ESCRT machinery mediates selective microautophagy of endoplasmic reticulum in yeast

ER-phagy, the selective autophagy of endoplasmic reticulum (ER), safeguards organelle homeostasis by eliminating misfolded proteins and regulating ER size. ER-phagy can occur by macroautophagic and microautophagic mechanisms. While dedicated machinery for macro-ER-phagy has been discovered, the molecules and mechanisms mediating micro-ER-phagy remain unknown. Here, we first show that micro-ER-phagy in yeast involves the conversion of stacked cisternal ER into multilamellar ER whorls during microautophagic uptake into lysosomes. Second, we identify the conserved Nem1-Spo7 phosphatase complex and the ESCRT machinery as key components for micro-ER-phagy. Third, we demonstrate that macro- and micro-ER-phagy are parallel pathways with distinct molecular requirements. Finally, we provide evidence that the ESCRT machinery directly functions in scission of the lysosomal membrane to complete the microautophagic uptake of ER. These findings establish a framework for a mechanistic understanding of micro-ER-phagy and, thus, a comprehensive appreciation of the role of autophagy in ER homeostasis

Manipulator control with obstacle avoidance using local guidance

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Aeronautics and Astronautics, 1988.Includes bibliographical references.by Koichi Funaya.M.S

Automation and crew time saving in the space experiment

We describe preliminary results of the feasibility study of automation and crew workload saving in space experiments on the space station. Some functions have been studied that can be automated within a single rack and without major impact to the development process and costs. In addition, we assume the following premises: (1) applicable as the second generation apparatuses; (2) maximum reduction of the crew workload; and (3) automation between racks including storage. Four apparatuses have been selected as the study case; results for three are summarized

Minor zygotic gene activation is essential for mouse preimplantation development.

In mice, transcription initiates at the mid-one-cell stage and transcriptional activity dramatically increases during the two-cell stage, a process called zygotic gene activation (ZGA). Associated with ZGA is a marked change in the pattern of gene expression that occurs after the second round of DNA replication. To distinguish ZGA before and after the second-round DNA replication, the former and latter are called minor and major ZGA, respectively. Although major ZGA are required for development beyond the two-cell stage, the function of minor ZGA is not well understood. Transiently inhibiting minor ZGA with 5, 6-dichloro-1-β-d-ribofuranosyl-benzimidazole (DRB) resulted in the majority of embryos arresting at the two-cell stage and retention of the H3K4me3 mark that normally decreases. After release from DRB, at which time major ZGA normally occurred, transcription initiated with characteristics of minor ZGA but not major ZGA, although degradation of maternal mRNA normally occurred. Thus, ZGA occurs sequentially starting with minor ZGA that is critical for the maternal-to-zygotic transition

Arbuscular cell invasion coincides with extracellular vesicles and membrane tubules

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Robust Online Time Series Prediction with Recurrent Neural Networks

Time series forecasting for streaming data plays an important role in many real applications, ranging from IoT systems, cyber-networks, to industrial systems and healthcare. However the real data is often complicated with anomalies and change points, which can lead the learned models deviating from the underlying patterns of the time series, especially in the context of online learning mode. In this paper we present an adaptive gradient learning method for recurrent neural networks (RNN) to forecast streaming time series in the presence of anomalies and change points. We explore the local features of time series to automatically weight the gradients of the loss of the newly available observations with distributional properties of the data in real time. We perform extensive experimental analysis on both synthetic and real datasets to evaluate the performance of the proposed method

Evolutionary Programming based Recommendation System for Online Shopping

Abstract-In this paper, we propose an interactive evolutionary programming based recommendation system for online shopping that estimates the human preference based on eye movement analysis. Given a set of images of different clothes, the eye movement patterns of the human subjects while looking at the clothes they like differ from clothes they do not like. Therefore, in the proposed system, human preference is measured from the way the human subjects look at the images of different clothes. In other words, the human preference can be measured by using the fixation count and the fixation length using an eye tracking system. Based on the level of human preference, the evolutionary programming suggests new clothes that close the human preference by operations such as selection and mutation. The proposed recommendation is tested with several human subjects and the experimental results are demonstrated

