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1.
J Am Chem Soc ; 145(33): 18549-18559, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37579341

RESUMO

Organic-inorganic metal hybrids with their tailorable lattice dimensionality and intrinsic spin-splitting properties are interesting material platforms for spintronic applications. While the spin decoherence process is extensively studied in lead- and tin-based hybrids, these systems generally show short spin decoherence lifetimes, and their correlation with the lattice framework is still not well-understood. Herein, we synthesized magnetic manganese hybrid single crystals of (4-fluorobenzylamine)2MnCl4, ((R)-3-fluoropyrrolidinium)MnCl3, and (pyrrolidinium)2MnCl4, which represent a change in lattice dimensionality from 2D and 1D to 0D, and studied their spin decoherence processes using continuous-wave electron spin resonance spectroscopy. All manganese hybrids exhibit nanosecond-scale spin decoherence time τ2 dominated by the symmetry-directed spin exchange interaction strengths of Mn2+-Mn2+ pairs, which is much longer than lead- and tin-based metal hybrids. In contrast to the similar temperature variation laws of τ2 in 2D and 0D structures, which first increase and gradually drop afterward, the 1D structure presents a monotonous rise of τ2 with the temperatures, indicating the strong correlation of spin decoherence with the lattice rigidity of the inorganic framework. This is also rationalized on the basis that the spin decoherence is governed by the competitive contributions from motional narrowing (prolonging the τ2) and electron-phonon coupling interaction (shortening the τ2), both of which are thermally activated, with the difference that the former is more pronounced in rigid crystalline lattices.

2.
Nano Lett ; 22(22): 9020-9026, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36367392

RESUMO

Halide perovskites have been widely explored for numerous optoelectronic applications among which phototransistors have appeared as one of the most promising light signal detectors. However, it is still a great challenge to endow halide perovskites with both mobility and high photosensitivity because of their high sensitivity to moisture in ambient atmosphere. Here, we explore an FAPbBr3 perovskite quantum dot (QD) phototransistor with bandlike charge transport and measure a dark hole mobility of 14.2 cm2 V-1 s-1 at ambient atmosphere. Attaining both high mobility and good optical figures of merit, a detectivity of ∼1016 Jones is achieved, which is a record for halide perovskite nanocrystals. Simple A-site salt (FABr) treatments offer a mechanism for connecting between perovskite QDs for better charge transfer in high-quality devices. All of these important properties are superior to most advanced inorganic semiconductor phototransistors, indicating a promising future in optoelectronic applications.

3.
Mol Med ; 26(1): 59, 2020 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-32552660

RESUMO

BACKGROUND: Pancreatic Ductal Adenocarcinoma (PDAC) is a cancer of the exocrine pancreas and 5-year survival rates remain constant at 7%. Along with PDAC, Periampullary Adenocarcinoma (PAC) accounts for 0.5-2% of all gastrointestinal malignancies. Genomic observations were well concluded for PDAC and PACs in western countries but no reports are available from India till now. METHODS: Targeted Next Generation Sequencing were performed in 8 (5 PDAC and 3 PAC) tumour normal pairs, using a panel of 412 cancer related genes. Primary findings were replicated in 85 tumour samples (31 PDAC and 54 PAC) using the Sanger sequencing. Mutations were also validated by ASPCR, RFLP, and Ion Torrent sequencing. IHC along with molecular dynamics and docking studies were performed for the p.A138V mutant of TP53. Key polymorphisms at TP53 and its associated genes were genotyped by PCR-RFLP method and association with somatic mutations were evaluated. All survival analysis was done using the Kaplan-Meier survival method which revealed that the survival rates varied significantly depending on the somatic mutations the patients harboured. RESULTS: Among the total 114 detected somatic mutations, TP53 was the most frequently mutated (41%) gene, followed by KRAS, SMAD4, CTNNB1, and ERBB3. We identified a novel hotspot TP53 mutation (p.A138V, in 17% of all patients). Low frequency of KRAS mutation (33%) was detected in these samples compared to patients from Western counties. Molecular Dynamics (MD) simulation and DNA-protein docking analysis predicted p.A138V to have oncogenic characteristics. Patients with p.A138V mutation showed poorer overall survival (p = 0.01). So, our finding highlights elevated prevalence of the p53p.A138V somatic mutation in PDAC and pancreatobiliary PAC patients. CONCLUSION: Detection of p.A138V somatic variant in TP53 might serve as a prognostic marker to classify patients. It might also have a role in determining treatment regimes. In addition, low frequency of KRAS hotspot mutation mostly in Indian PDAC patient cohort indicates presence of other early drivers in malignant transformation.


