In eukaryotic cells, various membrane-bound organelles compartmentalize diverse cellular activities in a spatially and temporally controlled manner. Numerous membraneless organelles assembled via ...liquid-liquid phase separation (LLPS), known as condensates, also facilitate compartmentalization of cellular functions. Emerging evidence shows that these two organelle types interact in many biological processes. Membranes modulate the biogenesis and dynamics of phase-separated condensates by serving as assembly platforms or by forming direct contacts. Phase separation of membrane-associated proteins participates in various trafficking events, such as clustering of vesicles for temporally controlled fusion and storage, and transport of membraneless condensates on membrane-bound organelles. Phase separation also acts in cargo trafficking pathways by sorting and docking cargos for translocon-mediated transport across membranes, by shuttling cargos through the nuclear pore complex, and by triggering the formation of surrounding autophagosomes for delivery to lysosomes. The coordinated actions of membrane-bound and membraneless organelles ensure spatiotemporal control of various cellular functions.
Zhao and Zhang summarize the coordinated interactions between membrane-bound organelles and membraneless condensates in various biological processes. Membranes provide surfaces for assembling condensates and also modulate their dynamics and transport, while protein phase separation regulates the storage and trafficking of membrane-bound organelles and also facilitates protein translocation across membranes.
Macroautophagy involves the sequestration of cytoplasmic contents in a double-membrane autophagosome and their delivery to lysosomes for degradation. In multicellular organisms, nascent ...autophagosomes fuse with vesicles originating from endolysosomal compartments before forming degradative autolysosomes, a process known as autophagosome maturation. ATG8 family members, tethering factors, Rab GTPases, and SNARE proteins act coordinately to mediate fusion of autophagosomes with endolysosomal vesicles. The machinery mediating autophagosome maturation is under spatiotemporal control and provides regulatory nodes to integrate nutrient availability with autophagy activity. Dysfunction of autophagosome maturation is associated with various human diseases, including neurodegenerative diseases, Vici syndrome, cancer, and lysosomal storage disorders. Understanding the molecular mechanisms underlying autophagosome maturation will provide new insights into the pathogenesis and treatment of these diseases.
Autophagy is a versatile degradation system for maintaining cellular homeostasis whereby cytosolic materials are sequestered in a double-membrane autophagosome and subsequently delivered to ...lysosomes, where they are broken down. In multicellular organisms, newly formed autophagosomes undergo a process called 'maturation', in which they fuse with vesicles originating from endolysosomal compartments, including early/late endosomes and lysosomes, to form amphisomes, which eventually become degradative autolysosomes. This fusion process requires the concerted actions of multiple regulators of membrane dynamics, including SNAREs, tethering proteins and RAB GTPases, and also transport of autophagosomes and late endosomes/lysosomes towards each other. Multiple mechanisms modulate autophagosome maturation, including post-translational modification of key components, spatial distribution of phosphoinositide lipid species on membranes, RAB protein dynamics, and biogenesis and function of lysosomes. Nutrient status and various stresses integrate into the autophagosome maturation machinery to coordinate the progression of autophagic flux. Impaired autophagosome maturation is linked to the pathogenesis of various human diseases, including neurodegenerative disorders, cancer and myopathies. Furthermore, invading pathogens exploit various strategies to block autophagosome maturation, thus evading destruction and even subverting autophagic vacuoles (autophagosomes, amphisomes and autolysosomes) for survival, growth and/or release. Here, we discuss the recent progress in our understanding of the machinery and regulation of autophagosome maturation, the relevance of these mechanisms to human pathophysiology and how they are harnessed by pathogens for their benefit. We also provide perspectives on targeting autophagosome maturation therapeutically.
Because the biological and/or pharmacological properties of a given molecule often depend on the absolute and relative configurations of the stereogenic centers, different diastereomers may exhibit ...totally different biological and/or pharmacological activities. Therefore, for compounds containing multiple stereogenic centers, the stereoselective asymmetric synthesis of all of the individual diastereomers, preferably using a catalytic method, is of great interest and importance in organic synthesis and drug discovery. In this context, the development of catalytic diastereodivergent methods is highly desirable, since it provides one of the most efficient ways to access multiple diastereomers from the same substrates. The current review attempts to summarize the developments in the field of asymmetric diastereodivergent catalysis.
Sustainability in chemical synthesis is a major aspect of the current synthetic endeavors and, therefore, mimicking the biological process in the laboratory nowadays has the highest priority. Towards ...achieving this goal, designing organic reactions in domino mode rather than the multistep synthetic pathways and using organocatalysis instead of metal catalysis have received a lot of attention due to the inherent advantages of these processes in terms of synthetic efficiency and sustainability. As a result, the field of asymmetric organocatalytic domino reactions has witnessed tremendous progress in recent years. This review attempts to summarize the latest developments in asymmetric organocatalyzed domino reactions since 2012, with the emphasis on the catalysts and reaction modes. Discussions on the reaction mechanisms and the applications of the developed domino reaction methods in the synthesis of biologically active molecules and natural products are also included when appropriate.
