Structural evolution of a gneiss dome in the axial zone of the proterozoic south Delhi fold belt in central Rajasthan

The structural geometry of the Anasagar gneiss dome in the axial zone of the South Delhi Fold Belt is controlled by polyphase folding. It is classified as a thrust-related gneiss dome and not as a metamorphic core complex. Four phases of deformation have affected both the gneiss and the enveloping supracrustal rocks. D2 and D3 deformations probably represent early and late stages of a progressive deformation episode in a simple shear regime combined with compression. The contact between the gneiss and the supracrustal rocks is a dislocation plane (thrust) with top-to-east sense of movement which is consistent with the vergence of the D2 folds. The thrust had a ramp-and-flat geometry at depth. At the present level of exposure it is a footwall flat (that is, parallel to the gneissosity in the footwall), but it truncates the bedding of the hanging wall at some places and is parallel at others. The thrusting was probably broadly coeval with the D2 folds and the thrust plane is locally folded by D2. D2 and D3 folds have similar style and orientation as the first and second phases respectively of major folds in the Delhi Supergroup of the South Delhi Fold Belt and these are mutually correlatable. It is suggested that D1 may be Pre-Delhi in age. Available geochronological data indicate that the emplacement of the Anasagar gneiss predated the formation of volcanic rocks in the Delhi Supergroup and also predated the main crust forming event in the fold belt. The Anasagar gneiss and its enveloping supracrustal rocks are probably older than the Delhi Supergroup

Chaperone-like activity of tubulin

Tubulin, a ubiquitous protein of eukaryotic cytoskeleton, is a building block unit of microtubule. Although several cellular processes are known to be mediated through the tubulin-microtubule system, the participation of tubulin or microtubule in protein folding pathway has not yet been reported. Here we show that goat brain tubulin has some functions and features similar to many known molecular chaperones. Substoichiometric amounts of tubulin can suppress the non-thermal and thermal aggregation of a number of unrelated proteins such as insulin, equine liver alcohol dehydrogenase, and soluble eye lens proteins containing β- and γ-crystallins. This chaperone-like activity of tubulin becomes more pronounced as temperature increases. Aging of tubulin solution at 37° C also enhances its chaperone-like activity. Tubulin loses its chaperone-like activity upon removal of its flexible hydrophilic C-terminal tail. These results suggest that both electrostatic and hydrophobic interactions are important in substrate binding by tubulin and that the negatively charged C-terminal tails play a crucial role for its chaperone-like activity

The regulatory control of Cebpa enhancers and silencers in the myeloid and red-blood cell lineages

Cebpa encodes a transcription factor (TF) that plays an instructive role in the development of multiple myeloid lineages. The expression of Cebpa itself is finely modulated, as Cebpa is expressed at high and intermediate levels in neutrophils and macrophages respectively and downregulated in non-myeloid lineages. The cis-regulatory logic underlying the lineage-specific modulation of Cebpa’s expression level is yet to be fully characterized. Previously, we had identified 6 new cis-regulatory modules (CRMs) in a 78kb region surrounding Cebpa. We had also inferred the TFs that regulate each CRM by fitting a sequence-based thermodynamic model to a comprehensive reporter activity dataset. Here, we report the cis-regulatory logic of Cebpa CRMs at the resolution of individual binding sites. We tested the binding sites and functional roles of inferred TFs by designing and constructing mutated CRMs and comparing theoretical predictions of their activity against empirical measurements in a myeloid cell line. The enhancers were confirmed to be activated by combinations of PU.1, C/EBP family TFs, Egr1, and Gfi1 as predicted by the model. We show that silencers repress the activity of the proximal promoter in a dominant manner in G1ME cells, which are derived from the red-blood cell lineage. Dominant repression in G1ME cells can be traced to binding sites for GATA and Myb, a motif shared by all of the silencers. Finally, we demonstrate that GATA and Myb act redundantly to silence the proximal promoter. These results indicate that dominant repression is a novel mechanism for resolving hematopoietic lineages. Furthermore, Cebpa has a fail-safe cis-regulatory architecture, featuring several functionally similar CRMs, each of which contains redundant binding sites for multiple TFs. Lastly, by experimentally demonstrating the predictive ability of our sequence-based thermodynamic model, this work highlights the utility of this computational approach for understanding mammalian gene regulation