Assuntos
Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/mortalidade , Mutação , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Proteína Supressora de Tumor p53/genética , Alelos , Ampola Hepatopancreática/patologia , Biomarcadores Tumorais , Carcinoma Ductal Pancreático/diagnóstico , Feminino , Genótipo , Mutação em Linhagem Germinativa , Humanos , Estimativa de Kaplan-Meier , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Pancreáticas/diagnóstico , Prognóstico , Neoplasias Pancreáticas
4.
Proc Natl Acad Sci U S A ; 114(26): E5062-E5069, 2017 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-28607082

RESUMO

Interfaces between materials present unique opportunities for the discovery of intriguing quantum phenomena. Here, we explore the possibility that, in the case of superlattices, if one of the layers is made ultrathin, unexpected properties can be induced between the two bracketing interfaces. We pursue this objective by combining advanced growth and characterization techniques with theoretical calculations. Using prototype La2/3Sr1/3MnO3 (LSMO)/BaTiO3 (BTO) superlattices, we observe a structural evolution in the LSMO layers as a function of thickness. Atomic-resolution EM and spectroscopy reveal an unusual polar structure phase in ultrathin LSMO at a critical thickness caused by interfacing with the adjacent BTO layers, which is confirmed by first principles calculations. Most important is the fact that this polar phase is accompanied by reemergent ferromagnetism, making this system a potential candidate for ultrathin ferroelectrics with ferromagnetic ordering. Monte Carlo simulations illustrate the important role of spin-lattice coupling in LSMO. These results open up a conceptually intriguing recipe for developing functional ultrathin materials via interface-induced spin-lattice coupling.

5.
Eye Contact Lens ; 45(4): e15-e23, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31241605

RESUMO

OBJECTIVES: To highlight the clinical characteristics, and visual and corneal tomographic outcomes of central toxic keratopathy (CTK) after contact lens (CL) wear and mechanical debridement. METHODS: A retrospective observational case series with literature review. RESULTS: Four patients (4 eyes) were included in this study; 3 (75%) females, mean age 29.3±8.1 years. The mean follow-up was 13.5±7.5 months. Early central or paracentral stromal opacification, assuming an inverse dome-shaped pattern observed under anterior-segment optical coherence tomography, with corneal flattening (Kmean 40.4±1.3 D) and thinning (mean thinnest pachymetry=404.8±29.4 microns) were observed in all cases. All patients had a recent use of CL wear, with three after mechanical debridement for recurrent corneal erosion syndrome. None of them had any previous laser refractive surgery (LRS). The mean corrected distance visual acuity improved from 20/40 (ranged 20/25-20/50) initially to 20/30 (ranged 20/20-20/40) at final follow-up, and the outcome was not influenced by the use of topical steroids. A mean improvement of corneal flattening (+Kmean 1.2±1.2 D), thinning (+123.5±23.8 microns), and astigmatism (-3.0±2.7 D), via epithelial and stromal remodeling, was observed up to 15 months after CTK. Persisting reduced corneal sensation was noted in all patients at the final follow-up. CONCLUSIONS: Central toxic keratopathy is not an exclusive complication of LRS, and it may occur after CL wear and mechanical debridement. Our findings are similar to those of LRS-related CTK and toxic peripheral keratopathy. Awareness of the clinical associations and understanding of the clinical course and tomographic characteristics of CTK helps obviate unnecessary investigation and overtreatment. Further studies are required to elucidate the underlying pathogenesis of this rare clinical entity.


