Dr Manisha Ray - Academia.edu (original) (raw)
Papers by Dr Manisha Ray
Nature Communications, 2022
Lysophospholipids are bioactive lipids and can signal through G-protein-coupled receptors (GPCRs)... more Lysophospholipids are bioactive lipids and can signal through G-protein-coupled receptors (GPCRs). The best studied lysophospholipids are lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). The mechanisms of lysophospholipid recognition by an active GPCR, and the activations of lysophospholipid GPCR–G-protein complexes remain unclear. Here we report single-particle cryo-EM structures of human S1P receptor 1 (S1P1) and heterotrimeric Gi complexes formed with bound S1P or the multiple sclerosis (MS) treatment drug Siponimod, as well as human LPA receptor 1 (LPA1) and Gi complexes in the presence of LPA. Our structural and functional data provide insights into how LPA and S1P adopt different conformations to interact with their cognate GPCRs, the selectivity of the homologous lipid GPCRs for S1P versus LPA, and the different activation mechanisms of these GPCRs by LPA and S1P. Our studies also reveal specific optimization strategies to improve the MS-treating S1P1-targeting ...
The FASEB Journal, 2022
Ponesimod is a sphingosine 1‐phosphate (S1P) receptor (S1PR) modulator that was recently approved... more Ponesimod is a sphingosine 1‐phosphate (S1P) receptor (S1PR) modulator that was recently approved for treating relapsing forms of multiple sclerosis (MS). Three other FDA‐approved S1PR modulators for MS—fingolimod, siponimod, and ozanimod—share peripheral immunological effects via common S1P1 interactions, yet ponesimod may access distinct central nervous system (CNS) mechanisms through its selectivity for the S1P1 receptor. Here, ponesimod was examined for S1PR internalization and binding, human astrocyte signaling and single‐cell RNA‐seq (scRNA‐seq) gene expression, and in vivo using murine cuprizone‐mediated demyelination. Studies confirmed ponesimod’s selectivity for S1P1 without comparable engagement to the other S1PR subtypes (S1P2,3,4,5). Ponesimod showed pharmacological properties of acute agonism followed by chronic functional antagonism of S1P1. A major locus of S1P1 expression in the CNS is on astrocytes, and scRNA‐seq of primary human astrocytes exposed to ponesimod identified a gene ontology relationship of reduced neuroinflammation and reduction in known astrocyte disease‐related genes including those of immediate early astrocytes that have been strongly associated with disease progression in MS animal models. Remarkably, ponesimod prevented cuprizone‐induced demyelination selectively in the cingulum, but not in the corpus callosum. These data support the CNS activities of ponesimod through S1P1, including protective, and likely selective, effects against demyelination in a major connection pathway of the brain, the limbic fibers of the cingulum, lesions of which have been associated with several neurologic impairments including MS fatigue.
Meta Gene, 2020
Abstract Single nucleotide polymorphisms (SNPs) are regarded as one of the most common genetic va... more Abstract Single nucleotide polymorphisms (SNPs) are regarded as one of the most common genetic variations in the human genome, which can affect the structural and functional characteristics of gene/ protein to cause diseases. Thus this study aims to identify the genetic abnormality of papillary thyroid cancer (PTC) which is a complicated stuff to play a role in the evaluation, diagnosis or treatment of PTC patients. This study followed the identified up and down-regulated genes, associated in PTC related metabolic pathways from previous study for single nucleotide polymorphism (SNP) analysis through dbSNP, SIFT, PredictSNP1 and PredictSNP2 which predicted 8 and 6 highly deleterious rsIDS of non-synonymous SNPs for 5 up and 3 down-regulated target genes of PTC respectively, out of which rsIDs rs187536858, rs201950989 of nsSNPs in up-regulated target genes LPAR5, ZMAT3 and nsSNPs with rsIDs rs121913523, rs142070930, rs372232192, rs372333099 in down-regulated genes KIT, GSTM3 respectively were identified as novel nsSNPs from UniProt data for papillary thyroid carcinoma. Hence this study will help to develop a novel biomarker for solving the genetic disruption in PTC patients.
Nursing standard (Royal College of Nursing (Great Britain) : 1987), 2020
Young-onset dementia refers to dementia that develops before the age of 65 years. It can present ... more Young-onset dementia refers to dementia that develops before the age of 65 years. It can present with a wide variety of symptoms including cognitive, behavioural, neurological and systemic symptoms, which reflects the wide range of possible causes. Young-onset dementia profoundly affects all aspects of people's lives, including relationships, employment and finances, and it will also profoundly affect relatives and carers. This article outlines the causes, symptoms and effects of young-onset dementia and describes the role of nurses in providing care and support to people with this progressive condition.
Meta Gene, 2021
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Database, 2021
Developments in high-throughput sequencing (HTS) result in an exponential increase in the amount ... more Developments in high-throughput sequencing (HTS) result in an exponential increase in the amount of data generated by sequencing experiments, an increase in the complexity of bioinformatics analysis reporting and an increase in the types of data generated. These increases in volume, diversity and complexity of the data generated and their analysis expose the necessity of a structured and standardized reporting template. BioCompute Objects (BCOs) provide the requisite support for communication of HTS data analysis that includes support for workflow, as well as data, curation, accessibility and reproducibility of communication. BCOs standardize how researchers report provenance and the established verification and validation protocols used in workflows while also being robust enough to convey content integration or curation in knowledge bases. BCOs that encapsulate tools, platforms, datasets and workflows are FAIR (findable, accessible, interoperable and reusable) compliant. Providing...
