Pharmacogenetics of selective serotonin reuptake inhibitors (SSRI): A serotonin reuptake transporter (SERT)-based approach.

Neuropsychiatric disorders are considered to be the most common cause of disability worldwide. Serotonin and its transporter is a prominent paradigm in mood disorders. Response to selective serotonin reuptake inhibitors (SSRI) is altered due to heterogeneity in the serotonin transporter gene, SLC6A4 (solute carrier family 6 member 4). The reported polymorphisms are found to be in different regions of the transporter gene: promoter region (5-HTTLPR and various single nucleotide polymorphisms within it), intron (STin2), and exon 9 (I425V). The long and short alleles of the 5-HTTLPR gene, which are prevalent among variations, may mediate differential effects. In long allelic variant carriers, an increased response to SSRI and timely recovery is due to increased availability of SERT. Whereas, SERT availability is significantly decreased in short allelic carriers, necessitating a reduction in SSRI dosage due to the increased risk of adverse drug reactions. Thus, pharmacogenetic investigations are required to understand the impact of functional variations on the efficacy and tolerability of SSRI. Identifying the carrier variants may aid in clear-decision making of the treatment regimen, aiding the approach of personalized medication.

Regional and temporal variability of Indian summer monsoon rainfall in relation to El Niño southern oscillation.

The Indian summer monsoon rainfall (ISMR) exhibits significant variability, affecting the food and water security of the densely populated Indian subcontinent. The two dominant spatial modes of ISMR variability are associated with the El Niño Southern Oscillation (ENSO) and the strength of the semi-permanent monsoon trough along with related variability in monsoon depressions, respectively. Although the robust teleconnection between ENSO and ISMR has been well established for several decades, the major drivers leading to the time-varying relationship between ENSO and ISMR patterns across different regions of the country are not well understood. Our analysis shows a consistent increase from a moderate to substantially strong teleconnection strength between ENSO and ISMR from 1901 to 1940. This strengthened relationship remained stable and strong between 1941 and 1980. However, in the recent period from 1981 to 2018 the teleconnection decreased consistently again to a moderate strength. We find that the ENSO-ISMR relationship exhibits distinct regional variability with time-varying relationship over the north, central, and south India. Specifically, the teleconnection displays an increasing relationship for north India, a decreasing relationship for central India and a consistent relationship for south India. Warm SST anomalies over the eastern Pacific Ocean correspond to an overall decrease in the ISMR, while warm SST anomalies over the Indian Ocean corresponds to a decrease in rainfall over the north and increase over the south of India. The central Indian region experienced the most substantial variation in the ENSO-ISMR relationship. This variation corresponds to the variability of the monsoon trough and depressions, strongly influenced by the Pacific Decadal Oscillation and North Atlantic Oscillation, which regulate the relative dominance of the two spatial modes of ISMR. By applying the PCA-Biplot technique, our study highlights the significant impacts of various climate drivers on the two dominant spatial modes of ISMR which account for the evolving nature of the ENSO-ISMR relationship.

Ketone-derived 2,3-dihydroquinazolinones in N-heteroarene C-H alkylation via C-C bond scission under oxidative metal catalysis.

A silver-catalysed oxidative sp2 C-H alkylation of N-heteroarenes with ketone-derived 2,3-dihydroquinazolinones at room temperature is developed. The combination of a metal catalyst and perdisulfate oxidant promotes the rarely explored thermal activation of pre-aromatic 2,3-dihydroquinazolinone to generate an alkyl radical, supported by mechanistic studies. In addition to the broad scope, good functionality tolerance, late stage functionalization of APIs, and synthesis of a novel Papaverine analogue, the utilization of an N-heteroarene C-H bond and ketone as a non-trivial alkyl radical source represents the salient feature of this method.

Breast cancer stage prediction: a computational approach guided by transcriptome analysis.

