• Wilson Ellington opublikował 7 miesięcy temu

    ATG9A, the only multi-pass transmembrane protein among core ATG proteins, is an essential regulator of autophagy, yet its regulatory mechanisms and network of interactions are poorly understood. Through quantitative BioID proteomics, we identify a network of ATG9A interactions that includes members of the ULK1 complex and regulators of membrane fusion and vesicle trafficking, including the TRAPP, EARP, GARP, exocyst, AP-1, and AP-4 complexes. These interactions mark pathways of ATG9A trafficking through ER, Golgi, and endosomal systems. In exploring these data, we find that ATG9A interacts with components of the ULK1 complex, particularly ATG13 and ATG101. Using knockout/reconstitution and split-mVenus approaches to capture the ATG13-ATG101 dimer, we find that ATG9A interacts with ATG13-ATG101 independently of ULK1. Deletion of ATG13 or ATG101 causes a shift in ATG9A distribution, resulting in an aberrant accumulation of ATG9A at stalled clusters of p62/SQSTM1 and ubiquitin, which can be rescued by an ULK1 binding-deficient mutant of ATG13. Together, these data reveal ATG9A interactions in vesicle-trafficking and autophagy pathways, including a role for an ULK1-independent ATG13 complex in regulating ATG9A.Despite the wide use of cytometry for white blood cell classification, the performance of traditional cytometers in point-of-care testing remains to be improved. Microfluidic techniques have been shown with considerable potentials in the development of portable devices. Here we present a prototype of microfluidic cytometer which integrates a three-dimensional hydrodynamic focusing system and an on-chip optical system to count and classify white blood cells. By adjusting the flow speed of sheath flow and sample flow, the blood cells can be horizontally and vertically focused in the center of microchannel. Optical fibers and on-chip microlens are embedded for the excitation and detection of single-cell. The microfluidic chip was validated by classifying white blood cells from clinical blood samples.In the event of a contagious disease outbreak that reaches the level of a pandemic, the responsibility of providing care for patients increases for front-line nurses. However, being in a nursing role exposes professionals to a range of risks, including but not limited to contagion and mental health impacts. This qualitative study aimed to explore in-depth nurses’ experiences of providing care in the time of the COVID-19 global pandemic. The study followed the COREQ guidelines. Purposive sampling was applied to recruit participants. Semi-structured face-to-face interviews were used to collect the data from 16 nurses across five hospitals in Taiwan in 2020. Contents were analysed using Colaizzi’s seven-step method. The essential structure that was identified was 'Providing care cautiously and being alert to the changing environment’, which reflects the progress of Taiwanese nurses in providing care during the global COVID-19 pandemic. The essence of the phenomenon is presented through three themes (i) facing the emerging challenge, (ii) struggling with uncertainty, fear, stigma, and workload, and (iii) adapting to changes in the environment learning and innovation. The findings identified multi-dimensional impacts of nursing experiences during the COVID-19 pandemic, and the study yielded evidence and practices that can be used to guide and support adequate interventions to support nursing professionals. By understanding the various aspects of nurses’ experiences, policymakers and administrators can better address nursing care providers’ professional and mental health needs during a pandemic.Control of cation ordering in ABX3 perovskites is important to structural, physical and chemical properties. Here we show that thermal transformations of AA’BB’O6 double double perovskites, where both A and B sites have 11 cation order, to (A0.5 A’0.5 )2 BB’O6 double perovskites with fully disordered A/A’ cations can be achieved under pressure in CaMnMnWO6 and SmMnMnTaO6 , enabling both polymorphs of each material to be recovered. This leads to a dramatic switch of magnetic properties from ferrimagnetic order in double double perovskite CaMnMnWO6 to spin glass behaviour in the highly frustrated double perovskite polymorph. Comparison of double double and double perovskite polymorphs of other materials will enable effects of cation order and disorder on other properties such as ferroelectricity and conductivity to be explored.Bacterial infection is among the most common diseases that threaten human health. Antibiotics are effective in treating bacterial infections. However, the overuse of antibiotics will lead to an increase in bacterial resistance. To reduce the overuse of antibiotics and improve the effective use of antibiotics through slow release, silk fibroin (SF)/polyethylene oxide (PEO) nanofiber membranes with different SF and PEO proportions were prepared by electrospinning. The ecofriendly solvent ethanol solution was used for electrospinning for better protection of antibiotic activity. The SEM showed that the surface of SF/PEO (28) and SF/PEO (37) was smoother and more uniform. With the increase of SF content, the thermal stability and hydrophilicity of SF/PEO nanofiber membranes were improved. The SF/PEO (37) nanofiber membrane had the best mechanical property and its maximum stress and strain were 4.6 1 ± 0.24 MPa and 16.36 ± 0.41%, respectively. Based on these good properties, SF/PEO (37) nanofiber membrane was chosen for loading and releasing gentamicin sulfate (GS). The fabricated (GS)/SF/PEO (37) nanofiber membrane exhibited good release efficiency and showed the good antibacterial activity against Staphylococcus aureus and Escherichia coli. These investigations indicated the GS/SF/PEO (37) nanofiber membrane (GS/SF/PEO) has a great potential for application in antibacterial materials.We describe a first-semester, integrated, introductory