Extracellular vesicles from a muscle cell line (C2C12) enhance cell survival and neurite outgrowth of a motor neuron cell line (NSC-34)

Introduction: There is renewed interest in extracellular vesicles over the past decade or 2 after initially being thought of as simple cellular garbage cans to rid cells of unwanted components. Although there has been intense research into the role of extracellular vesicles in the fields of tumour and stem cell biology, the possible role of extracellular vesicles in nerve regeneration is just in its infancy. Background: When a peripheral nerve is damaged, the communication between spinal cord motor neurons and their target muscles is disrupted and the result can be the loss of coordinated muscle movement. Despite state-of-the-art surgical procedures only approximately 10% of adults will recover full function after peripheral nerve repair. To improve upon such results will require a better understanding of the basic mechanisms that influence axon outgrowth and the interplay between the parent motor neuron and the distal end organ of muscle. It has previously been shown that extracellular vesicles are immunologically tolerated, display targeting ligands on their surface, and can be delivered in vivo to selected cell populations. All of these characteristics suggest that extracellular vesicles could play a significant role in nerve regeneration. Methods: We have carried out studies using 2 very well characterized cell lines, the C2C12 muscle cell line and the motor neuron cell line NSC-34 to ask the question: Do extracellular vesicles from muscle influence cell survival and/or neurite outgrowth of motor neurons? Conclusion: Our results show striking effects of extracellular vesicles derived from the muscle cell line on the motor neuron cell line in terms of neurite outgrowth and survival

Thorium isotopes tracing the iron cycle at the Hawaii Ocean Time-series Station ALOHA

Author Posting. © The Author(s), 2015. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Geochimica et Cosmochimica Acta 169 (2015): 1-16, doi:10.1016/j.gca.2015.07.019.The role of iron as a limiting micronutrient motivates an effort to understand the supply and removal of lithogenic trace metals in the ocean. The long-lived thorium isotopes (232 Th and 230 Th) in seawater can be used to quantify the input of lithogenic metals attributable to the partial dissolution of aerosol dust. Thus, Th can help in disentangling the Fe cycle by providing an estimate of its ultimate supply and turnover rate. Here we present time-series (1994-2014) data on thorium isotopes and iron concentrations in seawater from the Hawaii Ocean Time-series Station ALOHA. By comparing Th-based dissolved Fe fluxes with measured dissolved Fe inventories, we derive Fe residence times of 6-12 months for the surface ocean. Therefore, Fe inventories in the surface ocean are sensitive to seasonal changes in dust input. Ultrafiltration results further reveal that Th has a much lower colloidal content than Fe does, despite a common source. On this basis, we suggest Fe colloids may be predominantly organic in composition, at least at Station ALOHA. In the deep ocean (>2 km), Fe approaches a solubility limit while Th, surprisingly, is continually leached from lithogenic particles. This distinction has implications for the relevance of Fe ligand availability in the deep ocean, but also suggests Th is not a good tracer for Fe in deep waters. While uncovering divergent behavior of these elements in the water column, this study finds that dissolved Th flux is a suitable proxy for the supply of Fe from dust in the remote surface ocean.We acknowledge funding from the W.O. Crosby Postdoctoral Fellowship to CTH and the National Science Foundation through C-MORE, NSF-OIA EF-0424599 to EAB, and NSF-DMR Author Posting

Thorium isotopes tracing the iron cycle at the Hawaii Ocean Time-series Station ALOHA

