- Biochemical and biophysical research communications
- Published over 2 years ago
Macroautophagy is a conserved degradative pathway and its deterioration is linked to disturbances in cellular proteostasis and multiple diseases. Here, we show that the RAB GTPase RAB18 modulates autophagy in primary human fibroblasts. The knockdown of RAB18 results in a decreased autophagic activity, while its overexpression enhances the degradative pathway. Importantly, this function of RAB18 is dependent on RAB3GAP1 and RAB3GAP2, which might act as RAB GEFs and stimulate the activity of the RAB GTPase. Moreover, the knockdown of RAB18 deteriorates proteostasis and results in the intracellular accumulation of ubiquitinated degradation-prone proteins. Thus, the RAB GTPase RAB18 is a positive modulator of autophagy and is relevant for the maintenance of cellular proteostasis.
There is an urgent need to improve the infrastructure supporting the reuse of scholarly data. A diverse set of stakeholders-representing academia, industry, funding agencies, and scholarly publishers-have come together to design and jointly endorse a concise and measureable set of principles that we refer to as the FAIR Data Principles. The intent is that these may act as a guideline for those wishing to enhance the reusability of their data holdings. Distinct from peer initiatives that focus on the human scholar, the FAIR Principles put specific emphasis on enhancing the ability of machines to automatically find and use the data, in addition to supporting its reuse by individuals. This Comment is the first formal publication of the FAIR Principles, and includes the rationale behind them, and some exemplar implementations in the community.
A substantial fraction of marine plastic debris originates from land-based sources and rivers potentially act as a major transport pathway for all sizes of plastic debris. We analyzed a global compilation of data on plastic debris in the water column across a wide range of river sizes. Plastic debris loads, both microplastic (particles <5 mm) and macroplastic (particles >5 mm) are positively related to the mismanaged plastic waste (MMPW) generated in the river catchments. This relationship is nonlinear where large rivers with population-rich catchments delivering a disproportionately higher fraction of MMPW into the sea. The 10 top-ranked rivers transport 88-95% of the global load into the sea. Using MMPW as a predictor we calculate the global plastic debris inputs form rivers into the sea to range between 0.41 and 4 × 10(6) t/y. Due to the limited amount of data high uncertainties were expected and ultimately confirmed. The empirical analysis to quantify plastic loads in rivers can be extended easily by additional potential predictors other than MMPW, for example, hydrological conditions.
The gut feelings of doctors can act as triggers and modulators of the diagnostic process. This study explored the existence, significance, determinants and triggers of gut feelings among Spanish general practitioners.
Miconazole nitrate is an imidazole derivative used to treat skin disorders caused by fungi. The aim of this study was to investigate in a systematic way whether miconazole nitrate can have skin penetration enhancing properties. Using Franz diffusion cells, three representative model compounds (caffeine, testosterone and ibuprofen) were applied to human skin as 10 mM aqueous-ethanolic solutions with or without 1 mM of miconazole nitrate. The apparent permeability coefficient K(p) for each of the model compounds was determined with and without miconazole nitrate. While a statistically significant penetration enhancement effect of 33% was found for testosterone, no overall statistically significant effect could be demonstrated for caffeine and ibuprofen. The increase in skin permeability of testosterone is mainly due to an improved partitioning from the dose solution into the skin, thereby resulting in a higher delivery through the human skin. Our results indicate that miconazole can act as a penetration enhancer.
Bi2Se3 initially emerged as a particularly promising host of topological physics. However, in actual materials, several issues have been uncovered including strong surface band bending and potential fluctuations. To investigate these concerns, we study nominally stoichiometric Bi2Se3 using scanning tunnelling microscopy. Here we identify two distinct distributions of BiSe antisites that act as nanometer-scale sensors for the surface band-bending field. To confirm this, we examine bulk Cu-doped Bi2Se3 and demonstrate a significantly reduced surface band-bending field. In addition, we find that in the case of unintentionally doped Bi2Se3, lateral fluctuations of the Dirac point can be directly correlated with specific near-surface point defects, namely Se vacancies.
Ribbon synapses are tonically active high-throughput synapses. The performance of the ribbon synapse is accomplished by a specialization of the cytomatrix at the active zone referred to as the synaptic ribbon (SR). Progress in our understanding of the structure-function relationship at the ribbon synapse has come from observations that, in photoreceptors lacking a full-size scaffolding protein Bassoon (BsnΔ(Ex4/5)), dissociation of SRs coincides with perturbed signal transfer. The aim of the present study has been to elaborate the role of Bassoon as a structural organizer of the ribbon synapse and to differentiate it with regard to the ambient lighting conditions. The ultrastructure of retinal ribbon synapses has been compared between wild-type and BsnΔ(Ex4/5) mice adapted to light (low activity) and darkness (high activity). The results obtained suggest that Bassoon and environmental illumination synergistically and complementarily act as organizers of the ribbon synapse. Thus, light-dependent and Bassoon-independent regulation involves initial SR tethering to the membrane and a basic shape transition of ribbon material from spherical to rod-like, since darkness induces these features in BsnΔ(Ex4/5) rod spherules. However, the tight anchorage of the SR via an arciform density and the proper assembly of SRs to the full-sized horseshoe-shaped complex depend on Bassoon, as these steps fail in BsnΔ(Ex4/5) rod spherules.
Women typically obtain higher subsequent college GPAs than men with the same admissions test score. A common reaction is to attribute this to a flaw in the admissions test. We explore the possibility that this underprediction of women’s performance reflects gender differences in conscientiousness and college course-taking patterns. In Study 1, we focus on using the ACT to predict performance in a single, large course where performance is decomposed into cognitive (exam and quiz scores) and less cognitive, discretionary components (discussion and extra credit points). The ACT does not underpredict female’s cognitive performance, but it does underpredict female performance on the less cognitive, discretionary components of academic performance, because it fails to measure and account for the personality trait of conscientiousness. In Study 2, we create 2 course-difficulty indices (Course Challenge and Mean Aptitude in Course) and add them to an HLM regression model to see if they reduce the degree to which SAT scores underpredict female performance. Including Course Challenge does result in a modest reduction of the gender coefficient; however, including Mean Aptitude in Course does not. Thus, differences in course-taking patterns is a partial (albeit small) explanation for the common finding of differential prediction by gender. (PsycINFO Database Record
A palygorskite (Pal)-based ratiometric fluorescent nanoprobe is designed in order to establish a real time, on-site visual, and highly sensitive detection method for tetracyclines (TCs). The nanoprobe comprises the green emissive dye molecules embedded in the natural Pal, which serve as the internal reference signal. The potential red-emissive seed-europium (Eu(3+)) ions are covalently bound on the surface of modified Pal, and they can act as the specific recognition element. The emission intensity of Eu(3+) ions significantly increases upon TC addition. The nanoprobe fluorescence changes from green to yellow, orange, or red, thereby accomplishing the visual ratiometric fluorescent detection. This nanoprobe exhibits a high sensitivity with a detection limit of 7.1nM and an excellent selectivity in monitoring the levels of TCs in milk samples. In addition, this nanoprobe is useful for quantitative determination of TCs, and it is not affected with intensity fluctuations due to instrumental or environmental factors. The nanoprobe-immobilized test paper realizes real-time TCs analysis by using a smartphone with an easy-to-access color-scanning APP as the detection platform. Moreover, the reported construction of visual ratiometric detection system follows the sustainable development idea, that is, from nature, for nature, and into the nature.
To fabricate multimodal nanoconstruct that act as a single node for photoacoustic imaging (PAI) and photothermal therapy (PTT) in the fight against cancer.