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In India, Mizoram has the highest incidence of gastric cancer (GC) which might be associated with environmental factors such as diet, Helicobacter pylori (H.pylori) and Epstein-Barr virus (EBV) infections, and somatic genomic alterations. We performed PCR cum sequencing and fragment analysis for detection of H. pylori/EBV infection and microsatellite Instability (MSI) in GC patients (N = 68). Somatic mutations were identified by targeted and exome sequencing. We found 87% of GC patients infected with H. pylori and or EBV. Pathogenic infections were mostly mutually exclusive with only 16% of coinfection. TP53, MUC6, and ARID1A were significantly mutated. Two molecular subgroups with distinctive mutational profiles were identified: (1) patients harboring mutations in TP53 and (2) patients harboring mutations in RTK/RAS/PI3-K signaling pathway and chromatin-remodeling genes. Therefore, EBV and H. pylori infections and somatic mutations in the genes involved in RTK/RAS/PI3K signaling pathway, chromatin-remodeling, and TP53 might drive GC development and progression in Mizo patients.
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Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Humanos , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Herpesvirus Humano 4/genética , Fosfatidilinositol 3-Quinases/genética , Mutação , Cromatina , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
Oral squamous cell carcinoma of the gingivo-buccal region (OSCC-GB) is the most common cancer among men in India, and is associated with poor prognosis and frequent recurrence. Cellular heterogeneity in OSCC-GB was investigated by single-cell RNA sequencing of tumors derived from the oral cavity of 12 OSCC-GB patients, 3 of whom had concomitant presence of a precancerous lesion (oral submucous fibrosis [OSMF]). Unique malignant cell types, features, and phenotypic shifts in the stromal cell population were identified in oral tumors with associated submucous fibrosis. Expression levels of FOS, ATP1A, and DUSP1 provided robust discrimination between tumors with or without the concomitant presence of OSMF. Malignant cell populations shared between tumors with and without OSMF were enriched with the expression of partial epithelial-mesenchymal transition (pEMT) or fetal cell type signatures indicative of two dominant cellular programs in OSCC-GB-pEMT and fetal cellular reprogramming. Malignant cells exhibiting fetal cellular and pEMT programs were enriched with the expression of immune-related pathway genes known to be involved in antitumor immune response. In the tumor microenvironment, higher infiltration of immune cells than the stromal cells was observed. The T cell population was large in tumors and diverse subtypes of T cells with varying levels of infiltration were found. We also detected double-negative PLCG2+ T cells and cells with intermediate M1-M2 macrophage polarization. Our findings shed light on unique aspects of cellular heterogeneity and cell states in OSCC-GB.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Fibrose Oral Submucosa , Masculino , Humanos , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Fibrose Oral Submucosa/patologia , Perfilação da Expressão Gênica , Microambiente Tumoral/genéticaRESUMO
Rare Earth (re) based intermetallics are a fascinating class of inorganic compounds due to the presence of highly localized f-electrons. Among the ternary intermetallics, RETX3 (RE - Rare Earth, T - Transition metals, X - 13-15th elements of the main groups) is one of the most widely studied RE-based intermetallic families in terms of diverse crystal structures as well as physical properties. This perspective presents a brief account of different structural variations observed in this family of compounds. We have also discussed structure-property correlations in selected compounds in this series that show interesting physical properties such as spin-glass behavior, superconductivity, heavy fermion behavior, Kondo behavior, etc. The origin of different physical properties of these compounds is also discussed in brief by correlating their crystal structures.
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We conceptually selected the compounds REPb3 (RE = Eu, Yb), which are unstable in air, and converted them to the stable materials in ambient conditions by the chemical processes of "nanoparticle formation" and "dimensional reduction". The nanoparticles and the bulk counterparts were synthesized by the solvothermal and high-frequency induction furnace heating methods, respectively. The reduction of the particle size led to the valence transition of the rare earth atom, which was monitored through magnetic susceptibility and X-ray absorption near edge spectroscopy (XANES) measurements. The stability was checked by X-ray diffraction and thermogravimetric analysis over a period of seven months in oxygen and argon atmospheres and confirmed by XANES. The nanoparticles showed outstanding stability toward aerial oxidation over a period of seven months compared to the bulk counterpart, as the latter one is more prone to the oxidation within a few days.
