2,456 research outputs found
Effects of niacin restriction on sirtuin and PARP responses to photodamage in human skin.
Sirtuins (SIRTs) and poly(ADP-ribose) polymerases (PARPs), NAD(+)-dependent enzymes, link cellular energy status with responses to environmental stresses. Skin is frequently exposed to the DNA damaging effects of UV irradiation, a known etiology in skin cancer. Thus, understanding the defense mechanisms in response to UV, including the role of SIRTs and PARPs, may be important in developing skin cancer prevention strategies. Here, we report expression of the seven SIRT family members in human skin. SIRTs gene expressions are progressively upregulated in A431 epidermoid carcinoma cells (SIRTs1 and 3), actinic keratoses (SIRTs 2, 3, 5, 6, and 7) and squamous cell carcinoma (SIRTs 1-7). Photodamage induces dynamic changes in SIRT expression with upregulation of both SIRT1 and SIRT4 mRNAs. Specific losses of SIRT proteins occur early after photodamage followed by accumulation later, especially for SIRT4. Niacin restriction, which decreases NAD(+), the sirtuin substrate, results in an increase in acetylated proteins, upregulation of SIRTs 2 and 4, increased inherent DNA damage, alterations in SIRT responses to photodamage, abrogation of PARP activation following photodamage, and increased sensitivity to photodamage that is completely reversed by repleting niacin. These data support the hypothesis that SIRTs and PARPs play important roles in resistance to photodamage and identify specific SIRTs that respond to photodamage and may be targets for skin cancer prevention
Recommended from our members
Heavenly HELLS? A potential new therapeutic target for retinoblastoma.
Use of textile waste as an addition in the elaboration of an ecological concrete block
The textile industry has grown significantly in recent years, reaching a global fiber production of 53 million tons which 12 % are recycled; Construction sector has been using more and more recycled materials from different industrial sources, to apply them in their constructions and to reduce CO2 emissions and final energy consumption. The present study aims to study the behavior of concrete blocks of fć= 210 kg/cm2 adding polyester textile waste with 3 %, 6 %, 9 %, 12 % and 15 %; void content, compressive strength and thermal conductivity decrease, and water absorption, acoustic insulation and unit price increase by 3 %, 34 % and 16 % compared to conventional concrete block
Recommended from our members
Chromatin remodeling protein HELLS is critical for retinoblastoma tumor initiation and progression.
Retinoblastoma is an aggressive childhood cancer of the developing retina that initiates by biallelic RB1 gene inactivation. Tumor progression in retinoblastoma is driven by epigenetics, as retinoblastoma genomes are stable, but the mechanism(s) that drive these epigenetic changes remain unknown. Lymphoid-specific helicase (HELLS) protein is an epigenetic modifier directly regulated by the RB/E2F pathway. In this study, we used novel genetically engineered mouse models to investigate the role of HELLS during retinal development and tumorigenesis. Our results indicate that Hells-null retinal progenitor cells divide, undergo cell-fate specification, and give rise to fully laminated retinae with minor bipolar cells defects, but normal retinal function. Despite the apparent nonessential role of HELLS in retinal development, failure to transcriptionally repress Hells during retinal terminal differentiation due to retinoblastoma (RB) family loss significantly contributes to retinal tumorigenesis. Loss of HELLS drastically reduced ectopic division of differentiating cells in Rb1/p107-null retinae, significantly decreased the incidence of retinoblastoma, delayed tumor progression, and increased overall survival. Despite its role in heterochromatin formation, we found no evidence that Hells loss directly affected chromatin accessibility in the retina but functioned as transcriptional co-activator of E2F3, decreasing expression of cell cycle genes. We propose that HELLS is a critical downstream mediator of E2F-dependent ectopic proliferation in RB-null retinae. Together with the nontoxic effect of HELLS loss in the developing retina, our results suggest that HELLS and its downstream pathways could serve as potential therapeutic targets for retinoblastoma
Influence of Surface Finishes and a Calcium Phosphate-Based Consolidant on the Decay of Sedimentary Building Stones Due to Acid Attack
