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1.
Genes Dev ; 33(3-4): 221-235, 2019 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-30692206

RESUMEN

Approximately 15% of cancers use homologous recombination for alternative lengthening of telomeres (ALT). How the initiating genomic lesions invoke homology-directed telomere synthesis remains enigmatic. Here, we show that distinct dependencies exist for telomere synthesis in response to replication stress or DNA double-strand breaks (DSBs). RAD52 deficiency reduced spontaneous telomeric DNA synthesis and replication stress-associated recombination in G2, concomitant with telomere shortening and damage. However, viability and proliferation remained unaffected, suggesting that alternative telomere recombination mechanisms compensate in the absence of RAD52. In agreement, RAD52 was dispensable for DSB-induced telomere synthesis. Moreover, a targeted CRISPR screen revealed that loss of the structure-specific endonuclease scaffold SLX4 reduced the proliferation of RAD52-null ALT cells. While SLX4 was dispensable for RAD52-mediated ALT telomere synthesis in G2, combined SLX4 and RAD52 loss resulted in elevated telomere loss, unresolved telomere recombination intermediates, and mitotic infidelity. These findings establish that RAD52 and SLX4 mediate distinct postreplicative DNA repair processes that maintain ALT telomere stability and cancer cell viability.


Asunto(s)
Proteína Recombinante y Reparadora de ADN Rad52/metabolismo , Recombinasas/metabolismo , Homeostasis del Telómero/genética , Línea Celular Tumoral , Roturas del ADN de Doble Cadena , Técnicas de Inactivación de Genes , Inestabilidad Genómica/genética , Células HEK293 , Células HeLa , Humanos , Interfase , Proteína Recombinante y Reparadora de ADN Rad52/genética , Recombinasas/genética
2.
Genes Dev ; 30(10): 1138-54, 2016 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-27222516

RESUMEN

DNA repair is essential to maintain genomic integrity and initiate genetic diversity. While gene conversion and classical nonhomologous end-joining are the most physiologically predominant forms of DNA repair mechanisms, emerging lines of evidence suggest the usage of several noncanonical homology-directed repair (HDR) pathways in both prokaryotes and eukaryotes in different contexts. Here we review how these alternative HDR pathways are executed, specifically focusing on the determinants that dictate competition between them and their relevance to cancers that display complex genomic rearrangements or maintain their telomeres by homology-directed DNA synthesis.


Asunto(s)
Reparación del ADN por Recombinación , Homología de Secuencia de Ácido Nucleico , Animales , Roturas del ADN de Doble Cadena , Replicación del ADN , ADN de Cadena Simple/genética , Humanos , Neoplasias/genética , Hibridación de Ácido Nucleico , Recombinasa Rad51/metabolismo , Telómero/genética , Telómero/metabolismo , Moldes Genéticos
3.
Mol Cell ; 60(4): 637-50, 2015 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-26585386

RESUMEN

Mycobacterium tuberculosis (Mtb) adaptation to hypoxia is considered crucial to its prolonged latent persistence in humans. Mtb lesions are known to contain physiologically heterogeneous microenvironments that bring about differential responses from bacteria. Here we exploit metabolic variability within biofilm cells to identify alternate respiratory polyketide quinones (PkQs) from both Mycobacterium smegmatis (Msmeg) and Mtb. PkQs are specifically expressed in biofilms and other oxygen-deficient niches to maintain cellular bioenergetics. Under such conditions, these metabolites function as mobile electron carriers in the respiratory electron transport chain. In the absence of PkQs, mycobacteria escape from the hypoxic core of biofilms and prefer oxygen-rich conditions. Unlike the ubiquitous isoprenoid pathway for the biosynthesis of respiratory quinones, PkQs are produced by type III polyketide synthases using fatty acyl-CoA precursors. The biosynthetic pathway is conserved in several other bacterial genomes, and our study reveals a redox-balancing chemicocellular process in microbial physiology.