Reconstitution of Mdm2-Dependent Post-Translational Modifications of p53 in Yeast

p53 mediates cell cycle arrest or apoptosis in response to DNA damage. Its activity is subject to a tight regulation involving a multitude of post-translational modifications. The plethora of functional protein interactions of p53 at present precludes a clear understanding of regulatory principles in the p53 signaling network. To circumvent this complexity, we studied here the minimal requirements for functionally relevant p53 post-translational modifications by expressing human p53 together with its best characterized modifier Mdm2 in budding yeast. We find that expression of the human p53-Mdm2 module in yeast is sufficient to faithfully recapitulate key aspects of p53 regulation in higher eukaryotes, such as Mdm2-dependent targeting of p53 for degradation, sumoylation at lysine 386 and further regulation of this process by p14ARF. Interestingly, sumoylation is necessary for the recruitment of p53-Mdm2 complexes to yeast nuclear bodies morphologically akin to human PML bodies. These results suggest a novel role for Mdm2 as well as for p53 sumoylation in the recruitment of p53 to nuclear bodies. The reductionist yeast model that was established and validated in this study will now allow to incrementally study simplified parts of the intricate p53 network, thus helping elucidate the core mechanisms of p53 regulation as well as test novel strategies to counteract p53 malfunctions

Renal Dysfunction in Acute Heart Failure

During treatment of acute heart failure (AHF), worsening renal function is often complicated and results in a complex clinical course. Furthermore, renal dysfunction is a strong independent predictor of long-term adverse outcomes in patients with AHF. Traditionally, the predominant cause of renal dysfunction has been attributed to impairment of cardiac output and relative underfilling of arterial perfusion. Recently, emerging data have led to the importance of venous congestion and elevated intra-abdominal pressure rather than confining it to impaired forward cardiac output as the primary driver of renal impairment. Relief of congestion is a major objective of AHF treatment but therapy is still based on the administration of loop diuretics. The results of the recently performed controlled studies for the assessment of new treatments to overcome resistance to diuretic treatment to protect kidneys from untoward effects have been mostly neutral. Better treatment of congestion in heart failure remains a major problem

Morphology-dependent entry kinetics and spread of influenza A virus

Influenza A viruses (IAV) display a broad variety of morphologies ranging from spherical to long filamentous virus particles. These diverse phenotypes are believed to allow the virus to overcome various immunological and pulmonary barriers during entry into the airway epithelium, and to influence the viral entry pathway. Notably, laboratory-adapted IAV strains predominantly adopt a spherical form, yet the factors driving this preference as well as the factors favoring filamentous morphology in physiological settings remain unclear. To address this, we generated fluorescent reporter viruses with identical surface glycoproteins but distinct morphologies and developed a correlative light and scanning electron microscopy workflow. This enabled us to investigate the impact of viral morphology on spread, and to identify conditions favoring either form. Our findings demonstrate that filamentous IAV spread significantly slower in various cell lines, consistent with delayed entry kinetics and in-cell cryo-electron tomography, explaining the predominance of spherical forms in laboratory-adapted strains. Cellular junction integrity, neuraminidase activity, and mucin do not inhibit IAV spread in a morphology-dependent manner. However, filamentous virions confer a selective advantage under neutralizing-antibody pressure against hemagglutinin.Synopsis Morphology of influenza A virus (IAV) particles has been shown to affect viral spread and is regulated by selective pressure in the host. Here, correlative light and scanning electron microscopy enables investigation of the effect of host barriers and drugs on viral spread kinetics and selective pressure induced morphological changes. Filamentous IAV particles exhibit slower spread in cell culture compared to spherical particles, consistent with delayed entry kinetics into the host cell. Neutralizing anti-hemagglutinin antibodies inhibit the entry and spread of spherical IAV particles better than that of filamentous viruses. Both viral morphologies remain structurally stable throughout serial passaging under antibody pressure in vitro.Neutralizing antibodies exert selective pressure favoring filamentous IAV by inhibiting cell entry and transmission of spherical particles.Deutsche Forschungsgemeinschaft (DFG)http://dx.doi.org/10.13039/501100001659Chica and Heinz Schaller Foundation (CHS-Stiftung)http://dx.doi.org/10.13039/501100012284EC | European Research Council (ERC)http://dx.doi.org/10.13039/501100000781Bundesministerium für Bildung und Forschung (BMBF)http://dx.doi.org/10.13039/501100002347Daimler und Benz Stiftung (Daimler and Benz Foundation)http://dx.doi.org/10.13039/50110000297