Retinal ganglion cell survival and axon regeneration in WldS transgenic rats after optic nerve crush and lens injury.

BACKGROUND: We have previously shown that the slow Wallerian degeneration mutation, whilst delaying axonal degeneration after optic nerve crush, does not protect retinal ganglion cell (RGC) bodies in adult rats. To test the effects of a combination approach protecting both axons and cell bodies we performed combined optic nerve crush and lens injury, which results in both enhanced RGC survival as well as axon regeneration past the lesion site in wildtype animals. RESULTS: As previously reported we found that the Wld(S) mutation does not protect RGC bodies after optic nerve crush alone. Surprisingly, we found that Wld(S) transgenic rats did not exhibit the enhanced RGC survival response after combined optic nerve crush and lens injury that was observed in wildtype rats. RGC axon regeneration past the optic nerve lesion site was, however, similar in Wld(S) and wildtypes. Furthermore, activation of retinal glia, previously shown to be associated with enhanced RGC survival and axon regeneration after optic nerve crush and lens injury, was unaffected in Wld(S) transgenic rats. CONCLUSIONS: RGC axon regeneration is similar between Wld(S) transgenic and wildtype rats, but Wld(S) transgenic rats do not exhibit enhanced RGC survival after combined optic nerve crush and lens injury suggesting that the neuroprotective effects of lens injury on RGC survival may be limited by the Wld(S) protein.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Bioink properties before, during and after 3D bioprinting

Bioprinting is a process based on additive manufacturing from materials containing living cells. These materials, often referred to as bioink, are based on cytocompatible hydrogel precursor formulations, which gel in a manner compatible with different bioprinting approaches. The bioink properties before, during and after gelation are essential for its printability, comprising such features as achievable structural resolution, shape fidelity and cell survival. However, it is the final properties of the matured bioprinted tissue construct that are crucial for the end application. During tissue formation these properties are influenced by the amount of cells present in the construct, their proliferation, migration and interaction with the material. A calibrated computational framework is able to predict the tissue development and maturation and to optimize the bioprinting input parameters such as the starting material, the initial cell loading and the construct geometry. In this contribution relevant bioink properties are reviewed and discussed on the example of most popular bioprinting approaches. The effect of cells on hydrogel processing and vice versa is highlighted. Furthermore, numerical approaches were reviewed and implemented for depicting the cellular mechanics within the hydrogel as well as for prediction of mechanical properties to achieve the desired hydrogel construct considering cell density, distribution and material-cell interaction

Neurology

Contains reports on six research projects.United States Public Health Service (B-3055-4, B-3090-4, MH-06175-02)United States Navy, Office of Naval Research (Contract Nonr-1841(70))United States Air Force (AF49(638)-1313), administered by the Electronic Systems Laboratory, M. I. T

Relative Reactivity of the Metal-Amido versus Metal-Imido Bond in Linked Cp-Amido and Half-Sandwich Complexes of Vanadium

Treatment of (η5-C5H4C2H4NR)V(N-t-Bu)Me (R = Me, i-Pr) and CpV(N-p-Tol)(N-i-Pr2)Me (Cp = η5-C5H5) with B(C6F5)3 or [Ph3C][B(C6F5)4] results in formation of the corresponding cations, [(η5-C5H4C2H4NR)V(N-t-Bu)]+ and [CpV(N-p-Tol)(N-i-Pr2)]+. The latter could also be generated as its N,N-dimethylaniline adduct by treatment of the methyl complex with [PhNMe2H][BAr4] (Ar = Ph, C6F5). Instead, the analogous reaction with the linked Cp-amido precursor results in protonation of the imido-nitrogen atom. Sequential cyclometalation of the amide substituents gave cationic imine complexes [(η5-C5H4C2H4NCR'2)V(NH-t-Bu)]+ (R' = H, Me) and methane. Reaction of cationic [(η5-C5H4C2H4NR)V(N-t-Bu)]+ with olefins affords the corresponding olefin adducts, whereas treatment with 1 or 2 equiv of 2-butyne results in insertion of the alkyne into the vanadium-nitrogen single bond, affording the mono- and bis-insertion products [(η5-C5H4C2H4N(i-Pr)C2Me2)V(N-t-Bu)]+ and [(η5-C5H4C2H4N(i-Pr)C4Me4)V(N-t-Bu)]+. The same reaction with the half-sandwich compound [CpV(N-p-Tol)(N-i-Pr2)]+ results in a paramagnetic compound that, upon alcoholysis, affords sec-butylidene-p-tolylamine, suggesting an initial [2+2] cycloaddition reaction. The difference in reactivity between the V-N bond versus the V=N bond was further studied using computational methods. Results were compared to the isoelectronic titanium system CpTi(NH)(NH2). These studies indicate that the kinetic product in each system is derived from a [2+2] cycloaddition reaction. For titanium, this was found as the thermodynamic product as well, whereas the insertion reaction was found to be thermodynamically more favorable in the case of vanadium.

