in un-irradiated and irradiated treatments. It is concluded that onion bulbs irradiated with gamma rays @ 120 Gy resulted in minimum loss in weight, rotting and sprouting while maintained best quality for 3 months of storage at ambient storage conditions., (© Association of Food Scientists & Technologists (India) 2020.)

Background: One rarely finds Indian women talking about their sexuality like this due to sex taboo in our society. This does not mean that sexual dysfunction is uncommon in Indian women. Female sexual dysfunction is widely prevalent., Aim and Objective: Indian women seek less assistance for them, despite undergoing physical and marital problems. Data of prevalence of such problems was collected to understand the scope of these problems and how Indian women deal with it. The objective was to understand prevalence of sexual dysfunction in women attending Gynaecology OPD and their perception about sex., Material and Methods: A questionnaire based prevalence study comprising of 520 patients from January, 2018 to June, 2018 was done. The questionnaire was designed on the basis of prior used ones in various studies and modified according to current patient scenario at the tertiary centre where study was conducted., Results: The data collected showed that sexual problems are not reported even when they were widely prevalent. 64% of women can't talk regarding this to their partners too. 82% patients had some sort of sexual problem. Only 18% patients said that they have no sexual problem and were satisfied with their sexual life. However, none of them consulted or took any form of assistance from any medical personnel., Conclusion: Indian women are reluctant and shy to discuss sexual problem unlike westerners who are more open and demanding when it comes to their needs. Gynecologists need to discuss with the patients about their sexuality and pertaining issues with utmost warmth, care and respect. They need to pull out the problem from within their patients and handle it effectively., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Indian Journal of Community Medicine.)

Objectives: Apigenin is the most common bioflavonoid known to be biologically active after systemic administration and show multiple pharmacological effects. The present study was designed to explore the role of apigenin in pentylenetetrazole (PTZ) kindling associated cognitive and behavioural impairments in the mouse model. Methods: The animals were kindled by injecting a sub-convulsive dose of PTZ (35 mg/kg) on every alternate day, followed by 20 days treatment with apigenin at two different doses (10 and 20 mg/kg). Seizure severity was assessed on every 5th, 10th, 15th, and 20th day during apigenin treatment after a PTZ injection, followed by analysis of cognitive and behavioural functions. Results: Apigenin treatment displayed insignificant effect on seizure severity in kindled mice at both the tested doses, in comparison to control. However, the treatment showed marked increase in per cent spontaneous alterations and decline in the anxiety index in T-maze and elevated plus maze tests, respectively. Apigenin-treated groups showed significant decrease in immobility period in both forced swim and tail suspension tests, without any change in the total locomotor activity in the open field test. Furthermore, increase in the hippocampus protein expression of brain-derived neurotrophic factor (BDNF), cAMP response element binding protein (CREB), and phosphorylated CREB, with increased serotonin level were also observed in the treated animals. Discussion: The results of the present study showed that apigenin treatment prevents cognitive deficit and reverses behaviour impairments, without altering seizures severity in kindled mice. The observed effects can be attributed to CREB-BDNF upregulation in the hippocampus.