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We have demonstrated engineering of the electronic band gap of the hybrid materials based on POMs (polyoxometalates), by controlling its structural complexity through variation in the conditions of synthesis. The pH- and temperature-dependent studies give a clear insight into how these experimental factors affect the overall hybrid structure and its properties. Our structural manipulations have been successful in effectively tuning the optical band gap and electronic band structure of this kind of hybrids, which can find many applications in the field of photovoltaic and semiconducting devices. We have also addressed a common crystallographic disorder observed in Keggin-ion (one type of heteropolyoxometalate [POMs])-based hybrid materials. Through a combination of crystallographic, spectroscopic, and theoretical analysis of four new POM-based hybrids synthesized with tactically varied reaction conditions, we trace the origin and nature of the disorder associated with it and the subtle local structural coordination involved in its core picture. While the crystallography yields a centrosymmetric structure with planar coordination of Si, our analysis with XPS, IR, and Raman spectroscopy reveals a tetrahedral coordination with broken inversion symmetry, corroborated by first-principles calculations.
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Single crystals (SCs) of the compounds Eu3Ag2In9 and EuCu2Ge2 were synthesized through the reactions run in liquid indium. Eu3Ag2In9 crystallizes in the La3Al11 structure type [orthorhombic space group (SG) Immm] with the lattice parameters: a = 4.8370(1) Å, b = 10.6078(3) Å, and c = 13.9195(4) Å. EuCu2Ge2 crystallizes in the tetragonal ThCr2Si2 structure type (SG I4/mmm) with the lattice parameters: a = b = 4.2218(1) Å, and c = 10.3394(5) Å. The crystal structure of Eu3Ag2In9 is comprised of edge-shared hexagonal rings consisting of indium. The one-dimensional chains of In6 rings are shared through the edges, which are further interconnected with other six-membered rings forming a three-dimensional (3D) stable crystal structure along the bc plane. The crystal structure of EuCu2Ge2 can be explained as the complex [CuGe](2+δ)- polyanionic network embedded with Eu ions. These polyanionic networks present in the crystal structure of EuCu2Ge2 are shared through the edges of the 011 plane containing Cu and Ge atoms, resulting in a 3D network. The structural relationship between Eu3T2In9 and EuCu2Ge2 has been discussed in detail, and we conclude that Eu3T2In9 is the metal deficient variant of EuCu2Ge2. The magnetic susceptibilities of Eu3T2In9 (T = Cu and Ag) and EuCu2Ge2 were measured between 2 and 300 K. In all cases, magnetic susceptibility data followed Curie-Weiss law above 150 K. Magnetic moment values obtained from the measurements indicate the probable mixed/intermediate valent behavior of the europium atoms, which was further confirmed by X-ray absorption studies and bond distances around the Eu atoms. Electrical resistivity measurements suggest that Eu3T2In9 and EuCu2Ge2 are metallic in nature.
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A new compound, Eu3Ir2In15, has been synthesized using indium as an active metal flux. The compound crystallizes in the tetragonal P4/mbm space group with lattice parameters a = 14.8580(4) Å, b = 14.8580(4) Å, and c = 4.3901(2) Å. It was further characterized by SEM-EDX studies. The effective magnetic moment (µeff) of this compound is 7.35 µB/Eu ion with a paramagnetic Curie temperature (θp) of -28 K, suggesting antiferromagnetic interaction. The mixed-valent nature of Eu observed in magnetic measurements was confirmed by XANES measurements. The compound undergoes demagnetization at a low magnetic field (10 Oe), which is quite unusual for Eu-based intermetallic compounds. Temperature-dependent resistivity studies reveal that the compound is metallic in nature. A comparative study was made between Eu3Ir2In15 and hypothetical vacancy-variant Eu5Ir4In10, which also crystallizes in the same crystal structure. However, our computational studies along with control experiments suggest that the latter is thermodynamically less feasible compared to the former, and hence we propose that it is highly unlikely that an RE5T4X10 would exist with X as a group 13 element.
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A new intermetallic compound Eu2AgGe3 has been synthesized using high-frequency induction heating method. Single-crystal X-ray diffraction data showed that Eu2AgGe3 crystallizes in the orthorhombic Ba2LiSi3 structure type, with Fddd space group and lattice parameters a = 8.7069(17) Å, b = 15.011(3) Å, c = 17.761(4) Å. Eu2AgGe3 is composed of infinite arrays of hexagonal [Ag3Ge3] units stacked along the [001] direction, and the Eu sites are sandwiched between these parallel hexagonal networks. Temperature-dependent powder XRD data and DTA hint toward a structural phase transition from orthorhombic to hexagonal above 477 K and an unusual reversible transition to the original phase, i.e., orthorhombic phase at around 718 K. Magnetic measurements on Eu2AgGe3 sample show paramagnetic behavior above 100 K and weak ferromagnetic interactions below 80 K. Mössbauer spectroscopy and X-ray absorption near-edge spectroscopic (XANES) studies reveal that Eu atoms in Eu2AgGe3 exist in the divalent oxidation state.
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A new compound Yb5Ga2Sb6 was synthesized by the metal flux technique as well as high frequency induction heating. Yb5Ga2Sb6 crystallizes in the orthorhombic space group Pbam (no. 55), in the Ba5Al2Bi6 structure type, with a unit cell of a = 7.2769(2) Å, b = 22.9102(5) Å, c = 4.3984(14) Å, and Z = 2. Yb5Ga2Sb6 has an anisotropic structure with infinite anionic double chains (Ga2Sb6)(10-) cross-linked by Yb(2+) and Yb(3+) ions. Each single chain is made of corner-sharing GaSb4 tetrahedra. Two such chains are bridged by Sb2 groups to form double chains of 1/∞ [Ga2Sb6(10-)]. The compound satisfies the classical Zintl-Klemm concept and is a narrow band gap semiconductor with an energy gap of around 0.36 eV calculated from the electrical resistivity data corroborating with the experimental absorption studies in the IR region (0.3 eV). Magnetic measurements suggest Yb atoms in Yb5Ga2Sb6 exist in the mixed valent state. Temperature dependent magnetic susceptibility data follows the Curie-Weiss behavior above 100 K and no magnetic ordering was observed down to 2 K. Experiments are accompanied by all electron full-potential linear augmented plane wave (FP-LAPW) calculations based on density functional theory to calculate the electronic structure and density of states. The calculated band structure shows a weak overlap of valence band and conduction band resulting in a pseudo gap in the density of states revealing semimetallic character.
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The intermetallic compound Yb(2)AuGe(3) was synthesized from indium flux. Yb(2)AuGe(3) crystallizes in the orthorhombic Ca(2)AgSi(3)-type structure which is an ordered superstructure of the AlB(2) structure type. The structure was refined in the Fmmm space group with lattice parameters a = 8.5124(17) Å, b = 14.730(3) Å, c = 8.4995(17) Å. Temperature-dependent powder X-ray diffraction studies show that Yb(2)AuGe(3) undergoes a phase transition from orthorhombic to hexagonal upon heating above 773 K. The compound shows weak paramagnetism that derives from a combination of Curie and Pauli paramagnetism with a magnetic moment value of 0.33(2) µ(B)/Yb atom. Magnetic ordering was not observed down to 2 K. Yb(2)AuGe(3) is metallic, and at low temperature the resistivity varies as T(2), indicating possible Fermi liquid behavior. Heat capacity measurements suggest that Yb(2)AuGe(3) is possibly a moderate heavy fermion system.