IUPHAR/BPS Guide to Pharmacology CITE, 2021
Lysophosphatidic acid (LPA) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Ly... more Lysophosphatidic acid (LPA) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Lysophospholipid Receptors [55, 19, 82, 129]) are activated by the endogenous phospholipid LPA. The first receptor, LPA1, was identified as ventricular zone gene-1 (vzg-1) [40], This discovery represented the beginning of the de-orphanisation of members of the endothelial differentiation gene (edg) family, as other LPA and sphingosine 1-phosphate (S1P) receptors were found. Five additional LPA receptors (LPA2,3,4,5,6) have since been identified [82] and their gene nomenclature codified for human LPAR1, LPAR2, etc. (HUGO Gene Nomenclature Committee, HGNC) and Lpar1, Lpar2, etc. for mice (Mouse Genome Informatics Database, MGI) to reflect species and receptor function of their corresponding proteins. The crystal structure of LPA1 is solved and indicates that LPA accesses the extracellular binding pocket, consistent with its proposed delivery via autotaxin [13]. These studies have also implic...
Gene Reports, 2020
Parkinson's disease is a well known neurological disorder across the globe. Even after decades of... more Parkinson's disease is a well known neurological disorder across the globe. Even after decades of research, precise knowledge on molecular basis of the disease pathology is still imprecise. However, advancement in experimental and computational techniques have generated high frequency of genomics data which offers a scope to discover effective non synonymous SNPs within PD associated genes. Here, authors have attempted to discovered non-synonymous, deleterious SNPs for the target gene pool with a plausible threat towards PD pathophysiology using dbSNP, SIFT, PredictSNP1 and PredictSNP2 tool. PD related genes list was prepared on the basis of literature evidence and reports from different public repositories such as Gene Cards, GWAS CATALOG , GenAtlas and MalaCards. The present study was identified six novel SNPs such as rs372675589, rs150966634, rs184532476, rs373099722, rs201188374 and rs201555827 for five PD targets (PSMC4, NDUFV1, GSK3B, GPR37 and CUL1). Possibly, all of these six SNPs such as P199H (PSMC4), R386C (NDUFV1), V70I (GSK3B), V399G (GPR37), S424F (GPR37), and L140P (CUL1) in their respective PD targets have remarkable association in the disease pathways. The present observation would provide insights into the complicated structure of PD pathophysiology.
The COVID-19 pandemic is having a devastating effect on the healthcare system and the economy of ... more The COVID-19 pandemic is having a devastating effect on the healthcare system and the economy of the world. The unavailability of a specific treatment regime and a candidate vaccine yet opens up scope for new approaches and discoveries of drugs for mitigation of the sufferings of humankind due to the disease. The present isolated whole-genome sequences of SARS-CoV-2 from 11 different nations subjected to evolutionary study and genome-wide association study through in silico approaches including multiple sequence alignment, phylogenetic study through MEGA7 and have been analyzed through DNAsp respectively. These investigations recognized the nucleotide varieties and single nucleotide mutations/polymorphisms on the genomic regions as well as protein-coding regions. The resulted mutations have diversified the genomic contents of SARS-CoV-2 according to the altered nucleotides found in 11 genome sequences. India and Nepal have found to have progressively more distinct species of SARS-Co...
Gene Reports, 2019
Abstract Microarrays can simultaneously measure the expression level of thousands of genes within... more Abstract Microarrays can simultaneously measure the expression level of thousands of genes within a particular mRNA sample, which permits description of genome-wide expression changes in health and disease. Systematic observe of gene expression profiling allows the establishment of new taxonomy of disease, so here differential gene expression analysis of Papillary thyroid cancer (PTC) from microarray profile, was executed with various computational applications like RStudio Bioconductor Package, DAVID, KEGG mapper, miRNet, which explains the expression level (132 up, 260 down) based on log2 ratio, functional annotations, enriched metabolic pathways and highly linked miRNAs (has-mir-335p, has-mir-335-5p, has-mir-26b-5p) respectively for the resulted significant genes (P value
Maturitas, 2019
Dementia and hearing loss are highly prevalent in older people. Both these conditions together in... more Dementia and hearing loss are highly prevalent in older people. Both these conditions together increase complexities in all aspects of an individual's care and management plan. There has been increasing research interest about the relationship between dementia and hearing loss in recent years. In this review we discuss the relationship between hearing loss and dementia, including hearing loss as a risk factor for dementia; the effects of dementia with hearing loss on affected persons' quality of life and the care they receive; screening and available interventions; and opportunities for prevention. We also discuss dementia and hearing loss in the care home setting, as the majority of residents have either, or indeed both, dementia and/or hearing loss. Several mechanisms have been suggested for how hearing loss and dementia may be related but the evidence for how these may operate together is still unclear. Similarly, although it is to be hoped that the active identification and management of hearing problems may help to reduce the future development of cognitive impairment, evidence for this is still lacking. Highlights Hearing loss and dementia are often associated-they may occur together, though longitudinal studies suggest that hearing loss may be a genuine risk factor for subsequent dementia. There may be several mechanisms that contribute to the association, including brain pathology but also social factors. The relationship of central hearing loss with dementia needs further exploration. Multiple barriers exist in both screening and treatment of hearing loss among people with dementia emphasising the need for an integrated patient centred approach. Hearing loss is linked to multiple physical and psychological comorbidities in persons with dementia. Extended clinical trials are needed to establish whether treating hearing loss is effective in the prevention of dementia.