It is generally believed that due to evolutionary differences and adaptation to tropical conditions, Indian native cattle has superior heat tolerant ability than Bos taurus cattle. In the present study, 3'-UTR of two most important heat responsive genes i.e., heat shock protein 70.1 (HSP70.1) and heat shock factor- 1 (HSF-1) were sequence characterized in different breeds of Indian native cattle to identify the variations and miRNA binding sites. In addition, the impact of heat stress was assessed in a total of 57 PBMCs samples of native Sahiwal cows (Bos indicus), exotic Holstein cows (Bos taurus) and Murrah buffaloes (Bubalus bubalis) using various cellular parameters like cell viability, cytotoxicity and apoptosis. Further, expression profile of 12 heat responsive miRNAs were also evaluated in unstressed and stressed PBMCs to understand post transcriptional changes in native cows, exotic cows and Murrah buffaloes. The sequence data showed 3'-UTR of HSP70.1 gene of Indian cattle to be exactly similar to Bos taurus with no miRNA binding site. Whereas, sequencing of 3'-UTR of HSF-1 gene revealed 3 SNPs at positions G1762T; C1811T and C1983T with 7 well conserved miRNA binding sites. The impact of heat stress on various cellular parameters in terms of cell viability, cytotoxicity and apoptosis was highest in PBMCs of Holstein cows followed by Murrah buffaloes and Sahiwal cows. Further, in contrast to Holstein Frisian cows and Murrah buffaloes, the expression pattern of 12 heat responsive miRNAs, in heat stressed PBMCs of Sahiwal cows were quite distinct. There was a significant (p < 0.05) induction in expression of most of the miRNAs after heat stress in PBMCs of Sahiwal cows followed by a rapid decline. The distinct cellular response and pattern of miRNA expression across cattle types and buffaloes might be influencing their PBMCs tolerance level to heat stress.

Effect of arsenate [As(V)] on biomass, photosynthetic rate, stomatal conductance, transpiration, oxidative stress, accumulation of As, Fe, Zn, Cu and Mn and expression of NRAMP genes was investigated in As(V) tolerant and sensitive genotypes of bioenergy crop Ricinus communis. As(V) treatments (100 and 200 μM) led to significant reduction in root and leaf biomass, photosynthetic rate, stomatal conductance and transpiration in GCH 2 and GCH 4 genotypes but no significant change or increase was observed in WM and DCH 177 genotypes. No significant difference was observed in hydrogen peroxide content and lipid peroxidation in As(V)-treated tolerant genotypes compared to control, whereas these parameters enhanced significantly in As(V)-treated sensitive genotypes. GCH 2 accumulated around two times As in leaves and showed significant reduction in concentration of Zn and Mn in the leaves and roots due to 200 μM As(V) treatment compared to WM. NRAMP genes are critical for uptake and distribution of essential divalent metal cations, photosynthesis and controlled production of reactive oxygen species in plants. RcNRAMP2, RcNRAMP3 and RcNRAMP5 genes showed differential expression in response to 200 μM As(V) in GCH 2 and WM suggesting that NRAMP genes are associated with differential responses of WM and GCH 2 genotypes to As(V) stress.

Inhibition of vascular endothelial growth factor, a key contributor to the choroidal neovascularization associated with wet age-related macular degeneration, is the mode of action of several approved therapies, including aflibercept, which requires frequent intravitreal injections to provide clinical benefit. Lack of compliance with the dosing schedule may result in recurrence of active wet macular degeneration, leading to irreversible vision impairment. Gene therapy providing sustained anti-vascular endothelial growth factor levels in the retina following a single injection could drastically reduce the treatment burden and improve visual outcomes. ADVM-022, an adeno-associated virus vector encoding aflibercept, is optimized for intravitreal delivery and strong protein expression. Here, we report the long-term expression and efficacy of ADVM-022-derived aflibercept in a laser-induced choroidal neovascularization model in non-human primates. Intravitreal administration of ADVM-022 was well tolerated and resulted in sustained aflibercept levels. In addition, ADVM-022 administration 13 months before lasering prevented the occurrence of clinically relevant choroidal neovascularization lesions, similar to animals that received a bolus of intravitreal aflibercept (standard of care) at the time of lesioning. These results demonstrate that a single intravitreal administration of ADVM-022 may provide a safe and effective long-term treatment option for wet macular degeneration and may ultimately improve patients' visual outcomes., (Copyright © 2018 ADVERUM BIOTECHNOLOGIES, INC. Published by Elsevier Inc. All rights reserved.)

