227 research outputs found
Cell polarity in myelinating glia: From membrane flow to diffusion barriers
Myelin-forming glia are highly polarized cells that synthesize as an extension of their plasma membrane, a multilayered myelin membrane sheath, with a unique protein and lipid composition. In most cells polarity is established by the polarized exocytosis of membrane vesicles to the distinct plasma membrane domains. Since myelin is composed of a stack of tightly packed membrane layers that do not leave sufficient space for the vesicular trafficking, we hypothesize that myelin does not use polarized exocytosis as a primary mechanism, but rather depends on lateral transport of membrane components in the plasma membrane. We suggest a model in which vesicle-mediated transport is confined to the cytoplasmic channels, from where transport to the compacted areas occurs by lateral flow of cargo within the plasma membrane. A diffusion barrier that is formed by MBP and the two adjacent cytoplasmic leaflets of the myelin bilayers acts a molecular sieve and regulates the flow of the components. Finally, we highlight potential mechanism that may contribute to the assembly of specific lipids within myelin. This article is part of a Special Issue entitled Lipids and Vesicular Transport. (C) 2012 Elsevier B.V. All rights reserved
Central nervous system myelin: structure, synthesis and assembly
The wrapping of multiple layers of myelin membrane sheets around an axon is of fundamental importance for the function of the nervous system. In the central nervous system (CNS) oligodendrocytes synthesize tremendous amounts of cellular membrane to form multiple myelin internodes of highly stable membranes with a specific set of tightly packed lipids and proteins. In recent years, mouse mutants have allowed great advances in our understanding of the functional and structural role of many of the major components of myelin. The challenge now is to extend this knowledge to unravel the molecular machinery and mechanisms required to synthesize, assemble and wrap myelin multiple times around an axon at the appropriate developmental time. Such insight will be essential in designing new therapeutic strategies to promote remyelination in demyelinating disorders such as multiple sclerosis.European Research Council; EMBO Young Investigator Progra
Myelin architecture: zippering membranes tightly together
Rapid nerve conduction requires the coating of axons by a tightly packed multilayered myelin membrane. In the central nervous system, myelin is formed from cellular processes that extend from oligodendrocytes and wrap in a spiral fashion around an axon, resulting in the close apposition of adjacent myelin membrane bilayers. In this review, we discuss the physical principles underlying the zippering of the plasma membrane of oligodendrocytes at the cytoplasmic and extracellular leaflet. We propose that the interaction of the myelin basic protein with the cytoplasmic leaflet of the myelin bilayer triggers its polymerization into a fibrous network that drives membrane zippering and protein extrusion. In contrast, the adhesion of the extracellular surfaces of myelin requires the down-regulation of repulsive components of the glycocalyx, in order to uncover weak and unspecific attractive forces that bring the extracellular surfaces into close contact. Unveiling the mechanisms of myelin membrane assembly at the cytoplasmic and extracelluar sites may help to understand how the myelin bilayers are disrupted and destabilized in the different demyelinating diseases
First person – Shweta Yadav
ABSTRACT
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Shweta Yadav is the first author on ‘RDGBα localization and function at membrane contact sites is regulated by FFAT–VAP interactions’, published in Journal of Cell Science. Shweta is a post-doctoral associate in the laboratory of Prof. Juan Botas at Baylor College of Medicine, Texas, USA, investigating neurodegenerative diseases.</jats:p
The social correlates of value consensus
This paper examines societal value consensus, or the extent to which individuals within a culture share similar values. This topic has been extensively theoretically discussed, but has received limited empirical attention. This paper explores the social variables of economic equality, religiosity and religious homogeneity and their relation to value consensus. Publicly available data from the latest wave of World Values Survey (N = 73,256), CIA world factbook and the World Bank World Development Indicators are used for analysis. Results reveal that value consensus is not correlated with religiosity, religious homogeneity or economic equality. Implications of these findings, with specific reference to economic developmental theories are discussed.M.A.Includes bibliographical referencesby Shweta A. Kulkarn
Sorting in early endosomes reveals connections to docking- and fusion-associated factors.
