Sorting Mechanism Research Articles

Emerging role of exosomal long non-coding RNAs in lung cancer.

Lung cancer is one of the most common malignancies worldwide. Also, it is the leading cause of cancer morbidity and mortality in men. Despite advances in lung cancer diagnosis and treatment, novel approaches are strongly needed to promote early diagnosis and effective treatment of lung cancer. Presently, accumulating data reveal that long noncoding RNAs (lncRNAs) are differentially enriched in exosomes and mediate multiple biological processes in lung cancer, suggesting the potential application of exosomal lncRNAs as diagnostic biomarkers and therapeutic targets. In this review, we described the emerging roles of lncRNAs specifically sorted into exosomes in lung cancer. We discussed the current knowledge of the exosomal lncRNA sorting mechanism and highlighted opportunities for exosome-derived lncRNAs as biomarkers in clinical practice. In particular, we systematically summarized the biological functions of exosomal lncRNAs in lung cancer.

Market models and segregation: examining mechanisms of student sorting

ABSTRACT In recent decades, policymakers around the globe have adopted market mechanisms such as consumer-style choice, provider autonomy and competition. Such policies may improve educational equity since families can choose options outside of their assigned local school. Yet research from multiple countries is finding a link between greater use of such policies and increases in social segregation in schooling. This comprehensive analysis is a first step in examining the specific policies and institutional and contextual factors that may alleviate or exacerbate different types of student sorting. Rather than focus only on the question of causation, we instead examine the potential pathways through which market mechanisms might impact student sorting, and highlight the role of incentives in shaping these pathways. In specifying several such pathways, we then present a framework through which further research might conceptualize and theorize the relationship between market mechanisms and student opportunity.

$\mathit {O(N)}$ Memory-Free Hardware Architecture for Burrows-Wheeler Transform

A novel hardware architecture for Burrows-Wheeler Transform (BWT) scheme is presented. The core idea is to have a memory-free strategy that does not involve any software overhead during BWT operation. This is achieved by introducing a register-file concept and utilizing basic digital logic circuits to perform the entire BWT operation. Additionally, this is a kind of transformation scheme that does not utilize any kind of matrix during transformation, and thereby, it is free from run-time memory consumption. It efficiently handles the string terminating mechanism in the proposed design without involving any extra terminating symbol. This string terminator-free architecture eventually reduces additional operation and storage space to maintain the string, and thereby, the architecture does not necessitate any register read and write operations. This architecture exhibits efficient transformation without involving any indexing method or sorting mechanism during an inverse transformation operation. This architecture achieves <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$O(N)$</tex-math></inline-formula> time complexity compared to <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$O(N^{2})$</tex-math></inline-formula> and <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$O(N \log N)$</tex-math></inline-formula> as experienced by the existing state-of-the-art approaches.

Smuggling and Border Enforcement

AbstractThis article analyzes the efficacy of border enforcement against smuggling. We argue that walls, fences, patrols, and other efforts to secure porous borders can reduce smuggling, but only in the absence of collusion between smugglers and state agents at official border crossings. When such corruption occurs, border enforcement merely diverts smuggling flows without reducing their overall volume. We also identify the conditions under which corruption occurs and characterize border enforcement as a sorting mechanism that allows high-skilled smugglers to forge alternative border-crossing routes while deterring low-skilled smugglers or driving them to bribe local border agents. Combining a formal model and an archival case study of opium smuggling in Southeast Asia, we demonstrate that border enforcement has conditional effects on the routes and volumes of smuggling, depending on the nature of interactions between smugglers and border agents. By drawing attention to the technological and organizational aspects of smuggling, this article brings scholarship on criminal governance into the study of international relations, and contributes to debates on the effects of border enforcement and border politics more generally.

PKD-dependent PARP12-catalyzed mono-ADP-ribosylation of Golgin-97 is required for E-cadherin transport from Golgi to plasma membrane

Significance Proteins are modified by many posttranslational modifications (PTMs) with crucial regulatory functions. A PTM attracting increasing interest is ADP-ribosylation, capable of altering crucial cellular targets. We show that mono-ADP-ribosylation by PARP12 of the protein Golgin-97 regulates transport to the plasma membrane of a specific group of functionally crucial cargo proteins. PARP12 is shown to be part of a regulatory cascade initiated by PKD and involving the direct phosphorylation and activation of PARP12. These events define, through Golgin-97 mono-ADP-ribosylation, a Golgi sorting mechanism for specific basolateral cargoes, including E-cadherin. Defects in this cascade impair E-cadherin transport and formation of cell–cell contacts, with potential consequences for the formation of adherens junctions, polarization of epithelial cells, and development of epithelial–mesenchymal transformation.

