Extracellular vesicles as emerging intercellular communicasomes

All living cells release extracellular vesicles having pleiotropic functions in intercellular communication. Mammalian extracellular vesicles, also known as exosomes and microvesicles, are spherical bilayered proteolipids composed of various bioactive molecules, including RNAs, DNAs, proteins, and lipids. Extracellular vesicles directly and indirectly control a diverse range of biological processes by transferring membrane proteins, signaling molecules, mRNAs, and miRNAs, and activating receptors of recipient cells. The active interaction of extracellular vesicles with other cells regulates various physiological and pathological conditions, including cancer, infectious diseases, and neurodegenerative disorders. Recent developments in high-throughput proteomics, transcriptomics, and lipidomics tools have provided ample data on the common and specific components of various types of extracellular vesicles. These studies may contribute to the understanding of the molecular mechanism involved in vesicular cargo sorting and the biogenesis of extracellular vesicles, and, further, to the identification of disease-specific biomarkers. This review focuses on the components, functions, and therapeutic and diagnostic potential of extracellular vesicles under various pathophysiological conditions.X115449Ysciescopu

Egr-1 Activation by Cancer-Derived Extracellular Vesicles Promotes Endothelial Cell Migration via ERK1/2 and JNK Signaling Pathways

Various mammalian cells, including cancer cells, shed extracellular vesicles (EVs), also known as exosomes and microvesicles, into surrounding tissues. These EVs play roles in tumor growth and metastasis by promoting angiogenesis. However, the detailed mechanism of how cancer-derived EVs elicit endothelial cell activation remains unknown. Here, we provide evidence that early growth response-1 (Egr-1) activation in endothelial cells is involved in the angiogenic activity of colorectal cancer cell-derived EVs. Both RNA interference-mediated downregulation of Egr-1 and ERK1/2 or JNK inhibitor significantly blocked EV-mediated Egr-1 activation and endothelial cell migration. Furthermore, lipid raft-mediated endocytosis inhibitor effectively blocked endothelial Egr-1 activation and migration induced by cancer-derived EVs. Our results suggest that Egr-1 activation in endothelial cells may be a key mechanism involved in the angiogenic activity of cancer-derived EVs. These findings will improve our understanding regarding the proangiogenic activities of EVs in diverse pathological conditions including cancer, cardiovascular diseases, and neurodegenerative diseases.open11617sciescopu

Cardiovascular health status between standard and nonstandard workers in Korea

OBJECTIVES: The effect of employment insecurity on employee health is an important public health issue due to the recent effects of neoliberalism and the global financial crisis (2007-2008) on labor markets. This study aims to evaluate the differences in cardiovascular health status and the use of preventive screening services between standard and nonstandard workers. METHODS: Waged employees (N = 5,338) between the ages of 20 and 64 were grouped into standard (full-time, permanent) and nonstandard (part-time, temporary, or daily) employees. Data from the Fourth Korea National Health and Nutrition Examination Survey, 2007-2009, a nationwide representative survey, were examined, including cardiovascular health risk behaviors (tobacco, alcohol, physical inactivity), measured morbidities (blood pressure, blood glucose level, lipid profiles, body mass index), and the use of screening services for hypertension and diabetes mellitus. RESULTS: Female nonstandard employees tended to have higher blood pressure than did female standard employees (adjusted odds ratio, aOR 1.42, 95% confidence interval, CI 1.02 to 1.98). However, nonstandard employees (both men and women) were less likely to use preventive screening services for hypertension (aOR 0.72, 95% CI 0.54 to 0.94 in men; aOR 0.56, 95% CI 0.43 to 0.73 in women) and diabetes (aOR 0.58, 95% CI 0.43 to 0.79 in men; aOR 0.55, 95% CI 0.43 to 0.71 in women). CONCLUSION: Nonstandard work is associated with the underuse of screening services and poorer cardiovascular health in a specific population. Policies to reduce employment insecurity and encourage nonstandard employees to receive health screening services should be prioritized

Giant Magnetic Fluctuations at the Critical Endpoint in Insulating HoMnO3

Although abundant research has focused recently on the quantum criticality of itinerant magnets, critical phenomena of insulating magnets in the vicinity of critical endpoints (CEP's) have rarely been revealed. Here we observe an emergent CEP at 2.05 T and 2.2 K with a suppressed thermal conductivity and concomitant strong critical fluctuations evident via a divergent magnetic susceptibility (e.g., ????????(2.05 T,2.2 K)/????????(3 T,2.2 K)≈23,500%, comparable to the critical opalescence in water) in the hexagonal insulating antiferromagnet HoMnO3. © 2013 American Physical Society.open1

Neural Tissue-Like, not Supraphysiological, Electrical Conductivity Stimulates Neuronal Lineage Specification through Calcium Signaling and Epigenetic Modification

Electrical conductivity is a pivotal biophysical factor for neural interfaces, though optimal values remain controversial due to challenges isolating this cue. To address this issue, conductive substrates made of carbon nanotubes and graphene oxide nanoribbons, exhibiting a spectrum of conductivities from 0.02 to 3.2 S m−1, while controlling other surface properties is designed. The focus is to ascertain whether varying conductivity in isolation has any discernable impact on neural lineage specification. Remarkably, neural-tissue-like low conductivity (0.02–0.1 S m−1) prompted neural stem/progenitor cells to exhibit a greater propensity toward neuronal lineage specification (neurons and oligodendrocytes, not astrocytes) compared to high supraphysiological conductivity (3.2 S m−1). High conductivity instigated the apoptotic process, characterized by increased apoptotic fraction and decreased neurogenic morphological features, primarily due to calcium overload. Conversely, cells exposed to physiological conductivity displayed epigenetic changes, specifically increased chromatin openness with H3acetylation (H3ac) and neurogenic-transcription-factor activation, along with a more balanced intracellular calcium response. The pharmacological inhibition of H3ac further supported the idea that such epigenetic changes might play a key role in driving neuronal specification in response to neural-tissue-like, not supraphysiological, conductive cues. These findings underscore the necessity of optimal conductivity when designing neural interfaces and scaffolds to stimulate neuronal differentiation and facilitate the repair process

