Hyaluronan, neural stem cells and tissue reconstruction after acute ischemic stroke.

Focal stroke is a disabling disease with lifelong sensory, motor and cognitive impairments. Given the paucity of effective clinical treatments, basic scientists are developing novel options for protection of the affected brain and regeneration of lost tissue. Tissue bioengineering and stem/progenitor cell treatments have both been individually pursued for stroke neural repair therapies, with some benefit in tissue recovery. Emerging directions in stroke neural repair approaches combine these two therapies to use biopolymers with stem/progenitor transplants to promote greater cell survival in the transplant and directed delivery of bioactive molecules to the transplanted cells and the adjacent injured tissue. In this review the background literature on a combined use of neural stem/progenitor cells encapsulated in hyaluronan gels is discussed and the way this therapeutic approach can affect the important processes involved in brain tissue reconstruction, such as angiogenesis, axon regeneration, neural differentiation and inflammation is clarified. The glycosaminoglycan hyaluronan can optimize those processes and be employed in a successful neural tissue engineering approach

Dual-function injectable angiogenic biomaterial for the repair of brain tissue following stroke.

Stroke is the primary cause of disability due to the brain's limited ability to regenerate damaged tissue. After stroke, an increased inflammatory and immune response coupled with severely limited angiogenesis and neuronal growth results in a stroke cavity devoid of normal brain tissue. In the adult, therapeutic angiogenic materials have been used to repair ischaemic tissues through the formation of vascular networks. However, whether a therapeutic angiogenic material can regenerate brain tissue and promote neural repair is poorly understood. Here we show that the delivery of an engineered immune-modulating angiogenic biomaterial directly to the stroke cavity promotes tissue formation de novo, and results in axonal networks along thee generated blood vessels. This regenerated tissue produces functional recovery through the established axonal networks. Thus, this biomaterials approach generates a vascularized network of regenerated functional neuronal connections within previously dead tissue and lays the groundwork for the use of angiogenic materials to repair other neurologically diseased tissues

Injectable and Spatially Patterned Microporous Annealed Particle (MAP) Hydrogels for Tissue Repair Applications.

Spatially patterned hydrogels are becoming increasingly popular in the field of regenerative medicine and tissue repair because of their ability to guide cell infiltration and migration. However, postfabrication technologies are usually required to spatially pattern a hydrogel, making these hydrogels difficult to translate into the clinic. Here, an injectable spatially patterned hydrogel is reported using hyaluronic acid (HA)-based particle hydrogels. These particle hydrogels are sequentially loaded into a syringe to form a pattern and, once injected, they maintain the pattern. The applicability of this hydrogel in a wound healing skin model, a subcutaneous implant model, as well as a stroke brain model is examined and distinct patterning in all models tested is shown. This injectable and spatially patterned hydrogel can be used to create physical or biochemical gradients. Further, this design can better match the scaffold properties within the physical location of the tissue (e.g., wound border vs wound center). This allows for better design features within the material that promote repair and regeneration

Region-specific and activity-dependent regulation of SVZ neurogenesis and recovery after stroke.

Stroke is the leading cause of adult disability. Neurogenesis after stroke is associated with repair; however, the mechanisms regulating poststroke neurogenesis and its functional effect remain unclear. Here, we investigate multiple mechanistic routes of induced neurogenesis in the poststroke brain, using both a forelimb overuse manipulation that models a clinical neurorehabilitation paradigm, as well as local manipulation of cellular activity in the peri-infarct cortex. Increased activity in the forelimb peri-infarct cortex via either modulation drives increased subventricular zone (SVZ) progenitor proliferation, migration, and neuronal maturation in peri-infarct cortex. This effect is sensitive to competition from neighboring brain regions. By using orthogonal tract tracing and rabies virus approaches in transgenic SVZ-lineage-tracing mice, SVZ-derived neurons synaptically integrate into the peri-infarct cortex; these effects are enhanced with forelimb overuse. Synaptic transmission from these newborn SVZ-derived neurons is critical for spontaneous recovery after stroke, as tetanus neurotoxin silencing specifically of the SVZ-derived neurons disrupts the formation of these synaptic connections and hinders functional recovery after stroke. SVZ-derived neurogenesis after stroke is activity-dependent, region-specific, and sensitive to modulation, and the synaptic connections formed by these newborn cells are functionally critical for poststroke recovery

Development of an Accelerated Test Design for Predicting the Service Life of the Solar Array at Mead, Nebraska

Potential long-term degradation modes for the two types of modules in the Mead array were determined and judgments were made as to those environmental stresses and combinations of stresses which accelerate the degradation of the power output. Hierarchical trees representing the severity of effects of stresses (test conditions) on eleven individual degradation modes were constructed and were pruned of tests judged to be nonessential. Composites of those trees were developed so that there is now one pruned tree covering eight degradation modes, another covering two degradation modes, and a third covering one degradation mode. These three composite trees form the basis for selection of test conditions in the final test plan which is now being prepared