Breast cancer is the second leading cancer among women in terms of mortality rate. In recent years, its incidence frequency has been continuously rising across the globe. In this context, the new therapeutic strategies to manage the deadly disease attracts tremendous research focus. However, finding new prognostic predictors to refine the selection of therapy for the various stages of breast cancer is an unattempted issue. Aberrant expression of genes at various stages of cancer progression can be studied to identify specific genes that play a critical role in cancer staging. Moreover, while many schemes for subtype prediction in breast cancer have been explored in the literature, stage-wise classification remains a challenge. These observations motivated the proposed two-phased method: stage-specific gene signature selection and stage classification. In the first phase, meta-analysis of gene expression data is conducted to identify stage-wise biomarkers that were then used in the second phase of cancer classification. From the analysis, 118, 12 and 4 genes respectively in stage I, stage II and stage III are determined as potential biomarkers. Pathway enrichment, gene network and literature analysis validate the significance of the identified genes in breast cancer. In this study, machine learning methods were combined with principal component and posterior probability analysis. Such a scheme offers a unique opportunity to build a meaningful model for predicting breast cancer staging. Among the machine learning models compared, Support Vector Machine (SVM) is found to perform the best for the selected datasets with an accuracy of 92.21% during test data evaluation. Perhaps, biomarker identification performed here for stage-specific cancer treatment would be a meaningful step towards predictive medicine. Significantly, the determination of correct cancer stage using the proposed 134 gene signature set can possibly act as potential target for breast cancer therapeutics.

Self-Assembly and Photochemistry of a Pyrene-Methyl Viologen Supramolecular Fiber System.

This paper reports the self-assembly of a donor-acceptor system into nanoscopic structures and the photo processes taking place within these structures. The donor employed is pyrene linked to two ß-cyclodextrin molecules (CD-PY-CD), and adamantane-linked methyl viologen attached to the three arms of mesitylene (Ms-(MV2+-AD)3) is the acceptor. CD-PY-CD and Ms-(MV2+-AD)3 when dissolved in water self-assembled into vesicles, which joined together to give long fibers. The self-assembly was studied using spectroscopic and microscopic techniques. Fluorescence of the pyrene chromophore was quenched within the self-assembled system due to efficient photoinduced electron transfer to methyl viologen. Photoinduced electron transfer within the assembly is confirmed through identification of product radical ions in flash photolysis experiments. Steady-state irradiation of the self-assembled system in an optical bench led to the formation of methyl viologen radical cation, which was stable for a few hours. Longevity of the radical cation was attributed to the fast reaction of pyrene radical cation with adjacent pyrene to give an unstable adduct, which slows down the back electron transfer process.

Repurposing Vorinostat for the Treatment of Disorders Affecting Brain.

Based on the findings in recent years, we summarize the therapeutic potential of vorinostat (VOR), the first approved histone deacetylase (HDAC) inhibitor, in disorders of brain, and strategies to improve drug efficacy and reduce side effects. Scientific evidences provide a strong case for the therapeutic utility of VOR in various disorders affecting brain, including stroke, Alzheimer's disease, frontotemporal dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, X-linked adrenoleukodystrophy, epilepsy, Niemann-Pick type C disease, and neuropsychiatric disorders. Further elucidation of the neuroprotective and neurorestorative properties of VOR using proper clinical study designs could provide momentum towards its clinical application. To improve the therapeutic prospect, concerns on systemic toxicity and off-target actions need to be addressed along with the improvement in formulation and delivery aspects, especially with respect to solubility, permeability, and pharmacokinetic properties. Newer approaches in this regard include poly(ethylene glycol)-b-poly(DL-lactic acid) micelles, VOR-pluronic F127 micelles, encapsulation of iron complexes of VOR into PEGylated liposomes, human serum albumin bound VOR nanomedicine, magnetically guided layer-by-layer assembled nanocarriers, as well as convection-enhanced delivery. Even though targeting specific class or isoform of HDAC is projected as advantageous over pan-HDAC inhibitor like VOR, in terms of adverse effects and efficacy, till clinical validation, the idea is debated. As the VOR treatment-related adverse changes are mostly found reversible, further optimization of the therapeutic strategies with respect to dose, dosage regimen, and formulations of VOR could propel its clinical prospects.

Primary Health-Care Innovations with Superior Allusion to Family Health Centers.

