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1.
J Clin Exp Hepatol ; 14(5): 101411, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38699514

RESUMO

Aim: Hepatogenous diabetes (HD) is frequently underestimated among cirrhosis patients. The current study assessed the magnitude, clinical characteristics, and implications of HD in cirrhosis patients as compared to the patients with type-2 diabetes mellitus (T2DM) and non-diabetes (ND) cirrhosis. Methods: In a prospective observational study, 338 consecutive eligible cirrhosis patients were screened for diabetes mellitus. A 2-hour oral glucose tolerance test (OGTT) was used to detect HD. The clinical characteristics, complications, and outcomes were ascertained and compared amongst HD, T2DM, and ND patients. Results: In the final study cohort of 316 patients, the proportion of HD, T2DM, and ND was 22.5% (n = 71), 26.3% (n = 83), and 51.3% (n = 162), respectively. HD was the predominant form of diabetes (68.9%) in Child-Pugh class-C cirrhosis. The majority (73%) of HD patients had abnormal OGTT without fasting hyperglycaemia. A lower cut-off of 98.5 mg/dl for fasting blood glucose had a modest sensitivity (72%) and specificity (75%) for predicting HD. In comparison to T2DM patients, HD patients were younger, leaner, and had more advanced cirrhosis. In comparison to ND patients, HD patients were leaner but had higher glycemic indices, serum cholesterol, and arterial ammonia levels. During a median follow-up period of 12 (03-21) months, the frequency of hepatic encephalopathy and variceal haemorrhage were higher in HD and T2DM patients compared to that in the ND group. Conclusions: HD is prevalent in about one fifth of cirrhosis patients. It differs from T2DM and ND in a number of ways, and has association with complications of cirrhosis.

2.
Environ Sci Pollut Res Int ; 31(3): 4012-4024, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38097829

RESUMO

In developing nations, solid residential fuels are the major sources of primary energy for various domestic activities. To date, the emission inventory of inorganic trace gases over National Capital Territory (NCT) was prepared using either default or country-specific emission factors. In this paper, we report (for the first time) the spatial variation of emission factors (EFs) of inorganic trace gases (SO2, NO, NO2, CO, CO2, and CH4) from the residential fuels used in slums and rural areas of NCT determined using dilution chamber in the laboratory. 147 residential fuel samples, including fuelwood, dung cake, crop residues, coal, etc., were collected at 149 NCT locations out of 675 slum clusters and 146 rural villages. The range of EF(s) of SO2 (0.02 ± 0.01 to 0.04 ± 0.01 g kg-1), CH4 (0.10 to 0.34 g kg-1), NO2 (0.01 to 0.02 g kg-1) is lower than the CO (3.55 ± 1.72 to 6.07 ± 1.53 g kg-1) and CO2 (0 to 129.45 ± 46.94 g kg-1). The north and north west districts of NCT are emission hotspots for CH4, NO, and NO2 emissions, whereas, the southern and northern areas of NCT are for CO2. These citywide emission inventories (0.05° × 0.05°) of inorganic trace gases are prepared using laboratory-determined EFs and available consumption data determined by recent survey information. Among solid residential fuels, fuel wood, and dung cake are two major contributors to inorganic trace gases in NCT.


Assuntos
Poluentes Atmosféricos , Poluentes Atmosféricos/análise , Gases , Dióxido de Carbono/análise , Dióxido de Nitrogênio , Carvão Mineral
3.
World J Hepatol ; 15(10): 1140-1152, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37970615