Assuntos
Lentes de Contato Hidrofílicas/efeitos adversos , Opacidade da Córnea/etiologia , Substância Própria/patologia , Desbridamento , Acuidade Visual/fisiologia , Adulto , Opacidade da Córnea/fisiopatologia , Opacidade da Córnea/cirurgia , Paquimetria Corneana , Substância Própria/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Microscopia com Lâmpada de Fenda , Tomografia de Coerência Óptica , Transtornos da Visão/etiologia , Transtornos da Visão/fisiopatologia , Transtornos da Visão/cirurgia , Adulto Jovem
6.
Eye Contact Lens ; 45(2): e5-e10, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29944507

RESUMO

OBJECTIVES: To report the first case of fungal keratitis caused by Cryptococcus curvatus after penetrating keratoplasty (PK) in an immunocompetent patient and to describe its therapeutic challenge and long-term outcome. METHODS: An interventional case report. RESULTS: A 54-year-old female patient underwent right PK for lattice dystrophy. At 5-year post-PK, she developed a polymicrobial keratitis caused by Candida parapsilosis, and Stenotrophomonas maltophilia at the peripheral graft, which was successfully treated with topical antibiotic and antifungal drops. One year later, another fungal keratitis occurred which apparently resolved with antifungal treatment but recurred in an unusual fashion and required a repeat PK revealing the diagnosis of C. curvatus keratitis. This was confirmed by microbiological culture on Sabouraud dextrose agar, nuclear ribosomal repeat regional sequencing of the D1-D2 and internal transcribed spacer regions, and histopathological examination. Various topical, intracorneal, and systemic antifungal treatments had been attempted but failed to resolve the infection completely, necessitating a subsequent third PK. A further recurrence was noted 16-month post-third PK, which was eradicated with multiple topical and intracorneal antifungal treatment, and direct cryotherapy to the corneal abscess. No further recurrence of C. curvatus was noted at 4-year follow-up. CONCLUSIONS: Cryptococcus curvatus should be added to the known list of organisms capable of causing fungal keratitis. Our experience suggests that this type of organism could cause low-grade, grumbling infection, which may however be exceptionally difficult to treat. Long-term eradication of this rare fungal keratitis could be potentially achieved by intensive ocular and systemic antifungal treatment, repeat therapeutic keratoplasties, and focal cryotherapy.


Assuntos
Candida parapsilosis/isolamento & purificação , Cryptococcus/isolamento & purificação , Infecções Oculares Fúngicas/microbiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Ceratite/microbiologia , Ceratoplastia Penetrante/efeitos adversos , Stenotrophomonas maltophilia/isolamento & purificação , Anti-Infecciosos/uso terapêutico , Candidíase/diagnóstico , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/tratamento farmacológico , Feminino , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Ceratite/diagnóstico , Ceratite/tratamento farmacológico , Pessoa de Meia-Idade , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/microbiologia
7.
BMC Genet ; 19(Suppl 1): 73, 2018 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-30255818

RESUMO

BACKGROUND: The GAW20 group formed on the theme of methods for association analyses of repeated measures comprised 4sets of investigators. The provided "real" data set included genotypes obtained from a human whole-genome association study based on longitudinal measurements of triglycerides (TGs) and high-density lipoprotein in addition to methylation levels before and after administration of fenofibrate. The simulated data set contained 200 replications of methylation levels and posttreatment TGs, mimicking the real data set. RESULTS: The different investigators in the group focused on the statistical challenges unique to family-based association analyses of phenotypes measured longitudinally and applied a wide spectrum of statistical methods such as linear mixed models, generalized estimating equations, and quasi-likelihood-based regression models. This article discusses the varying strategies explored by the group's investigators with the common goal of improving the power to detect association with repeated measures of a phenotype. CONCLUSIONS: Although it is difficult to identify a common message emanating from the different contributions because of the diversity in the issues addressed, the unifying theme of the contributions lie in the search for novel analytic strategies to circumvent the limitations of existing methodologies to detect genetic association.