Atomic position localization via dual measurement

We study localization of atomic position when a three-level atom interacts with a quantized standing-wave field in the Ramsey interferometer setup. Both the field quadrature amplitude and the atomic internal state are measured to obtain the atomic position information. It is found that this dual measurement scheme produces an interference pattern superimposed on a diffraction-like pattern in the atomic position distribution, where the former pattern originates from the state-selective measurement and the latter from the field measurement. The present scheme results in a better resolution in the position localization than the field-alone measurement schemes. We also discuss the measurement-correlated mechanical action of the standing-wave field on the atom in the light of Popper's test.Comment: 6.5 pages and 5 figure

Assigning stranded bottlenose dolphins to source stocks using stable isotope ratios following the Deepwater Horizon oil spill

The potential for stranded dolphins to serve as a tool for monitoring free-ranging populations would be enhanced if their stocks of origin were known. We used stable isotopes of carbon, nitrogen, and sulfur from skin to assign stranded bottlenose dolphins Tursiops truncatus to different habitats, as a proxy for stocks (demographically independent populations), following the Deepwater Horizon oil spill. Model results from biopsy samples collected from dolphins from known habitats (n = 205) resulted in an 80.5% probability of correct assignment. These results were applied to data from stranded dolphins (n = 217), resulting in predicted assignment probabilities of 0.473, 0.172, and 0.355 to Estuarine, Barrier Island (BI), and Coastal stocks, respectively. Differences were found west and east of the Mississippi River, with more Coastal dolphins stranding in western Louisiana and more Estuarine dolphins stranding in Mississippi. Within the Estuarine East Stock, 2 groups were identified, one predominantly associated with Mississippi and Alabama estuaries and another with western Florida. δ15N values were higher in stranded samples for both Estuarine and BI stocks, potentially indicating nutritional stress. High probabilities of correct assignment of the biopsy samples indicate predictable variation in stable isotopes and fidelity to habitat. The power of δ34S to discriminate habitats relative to salinity was essential. Stable isotopes may provide guidance regarding where additional testing is warranted to confirm demographic independence and aid in determining the source habitat of stranded dolphins, thus increasing the value of biological data collected from stranded individuals.Publisher PDFPeer reviewe

Agreed definitions and a shared vision for new standards in stroke recovery research: The Stroke Recovery and Rehabilitation Roundtable taskforce.

The first Stroke Recovery and Rehabilitation Roundtable established a game changing set of new standards for stroke recovery research. Common language and definitions were required to develop an agreed framework spanning the four working groups: translation of basic science, biomarkers of stroke recovery, measurement in clinical trials and intervention development and reporting. This paper outlines the working definitions established by our group and an agreed vision for accelerating progress in stroke recovery research

Molecular Mechanisms of the Diabetogenic Effects of Arsenic: Inhibition of Insulin Signaling by Arsenite and Methylarsonous Acid

BACKGROUND: Increased prevalences of diabetes mellitus have been reported among individuals chronically exposed to inorganic arsenic (iAs). However, the mechanisms underlying the diabetogenic effects of iAs have not been characterized. We have previously shown that trivalent metabolites of iAs, arsenite (iAs(III)) and methylarsonous acid (MAs(III)) inhibit insulin-stimulated glucose uptake (ISGU) in 3T3-L1 adipocytes by suppressing the insulin-dependent phosphorylation of protein kinase B (PKB/Akt). OBJECTIVES: Our goal was to identify the molecular mechanisms responsible for the suppression of PKB/Akt phosphorylation by iAs(III) and MAs(III). METHODS: The effects of iAs(III) and MAs(III) on components of the insulin-activated signal transduction pathway that regulate PKB/Akt phosphorylation were examined in 3T3-L1 adipocytes. RESULTS: Subtoxic concentrations of iAs(III) or MAs(III) had little or no effect on the activity of phosphatidylinositol 3-kinase (PI-3K), which synthesizes phosphatidylinositol-3,4,5-triphosphate (PIP(3)), or on phosphorylation of PTEN (phosphatase and tensin homolog deleted on chromosome ten), a PIP(3) phosphatase. Neither iAs(III) nor MAs(III) interfered with the phosphorylation of 3-phosphoinositide-dependent kinase-1 (PDK-1) located downstream from PI-3K. However, PDK-1 activity was inhibited by both iAs(III) and MAs(III). Consistent with these findings, PDK-1-catalyzed phosphorylation of PKB/Akt(Thr308) and PKB/Akt activity were suppressed in exposed cells. In addition, PKB/Akt(Ser473) phosphorylation, which is catalyzed by a putative PDK-2, was also suppressed. Notably, expression of constitutively active PKB/Akt restored the normal ISGU pattern in adipocytes treated with either iAs(III) or MAs(III). CONCLUSIONS: These results suggest that inhibition of the PDK-1/PKB/Akt-mediated transduction step is the key mechanism for the inhibition of ISGU in adipocytes exposed to iAs(III) or MAs(III), and possibly for impaired glucose tolerance associated with human exposures to iAs