RESUMO

BACKGROUND: The lymphatic system is crucial in maintaining the body fluid homeostasis. A dysfunctional lymphatic system may contribute to the refractoriness of ascites and edema in cirrhosis patients. Therefore, assessment of lymphatic dysfunction in cirrhosis patients with refractory ascites (RA) can be crucial as it would call for using different strategies for fluid mobilization. AIM: To assessing the magnitude, spectrum, and clinical associations of lymphatic dysfunction in liver cirrhosis patients with RA. METHODS: This observational study included 155 consecutive cirrhosis patients with RA. The presence of clinical signs of lymphedema, such as peau d'orange appearance and positive Stemmer sign, intestinal lymphangiectasia (IL) on duodenal biopsy seen as dilated vessels in the lamina propria with strong D2-40 immunohistochemistry, and chylous ascites were used to diagnose the overt lymphatic dysfunctions. RESULTS: A total of 69 (44.5%) patients out of 155 had evidence of lymphatic dysfunction. Peripheral lymphedema, found in 52 (33.5%) patients, was the most common manifestation, followed by IL in 42 (27.0%) patients, and chylous ascites in 2 (1.9%) patients. Compared to patients without lymphedema, those with lymphedema had higher mean age, median model for end-stage liver disease scores, mean body mass index, mean ascitic fluid triglyceride levels, and proportion of patients with hypoproteinemia (serum total protein < 5 g/dL) and lymphocytopenia (< 15% of total leukocyte count). Patients with IL also had a higher prevalence of lymphocytopenia and hypoproteinemia (28.6% vs. 9.1%, P = 0.004). Seven (13%) patients with lymphedema had lower limb cellulitis compared to none in those without it. On multivariate regression analysis, factors independently associated with lymphatic dysfunction included obesity [odds ratio (OR): 4.2, 95% confidence intervals (95%CI): 1.1-15.2, P = 0.027], lymphocytopenia [OR: 6.2, 95%CI: 2.9-13.2, P < 0.001], and hypoproteinemia [OR: 3.7, 95%CI: 1.5-8.82, P = 0.003]. CONCLUSION: Lymphatic dysfunction is common in cirrhosis patients with RA. Significant indicators of its presence include hypoproteinemia and lymphocytopenia, which are likely due to the loss of lymphatic fluid from the circulation. Future efforts to mobilize fluid in these patients should focus on methods to improve lymphatic drainage.

4.
J Environ Manage ; 341: 118055, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37141725

RESUMO

Second-generation bioenergy, a carbon neutral or negative renewable resource, is crucial to achieving India's net-zero emission targets. Crop residues are being targeted as a bioenergy resource as they are otherwise burned on-field, leading to significant pollutant emissions. But estimating their bioenergy potential is problematic because of broad assumptions about their surplus fractions. Here, we use comprehensive surveys and multivariate regression models to estimate the bioenergy potential of surplus crop residues in India. These are with high sub-national and crop disaggregation that can facilitate the development of efficient supply chain mechanisms for its widespread usage. The estimated potential for 2019 of 1313 PJ can increase the present bioenergy installed capacity by 82% but is likely insufficient alone to meet India's bioenergy targets. The shortage of crop residue for bioenergy, combined with the sustainability concerns raised by previous studies, imply a need to reassess the strategy for the use of this resource.


Assuntos
Agricultura , Poluentes Ambientais , Índia , Carbono
5.
World J Virol ; 11(5): 237-251, 2022 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-36188741

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic continues to be a global problem with over 438 million cases reported so far. Although it mostly affects the respiratory system, the involvement of extrapulmonary organs, including the liver, is not uncommon. Since the beginning of the pandemic, metabolic com-orbidities, such as obesity, diabetes, hypertension, and dyslipidemia, have been identified as poor prognostic indicators. Subsequent metabolic and lipidomic studies have identified several metabolic dysfunctions in patients with COVID-19. The metabolic alterations appear to be linked to the course of the disease and inflammatory reaction in the body. The liver is an important organ with high metabolic activity, and a significant proportion of COVID-19 patients have metabolic comorbidities; thus, this factor could play a key role in orchestrating systemic metabolic changes during infection. Evidence suggests that metabolic dysregulation in COVID-19 has both short- and long-term metabolic implications. Furthermore, COVID-19 has adverse associations with metabolic-associated fatty liver disease. Due to the ensuing effects on the renin-angiotensin-aldosterone system and ammonia metabolism, COVID-19 can have significant implications in patients with advanced chronic liver disease. A thorough understanding of COVID-19-associated metabolic dysfunction could lead to the identification of important plasma biomarkers and novel treatment targets. In this review, we discuss the current understanding of metabolic dysfunction in COVID-19, focusing on the liver and exploring the underlying mechanistic pathogenesis and clinical implications.

6.
Sci Adv ; 8(23): eabj2820, 2022 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-35675405

RESUMO

A notable number of acute lymphoblastic leukemia (ALL) patients develop CD19-positive relapse within 1 year after receiving chimeric antigen receptor (CAR) T cell therapy. It remains unclear if the long-term response is associated with the characteristics of CAR T cells in infusion products, hindering the identification of biomarkers to predict therapeutic outcomes. Here, we present 101,326 single-cell transcriptomes and surface protein landscape from the infusion products of 12 ALL patients. We observed substantial heterogeneity in the antigen-specific activation states, among which a deficiency of T helper 2 function was associated with CD19-positive relapse compared with durable responders (remission, >54 months). Proteomic data revealed that the frequency of early memory T cells, rather than activation or coinhibitory signatures, could distinguish the relapse. These findings were corroborated by independent functional profiling of 49 patients, and an integrative model was developed to predict the response. Our data unveil the molecular mechanisms that may inform strategies to boost specific T cell function to maintain long-term remission.


Assuntos
Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras , Antígenos CD19 , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Proteômica , Receptores de Antígenos Quiméricos/metabolismo , Recidiva
7.
Exp Appl Acarol ; 86(4): 549-566, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35445372

RESUMO

An epidemiological study was performed to determine the role of dogs and ticks infesting dogs in the transmission of Q fever in humans and animals from April 2019 to March 2020 in the northeastern hill states of India. In total, 245 pet and stray dogs irrespective of age or sex were sampled, without specific inclusion or exclusion criteria. In total, 478 ticks belonging to three species were detected, namely Rhipicephalus sanguineus, Rhipicephalus (Boophilus) microplus and Hyalomma anatolicum anatolicum. The DNA extracted from blood and tick samples was assayed for molecular characterization of Coxiella burnetii targeting the 16S rRNA and superoxide dismutase (SOD) genes. Amplified PCR products were purified, cloned and custom sequenced. PCR assay showed 3.3% (8/245) of the dogs were positive for Coxiella-like bacteria. Coxiella-like bacterial DNA was detected in adult fully engorged females of R. sanguineus (7.7%, 13/168), R. (B.) microplus (3.3%, 4/123) and H. anatolicum (1.9%, 1/54). Coxiella-like bacterial DNA lacked in adult male or nymphal stage. The infection rate did not vary significantly between seasons, nor according to sex or age of the host. Six nucleotide sequences of 16S rRNA and SOD genes are discussed.


Assuntos
Rhipicephalus sanguineus , Rhipicephalus , Animais , Coxiella/genética , DNA Bacteriano/genética , Cães , Feminino , Masculino , Filogenia , RNA Ribossômico 16S/genética , Rhipicephalus/genética , Rhipicephalus sanguineus/genética , Superóxido Dismutase/genética
8.
Cureus ; 14(2): e21920, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35273865

RESUMO

For decades, endoscopic retrograde cholangiopancreatography (ERCP) has been the cornerstone in the treatment of several biliopancreatic diseases. Although it is a relatively safe procedure, there are certain hazards involved. Hepatic subcapsular hematoma (HSH) is an uncommon complication of ERCP, with only a few cases reported in the literature to date. We present here a case of large HSH that developed 48 hours after an otherwise uneventful ERCP for choledocholithiasis. After being apparently well for the first two days post-ERCP, the patient began to develop abdominal pain and restlessness associated with hemodynamic instability and a decline in hemoglobin levels. Computed tomography (CT) confirmed the presence of a large HSH. The patient was managed nonsurgically with vascular angioembolization followed by ultrasound-guided percutaneous catheter drainage of hematoma. This case highlights the necessity of increasing awareness about this complication in order to aid in early diagnosis and management.

9.
Environ Sci Pollut Res Int ; 29(12): 17892-17918, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34686959

RESUMO

In the present study, total suspended particulate matter (TSP) samples were collected at 47 different sites (47 grids of 5 × 5 km2 area) of Delhi during winter (January-February 2019) in campaign mode. To understand the spatial variation of sources, TSP samples were analyzed for chemical compositions including carbonaceous species [organic carbon (OC), elemental carbon (EC), and water-soluble organic carbon (WSOC)], water-soluble total nitrogen (WSTN), water-soluble inorganic nitrogen (WSIN), polycyclic aromatic hydrocarbons (16 PAHs), water-soluble inorganic species (WSIS) (F-, Cl-, SO42-, NO2-, NO3-, PO43-, NH4+, Ca2+, Mg2+, Na+, and K+), and major and minor trace elements (B, Na, Mg, Al, P, S, Cl, K, Ca, Ti, Fe, Zn, Cr, Mn, Cu, As, Pd, F, and Ag). During the campaign, the maximum concentration of several components of TSP (996 µg/m3) was recorded at the Rana Pratap Bagh area, representing a pollution hotspot of Delhi. The maximum concentrations of PAHs were recorded at Udhyog Nagar, a region close to heavily loaded diesel vehicles, small rubber factories, and waste burning areas. Higher content of Cl- and Cl-/Na+ ratio (>1.7) suggests the presence of nonmarine anthropogenic sources of Cl- over Delhi. Minimum concentrations of OC, EC, WSOC, PAHs, and WSIS in TSP were observed at Kalkaji, representing the least polluted area in Delhi. Enrichment factor <5.0 at several locations and a significant correlation of Al with Mg, Fe, Ti, and Ca and C/N ratio indicated the abundance of mineral/crustal dust in TSP over Delhi. Principal component analysis (PCA) was also performed for the source apportionment of TSP, and extracted soil dust was found to be the major contributor to TSP, followed by biomass burning, open waste burning, secondary aerosol, and vehicular emissions.