Nonequilibrium lateral force and torque by thermally excited nonreciprocal surface electromagnetic waves

We show that an isotropic dipolar particle in the vicinity of a substrate made of nonreciprocal plasmonic materials can experience a lateral thermal-fluctuations-induced force and torque when the particle's temperature differs from that of the slab and the environment. We connect the existence of the lateral force to the asymmetric dispersion of nonreciprocal surface polaritons and the existence of the lateral torque to the spin-momentum locking of such surface waves. Using the formalism of fluctuational electrodynamics, we show that the features of lateral force and torque should be experimentally observable using a substrate of doped indium antimonide (InSb) placed in an external magnetic field, and for a variety of dielectric particles. Interestingly, we also find that the directions of the lateral force and the torque depend on the constituent materials of the particles, which suggests a sorting mechanism based on nonequilibrium fluctuational electrodynamics.

Liquid-Liquid Phase Separation Phenomenon on Protein Sorting Within Chloroplasts.

In higher plants, chloroplasts are vital organelles possessing highly complex compartmentalization. As most chloroplast-located proteins are encoded in the nucleus and synthesized in the cytosol, the correct sorting of these proteins to appropriate compartments is critical for the proper functions of chloroplasts as well as plant survival. Nuclear-encoded chloroplast proteins are imported into stroma and further sorted to distinct compartments via different pathways. The proteins predicted to be sorted to the thylakoid lumen by the chloroplast twin arginine transport (cpTAT) pathway are shown to be facilitated by STT1/2 driven liquid-liquid phase separation (LLPS). Liquid-liquid phase separation is a novel mechanism to facilitate the formation of membrane-less sub-cellular compartments and accelerate biochemical reactions temporally and spatially. In this review, we introduce the sorting mechanisms within chloroplasts, and briefly summarize the properties and significance of LLPS, with an emphasis on the novel function of LLPS in the sorting of cpTAT substrate proteins. We conclude with perspectives for the future research on chloroplast protein sorting and targeting mechanisms.

Endosomal sorting drives the formation of axonal prion protein endoggresomes.

The pathogenic aggregation of misfolded prion protein (PrP) in axons underlies prion disease pathologies. The molecular mechanisms driving axonal misfolded PrP aggregate formation leading to neurotoxicity are unknown. We found that the small endolysosomal guanosine triphosphatase (GTPase) Arl8b recruits kinesin-1 and Vps41 (HOPS) onto endosomes carrying misfolded mutant PrP to promote their axonal entry and homotypic fusion toward aggregation inside enlarged endomembranes that we call endoggresomes. This axonal rapid endosomal sorting and transport-dependent aggregation (ARESTA) mechanism forms pathologic PrP endoggresomes that impair calcium dynamics and reduce neuronal viability. Inhibiting ARESTA diminishes endoggresome formation, rescues calcium influx, and prevents neuronal death. Our results identify ARESTA as a key pathway for the regulation of endoggresome formation and a new actionable antiaggregation target to ameliorate neuronal dysfunction in the prionopathies.

Environmental disparities in urban Mexico: Evidence from toxic water pollution

All else equal, disparities in environmental exposure are associated with disparities in health and economic well-being. Here, we combine 9 years of data on toxic water pollution discharges from more than 1600 industrial facilities across urban Mexico with geographic, economic, and sociodemographic data from ≈ 50,000 Mexican urban block groups. We first show that industrial facilities pollute more in marginalized neighborhoods and in neighborhoods that are becoming more marginalized over time. In contrast, we find no evidence for relationships between toxic water pollution and indigenous race. We then explore channels driving observed exposure disparities. We find evidence that environmental disparities in urban Mexico are associated with collective action, community pressure, and Coasian bargaining. We do not find evidence consistent with political economic or amenity-based sorting mechanisms.

A Role for Lipids in Protein Sorting?