Asunto(s)
Biopelículas , Mycobacterium smegmatis/fisiología , Mycobacterium tuberculosis/fisiología , Policétidos/metabolismo , Quinonas/metabolismo , Acilcoenzima A/metabolismo , Proteínas Bacterianas/metabolismo , Vías Biosintéticas , Hipoxia de la Célula , Oxidación-Reducción , Sintasas Poliquetidas/metabolismo
4.
Indian J Microbiol ; 63(1): 25-32, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37188234

RESUMEN

This study was undertaken to assess the changes in the community structure, diversity, and composition of sediment bacteria in a shallow lake, Najafgarh Lake (NL), that receives untreated sewage effluent through drains connected to it. These changes were analyzed by comparing the sediment bacterial community structure of NL to the sediment bacterial community structure of Dhansa Barrage (DB), which receives no such effluents. 16S rRNA amplicon was used for bacterial community analysis. Water and sediment samples were also analyzed and compared revealing high conductivity, ammonia, nitrite content, and low dissolved oxygen in NL. The organic matter content is also higher in the sediments of NL. Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria are the predominant phyla in both sites and account for 91% of total bacterial abundance in DB and only 77% in the case of NL. Proteobacteria have the highest relative abundance, accounting for around 42% of the total bacterial population in the case of DB and Firmicutes has the highest relative abundance in Najafgarh at 30%. The diversity analysis found significant differences in the community structure at the two sites. The variation in the bacterial communities in the two wetlands is significantly associated with two water parameters (conductivity and temperature) and two sediment parameters (Sediment Nitrogen and Sediment Organic Matter). Correlation Analysis showed that high ammonia, nitrite, and conductance in NL resulted in bacterial communities shifting towards phyla abundant in degraded ecosystems like Acidobacteria, Choloroflexi, Caldiserica, Aminicenantes, Thaumarchaeota, and Planctomycetes.

5.
Clin Endocrinol (Oxf) ; 96(2): 190-199, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34498757

RESUMEN

OBJECTIVE: Literature regarding utility of 68 Ga-DOTATATE PET/CT in insulinoma localization across various subgroups [benign/malignant/multiple endocrine neoplasia-1 (MEN-1) syndrome associated] remains scarce. In this study, the performance of 68 Ga-DOTATATE PET/CT was compared with contrast-enhanced computed tomography (CECT) and 68 Ga-NODAGA-Exendin-4 PET/CT (whenever available) in an endogenous hyperinsulinemic hypoglycemia (EHH) cohort. DESIGN: Retrospective audit. PATIENTS: EHH patients [N = 36, lesions (n) = 49, final diagnosis: benign sporadic insulinoma (BSI) (N = 20), malignant insulinoma (N = 4, n = 14), MEN-1 syndrome associated insulinoma (N = 9, n = 15), Munchausen syndrome (N = 2) and drug-induced hypoglycemia (N = 1)] having both preoperative imaging modalities (CECT and 68 Ga-DOTATATE PET/CT). MEASUREMENTS: Per-lesion sensitivity (Sn) and positive predictive value (PPV) for histopathological diagnosis of insulinoma. RESULTS: Sn and PPV of 68 Ga-DOTATATE PET/CT were 67.3% and 89.2%; 55% and 100%; 85.7% and 100%; and 66.7% and 77% for overall EHH, BSI, malignant, and MEN-1 syndrome associated insulinoma cohorts respectively. Despite having comparatively lower sensitivity in BSI cohort, 68 Ga-DOTATATE PET/CT localized a pancreatic tail lesion missed by other modalities. 68 Ga-DOTATATE PET/CT had comparatively higher sensitivity in malignant insulinoma than BSI cohort. 68 Ga-DOTATATE PET/CT also paved the way for successful response to 177 Lu-based peptide receptor radionuclide therapy (PRRT). In MEN-1 cases, lower PPV as compared with BSI was due to uptake in non-insulinoma pancreatic neuroendocrine tumours (Pan-NET). CONCLUSIONS: 68 Ga-DOTATATE PET/CT has supplemental role in selected cases of BSI with negative and/or discordant results with CECT and 68 Ga-NODAGA-Exendin-4 PET/CT. In malignant insulinoma, 68 Ga-DOTATATE-PET/CT has an additional theranostic potential. Interference due to uptake in non-insulinoma Pan-NET in MEN-1 syndrome may hinder insulinoma localization with 68 Ga-DOTATATE-PET/CT.


Asunto(s)
Hiperinsulinismo Congénito , Insulinoma , Tumores Neuroendocrinos , Compuestos Organometálicos , Humanos , Insulinoma/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , Cintigrafía , Estudios Retrospectivos
6.
Mol Biol Rep ; 49(6): 5535-5545, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35411480

RESUMEN

BACKGROUND: The cytoplasmic-genic male-sterility system has been extensively employed for the production of onion hybrids. Molecular marker-assisted characterization of the cytotypes and genotyping at the restorer-of male-fertility (Ms) locus is important for the accelerated breeding of onion hybrids. Indian onion breeding has focussed more on open-pollinated varieties than hybrids. To accelerate the breeding efforts, marker-assisted selection (MAS) plays a pivotal role. METHODS AND RESULTS: This study aimed to characterize the Indian breeding lines, varieties, hybrids, and exotic accessions for cytotype and Ms locus. For cytoplasm, cytotype markers, accD, and MKFR and for Ms locus identification, PCR markers AcPMS1 and AcSKP1 were employed. Bulk strategy to identify cytoplasm and Ms locus was tested. Sequencing of PCR products amplified by accD was also tried. Both the accD and MKFR were synonymous in cytoplasm identification except in T821 where T cytoplasm was identified. AcPMS1 was more reliable than AcSKP1 for Ms locus identification. Sequencing proved that N and T cytoplasm are identical. Bulking strategy can be used for cytotype identification but not for Ms locus. CONCLUSIONS: Indian onions have a predominance of normal (N) cytoplasm and homozygous recessive (msms) locus. This might be beneficial for hybrid development. S cytoplasm was identified in exotic varieties. For the first time, T cytoplasm has been reported from India. These findings will assist Indian onion breeders to develop MAS strategies for accelerating hybrid development programs. And for the release of onion hybrids with high productivity and uniformity.


Asunto(s)
Infertilidad Masculina , Cebollas , Citoplasma/genética , Humanos , India , Masculino , Fitomejoramiento
7.
Nature ; 539(7627): 54-58, 2016 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-27760120

RESUMEN

Homology-directed DNA repair is essential for genome maintenance through templated DNA synthesis. Alternative lengthening of telomeres (ALT) necessitates homology-directed DNA repair to maintain telomeres in about 10-15% of human cancers. How DNA damage induces assembly and execution of a DNA replication complex (break-induced replisome) at telomeres or elsewhere in the mammalian genome is poorly understood. Here we define break-induced telomere synthesis and demonstrate that it utilizes a specialized replisome, which underlies ALT telomere maintenance. DNA double-strand breaks enact nascent telomere synthesis by long-tract unidirectional replication. Proliferating cell nuclear antigen (PCNA) loading by replication factor C (RFC) acts as the initial sensor of telomere damage to establish predominance of DNA polymerase δ (Pol δ) through its POLD3 subunit. Break-induced telomere synthesis requires the RFC-PCNA-Pol δ axis, but is independent of other canonical replisome components, ATM and ATR, or the homologous recombination protein Rad51. Thus, the inception of telomere damage recognition by the break-induced replisome orchestrates homology-directed telomere maintenance.


Asunto(s)
Roturas del ADN de Doble Cadena , Replicación del ADN , Neoplasias/genética , Homeostasis del Telómero , Telómero/metabolismo , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Línea Celular Tumoral , Daño del ADN , ADN Polimerasa III/metabolismo , Reparación del ADN , ADN Polimerasa Dirigida por ADN/metabolismo , Humanos , Complejos Multienzimáticos/metabolismo , Neoplasias/enzimología , Neoplasias/metabolismo , Neoplasias/patología , Antígeno Nuclear de Célula en Proliferación/metabolismo , Proteína de Replicación C/metabolismo , Homología de Secuencia
8.
Indian J Med Res ; 156(2): 291-298, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-36629189