Relationship between cloud condensation nuclei (CCN) concentration and aerosol optical depth in the Arctic region

To determine the direct and indirect effects of aerosols on climate, it is important to know the spatial and temporal variations in cloud condensation nuclei (CCN) concentrations. Although many types of CCN measurements are available, extensive CCN measurements are challenging because of the complexity and high operating cost, especially in remote areas. As aerosol optical depth (AOD) can be readily observed by remote sensing, many attempts have been made to estimate CCN concentrations from AOD. In this study, the CCN–AOD relationship is parameterized based on CCN ground measurements from the Zeppelin Observatory (78.91° N, 11.89° E, 474 m asl) in the Arctic region. The AOD measurements were obtained from the Ny-Ålesund site (78.923° N, 11.928° E) and Modern-Era Retrospective Analysis for Research and Applications, Version 2 reanalysis. Our results show a CCN–AOD correlation with a coefficient of determination R2 of 0.59. Three additional estimation models for CCN were presented based on the following data: (i) in situ aerosol chemical composition, (ii) in situ aerosol optical properties, and (iii) chemical composition of AOD obtained from reanalysis data. The results from the model using in situ aerosol optical properties reproduced the observed CCN concentration most efficiently, suggesting that the contribution of BC to CCN concentration should be considered along with that of sulfate

Chiral nematic self-assembly of minimally surface damaged chitin nanofibrils and its load bearing functions

Chitin is one of the most abundant biomaterials in nature, with 1010 tons produced annually as hierarchically organized nanofibril fillers to reinforce the exoskeletons of arthropods. This green and cheap biomaterial has attracted great attention due to its potential application to reinforce biomedical materials. Despite that, its practical use is limited since the extraction of chitin nanofibrils requires surface modification involving harsh chemical treatments, leading to difficulties in reproducing their natural prototypal hierarchical structure, i.e. chiral nematic phase. Here, we develop a chemical etching-free approach using calcium ions, called "natural way", to disintegrate the chitin nanofibrils while keeping the essential moiety for the self-assembly, ultimately resulting in the reproduction of chitin's natural chiral structure in a polymeric matrix. This chiral chitin nanostructure exceptionally toughens the composite. Our resultant chiral nematic phase of chitin materials can contribute to the understanding and use of the reinforcing strategy in nature.open119sciescopu

Global distribution and diversity of marine Verrucomicrobia

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in The ISME Journal 6 (2012): 1499-1505, doi:10.1038/ismej.2012.3.Verrucomicrobia is a bacterial phylum that is commonly detected in soil but little is known about the distribution and diversity of this phylum in the marine environment. To address this, we analyzed the marine microbial community composition in 506 samples from the International Census of Marine Microbes as well as eleven coastal samples taken from the California Current. These samples from both the water column and sediments covered a wide range of environmental conditions. Verrucomicrobia were present in 98% of the analyzed samples and thus appeared nearly ubiquitous in the ocean. Based on the occurrence of amplified 16S rRNA sequences, Verrucomicrobia constituted on average 2% of the water column and 1.4% of the sediment bacterial communities. The diversity of Verrucomicrobia displayed a biogeography at multiple taxonomic levels and thus, specific lineages appeared to have clear habitat preference. We found that Subdivision 1 and 4 generally dominated marine bacterial communities, whereas Subdivision 2 was confined to low salinity waters. Within the subdivisions, Verrucomicrobia community composition were significantly different in the water column compared to sediment as well as within the water column along gradients of salinity, temperature, nitrate, depth, and overall water column depth. Although we still know little about the ecophysiology of Verrucomicrobia lineages, the ubiquity of this phylum suggests that it may be important for the biogeochemical cycle of carbon in the ocean.We would like to thank the UCI Undergraduate Research Opportunity Program (S.F.), the National Science Foundation (OCE-0928544 and OCE-1046297, A.C.M.) and the Alfred P. Sloan Foundation (S.H., D.M.W., M.S.) for supporting the work

Control of Mitochondrial Morphology Through Differential Interactions of Mitochondrial Fusion and Fission Proteins

Mitochondria in mammals are organized into tubular networks that undergo frequent shape change. Mitochondrial fission and fusion are the main components mediating the mitochondrial shape change. Perturbation of the fission/fusion balance is associated with many disease conditions. However, underlying mechanisms of the fission/fusion balance are not well understood. Mitochondrial fission in mammals requires the dynamin-like protein DLP1/Drp1 that is recruited to the mitochondrial surface, possibly through the membrane-anchored protein Fis1 or Mff. Additional dynamin-related GTPases, mitofusin (Mfn) and OPA1, are associated with the outer and inner mitochondrial membranes, respectively, and mediate fusion of the respective membranes. In this study, we found that two heptad-repeat regions (HR1 and HR2) of Mfn2 interact with each other, and that Mfn2 also interacts with the fission protein DLP1. The association of the two heptad-repeats of Mfn2 is fusion inhibitory whereas a positive role of the Mfn2/DLP1 interaction in mitochondrial fusion is suggested. Our results imply that the differential binding of Mfn2-HR1 to HR2 and DLP1 regulates mitochondrial fusion and that DLP1 may act as a regulatory factor for efficient execution of both fusion and fission of mitochondria