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Background: Catecholamines increase heart rate by augmenting the cAMP-responsive hyperpolarization-activated cyclic nucleotide-gated channel 4 pacemaker current (I(f)) and by promoting inward Na(+)/Ca(2+) exchanger current (I(NCX)) by a "Ca(2+) clock" mechanism in sinoatrial nodal cells (SANCs). The importance, identity, and function of signals that connect I(f) and Ca(2+) clock mechanisms are uncertain and controversial, but the multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is required for physiological heart rate responses to β-adrenergic receptor (β-AR) stimulation. The aim of this study was to measure the contribution of the Ca(2+) clock and CaMKII to cardiac pacing independent of β-AR agonist stimulation.Methods and Results: We used the L-type Ca(2+) channel agonist Bay K8644 (BayK) to activate the SANC Ca(2+) clock. BayK and isoproterenol were similarly effective in increasing rates in SANCs and Langendorff-perfused hearts from wild-type control mice. In contrast, SANCs and isolated hearts from mice with CaMKII inhibition by transgenic expression of an inhibitory peptide (AC3-I) were resistant to rate increases by BayK. BayK only activated CaMKII in control SANCs but increased L-type Ca(2+) current (I(Ca)) equally in all SANCs, indicating that increasing I(Ca) was insufficient and suggesting that CaMKII activation was required for heart rate increases by BayK. BayK did not increase I(f) or protein kinase A-dependent phosphorylation of phospholamban (at Ser16), indicating that increased SANC Ca(2+) by BayK did not augment cAMP/protein kinase A signaling at these targets. Late-diastolic intracellular Ca(2+) release and I(NCX) were significantly reduced in AC3-I SANCs, and the response to BayK was eliminated by ryanodine in all groups.Conclusions: The Ca(2+) clock is capable of supporting physiological fight-or-flight responses, independent of β-AR stimulation or I(f) increases. Complete Ca(2+) clock and β-AR stimulation responses require CaMKII. [ABSTRACT FROM AUTHOR]

Objective: Sulfonylureas have been used to improve performance in strength sports. However, this hypothetical effect has not been proven. We examined the ergogenic acute effect of gliclazide on resistance training performance and muscle recovery., Subjects and Methods: We conducted a double-blind, randomized, crossover pilot study with 10 healthy resistance-trained adults (29.3 ± 4.4 years), nonusers of anabolic steroids. The participants were randomized to two exercise sessions. In the first session, five participants received placebo and the other five received gliclazide modified release, both administered 8 hours before the session. Session two was performed in a crossover fashion a week later. The volume load was calculated as the maximum number of repetitions of four sets multiplied by load (65% 1-RM). Blood samples were collected before and after exercise, as well as 24 hours and 48 hours after exercise for measurement of creatine kinase (CK-MM) and lactate dehydrogenase (LDH) activity. Blood glucose was measured with a glucometer before, during, and after the exercise sessions., Results: Gliclazide did not enhance volume load for bench press (placebo: 2,698.0 ± 923.0 kg; gliclazide: 2,675.0 ± 1,088.0 kg; p = 0.073) or leg press (placebo: 10,866.0 ± 2,671.0 kg; gliclazide: 10,817.0 ± 2,888.0 kg; p = 0.135). However, CK-MM (-27.7%; p = 0.034) and LDH (-21.1%; p = 0.021) activities were decreased with gliclazide 48 hours after exercise. There was also a decrease in blood glucose in the gliclazide compared with the placebo session (p = 0.018)., Conclusion: Gliclazide did not enhance performance in a single resistance training session, but promoted faster muscle recovery. The decrease in blood glucose post-exercise with gliclazide was an undesirable effect that could lead to long-term glucose metabolism disorders. Registered in ClinicalTrials.gov under number NCT04443777., Competing Interests: Competing interests: the authors declare that they have no competing interests. Disclosure: no potential conflict of interest relevant to this article was reported.

X-ray photoelectron spectroscopy (XPS) and reflection electron energy loss spectroscopy (REELS) were employed to characterize the electronic properties of Prussian blue (PB) and its analogs when electrodeposited over metal-decorated carbon nanotubes (CNTs). Through an investigation of the influence of carbon nanotubes (CNTs) and preparation conditions on the electronic structure, valuable insights were obtained regarding their effects on electrochemical properties. XPS analysis enabled the probing of the chemical composition and oxidation states of the film materials, unveiling synthesis-driven variations in their electronic properties. REELS provided information on energy loss and electronic transitions, enabling further characterization of the changes in the electronic structure induced by different preparation methods. Such findings emphasize the importance of surface characterization to understand how the unique electronic properties of such materials can be harnessed to enhance their performance and functionality., (© 2023 Wiley-VCH GmbH.)

We explore ultrafast charge transfer (CT) resonantly induced by hard X-ray radiation in organic thiophene-based polymers at the sulfur K-edge. A combination of core-hole clock spectroscopy with real-time propagation time-dependent density functional theory simulations gives an insight into the electron dynamics underlying the CT process. Our method provides control over CT by a selective excitation of a specific resonance in the sulfur atom with monochromatic X-ray radiation. Our combined experimental and theoretical investigation establishes that the dominant mechanism of CT in polymer powders and films consists of electron delocalisation along the polymer chain occurring on the low-femtosecond time scale.