![Research paper thumbnail of Mixed cerium-platinum oxides: Electronic structure of [CeO]Ptn (n = 1, 2) and [CeO2]Pt complex anions and neutrals](https://attachments.academia-assets.com/107833162/thumbnails/1.jpg)
](The Journal of chemical physics, Jan 28, 2016
The electronic structures of several small Ce-Pt oxide complexes were explored using a combinatio... more The electronic structures of several small Ce-Pt oxide complexes were explored using a combination of anion photoelectron (PE) spectroscopy and density functional theory calculations. Pt and Pt2 both accept electron density from CeO diatomic molecules, in which the cerium atom is in a lower-than-bulk oxidation state (+2 versus bulk +4). Neutral [CeO]Pt and [CeO]Pt2 complexes are therefore ionic, with electronic structures described qualitatively as [CeO(+2)]Pt(-2) and [CeO(+)]Pt2 (-), respectively. The associated anions are described qualitatively as [CeO(+)]Pt(-2) and [CeO(+)]Pt2 (-2), respectively. In both neutrals and anions, the most stable molecular structures determined by calculations feature a distinct CeO moiety, with the positively charged Ce center pointing toward the electron rich Pt or Pt2 moiety. Spectral simulations based on calculated spectroscopic parameters are in fair agreement with the spectra, validating the computationally determined structures. In contrast, wh...
Methods in molecular biology (Clifton, N.J.), 2018
Single-cell RNA sequencing has evolved into a benchmark application to study cellular heterogenei... more Single-cell RNA sequencing has evolved into a benchmark application to study cellular heterogeneity, advancing our understanding of cellular differentiation, disease progression, and gene regulation in a multitude of research areas. The generation of high-quality cDNA, an important step in the experimental workflow when generating sequence-ready libraries, is critical to maximizing data quality. Here we describe a strategy that uses a microfluidic device (i.e., the C1™ IFC) to synthesize full-length cDNA from single cells in a fully automated, nanoliter-scale format. The device also facilitates confirmation of the presence of a single, viable cell and recording of phenotypic information, quality control measures that are crucial for streamlining downstream data processing and enhancing overall data validity.
Cancer Research, 2017
The low RNA content of single human T cells has limited the success of single-cell transcriptome ... more The low RNA content of single human T cells has limited the success of single-cell transcriptome profiling, an approach that can generate data to reconstruct paired α,β T cell receptor (TCR) chains¹. Single-cell TCR sequencing is a powerful molecular tool to analyze tumor-infiltrating lymphocytes and production of cellular therapeutics. We compared the sensitivity and overall performance of the new Clontech® SMART-Seq® v4 Kit to the previously validated SMART-Seq v1 Kit on single primary human CD3+ cells captured and processed on the C1™ system (Fluidigm®). Sequenced libraries were analyzed using the TraCeR bioinformatics pipeline¹ to identify the TCR α and β chains expressed in each T cell. Cryopreserved CD3+ T cells were prepared as a single-cell suspension for capture on C1 using SMART-Seq v1 and v4, according to manufacturer instructions (AllCells®, Fluidigm, Clontech). Single-cell libraries were sequenced at 1.9 million reads per single cell. After data processing, the aligned ...
Cancer Research, 2017
Single-cell mRNA sequencing has enabled scientists to gain new insight into the diversity of cell... more Single-cell mRNA sequencing has enabled scientists to gain new insight into the diversity of cell populations. However, only approximately 20% of all transcripts are detected in a single cell¹, with low-expressed transcripts affected most. These transcripts can play a critical role in regulating cell function, so detecting their expression levels is key for deeper characterization studies subsequent to atlasing studies that utilize mRNA sequencing. Here we demonstrate the benefit of utilizing single-cell qPCR to explore expression levels of transcription factor (TF) genes involved in pathway activation and inactivation in cell lines derived from breast, lung and bone marrow cancers. In parallel, we have also performed single-cell sequencing to compare the sensitivity of both methods in capturing information on these low-expressed TF genes. Single-cell suspensions were used for capture and processing on the C1™ system (Fluidigm®) using SMART-Seq® v1 (Clontech®) and Ambion® Single Cel...