Magnetic skyrmions are localized and topologically protected spin configurations, which are of both fundamental and applied interests for future electronics. In this work, we propose a voltage-gated ...skyrmion transistor within the well-established framework of micromagnetics. Its operating conditions and processes have been theoretically investigated and demonstrated, in which the gate voltage can be used to switch on/off a circuit. Our results provide the first time guidelines for practical realization of hybrid skyrmionic-electronic devices.
Modelling strengthening mechanisms in beta-type Ti alloys Zhao, G.-H.; Liang, X.Z.; Kim, B. ...
Materials science & engineering. A, Structural materials : properties, microstructure and processing,
05/2019, Volume:
756
Journal Article
Peer reviewed
Open access
An integral modelling approach for understanding the strengthening mechanisms in Ti alloys is presented and applied to alloys undergoing deformation via dislocation slip. The model incorporates ...contributions from solid solution, grain boundary, dislocation forest and strain hardening. The metal forming and thermomechanical processing factors influence both grain size and the stored strain energy. The strain hardening of Ti-Fe-Sn-Nb alloys was modelled by considering dislocation accumulation and annihilation terms. By tailoring the contribution of each strengthening effect, the yield stress and plasticity of advanced Ti alloys can be optimised.
Both enantiomers of cis‐ and trans‐fused 3,4,4a,8a‐tetrahydro‐2H,5H‐pyrano2,3‐bpyran‐7‐carboxylates have been obtained in high diastereoselectivities and enantioselectivities from the same starting ...materials using a tandem inverse‐electron‐demand hetero‐Diels–Alder/oxa‐Michael reaction catalyzed by modularly designed organocatalysts (MDOs). Diastereodivergence was achieved in these reactions through the direct control of the stereochemistry of the bridgehead atoms of the fused ring using new MDOs self‐assembled from both enantiomers of proline and cinchona alkaloid thiourea derivatives.
Designer cat.: Both enantiomers of the title compounds are obtained with high diastereo‐ and enantioselectivities from the same starting materials by using an inverse‐electron‐demand hetero‐Diels–Alder/oxa‐Michael reaction catalyzed by modularly designed organocatalysts (MDOs). Diastereodivergence was achieved using MDOs self‐assembled from both enantiomers of proline and cinchona alkaloid thiourea derivatives.
•Propose a carbon nanoparticle-decorated graphite felt electrode for VRFBs.•The energy efficiency is up to 84.8% at 100mAcm−2.•The new electrode allows the peak power density to reach 508mWcm−2.
...Increasing the performance of vanadium redox flow batteries (VRFBs), especially the energy efficiency and power density, is critically important to reduce the system cost to a level for widespread commercialization. Unlike conventional VRFBs with flow-through structure, in this work we create a VRFB featuring a flow-field structure with a carbon nanoparticle-decorated graphite felt electrode for the battery. This novel structure, exhibiting a significantly reduced ohmic loss through reducing electrode thickness, an increased surface area and improved electrocatalytic activity by coating carbon nanoparticles, allows the energy efficiency up to 84.8% at a current density of as high as 100mAcm−2 and the peak power density to reach a value of 508mWcm−2. In addition, it is demonstrated that the battery with this proposed structure exhibits a substantially improved rate capability and capacity retention as opposed to conventional flow-through structured battery with thick graphite felt electrodes.
Abstract
We describe the algorithm used to select the emission line galaxy (ELG) sample at z ∼ 0.85 for the extended Baryon Oscillation Spectroscopic Survey of the Sloan Digital Sky Survey IV, using ...photometric data from the DECam Legacy Survey. Our selection is based on a selection box in the g − r versus r − z colour–colour space and a cut on the g-band magnitude, to favour galaxies in the desired redshift range with strong
${{\rm O}\,\small {II}}$
emission. It provides a target density of 200 deg−2 on the North Galactic Cap and of 240 deg−2 on the South Galactic Cap (SGC), where we use a larger selection box because of deeper imaging. We demonstrate that this selection passes the extended Baryon Oscillation Spectroscopic Survey requirements in terms of homogeneity. About 50 000 ELGs have been observed since the observations have started in 2016, September. These roughly match the expected redshift distribution, though the measured efficiency is slightly lower than expected. The efficiency can be increased by enlarging the redshift range and with incoming pipeline improvement. The cosmological forecast based on these first data predict
$\sigma _{D_V}/D_V = 0.023$
, in agreement with previous forecasts. Lastly, we present the stellar population properties of the ELG SGC sample. Once observations are completed, this sample will be suited to provide a cosmological analysis at z ∼ 0.85, and will pave the way for the next decade of massive spectroscopic cosmological surveys, which heavily rely on ELGs. The target catalogue over the SGC will be released along with DR14.
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