Background/objective: Guidelines on obesity management reinforce regular exercise to reduce body fat. Exercise modalities, including high-intensity interval training (HIIT), appear to produce a similar effect to continuous aerobic training (CAT) on body fat. However, they have not addressed the chronic effect of HIIT vs. CAT on body fat assessed by dual energy X-ray absorptiometry (DEXA). Thus, we compared the effectiveness of CAT vs. HIIT protocols on body fat (absolute or relative) (%BF) and abdominal visceral fat reduction, assessed by DEXA, in adults with overweight and obesity., Methods: We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) including both female or male adults with excess body weight. We performed searches in the databases MEDLINE (PubMed), EMBASE, Scopus, LILACS, Web of Science and Cochrane., Results: In our analysis (11 RCTs), we found no greater benefit on %BF of HIIT vs. CAT (MD -0.55%, 95% CI -1.42 to 0.31; p = 0.209). As for abdominal visceral fat, no training modality was superior (SMD: -0.05, 95% CI -0.29 to 0.19; p = 0.997). Regarding secondary outcomes (body weight, BMI, VO 2 max, glycemic and lipid profiles), HIIT shows greater benefit than CAT in increasing VO 2 max and fasting blood glucose and reducing total cholesterol., Conclusion: HIIT is not superior to CAT in reducing %BF or abdominal visceral fat in individuals characterized by excess weight. However, HIIT showed beneficial effects on cardiorespiratory fitness, total cholesterol and fasting blood glucose when compared to CAT., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Society of Chinese Scholars on Exercise Physiology and Fitness. Published by Elsevier (Singapore) Pte Ltd.)

Background: Breast cancer treatment leads to several side effects. Exercise can help to reduce these side effects. However, it is unknown whether a mat Pilates or a belly dance intervention can improve the patient-reported outcomes of these women., Objective: Examine the effects of a 16-week exercise intervention (mat Pilates or belly dance) on patient reported outcomes (PROs) among breast cancer survivors, at 16 weeks, six months, and 12 months; and investigate sociodemographic and clinical predictors of intervention adherence., Methods: Seventy-four breast cancer survivors who were receiving hormone therapy were randomly allocated into mat Pilates (n = 25), belly dance (n = 25) or control group (educational sessions) (n = 24). Mat Pilates and belly dance groups received a 16-week intervention, delivered three days a week and 60 min a session. The control group received three education sessions and continue usual care. The patient reported outcomes assessed were depressive symptoms (Beck Depression Inventory), stress (Perceived Stress Scale), optimism (Life Orientation Test), fatigue (FACT-F), sleep quality (Pittsburgh Sleep Quality Index) and pain (VAS), clinical and sociodemographic characteristics, and habitual physical activity (IPAQ short)., Results: All three groups showed a significant improvement in fatigue, and this effect was maintained during follow-up. No significant effects were found for depressive symptoms, optimism, stress, or pain. A history of exercise prior to breast cancer and be inactive after diagnosis were significant predictors of adherence to interventions., Conclusion: Mat Pilates, belly dance and a few educational sessions can be effective in improving fatigue after 16 weeks of intervention., Registration: ClinicalTrials.gov (NCT03194997)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: We previously reported that datumetine possesses binding affinity with N-methyl-D-aspartate receptor (NMDAR) and that 14-day exposure to datumetine altered NMDAR signaling by mimicking glutamate toxicity. Here, we investigated the potential neuroprotective effect of a single shot of a low dose of datumetine administration in BALB/c mice., Methods: 30 male adult BALB/c mice were used for the study. The mice were randomly divided into three groups of ten mice each with an intraperitoneal injection of 0.1 mL of 10% DMSO for the Vehicle group, Datumetine group were administered 0.1 mg/kg body weight (bw) of datumetine and MK-801+Datumetine group were administered 0.5 mg/kg bw of MK-801 (to block NMDAR) followed by 0.1 mg/kg bw of datumetine after 30 minutes. 24 hours after administration, mice were euthanized in an isoflurane chamber followed by perfusion with 1X PBS. Brains were excised and stored at -20°C till further processing. Mice designated for IHC were further perfused with 4% PFA and brain excised and stored in 4% PFA till further processing. NMDAR signalling molecules expression was evaluated in frozen brain samples and the fixed brain samples were stained for neuron, vGlut and NMDAR subtypes., Results: Relative to vehicle (Veh), datumetine downregulate calcium calmodulin kinase II alpha (CamKIIα) expression in the hippocampus and prefrontal cortex (PFC) but not in the cerebellum, cyclic AMP response element binding protein (CREB) was also upregulated only in the PFC but phosphorylated CREB (pCREB) was also upregulated in three brain regions observed, while brain-derived neurotrophic factor (BDNF) was only upregulated in hippocampus and PFC of Datumetine relative to vehicle (Veh). On the other hand, dizocilpine (MK-801) reversed some of the effects of datumetine in the observed brain regions. No major histological alterations were observed in the different brain regions immunohistochemically., Conclusion: We conclude that a low dose of datumetine moderately enhances NMDAR activity. This showed the neuroprotective potentials of low datumetine exposure., Competing Interests: Conflict of interest The authors declared no conflict of interest., (Copyright© 2023 Iranian Neuroscience Society.)