RESUMEN

Background & objectives: Globally, mental disorders are rising with increasing urbanization. India has the world's second-largest tribal population and it is critical to appreciate the mental health problems in this population. However, the extent of mental health issues among tribal populations is unknown. Against this background, we systematically reviewed community-based studies on mental health issues among tribal populations in India. Methods: Online databases PubMed, Embase, ProQuest databases and Google Scholar were searched and articles published between January 1990 and May 2021 including primary community-based quantitative observational studies focused exclusively on tribal population were retrieved. PRISMA guidelines were followed and this review was registered on PROSPERO (CRD42020178099). Results: A total of 935 articles were identified, of which 63 were selected for full-text review, and finally, 11 studies were included. Seven studies examined alcohol use disorder with a pooled prevalence of 40 per cent. Two studies reported on suicidal attempts. A few studies mentioned anxiety, depression and other mental health conditions. Interpretation & conclusions: : This systematic review established that a few community-based primary studies were conducted on mental health issues among tribal populations over the last three decades. Among these, fewer studies focused exclusively on tribal communities. The studies differed in their study design and the tools used. The findings of these investigations highlighted a limited range of mental health issues, primarily alcoholism, anxiety, depression and suicide.


Asunto(s)
Trastornos Mentales , Suicidio , Humanos , Salud Mental , Trastornos Mentales/epidemiología , Ansiedad/epidemiología , India/epidemiología
9.
Sensors (Basel) ; 22(22)2022 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-36433569

RESUMEN

The rapid development in manufacturing industries due to the introduction of IIoT devices has led to the emergence of Industry 4.0 which results in an industry with intelligence, increased efficiency and reduction in the cost of manufacturing. However, the introduction of IIoT devices opens up the door for a variety of cyber threats in smart industries. The detection of cyber threats against such extensive, complex, and heterogeneous smart manufacturing industries is very challenging due to the lack of sufficient attack traces. Therefore, in this work, a Federated Learning enabled Deep Intrusion Detection framework is proposed to detect cyber threats in smart manufacturing industries. The proposed FLDID framework allows multiple smart manufacturing industries to build a collaborative model to detect threats and overcome the limited attack example problem with individual industries. Moreover, to ensure the privacy of model gradients, Paillier-based encryption is used in communication between edge devices (representative of smart industries) and the server. The deep learning-based hybrid model, which consists of a Convolutional Neural Network, Long Short Term Memory, and Multi-Layer Perceptron is used in the intrusion detection model. An exhaustive set of experiments on the publically available dataset proves the effectiveness of the proposed framework for detecting cyber threats in smart industries over the state-of-the-art approaches.


Asunto(s)
Industrias , Industria Manufacturera , Comercio , Comunicación , Inteligencia
10.
Mol Pharm ; 18(10): 3832-3842, 2021 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-34499836

RESUMEN

Use of tumor-associated antigens for cancer immunotherapy is limited due to their poor in vivo stability and low cellular uptake. Delivery of antigenic peptides using synthetic polymer-based nanostructures has been actively pursued but with limited success. Peptide-based nanostructures hold much promise as delivery vehicles due to their easy design and synthesis and inherent biocompatibility. Here, we report self-assembly of a dipeptide containing a non-natural amino acid, α,ß-dehydrophenylalanine (ΔF), into nanotubes, which efficiently entrapped a MAGE-3-derived peptide (M3). M3 entrapped in F-ΔF nanotubes was more stable to a nonspecific protease treatment and both F-ΔF and F-ΔF-M3 showed no cellular toxicity for four cancerous and noncancerous cell lines used. F-ΔF-M3 showed significantly higher cellular uptake in RAW 267.4 macrophage cells compared to M3 alone and also induced in vitro maturation of dendritic cells (DCs). Immunization of mice with F-ΔF-M3 selected a higher number of IFN-γ secreting CD8+ T cells and CD4+ T compared to M3 alone. On day 21, a tumor growth inhibition ratio (TGI, %) of 41% was observed in a murine melanoma model. These results indicate that F-ΔF nanotubes are highly biocompatible, efficiently delivered M3 to generate cytotoxic T lymphocytes responses, and able to protect M3 from degradation under in vivo conditions. The F-ΔF dipeptide-based nanotubes may be considered as a good platform for further development as delivery agents.


