Hypermobile Ehlers-Danlos syndrome (hEDS), mainly characterized by generalized joint hypermobility and its complications, minor skin changes, and apparently segregating with an autosomal dominant pattern, is still without a known molecular basis. Hence, its diagnosis is only clinical based on a strict set of criteria defined in the revised EDS nosology. Moreover, the hEDS phenotypic spectrum is wide-ranging and comprises multiple associated signs and symptoms shared with other heritable or acquired connective tissue disorders and chronic inflammatory diseases. In this complex scenario, we previously demonstrated that hEDS patients' skin fibroblasts show phenotypic features of myofibroblasts, widespread extracellular matrix (ECM) disarray, perturbation of ECM-cell contacts, and dysregulated expression of genes involved in connective tissue architecture and related to inflammatory and pain responses. Herein, the cellular proteome of 6 hEDS dermal myofibroblasts was compared to that of 12 control fibroblasts to deepen the knowledge on mechanisms involved in the disease pathogenesis. Qualitative and quantitative differences were assessed based on top-down and bottom-up approaches and some differentially expressed proteins were proofed by biochemical analyses. Proteomics disclosed the differential expression of proteins principally implicated in cytoskeleton organization, energy metabolism and redox balance, proteostasis, and intracellular trafficking. Our findings offer a comprehensive view of dysregulated protein networks and related pathways likely associated with the hEDS pathophysiology. The present results can be regarded as a starting point for future in-depth investigations aimed to decipher the functional impact of potential bioactive molecules for the development of targeted management and therapies. 相似文献
The building sector is one of the most relevant sectors in terms of environmental impact. Different functional units (FUs) can be used in life cycle assessment (LCA) studies for a variety of purposes. This paper aimed to present different FUs used in the LCA of buildings and evaluate the influence of FU choice and setting in comparative studies.
Methods
As an example, we compared the “cradle to grave” environmental performance of four typical Brazilian residential buildings with different construction typologies, i.e., multi-dwelling and single dwelling, each with high and basic standards. We chose three types of FU for comparison: a dwelling with defined lifetime and occupancy parameters, an area of 1 m2 of dwelling over a year period, and the accommodation of an occupant person of the dwelling over a day.
Results and discussion
The FU choice was found to bias the results considerably. As expected, the largest global warming indicator (GWi) values per dwelling unit and occupant were identified for the high standard dwellings. However, when measured per square meter, lower standard dwellings presented the largest GWi values. This was caused by the greater concentration of people per square meter in smaller area dwellings, resulting in larger water and energy consumption per square meter. The sensitivity analysis of FU variables such as lifetime and occupancy showed the GWi contribution of the infrastructure more relevant compared with the operation in high and basic standard dwellings. The definition of lifetime and occupancy parameters is key to avoid bias and to reduce uncertainty of the results when performing a comparison of dwelling environmental performances.
Conclusions
This paper highlights the need for adequate choice and setting of FU to support intended decision-making in LCA studies of the building sector. The use of at least two FUs presented a broader picture of building performance, helping to guide effective environmental optimization efforts from different approaches and levels of analysis. Information regarding space, time, and service dimensions should be either included in the FU setting or provided in the building LCA study to allow adjustment of the results for subsequent comparison.
Antonie van Leeuwenhoek - A Gram-reaction-negative halotolerant bacterial strain, designated Ka21T, was isolated from agricultural soil and characterised using a polyphasic approach to determine... 相似文献
Mechanobiology is focused on how the physical forces and mechanical properties of proteins, cells, and tissues contribute to physiology and disease. Although the response of proteins and cells to mechanical stimuli is critical for function, the tools to probe these activities are typically restricted to single-molecule manipulations. Here, we have developed a novel microplate reader assay to encompass mechanical measurements with ensemble biochemical and cellular assays, using a microplate lid modified with magnets. This configuration enables multiple static magnetic tweezers to function simultaneously across the microplate, thereby greatly increasing throughput. We demonstrate the broad applicability and versatility through in vitro and in cellulo approaches. Overall, our methodology allows, for the first time (to our knowledge), ensemble biochemical and cell-based assays to be performed under force in high-throughput format. This approach substantially increases the availability of mechanobiology measurements. 相似文献
Hydrobiologia - The genus Rutilus is widespread in the western and central Palearctic region. In the Caspian Sea, the taxonomic status of different populations of Rutilus lacustris has... 相似文献
Vertebrate Hedgehog signals are transduced through the primary cilium, a specialized lipid microdomain that is required for Smoothened activation. Cilia-associated sterol and oxysterol lipids bind to Smoothened to activate the Hedgehog pathway, but how ciliary lipids are regulated is incompletely understood. Here we identified DHCR7, an enzyme that produces cholesterol, activates the Hedgehog pathway, and localizes near the ciliary base. We found that Hedgehog stimulation negatively regulates DHCR7 activity and removes DHCR7 from the ciliary microenvironment, suggesting that DHCR7 primes cilia for Hedgehog pathway activation. In contrast, we found that Hedgehog stimulation positively regulates the oxysterol synthase CYP7A1, which accumulates near the ciliary base and produces oxysterols that promote Hedgehog signaling in response to pathway activation. Our results reveal that enzymes involved in lipid biosynthesis in the ciliary microenvironment promote Hedgehog signaling, shedding light on how ciliary lipids are established and regulated to transduce Hedgehog signals. 相似文献