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

Timescale of Stellar Feedback-Driven Turbulence in the ISM: A Deep Dive into UGC 4305

Understanding the interplay of stellar feedback and turbulence in the interstellar medium (ISM) is essential to modeling the evolution of galaxies. To determine the timescales over which stellar feedback drives turbulence in the ISM, we performed a spatially resolved, multi-wavelength study of the nearby star-forming dwarf galaxy UGC 4305 (aka Holmberg II). As indicators of turbulence on local scales (400 pc), we utilized ionized gas velocity dispersion derived from IFU H$\alpha$ observations and atomic gas velocity dispersion and energy surface densities derived from HI synthesis observations with the Very Large Array. These indicators of turbulence were tested against star formation histories over the past 560 Myr derived from Color-Magnitude Diagrams (CMD) using Spearman's rank correlation coefficient. The strongest correlation identified at the 400 pc scale is between measures of HI turbulence and star formation 70-140 Myr ago. We repeated our analysis of UGC 4305's current turbulence and past star formation activity on multiple physical scales ($\sim$560, and 800 pc) to determine if there are indications of changes in the correlation timescale with changes to the physical scale. No notable correlations were found at larger physical scales emphasizing the importance of analyzing star formation driven turbulence as a local phenomenon.Comment: 17 pages, 9 figure, accepted to A

Acidic fibroblast growth factor enhances regeneration of processes by postnatal mammalian retinal ganglion cells in culture.

Postnatal rat retinal ganglion cells (RGCs) were identified with specific fluorescent labels and placed in culture. Under these conditions, the outgrowth of processes by RGCs was found to be promoted to a far greater degree by acidic fibroblast growth factor (aFGF) than by basic fibroblast growth factor (bFGF). The effect of aFGF and bFGF on process extension by solitary RGCs was quantified after 24 hr in culture, a time when neither a FGF nor bFGF enhanced RGC survival. The action of aFGF on process outgrowth was markedly potentiated by the addition of heparin (10 micrograms/ml) to the medium, but heparin alone had no effect. In the presence of heparin, half-maximal process outgrowth occurred at an aFGF concentration of less than 20 pg/ml (1 pM). Since all of the centrally projecting processes have already been formed in the living animal prior to use (at 7-12 days of age), at least a portion of the process outgrowth in culture appears to represent a regenerative phenomenon. Statistical analysis of the increase in process growth revealed that aFGF with heparin contributed to both neurite initiation and elongation. The mean number of glial cells, identified with polyclonal antiserum against glial fibrillary acidic protein, was slightly increased in cultures receiving aFGF plus heparin, but this effect was variable, and these glial cells were not in contact with the solitary RGCs that were scored for regeneration of processes. Thus, glial cells probably did not exert a direct physical influence on the degree of process outgrowth observed in the solitary RGCs, although a humoral effect cannot be totally excluded. These results suggest that aFGF has a potent influence on the outgrowth of processes by a neuron in the mammalian central nervous system. The potentiation of this effect by heparin leads us to speculate that the interaction of aFGF with a heparin-like molecule located in the extracellular matrix (such as heparan sulfate proteoglycan) may produce physiological effects in vivo. Furthermore, the lack of a substantial effect of bFGF in this system under these conditions shows that a specific population of mammalian central neurons may be differentially influenced by these two closely related peptide growth factors

Cluster M Mycobacteriophages Bongo, PegLeg, and Rey with Unusually Large Repertoires of tRNA Isotopes

Genomic analysis of a large set of phages infecting the common hostMycobacterium smegmatis mc2155 shows that they span considerable genetic diversity. There are more than 20 distinct types that lack nucleotide similarity with each other, and there is considerable diversity within most of the groups. Three newly isolated temperate mycobacteriophages, Bongo, PegLeg, and Rey, constitute a new group (cluster M), with the closely related phages Bongo and PegLeg forming subcluster M1 and the more distantly related Rey forming subcluster M2. The cluster M mycobacteriophages have siphoviral morphologies with unusually long tails, are homoimmune, and have larger than average genomes (80.2 to 83.7 kbp). They exhibit a variety of features not previously described in other mycobacteriophages, including noncanonical genome architectures and several unusual sets of conserved repeated sequences suggesting novel regulatory systems for both transcription and translation. In addition to containing transfer-messenger RNA and RtcB-like RNA ligase genes, their genomes encode 21 to 24 tRNA genes encompassing complete or nearly complete sets of isotypes. We predict that these tRNAs are used in late lytic growth, likely compensating for the degradation or inadequacy of host tRNAs. They may represent a complete set of tRNAs necessary for late lytic growth, especially when taken together with the apparent lack of codons in the same late genes that correspond to tRNAs that the genomes of the phages do not obviously encode

Estimated Benefits of IBWC Rio Grande Flood-Control Projects in the United States

The International Boundary and Water Commission (IBWC) is responsible for maintaining a series of flood-control projects beginning in New Mexico and extending along the Rio Grande’s international border dividing the United States and Mexico. A review by the USIBWC indicate that, over time, the flood-control capability of the levees has been compromised, possibly to the point where the level of protection is below original-design capacities. Prior to investing federal monies in the rehabilitation of major flood-system infrastructure, the U.S. Office of Management and Budget requires an economic analysis of expected benefits, or losses avoided with implemented protection measures. Recent flood events along the international border, resulting in significant economic damages and loss of human life, emphasized the need for a timely assessment of impacts of potential flood-control failure. Given a short project time line mandated by IBWC and the large geographic extent of the river- and floodway-levee system, innovative methods were developed to conduct a rapid and preliminary economic assessment of the flood-control infrastructure. Estimates for four major project areas relating only to the U.S.-side of the border only (stretching from Caballo Reservoir in New Mexico to the Rio Grande’s mouth, near Brownsville, TX.) comprise the study’s focus. Millions populate the cities and towns along these economic reaches of the Rio Grande where extensive housing, commerce, industry, tourism, and irrigated agricultural production exist. Areas susceptible to flooding, along with land-use, were identified and quantified through high-resolution map imagery. Estimates of representative residential, commercial, and industrial property values and agricultural production values were developed from property assessment records, economic development councils, crop enterprise budgets and cropping patterns, census data, previous U.S. Army Corps of Engineers’ flooding studies, etc. Gross economic values of flood-control benefits for a sample of each of the land-use types were determined and extrapolated to similar land-use areas in the flood zone. This analytical method provides a rapidassessment of potential flood-control benefits for a single event for each of the four IBWCdesignated flood-control project areas. An aggregate estimate arrived at by summing the potential benefits across all four project areas assumes avoidance of, or protection against, a simultaneous breach in all areas. Baseline economic benefits for agriculture and developed property along the Rio Grande Canalization project are estimated at $13.7 million (basis FY 2004). Comparable estimates for the Rio Grande Rectification project are$139.1 million, while those for the Presidio Valley Flood Control project amount to $2.9 million. The Lower Rio Grande Flood Control project is estimated to provide$167.2 million in flood-control benefits. Combined, the four project areas provide $322.9 million in flood-control protection benefits in the baseline analysis. When preliminary estimates of$183.0 million in other costs (i.e., emergency, roads, utilities, and vehicles) are added to the baseline estimate, the total floodcontrol protection benefits provided by the four project areas increases to $506.0 million

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead