Miracle-dz/UniFAR-FTUs huggingface dataset:
PPARδ agonism inhibits skeletal muscle PDC activity, mitochondrial ATP production and force generation during prolonged contraction

We have recently shown that PPARδ agonism, used clinically to treat insulin resistance, increases fat oxidation and up‐regulates mitochondrial PDK4 mRNA and protein expression in resting skeletal muscle. We hypothesized that PDK4 up‐regulation, which inhibits pyruvate dehydrogenase complex (PDC)‐dependent carbohydrate (CHO) oxidation, would negatively affect muscle function during sustained contraction where the demand on CHO is markedly increased. Three groups of eight male Wistar rats each received either vehicle or a PPARδ agonist (GW610742X) at two doses (5 and 100 mg (kg body mass (bm))−1 orally for 6 days. On the seventh day, the gastrocnemius–soleus–plantaris muscle group was isolated and snap frozen, or underwent 30 min of electrically evoked submaximal intensity isometric contraction using a perfused hindlimb model. During contraction, the rate of muscle PDC activation was significantly lower at 100 mg (kg bm)−1 compared with control (P < 0.01). Furthermore, the rates of muscle PCr hydrolysis and lactate accumulation were significantly increased at 100 mg (kg bm)−1 compared with control, reflecting lower mitochondrial ATP generation. Muscle tension development during contraction was significantly lower at 100 mg (kg bm)−1 compared with control (25%; P < 0.05). The present data demonstrate that PPARδ agonism inhibits muscle CHO oxidation at the level of PDC during prolonged contraction, and is paralleled by the activation of anaerobic metabolism, which collectively impair contractile function.
Carbohydrate sensing in the human mouth: effects on exercise performance and brain activity

Exercise studies have suggested that the presence of carbohydrate in the human mouth activates regions of the brain that can enhance exercise performance but direct evidence of such a mechanism is limited. The first aim of the present study was to observe how rinsing the mouth with solutions containing glucose and maltodextrin, disguised with artificial sweetener, would affect exercise performance. The second aim was to use functional magnetic resonance imaging (fMRI) to identify the brain regions activated by these substances. In Study 1A, eight endurance‐trained cyclists ( 60.8 ± 4.1 ml kg−1 min−1) completed a cycle time trial (total work = 914 ± 29 kJ) significantly faster when rinsing their mouths with a 6.4% glucose solution compared with a placebo containing saccharin (60.4 ± 3.7 and 61.6 ± 3.8 min, respectively, P= 0.007). The corresponding fMRI study (Study 1B) revealed that oral exposure to glucose activated reward‐related brain regions, including the anterior cingulate cortex and striatum, which were unresponsive to saccharin. In Study 2A, eight endurance‐trained cyclists ( 57.8 ± 3.2 ml kg−1 min−1) tested the effect of rinsing with a 6.4% maltodextrin solution on exercise performance, showing it to significantly reduce the time to complete the cycle time trial (total work = 837 ± 68 kJ) compared to an artificially sweetened placebo (62.6 ± 4.7 and 64.6 ± 4.9 min, respectively, P= 0.012). The second neuroimaging study (Study 2B) compared the cortical response to oral maltodextrin and glucose, revealing a similar pattern of brain activation in response to the two carbohydrate solutions, including areas of the insula/frontal operculum, orbitofrontal cortex and striatum. The results suggest that the improvement in exercise performance that is observed when carbohydrate is present in the mouth may be due to the activation of brain regions believed to be involved in reward and motor control. The findings also suggest that there may be a class of so far unidentified oral receptors that respond to carbohydrate independently of those for sweetness.
Analysing User's Queries for Cross-Language Image Retrieval from Digital Library Collections

Purpose – This paper aims to describe a study of the queries generated from a user experiment for cross‐language information retrieval (CLIR) from a historic image archive.Design/methodology/approach – A controlled lab‐based user study was carried out using a prototype Italian‐English image retrieval system. Participants were asked to carry out searches for 16 images provided to them, a known‐item search task. Italian speaking users generated 618 queries for a set of known‐item search tasks. User's interactions with the system were recorded and queries were analysed manually quantitatively and qualitatively. The queries generated by user's interaction with the system were analysed and the results used to suggest recommendations for the future development of cross‐language retrieval systems for digital image libraries.Findings – Results highlight the diversity in requests for similar visual content and the weaknesses of machine translation for query translation. Through the manual translation of queries th.
Effect of Synthesis Condition on Thermal Diffusivity of Molybdenum Thin Films Observed by a Picosecond Light Pulse Thermoreflectance Method