The Journal of Physical Chemistry A, 2016
A systematic comparison of M x O y − + ROH (M = Mo versus W; R = Me versus Et) reaction rate coef... more A systematic comparison of M x O y − + ROH (M = Mo versus W; R = Me versus Et) reaction rate coefficients and product distributions combined with results of calculations on weakly-bound M x O y − ⋅ROH complexes suggest that the overall reaction mechanism has three distinct steps, consistent with recently reported results on analogous M x O y − + H 2 O reactivity studies. M x O y − + ROH → M x O y+1 − + RH oxidation reactions are observed for the least oxidized clusters, and M x O y − + ROH → M x O y ROH − addition reactions are observed for clusters in intermediate oxidation states, as observed previously in M x O y − + H 2 O reactions. The first step is weakly-bound complex formation, the rate of which is governed by the relative stability of the M x O y − ⋅ROH charge-dipole complexes and the Lewis acid-base complexes. Calculations predict that Mo x O y − clusters form more stable Lewis acid-base complexes than W x O y − , and the stability of EtOH complexes is enhanced relative to MeOH. Consistent with this result, Mo x O y − + ROH rate coefficients are higher than analogous W x O y − clusters. Rate coefficients range from 2.7 x 10-13 cm 3 s −1 for W 3 O 8 − + MeOH to 3.4 x 10 −11 cm 3 s −1 for Mo 2 O 4 − + EtOH. Second, a covalently-bound complex is formed, and anion PE spectra of the several M x O y ROH − addition products observed are consistent with hydroxyl-alkoxy structures that are formed readily from the Lewis acid-base complexes. Calculations indicate that addition products are trapped intermediates in the M x O y − + ROH → M x O y+1 − + RH reaction, and the third step is rearrangement of the hydroxyl group to a metal hydride group to facilitate RH release. Trapped intermediates are more prevalent in Mo x O y − reaction product distributions, indicating that the rate of this step is higher for W x O y+1 RH − than for Mo x O y+1 RH −. This result is consistent with previous computational studies on analogous M x O y − + H 2 O reactions predicting that barriers along the pathway in the rearrangement step are higher for Mo x O y − reactions than for W x O y − .
Genomics & Informatics, 2016
Environmental microbes like Bordetella petrii has been established as a causative agent for vario... more Environmental microbes like Bordetella petrii has been established as a causative agent for various infectious diseases in human. Again, development of drug resistance in B. petrii challenged to combat against the infection. Identification of potential drug target and proposing a novel lead compound against the pathogen has a great aid and value. In this study, bioinformatics tools and technology have been applied to suggest a potential drug target by screening the proteome information of B. petrii DSM 12804 (accession No. PRJNA28135) from genome database of National Centre for Biotechnology information. In this regards, the inhibitory effect of nine natural compounds like ajoene (Allium sativum), allicin (A. sativum), cinnamaldehyde (Cinnamomum cassia), curcumin (Curcuma longa), gallotannin (active component of green tea and red wine), isoorientin (Anthopterus wardii), isovitexin (A. wardii), neral (Melissa officinalis), and vitexin (A. wardii) have been acknowledged with anti-bacterial properties and hence tested against identified drug target of B. petrii by implicating computational approach. The in silico studies revealed the hypothesis that lpxD could be a potential drug target and with recommendation of a strong inhibitory effect of selected natural compounds against infection caused due to B. petrii, would be further validated through in vitro experiments.
![Research paper thumbnail of SPECTROSCOPIC STUDY OF LOCAL INTERACTIONS OF PLATINUM IN SMALL [CexOy]Ptx′ − CLUSTERS](https://attachments.academia-assets.com/107833158/thumbnails/1.jpg)
](Proceedings of the 71st International Symposium on Molecular Spectroscopy, 2016
Cerium oxide is a good ionic conductor, and the conductivity can be enhanced with oxygen vacancie... more Cerium oxide is a good ionic conductor, and the conductivity can be enhanced with oxygen vacancies and doping. This conductivity may play an important role in the enhancement of noble or coinage metal toward the water-gas shift reaction when supported by cerium oxide. The ceria-supported platinum catalyst in particular has received much attention because of higher activity at lower temperatures (LT) compared to the most common commercial LT-WGS catalyst. We have used a combination of anion photoelectron spectroscopy and density functional theory calculations to study the interesting molecular and electronic structures and properties of cluster models of ceria-supported platinum. [Ce x O y ]Pt x − (x,x =1,2 ; y≤2x) clusters exhibit evidence of ionic bonding possible because of the high electron affinity of Pt and the low ionization potential of cerium oxide clusters. In addition, Pt − is a common daughter ion resulting from photodissociation of [Ce x O y ]Pt x − clusters. Finally, several of the anion and neutral clusters have profoundly different structures. These features may play a role in the enhancement of catalytic activity toward the water-gas shift reaction.
Proceedings of the 71st International Symposium on Molecular Spectroscopy, 2016
Proceedings of the 71st International Symposium on Molecular Spectroscopy, 2016
Lanthanide-based materials have unusual electronic properties because of the high number of elect... more Lanthanide-based materials have unusual electronic properties because of the high number of electronic degrees of freedom arising from partial occupation of 4f orbitals, which make these materials optimal for their utilization in many applications including electronics and catalysis. Electronic spectroscopy of small lanthanide molecules helps us understand the role of these 4f electrons, which are generally considered core-like because of orbital contraction, but are energetically similar to valence electrons. The spectroscopy of small lanthanide-containing molecules is relatively unexplored and to broaden this understanding we have completed the characterization of small cerium, praseodymium, and europium molecules using photoelectron spectroscopy coupled with DFT calculations. The characterization of PrO, EuH, EuO/EuOH, and Ce x O y molecules have allowed for the determination of their electron affinity, the assignment of numerous anion to neutral state transitions, modeling of anion/neutral structures and electron orbital occupation.