Assuntos
Poluentes Atmosféricos , Material Particulado , Aerossóis/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental , Índia , Tamanho da Partícula , Material Particulado/análise , Estações do Ano , Emissões de Veículos/análise
10.
J Hazard Mater ; 424(Pt B): 127507, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34879512

RESUMO

Red mud is a solid hazardous alumina industrial waste, which is rich in iron, titanium, aluminum, silicon, calcium, etc. The red mud contains 30-60% of hematite, which is suitable for shielding high energy X- and gamma rays. So, the iron rich red mud was converted into diagnostic X-ray shielding tiles through ceramic route by adding a certain weight percentage of BaSO4 and binders (kaolin clay or sodium hexametaphosphate) with it. The kaolin clay tile possess sufficient impact strength (failure point is 852 mm for 19 mm steel ball) and flexural strength of ~25 N/mm2, which is suitable for wall applications. The 10.3 mm and 14.7 mm thick red mud:BaSO4:kaolin clay tile possess the attenuation equivalent to 2 mm and 2.3 mm lead at 125 kVp and 140 kVp, respectively. No heavy elements were found to leach out except chromium and arsenic from the sintered tiles. However, the leaching of Cr (0.6 ppm) and As (0.015 ppm) was found to be well below the permissible limit. These tiles can be used in the X-ray diagnosis, CT scanner, bone densitometry, and cath labs instead of toxic lead sheet and thereby to protect the operating personnel, public, and environment from radiation hazards.


Assuntos
Óxido de Alumínio , Resíduos Perigosos , Cerâmica , Resíduos Industriais/análise , Ferro , Radiografia
11.
J Exp Med ; 218(10)2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34402853

RESUMO

Immunoglobulin and T cell receptor gene assembly depends on V(D)J recombination initiated by the RAG1-RAG2 recombinase. The RAG1 N-terminal region (NTR; aa 1-383) has been implicated in regulatory functions whose influence on V(D)J recombination and lymphocyte development in vivo is poorly understood. We generated mice in which RAG1 lacks ubiquitin ligase activity (P326G), the major site of autoubiquitination (K233R), or its first 215 residues (Δ215). While few abnormalities were detected in R1.K233R mice, R1.P326G mice exhibit multiple features indicative of reduced recombination efficiency, including an increased Igκ+:Igλ+ B cell ratio and decreased recombination of Igh, Igκ, Igλ, and Tcrb loci. Previous studies indicate that synapsis of recombining partners during Igh recombination occurs through two pathways: long-range scanning and short-range collision. We find that R1Δ215 mice exhibit reduced short-range Igh and Tcrb D-to-J recombination. Our findings indicate that the RAG1 NTR regulates V(D)J recombination and lymphocyte development by multiple pathways, including control of the balance between short- and long-range recombination.


Assuntos
Proteínas de Homeodomínio/metabolismo , Recombinação V(D)J/fisiologia , Animais , Linfócitos B/fisiologia , Feminino , Proteínas de Homeodomínio/genética , Imunoglobulinas/genética , Linfócitos/fisiologia , Masculino , Camundongos Mutantes , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Subpopulações de Linfócitos T/fisiologia , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
12.
Cancer J ; 27(2): 151-158, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33750075

RESUMO

ABSTRACT: Chimeric antigen receptor T therapy has heralded a new era in the treatment of acute lymphoblastic leukemia (ALL) and other hematologic malignancies. In this autologous immunotherapy, patient-derived T cells are genetically engineered and then infused back to kill the leukemia cells. The observed response rates in ALL are a testament to the success of this therapy. However, there have been instances where the patients either did not respond or relapsed after initial response. Emergence of resistance due to antigen loss and T-cell exhaustion has been observed. This poses a challenge in making this therapy successful for every ALL patient and warrants deeper understanding of emergence of resistance and potential approaches to overcome them. Here we discuss current perspectives and advances in this area.