Assuntos
Estudo de Associação Genômica Ampla , Lipoproteínas HDL/sangue , Triglicerídeos/sangue , Humanos , Hipertrigliceridemia/tratamento farmacológico , Hipertrigliceridemia/genética , Hipoglicemiantes/uso terapêutico , Funções Verossimilhança , Modelos Lineares , Estudos Longitudinais , Fenótipo , Polimorfismo de Nucleotídeo Único
8.
BMC Ophthalmol ; 18(Suppl 1): 224, 2018 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-30255796

RESUMO

BACKGROUND: Suprachoroidal haemorrhage is a rare complication of either medical anticoagulation treatment or intraocular surgical procedures. Suprachoroidal haemorrhages often have devastating visual outcome despite conservative and/or surgical intervention. CASE PRESENTATION: A patient with known Open Angle Glaucoma and Atrial Fibrillation on warfarin presents symptoms and signs suggestive acute angle closure. Examination reveals the underlying cause is a large, macula involving, spontaneous suprachoroidal haemorrhage secondary to loss of anti-coagulation control. Following aggressive medical treatment and surgical intervention, including drainage combined cataract extraction with intraocular lens implant, pars-plana vitrectomy, and external drainage of suprachoroidal haematoma, we managed to preserve the patient's eye and some of its function. CONCLUSION: Spontaneous suprachoroidal haemorrhages are rare complications of loss of anticoagulation control. Our case shows that aggressive treatment in selected cases can offer a relatively good outcome.


Assuntos
Anticoagulantes/efeitos adversos , Transtornos da Coagulação Sanguínea/induzido quimicamente , Hemorragia da Coroide/etiologia , Glaucoma de Ângulo Fechado/etiologia , Varfarina/efeitos adversos , Doença Aguda , Idoso , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Transtornos da Coagulação Sanguínea/diagnóstico , Humanos , Pressão Intraocular , Masculino , Acuidade Visual , Varfarina/uso terapêutico
9.
J Hum Genet ; 62(6): 621-629, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28202950

RESUMO

The classical transmission disequilibrium test (TDT) based on a trio design uses information only on the allele transmitted by a heterozygous parent at a marker locus as homozygous parents are non-informative about linkage. However, the phenotype of an offspring depends on the alleles transmitted by both parents, irrespective of whether the parents are homozygous or heterozygous, and hence carry useful information on association. In this article, we propose modifications to the TDT procedures by incorporating transmission data on both parents in an informative trio to explore possible gain in power in detecting association. For a binary trait, we use a goodness-of-fit χ2 test, whereas for a quantitative trait, we devise two tests: one based on a bivariate response logistic model and the other using a quasi-likelihood approach. We evaluate the type 1 errors and the powers of the proposed tests with those of the classical TDT procedures for both binary and quantitative traits based on extensive simulations. We find that the inclusion of transmission data on non-informative parents yields marginally higher power in the logistic regression approach but results in substantial gain in power in the quasi-likelihood approach. We apply our proposed methods to analyze a count phenotype related to alcoholism.


Assuntos
Estudos de Associação Genética/estatística & dados numéricos , Doenças Genéticas Inatas/genética , Ligação Genética/genética , Locos de Características Quantitativas/genética , Alelos , Simulação por Computador/estatística & dados numéricos , Heterozigoto , Homozigoto , Humanos , Funções Verossimilhança , Desequilíbrio de Ligação , Modelos Genéticos , Fenótipo
10.
J Hum Genet ; 62(3): 389-395, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27829679

RESUMO

Psoriasis is a complex multifactorial chronic inflammatory skin disorder involving both genetic and environmental susceptibility factors. It is strongly associated with HLA-Cw6, but several studies suggested that further genetic factors may confer additional risk. We investigated the association of two single-nucleotide polymorphisms (SNPs), rs3212227 at the 3'-untranslated region and rs7709212 located at ~6.7 kb upstream from the transcription start site of IL12B gene in a case-control study comprising 1702 individuals from India. We found both SNPs were significantly associated with psoriasis (rs7709212: odds ratio (OR)=1.37, P-value=1.09 × 10-5; rs3212227: OR=1.38, P-value=8.88 × 10-6). IL12B gene was significantly upregulated in involved skin of psoriasis patients with risk genotype carriers (rs7709212_TT and rs3212227_TT) compared with non-risk genotype carriers (rs7709212_CC and rs3212227_GG). Significantly higher serum protein concentration of IL12 was also observed among risk allele carriers compared with non-risk allele carriers irrespective of the presence of HLA-Cw6 allele. Haplotype analysis suggested significant increased risk (OR=1.50, P-value=5.01 × 10-8) to the disease when both risk alleles of IL12B were present. IL12 serum protein concentration of risk haplotype (TT-TT) carriers showed significant upregulation compared with the non-risk carriers independent of HLA-Cw6 alleles. Our data suggested the association of IL12B with the psoriasis, however no evidence was observed for the epistatic effect of IL12B with HLA-Cw6 among the psoriasis patients in India.