The relation between out-of-plane thermal diffusivity of Mo thin film and its synthesized condition is studied. Two types of molybdenum thin film with nominal 100 nm thickness are prepared, one is dc-sputtered at 0.4 Pa in Ar pressure on a Pyrex 7740 glass substrate (film A), and the other is rf-sputtered at 11 Pa in Ar pressure on the Pyrex 7740 glass substrate (film B). Each thermal diffusivity was measured by rear-heating front-detection type (RF-type) picosecond light pulse thermoreflectance method. The thermal diffusivity of film A was 3.9 ×10-5 m2·s-1 and that of film B was 4.4 ×10-6 m2·s-1. This demonstrates that the synthesis condition is strongly related to the out-of-plane thermal diffusivity and that the thermal diffusivity can become less than one-tenth of that for bulk Mo. To elucidate the heat transfer mechanism, transmission electron microscopy (TEM), X-ray diffraction (XRD), and in-plane electrical conductivity measurements were performed. Mean free paths calculated from in-plane resistivities were smaller than the grain sizes estimated from XRD peaks and TEM image. Those results suggested that not only grain boundary but also other impurities or defects might play a role as scattering objects.
Expectations on Post-college Housing and Parental Supports of Workforce Entry Preparers from Non-Capital Regions

The purpose of the study was to explore expectations of workforce entry preparers from non-capital regions on post-college housing and financial support from their parents. From July 26 to August 8, 2013, an on-line questionnaire survey was conducted to juniors and seniors in colleges nationwide and 692 useable responses were collected from college students who were from non-capital regions. Findings from this study are summarized as follows: (1) About 44% of the respondents expected to live apart from their parents and other relatives within two years from their college graduation and 48% of them expected to live in Seoul Metropolitan Area; (2) among those who expected to live apart from their parents and other relatives, 61% expected to be monthly renters; 75% expected to live in small-sized units such as studios; 85% expected parental support to afford post-college housing costs; (3) female respondents, younger respondents and/or respondents with a greater parent income showed more stronger expectation on parental support to afford housing costs; and (4) most respondents perceived influence of housing cost burden strong enough to affect their job choices.
Brain‐derived neurotrophic factor drives the changes in excitatory synaptic transmission in the rat superficial dorsal horn that follow sciatic nerve injury

Peripheral nerve injury can promote neuropathic pain. The basis of the ‘central sensitization’ that underlies this often intractable condition was investigated using 14–20‐day chronic constriction injury (CCI) of the sciatic nerve of 20‐day‐old rats followed by electrophysiological analysis of acutely isolated spinal cord slices. In addition, defined‐medium organotypic spinal cord slice cultures were exposed for 5–6 days to brain‐derived neurotrophic factor (BDNF, 200 ng ml−1) or to medium conditioned with activated microglia (aMCM). Since microglial activation is an early consequence of CCI, the latter manipulation allowed us to model the effect of peripheral nerve injury on the dorsal horn in vitro. Using whole‐cell recording from superficial dorsal horn neurons, we found that both BDNF and CCI increased excitatory synaptic drive to putative excitatory ‘radial delay’ neurons and decreased synaptic excitation of inhibitory ‘tonic islet/central’ neurons. BDNF also attenuated synaptic excitation of putative GABAergic neurons identified by glutamic acid decarboxylase (GAD) immunoreactivity. Intrinsic neuronal properties (rheobase, input resistance and action potential discharge rates) were unaffected. Exposure of organotypic cultures to either BDNF or aMCM increased overall excitability of the dorsal horn, as seen by increased cytoplasmic Ca2+ responses to 35 mm K+ as monitored by confocal Fluo‐4AM imaging. The effect of aMCM was attenuated by the recombinant BDNF binding protein TrkBd5 and the effect of BDNF persisted when GABAergic inhibition was blocked with SR95531. These findings suggest that CCI enhances excitatory synaptic drive to excitatory neurons but decreases that to inhibitory neurons. Both effects are mediated by nerve injury‐induced release of BDNF from microglia.
Dynamic pressure–flow relationship of the cerebral circulation during acute increase in arterial pressure