cAMP response element binding protein (CREB) is a key transcriptional regulator that regulates the transcription of genes related with neuronal differentiation, synaptic plasticity, learning and memory. Brain derived neurotrophic factor (BDNF), is a CREB dependent gene which plays a pivotal role in the pathogenesis of epilepsy and central comorbid conditions associated with epilepsy. However, the beneficial or detrimental consequences of CREB-BDNF activation on the induction and/or progression of seizures depend specifically on the region of brain involved and the time of activation. The bioactive molecules that alter the activity of CREB in a way to have specialized effects in different brain regions and neural circuits involved could potentially be utilized for therapeutic purposes. Flavonoids are the polyphenolic compounds which lead to phosphorylation of CREB in the hippocampus, followed by increase in extracellular signal regulated kinase (ERK) and BDNF. Several members of flavonoid family have also showed suppression of epileptic seizures via interaction with CREB/BDNF pathway. Moreover, epilepsy is often accompanied by a number of behavioural and psychological comorbid conditions that further gets aggravated by the use of conventional antiepileptic drug therapy. Multiple studies have also supported the beneficial effects of flavonoids in cognitive and memory impairments by upregulation of CREB-BDNF pathway. The current review is an attempt to collate the available preclinical and clinical studies to establish the therapeutic potential of various dietary flavonoids in comprehensive management of epilepsy with relation to CREB-BDNF pathway., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: The placement of composite in teeth is not an easy task and it poses many challenges. Microleakage is one of the factors that affects the success of any composite restoration. It influences the longevity of dental restorations. The present study was aimed to evaluate and compare microleakage of two restorative composites resins in class II cavities using confocal laser scanning microscopy (CLSM)., Materials and Methods: This was an in vitro study, which included 20 permanent mandibular first molar. On each tooth, 40 class II cavities were prepared with a carbide bur. The teeth were then randomly divided into two groups of 10 each. Group I included teeth in which SonicFill Bulk Fill composite was used. Group II included teeth in which Tetric EvoCeram Bulk Fill composite was used. The microleakage was measured using confocal microscopy at 10* magnification in the fluorescent mode by a scoring system., Results: Estimation was done at cervical and occlusal levels, wherein group I included 10 teeth which were restored with SonicFill Bulk Fill composite and group II included 10 teeth which were restored with Tetric EvoCeram Bulk Fill composite. Microleakage was quantified on scoring basis, which was consecutively based on the dye penetration at different levels. Data thus obtained statistically revealed that microleakage was comparatively more in group II as compared with group I. In addition, it was somewhat similar on both cervical as well as occlusal regions. The difference was significant (p = 0.05). Comparison was also done at cervical and occlusal levels using Wilcoxon signed-rank test, which showed significant levels of differences (p > 0.05)., Conclusion: There is more microleakage in Tetric EvoCeram Bulk Fill composite as compared with SonicFill Bulk Fill composite., Clinical Significance: No material seems to totally eliminate microleakage in class II situations with gingival margin ended in dentine. However, CLSM is a useful tool in microleakage evaluation that could be used successfully to estimate the severity of microbial penetrations and material of choice as well.

Communications across chemical synapses are primarily mediated by neurotransmitters and their postsynaptic receptors. There are diverse molecular systems to localize and regulate the receptors at the synapse. Here, we identify HPO-30, a member of the claudin superfamily of membrane proteins, as a positive regulator for synaptic localization of levamisole-dependent AChRs (LAChRs) at the Caenorhabditis elegans neuromuscular junction (NMJ). The HPO-30 protein localizes at the NMJ and shows genetic and physical association with the LAChR subunits LEV-8, UNC-29, and UNC-38. Using genetic and electrophysiological assays in the hermaphrodite C. elegans , we demonstrate that HPO-30 functions through Neuroligin at the NMJ to maintain postsynaptic LAChR levels at the synapse. Together, this work suggests a novel function for a tight junction protein in maintaining normal receptor levels at the NMJ. SIGNIFICANCE STATEMENT Claudins are a large superfamily of membrane proteins. Their role in maintaining the functional integrity of tight junctions has been widely explored. Our experiments suggest a critical role for the claudin-like protein, HPO-30, in maintaining synaptic levamisole-dependent AChR (LAChR) levels. LAChRs contribute to <20% of the acetylcholine-mediated conductance in adult Caenorhabditis elegans ; however, they play a significant functional role in worm locomotion. This study provides a new perspective in the study of LAChR physiology., (Copyright © 2018 Sharma, Li et al.)