Assuntos
Predisposição Genética para Doença , Antígenos HLA-C/genética , Subunidade p40 da Interleucina-12/genética , Polimorfismo de Nucleotídeo Único , Psoríase/genética , Regiões 3' não Traduzidas , Adulto , Alelos , Estudos de Casos e Controles , Epistasia Genética , Feminino , Expressão Gênica , Frequência do Gene , Antígenos HLA-C/imunologia , Haplótipos , Humanos , Índia , Subunidade p40 da Interleucina-12/imunologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Psoríase/imunologia , Psoríase/patologia , Risco , Pele/imunologia , Pele/metabolismo , Pele/patologia
11.
Phys Rev Lett ; 119(17): 177603, 2017 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-29219470

RESUMO

The recent discovery of "polar metals" with ferroelectriclike displacements offers the promise of designing ferroelectrics with tunable energy gaps by inducing controlled metal-insulator transitions. Here we employ first-principles calculations to design a metallic polar superlattice from nonpolar metal components and show that controlled intermixing can lead to a true insulating ferroelectric with a tunable band gap. We consider a 2/2 superlattice made of two centrosymmetric metallic oxides, La_{0.75}Sr_{0.25}MnO_{3} and LaNiO_{3}, and show that ferroelectriclike displacements are induced. The ferroelectriclike distortion is found to be strongly dependent on the carrier concentration (Sr content). Further, we show that a metal-to-insulator (MI) transition is feasible in this system via disproportionation of the Ni sites. Such a disproportionation and, hence, a MI transition can be driven by intermixing of transition metal ions between Mn and Ni layers. As a result, the energy gap of the resulting ferroelectric can be tuned by varying the degree of intermixing in the experimental fabrication method.

12.
Nano Lett ; 16(4): 2307-13, 2016 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-26959195

RESUMO

Since the discovery of two-dimensional electron gas (2DEG) at the oxide interface of LaAlO3/SrTiO3 (LAO/STO), improving carrier mobility has become an important issue for device applications. In this paper, by using an alternate polar perovskite insulator (La0.3Sr0.7) (Al0.65Ta0.35)O3 (LSAT) for reducing lattice mismatch from 3.0% to 1.0%, the low-temperature carrier mobility has been increased 30 fold to 35,000 cm(2) V(-1) s(-1). Moreover, two critical thicknesses for the LSAT/STO (001) interface are found, one at 5 unit cells for appearance of the 2DEG and the other at 12 unit cells for a peak in the carrier mobility. By contrast, the conducting (110) and (111) LSAT/STO interfaces only show a single critical thickness of 8 unit cells. This can be explained in terms of polar fluctuation arising from LSAT chemical composition. In addition to lattice mismatch and crystal symmetry at the interface, polar fluctuation arising from composition has been identified as an important variable to be tailored at the oxide interfaces to optimize the 2DEG transport.

13.
Genet Epidemiol ; 39(8): 635-50, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26493781

RESUMO

Binary phenotypes commonly arise due to multiple underlying quantitative precursors and genetic variants may impact multiple traits in a pleiotropic manner. Hence, simultaneously analyzing such correlated traits may be more powerful than analyzing individual traits. Various genotype-level methods, e.g., MultiPhen (O'Reilly et al. []), have been developed to identify genetic factors underlying a multivariate phenotype. For univariate phenotypes, the usefulness and applicability of allele-level tests have been investigated. The test of allele frequency difference among cases and controls is commonly used for mapping case-control association. However, allelic methods for multivariate association mapping have not been studied much. In this article, we explore two allelic tests of multivariate association: one using a Binomial regression model based on inverted regression of genotype on phenotype (Binomial regression-based Association of Multivariate Phenotypes [BAMP]), and the other employing the Mahalanobis distance between two sample means of the multivariate phenotype vector for two alleles at a single-nucleotide polymorphism (Distance-based Association of Multivariate Phenotypes [DAMP]). These methods can incorporate both discrete and continuous phenotypes. Some theoretical properties for BAMP are studied. Using simulations, the power of the methods for detecting multivariate association is compared with the genotype-level test MultiPhen's. The allelic tests yield marginally higher power than MultiPhen for multivariate phenotypes. For one/two binary traits under recessive mode of inheritance, allelic tests are found to be substantially more powerful. All three tests are applied to two different real data and the results offer some support for the simulation study. We propose a hybrid approach for testing multivariate association that implements MultiPhen when Hardy-Weinberg Equilibrium (HWE) is violated and BAMP otherwise, because the allelic approaches assume HWE.