The role of iron as a limiting micronutrient motivates an effort to understand the supply and removal of lithogenic trace metals in the ocean. The long-lived thorium isotopes (²³²Th and ²³⁰Th) in seawater can be used to quantify the input of lithogenic metals attributable to the partial dissolution of aerosol dust. Thus, Th can help in disentangling the Fe cycle by providing an estimate of its ultimate supply and turnover rate. Here we present time-series (1994–2014) data on thorium isotopes and iron concentrations in seawater from the Hawaii Ocean Time-series Station ALOHA. By comparing Th-based dissolved Fe fluxes with measured dissolved Fe inventories, we derive Fe residence times of 6–12 months for the surface ocean. Therefore, Fe inventories in the surface ocean are sensitive to seasonal changes in dust input. Ultrafiltration results further reveal that Th has a much lower colloidal content than Fe does, despite a common source. On this basis, we suggest Fe colloids may be predominantly organic in composition, at least at Station ALOHA. In the deep ocean (>2 km), Fe approaches a solubility limit while Th, surprisingly, is continually leached from lithogenic particles. This distinction has implications for the relevance of Fe ligand availability in the deep ocean, but also suggests Th is not a good tracer for Fe in deep waters. While uncovering divergent behavior of these elements in the water column, this study finds that dissolved Th flux is a suitable proxy for the supply of Fe from dust in the remote surface ocean.National Science Foundation (U.S.) (Grant NS-OIA E-0424599

Glacial to Holocene changes in trans-Atlantic Saharan dust transport and dust-climate feedbacks

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Science Advances 2 (2016): e1600445, doi:10.1126/sciadv.1600445.Saharan mineral dust exported over the tropical North Atlantic is thought to have significant impacts on regional climate and ecosystems, but limited data exist documenting past changes in long-range dust transport. This data gap limits investigations of the role of Saharan dust in past climate change, in particular during the mid-Holocene, when climate models consistently underestimate the intensification of the West African monsoon documented by paleorecords. We present reconstructions of African dust deposition in sediments from the Bahamas and the tropical North Atlantic spanning the last 23,000 years. Both sites show early and mid-Holocene dust fluxes 40 to 50% lower than recent values and maximum dust fluxes during the deglaciation, demonstrating agreement with records from the northwest African margin. These quantitative estimates of trans-Atlantic dust transport offer important constraints on past changes in dust-related radiative and biogeochemical impacts. Using idealized climate model experiments to investigate the response to reductions in Saharan dust’s radiative forcing over the tropical North Atlantic, we find that small (0.15°C) dust-related increases in regional sea surface temperatures are sufficient to cause significant northward shifts in the Atlantic Intertropical Convergence Zone, increased precipitation in the western Sahel and Sahara, and reductions in easterly and northeasterly winds over dust source regions. Our results suggest that the amplifying feedback of dust on sea surface temperatures and regional climate may be significant and that accurate simulation of dust’s radiative effects is likely essential to improving model representations of past and future precipitation variations in North Africa.This study was supported, in part, by NSF awards OCE-1030784 (to D.M. and P.B.d.) and OCE-09277247 (to P.B.d.); NASA grant NN14AP38G (to C. Heald, Massachusetts Institute of Technology), which supports D.A.R.; and the Columbia University Center for Climate and Life. A.F. is supported by the NSF grant AGS-1116885 and the National Oceanic and Atmospheric Administration (NOAA) grant NA14OAR4310277. S.H. is supported by the NASA Earth and Space Sciences Fellowship. We also acknowledge computational support from the NSF/NCAR Yellowstone Supercomputing Center and the Yale University High Performance Computing Center

The AST/RO Survey of the Galactic Center Region. I. The Inner 3 Degrees

We present fully-sampled maps of 461 GHz CO (4-3), 807 GHz CO (7-6), and 492 GHz [CI] (3P1-3P0) emission from the inner 3 degrees of the Galactic Center region taken with the Antarctic Submillimeter Telescope and Remote Observatory (AST/RO) in 2001--2002. The data cover -1.3 < l < 2, -0.3 < b < 0.2 with 0.5 arcmin spacing, resulting in spectra in 3 transitions at over 24,000 positions on the sky. The CO (4-3) emission is found to be essentially coextensive with lower-J transitions of CO. The CO (7-6) emission is spatially confined to a far smaller region than the lower-J CO lines. The [CI] (3P1-3P0) emission has a spatial extent similar to the low-J CO emission, but is more diffuse. Bright CO (7-6) emission is detected in the well-known Galactic Center clouds Sgr A and Sgr B. We also detect CO (4-3) and CO (7-6) absorption from spiral arms in the galactic disk at velocities near 0 km s^-1 along the line of sight to the Galactic Center. Analyzing our CO (7-6) and CO (4-3) data in conjunction with J = 1 - 0 12CO and 13CO data previously observed with the Bell Laboratories 7-m antenna, we apply a Large Velocity Gradient (LVG) model to estimate the kinetic temperature and density of molecular gas in the inner 200 pc of the Galactic Center region. We show maps of the derived distribution of gas density and kinetic temperature as a function of position and velocity for the entire region. Kinetic temperature was found to decrease from relatively high values (>70K) at cloud edges to low values (<50K) in the interiors. Typical gas pressures in the Galactic Center gas are n(H_2) T_kin approx 10^5.2 K cm^-3. We also present an (l,b) map of molecular hydrogen column density derived from our LVG results.Comment: 41 pages, 29 figures reduced to low resolution for astro-ph, for high resolution figures please go to http://cfa-www.harvard.edu/ASTRO/galcen_1.pdf this version incorporates changes due to accepted erratum (to appear in ApJS 153

