Occipital Proton Magnetic Resonance Spectroscopy ((1)H-MRS) Reveals Normal Metabolite Concentrations in Retinal Visual Field Defects

BACKGROUND: Progressive visual field defects, such as age-related macular degeneration and glaucoma, prevent normal stimulation of visual cortex. We investigated whether in the case of visual field defects, concentrations of metabolites such as N-acetylaspartate (NAA), a marker for degenerative processes, are reduced in the occipital brain region. METHODOLOGY/PRINCIPAL FINDINGS: Participants known with glaucoma, age-related macular degeneration (the two leading causes of visual impairment in the developed world), and controls were examined by proton MR spectroscopic ((1)H-MRS) imaging. Absolute NAA, Creatine and Choline concentrations were derived from a single-voxel in the occipital region of each brain hemisphere. No significant differences in metabolites concentrations were found between the three groups. CONCLUSIONS/SIGNIFICANCE: We conclude that progressive retinal visual field defects do not affect metabolite concentration in visual brain areas suggesting that there is no ongoing occipital degeneration. We discuss the possibility that metabolite change is too slow to be detectable

Energy Transfer and Spectra in Simulations of Two-dimensional Compressible Turbulence

We present results of high-resolution numerical simulations of compressible 2D turbulence forced at intermediate spatial scales with a solenoidal white-in-time external acceleration. A case with an isothermal equation of state, low energy injection rate, and turbulent Mach number $M\approx0.34$ without energy condensate is studied in detail. Analysis of energy spectra and fluxes shows that the classical dual-cascade picture familiar from the incompressible case is substantially modified by compressibility effects. While the small-scale direct enstrophy cascade remains largely intact, a large-scale energy flux loop forms with the direct acoustic energy cascade compensating for the inverse transfer of solenoidal kinetic energy. At small scales, the direct enstrophy and acoustic energy cascades are fully decoupled at small Mach numbers and hence the corresponding spectral energy slopes comply with theoretical predictions, as expected. At large scales, dispersion of acoustic waves on vortices softens the dilatational velocity spectrum, while the pseudo-sound component of the potential energy associated with coherent vortices steepens the potential energy spectrum.Comment: 10 pages, 6 figures. To appear in: Turbulence in Complex Conditions, Proc. Euromech/Ercoftac Colloquium 589, ed. M. Gorokhovski, Springer, 201

Do aluminium-based phosphate binders continue to have a role in contemporary nephrology practice?

Background: Aluminium-containing phosphate binders have long been used for treatment of hyperphosphatemia in dialysis patients. Their safety became controversial in the early 1980's after reports of aluminium related neurological and bone disease began to appear. Available historical evidence however, suggests that neurological toxicity may have primarily been caused by excessive exposure to aluminium in dialysis fluid, rather than aluminium-containing oral phosphate binders. Limited evidence suggests that aluminium bone disease may also be on the decline in the era of aluminium removal from dialysis fluid, even with continued use of aluminium binders

Delayed mGluR5 activation limits neuroinflammation and neurodegeneration after traumatic brain injury

<p>Abstract</p> <p>Background</p> <p>Traumatic brain injury initiates biochemical processes that lead to secondary neurodegeneration. Imaging studies suggest that tissue loss may continue for months or years after traumatic brain injury in association with chronic microglial activation. Recently we found that metabotropic glutamate receptor 5 (mGluR5) activation by (<it>RS</it>)-2-chloro-5-hydroxyphenylglycine (CHPG) decreases microglial activation and release of associated pro-inflammatory factors <it>in vitro</it>, which is mediated in part through inhibition of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Here we examined whether delayed CHPG administration reduces chronic neuroinflammation and associated neurodegeneration after experimental traumatic brain injury in mice.</p> <p>Methods</p> <p>One month after controlled cortical impact traumatic brain injury, C57Bl/6 mice were randomly assigned to treatment with single dose intracerebroventricular CHPG, vehicle or CHPG plus a selective mGluR5 antagonist, 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine. Lesion volume, white matter tract integrity and neurological recovery were assessed over the following three months.</p> <p>Results</p> <p>Traumatic brain injury resulted in mGluR5 expression in reactive microglia of the cortex and hippocampus at one month post-injury. Delayed CHPG treatment reduced expression of reactive microglia expressing NADPH oxidase subunits; decreased hippocampal neuronal loss; limited lesion progression, as measured by repeated T2-weighted magnetic resonance imaging (at one, two and three months) and white matter loss, as measured by high field <it>ex vivo </it>diffusion tensor imaging at four months; and significantly improved motor and cognitive recovery in comparison to the other treatment groups.</p> <p>Conclusion</p> <p>Markedly delayed, single dose treatment with CHPG significantly improves functional recovery and limits lesion progression after experimental traumatic brain injury, likely in part through actions at mGluR5 receptors that modulate neuroinflammation.</p

Understanding within-session loss-chasing: an experimental investigation of the impact of stake size on cognitive control

Loss-chasing is a central feature of problematic gambling, yet it remains a poorly conceived and understood concept. Loss-chasing is believed to stem from an ero- sion of cognitive control when gambling. The opportunity to gamble at significantly dis- parate stake sizes on a gambling activity is considered to be a risk factor for loss-chasing. This study investigated the impact of gambling at disparate stake sizes on executive processes integral to maintaining cognitive control when gambling, namely response inhibition and reflection impulsivity. Frequent adult non-problem gamblers (n = 32) participated in a repeated measures experiment; and gambled at three disparate stake sizes (£20, £2 and no stake per bet) on a simulated gambling task. Participants’ response inhibition performance and reflection impulsivity levels after gambling at various stake sizes were compared via a go/no-go task and information sampling task, respectively. Quality of decision-making i.e. the evaluation of available information to make probability judgements was impaired after gambling at higher stakes in comparison to lower stakes, indicating an increase in reflection impulsivity. No effect on response inhibition was observed. Although exploratory, this suggests that the opportunity for participants to substantially increase stake size on a gambling activity may be a risk factor for impaired cognitive performance when gambling, and perhaps create vulnerability for within-session loss-chasing in some players. Keywords Problem gambling - Cognitive control - Loss-chasing - Response inhibition - Reflection impulsivit