Assuntos
Simulação por Computador/estatística & dados numéricos , Frequência do Gene/genética , Estudo de Associação Genômica Ampla/métodos , Modelos Genéticos , Análise de Regressão , Alelos , Distribuição Binomial , Marcadores Genéticos/genética , Variação Genética/genética , Genótipo , Humanos , Modelos Estatísticos , Fenótipo , Polimorfismo de Nucleotídeo Único/genética
14.
Ann Hum Genet ; 80(6): 336-341, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27699784

RESUMO

This study reports on the association of genetic variants selected from previous genome-wide association studies for type 2 diabetic nephropathy in south Indians. Eight variants were genotyped in 601 type 2 diabetic subjects without nephropathy (DM) and 583 type 2 diabetic subjects with nephropathy (DN) by MassARRAY. The minor allele frequencies of rs11643718 SLC12A3 variant and rs741301 ELMO1 variant were significantly different between DM and DN groups (P = 0.029 and 0.016, respectively). A combined analysis showed that the subjects carrying the risk genotypes of both these variants (GG of rs11643718 + AG/AA of rs741301) had a significant association with DN with an odds ratio [adjusted for age, sex, Body Mass Index (BMI), HbA1c, and systolic Blood Pressure (BP)] of 1.73 (1.30-2.30, P = 1.72 × 10-4 ) as compared to subjects carrying all other genotype combinations. This is the first study to report a significant association of the SLC12A3 rs11643718 and ELMO1 rs741301 (Single nucleotide Polymorphism) SNPs with diabetic nephropathy in south Indians.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Diabetes Mellitus Tipo 2/genética , Nefropatias Diabéticas/genética , Idoso , Povo Asiático , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Feminino , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , Membro 3 da Família 12 de Carreador de Soluto/genética
15.
Genet Epidemiol ; 38 Suppl 1: S63-7, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25112191

RESUMO

Our working group studied methods for joint analyses of multiple phenotypes using the data provided by Genetic Analysis Workshop 18. Two data sets were available: one containing genotypes obtained from a real human whole-genome sequencing study along with longitudinal measurements on systolic and diastolic blood pressure, age, sex, medication use, and tobacco smoking; and the other a simulated data set using the same set of genotypes and phenotype structure as the real data set. The nine sets of investigators in our working group focused on the statistical challenges posed by association analyses of multivariate phenotypes; they applied a wide spectrum of statistical methods, such as linear mixed models, copula models, and semiparametric regression models for simultaneous analyses of longitudinal data on the two blood pressure phenotypes at the genome-wide level. In this report, we discuss the various strategies explored by the different investigators whose common goal was improving the power to detect association with multivariate phenotypes.


Assuntos
Pressão Sanguínea/genética , Estudo de Associação Genômica Ampla , Modelos Genéticos , Fatores Etários , Feminino , Humanos , Estudos Longitudinais , Masculino , Análise Multivariada , Fenótipo , Polimorfismo de Nucleotídeo Único , Fatores Sexuais , Fumar
16.
J Transl Med ; 13: 184, 2015 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-26047609