Lipid and protein diversity provides structural and functional identity to the membrane compartments that define the eukaryotic cell. This compositional heterogeneity is maintained by the secretory pathway, which feeds newly synthesized proteins and lipids to the endomembrane systems. The precise sorting of lipids and proteins through the pathway guarantees the achievement of their correct delivery. Although proteins have been shown to be key for sorting mechanisms, whether and how lipids contribute to this process is still an open discussion. Our laboratory, in collaboration with other groups, has recently addressed the long-postulated role of membrane lipids in protein sorting in the secretory pathway, by investigating in yeast how a special class of lipid-linked cell surface proteins are differentially exported from the endoplasmic reticulum. Here we comment on this interdisciplinary study that highlights the role of lipid diversity and the importance of protein-lipid interactions in sorting processes at the cell membrane.

SmartBin system with waste tracking and sorting mechanism using IoT

Effective waste administration is one of the major environmental issues of the present time. The isolation, taking care of, transportation and transfer of waste is to be appropriately overseen in order to limit the hazard to nature. The efficient estimation of waste is best acknowledged when it is isolated. The customary method for physically isolating the waste uses exertion that is more human, time and cost. This work proposes a waste tracking system with integrated waste sorting mechanism, which is an easy and economical way to segregate and track domestic waste. It is intended to sort the domestic waste into metallic, plastic and glass categories. After segregation, the tracking system informs the server how much waste each household is producing. Along these lines, a successful framework for waste management is made helpful for recycling procedures for better environmental cleaning ecosystem with proper waste management operations.

Cargo sorting at the trans-Golgi network at a glance.

The Golgi functions principally in the biogenesis and trafficking of glycoproteins and lipids. It is compartmentalized into multiple flattened adherent membrane sacs termed cisternae, which each contain a distinct repertoire of resident proteins, principally enzymes that modify newly synthesized proteins and lipids sequentially as they traffic through the stack of Golgi cisternae. Upon reaching the final compartments of the Golgi, the trans cisterna and trans-Golgi network (TGN), processed glycoproteins and lipids are packaged into coated and non-coated transport carriers derived from the trans Golgi and TGN. The cargoes of clathrin-coated vesicles are chiefly residents of endo-lysosomal organelles, while uncoated carriers ferry cargo to the cell surface. There are outstanding questions regarding the mechanisms of protein and lipid sorting within the Golgi for export to different organelles. Nonetheless, conceptual advances have begun to define the key molecular features of cargo clients and the mechanisms underlying their sorting into distinct export pathways, which we have collated in this Cell Science at a Glance article and the accompanying poster.

Polymer-Coated Magnetic Microspheres Conjugated with Growth Factor Receptor Binding Peptides Enable Cell Sorting.

The separation and sorting of human cells is an important step in the bioprocessing of cell-based therapeutics. Heterogeneous mixtures of cells must be sorted to isolate the desired cell type and purify the final product. This process is often achieved by antibody-based sorting techniques. In this work, we demonstrate that magnetic microspheres may be functionalized with peptides that selectively bind to cells on the basis of their relative concentration of specific surface proteins. Five-micrometer-magnetic microspheres were coated with the synthetic copolymer PVG (poly(poly(ethylene glycol)methyl ether methacrylate-ran-vinyl dimethyl azlactone-ran-glycidyl methacrylate) and functionalized with the vascular endothelial growth factor receptor binding peptide (VRBP), which binds to the vascular endothelial growth factor receptor (VEGFR). These microspheres exhibited low cytotoxicity and bind to cells depending on their relative surface protein expression. Finally, coated, magnetic microspheres were used to separate heterogeneous populations of cells dependent on their VEGFR expression through magnetic-assisted cell sorting (MACS), demonstrating that peptide-based cell sorting mechanisms may be useful in the bioprocessing of human-cell-based products.

Deciphering the Role of Extracellular Vesicles Derived from ZIKV-Infected hcMEC/D3 Cells on the Blood-Brain Barrier System.

To date, no vaccines or antivirals are available against Zika virus (ZIKV). In addition, the mechanisms underlying ZIKV-associated pathogenesis of the central nervous system (CNS) are largely unexplored. Getting more insight into the cellular pathways that ZIKV recruits to facilitate infection of susceptible cells will be crucial for establishing an effective treatment strategy. In general, cells secrete a number of vesicles, known as extracellular vesicles (EVs), in response to viral infections. These EVs serve as intercellular communicators. Here, we investigated the role of EVs derived from ZIKV-infected human brain microvascular endothelial cells on the blood–brain barrier (BBB) system. We demonstrated that ZIKV-infected EVs (IEVs) can incorporate viral components, including ZIKV RNA, NS1, and E-protein, and further transfer them to several types of CNS cells. Using label-free impedance-based biosensing, we observed that ZIKV and IEVs can temporally disturb the monolayer integrity of BBB-mimicking cells, possibly by inducing structural rearrangements of the adherent protein VE-cadherin (immunofluorescence staining). Finally, differences in the lipidomic profile between EVs and their parental cells possibly suggest a preferential sorting mechanism of specific lipid species into the vesicles. To conclude, these data suggest that IEVs could be postulated as vehicles (Trojan horse) for ZIKV transmission via the BBB.