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Background: There is a dearth of studies on non-motor symptoms of Wilson's disease (WD) which is primarily because of the non-availability of a suitable scale. Objective: To assess the suitability of the Parkinson's Disease non motor symptoms questionnaire (PD-NMS Quest) in the assessment of non-motor symptoms of WD patients. Methods: In this case-control study, patients of WD above ≥12 years of age diagnosed by Leipzig's criteria and age and gender-matched control subjects were recruited. Critically ill patients, patients with severe hepatic impairment, or with pure hepatic WD were excluded. PD-NMS Quest was applied and relevant statistical analyses were performed. Results: A total of 18 cases and 25 controls were studied. Patients had a mean age of 22.6 years and a median disease duration of 8 years. WD patients had higher frequencies of all NMS than controls. Drooling (P = 0.0037), dysphagia or choking (P = 0.0088), nocturia (P = 0.0471), anxiety/fear (P = 0.0337), feeling sad or blue (P = 0.0020) and falling (P = 0.0197) were significantly higher in WD patients than controls. Conclusions: Although many NMS of WD patients are picked up effectively with PD-NMS Quest, some of them need detail assessment including cognitive, behavioral, and psychiatric symptoms, drooling and dysphagia, sleep as well as autonomic disturbances. Questions pertaining to sexual activity may be omitted from the questionnaire.
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The evolution of viral variants and their impact on viral transmission have been an area of considerable importance in this pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed the viral variants in different phases of the pandemic in West Bengal, a state in India that is important geographically, and compared the variants with other states like Delhi, Maharashtra, and Karnataka, located in other regions of the country. We have identified 57 pango-lineages in 3,198 SARS-CoV-2 genomes, alteration in their distribution, as well as contrasting profiles of amino acid mutational dynamics across different waves in different states. The evolving characteristics of Delta (B.1.617.2) sublineages and alterations in hydrophobicity profiles of the viral proteins caused by these mutations were also studied. Additionally, implications of predictive host miRNA binding/unbinding to emerging spike or nucleocapsid mutations were highlighted. Our results throw considerable light on interesting aspects of the viral genomic variation and provide valuable information for improved understanding of wave-defining mutations in unfolding the pandemic. IMPORTANCE Multiple waves of infection were observed in many states in India during the coronavirus disease 2019 (COVID19) pandemic. Fine-scale evolution of major SARS-CoV-2 lineages and sublineages during four wave-window categories: Pre-Wave 1, Wave 1, Pre-Wave 2, and Wave 2 in four major states of India: Delhi (North), Maharashtra (West), Karnataka (South), and West Bengal (East) was studied using large-scale virus genome sequencing data. Our comprehensive analysis reveals contrasting molecular profiles of the wave-defining mutations and their implications in host miRNA binding/unbinding of the lineages in the major states of India.
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COVID-19 , MicroRNAs , COVID-19/epidemiologia , Genoma Viral , Humanos , Índia/epidemiologia , Mutação , Pandemias , Filogenia , SARS-CoV-2/genéticaRESUMO
Hepatitis B virus (HBV) strains isolated from members of the primitive Paharia ethnic community of Eastern India were studied to gain insight into the genetic diversity and evolution of the virus. The Paharia tribe has remained quite separate from the rest of the Indians and differs culturally, genetically, and linguistically from the mainstream East Indian population, whose HBV strains were previously characterized. Full-length HBV DNA was PCR amplified, cloned, and sequenced. Phylogenetic relationships between the tribal sequences and reference sequences from the mainstream population were assessed, and divergence times of subgenotypes of HBV genotype D were estimated. HBV was found in 2% of the Paharias participating in the study. A predominance of hepatitis B e antigen-negative infection (73%) was observed among the Paharias, and the genome sequences of the HBV strains exhibited relative homogeneity, with a very low prevalence of mutations. The novel feature of Paharia HBV was the exclusive presence of the D5 subgenotype, which was recently identified in Eastern India. Analysis of the four open reading frames (ORFs) of these tribal HBV D5 sequences and comparison with previously reported D1 to D7 sequences enabled the identification of 27 specific amino acid residues, including 6 unique ones, that could be considered D5 signatures. The estimated divergence times among subgenotypes D1 to D5 suggest that D5 was the first to diverge and hence is the most ancient of the D subgenotypes. The presence of a specific, ancient subgenotype of HBV within an ethnically primitive, endogamous population highlights the importance of studies of HBV genetics in well-separated human populations to understand viral transmission between communities and genome evolution.