Asunto(s)
Antígenos de Neoplasias/administración & dosificación , Sistema de Administración de Fármacos con Nanopartículas/administración & dosificación , Testículo/inmunología , Animales , Humanos , Inmunoterapia/métodos , Células MCF-7 , Masculino , Melanoma/inmunología , Melanoma/terapia , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica de Transmisión , Nanotubos de Péptidos , Trasplante de Neoplasias , Células RAW 264.7
11.
Mol Cell Biochem ; 476(8): 2975-2987, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33770316

RESUMEN

Aldo-keto reductase 1C1 (AKR1C1) is a hydroxysteroid dehydrogenase, known to inactivate the biologically active progesterone into its corresponding 20 α-hydroxyprogesterone. Increased expression of the AKR1C1 gene in oncogenesis is linked with resistance to various anticancer agents and hence it is considered as an emerging drug target for the design and developing the novel anticancer drugs. We have performed QSAR pharmacophore modeling for AKR1C1 inhibitors followed by a virtual screening of ~ 59,000 compounds present at the Maybridge database. The screened compounds were refined using drug-like filters of Lipinski rule, ADMET plot, molecular docking and scoring and subsequently top 20 hits were selected. Selected compounds were subjected to the in vitro for AKR1C1 inhibition assay and best seven compounds bearing excellent binding affinity to the AKR1C1 were finally selected. The identified compounds may be exploited in hit-to-lead development and may also prove as an interventional strategy in preventing a pre-term birth due to declining levels of progesterone.


Asunto(s)
20-Hidroxiesteroide Deshidrogenasas/antagonistas & inhibidores , Neoplasias de la Mama/tratamiento farmacológico , Diseño de Fármacos , Descubrimiento de Drogas , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Ensayos Analíticos de Alto Rendimiento/métodos , Neoplasias de la Mama/patología , Proliferación Celular , Femenino , Humanos , Modelos Moleculares , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad , Células Tumorales Cultivadas
12.
J Pediatr Hematol Oncol ; 43(4): e466-e471, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-32925402

RESUMEN

BACKGROUND: Cisplatin and doxorubicin are integral components of chemotherapy regimens in the treatment of osteosarcoma. Choice of third agent high-dose methotrexate (HDMTX) or an alkylating agent such as ifosfamide is debatable. The present study compared the impact of MAP (HDMTX-doxorubicin-cisplatin) and IAP (ifosfamide-doxorubicin-cisplatin) chemotherapy regimens on toxicity and survival in children and adolescents with osteosarcoma. MATERIALS AND METHODS: This was a retrospective study including patients 18 years and younger with osteosarcoma during the study period. Clinical, demographic, chemotherapy regimen, and surgical details and treatment-related toxicity were retrieved from hospital medical records. Prognostic factors affecting overall survival (OS) and event-free survival (EFS) were analyzed. RESULTS: Among 102 patients included in the study, 59 (57.8%) and 43 (42.2%) patients were treated with MAP and IAP regimens, respectively. Two groups were comparable in terms of pretreatment characteristics and surgical treatment. Overall, 95.9% patients underwent limb salvage surgery. There was a statistically increased incidence in supportive care admissions and delay in starting the next cycle of chemotherapy in the MAP group. Among the MAP cohort, the 5-year OS and EFS were 62% and 55% compared with 47% and 44%, respectively, in the IAP cohort (P=0.143 and 0.316, respectively). On univariate and multivariate analyses, statistically significant factors affecting EFS of the whole group included tumor size, stage, site of metastasis, histologic necrosis, and type of surgery. CONCLUSIONS: OS and EFS with both regimens were similar. However, the MAP regimen was associated with a statistically significant increase in incidence of supportive care admissions, delay in next cycle of chemotherapy, and predicted higher cost of treatment.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Metotrexato/uso terapéutico , Osteosarcoma/tratamiento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Neoplasias Óseas/economía , Niño , Cisplatino/efectos adversos , Cisplatino/economía , Cisplatino/uso terapéutico , Análisis Costo-Beneficio , Supervivencia sin Enfermedad , Doxorrubicina/efectos adversos , Doxorrubicina/economía , Doxorrubicina/uso terapéutico , Femenino , Humanos , Ifosfamida/efectos adversos , Ifosfamida/economía , Ifosfamida/uso terapéutico , Masculino , Metotrexato/efectos adversos , Metotrexato/economía , Osteosarcoma/economía , Estudios Retrospectivos , Terapia Recuperativa/economía
13.
Molecules ; 26(14)2021 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-34299457