The physiological mechanism(s) for the regulation of the dynamic pressure–flow relationship of the cerebral circulation are not well understood. We studied the effects of acute cerebral vasoconstriction on the transfer function between spontaneous changes in blood pressure (BP) and cerebral blood flow velocity (CBFV) in 13 healthy subjects (30 ± 7 years). CBFV was measured in the middle cerebral artery using transcranial Doppler. BP was increased stepwise with phenylephrine infusion at 0.5, 1.0 and 2.0 μg kg–1 min–1. Phenylephrine increased BP by 11, 23 and 37% from baseline, while CBFV increased (11%) only with the highest increase in BP. Cerebrovascular resistance index (BP/CBFV) increased progressively by 6, 17 and 23%, demonstrating effective steady‐state autoregulation. Transfer function gain at the low frequencies (LF, 0.07–0.20 Hz) was reduced by 15, 14 and 14%, while the phase was reduced by 10, 17 and 31%. A similar trend of changes was observed at the high frequencies (HF, 0.20–0.35 Hz), but gain and phase remained unchanged at the very low frequencies (VLF, 0.02–0.07 Hz). Windkessel model simulation suggests that increases in steady‐state cerebrovascular resistance and/or decreases in vascular compliance during cerebral vasoconstriction contribute to the changes in gain and phase. These findings suggest that changes in steady‐state cerebrovascular resistance and/or vascular compliance modulate the dynamic pressure–flow relationship at the low and high frequencies, while dynamic autoregulation is likely to be dominant at the very low frequencies. Thus, oscillations in CBFV are modulated not only by dynamic autoregulation, but also by changes in steady‐state cerebrovascular resistance and/or vascular compliance.
Divergent regulation of cardiac KCND3 potassium channel expression by the thyroid hormone receptors α1 and β1

The cardiac transient outward current Ito is regulated by thyroid hormone (T3). However, it remains unclear whether T3 directly modulates underlying gene transcription and which thyroid receptor (TR) isoform might be responsible for gene transactivation. To clarify this situation, we analysed the role of T3 and its receptors α1 (TRα1) and β1 (TRβ1) in regulation of KCNA4, KCND2, KCND3 and KCNIP2 transcription in rat cardiomyocytes. Initial results demonstrated a T3‐mediated increase of Ito current density. T3 stimulation enhanced KCND2 and KCND3 expression and decreased KCNA4 transcription, while KCNIP2 remained unaffected. To dissect the role of TRα1 and TRβ1 in T3‐dependent Ito modulation, TRα1 and TRβ1 were overexpressed in cardiomyocytes by adenovirus‐mediated gene transfer. TRα1 increased Ito, while TRβ1 significantly reduced Ito in size, which was associated with TRα1‐mediated increase and TRβ1‐mediated reduction of KCND2/3 transcription. To further evaluate a possible direct interaction of TRα1 and TRβ1 with the KCND3 promoter, TR expression vectors were cotransfected with a construct containing 2335 bp of the KCND3 5′‐flanking sequence linked to a luciferase reporter into ventricular myocytes. While the TRα1 aporeceptor enhanced KCND3 transcription, the TRβ1 aporeceptor suppressed KCND3 expression, with both effects exhibiting ligand‐dependent amplification upon T3 stimulation. Deletion of the KCND3 5′‐flanking region localized the suppressible promoter sequence for TRβ1 to within −293 bp and the activating promoter sequence for TRα1 to within −2335 to −1654 bp of the transcription start site. Disruption of putative TR binding sites by mutagenesis abolished the TRα1‐ (G‐1651T) and TRβ1‐ (G‐73T) mediated effects, indicating that TRα1 and TRβ1 response elements map to different regions of the KCND3 promoter. Thus, Ito is modulated by diverse T3‐dependent regulation of underlying gene transcription. TRα1 and TRβ1 exhibit distinct effects on KCND3 transactivation with TRα1 enhancing and TRβ1 suppressing KCND3 transcription.
Fetal cerebral blood flow, electrocorticographic activity, and oxygenation: responses to acute hypoxia