Assuntos
Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Antígenos Quiméricos , Terapia Baseada em Transplante de Células e Tecidos , Criança , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos Quiméricos/genética
13.
Immunity ; 49(4): 764-779.e9, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30332632

RESUMO

The major types of non-small-cell lung cancer (NSCLC)-squamous cell carcinoma and adenocarcinoma-have distinct immune microenvironments. We developed a genetic model of squamous NSCLC on the basis of overexpression of the transcription factor Sox2, which specifies lung basal cell fate, and loss of the tumor suppressor Lkb1 (SL mice). SL tumors recapitulated gene-expression and immune-infiltrate features of human squamous NSCLC; such features included enrichment of tumor-associated neutrophils (TANs) and decreased expression of NKX2-1, a transcriptional regulator that specifies alveolar cell fate. In Kras-driven adenocarcinomas, mis-expression of Sox2 or loss of Nkx2-1 led to TAN recruitment. TAN recruitment involved SOX2-mediated production of the chemokine CXCL5. Deletion of Nkx2-1 in SL mice (SNL) revealed that NKX2-1 suppresses SOX2-driven squamous tumorigenesis by repressing adeno-to-squamous transdifferentiation. Depletion of TANs in SNL mice reduced squamous tumors, suggesting that TANs foster squamous cell fate. Thus, lineage-defining transcription factors determine the tumor immune microenvironment, which in turn might impact the nature of the tumor.


Assuntos
Diferenciação Celular/imunologia , Regulação Neoplásica da Expressão Gênica/imunologia , Fatores de Transcrição SOXB1/imunologia , Microambiente Tumoral/imunologia , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Diferenciação Celular/genética , Linhagem Celular Tumoral , Linhagem da Célula/genética , Linhagem da Célula/imunologia , Células Cultivadas , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Células HEK293 , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Fator Nuclear 1 de Tireoide/genética , Fator Nuclear 1 de Tireoide/metabolismo , Microambiente Tumoral/genética
14.
Genome Announc ; 6(24)2018 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-29903807

RESUMO

The complete genome sequence of classical swine fever virus (CSFV) strain CSFV-UP-BR-KHG-06, from genotype 2.2, was determined. Comparative analysis based on the amino acid sequence of some important B-cell epitopes, T-cell epitopes, glycosylation sites, and conformational residues showed the striking differences between the group 2 virus KHG-06 and the vaccine strains HCLV/India and C-strain.

15.
Avian Dis ; 62(2): 218-225, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29944399

RESUMO

In recent years, acute severe outbreaks of infectious bursal disease (IBD) are frequently observed in commercial chicken populations of the North East Region (NER) of India, resulting in huge economic loses to poultry farmers. Field outbreaks of IBD in 30 different poultry farms in the NER were confirmed by clinicopathologic examination and reverse transcriptase PCR. A total of 10 isolates of IBD virus (IBDV) from these outbreaks were characterized by the genetic analysis of VP1 and the hypervariable region of the VP2 gene. Nucleotide sequences, deduced amino acid sequences, and phylogenetic analysis of both VP2 and VP1 genes revealed two genetically diverse strains of very virulent IBDV (vvIBDV) and one intermediate strain circulating in the NER. These isolates differ at nucleotide and amino acid levels from vvIBDV isolates of mainland India and are clustered in distinctly separate groups in the phylogenetic tree. Six of the isolates revealed a unique combination of vvIBDV amino acid signatures in the VP2 gene (A222, I256, I294), while bearing the non-vvIBDV amino acid signatures of the VP1 gene (146E, 147G, 242D), but they are clearly classified as vvIBDV in a phylogenetic analysis of both genes. Interestingly, one of the isolates showed 99% sequence homology with attenuated vaccine strains in the VP2 gene and clustered together. This study demonstrates the diversity of IBDVs in India and document for the first time the possible involvement of attenuated vaccine strains in the epidemiology of IBD in India.