RESUMEN

Harnessing solar energy and converting it into renewable fuels by chemical processes, such as water splitting and carbon dioxide (CO2) reduction, is a highly promising yet challenging strategy to mitigate the effects arising from the global energy crisis and serious environmental concerns. In recent years, covalent organic framework (COF)-based materials have gained substantial research interest because of their diversified architecture, tunable composition, large surface area, and high thermal and chemical stability. Their tunable band structure and significant light absorption with higher charge separation efficiency of photoinduced carriers make them suitable candidates for photocatalytic applications in hydrogen (H2) generation, CO2 conversion, and various organic transformation reactions. In this article, we describe the recent progress in the topology design and synthesis method of COF-based nanomaterials by elucidating the structure-property correlations for photocatalytic hydrogen generation and CO2 reduction applications. The effect of using various kinds of 2D and 3D COFs and strategies to control the morphology and enhance the photocatalytic activity is also summarized. Finally, the key challenges and perspectives in the field are highlighted for the future development of highly efficient COF-based photocatalysts.

14.
Health Care Women Int ; 42(4-6): 580-597, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32701388

RESUMEN

We investigated the impact of socio-demographic variables on antenatal care (ANC) utilization and the low birth weight of a child. Data were collected from 300 pregnant females. Only 22.5% of females received full antenatal care (≥4 visits). Our results showed that female's age at marriage and education plays a significant role in improving ANC. We observed an overall decrease in the utilization of services provided during each antenatal visit. ANC visits from the first trimester decrease the risk of having a baby with low birth weight. Awareness programs and educating families about pregnancy care are recommended to improve ANC utilization.


Asunto(s)
Aceptación de la Atención de Salud , Atención Prenatal , Niño , Femenino , Humanos , India , Matrimonio , Embarazo , Mujeres Embarazadas
15.
Physiol Mol Biol Plants ; 27(7): 1437-1453, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34366588

RESUMEN

The present study was carried out to silence the transcription factor genes ZCT1, ZCT2 and ZCT3 via lipofectamine based antisense LNA GapmeRs transfection into the protoplasts of established photomixotrophic cell suspensions. The photomixotrophic cell suspensions with a threshold of 0.5% sucrose were raised and established using two-tiered CO2 providing flasks kept under high light intensity. The photomixotrophic cell suspensions showed morphologically different thick-walled cells under scanning electron microscopic analysis in comparison to the simple thin-walled parenchymatous control cell suspensions. The LC-MS analysis registered the vindoline production (0.0004 ± 0.0001 mg/g dry wt.) in photomixotrophic cell suspensions which was found to be absent in control cell suspensions. The protoplasts were isolated from the photomixotrophic cell suspensions and subjected to antisense LNA GapmeRs silencing. Three lines, viz. Z1A, Z2C and Z3G were obtained where complete silencing of ZCT1, ZCT2 and ZCT3 genes, respectively, was observed. The Z3G line was found to show maximum production of vindoline (0.038 ± 0.001 mg/g dry wt.), catharanthine (0.165 ± 0.008 mg/g dry wt.) and vinblastine (0.0036 ± 0.0003 mg/g dry wt.). This was supported by the multifold increment in the gene expression of TDC, SLS, STR, SGD, d4h, dat, CrT16H and Crprx. The present work indicates the master regulation of ZCT3 knockdown among all three ZCTs transcription factors in C. roseus to enhance the terpenoid indole alkaloids production. The successful silencing of transcription repressor genes has been achieved in C. roseus plant system by using photomixotrophic cell cultures through GapmeR based silencing. The present study is a step towards metabolic engineering of the TIAs pathway using protoplast transformation in C. roseus. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01017-y.