Positional Cloning of Zinc Finger Domain Transcription Factor Zfp69, a Candidate Gene for Obesity-Associated Diabetes Contributed by Mouse Locus Nidd/SJL

Polygenic type 2 diabetes in mouse models is associated with obesity and results from a combination of adipogenic and diabetogenic alleles. Here we report the identification of a candidate gene for the diabetogenic effect of a QTL (Nidd/SJL, Nidd1) contributed by the SJL, NON, and NZB strains in outcross populations with New Zealand Obese (NZO) mice. A critical interval of distal chromosome 4 (2.1 Mbp) conferring the diabetic phenotype was identified by interval-specific congenic introgression of SJL into diabetes-resistant C57BL/6J, and subsequent reporter cross with NZO. Analysis of the 10 genes in the critical interval by sequencing, qRT–PCR, and RACE–PCR revealed a striking allelic variance of Zfp69 encoding zinc finger domain transcription factor 69. In NZO and C57BL/6J, a retrotransposon (IAPLTR1a) in intron 3 disrupted the gene by formation of a truncated mRNA that lacked the coding sequence for the KRAB (Krüppel-associated box) and Znf-C2H2 domains of Zfp69, whereas the diabetogenic SJL, NON, and NZB alleles generated a normal mRNA. When combined with the B6.V-Lepob background, the diabetogenic Zfp69SJL allele produced hyperglycaemia, reduced gonadal fat, and increased plasma and liver triglycerides. mRNA levels of the human orthologue of Zfp69, ZNF642, were significantly increased in adipose tissue from patients with type 2 diabetes. We conclude that Zfp69 is the most likely candidate for the diabetogenic effect of Nidd/SJL, and that retrotransposon IAPLTR1a contributes substantially to the genetic heterogeneity of mouse strains. Expression of the transcription factor in adipose tissue may play a role in the pathogenesis of type 2 diabetes

The Real maccoyii: Identifying Tuna Sushi with DNA Barcodes – Contrasting Characteristic Attributes and Genetic Distances

BACKGROUND:The use of DNA barcodes for the identification of described species is one of the least controversial and most promising applications of barcoding. There is no consensus, however, as to what constitutes an appropriate identification standard and most barcoding efforts simply attempt to pair a query sequence with reference sequences and deem identification successful if it falls within the bounds of some pre-established cutoffs using genetic distance. Since the Renaissance, however, most biological classification schemes have relied on the use of diagnostic characters to identify and place species. METHODOLOGY/PRINCIPAL FINDINGS:Here we developed a cytochrome c oxidase subunit I character-based key for the identification of all tuna species of the genus Thunnus, and compared its performance with distance-based measures for identification of 68 samples of tuna sushi purchased from 31 restaurants in Manhattan (New York City) and Denver, Colorado. Both the character-based key and GenBank BLAST successfully identified 100% of the tuna samples, while the Barcode of Life Database (BOLD) as well as genetic distance thresholds, and neighbor-joining phylogenetic tree building performed poorly in terms of species identification. A piece of tuna sushi has the potential to be an endangered species, a fraud, or a health hazard. All three of these cases were uncovered in this study. Nineteen restaurant establishments were unable to clarify or misrepresented what species they sold. Five out of nine samples sold as a variant of "white tuna" were not albacore (T. alalunga), but escolar (Lepidocybium flavorunneum), a gempylid species banned for sale in Italy and Japan due to health concerns. Nineteen samples were northern bluefin tuna (T. thynnus) or the critically endangered southern bluefin tuna (T. maccoyii), though nine restaurants that sold these species did not state these species on their menus. CONCLUSIONS/SIGNIFICANCE:The Convention on International Trade Endangered Species (CITES) requires that listed species must be identifiable in trade. This research fulfills this requirement for tuna, and supports the nomination of northern bluefin tuna for CITES listing in 2010

Simultaneous consumption of pentose and hexose sugars: an optimal microbial phenotype for efficient fermentation of lignocellulosic biomass

Lignocellulosic biomass is an attractive carbon source for bio-based fuel and chemical production; however, its compositional heterogeneity hinders its commercial use. Since most microbes possess carbon catabolite repression (CCR), mixed sugars derived from the lignocellulose are consumed sequentially, reducing the efficacy of the overall process. To overcome this barrier, microbes that exhibit the simultaneous consumption of mixed sugars have been isolated and/or developed and evaluated for the lignocellulosic biomass utilization. Specific strains of Escherichia coli, Saccharomyces cerevisiae, and Zymomonas mobilis have been engineered for simultaneous glucose and xylose utilization via mutagenesis or introduction of a xylose metabolic pathway. Other microbes, such as Lactobacillus brevis, Lactobacillus buchneri, and Candida shehatae possess a relaxed CCR mechanism, showing simultaneous consumption of glucose and xylose. By exploiting CCR-negative phenotypes, various integrated processes have been developed that incorporate both enzyme hydrolysis of lignocellulosic material and mixed sugar fermentation, thereby enabling greater productivity and fermentation efficacy