We propose a novel approach for an indirect probing of conjugation and hyperconjugation in core-excited molecules using resonant Auger spectroscopy. Our work demonstrates that the changes in the electronic structure of thiophene (C 4 H 4 S) and thiazole (C 3 H 3 NS), occurring in the process of resonant sulfur K-shell excitation and Auger decay, affect the stabilisation energy resulting from π-conjugation and hyperconjugation. The variations in the stabilisation energy manifest themselves in the resonant S KL 2,3 L 2,3 Auger spectra of thiophene and thiazole. The comparison of the results obtained for the conjugated molecules and for thiolane (C 4 H 8 S), the saturated analogue of thiophene, has been performed. The experimental observations are interpreted using high-level quantum-mechanical calculations and the natural bond orbital analysis.

Using synchrotron radiation in the tender X-ray regime, a photoelectron spectrum showing the formation of single site double-core-hole pre-edge states, involving the K shell of the O atom in CO, has been recorded by means of high-resolution electron spectroscopy. The experimentally observed structures have been simulated, interpreted and assigned, employing state-of-the-art ab initio quantum chemical calculations, on the basis of a theoretical model, accounting for their so-called direct or conjugate character. Features appearing above the double ionization threshold have been reproduced by taking into account the strong mixing between multi-excited and continuum states. The shift of the σ* resonance below the double ionization threshold, in combination with the non-negligible contributions of multi-excited configurations in the final states reached, gives rise to a series of avoided crossings between the different potential energy curves.

Objective: Adaptive changes in DHEA and sulfated-DHEA (DHEAS) production from adrenal zona reticularis (ZR) have been observed in normal and pathological conditions. Here we used three different cohorts to assess timing differences in DHEAS blood level changes and characterize the relationship between early blood DHEAS reduction and cell number changes in women ZR., Materials and Methods: DHEAS plasma samples (n = 463) were analyzed in 166 healthy prepubertal girls before pubarche (<9 years) and 324 serum samples from 268 adult females (31.9-83.8 years) without conditions affecting steroidogenesis. Guided by DHEAS blood levels reduction rate, we selected the age range for ZR cell counting using DHEA/DHEAS and phosphatase and tensin homolog (PTEN), tumor suppressor and cell stress marker, immunostaining, and hematoxylin stained nuclei of 14 post-mortem adrenal glands., Results: We confirmed that overweight girls exhibited higher and earlier DHEAS levels and no difference was found compared with the average European and South American girls with a similar body mass index (BMI). Adrenopause onset threshold (AOT) defined as DHEAS blood levels <2040 nmol/L was identified in >35% of the females >40 years old and associated with significantly reduced ZR cell number (based on PTEN and hematoxylin signals). ZR cell loss may in part account for lower DHEA/DHEAS expression, but most cells remain alive with lower DHEA/DHEAS biosynthesis., Conclusion: The timely relation between significant reduction of blood DHEAS levels and decreased ZR cell number at the beginning of the 40s suggests that adrenopause is an additional burden for a significant number of middle-aged women, and may become an emergent problem associated with further sex steroids reduction during the menopausal transition.

Polymyxins (colistin and polymyxin B) have recently regained significant importance as last-line drugs to treat infectious diseases due to multidrug-resistant gram-negative bacteria. However, resistance to polymyxins has increased, and the recognition of plasmid-mediated resistance (by the mcr gene) has led to an epidemiological concern. We aimed to evaluate the reduction of the polymyxin B minimum inhibitory concentration (MIC) in the presence of EDTA or dipicolinic acid (DPA) by using the broth microdilution (BMD) method for phenotypic screening of acquired polymyxin resistance mediated by the mcr -1 gene. Overall, 94 Enterobacterales (48 polymyxin-resistant and 46 polymyxin-susceptible) were evaluated: 47 mcr -1 positive (36 Escherichia coli , 2 Klebsiella pneumoniae , and 9 Salmonella spp.) and 47 mcr -1 negative (3 E. coli and 44 K. pneumoniae- 27 isolates with MIC from ≤0.125 to 8 μg/mL and 20 isolates with MIC from 16 to 64 μg/mL). Results were categorized as positive when the chelator decreased the original BMD MIC by ≥2 logs. The majority (95.7%) of mcr -1 positive isolates displayed at least a 3 log dilution decrease in the MIC of polymyxin B with EDTA or DPA. The EDTA-based BMD assay detected 45 mcr -1-positive isolates, with only one false-positive among the mcr -1-negative isolates (sensitivity [SN], 95.7%; specificity [SP], 97.9%), whereas the DPA-based BMD assay detected 44 mcr -1-positive isolates (SN, 93.6%; SP, 95.7%), with two false-positive results. The accuracy of EDTA- and DPA-based BMD assays were 97% and 95%, respectively. The EDTA- and DPA-based assays were demonstrated to be reliable methods to detect mcr -1 positive isolates with excellent accuracy.