16.
Physiol Mol Biol Plants ; 27(11): 2517-2532, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34924708

RESUMEN

Bulb onion is cultivated throughout the world for consumption as vegetable and processed products. Although having high global demand and economic significance, information about genetic diversity and genomic resources is limited. This study investigated the variability of 96 accessions representing seventeen countries. Out of 145 SSR markers, 62 SSRs amplified and 15 SSRs gave consistent polymorphic bands. Fifty three alleles were detected with an average of 3.533 alleles per locus. PIC value ranged from 0.219 (ACM463) to 0.715 (ACM091). Structure and cluster analysis grouped the onion accessions into two clusters. Discriminant analysis of principal components, a tool that maximizes variation between groups while minimizing that within groups, assorted accessions into five clusters. Analysis of molecular variance revealed maximum variation within the populations than among the populations. Highest genetic differentiation (FST = 0.11045; p < 0.001) was observed between Europe and Japan populations whereas the lowest genetic differentiation (FST = 0.05714; p < 0.001) was recorded between India and Japan. Principal component analysis of morphological traits suggested two principal components cumulatively accounting for 74.4% of the total variance. First component (PC1) was positively and strongly correlated with bulbing whereas second component (PC2) had leaf colour with the highest coefficient. Clustering was not on the basis of bulb colour, bulb formation, or flowering but on the basis of geographical origin. Based on clustering, crossing of distantly related accessions can provide an insight about the hybrid vigour of these diverse accessions. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01101-3.

17.
Clin Endocrinol (Oxf) ; 93(6): 678-686, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32716527

RESUMEN

CONTEXT: Insulinoma needs accurate preoperative localization for minimally invasive surgery. Exendin-4-based imaging has shown promising results. OBJECTIVE: To evaluate performance parameters of exendin-4-based imaging in insulinoma localization and compare with other imaging modalities. DESIGN: Retrospective cross-sectional study. PATIENTS: We report 14 patients with endogenous hyperinsulinemic hypoglycaemia (EHH) managed at our centre; in whom, the final diagnosis was insulinoma (n = 11), Munchausen syndrome (MS) (n = 2) and inconclusive (n = 1). Retrospective reporting of CECT, 68 Ga-DOTATATE PET/CT and 68 Ga-NODAGA-exendin-4-PET/CT was done. With per-lesion analysis, performance parameters were calculated for the histopathological diagnosis of insulinoma. MAIN OUTCOME MEASURES: True positive (TP), false positive (FP), false negative (FN), true negative (TN), sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) for insulinoma localization. RESULTS: In our cohort, 12 histopathologically proven insulinoma lesions [(TP): 11 primary lesions, 1 metastasis] were detected in 11 patients, whereas two patients had MS (TN). Sn and PPV were 75% and 100%, 33.3% and 80% and 83.3% and 71.4% for CECT, 68 Ga-DOTATATE PET/CT and 68 Ga-NODAGA-exendin-4-PET/CT, respectively. With exendin-4-based imaging, FP uptake in normal pancreatic tissue and FN results in the pancreatic tail lesion was seen. In one patient, TN result suggested the correct diagnosis of MS. CONCLUSION: 68 Ga-NODAGA-exendin-4-PET/CT has higher sensitivity than 68 Ga-DOTATATE PET/CT and CECT for insulinoma localization. FP uptake in normal pancreas and FN result in tail lesions are limitations of currently utilized exendin-4-based imaging.