Assuntos
Infecções por Birnaviridae/veterinária , Variação Genética , Vírus da Doença Infecciosa da Bursa/genética , Doenças das Aves Domésticas/virologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Infecções por Birnaviridae/epidemiologia , Infecções por Birnaviridae/virologia , Proteínas do Capsídeo/química , Proteínas do Capsídeo/genética , Galinhas , Surtos de Doenças/veterinária , Índia/epidemiologia , Vírus da Doença Infecciosa da Bursa/classificação , Vírus da Doença Infecciosa da Bursa/isolamento & purificação , Filogenia , Doenças das Aves Domésticas/epidemiologia , Alinhamento de Sequência
16.
Phys Chem Chem Phys ; 19(46): 31452-31460, 2017 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-29159331

RESUMO

Geometry optimizations of anion (C and N) doped anatase TiO2 were carried out by using DFT+U calculations. Various anion vacancy sites were examined to study the synergistic effects of anion doping accompanied with anion vacancy formation on lattice oxygen activation. Two non-identical crystal planes (0 0 1) and (1 0 0) were chosen for C and N substitutions. Energetically favoured N-vacancy pairs were identified on TiO2 surfaces. Substitution of N along with anion vacancies at various sites was energetically more favoured than that of C-doping in bulk TiO2 while the energies were comparable for surface substitutions. Bond length distributions due to the formation of differential bonds were determined. Net oxygen activation and accompanying reversible oxygen exchange capacities were compared for TiO2-2xCx and TiO2-3xN2x. Substitution of C in the surface exposed (1 0 0) plane of TiO2 resulted in 47.6% and 23.8% of bond elongation and compression, respectively, resulting in 23.8% of net oxygen activation which was higher when compared to N substitution in the (1 0 0) plane of TiO2 resulting in a net oxygen activation of 17%.

17.
Trends Genet ; 33(7): 479-489, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28532625

RESUMO

It has been recognized for 40 years that the variable (diversity) joining [V(D)J] recombination-mediated assembly of diverse B and T lymphocyte antigen receptor (AgR) genes is not only essential for adaptive immunity, but also a risk for autoimmunity and lymphoid malignancies. Over the past few years, several studies have revealed that recombination-activating gene (RAG) endonuclease-induced DNA double-strand breaks (DSBs) transcend hazardous intermediates during antigen receptor gene assembly. RAG cleavage within the genomes of lymphocyte progenitors and immature lymphocytes regulates the expression of ubiquitous and lymphocyte-specific gene transcripts to control the differentiation and function of both adaptive and innate immune cell lineages. These unexpected discoveries raise important new questions that have broad implications for basic immunology research and the screening, diagnosis, and treatment of human immunological disease.


Assuntos
Dano ao DNA , Imunidade/genética , Recombinação V(D)J , Animais , Humanos
18.
J Neuroimaging ; 27(4): 421-427, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-27996178

RESUMO

PURPOSE: Compared to the intracranial vasculature in sickle cell disease (SCD) patients, the morphologic changes of the extracranial vasculature in SCD patients are less well understood. The purpose of this study was to evaluate the tortuosity of the extracranial carotid and vertebral arteries in patients with SCD compared to age-matched controls. METHODS: Following Institution Review Board approval, between January 2004 and December 2013, Magnetic resonance angiogram neck examinations were retrospectively reviewed on 56 patients with SCD and 56 age-matched controls. Vessel tortuosity was measured as curved vector lengths in the common carotid, extracranial internal carotid, and vertebral arteries bilaterally. Correlation of vessel tortuosity with age and hematocrit level was assessed. Paired and unpaired Student's t-tests were performed to determine within and between group differences. RESULTS: Greater tortuosity in extracranial carotid and vertebral arteries were noted in patients with SCD as compared to age-matched control patients (P < .001). Greater differences in tortuosity between carotid and vertebral arteries were noted in SCD patients as compared to differences in control patients. Incidence of infarction was significantly associated with greater tortuosity of right carotid (P = .002), right (P = .004), and left (P = .020) vertebral arteries. CONCLUSIONS: Extracranial carotid and vertebral arterial tortuosity is increased in SCD patients. This could be related to aberrations in hemodynamics from nonlaminar flow in these vessels. These increases in extracranial vascular tortuosity could potentially lead to alterations in intracranial vascular tortuosity and may be an independent risk factor for cerebral infarct.