Nature Communications, 2022
Lysophospholipids are bioactive lipids and can signal through G-protein-coupled receptors (GPCRs)... more Lysophospholipids are bioactive lipids and can signal through G-protein-coupled receptors (GPCRs). The best studied lysophospholipids are lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). The mechanisms of lysophospholipid recognition by an active GPCR, and the activations of lysophospholipid GPCR–G-protein complexes remain unclear. Here we report single-particle cryo-EM structures of human S1P receptor 1 (S1P1) and heterotrimeric Gi complexes formed with bound S1P or the multiple sclerosis (MS) treatment drug Siponimod, as well as human LPA receptor 1 (LPA1) and Gi complexes in the presence of LPA. Our structural and functional data provide insights into how LPA and S1P adopt different conformations to interact with their cognate GPCRs, the selectivity of the homologous lipid GPCRs for S1P versus LPA, and the different activation mechanisms of these GPCRs by LPA and S1P. Our studies also reveal specific optimization strategies to improve the MS-treating S1P1-targeting ...
The FASEB Journal, 2022
Ponesimod is a sphingosine 1‐phosphate (S1P) receptor (S1PR) modulator that was recently approved... more Ponesimod is a sphingosine 1‐phosphate (S1P) receptor (S1PR) modulator that was recently approved for treating relapsing forms of multiple sclerosis (MS). Three other FDA‐approved S1PR modulators for MS—fingolimod, siponimod, and ozanimod—share peripheral immunological effects via common S1P1 interactions, yet ponesimod may access distinct central nervous system (CNS) mechanisms through its selectivity for the S1P1 receptor. Here, ponesimod was examined for S1PR internalization and binding, human astrocyte signaling and single‐cell RNA‐seq (scRNA‐seq) gene expression, and in vivo using murine cuprizone‐mediated demyelination. Studies confirmed ponesimod’s selectivity for S1P1 without comparable engagement to the other S1PR subtypes (S1P2,3,4,5). Ponesimod showed pharmacological properties of acute agonism followed by chronic functional antagonism of S1P1. A major locus of S1P1 expression in the CNS is on astrocytes, and scRNA‐seq of primary human astrocytes exposed to ponesimod identified a gene ontology relationship of reduced neuroinflammation and reduction in known astrocyte disease‐related genes including those of immediate early astrocytes that have been strongly associated with disease progression in MS animal models. Remarkably, ponesimod prevented cuprizone‐induced demyelination selectively in the cingulum, but not in the corpus callosum. These data support the CNS activities of ponesimod through S1P1, including protective, and likely selective, effects against demyelination in a major connection pathway of the brain, the limbic fibers of the cingulum, lesions of which have been associated with several neurologic impairments including MS fatigue.
Meta Gene, 2020
Abstract Single nucleotide polymorphisms (SNPs) are regarded as one of the most common genetic va... more Abstract Single nucleotide polymorphisms (SNPs) are regarded as one of the most common genetic variations in the human genome, which can affect the structural and functional characteristics of gene/ protein to cause diseases. Thus this study aims to identify the genetic abnormality of papillary thyroid cancer (PTC) which is a complicated stuff to play a role in the evaluation, diagnosis or treatment of PTC patients. This study followed the identified up and down-regulated genes, associated in PTC related metabolic pathways from previous study for single nucleotide polymorphism (SNP) analysis through dbSNP, SIFT, PredictSNP1 and PredictSNP2 which predicted 8 and 6 highly deleterious rsIDS of non-synonymous SNPs for 5 up and 3 down-regulated target genes of PTC respectively, out of which rsIDs rs187536858, rs201950989 of nsSNPs in up-regulated target genes LPAR5, ZMAT3 and nsSNPs with rsIDs rs121913523, rs142070930, rs372232192, rs372333099 in down-regulated genes KIT, GSTM3 respectively were identified as novel nsSNPs from UniProt data for papillary thyroid carcinoma. Hence this study will help to develop a novel biomarker for solving the genetic disruption in PTC patients.
Nursing standard (Royal College of Nursing (Great Britain) : 1987), 2020
Young-onset dementia refers to dementia that develops before the age of 65 years. It can present ... more Young-onset dementia refers to dementia that develops before the age of 65 years. It can present with a wide variety of symptoms including cognitive, behavioural, neurological and systemic symptoms, which reflects the wide range of possible causes. Young-onset dementia profoundly affects all aspects of people's lives, including relationships, employment and finances, and it will also profoundly affect relatives and carers. This article outlines the causes, symptoms and effects of young-onset dementia and describes the role of nurses in providing care and support to people with this progressive condition.