Arterial blood gases are critical in regulation of cerebral blood flow (CBF) and cerebral metabolic rate for O2 (CMRO2). However, the relation of these variables to cortical tissue (t), and electrocorticographic (ECoG) activity (high voltage low frequency, HVLF, versus low voltage high frequency, LVHF), are not well defined. In the fetus, we tested the hypothesis that ECoG pattern is associated closely with cerebral oxygenation. In fetal sheep (n= 8) with laser Doppler flowmeter, fluorescent O2 probe and ECoG electrodes, we measured laser Doppler CBF (LD‐CBF), t, ECoG and spectral edge frequency‐90 (SEF90) in response to 40 min isocapnic hypoxia. In the normoxic fetus, LD‐CBF and CMRO2 correlated highly with ECoG state. With a shift from HVLF to LVHF, t decreased followed by increased LD‐CBF (18%) and CMRO2 (13%). With acute hypoxia (= 12 ± 1 Torr), t decreased to ∼3 Torr, LD‐CBF increased 48 ± 10%, ECoG shifted to chiefly the HVLF state, SEF90 decreased ∼15%, and CMRO2 decreased ∼20% (P < 0.05 for each). For the normoxic fetus, CBF was closely related to ECoG state, but this association was less evident during acute hypoxia. We speculate that, in the otherwise stressed fetus, acute hypoxia may further compromise cerebral oxygenation.
Anthraquinonedisulfonate electrochemistry:  a comparison of glassy carbon, hydrogenated glassy carbon, highly oriented pyrolytic graphite, and diamond electrodes.

The electrochemistry of anthraquinone-2,6-disulfonate (2,6-AQDS) at glassy carbon (GC), hydrogenated glassy carbon (HGC), the basal plane of highly oriented pyrolytic graphite (HOPG), and boron-doped diamond was investigated by cyclic voltammetry and chronocoulometry. Quantitative determination of the surface coverage and qualitative assessment of the physisorption strength of 2,6-AQDS adsorption on each of these electrodes were done. The diamond and HGC surfaces are nonpolar and relatively oxygen-free, with the surface carbon atoms terminated by hydrogen. The polar 2,6-AQDS does not adsorb on these surfaces, and the electrolysis proceeds by a diffusion-controlled reaction. Conversely, the GC and HOPG surfaces are polar, with the exposed defect sites terminated by carbon-oxygen functionalities. 2,6-AQDS strongly physisorbs on both of these surfaces at near monolayer or greater coverages, such that the electrolysis proceeds through a surface-confined state. Less than 40% of the initial surface coverage can be removed by rinsing and solution replacement, reflective of strong physisorption. The results show the important role of the surface carbon-oxygen functionalities in promoting strong dipole-dipole and ion-dipole interactions with polar and ionic molecules such as 2,6-AQDS. The results also support the theory that diamond electrodes may be less subject to fouling by polar adsorbates, as compared to GC, leading to improved response stability in electroanalytical measurements. The relationship between the 2,6-AQDS surface coverage, the double-layer capacitance, and the heterogeneous electron-transfer rate constant for Fe(CN)(6)(3)(-)(/4)(-) for these four carbon electrodes is presented.
Direct evidence of nitric oxide release from neuronal nitric oxide synthase activation in the left ventricle as a result of cervical vagus nerve stimulation

Information regarding vagal innervation in the cardiac ventricle is limited and the direct effect of vagal stimulation on ventricular myocardial function is controversial. We have recently provided indirect evidence that the anti‐fibrillatory effect of vagus nerve stimulation on the ventricle is mediated by nitric oxide (NO). The aim of this study was to provide direct evidence for the release of nitric oxide in the cardiac ventricle during stimulation of the efferent parasympathetic fibres of the cervical vagus nerve. The isolated innervated rabbit heart was employed with the use of the NO fluorescent indicator 4,5‐diaminofluorescein diacetate (DAF‐2 DA) during stimulation of the cervical vagus nerves and acetylcholine perfusion in the absence and presence of the non‐specific NO synthase inhibitor NG‐nito‐l‐arginine (l‐NNA) and the neuronal NO synthase selective inhibitor 1‐(2‐trifluormethylphenyl)imidazole (TRIM). Using the novel fluorescence method in the beating heart, we have shown that NO‐dependent fluorescence is increased by 0.92 ± 0.26, 1.20 ± 0.30 and 1.91 ± 0.27% (during low, medium and high frequency, respectively) in the ventricle in a stimulation frequency‐dependent manner during vagus nerve stimulation, with comparable increases seen during separate stimulation of the left and right cervical vagus nerves. Background fluorescence is reduced during perfusion with l‐NNA and the increase in fluorescence during high frequency vagal stimulation is inhibited during perfusion with both l‐NNA (1.97 ± 0.35% increase before l‐NNA, 0.00 ± 0.02% during l‐NNA) and TRIM (1.78 ± 0.18% increase before TRIM, −0.11 ± 0.08% during TRIM). Perfusion with 0.1 μm acetylcholine increased NO fluorescence by 0.76 ± 0.09% which was blocked by l‐NNA (change of 0.00 ± 0.03%) but not TRIM (increase of 0.82 ± 0.21%). Activation of cardiac parasympathetic efferent nerve fibres by stimulation of the cervical vagus is associated with NO production and release in the ventricle of the rabbit, via the neuronal isoform of nitric oxide synthase.
Motoneuron survival is promoted by specific exercise in a mouse model of amyotrophic lateral sclerosis

