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- Winick-Ng, W, et al.
(författare)
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Cell-type specialization is encoded by specific chromatin topologies
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 599:7886, s. 684-
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Tidskriftsartikel (refereegranskat)abstract
- The three-dimensional (3D) structure of chromatin is intrinsically associated with gene regulation and cell function1–3. Methods based on chromatin conformation capture have mapped chromatin structures in neuronal systems such as in vitro differentiated neurons, neurons isolated through fluorescence-activated cell sorting from cortical tissues pooled from different animals and from dissociated whole hippocampi4–6. However, changes in chromatin organization captured by imaging, such as the relocation of Bdnf away from the nuclear periphery after activation7, are invisible with such approaches8. Here we developed immunoGAM, an extension of genome architecture mapping (GAM)2,9, to map 3D chromatin topology genome-wide in specific brain cell types, without tissue disruption, from single animals. GAM is a ligation-free technology that maps genome topology by sequencing the DNA content from thin (about 220 nm) nuclear cryosections. Chromatin interactions are identified from the increased probability of co-segregation of contacting loci across a collection of nuclear slices. ImmunoGAM expands the scope of GAM to enable the selection of specific cell types using low cell numbers (approximately 1,000 cells) within a complex tissue and avoids tissue dissociation2,10. We report cell-type specialized 3D chromatin structures at multiple genomic scales that relate to patterns of gene expression. We discover extensive ‘melting’ of long genes when they are highly expressed and/or have high chromatin accessibility. The contacts most specific of neuron subtypes contain genes associated with specialized processes, such as addiction and synaptic plasticity, which harbour putative binding sites for neuronal transcription factors within accessible chromatin regions. Moreover, sensory receptor genes are preferentially found in heterochromatic compartments in brain cells, which establish strong contacts across tens of megabases. Our results demonstrate that highly specific chromatin conformations in brain cells are tightly related to gene regulation mechanisms and specialized functions.
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- Cook, T. D., et al.
(författare)
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Temporal Changes in Postdischarge Mortality Risk After Hospitalization for Heart Failure (from the EVEREST Trial)
- 2016
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 117:4, s. 611-616
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Tidskriftsartikel (refereegranskat)abstract
- In observational studies of patients hospitalized for heart failure (HHF), risk of death is highest immediately after discharge and decreases over time. It is unclear whether this population risk trajectory reflects (1) lowering of individual patient mortality risk with increasing time from index hospitalization or (2) temporal changes in population case-mix with earlier postdischarge death for "sicker" patients. Survival rate and longitudinal models were used to estimate temporal changes in postdischarge all-cause mortality risk in 3,993 HHF patients discharged alive in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with, Tolvaptan (EVEREST) trial. After median 'follow-up of 9.9 months, 971 patients died (24.2%). Predicted mortality rate decreased from 15.9 per 100 patient-years immediately after discharge to 13.4 at 30 days and 12.8 at 90 days; mortality rate increased steadily thereafter. Risk variation between quintiles of risk was considerably larger than the temporal variation within risk strata. In a longitudinal model serially reassessing predicted patient mortality risk after each follow-up visit using data collected at these visits, predicted mortality risk increased during the 90 days preceding subsequent heart failure readmission and then followed' a postdischarge trajectory similar to the index admission. In conclusion, although there is transiently elevated individual patient risk in the 90 days before and after discharge, the patient's individual risk profile, rather than temporal change in risk relative to hospitalization, remains the main determinant of mortality. For purposes of reducing all-cause mortality in HF patients, preventative and therapeutic measures may be best implemented as long-term interventions for high mortality risk patients based on serial risk assessments, irrespective of recent hospitalization. (C) 2016 Elsevier Inc. All rights reserved.
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- Duarte, T. A. G., et al.
(författare)
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A Glance at Novel Ionanofluids Incorporating Silk-Derived Carbon Dots
- 2024
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Ingår i: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 36:3, s. 1136-1152
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Tidskriftsartikel (refereegranskat)abstract
- One of the hallmarks of the current efforts in the field of thermal energy is heat transfer enhancement. Ionanofluids (INFs), a combination of nanomaterials and ionic liquids (ILs), are an appealing category of thermal fluids. In this work, we introduce sustainable INFs composed of carbon dots derived from Bombyx mori silk fibroin (SF) dispersed in a mixture of 1-butyl-3-methylimidazolium chloride (IL1) and 1-(4-sulfobutyl)-3-methylimidazolium triflate (IL2). The syntheses were performed at mild conditions, with reaction times of 3, 4, and 5 h, and without purification steps. The INFs display room-temperature emission in the visible spectral range with quantum yield values up to 0.09 and are essentially viscous fluids (G″ > G′). A marked shear thinning behavior is observed at high shear rates, particularly for the systems SFIL1IL2-3h and SFIL1IL2-4h. The INFs demonstrate relatively high heat capacity and thermal conductivity values in comparison to state-of-the-art INFs. Under suitable illumination conditions, the INFs can convert light into heat in an efficient manner, with photothermal conversion efficiencies of up to 28%, similar to other reported INFs. SFIL1IL2-5h exhibits remarkable stability over time within the range of working temperatures. This work paves the way for the development of new thermal fluids for enhanced heat transfer technologies using sustainable synthesis routes and natural raw precursor materials.
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- Nunes, P., et al.
(författare)
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The leaf of Agapanthus africanus (L.) Hoffm. : A physical-chemical perspective of terrestrialization in the cuticle
- 2023
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Ingår i: Environmental and Experimental Botany. - : Elsevier BV. - 0098-8472 .- 1873-7307. ; 208
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Tidskriftsartikel (refereegranskat)abstract
- Although Agapanthus africanus (L.) Hoffm. is one of the most popular ornamental species in both hemispheres, it has an extremely restricted wild occurrence (Cape province, South Africa). This contradiction between gener-alized ornamental application and natural distribution was the basis for the analytical approach adopted in the present work. We hypothesized that characteristic features of the cuticular waxes were adopted by this species to help it cope with severe dehydration associated with marine salinity on account of the short distance of the wild populations to the sea. A comprehensive morpho-anatomical, histological and physical-chemical analysis was performed on the epicuticular and intracuticular layers of the adaxial and abaxial surfaces of leaves of specimens of A. africanus. The adaxial epicuticular surface is hydrophilic and the abaxial epicuticular surface exhibits globally hydrophobic behavior. The main chemical compounds detected in the wax layers of both surfaces of the leaf are the short-chain monocaprylin monoglyceride (C8), and very long-chain 1-hexacosanol (C26) and 1-octa-cosanol (C28) alcohols. While monocaprylin is particularly abundant in the intracuticular layers, the epicuticular adaxial surface revealed the highest concentration of both alcohols. We demonstrate that the smart combination of these two classes of molecules with opposite water affinity endows the A. africanus leaf cuticle with a unique water management system combining the efficient entrapment of water in the disordered alpha-gel phase formed by monocaprylin and the high resistance to water transport provided by ordered domains composed of tightly packed, all-trans alkyl chains of the above pair of alcohols. The remarkable structural similarity existing between the monocaprylin alpha-gel and the mucilage of algae is an evidence of the terrestrialization process.
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