Background: Knee osteoarthritis ( k OA) is a common chronic disease that induces changes in redox status and inflammatory biomarkers, cell death, and motor impairment. Aerobic training can be a non-pharmacological alternative to prevent the progression of the disease., Objective: To evaluate the effects of an 8 weeks moderate-intensity treadmill aerobic training program on redox status and inflammatory biomarkers and motor performance in k OA-like changes induced by monosodium iodoacetate (MIA) in rats., Methods: Twenty-seven rats were randomly divided into three groups: SHAM; induced k OA (OA); and induced k OA + aerobic training (OAE). Motor performance was evaluated by the number of falls on rotarod test, the total time of displacement and the number of failures on a 100 cm footbridge. Data for cytokines and histology were investigated locally, whereas plasma was used for redox status biomarkers., Results: The OA group, compared to the SHAM group, increased 1.13 times the total time of displacement, 6.05 times the number of failures, 2.40 times the number of falls. There was also an increase in cytokine and in thiobarbituric acid reactive substances (TBARS) (IL1β: 5.55-fold, TNF: 2.84-fold, IL10: 1.27-fold, IL6: 1.50-fold, TBARS: 1.14-fold), and a reduction of 6.83% in the total antioxidant capacity (FRAP), and of 35% in the number of chondrocytes. The aerobic training improved the motor performance in all joint function tests matching to SHAM scores. Also, it reduced inflammatory biomarkers and TBARS level at values close to those of the SHAM group, with no change in FRAP level. The number of falls was explained by IL1β and TNF (58%), and the number of failures and the total time of displacement were also explained by TNF (29 and 21%, respectively)., Conclusion: All findings indicate the efficacy of moderate-intensity aerobic training to regulate inflammatory biomarkers associated with improved motor performance in induced k OA-like changes, thus preventing the loss of chondrocytes., (Copyright © 2019 Martins, Mendonça, Aguiar, Fonseca, Santos, Tossige-Gomes, Melo, Oliveira, Leite, Camargos, Ferreira, Coimbra, Poortmans, Oliveira, Silva, Domingues, Bernardo-Filho and Lacerda.)

This study evaluated the biocompatibility of a new silicone-based sealer (GuttaFlow Bioseal) in rat subcutaneous tissue and compared the results with those for GuttaFlow2 and AH Plus. Each of 16 Wistar rats received four subcutaneous tissue implants, namely, GuttaFlow Bioseal, GuttaFlow2, AH Plus, and one empty polyethylene tube. Eight rats were euthanized at day 8 and the remaining eight at day 30. Histological sections were stained with haematoxylin and eosin and analysed with a light microscope. Scores were established for inflammatory reaction, macrophage infiltrate, thickness of the fibrous capsule, and vascular changes. Differences between groups were assessed by using the Friedman test with Bonferroni correction. Histological analysis showed that GuttaFlow Bioseal had the lowest inflammatory reaction of all tested sealers at day 8. At day 30, the silicone-based sealers had similar inflammation profiles, but inflammation scores were nonsignificantly higher for AH Plus than for the negative control. The inflammatory reaction decreased from day 8 to day 30 in all sealers. GuttaFlow Bioseal had the most macrophage infiltrate. Under the present experimental conditions, GuttaFlow Bioseal induced limited inflammatory reactions at days 8 and 30, and initial inflammatory reactions to GuttaFlow2 and AH Plus subsided within 30 days. All tested sealers exhibited satisfactory biocompatibility at day 30 after subcutaneous implantation.

The objective of this study was to investigate the effect of whole body vibration (WBV) exercise on oxidative stress markers in a group of women with fibromyalgia (FM) compared to a group of healthy women (CT). Twenty-one women diagnosed with FM and 21 age- and weight-matched healthy women were enrolled the study. Plasma oxidative stress markers (primary outcomes) were evaluated at rest and after WBV, and included thiobarbituric acid reactive substances (TBARS), iron reduction capacity (FRAP), superoxide dismutase antioxidant enzymes activity (SOD), and catalase (CAT). At rest, the FM group had higher TBARS (P<0.001) and FRAP (P<0.001), and lower CAT (P=0.005) compared to the CT. In the CT group, the WBV had no effect on TBARS (P=0.559) and FRAP (P=0.926), whereas it increased both SOD (P<0.001) and CAT (P<0.001). In the FM group, the WBV reduced TBARS (p <0.001), FRAP (P<0.001), and CAT (P=0.005), while it increased SOD (P=0.019). There was an interaction effect (moments vs groups) in the TBARS (effect size=1.34), FRAP (effect size=0.93), CAT (effect size=1.45), and SOD (effect size=1.44) (P<0.001). A single trial of WBV exercise improved all oxidant and antioxidant parameters towards a greater adaptation to the stress response in FM women.