Diabetes and Driving

Of the nearly 19 million people in the U.S. with diagnosed diabetes (1), a large percentage will seek or currently hold a license to drive. For many, a driver's license is essential to work; taking care of family; securing access to public and private facilities, services, and institutions; interacting with friends; attending classes; and/or performing many other functions of daily life. Indeed, in many communities and areas of the U.S. the use of an automobile is the only (or the only feasible or affordable) means of transportation available. There has been considerable debate whether, and the extent to which, diabetes may be a relevant factor in determining driver ability and eligibility for a license. This position statement addresses such issues in light of current scientific and medical evidence. Sometimes people with a strong interest in road safety, including motor vehicle administrators, pedestrians, drivers, other road users, and employers, associate all diabetes with unsafe driving when in fact most people with diabetes safely operate motor vehicles without creating any meaningful risk of injury to themselves or others. When legitimate questions arise about the medical fitness of a person with diabetes to drive, an individual assessment of that person's diabetes management—with particular emphasis on demonstrated ability to detect and appropriately treat potential hypoglycemia—is necessary in order to determine any appropriate restrictions. The diagnosis of diabetes is not sufficient to make any judgments about individual driver capacity. This document provides an overview of existing licensing rules for people with diabetes, addresses the factors that impact driving for this population, and identifies general guidelines for assessing driver fitness and determining appropriate licensing restrictions

Discovery of Sexual Dimorphisms in Metabolic and Genetic Biomarkers

Metabolomic profiling and the integration of whole-genome genetic association data has proven to be a powerful tool to comprehensively explore gene regulatory networks and to investigate the effects of genetic variation at the molecular level. Serum metabolite concentrations allow a direct readout of biological processes, and association of specific metabolomic signatures with complex diseases such as Alzheimer's disease and cardiovascular and metabolic disorders has been shown. There are well-known correlations between sex and the incidence, prevalence, age of onset, symptoms, and severity of a disease, as well as the reaction to drugs. However, most of the studies published so far did not consider the role of sexual dimorphism and did not analyse their data stratified by gender. This study investigated sex-specific differences of serum metabolite concentrations and their underlying genetic determination. For discovery and replication we used more than 3,300 independent individuals from KORA F3 and F4 with metabolite measurements of 131 metabolites, including amino acids, phosphatidylcholines, sphingomyelins, acylcarnitines, and C6-sugars. A linear regression approach revealed significant concentration differences between males and females for 102 out of 131 metabolites (p-values<3.8 x 10(-4); Bonferroni-corrected threshold). Sex-specific genome-wide association studies (GWAS) showed genome-wide significant differences in beta-estimates for SNPs in the CPS1 locus (carbamoyl-phosphate synthase 1, significance level: p<3.8 x 10(-10); Bonferroni-corrected threshold) for glycine. We showed that the metabolite profiles of males and females are significantly different and, furthermore, that specific genetic variants in metabolism-related genes depict sexual dimorphism. Our study provides new important insights into sex-specific differences of cell regulatory processes and underscores that studies should consider sex-specific effects in design and interpretation