Meta Gene, 2021
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Database, 2021
Developments in high-throughput sequencing (HTS) result in an exponential increase in the amount ... more Developments in high-throughput sequencing (HTS) result in an exponential increase in the amount of data generated by sequencing experiments, an increase in the complexity of bioinformatics analysis reporting and an increase in the types of data generated. These increases in volume, diversity and complexity of the data generated and their analysis expose the necessity of a structured and standardized reporting template. BioCompute Objects (BCOs) provide the requisite support for communication of HTS data analysis that includes support for workflow, as well as data, curation, accessibility and reproducibility of communication. BCOs standardize how researchers report provenance and the established verification and validation protocols used in workflows while also being robust enough to convey content integration or curation in knowledge bases. BCOs that encapsulate tools, platforms, datasets and workflows are FAIR (findable, accessible, interoperable and reusable) compliant. Providing...
IUPHAR/BPS Guide to Pharmacology CITE, 2021
Lysophosphatidic acid (LPA) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Ly... more Lysophosphatidic acid (LPA) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Lysophospholipid Receptors [55, 19, 82, 129]) are activated by the endogenous phospholipid LPA. The first receptor, LPA1, was identified as ventricular zone gene-1 (vzg-1) [40], This discovery represented the beginning of the de-orphanisation of members of the endothelial differentiation gene (edg) family, as other LPA and sphingosine 1-phosphate (S1P) receptors were found. Five additional LPA receptors (LPA2,3,4,5,6) have since been identified [82] and their gene nomenclature codified for human LPAR1, LPAR2, etc. (HUGO Gene Nomenclature Committee, HGNC) and Lpar1, Lpar2, etc. for mice (Mouse Genome Informatics Database, MGI) to reflect species and receptor function of their corresponding proteins. The crystal structure of LPA1 is solved and indicates that LPA accesses the extracellular binding pocket, consistent with its proposed delivery via autotaxin [13]. These studies have also implic...
Gene Reports, 2020
Parkinson's disease is a well known neurological disorder across the globe. Even after decades of... more Parkinson's disease is a well known neurological disorder across the globe. Even after decades of research, precise knowledge on molecular basis of the disease pathology is still imprecise. However, advancement in experimental and computational techniques have generated high frequency of genomics data which offers a scope to discover effective non synonymous SNPs within PD associated genes. Here, authors have attempted to discovered non-synonymous, deleterious SNPs for the target gene pool with a plausible threat towards PD pathophysiology using dbSNP, SIFT, PredictSNP1 and PredictSNP2 tool. PD related genes list was prepared on the basis of literature evidence and reports from different public repositories such as Gene Cards, GWAS CATALOG , GenAtlas and MalaCards. The present study was identified six novel SNPs such as rs372675589, rs150966634, rs184532476, rs373099722, rs201188374 and rs201555827 for five PD targets (PSMC4, NDUFV1, GSK3B, GPR37 and CUL1). Possibly, all of these six SNPs such as P199H (PSMC4), R386C (NDUFV1), V70I (GSK3B), V399G (GPR37), S424F (GPR37), and L140P (CUL1) in their respective PD targets have remarkable association in the disease pathways. The present observation would provide insights into the complicated structure of PD pathophysiology.
The COVID-19 pandemic is having a devastating effect on the healthcare system and the economy of ... more The COVID-19 pandemic is having a devastating effect on the healthcare system and the economy of the world. The unavailability of a specific treatment regime and a candidate vaccine yet opens up scope for new approaches and discoveries of drugs for mitigation of the sufferings of humankind due to the disease. The present isolated whole-genome sequences of SARS-CoV-2 from 11 different nations subjected to evolutionary study and genome-wide association study through in silico approaches including multiple sequence alignment, phylogenetic study through MEGA7 and have been analyzed through DNAsp respectively. These investigations recognized the nucleotide varieties and single nucleotide mutations/polymorphisms on the genomic regions as well as protein-coding regions. The resulted mutations have diversified the genomic contents of SARS-CoV-2 according to the altered nucleotides found in 11 genome sequences. India and Nepal have found to have progressively more distinct species of SARS-Co...
Gene Reports, 2019
Abstract Microarrays can simultaneously measure the expression level of thousands of genes within... more Abstract Microarrays can simultaneously measure the expression level of thousands of genes within a particular mRNA sample, which permits description of genome-wide expression changes in health and disease. Systematic observe of gene expression profiling allows the establishment of new taxonomy of disease, so here differential gene expression analysis of Papillary thyroid cancer (PTC) from microarray profile, was executed with various computational applications like RStudio Bioconductor Package, DAVID, KEGG mapper, miRNet, which explains the expression level (132 up, 260 down) based on log2 ratio, functional annotations, enriched metabolic pathways and highly linked miRNAs (has-mir-335p, has-mir-335-5p, has-mir-26b-5p) respectively for the resulted significant genes (P value
Maturitas, 2019
Dementia and hearing loss are highly prevalent in older people. Both these conditions together in... more Dementia and hearing loss are highly prevalent in older people. Both these conditions together increase complexities in all aspects of an individual's care and management plan. There has been increasing research interest about the relationship between dementia and hearing loss in recent years. In this review we discuss the relationship between hearing loss and dementia, including hearing loss as a risk factor for dementia; the effects of dementia with hearing loss on affected persons' quality of life and the care they receive; screening and available interventions; and opportunities for prevention. We also discuss dementia and hearing loss in the care home setting, as the majority of residents have either, or indeed both, dementia and/or hearing loss. Several mechanisms have been suggested for how hearing loss and dementia may be related but the evidence for how these may operate together is still unclear. Similarly, although it is to be hoped that the active identification and management of hearing problems may help to reduce the future development of cognitive impairment, evidence for this is still lacking. Highlights Hearing loss and dementia are often associated-they may occur together, though longitudinal studies suggest that hearing loss may be a genuine risk factor for subsequent dementia. There may be several mechanisms that contribute to the association, including brain pathology but also social factors. The relationship of central hearing loss with dementia needs further exploration. Multiple barriers exist in both screening and treatment of hearing loss among people with dementia emphasising the need for an integrated patient centred approach. Hearing loss is linked to multiple physical and psychological comorbidities in persons with dementia. Extended clinical trials are needed to establish whether treating hearing loss is effective in the prevention of dementia.
