Low Intensity, High Frequency Vibration Training to Improve Musculoskeletal Function in a Mouse Model of Duchenne Muscular Dystrophy

The objective of the study was to determine if low intensity, high frequency vibration training impacted the musculoskeletal system in a mouse model of Duchenne muscular dystrophy, relative to healthy mice. Three-week old wildtype (n = 26) and mdx mice (n = 22) were randomized to non-vibrated or vibrated (45 Hz and 0.6 g, 15 min/d, 5 d/wk) groups. In vivo and ex vivo contractile function of the anterior crural and extensor digitorum longus muscles, respectively, were assessed following 8 wks of vibration. Mdx mice were injected 5 and 1 days prior to sacrifice with Calcein and Xylenol, respectively. Muscles were prepared for histological and triglyceride analyses and subcutaneous and visceral fat pads were excised and weighed. Tibial bones were dissected and analyzed by micro-computed tomography for trabecular morphometry at the metaphysis, and cortical geometry and density at the mid-diaphysis. Three-point bending tests were used to assess cortical bone mechanical properties and a subset of tibiae was processed for dynamic histomorphometry. Vibration training for 8 wks did not alter trabecular morphometry, dynamic histomorphometry, cortical geometry, or mechanical properties (P≥0.34). Vibration did not alter any measure of muscle contractile function (P≥0.12); however the preservation of muscle function and morphology in mdx mice indicates vibration is not deleterious to muscle lacking dystrophin. Vibrated mice had smaller subcutaneous fat pads (P = 0.03) and higher intramuscular triglyceride concentrations (P = 0.03). These data suggest that vibration training at 45 Hz and 0.6 g did not significantly impact the tibial bone and the surrounding musculature, but may influence fat distribution in mice

Projection Stereolithographic Fabrication of Human Adipose Stem Cell-Incorporated Biodegradable Scaffolds for Cartilage Tissue Engineering

Poor self-healing ability of cartilage necessitates the development of methods for cartilage regeneration. Scaffold construction with live stem cell incorporation and subsequent differentiation presents a promising route. Projection stereolithography (PSL) offers high resolution and processing speed as well as the ability to fabricate scaffolds that precisely fit the anatomy of cartilage defects using medical imaging as the design template. We report here the use of a visible-light based PSL (VL-PSL) system to encapsulate human adipose-derived stem cells (hASCs) into a biodegradable polymer (poly-D,L-lactic acid/polyethylene glycol/ poly-D,L-lactic acid (PDLLA-PEG))/hyaluronic acid (HA) matrix to produce live cell constructs with customized architectures. After fabrication, hASCs showed high viability (84%) and were uniformly distributed throughout the constructs, which possessed high mechanical property with a compressive modulus of 780 kPa. The hASC-seeded constructs were then cultured in Control or TGF-β3-containing chondrogenic medium for up to 28 days. In chondrogenic medium treated group (TGF-β3 group) hASCs maintained 77% viability and expressed chondrogenic genes Sox9, collagen type II, and aggrecan at 11, 232, and 2.29 x 10(5) fold increases, respectively, compared to levels at day 0 in non-chondrogenic medium. The TGF-β3 group also produced a collagen type II and glycosaminoglycan (GAG)-rich extracellular matrix, detected by immunohistochemistry, and Alcian blue and Safranin O staining suggesting robust chondrogenesis within the scaffold. Without chondroinductive addition (Control group), cell viability decreased with time (65% at 28 days) and showed poor cartilage matrix deposition. After 28 days, mechanical strength of the TGF-β3 group remained high at 240 kPa. Thus, the PSL- and PLLA-PEG/HA based fabrication method using adult stem cells is a promising approach in producing mechanically competent engineered cartilage for joint cartilage resurfacing

Census of the Local Universe (CLU) Narrow-Band Survey I: Galaxy Catalogs from Preliminary Fields

We present the Census of the Local Universe (CLU) narrow-band survey to search for emission-line (\ha) galaxies. CLU-\ha~has imaged $\approx$3$\pi$ of the sky (26,470~deg$^2$) with 4 narrow-band filters that probe a distance out to 200~Mpc. We have obtained spectroscopic follow-up for galaxy candidates in 14 preliminary fields (101.6~deg$^2$) to characterize the limits and completeness of the survey. In these preliminary fields, CLU can identify emission lines down to an \ha~flux limit of $10^{-14}$~$\rm{erg~s^{-1}~cm^{-2}}$ at 90\% completeness, and recovers 83\% (67\%) of the \ha~flux from catalogued galaxies in our search volume at the $\Sigma$=2.5 ($\Sigma$=5) color excess levels. The contamination from galaxies with no emission lines is 61\% (12\%) for $\Sigma$=2.5 ($\Sigma$=5). Also, in the regions of overlap between our preliminary fields and previous emission-line surveys, we recover the majority of the galaxies found in previous surveys and identify an additional $\approx$300 galaxies. In total, we find 90 galaxies with no previous distance information, several of which are interesting objects: 7 blue compact dwarfs, 1 green pea, and a Seyfert galaxy; we also identified a known planetary nebula. These objects show that the CLU-\ha~survey can be a discovery machine for objects in our own Galaxy and extreme galaxies out to intermediate redshifts. However, the majority of the CLU-\ha~galaxies identified in this work show properties consistent with normal star-forming galaxies. CLU-\ha~galaxies with new redshifts will be added to existing galaxy catalogs to focus the search for the electromagnetic counterpart to gravitational wave events.Comment: 28 pages, 22 figures, 4 tables (Accepted to ApJ

Integrated approach to designing growth factor delivery systems

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154661/1/fsb2fj067873com-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154661/2/fsb2fj067873com.pd

Chikungunya Outbreak, Singapore, 2008

10.3201/eid1505.081390Emerging Infectious Diseases155836-83

Fine Mapping of the Interaction between C4b-Binding Protein and Outer Membrane Proteins LigA and LigB of Pathogenic Leptospira interrogans.

The complement system consists of more than 40 proteins that participate in the inflammatory response and in pathogen killing. Complement inhibitors are necessary to avoid the excessive consumption and activation of this system on host cells. Leptospirosis is a worldwide zoonosis caused by spirochetes from the genus Leptospira. Pathogenic leptospires are able to escape from complement activation by binding to host complement inhibitors Factor H [FH] and C4b-binding protein (C4BP) while non-pathogenic leptospires are rapidly killed in the presence of fresh serum. In this study, we demonstrate that complement control protein domains (CCP) 7 and 8 of C4BP α-chain interact with the outer membrane proteins LcpA, LigA and LigB from the pathogenic leptospire L. interrogans. The interaction between C4BP and LcpA, LigA and LigB is sensitive to ionic strength and inhibited by heparin. We fine mapped the LigA and LigB domains involved in its binding to C4BP and heparin and found that both interactions are mediated through the bacterial immunoglobulin-like (Big) domains 7 and 8 (LigA7-8 and LigB7-8) of both LigA and LigB and also through LigB9-10. Therefore, C4BP and heparin may share the same binding sites on Lig proteins