The present case study discusses about the Primary Health Care system of Kerala and the Government's innovative step to promote the Primary Health Centres to Family Health Centres. The case study also deliberates about the FHC working model and its superiority over the current PHCs in the areas of manpower, OP time, lab services, nursing services, social security projects etc. and the transformation of PHCs to a well-functioning PHC, thereby it can become a model for other states.

Photoinduced Electron Transfer in a Self-Assembled Bis(ß-cyclodextrin)-Linked Pyrene/Bis(adamantane)-Linked Methyl Viologen Donor-Acceptor System in Aqueous Solution.

Pyrene linked to two ß-CD (CD = cyclodextrin; PY = pyrene) molecules (CD-PY-CD) and methylviologen (MV2+) linked to two adamantane (AD) groups (AD-MV2+-AD) self-assembled in water to give toroidal nanostructures. Photoprocesses taking place in the femtosecond and nanosecond time ranges within the assembly are reported. Fluorescence of the pyrene chromophore was quenched in the toroid, suggesting very efficient electron transfer. Fast quenching of the pyrene fluorescence with a time constant of 6.85 ns was attributed to photoinduced electron transfer from pyrene to methyl viologen within the toroid assembly. Electron transfer leads to the formation of radical ion products, PY•+ and MV•+, which were identified in the nanosecond transient absorption spectra. Because of the close packing of chromophores, the radical ions undergo fast reactions with chromophores or similar ions in adjacent stacks to give dimeric products. Since the dimeric species are not very stable, the reactions are reversed at longer time scales to generate the radical ions, which then undergo back electron transfer and regenerate the starting materials.

New lanthanide-free self-activated full-color emission phosphor in Y3+ doped Sr3 Bi(VO4 )3 system for white light emitting diode applications.

Commercially used inorganic phosphors heavily depend on lanthanide doped host materials which are becoming more expensive and also their availability is limited due to scarcity. In this regard, a new lanthanide-free self-activated full-color emission phosphor in Y3+ doped Sr3 Bi(VO4 )3 system was developed by the conventional ceramic route. These phosphors crystallize into a hexagonal-type palmierite mineral structure. They exhibit broad excitation bands in the wavelength region of 250-400 nm, owing to the charge transfer transitions from both O2- and Bi6s2 electrons to V5+ . Upon excitation, these phosphors show bright broad emissions in the 400-750 nm wavelength range, peaking around 535 nm, with a large full width half maximum of 160 nm. The Y substitution allows tuning of the emission from yellowish green to bluish white due to increased distortion of [VO4 ]3- tetrahedron. Consequently, the CIE color coordinates changed from (0.42, 0.50) to (0.31, 0.35) which lies in the near-white region in the chromaticity diagram. Thus, the newly developed Y doped Sr3 Bi(VO4 )3 is a promising lanthanide-free full-color emission phosphor for applications in pc-white light emitting diodes.

An integrated method for identifying essential proteins from multiplex network model of protein-protein interactions.

Cell survival requires the presence of essential proteins. Detection of essential proteins is relevant not only because of the critical biological functions they perform but also the role played by them as a drug target against pathogens. Several computational techniques are in place to identify essential proteins based on protein-protein interaction (PPI) network. Essential protein detection using only physical interaction data of proteins is challenging due to its inherent uncertainty. Hence, in this work, we propose a multiplex network-based framework that incorporates multiple protein interaction data from their physical, coexpression and phylogenetic profiles. An extended version termed as multiplex eigenvector centrality (MEC) is used to identify essential proteins from this network. The methodology integrates the score obtained from the multiplex analysis with subcellular localization and Gene Ontology information and is implemented using Saccharomyces cerevisiae datasets. The proposed method outperformed many recent essential protein prediction techniques in the literature.

Nanocellulose, a Versatile Green Platform: From Biosources to Materials and Their Applications.