There is evidence that central cholinergic stimulation increases heat dissipation in normotensive rats besides causing changes on the cardiovascular system via modulation of baroreceptors activity. However, the contribution of the central cholinergic system on thermoregulatory responses and its relationship with cardiovascular adjustments in spontaneously hypertensive rats (SHRs), an animal model of reduced baroreceptor sensitivity and thermoregulatory deficit, has not been completely clarified. Therefore, the aim of this study was to verify the involvement of the central cholinergic system in cardiovascular and thermoregulatory adjustments in SHRs. Male Wistar rats (n = 17) and SHRs (n = 17) were implanted with an intracerebroventricular cannula for injections of 2 µL of physostigmine (phy) or saline solution. Tail temperature (T tail ), internal body temperature (T int ), systolic arterial pressure (SAP), heart rate (HR) and metabolic rate were registered during 60 min while the animals remained at rest after randomly receiving the injections. The variability of the SAP and the HR was estimated by the fast Fourier transform. Phy treatment began a succession of cardiovascular and thermoregulatory responses that resulted in increased SAP, reduced HR and increased T tail in both Wistar and SHRs groups. The magnitude of these effects seems to be more intense in SHRs, since the improvement of heat dissipation reflected in T int . Taken together, these results provide evidence that hypertensive rats present greater cardiovascular and thermoregulatory responses than normotensive rats after central cholinergic stimulation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: Evaluate and compare the isolated and combined effects of Inspiratory Muscle Training (IMT) and Aerobic Training (AT) on respiratory and functional parameters, inflamatory biomarkers, redox status and health-related quality of life (HRQoL) in hemodialysis patients., Methods: A randomised controlled trial with factorial allocation and intention-to-treat analysis was performed in hemodialysis patients. Volunteers were randomly assigned to performe 8-weeks of IMT at 50% of maximal inspiratory pressure (MIP), low intensity AT or combined training (CT). Before the interventions, all the volunteers went 8-weeks through a control period (without training). Measures are taken at baseline, 8-week (after control period) and 16-week (after the interventions). Primary outcomes were functional capacity (incremental shuttle walk test), MIP and lower limbs strength (Sit-to-Stand test of 30 seconds). Plasma levels of interleukin-6 (IL-6), soluble tumor necrosis factor receptor 1 (sTNFR1) and 2 (sTNFR2), adiponectin, resistin and leptin, redox status parameters and HRQoL (KDQOL-SF questionnaire) were the scondary outcomes. Data analyses were performed by two-way repeated measurements ANOVA., Results: 37 hemodialysis patients aged 48.2 years old (IC95% 43.2-54.7) were randomized. Increase of MIP, functional capacity, lower limbs strength and resistin levels, and reduction of sTNFR2 levels in 16-week, compared to baseline and 8-week, were observed in all the groups (p<0.001). IMT improved functional capacity, MIP and lower limbs strength in 96.7m (IC95% 5.6-189.9), 34.5cmH2O (IC95% 22.4-46.7) and 2.2repetitions (IC95% 1.1-3.2) respectively. Increase in resistin leves and reduction in sTNFR2 leves after IMT was 0.8ng/dL (IC95% 0.5-1.1) and 0.8ng/dL (IC95% 0.3-1.3), respectively, without between-group differences. Compared to baseline and 8-week, adiponectin levels (p<0.001) and fatigue domain of the HRQoL (p<0.05) increased in 16-week only in CT., Conclusion: IMT, AT and CT improved functional parameters and modulated inflammatory biomarkers, in addition, IMT provoked a similar response to low intensity AT in hemodialysis patients., Trial Registration: Registro Brasileiro de Ensaios clínicos RBR-4hv9rs., Competing Interests: The authors have declared that no competing interests exist.

Whole-body vibration (WBV) has gained prominence in the rehabilitation of individuals with chronic obstructive pulmonary disease (COPD) because it is a safe and low intensity exercise that promises beneficial effects on physical performance and quality of life. However, its effects on plasma cytokine levels in COPD are still unclear. The aim of the current study was to investigate the acute effects of WBV on inflammatory biomarkers in people with COPD. Twenty-six participants, COPD people (n=13) and healthy controls (n=13), were included. Both groups performed WBV at amplitude of 2 mm and frequency of vibration of 35 Hz, during six series of 30 seconds. They were assessed for lung function, body composition, 6-minute walking test (6MWT), handgrip strength test, plasma concentrations of interleukin (IL), IL-6, IL-8, and IL-10, and soluble tumor necrosis factor alpha (TNF- α ) receptors (sTNFR-1 and sTNFR-2). People with COPD had moderate disease [forced expiratory volume in the first second (FEV 1 ) = 58.1%], as well as a worse performance in the 6MWT. The plasma cytokine profile at rest showed that participants with COPD had higher levels of IL-8 and lower levels of IL-10. After one session of WBV, we found an increased plasma IL-10 level in the COPD group, with similar levels for healthy controls. One session of WBV modified the plasma IL-10 level. No effects were found on the other investigated cytokines.