The Journal of chemical physics, Jan 28, 2016
The electronic structures of several small Ce-Pt oxide complexes were explored using a combinatio... more The electronic structures of several small Ce-Pt oxide complexes were explored using a combination of anion photoelectron (PE) spectroscopy and density functional theory calculations. Pt and Pt2 both accept electron density from CeO diatomic molecules, in which the cerium atom is in a lower-than-bulk oxidation state (+2 versus bulk +4). Neutral [CeO]Pt and [CeO]Pt2 complexes are therefore ionic, with electronic structures described qualitatively as [CeO(+2)]Pt(-2) and [CeO(+)]Pt2 (-), respectively. The associated anions are described qualitatively as [CeO(+)]Pt(-2) and [CeO(+)]Pt2 (-2), respectively. In both neutrals and anions, the most stable molecular structures determined by calculations feature a distinct CeO moiety, with the positively charged Ce center pointing toward the electron rich Pt or Pt2 moiety. Spectral simulations based on calculated spectroscopic parameters are in fair agreement with the spectra, validating the computationally determined structures. In contrast, wh...
Methods in molecular biology (Clifton, N.J.), 2018
Single-cell RNA sequencing has evolved into a benchmark application to study cellular heterogenei... more Single-cell RNA sequencing has evolved into a benchmark application to study cellular heterogeneity, advancing our understanding of cellular differentiation, disease progression, and gene regulation in a multitude of research areas. The generation of high-quality cDNA, an important step in the experimental workflow when generating sequence-ready libraries, is critical to maximizing data quality. Here we describe a strategy that uses a microfluidic device (i.e., the C1™ IFC) to synthesize full-length cDNA from single cells in a fully automated, nanoliter-scale format. The device also facilitates confirmation of the presence of a single, viable cell and recording of phenotypic information, quality control measures that are crucial for streamlining downstream data processing and enhancing overall data validity.
Cancer Research, 2017
The low RNA content of single human T cells has limited the success of single-cell transcriptome ... more The low RNA content of single human T cells has limited the success of single-cell transcriptome profiling, an approach that can generate data to reconstruct paired α,β T cell receptor (TCR) chains¹. Single-cell TCR sequencing is a powerful molecular tool to analyze tumor-infiltrating lymphocytes and production of cellular therapeutics. We compared the sensitivity and overall performance of the new Clontech® SMART-Seq® v4 Kit to the previously validated SMART-Seq v1 Kit on single primary human CD3+ cells captured and processed on the C1™ system (Fluidigm®). Sequenced libraries were analyzed using the TraCeR bioinformatics pipeline¹ to identify the TCR α and β chains expressed in each T cell. Cryopreserved CD3+ T cells were prepared as a single-cell suspension for capture on C1 using SMART-Seq v1 and v4, according to manufacturer instructions (AllCells®, Fluidigm, Clontech). Single-cell libraries were sequenced at 1.9 million reads per single cell. After data processing, the aligned ...
Cancer Research, 2017
Single-cell mRNA sequencing has enabled scientists to gain new insight into the diversity of cell... more Single-cell mRNA sequencing has enabled scientists to gain new insight into the diversity of cell populations. However, only approximately 20% of all transcripts are detected in a single cell¹, with low-expressed transcripts affected most. These transcripts can play a critical role in regulating cell function, so detecting their expression levels is key for deeper characterization studies subsequent to atlasing studies that utilize mRNA sequencing. Here we demonstrate the benefit of utilizing single-cell qPCR to explore expression levels of transcription factor (TF) genes involved in pathway activation and inactivation in cell lines derived from breast, lung and bone marrow cancers. In parallel, we have also performed single-cell sequencing to compare the sensitivity of both methods in capturing information on these low-expressed TF genes. Single-cell suspensions were used for capture and processing on the C1™ system (Fluidigm®) using SMART-Seq® v1 (Clontech®) and Ambion® Single Cel...