RESUMO

BACKGROUND: Extreme constitution "Prakriti" types of Ayurveda exhibit systemic physiological attributes. Our earlier genetic study has revealed differences in EGLN1, key modulator of hypoxia axis between Prakriti types. This was associated with differences in high altitude adaptation and susceptibility to high altitude pulmonary edema (HAPE). In this study we investigate other molecular differences that contribute to systemic attributes of Prakriti that would be relevant in predictive marker discovery. METHODS: Genotyping of 96 individuals of the earlier cohort was carried out in a panel of 2,800 common genic SNPs represented in Indian Genomic Variation Consortium (IGVC) panel from 24 diverse populations. Frequency distribution patterns of Prakriti differentiating variations (FDR correction P < 0.05) was studied in IGVC and 55 global populations (HGDP-CEPH) panels. Genotypic interactions between VWF, identified from the present analysis, and EGLN1 was analyzed using multinomial logistic regression in Prakriti and Indian populations from contrasting altitudes. Spearman's Rank correlation was used to study this genotypic interaction with respect to altitude in HGDP-CEPH panel. Validation of functional link between EGLN1 and VWF was carried out in a mouse model using chemical inhibition and siRNA studies. RESULT: Significant differences in allele frequencies were observed in seven genes (SPTA1, VWF, OLR1, UCP2, OR6K3, LEPR, and OR10Z1) after FDR correction (P < 0.05). A non synonymous variation (C/T, rs1063856) associated with thrombosis/bleeding susceptibility respectively, differed significantly between Kapha (C-allele) and Pitta (T-allele) constitution types. A combination of derived EGLN1 allele (HAPE associated) and ancestral VWF allele (thrombosis associated) was significantly high in Kapha group compared to Pitta (p < 10(-5)). The combination of risk-associated Kapha alleles was nearly absent in natives of high altitude. Inhibition of EGLN1 using (DHB) and an EGLN1 specific siRNA in a mouse model lead to a marked increase in vWF levels as well as pro-thrombotic phenotype viz. reduced bleeding time and enhanced platelet count and activation. CONCLUSION: We demonstrate for the first time a genetic link between EGLN1 and VWF in a constitution specific manner which could modulate thrombosis/bleeding susceptibility and outcomes of hypoxia. Integration of Prakriti in population stratification may help assemble common variations in key physiological axes that confers differences in disease occurrence and patho-phenotypic outcomes.


Assuntos
Predisposição Genética para Doença , Genômica , Prolina Dioxigenases do Fator Induzível por Hipóxia/genética , Hipóxia/genética , Ayurveda , Trombose/genética , Fator de von Willebrand/genética , Adaptação Fisiológica/genética , Alelos , Altitude , Animais , Modelos Animais de Doenças , Frequência do Gene/genética , Técnicas de Silenciamento de Genes , Homozigoto , Humanos , Hipóxia/sangue , Hipóxia/complicações , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Índia , Masculino , Camundongos Endogâmicos BALB C , Polimorfismo de Nucleotídeo Único/genética , Reprodutibilidade dos Testes , Trombose/sangue , Trombose/complicações
17.
Tumour Biol ; 35(4): 3409-14, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24297336

RESUMO

Genetic variations at microRNA and microRNA processing genes are known to confer risk of cancer in different populations. Here, we studied variations at eight microRNA (miRNA) and four miRNA processing genes in 452 controls and 451 oral cancer patients by TaqMan genotyping assays. Variant allele-containing genotypes at mir-196a2 and variant allele homozygous genotype at Ran increased the risk of cancer significantly [adjusted odds ratio (OR) (95% confidence interval (CI)) = 1.3 (1-1.7) and 2.3 (1.1-4.6), respectively]. Conversely, variant allele-containing genotypes at mir-34b and variant allele homozygous genotype at Gemin3 reduced the risk of cancer significantly [adjusted OR (95% CI) = 0.7 (0.5-0.9) and 0.6 (0.4-1), respectively]. Cumulative risk was also increased by three times with increase in the number of risk alleles at these four loci. In tobacco stratified analysis, variant allele homozygous genotypes at mir-29a and Ran increased [adjusted OR (95% CI) = 1.5 (1-2.3) and 3 (1.1-8.4) respectively], while variant allele-containing genotypes at mir-34b decreased [adjusted OR (95% CI) = 0.6 (0.4-0.9)] the risk of cancer significantly. Thus, genetic variation at miRNA and processing genes altered the risk of oral cancer in this population thereby corroborating studies in other populations. However, it is necessary to validate this result in different Indian sub populations with larger sample sizes and examine the effect of these variations in tumour tissues to explain the mechanism of risk alteration.