Although High Intensity Interval Training (HIIT) are being associated to increase cardiovascular and metabolic adaptation, there is controversy and limited information about the effects of HIIT on hippocampal oxidative stress, pro- and anti-inflammatory cytokines balance and neurotrophic status. Thus, this study evaluated the effects of six weeks of HIIT on hippocampal redox state (oxidative damage and enzymatic and non-enzymatic antioxidant defenses), neuroimmune mediators (TNFα, IL-6, IL-1β and IL-10) and brain-derived neurotrophic (BDNF) levels. After six weeks of HIIT young adults male Wistar rats presented reduced oxidative damage and increased enzymatic (superoxide dismutase) and non-enzymatic activity in hippocampus. Moreover HIIT induced a decrease in cytokine content (TNFα, IL-6, IL-1β and IL-10) and enhanced hippocampal BDNF levels. In conclusion, the present study showed for the first time a positive effect of six weeks of HIIT on reducing hippocampal oxidative stress by decreasing lipoperoxidation and inflammatory markers, as well enhancing antioxidant defenses and BDNF content., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: The aim of this study was to evaluate histologically the newly formed tissues after regenerative endodontic procedures (REPs) in dogs using either a blood clot (BC) or 2 different formulations of a chitosan hydrogel as scaffolds., Methods: Apical periodontitis was induced by inoculating immature teeth with oral plaque in 4 beagle dogs. Teeth (n = 96) were divided into 2 control (n = 20) and 4 test groups (n = 76) according to the treatment: apexification and REPs with BC, sodium hyaluronate:chitosan (HA:CS) scaffolds, or pectin:chitosan (P:CS) scaffolds. All root canals were disinfected with 2.5% sodium hypochlorite and a triple antibiotic paste intracanal medicament before evoked bleeding, clot formation, or scaffold placement. Thirteen weeks after treatment, the animals were sacrificed and the jaw blocks harvested for histologic processing, histomorphometric analysis, and statistical analysis., Results: The lumens of the root canals were completely filled with mineral trioxide aggregate with evidence of a mineralized apical bridge between the root canal walls in 83% of the samples in the apexification group. Vital vascularized tissue was found in the REP groups; apical closure happened in 66.7% of these treatments, and root growth was detected more often as an increase in thickness (85.6%) than in length (45.6%). The greatest amount of mineralized tissue inside the canal was observed in the BC group, with statistical significance compared with the HA:CS and P:CS groups (P < .05). Further histologic evaluation revealed the presence of apical papilla., Conclusions: The addition of chitosan scaffolds to blood in regenerative procedures in dogs did not improve the formation of new mineralized tissues along the root canal walls or the histologic evidence of the regeneration of a pulp-dentin complex., (Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

In this work, we used diffusion quantum Monte Carlo with density matrix (d-DMC) and variational quantum Monte Carlo (d-VMC) to determine the potential energy curve (PEC) and obtain the spectroscopic constants of H 2 molecule in the ground state, in order to evaluate the capability of these methods to provide an accurate PEC description. These quantum Monte Carlo methods build with density matrix are new approaches to conventional quantum Monte Carlo methods based on wave function formed by product of α and β determinants. To investigate the robustness of d-DMC, we performed calculations with two different basis sets and analyzed the influence of the size of these sets on results. To the best of our knowledge, this is the first study that shows the dissociation energy and rotational constant obtained from d-QMC. We found that the quality of PEC described by the d-DMC is essentially coincident with the most accurate results available in the literature, regardless of the complexity of basis set employed.

This paper deals with molecular modeling of new therapeutic agents for treating the Alzheimer's disease. The therapeutic line adopted for this study is the cholinergic hypothesis. To modulate positively the cholinergic function through the inhibition of the acetylcholinesterase, a set of candidates was designed from a natural compound extracted from the cashew nutshell liquid, anacardic acid. In silico screening of this chemical library revealed a ligand that is more promising once it is correlated with an active drug through specific topological and electronic descriptors. The protein-ligand docking showed stable binding modes and the binding free energy computed for the active site of the receptor suggests that our ligand presents a potential biological response. Graphical Abstract Representation of the three dimensional structure of the AChE, showing the important binding sites of the Gorge and the conformation of the ligand.

MicroRNAs (miRNAs) are small, non-coding RNAs that mediate post-transcriptional gene silencing, fine tuning gene expression. In an initial screen, miRNAs were found to be globally down-regulated in prostate cancer (PCa) cell lines and primary tumours. Exposure of PCa cell lines to a demethylating agent, 5-Aza-CdR resulted in an increase in the expression levels of miRNAs in general. Using stringent filtering criteria miR-130a was identified as the most promising candidate and selected for validation analyses in our patient series. Down-regulation of miR-130a was associated with promoter hypermethylation. MiR-130a methylation levels discriminated PCa from non-malignant tissues (AUC = 0.956), and urine samples revealed high specificity for non-invasive detection of patients with PCa (AUC = 0.89). Additionally, repressive histone marks were also found in the promoter of miR-130a. Over-expression of miR-130a in PCa cells reduced cell viability and invasion capability, and increased apoptosis. Putative targets of miR-130a were assessed by microarray expression profiling and DEPD1C and SEC23B were selected for validation. Silencing of both genes resembled the effect of over-expressing miR-130a in PCa cells. Our data indicate that miR-130a is an epigenetically regulated miRNA involved in regulation of key molecular and phenotypic features of prostate carcinogenesis, acting as a tumour suppressor miRNA., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

In this work we use gap-fitting procedure to tune the long-range corrected functionals and accurately investigate the electronic and optical properties of the five main molecules composing Buriti oil (extracted from Mauritia flexuosa L.) in the framework of density functional theory (DFT) and time-dependent (TD) DFT. The characteristic length (1/ω) was observed to be entirely system dependent, though we concluded that its determination is of fundamental importance to rescue geometrical, electronic, and optical properties with accuracy. We demonstrate that our approach of tuning characteristic length for each system resulted in an absorbance spectra in better experimental agreement when compared to the traditional methodology. Therefore, this study indicates that the tuning of the range-separation parameter is crucial to improve the description of the optical properties of conjugated molecules when TDDFT is used. For example, the wavelength of maximum absorption, λmax, for the phytofluene, obtained using B3LYP, is 381 nm, while using the gap-fitting procedure for the tuned-LC-BLYP the estimated λmax changed to 358 nm. The latter estimate is in better agreement with the experimental value of 350 nm.