What is holding farmers back? Endowments and mobility choice of rural citizens in China

For the roughly 300 million rural migrant workers in China, migrating to urban destinations offers the primary opportunities for poverty alleviation and upward social mobility. However, studies on migration in China, mostly through the lens of the push-pull theory, have left immobile rural residents unexamined. This paper explores how the mobility choices of rural citizens are determined by individual and familial endowments at the sending end, including their physical wellbeing, basic education, family livelihoods and landholdings. Drawing on the China Household Finance Survey data, our analyses suggest that good health, adequate educational attainment and non-local family livelihoods increase the propensities of out-migration while a lack of these endowments likely bars rural citizens from migration. The possession of rural land and other local resources, in contrast, tends to deter migration to urban destinations. The requisition of rural land, however, encourages migration to a local town while deterring longer-distance migration. These findings add to the literature of migration in China by unraveling the sorting mechanism of endowments that shapes the (im)mobility and divergent life outcomes of China's rural population.

Viral Membrane Fusion Proteins and RNA Sorting Mechanisms for the Molecular Delivery by Exosomes.

The advancement of precision medicine critically depends on the robustness and specificity of the carriers used for the targeted delivery of effector molecules in the human body. Numerous nanocarriers have been explored in vivo, to ensure the precise delivery of molecular cargos via tissue-specific targeting, including the endocrine part of the pancreas, thyroid, and adrenal glands. However, even after reaching the target organ, the cargo-carrying vehicle needs to enter the cell and then escape lysosomal destruction. Most artificial nanocarriers suffer from intrinsic limitations that prevent them from completing the specific delivery of the cargo. In this respect, extracellular vesicles (EVs) seem to be the natural tool for payload delivery due to their versatility and low toxicity. However, EV-mediated delivery is not selective and is usually short-ranged. By inserting the viral membrane fusion proteins into exosomes, it is possible to increase the efficiency of membrane recognition and also ease the process of membrane fusion. This review describes the molecular details of the viral-assisted interaction between the target cell and EVs. We also discuss the question of the usability of viral fusion proteins in developing extracellular vesicle-based nanocarriers with a higher efficacy of payload delivery. Finally, this review specifically highlights the role of Gag and RNA binding proteins in RNA sorting into EVs.

A new QoS prediction model using hybrid IOWA-ANFIS with fuzzy C-means, subtractive clustering and grid partitioning

Quality of Service (QoS) is one of the key indicators to measure the overall performance of cloud services. The quantitative measurement of the QoS enables the service provider to manage its Service Level Agreement (SLA) in a viable way. It also supports a consumer in service selection and allows measuring the received services to comply with agreed services. There is much existing literature that tries to predict the QoS and assist stakeholders in their decision-making process. However, it is tricky to deal with multidimensional data in time series prediction methods. The computational complexity increases with an increase in data dimension, and it is a challenging task to give precise weights to each time interval. Existing prediction methods could not deal with the intricate reordering of input weights. To address this problem, we propose a novel Clustered Induced Ordered Weighted Averaging (IOWA) Adaptive Neuro-Fuzzy Inference System (ANFIS), (CI-ANFIS) model. This fuzzy time series prediction model reduces data dimension and handles the nonlinear relationship of the cloud QoS dataset. The proposed method uses an intelligent sorting mechanism that regulates uncertainty in prediction while incorporating a fuzzy neural network structure for optimal prediction results. The proposed method employs the IOWA operator to sort input arguments based on associated order-inducing variables and assign customised weights accordingly. The inputs are further classified using three fuzzy clustering methods - fuzzy c-means (FCM), subtractive clustering and grid partitioning. The inputs further pass to the ANFIS structure that takes the benefits of both the fuzzy and neural networks. The fuzzy structure in ANFIS builds understandable rules for cloud stakeholders and deals with uncertain occurrences of data. The model uses a real cloud QoS dataset extracted from the Amazon Elastic Compute Cloud (EC2) US-West instance and predict its behaviour every five minutes for the next 24 h. The proposed method is further compared with the existing twelve methods. The comparative results show that the proposed CI-ANFIS model outperforms all current techniques. The proposed approach opens a new area of research in various complex prediction problems such as stock trading, big data, complex IoT sensors, and other social computing problems.