X-ray absorption spectroscopy systematics at the tungsten L-edge

A series of mononuclear six-coordinate tungsten compounds spanning formal oxidation states from 0 to +VI, largely in a ligand environment of inert chloride and/or phosphine, has been interrogated by tungsten L-edge X-ray absorption spectroscopy. The L-edge spectra of this compound set, comprised of [W&lt;sup&gt;0&lt;/sup&gt;(PMe&lt;sub&gt;3&lt;/sub&gt;)&lt;sub&gt;6&lt;/sub&gt;], [W&lt;sup&gt;II&lt;/sup&gt;Cl&lt;sub&gt;2&lt;/sub&gt;(PMePh&lt;sub&gt;2&lt;/sub&gt;)&lt;sub&gt;4&lt;/sub&gt;], [W&lt;sup&gt;III&lt;/sup&gt;Cl&lt;sub&gt;2&lt;/sub&gt;(dppe)&lt;sub&gt;2&lt;/sub&gt;][PF&lt;sub&gt;6&lt;/sub&gt;] (dppe = 1,2-bis(diphenylphosphino)ethane), [W&lt;sup&gt;IV&lt;/sup&gt;Cl&lt;sub&gt;4&lt;/sub&gt;(PMePh&lt;sub&gt;2&lt;/sub&gt;)&lt;sub&gt;2&lt;/sub&gt;], [W&lt;sup&gt;V&lt;/sup&gt;(NPh)Cl&lt;sub&gt;3&lt;/sub&gt;(PMe&lt;sub&gt;3&lt;/sub&gt;)&lt;sub&gt;2&lt;/sub&gt;], and [W&lt;sup&gt;VI&lt;/sup&gt;Cl&lt;sub&gt;6&lt;/sub&gt;] correlate with formal oxidation state and have usefulness as references for the interpretation of the L-edge spectra of tungsten compounds with redox-active ligands and ambiguous electronic structure descriptions. The utility of these spectra arises from the combined correlation of the estimated branching ratio (EBR) of the L&lt;sub&gt;3,2&lt;/sub&gt;-edges and the L&lt;sub&gt;1&lt;/sub&gt; rising-edge energy with metal Z&lt;sub&gt;eff&lt;/sub&gt;, thereby permitting an assessment of effective metal oxidation state. An application of these reference spectra is illustrated by their use as backdrop for the L-edge X-ray absorption spectra of [W&lt;sup&gt;IV&lt;/sup&gt;(mdt)&lt;sub&gt;2&lt;/sub&gt;(CO)&lt;sub&gt;2&lt;/sub&gt;] and [W&lt;sup&gt;IV&lt;/sup&gt;(mdt)&lt;sub&gt;2&lt;/sub&gt;(CN)&lt;sub&gt;2&lt;/sub&gt;]&lt;sup&gt;2–&lt;/sup&gt; (mdt&lt;sup&gt;2–&lt;/sup&gt; = 1,2-dimethylethene-1,2-dithiolate), which shows that both compounds are effectively W&lt;sup&gt;IV&lt;/sup&gt; species. Use of metal L-edge XAS to assess a compound of uncertain formulation requires: 1) Placement of that data within the context of spectra offered by unambiguous calibrant compounds, preferably with the same coordination number and similar metal ligand distances. Such spectra assist in defining upper and/or lower limits for metal Z&lt;sub&gt;eff&lt;/sub&gt; in the species of interest; 2) Evaluation of that data in conjunction with information from other physical methods, especially ligand K-edge XAS; 3) Increased care in interpretation if strong π-acceptor ligands, particularly CO, or π-donor ligands are present. The electron-withdrawing/donating nature of these ligand types, combined with relatively short metal-ligand distances, exaggerate the difference between formal oxidation state and metal Z&lt;sub&gt;eff&lt;/sub&gt; or, as in the case of [W&lt;sup&gt;IV&lt;/sup&gt;(mdt)&lt;sub&gt;2&lt;/sub&gt;(CO)&lt;sub&gt;2&lt;/sub&gt;], add other subtlety by modulating the redox level of other ligands in the coordination sphere

Vanadium (β-(Dimethylamino)ethyl)cyclopentadienyl Complexes with Diphenylacetylene Ligands

Reduction of the V(III) (β-(dimethylamino)ethyl)cyclopentadienyl dichloride complex [η5:η1-C5H4(CH2)2NMe2]VCl2(PMe3) with 1 equiv of Na/Hg yielded the V(II) dimer {[η5:η1-C5H4(CH2)2NMe2]V(µ-Cl)}2 (2). This compound reacted with diphenylacetylene in THF to give the V(II) alkyne adduct [η5:η1-C5H4(CH2)2NMe2]VCl(η2-PhC≡CPh). Further reduction of 2 with Mg in the presence of diphenylacetylene resulted in oxidative coupling of two diphenylacetylene groups to yield the diamagnetic, formally V(V), bent metallacyclopentatriene complex [η5:η1-C5H4(CH2)2NMe2]V(C4Ph4).