The aim of this study was to evaluate the hepatoprotection of organic and conventional grapevine leaves extract (Vitis labrusca). The total polyphenol content and the isolate polyphenols by HPLC were evaluate. The animals received intraperitoneal injections of saline or extracts (conventional or organic - 30 mg/kg) for 14 days. On day 15, the rats received carbon tetrachloride (CCl4) or mineral oil (i.p.). After 4h, the animals were euthanized. The analysis of the liver enzymes activity (AST, ALT, GGT) was performed using serum, obtained by blood and the levels of lipid peroxidation (TBARS), protein oxidation (carbonyl), and the activity of antioxidant enzymes superoxide dismutase and catalase were analyzed in the liver. The results showed that the organic extract is richer in polyphenol and resveratrol than the conventional one. Both extracts prevent lipid peroxidation and protein oxidation generated by CCl4. Moreover, the extracts demonstrated ability to modulate the activity of SOD and CAT, as well as to establish a balance in the ratio of SOD/CAT. We also found that the CCl4 increased the levels of AST and GGT, and that both extracts prevent this. These results indicate that grapevine leaves extracts, both, organic and conventional, can prevent liver disorders.

The purpose of this study was to compare the effects of light-emitting diode (LED) irradiation and whole-body vibration (WBV) delivered either in isolation or combination (LED + WBV), warm-up (WU), and a control (C) treatment on performance during a sprint bicycle exercise. Ten cyclists performed a 30-second sprint cycle test under these conditions. The LED light was applied at 4 points bilaterally. Whole-body vibration consisted of 5 minutes of squats associated with WBV. LED + WBV consisted of WBV followed by LED therapy. Warm-up consisted of 17 minutes of moderate-intensity bicycle exercise. Control consisted of 10 minutes at rest. Blood lactate (BL) and ammonia (BA) levels and skin temperature (ST) were determined. Peak power (842 ± 117 vs. 800 ± 106 vs. 809 ± 128 W [p = 0.02 and p = 0.01]), relative power (12.1 ± 1.0 vs. 11.5 ± 0.9 vs. 11.6 ± 1.0 W·kg [p = 0.02 and p = 0.02]), and relative work (277 ± 23 vs. 263 ± 24 vs. 260 ± 23 J·kg [p = 0.02 and p = 0.003]) were higher in the WU group compared with the control and LED groups. In the LED + WBV group, peak (833 ± 115 vs. 800 ± 106 W [p = 0.02]) and relative (11.9 ± 0.9 vs. 11.5 ± 0.9 W·kg [p = 0.02]) power were higher than those in the control group, and relative work (272 ± 22 vs. 260 ± 23 J·kg [p = 0.02]) were improved compared with the LED group. There were no differences for BL, BA, and ST. The findings of this study confirmed the effectiveness of a warm-up as a preparatory activity and demonstrated that LED + WBV and WBV were as effective as WU in improving cyclist performance during a sprint bicycle exercise.

In this work, rovibrational energies and spectroscopic constants for the water -Ng complexes (Ng = He, Ne, Ar, Kr and Xe) were calculated through two different approaches (by solving the Nuclear Schrödinger equation and by applying the Dunham's method) and using two different potential energy curves (PEC). These PEC were determined using potential parameters obtained through molecular beam scattering experiments and accurate theoretical calculation, respectively. It was found that the theoretical rovibrational energies are in a good agreement (only for the lowest numbers of vibrational states) with those obtained through experimental PEC. Another important conclusions was regarding the calculated first two rovibrational energies for the H 2 O-Ar system, that are in a good agreement with the experimental data.

Background: Ventricular tachycardia or fibrillation (VT/VF) of focal origin due to triggered activity (TA) from delayed afterdepolarizations (DADs) is reproducibly inducible after anterior coronary artery occlusion. Both VT/VF and TA can be blocked by reducing reactive oxygen species (ROS). We tested the hypothesis that inhibition of NADPH oxidase and xanthine oxidase would block VT/VF., Methods: 69 dogs received apocynin (APO), 4 mg/kg intraveneously (IV), oxypurinol (OXY), 4 mg/kg IV, or both APO and OXY (BOTH) agents, or saline 3 h after coronary occlusion. Endocardium from ischemic sites (3-D mapping) was sampled for Rac1 (GTP-binding protein in membrane NADPH oxidase) activation or standard microelectrode techniques. Results (mean±SE, * p<0.05): VT/VF originating from ischemic zones was blocked by APO in 6/10 *, OXY in 4/9 *, BOTH in 5/8 * or saline in 1/27; 11/16 VT/VFs blocked were focal. In isolated myocardium, TA was blocked by APO (10(-6) M) or OXY (10(-8) M). Rac1 levels in ischemic endocardium were decreased by APO or OXY., Conclusion: APO and OXY suppressed focal VT/VF due to DADs, but the combination of the drugs was not more effective than either alone. Both drugs inhibited ischemic Rac1 with inhibition by OXY suggesting ROS-induced ROS. The inability to totally prevent VT/VF suggests that other mechanisms also contribute to ischemic VT.