Assuntos
Anemia Falciforme/diagnóstico por imagem , Artérias/anormalidades , Artérias Carótidas/diagnóstico por imagem , Instabilidade Articular/diagnóstico por imagem , Dermatopatias Genéticas/diagnóstico por imagem , Malformações Vasculares/diagnóstico por imagem , Artéria Vertebral/diagnóstico por imagem , Adolescente , Adulto , Artérias/diagnóstico por imagem , Feminino , Humanos , Masculino , Estudos Retrospectivos , Adulto Jovem
19.
Cell Cycle ; 15(21): 2882-2894, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27327568

RESUMO

Mammalian cells are thought to protect themselves and their host organisms from DNA double strand breaks (DSBs) through universal mechanisms that restrain cellular proliferation until DNA is repaired. The Cyclin D3 protein drives G1-to-S cell cycle progression and is required for proliferation of immature T and B cells and of mature B cells during a T cell-dependent immune response. We demonstrate that mouse thymocytes and pre-B cells, but not mature B cells, repress Cyclin D3 protein levels in response to DSBs. This response requires the ATM protein kinase that is activated by DSBs. Cyclin D3 protein loss in thymocytes coincides with decreased association of Cyclin D3 mRNA with the HuR RNA binding protein that ATM regulates. HuR inactivation reduces basal Cyclin D3 protein levels without affecting Cyclin D3 mRNA levels, indicating that thymocytes repress Cyclin D3 expression via ATM-dependent inhibition of Cyclin D3 mRNA translation. In contrast, ATM-dependent transcriptional repression of the Cyclin D3 gene represses Cyclin D3 protein levels in pre-B cells. Retrovirus-driven Cyclin D3 expression is resistant to transcriptional repression by DSBs; this prevents pre-B cells from suppressing Cyclin D3 protein levels and from inhibiting DNA synthesis to the normal extent following DSBs. Our data indicate that immature B and T cells use lymphocyte lineage- and developmental stage-specific mechanisms to inhibit Cyclin D3 protein levels and thereby help prevent cellular proliferation in response to DSBs. We discuss the relevance of these cellular context-dependent DSB response mechanisms in restraining proliferation, maintaining genomic integrity, and suppressing malignant transformation of lymphocytes.


Assuntos
Linhagem da Célula , Ciclina D3/genética , Quebras de DNA de Cadeia Dupla , Crescimento e Desenvolvimento , Linfócitos/citologia , Animais , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Linfócitos B/citologia , Linfócitos B/efeitos da radiação , Linhagem da Célula/genética , Linhagem da Célula/efeitos da radiação , Proliferação de Células/efeitos da radiação , Ciclina D3/metabolismo , DNA/biossíntese , Quebras de DNA de Cadeia Dupla/efeitos da radiação , Regulação para Baixo/efeitos da radiação , Proteína Semelhante a ELAV 1/metabolismo , Crescimento e Desenvolvimento/genética , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Radiação Ionizante , Retroviridae/metabolismo , Transdução de Sinais/efeitos da radiação , Especificidade por Substrato/efeitos da radiação , Linfócitos T/citologia , Linfócitos T/efeitos da radiação , Transcrição Gênica/efeitos da radiação
20.
Tech Vasc Interv Radiol ; 18(3): 170-5, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26365547

RESUMO

Irreversible electroporation (IRE) induces cell death by exposing it to high-voltage, low-energy DC current pulses. The mechanism of cell death and healing is a departure from the other existing technologies such as radiofrequency ablation, microwave ablation, and cryoablation. These thermal ablative technologies have several applications in oncology but have limitations that have also been established. IRE has shown promise to overcome some of these limitations and has enabled the use of an ablative technology in treating lesions close to the bile ducts and vasculature and in organs such as the pancreas. This review highlights some of the niche applications of IRE and the data so far.


Assuntos
Técnicas de Ablação , Eletroporação/métodos , Neoplasias/cirurgia , Cirurgia Assistida por Computador/métodos , Técnicas de Ablação/efeitos adversos , Técnicas de Ablação/instrumentação , Idoso , Morte Celular , Eletroporação/instrumentação , Desenho de Equipamento , Feminino , Humanos , Masculino , Neoplasias/patologia , Tomografia por Emissão de Pósitrons , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Cirurgia Assistida por Computador/efeitos adversos , Cirurgia Assistida por Computador/instrumentação , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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