The Journal of Physical Chemistry A, 2016
A systematic comparison of M x O y − + ROH (M = Mo versus W; R = Me versus Et) reaction rate coef... more A systematic comparison of M x O y − + ROH (M = Mo versus W; R = Me versus Et) reaction rate coefficients and product distributions combined with results of calculations on weakly-bound M x O y − ⋅ROH complexes suggest that the overall reaction mechanism has three distinct steps, consistent with recently reported results on analogous M x O y − + H 2 O reactivity studies. M x O y − + ROH → M x O y+1 − + RH oxidation reactions are observed for the least oxidized clusters, and M x O y − + ROH → M x O y ROH − addition reactions are observed for clusters in intermediate oxidation states, as observed previously in M x O y − + H 2 O reactions. The first step is weakly-bound complex formation, the rate of which is governed by the relative stability of the M x O y − ⋅ROH charge-dipole complexes and the Lewis acid-base complexes. Calculations predict that Mo x O y − clusters form more stable Lewis acid-base complexes than W x O y − , and the stability of EtOH complexes is enhanced relative to MeOH. Consistent with this result, Mo x O y − + ROH rate coefficients are higher than analogous W x O y − clusters. Rate coefficients range from 2.7 x 10-13 cm 3 s −1 for W 3 O 8 − + MeOH to 3.4 x 10 −11 cm 3 s −1 for Mo 2 O 4 − + EtOH. Second, a covalently-bound complex is formed, and anion PE spectra of the several M x O y ROH − addition products observed are consistent with hydroxyl-alkoxy structures that are formed readily from the Lewis acid-base complexes. Calculations indicate that addition products are trapped intermediates in the M x O y − + ROH → M x O y+1 − + RH reaction, and the third step is rearrangement of the hydroxyl group to a metal hydride group to facilitate RH release. Trapped intermediates are more prevalent in Mo x O y − reaction product distributions, indicating that the rate of this step is higher for W x O y+1 RH − than for Mo x O y+1 RH −. This result is consistent with previous computational studies on analogous M x O y − + H 2 O reactions predicting that barriers along the pathway in the rearrangement step are higher for Mo x O y − reactions than for W x O y − .
Genomics & Informatics, 2016
Environmental microbes like Bordetella petrii has been established as a causative agent for vario... more Environmental microbes like Bordetella petrii has been established as a causative agent for various infectious diseases in human. Again, development of drug resistance in B. petrii challenged to combat against the infection. Identification of potential drug target and proposing a novel lead compound against the pathogen has a great aid and value. In this study, bioinformatics tools and technology have been applied to suggest a potential drug target by screening the proteome information of B. petrii DSM 12804 (accession No. PRJNA28135) from genome database of National Centre for Biotechnology information. In this regards, the inhibitory effect of nine natural compounds like ajoene (Allium sativum), allicin (A. sativum), cinnamaldehyde (Cinnamomum cassia), curcumin (Curcuma longa), gallotannin (active component of green tea and red wine), isoorientin (Anthopterus wardii), isovitexin (A. wardii), neral (Melissa officinalis), and vitexin (A. wardii) have been acknowledged with anti-bacterial properties and hence tested against identified drug target of B. petrii by implicating computational approach. The in silico studies revealed the hypothesis that lpxD could be a potential drug target and with recommendation of a strong inhibitory effect of selected natural compounds against infection caused due to B. petrii, would be further validated through in vitro experiments.
Proceedings of the 71st International Symposium on Molecular Spectroscopy, 2016
Cerium oxide is a good ionic conductor, and the conductivity can be enhanced with oxygen vacancie... more Cerium oxide is a good ionic conductor, and the conductivity can be enhanced with oxygen vacancies and doping. This conductivity may play an important role in the enhancement of noble or coinage metal toward the water-gas shift reaction when supported by cerium oxide. The ceria-supported platinum catalyst in particular has received much attention because of higher activity at lower temperatures (LT) compared to the most common commercial LT-WGS catalyst. We have used a combination of anion photoelectron spectroscopy and density functional theory calculations to study the interesting molecular and electronic structures and properties of cluster models of ceria-supported platinum. [Ce x O y ]Pt x − (x,x =1,2 ; y≤2x) clusters exhibit evidence of ionic bonding possible because of the high electron affinity of Pt and the low ionization potential of cerium oxide clusters. In addition, Pt − is a common daughter ion resulting from photodissociation of [Ce x O y ]Pt x − clusters. Finally, several of the anion and neutral clusters have profoundly different structures. These features may play a role in the enhancement of catalytic activity toward the water-gas shift reaction.
Proceedings of the 71st International Symposium on Molecular Spectroscopy, 2016
Proceedings of the 71st International Symposium on Molecular Spectroscopy, 2016
Lanthanide-based materials have unusual electronic properties because of the high number of elect... more Lanthanide-based materials have unusual electronic properties because of the high number of electronic degrees of freedom arising from partial occupation of 4f orbitals, which make these materials optimal for their utilization in many applications including electronics and catalysis. Electronic spectroscopy of small lanthanide molecules helps us understand the role of these 4f electrons, which are generally considered core-like because of orbital contraction, but are energetically similar to valence electrons. The spectroscopy of small lanthanide-containing molecules is relatively unexplored and to broaden this understanding we have completed the characterization of small cerium, praseodymium, and europium molecules using photoelectron spectroscopy coupled with DFT calculations. The characterization of PrO, EuH, EuO/EuOH, and Ce x O y molecules have allowed for the determination of their electron affinity, the assignment of numerous anion to neutral state transitions, modeling of anion/neutral structures and electron orbital occupation.