The early endosomes constitute a major sorting platform in eukaryotic cells. They receive material through fusion with endocytotic vesicles or with trafficking vesicles from the Golgi complex and later sort it into budding vesicles. While endosomal fusion is well understood, sorting is less characterized; the 2 processes are generally thought to be effected by different, unrelated machineries. We developed here a cell-free assay for sorting/budding from early endosomes, by taking advantage of their ability to segregate different cargoes (such as transferrin, cholera toxin subunit B, and low-density lipoprotein, LDL) into different carrier vesicles. Cargo separation required both carrier vesicle formation and active maturation of the endosomes. Sorting and budding were insensitive to reagents perturbing clathrin coats, coatomer protein complex-I (COPI) coats, dynamin, and actin, but were inhibited by anti-retromer subunit antibodies. In addition, the process required Rab-GTPases, phosphatidylinositol-3-phosphate, and, surprisingly, the docking factor early endosomal autoantigen 1 (EEA1). Sorting also required the function of the N-ethylmaleimide-sensitive factor (NSF), a well-known fusion cofactor, while it did not depend on preceding fusion of endosomes. We conclude that fusion, docking, and sorting/budding are interconnected at the molecular level
Adaptive geolocation based interference control for hierarchical cellular network with femtocells
This thesis presents adaptive interference control methods to mitigate undesirable interference effects from femtocells to macrocell users in hierarchical cellular networks. The study in this thesis begins by quantifying the deterioration in performance experienced by macrocell users on the downlink in a simulated 3G/CDMA environment. Our baseline results show that the median deterioration in signal-to-interference plus noise ratio (SINR) observed for the macrocell users may be up to 10dB and the outage probability increases by large extend. In the next part of study, we propose interference mitigation schemes - ‘Proximity Based Iterative’ (PBI) scheme and ‘Adaptive Interference Scaling’ (AIS) scheme to adjust femtocell power to reduce femtocell interference effect on macrocell users. We show that previously studied mechanisms like the load-spillage, utility based power adaptation usually require relatively high system overhead due to over-the-air signalling for estimation of interference. Proposed PBI and AIS schemes avoid such over-the-air signalling and make use of geo-location information and backhaul signalling for the femtocell interference estimation. These schemes achieve power re-distribution by scaling power uniformly across femtocells, while allowing the network operators to set desired target data rates. Results from simulations show that the PBI and AIS schemes are able to increase the number of macrocell users achieving chosen target data rates by up to 158% when compared with the value when femtocell transmission power is at maximum. However, in case of the PBI scheme, results shows that 25% of femtocell users may receive rates below the target rate. The AIS scheme provides an improvement over the PBI scheme by adjusting femtocell power according to the interference contribution by each femtocell. Thus, AIS achieves better performance and only up to 12:2% of femtocell users receive rates below the target rate. This study concludes with parametric evaluation of system throughput as a function of both macrocell and femtocell user densities. Qualitative results are provided to support the conclusion.M.S.Includes bibliographical referencesby Shweta Sagar
Evaluating Hydration of the Cement Mortar Blended With Calcinated Clay Using Piezoelectric Based Sensing Technique
Concrete is widely used in modern day construction as it can be moulded to the variety of shapes
and finishes. Mostly, it performs well throughout its service life of the structure. When it comes in
contact with water then it starts gaining strength. In this study, Calcinated Clay is utilized at
different percentage level such as 0%, 4%, 6%, 8%, 10% and 12% as a partial replacement of
cement. The aim of this study is to investigate the gain in Compressive Strength of cement-based
material with Calcinated Clay by utilizing Piezoelectric-based sensor Electromechanical
Impedance Technique.
An embedded Piezoelectric-based sensor is used for monitoring the early age as well as long term
hydration of binder paste. Change in Conductance indicates progressive changes of hydration in
cement-based mortar. The experimental results on mortar mix with 6% replacement of cement has
shown maximum compressive strength as compared to other mixes and similar trends of results
have been captured by EMI Technique. On the formulated binder paste, setting time and flow
value are also determined. Delay in setting time and approximately linearly decrease in flow value
has been recognized with increasing the percentage of Calcinated Clay. To compare the EMI
spectra, statistics metric such as Root Mean Square Deviation (RMSD) has been used for various
percentage of cement paste
Loss of electrostatic cell-surface repulsion mediates myelin membrane adhesion and compaction in the central nervous system
During the development of the central nervous system (CNS), oligodendrocytes wrap their plasma membrane around axons to form a multilayered stack of tightly attached membranes. Although in-tracellular myelin compaction and the role of myelin basic protein has been investigated, the forces that mediate the close interaction of myelin membranes at their external surfaces are poorly understood. Such extensive bilayer-bilayer interactions are usually prevented by repulsive forces generated by the glycocalyx, a dense and confluent layer of large and negatively charged oligosaccharides. Here we investigate the molecular mechanisms underlying myelin adhesion and compaction in the CNS. We revisit the role of the proteolipid protein and analyze the contribution of oligosaccharides using cellular assays, biophysical tools, and transgenic mice. We observe that differentiation of oligodendrocytes is accompanied by a striking down-regulation of components of their glycocalyx. Both in vitro and in vivo experiments indicate that the adhesive properties of the proteolipid protein, along with the reduction of sialic acid residues from the cell surface, orchestrate myelin membrane adhesion and compaction in the CNS. We suggest that loss of electrostatic cell-surface repulsion uncovers weak and unspecific attractive forces in the bilayer that bring the extracellular surfaces of a membrane into close contact over long distances
Roll-Call: an energy efficient radio frequency identification system.
In this thesis, we investigate two of the major challenges in pervasive systems: energy efficiency and co-existence of uncoordinated wireless messages by exploring the design of a Radio Frequency Identification (RFID) system intended to support the simultaneous and real time monitoring of thousands of entities. These entities, which may be individuals or inventory items, each carry a low-power transmit-only tag and are monitored by a collection of networked base-stations reporting to a central database. We have built a customized transmit-only tag with a small form-factor, and have implemented a real-time monitoring application intended to verify the presence of each tag in order to detect potential disappearance of a tag (perhaps due to item theft). Throughout the construction of our system, we have carefully engineered it for extended tag lifetime and reliable monitoring capabilities in the presence of packet collisions, while keeping the tags small and inexpensive.
The major challenge in this architecture (called Roll-Call) is to supply the energy needed for long range continuous tracking for a year or more of reporting once a second while keeping the tags (called PIPs) small and inexpensive. We have used this as a model problem for optimizing cost, size and lifetime across the entire pervasive, persistent system from firmware to protocol.M.S.Includes bibliographical references (p. 46-48)
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