Sulfhydryls of tubulin

The 20 cysteine residues of tubulin are heterogeneously distributed throughout its three-dimensional structure. In the present work, we have used the reactivity of these cysteine residues with 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) as a probe to detect the global conformational changes of tubulin under different experimental conditions. The 20 sulfhydryl groups can be classified into two categories: fast and slow reacting. Colchicine binding causes a dramatic decrease in the reactivity of the cysteine residues and causes complete protection of 1.4 cysteine residues. Similarly, other colchicine analogs that bind reversibly initially decrease the rate of reaction; but unlike colchicine they do not cause complete protection of any sulfhydryl groups. Interestingly, in all cases we find that all the slow reacting sulfhydryl groups are affected to the same extent, that is, have a single rate constant. Glycerol has a major inhibitory effect on all these slow reacting sulfhydryls, suggesting that the reaction of slow reacting cysteines takes place from an open state at equilibrium with the native. Ageing of tubulin at 37 ° C leads to loss of self-assembly and colchicine binding activity. Using DTNB kinetics, we have shown that ageing leads to complete protection of some of the sulfhydryl groups and increased reaction rate for other slow reacting sulfhydryl groups. Ageing at 37 ° C also causes aggregation of tubulin as indicated by HPLC analysis. The protection of some sulfhydryl groups may be a consequence of aggregation, whereas the increased rate of reaction of other slow reacting sulfhydryls may be a result of changes in global dynamics. CD spectra and acrylamide quenching support such a notion. Binding of 8-anilino-1-naphthalenesulfonate (ANS) and bis-ANS by tubulin cause complete protection of some cysteine residues as indicated by the DTNB reaction, but has little effect on the other slow reacting cysteines, suggesting local effects

Chaperone-like activity of tubulin. Binding and reactivation of unfolded substrate enzymes

The eukaryotic cytoskeletal protein tubulin is a heterodimer of two subunits, α and β , and is a building block unit of microtubules. In a previous communication we demonstrated that tubulin possesses chaperonelike activities by preventing the stress-induced aggregation of various proteins (Guha, S., Manna, T. K., Das, K. P., and Bhattacharyya, B. (1998) J. Biol. Chem. 273, 30077-30080). As an extension of this observation, we explored whether tubulin, like other known chaperones, also protected biological activity of proteins against thermal stress or increased the yields of active proteins during refolding from a denatured state. We show here that tubulin not only prevents the thermal aggregation of alcohol dehydrogenase and malic dehydrogenase but also protects them from loss of activity. We also show that tubulin prevents the aggregation of substrates during their refolding from a denatured state and forms a stable complex with denatured substrate. The activity of malic dehydrogenase, α -glucosidase, and lactate dehydrogenase during their refolding from urea or guanidium hydrochloride denatured states increased significantly in presence of tubulin compared with that without tubulin. These results suggest that tubulin, in addition to its role in mitosis, cell motility, and other cellular events, might be implicated in protein folding and protection from stress

Efecto antirradical y antiulceroso de las hojas de Sonneratia apetala Buch-Ham contra la lesión de la mucosa gástrica inducida por el alcohol

Introducción: Sonneratia apetala Buch-Ham es un verdadero habitante de los manglares en Sunderban indio y se utiliza en la medicina popular para los trastornos digestivos. Método: El extracto hidrometanólico (20:80) de hojas de Sonneratia apetala (SA) se estandarizó químicamente por HPTLC y se evaluó por sus propiedades antirradicales y gastroprotectoras. Se determinaron los fenólicos y flavonoides presentes en SA y se evaluaron las actividades antirradicales mediante métodos in vitro como, DPPH (1,1-difenil-2-picrilhidrazilo), óxidos nítricos, superóxidos, hidroxilo y ABTS (2,2 / -azino-bis- Ácido 3-etilbenztiazolin-6-sulfónico). Además, se evaluó la eficacia gastroprotectora de SA en la ulceración oxidativa inducida por alcohol (50% v / v, 5 ml / kg) en ratas. Resultados: El SA químicamente estandarizado mostró presencia de compuestos polifenólicos. También mostró fuertes propiedades antirradicales. Las administraciones orales de SA (125 mg / kg y 250 mg / kg) protegieron significativamente la membrana mucosa gástrica del daño ulcerativo causado por el alcohol, similar al omeprazol (20 mg / kg) en ratas. Además, el tratamiento con SA redujo significativamente la elevación de los peróxidos de lípidos; mientras que aumentó la concentración de glutatión y catalasa en la mucosa gástrica con respecto a las ratas de control no tratadas inducidas por etanol. Conclusiones: Los resultados obtenidos de este estudio sugieren que la hoja de Sonneratia apetala tiene propiedades antioxidantes y tiene capacidad para proteger la lesión de la mucosa gástrica causada por la ingestión de alcohol.Introduction: Sonneratia apetala Buch-Ham is a true mangrove inhabitant in Indian Sunderban and it is used in folk medicine for digestive disorders. Method: Hydro-methanolic (20:80) extract of Sonneratia apetala leaves (SA) was chemically standardized by HPTLC and evaluated for its antiradical and gastro-protective properties. Phenolics and flavonoids present in SA were determined and antiradical activities were assessed by in vitro methods like, DPPH (1,1-diphenyl-2-picrylhydrazyl), nitric oxides, superoxides, hydroxyl and ABTS (2,2/ -azino-bis-3-ethyl benzthiazoline-6-sulphonic acid). Further, gastro-protective efficacy of SA was assessed in alcohol (50% v/v, 5 ml/kg) induced oxidative ulceration in rats. Results: Chemically standardized SA exhibited presence of polyphenolic compounds. It also showed strong antiradical properties. Oral administrations of SA (125 mg/kg and 250 mg/kg) significantly protected gastric mucosal membrane from ulcerative damage caused by alcohol, similar to Omeprazole (20 mg/kg) in rats. Moreover, SA treatment significantly reduced the elevation of lipid peroxides; while enhanced the concentration of glutathione and catalase in gastric mucosa in respect to ethanol induced untreated control rats. Conclusions The results obtained from this study suggest Sonneratia apetala leaf has antioxidant properties and has capabilities to protect gastric mucosal injury caused by alcohol ingestion.Project 537(sanc)/ST/P/S&T/5G-4/2009-11 of the Department of Science & Technology, Govt. of West Bengal, Indi

Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019

Background: Updated data on chronic respiratory diseases (CRDs) are vital in their prevention, control, and treatment in the path to achieving the third UN Sustainable Development Goals (SDGs), a one-third reduction in premature mortality from non-communicable diseases by 2030. We provided global, regional, and national estimates of the burden of CRDs and their attributable risks from 1990 to 2019. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated mortality, years lived with disability, years of life lost, disability-adjusted life years (DALYs), prevalence, and incidence of CRDs, i.e. chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis, and other CRDs, from 1990 to 2019 by sex, age, region, and Socio-demographic Index (SDI) in 204 countries and territories. Deaths and DALYs from CRDs attributable to each risk factor were estimated according to relative risks, risk exposure, and the theoretical minimum risk exposure level input. Findings: In 2019, CRDs were the third leading cause of death responsible for 4.0 million deaths (95% uncertainty interval 3.6–4.3) with a prevalence of 454.6 million cases (417.4–499.1) globally. While the total deaths and prevalence of CRDs have increased by 28.5% and 39.8%, the age-standardised rates have dropped by 41.7% and 16.9% from 1990 to 2019, respectively. COPD, with 212.3 million (200.4–225.1) prevalent cases, was the primary cause of deaths from CRDs, accounting for 3.3 million (2.9–3.6) deaths. With 262.4 million (224.1–309.5) prevalent cases, asthma had the highest prevalence among CRDs. The age-standardised rates of all burden measures of COPD, asthma, and pneumoconiosis have reduced globally from 1990 to 2019. Nevertheless, the age-standardised rates of incidence and prevalence of interstitial lung disease and pulmonary sarcoidosis have increased throughout this period. Low- and low-middle SDI countries had the highest age-standardised death and DALYs rates while the high SDI quintile had the highest prevalence rate of CRDs. The highest deaths and DALYs from CRDs were attributed to smoking globally, followed by air pollution and occupational risks. Non-optimal temperature and high body-mass index were additional risk factors for COPD and asthma, respectively. Interpretation: Albeit the age-standardised prevalence, death, and DALYs rates of CRDs have decreased, they still cause a substantial burden and deaths worldwide. The high death and DALYs rates in low and low-middle SDI countries highlights the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for tobacco control, enhancing air quality, reducing occupational hazards, and fostering clean cooking fuels are crucial steps in reducing the burden of CRDs, especially in low- and lower-middle income countries

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Studies on the dehydration kinetics and rehydration of YAG precursor powder in the hydroxyhydrogel form

YAG precursor powder was prepared in the hydroxyhydrogel form. Dehydration kinetic study and rehydration experiment was carried out to know the behavior of water molecules and hydroxide bonds present in the hydroxyhydrogel network structure with temperature. Rate constants and activation energies for dehydration and dehydroxylation were evaluated by static thermogravimetry. Percent rehydration was determined at different heat treatment temperatures. The results obtained were explained, correlated to establish the thermal stability of hydroxyhydrogel network structure and finally supported by the FTIR analysis. (C) 2012 Elsevier Ltd and Techna Group S.r.l. All rights reserved