Working memory capacity, the maximum number of items that we can transiently store in working memory, is a good predictor of our general cognitive abilities. Neural activity in both dorsolateral prefrontal cortex and posterior parietal cortex has been associated with memory retention during visuospatial working memory tasks. The parietal cortex is thought to store the memories. However, the role of the dorsolateral prefrontal cortex, a top-down control area, during pure information retention is debated, and the mechanisms regulating capacity are unknown. Here, we propose that a major role of the dorsolateral prefrontal cortex in working memory is to boost parietal memory capacity. Furthermore, we formulate the boosting mechanism computationally in a biophysical cortical microcircuit model and derive a simple, explicit mathematical formula relating memory capacity to prefrontal and parietal model parameters. For physiologically realistic parameter values, lateral inhibition in the parietal cortex limits mnemonic capacity to a maximum of 2-7 items. However, at high loads inhibition can be counteracted by excitatory prefrontal input, thus boosting parietal capacity. Predictions from the model were confirmed in an fMRI study. Our results show that although memories are stored in the parietal cortex, interindividual differences in memory capacity are partly determined by the strength of prefrontal top-down control. The model provides a mechanistic framework for understanding topdown control of working memory and specifies two different contributions of prefrontal and parietal cortex to working memory capacity.computer model ͉ fMRI ͉ lateral inhibition ͉ prefrontal ͉ short-term memory ͉ parietal

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The cellular maturational processes behind cognitive development during childhood, including the development of working memory capacity, are still unknown. By using the most standard computational model of visuospatial working memory, we investigated the consequences of cellular maturational processes, including myelination, synaptic strengthening, and synaptic pruning, on working memory-related brain activity and performance. We implemented five structural developmental changes occurring as a result of the cellular maturational processes in the biophysically based computational network model. The developmental changes in memory activity predicted from the simulations of the model were then compared to brain activity measured with functional magnetic resonance imaging in children and adults. We found that networks with stronger fronto-parietal synaptic connectivity between cells coding for similar stimuli, but not those with faster conduction, stronger connectivity within a region, or increased coding specificity, predict measured developmental increases in both working memory-related brain activity and in correlations of activity between regions. Stronger fronto-parietal synaptic connectivity between cells coding for similar stimuli was thus the only developmental process that accounted for the observed changes in brain activity associated with development of working memory during childhood.

Fat oxidation during exercise is greater in females than in males. We sought to determine whether sex differences in substrate metabolism are paralleled by distinct skeletal muscle mitochondrial volume density and oxidative capacity. Whole-body substrate (fat and carbohydrate) utilization during submaximal treadmill running was assessed, and skeletal muscle biopsies were taken to determine mitochondrial volume density and function in healthy young females (n = 12) and males (n = 12) matched by aerobic exercise capacity and exercise performance. Females presented a lower respiratory exchange ratio (0.87 ± 0.04 versus 0.91 ± 0.04, P = 0.023) and whole-body carbohydrate oxidation (27.8 ± 8.3 versus 35.8 ± 6.5 mg kg min , P = 0.027), whereas fat oxidation was higher (8.7 ± 2.8 versus 5.9 ± 2.6 mg kg min , P = 0.034) during submaximal exercise compared with males. In skeletal muscle biopsies, females demonstrated augmented mitochondrial volume density (7.51 ± 1.77 versus 5.90 ± 1.72%, P = 0.035) and oxidative capacity for fatty acid [36.6 ± 12.8 versus 24.5 ± 7.3 pmol O s (mg wet weight) , P = 0.009] and lactate [71.1 ± 24.4 versus 53.2 ± 14.6 pmol O s (mg wet weight) , P = 0.040]. No sex differences in respiratory exchange ratio, whole-body fat oxidation and skeletal muscle variables were detected when adjusted for anthropometric variables including body mass or leg mass, which were lower in females. In conclusion, female prioritization of fat over carbohydrate oxidation during exercise is underpinned by augmented body size-related mitochondrial volume density, fatty acid and lactate oxidative capacity in skeletal muscle fibres.