Historical Perspective of Pore-Forming Activity Studies of Voltage-Dependent Anion Channel (Eukaryotic or Mitochondrial Porin) Since Its Discovery in the 70th of the Last Century.

Eukaryotic porin, also known as Voltage-Dependent Anion Channel (VDAC), is the most frequent protein in the outer membrane of mitochondria that are responsible for cellular respiration. Mitochondria are most likely descendants of strictly aerobic Gram-negative bacteria from the α-proteobacterial lineage. In accordance with the presumed ancestor, mitochondria are surrounded by two membranes. The mitochondrial outer membrane contains besides the eukaryotic porins responsible for its major permeability properties a variety of other not fully identified channels. It encloses also the TOM apparatus together with the sorting mechanism SAM, responsible for the uptake and assembly of many mitochondrial proteins that are encoded in the nucleus and synthesized in the cytoplasm at free ribosomes. The recognition and the study of electrophysiological properties of eukaryotic porin or VDAC started in the late seventies of the last century by a study of Schein et al., who reconstituted the pore from crude extracts of Paramecium mitochondria into planar lipid bilayer membranes. Whereas the literature about structure and function of eukaryotic porins was comparatively rare during the first 10years after the first study, the number of publications started to explode with the first sequencing of human Porin 31HL and the recognition of the important function of eukaryotic porins in mitochondrial metabolism. Many genomes contain more than one gene coding for homologs of eukaryotic porins. More than 100 sequences of eukaryotic porins are known to date. Although the sequence identity between them is relatively low, the polypeptide length and in particular, the electrophysiological characteristics are highly preserved. This means that all eukaryotic porins studied to date are anion selective in the open state. They are voltage-dependent and switch into cation-selective substates at voltages in the physiological relevant range. A major breakthrough was also the elucidation of the 3D structure of the eukaryotic pore, which is formed by 19 β-strands similar to those of bacterial porin channels. The function of the presumed gate an α-helical stretch of 20 amino acids allowed further studies with respect to voltage dependence and function, but its exact role in channel gating is still not fully understood.

Impact of native and external factors on exosome release: understanding reactive exosome secretion and its biogenesis.

Exosomes are minuscule vesicles secreted in the endolytic region of most mammalian cells. The release of exosomes from the cell engenders cell-to-cell signaling between cellular-compartments. The trading of exosomes between tumor and yonder cells plays a hypercritical role in tumor growth and progression. The exosome released from each tumor cell sequestrates a unique biogenetic pathway reflecting its cellular origin depending on the tumor type. However, treatment of tumor cells with certain physiological factors like drugs, chemotherapy, radiation, etc., enhance the release of exosomes and alters its biogenetic pathway compared with untreated tumor cells. In this review, we will discuss how the non-native physiological factors influence the release of exosomes and how these reactive exosomes orchestrate a unique patterning of a cargo sorting mechanism. We will also discuss the role of reactively secreted exosomes in mediating tumor metastasis, angiogenesis, and tumor progression.

Label‐Free Cell Viability Assay and Enrichment of Cryopreserved Cells Using Microfluidic Cytometry and On‐Demand Sorting

AbstractCryopreservation is essential for the long‐term storage of primary cell samples and enables accessing primary cells anytime via a simple thawing process. However, low viability and cell fragmentation are the major issues for cryopreserved cell samples due to the toxicity of cryoprotective agents and crystallization of intracellular contents during cooling at low temperature. Human peripheral blood mononuclear cells (PBMCs) in high viability are critical for pathophysiological and therapeutic research of infectious diseases, especially for the current worldwide pandemic of coronavirus disease 2019. Conventional viability enrichment techniques for primary PBMC samples provoke either cryoinjury caused by cell sorting mechanism or substantial cell loss due to multiple sample preparation steps. Here, a label‐free viability assessment and on‐demand enrichment system for cryopreserved primary human PBMCs with validation by fluorescent label‐based flow cytometry, is demonstrated. It can provide consistent viability assays by discriminating viable PBMCs from apoptotic, DMSO toxicity‐induced dead cells and cell debris, and deliver over 90% viability of sorted samples in one step after thawing. This integrated cell viability assay and on‐demand enrichment of viable cells has broad applications in diverse cellular biology research and cell‐related biomedical diagnostics.