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Variação Genética , Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Hepatite B/virologia , Adolescente , Adulto , Criança , Clonagem Molecular , Análise por Conglomerados , DNA Viral/química , DNA Viral/genética , Feminino , Genótipo , Vírus da Hepatite B/isolamento & purificação , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase , Grupos Populacionais , Análise de Sequência de DNA , Adulto JovemRESUMO
Direct massively parallel sequencing of SARS-CoV-2 genome was undertaken from nasopharyngeal and oropharyngeal swab samples of infected individuals in Eastern India. Seven of the isolates belonged to the A2a clade, while one belonged to the B4 clade. Specific mutations, characteristic of the A2a clade, were also detected, which included the P323L in RNA-dependent RNA polymerase and D614G in the Spike glycoprotein. Further, our data revealed emergence of novel subclones harbouring nonsynonymous mutations, viz. G1124V in Spike (S) protein, R203K, and G204R in the nucleocapsid (N) protein. The N protein mutations reside in the SR-rich region involved in viral capsid formation and the S protein mutation is in the S2 domain, which is involved in triggering viral fusion with the host cell membrane. Interesting correlation was observed between these mutations and travel or contact history of COVID-19 positive cases. Consequent alterations of miRNA binding and structure were also predicted for these mutations. More importantly, the possible implications of mutation D614G (in SD domain) and G1124V (in S2 subunit) on the structural stability of S protein have also been discussed. Results report for the first time a bird's eye view on the accumulation of mutations in SARS-CoV-2 genome in Eastern India.
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Betacoronavirus , Infecções por Coronavirus , Surtos de Doenças , Interações entre Hospedeiro e Microrganismos , Mutação , Pandemias , Pneumonia Viral , RNA Viral , Betacoronavirus/genética , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Interações entre Hospedeiro e Microrganismos/genética , Humanos , Índia/epidemiologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , RNA Viral/genética , SARS-CoV-2RESUMO
In this work, we present a facile aqueous-phase synthesis of a hybrid catalyst consisting of PtAu alloy supported on Bi2O3 microspheres. Multistep reduction of HAuCl4 and K2PtCl4 salts on Bi2O3 and subsequent annealing lead to the formation of this hybrid catalyst. To the best of our knowledge, this is the first report of using Bi2O3 as a catalyst support in fuel cell applications. The material was characterized by powder X-ray diffraction and various microscopic techniques. This composite showed remarkable activity as well as stability toward the electro-oxidation of ethanol in comparison to commercially available Pt/C. The order of the reactivity was found to be commercial Pt/C (50.4 mA/m2mgPt-1) < Pt/Bi2O3(10) (108 mA/m2mgPt-1) < PtAu/Bi2O3(10) (459 mA/m2mgPt-1). The enhancement in the activity can be explained through cooperative effects, namely, ligand effects of gold and Bi2O3 support, which helps in removing carbon monoxide molecules to avoid the poisoning of the Pt active sites.