Assuntos
Predisposição Genética para Doença , MicroRNAs/genética , Neoplasias Bucais/genética , Adulto , Idoso , Feminino , Variação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/etiologia , Polimorfismo de Nucleotídeo Único , Risco
18.
J Phys Chem Lett ; 15(15): 4206-4211, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38598716

RESUMO

Understanding the nanoscale elastic-size-effects of atomically thin transition-metal dichalcogenides (TMDs) as a function of thickness underpins the avenue of flexible 2D electronics. In this work, we employed the atomic force acoustic microscopy (AFAM) technique to investigate the thickness-dependent elastic properties of CVD grown 2H-MoS2 films. The monolayer MoS2 exhibited a Young's modulus of 273 ± 27 GPa. Our systematic analysis from bulk to monolayer suggests that the 2H-MoS2 phase exhibits nanoscale elastic-stiffening behavior with decreasing number of layers (thickness). The Young's modulus increased by a factor of ∼2.7 for monolayer MoS2 when compared with the bulk. First-principle DFT calculations affirm the nanoscale elastic-stiffening behavior of MoS2 with decreasing number of layers. Our findings suggest that the observed elastic stiffening is due to the interlayer sliding, which may be facilitated by defects in MoS2 layers. The observed elastic stiffening may be of potential importance for understanding TMD based nanomechanical devices.

19.
Nat Commun ; 15(1): 5556, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956033

RESUMO

Chiral multiferroics offer remarkable capabilities for controlling quantum devices at multiple levels. However, these materials are rare due to the competing requirements of long-range orders and strict symmetry constraints. In this study, we present experimental evidence that the coexistence of ferroelectric, magnetic orders, and crystallographic chirality is achievable in hybrid organic-inorganic perovskites [(R/S)-ß-methylphenethylamine]2CuCl4. By employing Landau symmetry mode analysis, we investigate the interplay between chirality and ferroic orders and propose a novel mechanism for chirality transfer in hybrid systems. This mechanism involves the coupling of non-chiral distortions, characterized by defining a pseudo-scalar quantity, ξ = p ⋅ r ( p represents the ferroelectric displacement vector and r denotes the ferro-rotational vector), which distinguishes between (R)- and (S)-chirality based on its sign. Moreover, the reversal of this descriptor's sign can be associated with coordinated transitions in ferroelectric distortions, Jahn-Teller antiferro-distortions, and Dzyaloshinskii-Moriya vectors, indicating the mediating role of crystallographic chirality in magnetoelectric correlations.

20.
J Hum Genet ; 58(1): 27-32, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23151679

RESUMO

Common variants near melanocortin 4 receptor (MC4R) gene are shown to be associated with adiposity but have varied effects in different age groups. Among Indians, studies have shown association of these variants with obesity in adults, but their association in children is yet to be confirmed. We evaluated association of rs17782313 and rs12970134 near MC4R with adiposity and related traits in Indians including 1362 children and 4077 adults (consisting of 2049 diabetic and 2028 nondiabetic adult subjects). Both variants rs17782313 and rs12970134 showed strong association with adiposity measures (weight, body mass index and waist circumference) in children (P-range 7.6 × 10(-5)-3.8 × 10(-12)) and nominal association in nondiabetic adults (P-range 0.05-0.003). Effect sizes on adiposity measures in children (ß range 0.22-0.26 Z-score) were ~3-fold higher compared with adults (ß range 0.06-0.08). The minor alleles of both variants showed borderline association (P-range 0.08-0.04) with risk of type 2 diabetes in adults. Meta-analysis of rs12970134 in >12 000 Indian adults corroborated its association with adiposity (P≤2.2 × 10(-9)), homeostasis model assessment-estimated insulin resistance (P=4.0 × 10(-5)) and type 2 diabetes (P=0.003) with only moderate heterogeneity, suggesting similar effect on adult Indians residing in different geographical regions. In conclusion, the study demonstrates association of variants near MC4R with obesity and related traits in Indian children and adults, with higher impact during childhood.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Variação Genética , Obesidade/genética , Receptor Tipo 4 de Melanocortina/genética , População Branca/genética , Adiposidade/genética , Adolescente , Adulto , Alelos , Peso Corporal , Criança , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Feminino , Predisposição Genética para Doença , Humanos , Índia , Resistência à Insulina/genética , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/fisiopatologia , Fenótipo , Polimorfismo de Nucleotídeo Único , Circunferência da Cintura
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