Addressing and Inspiring Vaccine Confidence in Black, Indigenous, and People of Color During the Coronavirus Disease 2019 Pandemic

During the coronavirus disease 2019 (COVID-19) pandemic, we have witnessed profound health inequities suffered by Black, Indigenous, and People of Color (BIPOC). These manifested as differential access to testing early in the pandemic, rates of severe disease and death 2-3 times higher than white Americans, and, now, significantly lower vaccine uptake compared with their share of the population affected by COVID-19. This article explores the impact of these COVID-19 inequities (and the underlying cause, structural racism) on vaccine acceptance in BIPOC populations, ways to establish trustworthiness of healthcare institutions, increase vaccine access for BIPOC communities, and inspire confidence in COVID-19 vaccines

Loss of histone methyltransferase Ezh2 stimulates an osteogenic transcriptional program in chondrocytes but does not affectcartilage development

Ezh2 is a histone methyltransferase that suppresses osteoblast maturation and skeletal development. We evaluated the roleof Ezh2 in chondrocyte lineage differentiation and endochondral ossification. Ezh2 was genetically inactivated in the mesenchymal, osteoblastic, and chondrocytic lineages in mice using the Prrx1-Cre,Osx1-Cre, and Col2a1-Cre drivers, respectively. Wild-type and conditional knockout mice were phenotypically assessed by grossmorphology, histology, and micro-CT imaging. Ezh2-deficient chondrocytes in micromass culture models were evaluated usingRNA-sequencing, histologic evaluation, and western blotting. Aged mice with Ezh2 deficiency were also evaluated for prematuredevelopment of osteoarthritis using radiographic analysis. Ezh2 deficiency in murine chondrocytes reduced bone density at 4 weeks of age, although caused no other gross developmentaleffects. Knockdown of Ezh2 in chondrocyte micromass cultures resulted in a global reduction in trimethylation of histone 3lysine 27 (H3K27me3) and altered differentiation in vitro. RNA-seq analysis revealed enrichment of an osteogenic gene expressionprofile in Ezh2 deficient chondrocytes. Joint development proceeded normally in the absence of Ezh2 in chondrocytes withoutinducing excessive hypertrophy or premature osteoarthritis in vivo. In summary, loss of Ezh2 reduced H3K27me3 levels, increased expression of osteogenic genes in chondrocytes, and resulted ina transient post-natal bone phenotype. Remarkably, Ezh2 activity is dispensable for normal chondrocyte maturation and endochondralossification in vivo, even though it appears to have a critical role during early stages of mesenchymal lineage-commitment

Differences in genotype and virulence among four multidrug-resistant <i>Streptococcus pneumoniae</i> isolates belonging to the PMEN1 clone