Asunto(s)
Hiperinsulinismo Congénito , Insulinoma , Neoplasias Pancreáticas , Estudios Transversales , Exenatida , Humanos , Insulinoma/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Estudios Retrospectivos
18.
Physiol Mol Biol Plants ; 26(8): 1695-1711, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32801497

RESUMEN

V. minor contains monomeric eburnamine-type of indole alkaloids having utilization as a neuro-medicinal plant. The biosynthetic pathway studies using miRNAs has been the focal point for plant genomic research in recent years and this technique is utilized to get an insight into a possible pathway level study in V. minor as understanding of genes in this prized medicinal plant is meagrely understood. The de novo transcriptomic analysis using Illumina Next gen sequencing has been performed in glasshouse shifted plant and transformed roots to elucidate the possible non confirmed steps of terpenoid indole alkaloids (TIAs) pathway in V. minor. A putative TIA pathway is elucidated in the study including twelve possible TIAs biosynthetic genes. The specific miRNA associated with TIAs pathway were identified and their roles were discussed for the first time in V. minor. The comparative analysis of transcriptomic data of glasshouse shifted plant and transformed roots showed that the raw reads of transformed roots were higher (83,740,316) compared to glasshouse shifted plant (67,733,538). The EST-SSR prediction showed the maximum common repeats among glasshouse shifted plant and transformed roots, although small variation was found in trinucleotide repeats restricted to glasshouse shifted plant. The study reveals overall 37 miRNAs which were observed to be true and can have a role in pathway as they can regulate the growth and alkaloid production. The identification of putative pathway genes plays an important role in establishing linkage between Aspidosperma and Eburnamine alkaloids.

19.
Indian J Clin Biochem ; 35(1): 43-53, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32071495

RESUMEN

ABSTRACT: The molecular mechanism of iron transfer across placenta in response to maternal anemic status/ iron supplementation is not clear. We hypothesized that maternal iron/ anemia status during early trimesters can be utilized as a biomarker tool to get estimates of placental iron status. Early interventions can be envisaged to maintain optimum placental/ foetal iron levels for healthy pregnancy outcomes. One hundred twenty primigravida were recruited and divided into non-anemic and anemic group on the basis of hemoglobin levels. The groups were randomly allocated to receive daily and weekly iron folic acid (IFA) tablets till six weeks postpartum. Hematological and iron status markers in blood and placenta were studied along with the delivery notes. Weekly IFA supplementation in anemic primigravidas resulted in significantly reduced levels of hematological markers (p < 0.01); whereas non-anemic primigravidas showed lower ferritin and iron levels, and higher soluble transferrin receptor levels (p < 0.05). At baseline, C-reactive protein and cortisol hormone levels were also significantly lower in non-anemic primigravidas (p < 0.05). A significantly decreased placental ferritin expression (p < 0.05); and an increased placental transferrin expression was seen in anemic primigravidas supplemented with weekly IFA tablets. A significant positive correlation was observed between serum and placental ferritin expression in anemic pregnant women (r = 0.80; p < 0.007). Infant weight, gestational length and placental weight were comparable in both the supplementation groups. To conclude, mother's serum iron / anemia status switches the modulation in placental iron transporter expression for delivering the optimum iron to the foetus for healthy pregnancy outcomes. TRIAL REGISTRATION: Clinical Trial Registry-India: CTRI/2014/10/005135.

20.
Chem Soc Rev ; 47(22): 8072-8096, 2018 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-29892768

RESUMEN

Silica-based micro-, meso-, macro-porous materials offer attractive routes for designing single-site photocatalysts, supporting semiconducting nanoparticles, anchoring light-responsive metal complexes, and encapsulating metal nanoparticles to drive photochemical reactions by taking advantage of their large surface area, controllable pore channels, remarkable transparency to UV/vis and tailorable physicochemical surface characteristics. This review mainly focuses on the fascinating photocatalytic properties of silica-supported Ti catalysts from single-site catalysts to nanoparticles, their surface-chemistry engineering, such as the hydrophobic modification and synthesis of thin films, and the fabrication of nanocatalysts including morphology controlled plasmonic nanostructures with localized surface plasmon resonance. The hybridization of visible-light responsive metal complexes with porous materials for the construction of functional inorganic-organic supramolecular photocatalysts is also included. In addition, the latest progress in the application of MOFs as excellent hosts for designing photocatalytic systems is described.

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