With increasing environmental and ecological concerns due to the use of petroleum-based chemicals and products, the synthesis of fine chemicals and functional materials from natural resources is of great public value. Nanocellulose may prove to be one of the most promising green materials of modern times due to its intrinsic properties, renewability, and abundance. In this review, we present nanocellulose-based materials from sourcing, synthesis, and surface modification of nanocellulose, to materials formation and applications. Nanocellulose can be sourced from biomass, plants, or bacteria, relying on fairly simple, scalable, and efficient isolation techniques. Mechanical, chemical, and enzymatic treatments, or a combination of these, can be used to extract nanocellulose from natural sources. The properties of nanocellulose are dependent on the source, the isolation technique, and potential subsequent surface transformations. Nanocellulose surface modification techniques are typically used to introduce either charged or hydrophobic moieties, and include amidation, esterification, etherification, silylation, polymerization, urethanization, sulfonation, and phosphorylation. Nanocellulose has excellent strength, high Young's modulus, biocompatibility, and tunable self-assembly, thixotropic, and photonic properties, which are essential for the applications of this material. Nanocellulose participates in the fabrication of a large range of nanomaterials and nanocomposites, including those based on polymers, metals, metal oxides, and carbon. In particular, nanocellulose complements organic-based materials, where it imparts its mechanical properties to the composite. Nanocellulose is a promising material whenever material strength, flexibility, and/or specific nanostructuration are required. Applications include functional paper, optoelectronics, and antibacterial coatings, packaging, mechanically reinforced polymer composites, tissue scaffolds, drug delivery, biosensors, energy storage, catalysis, environmental remediation, and electrochemically controlled separation. Phosphorylated nanocellulose is a particularly interesting material, spanning a surprising set of applications in various dimensions including bone scaffolds, adsorbents, and flame retardants and as a support for the heterogenization of homogeneous catalysts.

The prevalence of occult hepatitis B infection among the blood donors in a tertiary care hospital, Puducherry.

Occult hepatitis B infection (OBI) is a cause of concern while screening the blood donors to prevent transfusion-related transmission of infection. This study was conducted to assess the prevalence of OBI using total anti-HBc by ELISA and DNA detection by real time polymerase chain reaction (PCR). The samples included were negative for HBs Ag by ELISA. Out of 1102 samples tested, 156 were positive for total anti-hepatitis B core antigen and 52/156 by real-time PCR. Overall, the prevalence was found to be 4.71% (52/1102). The results indicate that nucleic acid-based testing should be an essential part of screening procedure to prevent missing of OBI.

Exploitation of Eu3+ red luminescence through order-disorder structural transitions in lanthanide stannate pyrochlores for warm white LED applications.

Eu3+ ions epitomize excellent structural probes for the detection of disorder induced by structural variations in stannate pyrochlores due to their relatively simple energy level structure. In this context, we have synthesized a series of Eu3+ doped Ln2.85YSnNbO10.5:0.15Eu3+ (Ln = La, Gd, Y, and Lu) red phosphors via a high temperature solid state reaction method to explore the influence of phase evolution on the luminescence properties. The substitution of Ln3+ ions in the A sites of the pyrochlore induces a structural transition from an ordered pyrochlore to a disordered fluorite structure with decreasing ionic radius. The diminishing trend of the characteristic superstructure peaks in the XRD pattern and the broadening of Raman modes with lanthanide substitution clearly substantiate the disorder induced in the cationic sublattice. These phosphors exhibit strong absorption in the near UV region and emit red luminescence under 392 nm excitation, which also correlates to their crystal structures. Their luminescence properties were enhanced with the increased ordering of cations from Lu to La. The more ordered structure of the La system favors a more uniform distribution of Eu3+ ions, preventing cluster formation, and thus improving the luminescence properties. The splitting of the 5D0-7F1 transition of the Eu3+ ions further provides a clue for the structural transition in support of the XRD and Raman analysis. The long range ordering, ligand polarizability, and covalent nature of the Eu3+ bonding influence the emission probability and improve the quantum efficiency of the La host. Eu3+ emissions resulting from 5D0-7FJ transitions are significantly improved with increases in the concentration of Eu3+ ions in the La host. The distortion of the A site symmetry and the red shift of the charge transfer band with Eu3+ doping in the La3YSnNbO10.5 system leads to an enhanced electric dipole transition. The extent of the distortion in the EuO8 polyhedra is reflected in the quantum efficiency values and J-O intensity parameters, Ω2 and Ω4, which are a measure of the degree of polarizability of the Eu-O bonds in the lattice. Our results suggest that we can manipulate the Eu3+ red luminescence in lanthanide stannate pyrochlores through order-disorder structural transitions.