Melt electrospinning is one aspect of electrospinning with relatively little published literature, although the technique avoids solvent accumulation and/or toxicity which is favoured in certain applications In the study reported, we melt-electrospun blends of poly(epsilon-caprolactone) (PCL) and an amphiphilic diblock copolymer consisting of poly(ethylene glycol) and PCL segments (PEG-block PCL) A custom-made electrospinning apparatus was built and various combinations of instrument parameters such as voltage and polymer feeding rate were investigated Pure PEG-block-PCL copolymer melt electrospinning did not result in consistent and uniform fibres due to the low molecular weight, while blends of PCL and PEG-block-PCL, for some parameter combinations and certain weight ratios of the two components, were able to produce continuous fibres significantly thinner (average diameter of ca 2 mu m) compared to pure PCL The PCL fibres obtained had average diameters ranging from 6 to 33 mu m and meshes were uniform for the lowest voltage employed while mesh uniformity decreased when the voltage was increased This approach shows that PCL and blends of PEG block-PCL and PCL can be readily processed by melt electrospinning to obtain fibrous meshes with varied average diameters and morphologies that are of interest for tissue engineering purpose

BackgroundWhilst the ergogenic effects of carbohydrate intake during prolonged exercise are well-documented, few investigations have studied the effects of carbohydrate ingestion during cross-country skiing, a mode of exercise that presents unique metabolic demands on athletes due to the combined use of large upper- and lower-body muscle masses. Moreover, no previous studies have investigated exogenous carbohydrate oxidation rates during cross-country skiing. The current study investigated the effects of a 13C-enriched 18% multiple-transportable carbohydrate solution (1:0.8 maltodextrin:fructose) with additional gelling polysaccharides (CHO-HG) on substrate utilization and gastrointestinal symptoms during prolonged cross-country skiing exercise in the cold, and subsequent double-poling time-trial performance in ~ 20 °C.MethodsTwelve elite cross-country ski athletes (6 females, 6 males) performed 120-min of submaximal roller-skiing (69.3 ± 2.9% of O2peak) in −5 °C while receiving either 2.2 g CHO-HG·min− 1 or a non-caloric placebo administered in a double-blind, randomized manner. Whole-body substrate utilization and exogenous carbohydrate oxidation was calculated for the last 60 min of the submaximal exercise. The maximal time-trial (2000 m for females, 2400 m for males) immediately followed the 120-min submaximal bout. Repeated-measures ANOVAs with univariate follow-ups were conducted, as well as independent and paired t-tests, and significance was set at P < 0.05. Data are presented as mean ± SD.ResultsExogenous carbohydrate oxidation contributed 27.6 ± 6.6% to the total energy yield with CHO-HG and the peak exogenous carbohydrate oxidation rate reached 1.33 ± 0.27 g·min− 1. Compared to placebo, fat oxidation decreased by 9.5 ± 4.8% with CHO-HG, total carbohydrate oxidation increased by 9.5 ± 4.8% and endogenous carbohydrate utilization decreased by 18.1 ± 6.4% (all P < 0.05). No severe gastrointestinal symptoms were reported in either trial and euhydration was maintained in both trials. Time-trial performance (8.4 ± 0.4 min) was not improved following CHO-HG compared to placebo (− 0.8 ± 3.5 s; 95% confidence interval − 3.0 to 1.5 s; P = 0.46). No sex differences were identified in substrate utilization or relative performance.ConclusionsIngestion of an 18% multiple-transportable carbohydrate solution with gelling polysaccharides was found to be well-tolerated during 120 min of submaximal whole-body exercise, but did not improve subsequent maximal double-poling performance.

Globally 360 million people have disabling hearing loss and, of these, 32 million are children. Human hearing relies on 15,000 hair cells that transduce mechanical vibrations to electrical signals in the auditory nerve. The process is powered by the endo-cochlear potential, which is produced by a vascularized epithelium that actively transports ions in conjunction with a gap junction (GJ) system. This "battery" is located "off-site" in the lateral wall of the cochlea. The GJ syncytium contains the GJ protein genes beta 2 (GJB2/connexin26 (Cx26)) and 6 (GJB6/connexin30 (Cx30)), which are commonly involved in hereditary deafness. Because the molecular arrangement of these proteins is obscure, we analyze GJ protein expression (Cx26/30) in human cochleae by using super-resolution structured illumination microscopy. At this resolution, the Cx26 and Cx30 proteins were visible as separate plaques, rather than being co-localized in heterotypic channels, as previously suggested. The Cx26 and Cx30 proteins thus seem not to be co-expressed but to form closely associated assemblies of GJ plaques. These results could assist in the development of strategies to treat genetic hearing loss in the future.

HighlightsPre- and post-somatic segments of type I spiral ganglion neurons (SGNs) are unmyelinated in man.Following hair cell loss and retrograde nerve degeneration SGNs survive as “mono-polar” cells in human deafness.Non-myelinated Schwann cells may consolidate the neural cell bodies and protect SGNs from further degeneration.Human SGNs can persist as electrically excitable mono-polar cells even after long-time deafness.Robust survival of human SGNs is a prerequisite for cochlear implant function.