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We characterized occult HBV (OHBV) from hepatitis B surface antigen (HBsAg)-negative chronic HCV carriers of Eastern India to explore the impact of genomic variability of HBV in causing undetectability of HBsAg and low viremia that define the occult phenomenon. Screening of sera samples revealed the presence of OHBV in 17.8% of HCV-infected patients. Determination of full-length OHBV sequences and comparison with that from HBsAg-positive carriers led to the detection of distinct substitutions/mutations in PreS2, S, P and X ORFs and in X-promoter and Enhancer-II of OHBV. These mutations were introduced in wild-type HBV and their effects were evaluated by transfection in Huh7 cells. In vitro assays demonstrated that S-substitutions resulted in antigenically modified HBsAg that escaped detection by immunoassays whereas those in ORF-P caused significant decline in viral replication. Impairment in Enhancer-II and X-promoter activities were noted due to occult-associated mutations that generated reduced pregenomic RNA and intracellular HBV-DNA. Additionally, Enhancer-II mutations altered the small to large surface protein ratio and diminished extracellular HBV-DNA and HBsAg secretion. Further, mutations in PreS2, X and enhancer-II increased Grp78-promoter activity, suggesting that OHBV could trigger endoplasmic reticulum stress. Thus viral mutations contribute synergistically towards the genesis of occult phenotype and disease progression.
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Portador Sadio/patologia , Portador Sadio/virologia , Genoma Viral , Vírus da Hepatite B/genética , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Mutação , Adolescente , Adulto , Idoso , Linhagem Celular , Criança , DNA Viral/química , DNA Viral/genética , Chaperona BiP do Retículo Endoplasmático , Feminino , Antígenos de Superfície da Hepatite B/sangue , Hepatócitos/virologia , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Fenótipo , Genética Reversa , Análise de Sequência de DNA , Carga Viral , Adulto JovemRESUMO
BACKGROUND: Gingivo-buccal squamous cell carcinoma (GBSCC) is one of the most common oral cavity cancers in India with less than 50% patients surviving past 5 years. Here, we report a whole transcriptome profile on a batch of GBSCC tumours with diverse tobacco usage habits. The study provides an entire landscape of altered expression with an emphasis on searching for targets with therapeutic potential. METHODS: Whole transcriptomes of 12 GBSCC tumours and adjacent normal tissues were sequenced and analysed to explore differential expression of genes. Expression changes were further compared with those in TCGA head and neck cohort (n = 263) data base and validated in an independent set of 10GBSCC samples. RESULTS: Differentially expressed genes (n = 2176) were used to cluster the patients based on their tobacco habits, resulting in 3 subgroups. Immune response was observed to be significantly aberrant, along with cell adhesion and lipid metabolism processes. Different modes of immune evasion were seen across 12 tumours with up-regulation or consistent expression of CD47, unlike other immune evasion genes such as PDL1, FUT4, CTLA4 and BTLA which were downregulated in a few samples. Variation in infiltrating immune cell signatures across tumours also indicates heterogeneity in immune evasion strategies. A few actionable genes such as ITGA4, TGFB1 and PTGS1/COX1 were over expressed in most samples. CONCLUSION: This study found expression deregulation of key immune evasion genes, such as CD47 and PDL1, and reasserts their potential as effective immunotherapeutic targets for GBSCC, which requires further clinical studies. Present findings reiterate the idea of using transcriptome profiling to guide precision therapeutic strategies.
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Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/imunologia , Neoplasias Bucais/genética , Neoplasias Bucais/imunologia , Transcriptoma/genética , Carcinoma de Células Escamosas/terapia , Ciclo Celular/genética , Ciclo Celular/fisiologia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imunoterapia , Índia , Masculino , MicroRNAs , Neoplasias Bucais/terapiaRESUMO
The indium-rich intermetallic compound EuIrIn4 was synthesized using indium as the active metal flux. The crystal structure of EuIrIn4 was investigated by X-ray powder and single crystal diffraction. EuIrIn4 crystallizes in the YNiAl4 type, Cmcm space group, with lattice parameters, a = 4.5206(9) Å, b = 16.937(3) Å, c = 7.2661(15) Å. Europium atoms in EuIrIn4 are surrounded by three dimensional [IrIn4] polyanionic networks. EuIrIn4 shows two successive antiferromagnetic transitions at 5.4 and 10.8 K. Modified Curie-Weiss fitting on the magnetic susceptibility data within the temperature region 15-300 K gives the effective magnetic moment of 8.45µB/Eu. EuIrIn4 shows pronounced magnetic anisotropy perpendicular to the direction of the applied magnetic field.