Influence of local structure on photoluminescence properties of Eu3+ doped CeO2 red phosphors through induced oxygen vacancies by contrasting rare earth substitutions.

A new family of red phosphors, Ce0.9-xRExO2-δ:0.1Eu3+ (RE = Y and La; x = 0, 0.20, 0.40, 0.60, 0.80, and 0.90), was synthesized by a conventional solid-state route. The influence of contrasting rare earth substitutions (Y and La) in the system was investigated on the local structure and associated photoluminescence properties by various characterization techniques. Both trivalent ion substitutions lead to the same kind of variation during phase transformation from fluorite to the respective parent oxide structure (x ≥ 0.6). On the other hand, the substitutions have a distinct effect on local structure, absorption, luminescence and lifetimes. The smaller Y3+ ion substitution enables the ordering of oxygen vacancies in a lattice, inhibiting the defect formation of Ce3+ oxidation states. In contrast, the larger La3+ ion substitution liberates oxygen vacancies, allowing defect formation. Consequently, the concentration of Ce3+ is dependent on the ionic radius of the metal ions and it has a bearing on the band gap and luminescence properties of the system. Ce0.1Y0.8O2-δ:0.1Eu3+ phosphor exhibited maximum red emission intensity at 612 nm, which is 8 times higher than that of Ce0.9O2-δ:0.1Eu3+ and better than that of commercial Philips red phosphor, whereas La substitution yielded poor emission intensities with higher concentrations. The co-substitution of contrasting rare earth metals with Eu3+ allow the understanding of local structure and a smaller ion like Y3+ greatly functionalizes CeO2:Eu3+ phosphor.

Habitat monitoring and conservation prioritisation of protected areas in Western Ghats, Kerala, India.

Spatially explicit approach is essential to prioritise the ecosystems for biodiversity conservation. In the present study, the conservation status of 20 protected areas of the Western Ghats of Kerala, India, was analysed based on long-term changes in forests (1975-1985-1995-2005-2013), landscape level changes in fragmentation and forest fires (2005-2015). This study has shown that a significant forest loss occurred in protected areas before declaration. Idukki is one of the major protected areas which showed a drastic reduction (18.83%) in its forest cover. During 1985-1995, Periyar tiger reserve had lost 24.19 km2 core 3 forest area followed by Peppara (18.54 km2), Parambikulam (17.93 km2), Chimmony (17.71 km2), Peechi-Vazhani (12.31 km2) and Neyyar (11.67 km2). An area of 71.33 km2 of the protected area was affected by fires in 2014. Overall protected area-wise decadal analysis indicates Periyar has the highest number of fire incidences followed by Wayanad, Kurinjimala, Silent Valley and Eravikulam. Disturbances in the form of fires and fragmentation still exist and may have significant conservation threat to flora and fauna. Among protected areas, many are having a probability to go under threat or dynamic stage. Chinnar, Thattekkad and Kurinjimala sanctuaries are representing high levels of vulnerability, or they are near to decline stage. Habitat level monitoring of the anthropogenic disturbances can be efficiently useful for the strategic conservation planning. The present study has provided geospatial database on spatial patterns of deforestation, fragmentation and forest fires in protected areas of Kerala. Conservation prioritization approach based on these parameters will be useful for the strategic planning in the state of Kerala.

Understanding the electron transfer process in ZnO-naphthol azobenzoic acid composites from photophysical characterisation.

Semiconductor nanoparticles surface modified with organic molecules capable of visible light absorption and effectively transferring the electrons to the catalytic sites have the potential to be good photocatalysts. ZnO nanoparticles of size ∼3 nm are grafted with two azonaphthols, one conjugated and the other non-conjugated. The photophysical properties of modified ZnO indicate an effective electron transfer from the conjugated azonaphthol to ZnO but not in the case of the non-conjugated molecule. It is also observed from lifetime studies that the conjugated molecule stabilises the defect sites on ZnO nanoparticles. It is possible that excited electrons from the conjugated molecule are transferred to specific defect sites in ZnO. This apparently does not occur in the non-conjugated molecule, bringing to focus the importance of the photophysical characteristics of organic modifiers in designing visible light active photocatalysts.