Several studies using transgenic mouse models of familial amyotrophic lateral sclerosis (ALS) have reported a life span increase in exercised animals, as long as animals are submitted to a moderate‐intensity training protocol. However, the neuroprotective potential of exercise is still questionable. To gain further insight into the cellular basis of the exercise‐induced effects in neuroprotection, we compared the efficiency of a swimming‐based training, a high‐frequency and ‐amplitude exercise that preferentially recruits the fast motor units, and of a moderate running‐based training, that preferentially triggers the slow motor units, in an ALS mouse model. Surprisingly, we found that the swimming‐induced benefits sustained the motor function and increased the ALS mouse life span by about 25 days. The magnitude of this beneficial effect is one of the highest among those induced by any therapeutic strategy in this disease. We have shown that, unlike running, swimming significantly delays spinal motoneuron death and, more specifically, the motoneurons of large soma area. Analysis of the muscular phenotype revealed a swimming‐induced relative maintenance of the fast phenotype in fast‐twitch muscles. Furthermore, the swimming programme preserved astrocyte and oligodendrocyte populations in ALS spinal cord. As a whole, these data are highly suggestive of a causal relationship not only linking motoneuron activation and protection, but also motoneuron protection and the maintenance of the motoneuron surrounding environment. Basically, exercise‐induced neuroprotective mechanisms provide an example of the molecular adaptation of activated motoneurons.
Odor Perception by Dogs: Evaluating Two Training Approaches for Odor Learning of Sniffer Dogs

In this study, a standardized experimental set-up with various combinations of herbs as odor sources was designed. Two training approaches for sniffer dogs were compared; first, training with a pure reference odor, and second, training with a variety of odor mixtures with the target odor as a common denominator. The ability of the dogs to identify the target odor in a new context was tested. Six different herbs (basil, St. John's wort, dandelion, marjoram, parsley, ribwort) were chosen to produce reference materials in various mixtures with (positive) and without (negative) chamomile as the target odor source. The dogs were trained to show 1 of 2 different behaviors, 1 for the positive, and 1 for the negative sample as a yes/no task. Tests were double blind with one sample presented at a time. In both training approaches, dogs were able to detect chamomile as the target odor in any presented mixture with an average sensitivity of 72% and a specificity of 84%. Dogs trained with odor mixture containing the target odor had more correct indications in the transfer task.
Co‐regulation of ocular dominance plasticity and NMDA receptor subunit expression in glutamic acid decarboxylase‐65 knock‐out mice

Experience can shape cortical circuits, especially during critical periods for plasticity. In visual cortex, imbalance of activity from the two eyes during the critical period shifts ocular dominance (OD) towards the more active eye. Inhibitory circuits are crucial in this process: OD plasticity is absent in GAD65KO mice that show diminished inhibition. This defect can be rescued by application of benzodiazepines, which increase GABAergic signalling. However, it is unknown how such changes in inhibition might disrupt and then restore OD plasticity. Since NMDA dependent synaptic plasticity mechanisms are also known to contribute to OD plasticity, we investigated whether NMDA receptor levels and function are also altered in GAD65KO. There are reduced NR2A levels and slower NMDA currents in visual cortex of GAD65KO mice. Application of benzodiazepines, which rescues OD plasticity, also increases NR2A levels. Thus it appears as if OD plasticity can be restored by adding a critical amount of excitatory transmission through NR2A‐containing NMDA receptors. Together, these observations can unify competing ideas of how OD plasticity is regulated: changes in either inhibition or excitation would engage homeostatic mechanisms that converge to regulate NMDA receptors, thereby enabling plasticity mechanisms and also ensuring circuit stability.