We report on the comparative genomics and characterization of the virulence phenotypes of four &lt;i&gt;S. pneumoniae&lt;/i&gt; strains that belong to the multidrug resistant clone PMEN1 (Spain&lt;sup&gt;23F&lt;/sup&gt; ST81). Strains SV35-T23 and SV36-T3 were recovered in 1996 from the nasopharynx of patients at an AIDS hospice in New York. Strain SV36-T3 expressed capsule type 3 which is unusual for this clone and represents the product of an in vivo capsular switch event. A third PMEN1 isolate - PN4595-T23 - was recovered in 1996 from the nasopharynx of a child attending day care in Portugal, and a fourth strain - ATCC700669 - was originally isolated from a patient with pneumococcal disease in Spain in 1984. We compared the genomes among four PMEN1 strains and 47 previously sequenced pneumococcal isolates for gene possession differences and allelic variations within core genes. In contrast to the 47 strains - representing a variety of clonal types - the four PMEN1 strains grouped closely together, demonstrating high genomic conservation within this lineage relative to the rest of the species. In the four PMEN1 strains allelic and gene possession differences were clustered into 18 genomic regions including the capsule, the blp bacteriocins, erythromycin resistance, the MM1-2008 prophage and multiple cell wall anchored proteins. In spite of their genomic similarity, the high resolution chinchilla model was able to detect variations in virulence properties of the PMEN1 strains highlighting how small genic or allelic variation can lead to significant changes in pathogenicity and making this set of strains ideal for the identification of novel virulence determinant

An Atlas of FUSE Sight Lines Toward the Magellanic Clouds

We present an atlas of 57 Large Magellanic Cloud (LMC) and 37 Small Magellanic Cloud (SMC) observations obtained with the Far Ultraviolet Spectroscopic Explorer (FUSE) satellite. The atlas highlights twelve interstellar absorption line transitions at a resolution of ~15 km/s. These transitions cover a broad range of temperatures, ionization states, and abundances. The species included are OVI, which probes hot (T~3x10^5 K) ionized gas; CIII and FeIII, which probe warm (T~10^4 K) ionized gas; SiII, PII, CII, FeII, and OI, warm neutral gas; and six different molecular hydrogen transitions, which trace cold (T<=500 K) gas. We include Schmidt Halpha CCD images of the region surrounding each sight line showing the morphology of warm ionized gas in the vicinity, along with continuum images near each FUSE aperture position. Finally, we present several initial scientific results derived from this dataset on the interstellar medium of the Magellanic Clouds and Galactic halo.Comment: 29 pages, 6 figures. Complete Atlas of 94 additional images (~800kB each) is available at http://fuse.pha.jhu.edu/~danforth/atlas Accepted to the ApJS March 200

Prediction of enteric methane production, yield and intensity in dairy cattle using an intercontinental database

Enteric methane (CH4) production from cattle contributes to global greenhouse gas emissions. Measurement of enteric CH4 is complex, expensive and impractical at large scales; therefore, models are commonly used to predict CH4 production. However, building robust prediction models requires extensive data from animals under different management systems worldwide. The objectives of this study were to (1) collate a global database of enteric CH4 production from individual lactating dairy cattle; (2) determine the availability of key variables for predicting enteric CH4 production (g/d per cow), yield [g/kg dry matter intake (DMI)], and intensity (g/kg energy corrected milk) and their respective relationships; (3) develop intercontinental and regional models and cross-validate their performance; and (4) assess the trade-off between availability of on-farm inputs and CH4 prediction accuracy. The intercontinental database covered Europe (EU), the US (US), Chile (CL), Australia (AU), and New Zealand (NZ). A sequential approach was taken by incrementally adding key variables to develop models with increasing complexity. Methane emissions were predicted by fitting linear mixed models. Within model categories, an intercontinental model with the most available independent variables performed best with root mean square prediction error (RMSPE) as a percentage of mean observed value of 16.6, 14.4, and 19.8% for intercontinental, EU, and US regions, respectively. Less complex models requiring only DMI had predictive ability comparable to complex models. Enteric CH4 production, yield, and intensity prediction models developed on an intercontinental basis had similar performance across regions, however, intercepts and slopes were different with implications for prediction. Revised CH4 emission conversion factors for specific regions are required to improve CH4 production estimates in national inventories. In conclusion, information on DMI is required for good prediction, and other factors such as dietary NDF concentration, improve the prediction. For enteric CH4 yield and intensity prediction, information on milk yield and composition is required for better estimation