Flavonoids, the emerging dietary supplement against cisplatin-induced nephrotoxicity.

The letter illustrates the emerging potential of flavonoids as dietary supplement to ameliorate cisplatin-induced nephrotoxicity and refers to the recent article on ''Anti-apoptotic and anti-inflammatory effects of naringin on cisplatin-induced renal injury in the rat'' by Chtourou et al. They demonstrated that supplementation of naringin, a flavanone glycoside, found in grape and citrus fruit species, can attenuate cisplatin-induced renal dysfunction via restoration of redox balance and suppression of inflammation, NF-κB activation and apoptosis. The chemotherapeutic efficacy of cisplatin has always compelled the researchers to find solution to ameliorate its side effects. In recent years, numerous candidates have been evaluated for their protective potential against cisplatin-induced nephrotoxicity and flavonoids have come up with promising results. The future prospects might be promising with a proper refinement and collective integration of the preclinical and clinical research in the field of flavonoid supplementation to cisplatin therapy.

Alternative mechanisms of inhibiting activity of poly (ADP-ribose) polymerase-1.

Poly ADP-ribose polymerase (PARP-1), a DNA nick-sensor enzyme, is an abundant nuclear protein. Upon sensing DNA breaks, PARP-1 gets activated and cleaves NAD into nicotinamide and ADP-ribose and polymerizes the latter onto nuclear acceptor proteins including histones, transcription factors, and PARP-1 itself. Poly(ADP-ribosylation) mainly contributes to DNA repairing mechanism. However, oxidative stress-induced over-activation of PARP-1 consumes excess of NAD and consequently ATP, culminating into cell necrosis. This cellular suicide pathway has been implicated in several conditions such as stroke, myocardial ischemia, diabetes. Thus, it can be a rationale approach to inhibit the activity of PARP-1 for reducing detrimental effects associated with oxidative stress-induced over-activation of PARP-1. Several preclinical as well as clinical studies of PARP-1 inhibitors have been used in conditions such as cancer, stroke and traumatic brain injury. Conventionally, there are many studies which employed the concept of direct inhibition of PARP-1 by competing with NAD. Here, in the present review, we highlight several prospective alternative approaches for the inhibition of PARP-1 activity.

Hesperidin and Silibinin Ameliorate Aluminum-Induced Neurotoxicity: Modulation of Antioxidants and Inflammatory Cytokines Level in Mice Hippocampus.

Mounting evidence suggests that long-term aluminum exposure results in severe toxic effects, including neurobehavioral and neurochemical anomalies. The present study was performed to examine the neuroprotective potential of hesperidin and silibinin against aluminum chloride (AlCl3)-induced neurotoxicity in mice. AlCl3 (100 mg/kg/day) was injected daily through oral gavage for 42 days. Concomitantly, hesperidin (50 and 100 mg/kg/day, p.o.) and silibinin (100 and 200 mg/kg/day, p.o.) was administered for 42 days in different groups. The extent of cognitive impairment was assessed by Morris water maze and novel object recognition test on the 43rd day. Neurotoxicity was assessed by measuring oxido-nitrosative stress and proinflammatory cytokines in the hippocampus of mice. Six weeks treatment with AlCl3 caused cognitive impairment as indicated by an increase in the retention latency time and reduction in the percentage of recognition index. AlCl3-treated group showed oxido-nitrosative stress as indicated by increase in the level of lipid peroxidation, nitrite and depleted reduced glutathione, catalase activity in the hippocampus. Moreover, the chronic AlCl3 administration raised the proinflammatory cytokines (interleukin-1ß and tumor necrosis factor-α) level and increased acetylcholinesterase activity and reduced the BDNF content in the hippocampus of AlCl3-treated animals. However, chronic treatment with hesperidin and silibinin at higher doses significantly ameliorated the AlCl3-induced cognitive impairment and hippocampal biochemical anomalies. The present study clearly indicated that hesperidin and silibinin exert neuroprotective effects against AlCl3-induced cognitive impairment and neurochemical changes. Amelioration of cognitive impairment may be attributed to the impediment of oxido-nitrosative stress and inflammation in the hippocampus.