biology and chemistry course for undergraduates at Wellesley College in Wellesley, MA, USA. Our vision was to create a supportive learning community in which students could comfortably make connections between scientific disciplines as they learned necessary content for subsequent courses, further developed problem solving, communication, and laboratory skills, and meaningfully connected with other students and with faculty during their first semester in college. Through highlighting five guiding principles that are central to the course, we describe the integrated course structure and content as well as our efforts to build community, provide support, and engage students in building skills crucial to scientists. We also highlight features of this course and institutional policies that facilitated its logistical and collaborative implementation that can be adapted to fit the needs, goals, and constraints of a diverse range of institutions. A companion article describes an assessment of our course in achieving academic and community building goals.Recognition of distinct phenotypic features is an important component of genetic diagnosis. Although CHARGE syndrome, Kabuki syndrome, and a recently delineated KMT2D Ex 38/39 allelic disorder exhibit significant overlap, differences on neuroimaging may help distinguish these conditions and guide genetic testing and variant interpretation. We present an infant clinically diagnosed with CHARGE syndrome but subsequently found to have a de novo missense variant in exon 38 of KMT2D, the gene implicated in both Kabuki syndrome and a distinct KMT2D allelic disorder. We compare her brain and inner ear morphology to a retrospective cohort of 21 patients with classic Kabuki syndrome and to typical CHARGE syndrome findings described in the literature. Thirteen of the 21 Kabuki syndrome patients had temporal bone imaging (5/13 CT, 12/13 MRI) and/or brain MRI (12/13) which revealed findings distinct from both CHARGE syndrome and the KMT2D allelic disorder. Our findings further elucidate the spectrum of inner ear dysmorphology distinguishing Kabuki syndrome and the KMT2D allelic disorder from CHARGE syndrome, suggesting that these three disorders may be differentiated at least in part by their inner ear anomalies.Racism in health and healthcare has long been recognised as a structural issue. While there has been growing research and a number of important initiatives that have come from approaching racism as a structural issue, there is a range of implications that yet have to be explored as they relate to health and healthcare. Conceptualising racism in this way provides a means to consider how it shapes and is shaped by a range of global injustices and serves as a foundation for more egregious harms. It also suggests that if we are to dismantle racism, we need to look both within and beyond the traditional domains of health and healthcare and account for a range of broader forces that sustain and re-enforce racism. We first discuss the issue of responsibility, drawing on Young’s social connection model to argue that we all have a responsibility to take action in addressing structural racism. We will then deal with a question that naturally follows, namely how we discharge our responsibilities, with a focus on the role of disruptive action in challenging power and ignorance in dismantling racism in health and healthcare.In the last few years, there has been an explosive growth in the area of para-quinone methide (p-QM) chemistry. This boom is actually due to the unique reactivity pattern of p-QMs, and also their remarkable synthetic applications. In fact, p-QMs serve as synthons for unsymmetrical diaryl- and triarylmethanes, and also for the construction of diverse range of carbocycles and heterocycles. In the last few years, a wide range of structurally complex heterocyclic frameworks could be accessed through the synthetic transformations of structurally modified stable p-QMs. Therefore, the main focus of this review article is to cover the recent advancements in the transition-metal, Lewis acid and base-catalyzed/mediated synthetic transformations of the stable p-quinone methides (p-QMs) to oxygen- and nitrogen-containing heterocycles.Tillandsia L. is the largest genus of the family Bromeliaceae, containing 755 species and seven subgenera. Morphoanatomical studies of leaves provide useful characteristics to phylogenetic, taxonomic, and ecological analyses. This study aims to characterize and compare the leaves of 24 species of the four subgenera of Tillandsia that occur in Bahia and also perform adaptative inferences to environmental responses. The results of the species’ morphoanatomical studies were compared through dissimilarity analysis. The species have rosulate leaves with varying lengths and widths. The peltate trichomes present variation in the indument density and the length of their wing and central disk. The stomata are longitudinally distributed in one or both sides of the limb. The mesophyll is dorsiventral and presents aquiferous and chlorophyllic parenchymas. The vascular bundles are collateral and partially covered by fibers, except for Tillandsia linearis. Based on the dissimilarity analysis, it was possible to identify the formation of five groups. Group G1 was composed of T. linearis, which diverged from the other species of the subgenus. Group G2 was formed by the remaining species of the subgenus Phytarrhiza. G3 and G4 presented the species of the subgenus Diaphoranthema and Tillandsia, respectively. Group G5 gathered 11 species of the subgenus Anoplophytum and presented higher variability than the other subgenera. Based on the results, the morphoanatomical characteristics can be used to characterize and group Tillandsia species, besides confirming the morphological variability of these species to the epiphyte habit in different environments, especially xeric ones.

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