A convenient method for the synthesis of 1,2,4-triazol-3-imines through a selective, formal, 1,3-dipolar cycloaddition of organo-cyanamide ions with nitrile imine dipoles is reported. Hydrolysis of the 1,2,4-triazol-3-imines yields the corresponding 1,2,4-triazol-5-ones. A stepwise mechanism, supported by DFT calculations, is invoked to explain the reaction selectivity.

An in vitro spike culture method was optimized to evaluate Fusarium head blight (FHB) resistance in wheat (Triticum aestivum) and used to screen a population of ethyl methane sulfonate treated spike culture-derived variants (SCDV). Of the 134 SCDV evaluated, the disease severity score of 47 of the variants was ≤30%. Single nucleotide polymorphisms (SNP) in the UDP-glucosyltransferase (UGT) genes, TaUGT-2B, TaUGT-3B, and TaUGT-EST, differed between AC Nanda (an FHB-susceptible wheat variety) and Sumai-3 (an FHB-resistant wheat cultivar). SNP at 450 and 1,558 bp from the translation initiation site in TaUGT-2B and TaUGT-3B, respectively were negatively correlated with FHB severity in the SCDV population, whereas the SNP in TaUGT-EST was not associated with FHB severity. Fusarium graminearum strain M7-07-1 induced early expression of TaUGT-2B and TaUGT-3B in FHB-resistant SCDV lines, which were associated with deoxynivalenol accumulation and reduced FHB disease progression. At 8 days after inoculation, deoxynivalenol concentration varied from 767 ppm in FHB-resistant variants to 2,576 ppm in FHB-susceptible variants. The FHB-resistant SCDV identified can be used as new sources of FHB resistance in wheat improvement programs.

Background: Picrorhiza kurroa Royle (Scrophulariaceae) is an important medicinal herb being widely used in variety of ailments., Purpose: The present study was envisaged to evaluate the effects of iridoid glycosides enriched fraction (IGs) from Picrorhiza kurroa rhizome against cyclophosphamide (CP) -induced renal toxicity and peripheral neuropathy., Methods: Mice in different groups were pretreated with 25, 50 and 100 mg/kg; p.o. doses of IGs for 21 days, followed by cyclophosphamide intoxication for consecutive two days. Further, to identify the putative role of PPAR-γ receptors for the protective effect of IGs, an additional group of mice were pretreated with PPAR-γ antagonist BADGE (5 mg/kg; i.p.) followed by IGs (100 mg/kg; p.o.) for 21 days before CP intoxication., Results: IGs pretreatment decreased the hyperalgesic responses toward acetone and heat in acetone drop and tail immersion tests. The abolition of intramyelin odema, cytoplasmic vacuolization and axonal degeneration of sciatic nerve were observed in IGs pretreated mice in a dose-dependent manner. IGs treatment also attenuated the altered serum biochemical markers for renal injury. Furthermore, the treatment prevented renal tubular swelling, granular degeneration and glomerular damage. The levels of IL-1β and TNFα in different group revealed the anti-inflammatory effect of IGs, which was further confirmed by improvement in altered expressions of NF-kB in kidney and sciatic serve. Bax/Bcl-2 expressions and caspase 3/9 activity in renal tissues showed the anti-apoptotic effect of IGs. IGs pretreatment also improved the PPAR-γ expression in the kidney tissues. All the observed protective effects of IGs were suppressed after pretreatment with BADGE., Conclusion: Present study concludes that IGs from Picrorhiza kurroa attenuates CP-induced renal toxicity and peripheral neuropathy via PPAR-γ -mediated pathways., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Ethnopharmacological Relevance: Ginkgo biloba L. (Ginkgoaceae) has been widely used in traditional medicine for variety of neurological conditions particularly behavioral and memory impairments., Aim of the Study: The present study was envisaged to explore the effect of a standardized fraction of Ginkgo biloba leaves (GBbf) in rat model of lithium-pilocarpine induced spontaneous recurrent seizures, and associated behavioral impairments and cognitive deficit., Materials and Methods: Rats showing appearance of spontaneous recurrent seizures following lithium pilocarpine (LiPc)-induced status epilepticus (SE) were treated with different doses of GBbf or vehicle for subsequent 4 weeks. The severity of seizures and aggression in rats were scored following treatment with GBbf. Further, open field, forced swim, novel object recognition and Morris water maze tests were conducted. Histopathological, protein levels and gene expression studies were performed in the isolated brains., Results: Treatment with GBbf reduced seizure severity score and aggression in epileptic animals. Improved spatial cognitive functions and recognition memory, along with reduction in anxiety-like behavior were also observed in the treated animals. Histopathological examination by Nissl staining showed reduction in neuronal damage in the hippocampal pyramidal layer. The dentate gyrus and Cornu Ammonis 3 regions of the hippocampus showed reduction in mossy fiber sprouting. GBbf treatment attenuated ribosomal S6 and pS6 proteins, and hippocampal mTOR, Rps6 and Rps6kb1 mRNA levels., Conclusions: The results of present study concluded that GBbf treatment suppressed lithium-pilocarpine induced spontaneous recurrent seizures severity and incidence with improved cognitive functions, reduced anxiety-like behavior and aggression. The effect was found to be due to inhibition of mTOR pathway hyperactivation linked with recurrent seizures., (Copyright © 2017. Published by Elsevier B.V.)