Natural stone has long been used as a building material because of its physical-mechanical resistance and its esthetic appeal. However, over the last century increasing industrial activity has produced more acidic environments, such as polluted urban areas, that can cause serious damage to many buildings and historic monuments, and in particular those made with carbonate rocks, which are most prone to decay. In order to mitigate the physicochemical processes that degrade these buildings, a number of phosphate-based consolidants have been developed, which are highly compatible with the carbonated substrate. Research about the role of the surface and its different possible finishes in the transmission of the agents that damage or protect the stone would therefore be very useful, both when choosing the most suitable stone for new constructions and when restoring historic buildings. The main objective of this research was to determine whether the roughness of three types of surface finish (saw-cut, honed and bush-hammered) influences the durability of four types of natural stone (two calcarenites, one travertine and one sandstone) widely used in Andalusia (Spain). The efficacy of a calcium phosphate-based consolidant as a mitigator of deterioration in polluted urban environments was also studied and to this end the physical properties of untreated and treated samples were measured and compared. The samples were exposed to artificial atmospheres with SO2 pollution in order to assess the damage caused to each surface finish. The results indicate that all the surface finishes were vulnerable to the decay caused by acidic atmospheres, although the saw-cut finish was less affected, perhaps because it did not require additional industrial processing. The mineral composition and texture of the rocks were critical factors in terms of the amount and type of decay they suffered, and the travertine and sandstone were more resistant to deterioration than the calcarenites. Similarly, the pore system of each rock was decisive in the penetration of the consolidant. Application of the consolidant improved the behavior of the treated samples by making them more resistant to acid attack without significantly altering the water vapor permeability, the color or the roughness of the surface
Experimental investigation of multiple industrial wastes for carbon dioxide removal strategies
Industrial solid waste by-products are being increasingly employed for geochemical carbon dioxide removal (CDR) strategies due to their fine grain size, accessibility, and large annual production tonnages. Here, a range of such by-products has been tested experimentally for their reactivities with CO2 and water. Sample solutions were monitored for 100 h for changes in chemistry, and solid samples were characterised pre- and post-experiment. Samples rich in Ca- and Mg-bearing minerals, such as dunite, kimberlite, and ilmenite mine tailings, as well as marble quarry cuttings, were key cation sources. Ni sulphide, fluorite and borax tailings, coal-fired power plant fly ashes, and red mud samples showed high dissolution rates. The highest reaction rates were often observed during the initial few hours, and compared well to rates determined for rocks typically targeted for CDR purposes, such as basalt and gabbro. Several samples also showed secondary carbonate precipitation, suggesting opportunities for the development of single-step CDR technologies. Overall, the results of this study indicate that several industrial by-products can provide sufficient cations at favourable dissolution rates for geochemical CDR purposes. Any on-site or near-site conditions for reaction acceleration such as heat, concentrated CO2 or microbes, could further increase favourability for geochemical CDR opportunities.LB and JLFT are funded under H2020-EU.1.3.2. (DETAILS Project, grant agreement ID: 101018312)
Tectonic and climatic controls on the Chuquibamba landslide (western Andes, southern Peru)
The contribution of landslides to the Quaternary evolution of relief is poorly documented in arid contexts. In southern Peru and northern Chile, several massive landslides disrupt the arid western Andean front. The Chuquibamba landslide, located in southern Peru, belongs to this set of large landslides. In this area, the Incapuquio fault system captures the intermittent drainage network and localizes rotational landslides. Seismic activity is significant in this region with recurrent Mw9 subduction earthquakes; however, none of the latest seismic events have triggered a major landslide. New terrestrial cosmogenic dating of the Chuquibamba landslide provides evidence that the last major gravitational mobilization of these rotational landslide deposits occurred at ~ 102 ka, during the Ouki wet climatic event identified on the Altiplano between 120 and 98 ka. Our results suggest that wet events in the arid and fractured context of the Andean forearc induced these giant debris flows. Finally, our study highlights the role of tectonics and climate on (i) the localization of large Andean landslides in the Western Cordillera and on (ii) the long-term mass transfer to the trench along the arid Andean front
- …