We present a selection of elegant and diverse biomimetic syntheses of complex natural product dimers. The dimerisation pathways discussed encompass the most prevalent strategies, including: Diels-Alder, Aldol, Mannich, conjugate addition, oxidative, radical and photochemical approaches; each underpinned through rational biosynthetic speculation.

A short synthesis of the revised structure of the marine natural product tridachiahydropyrone is described. A novel biomimetic photochemical electrocyclization was employed to construct the bicyclic carbon framework from an open-chain polyene precursor. The spectroscopic data matched that of the isolated natural product, supporting a revised structure of this complex metabolite.

When seedlings of rice (Oryza sativa L.) cultivar Pant-12 were raised in sand cultures containing 80 and 160 muM Al(3+) in the medium for 5-20 days, a regular increase in Al(3+) uptake with a concomitant decrease in the length of roots as well as shoots was observed. Al(3+) treatment of 160 muM resulted in increased generation of superoxide anion (O(2) (-)) and hydrogen peroxide (H(2)O(2)), elevated amount of malondialdehyde, soluble protein and oxidized glutathione and decline in the concentrations of thiols (-SH) and ascorbic acid. Among antioxidative enzymes, activities of superoxide dismutase (SOD EC 1.15.1.1), guaiacol peroxidase (Guaiacol POX EC 1.11.1.7), ascorbate peroxidase (APX EC 1.11.1.11), monodehydroascorbate reductase (MDHAR EC 1.6.5.4), dehydroascorbate reductase (EC 1.8.5.1) and glutathione reductase (EC 1.6.4.2) increased significantly, whereas the activities of catalase (EC EC 1.11.1.6) and chloroplastic APX declined in 160 muM Al(3+ )stressed seedlings as compared to control seedlings. The results suggest that Al(3+) toxicity is associated with induction of oxidative stress in rice plants and among antioxidative enzymes SOD, Guaiacol POX and cytosolic APX appear to serve as important components of an antioxidative defense mechanism under Al(3+) toxicity. PAGE analysis confirmed the increased activity as well as appearance of new isoenzymes of APX in Al(3+) stressed seedlings. Immunoblot analysis revealed that changes in the activities of APX are due to changes in the amounts of enzyme protein. Similar findings were obtained when the experiments were repeated using another popular rice cv. Malviya-36.