The covalent excited states and ground state of the Br2 molecule has been investigated by using four-component relativistic COSCI and MRCISD methods. These methods were performed for all covalent states in the representation Ω((±)). Calculated potential energy curves (PECs) were obtained at the four-component COSCI level, and spectroscopic constants (R(e), D(e), D0, ω(e), ω(e)x(e), ω(e)y(e), B(e), α(e), γ(e), Te, Dv) for bounded states are reported. The vertical excitations for all covalent states are reported at COSCI, MRCISD, and MRCISD+Q levels. We also present spectroscopic constants for two weakly bounded states (A':(1)2u and B':(1)0(-)u) not yet reported in the literature, as well as accurate analytical curves for all five relativistic molecular bounded sates [the ground state X:0 g(+) and the excited states A:(1)1(u), B:(1)0(u)(+), C:(2)1(u), and B':(1)0(u)(-)] found in this work.

When heterocyclic monomers are polymerized by electrochemical or chemical methods, they form fully conjugated polymers which have a wide range of applications due to their outstanding electronic properties. Among this class of compounds, thiophene derivatives are widely used due to their chemical stability and synthesis flexibility. With the goal to investigate the torsion barrier of polymer chains, a few units of 3,4-ethylenedioxythiophene (EDOT) were chosen and submitted to molecular mechanics (MM), density functional theory (DFT) and coupled cluster CCSD(T) calculations. This study helps to understand the performance and transferability of force fields used in molecular mechanics and molecular dynamics simulations often used to describe structure-property relationships of those systems. Determination of inter-ring torsion angle was performed in a comparative study using both force field, DFT and CCSD(T) methods. A good agreement was noticed between MM and QC results and highlights the importance of the description of the interactions involving the oxygen atoms present in the structure of EDOT. These observations are related to the α,α-coupling that occurs between the monomer units and yields a linear polymer. DFT HOMO and LUMO orbitals were also presented. Finally, UV-vis spectra of EDOT units were obtained using several levels of theory by means of time-dependent DFT calculations (TD-DFT).

In this work we apply quasiclassical trajectory theory to the X + Li2 → Li + LiX reactions, with X standing for H, D, T, and Mu, in order to determine dynamical properties such as state-to-state reactive cross-section, rotational, vibrational, and translational product distributions. By using the literature benchmark potential energy surface, we were able to predict the aforementioned dynamical property in remarkable qualitative agreement with data in the literature for the H + Li2 → Li + LiH channel. Particularly, our results points toward the well known cross section independence with ro-vibrational excitations for high excitation regimes. Since the methodology is known to be well suited for the other species, as we considered the same PES, our results are expected to be similarly accurate for D, T, and Mu. The present work consists on a significant progress in this area of research, since previous theoretical calculations-based on known potential energy surface-deviated from the experimental results.

In this work, we performed a thorough investigation of potential energy curves, rovibrational spectra, and spectroscopic constants for dimers whose interactions are mediated by hydrogen bonds and other hydrogen interactions. Particularly, we deal with CH4⋯CH4, CH4⋯H2O, CH4⋯CHF3, and H2O⋯CHF 3 dimers by employing accurate electronic energy calculations with two different basis sets at the MP2 level of theory. Following this, the discrete variable representation method was applied to solve the nuclear Schrödinger equation, thus obtaining spectroscopic constants and rovibrational spectra. The harmonic constant, ω e , presents a direct relation to the strength of dimer interactions. As a general rule, it was found that a decrease of interatomic distances is followed by the increase of D e for all dimers. This behavior suggests that the interaction of CH4⋯CH4 is the weakest among all dimers, followed by CH4⋯CHF3, CH4⋯H2O and the strongest interaction given by the H2O⋯CHF 3 dimer.

The objective of this study was to investigate the effect of running versus cycling exercises upon serum S100B levels and typical markers of skeletal muscle damage such as creatine kinase (CK), aspartate aminotransferase (AST) and myoglobin (Mb). Although recent work demonstrates that S100B is highly expressed and exerts functional properties in skeletal muscle, there is no previous study that tries to establish a relationship between muscle damage and serum S100B levels after exercise. We conducted a cross-sectional study on 13 male triathletes. They completed 2 submaximal exercise protocols at anaerobic threshold intensity. Running was performed on a treadmill with no inclination (RUN) and cycling (CYC) using a cycle-simulator. Three blood samples were taken before (PRE), immediately after (POST) and 1 h after exercise for CK, AST, Mb and S100B assessments. We found a significant increase in serum S100B levels and muscle damage markers in RUN POST compared with RUN PRE. Comparing groups, POST S100B, CK, AST and Mb serum levels were higher in RUN than CYC. Only in RUN, the area under the curve (AUC) of serum S100B is positively correlated with AUC of CK and Mb. Therefore, immediately after an intense exercise such as running, but not cycling, serum levels of S100B protein increase in parallel with levels of CK, AST and Mb. Additionally, the positive correlation between S100B and CK and Mb points to S100B as an acute biomarker of muscle damage after running exercise.

We performed a combined DFT and Monte Carlo (13)C NMR chemical-shift study of azadirachtin A, a triterpenoid that acts as a natural insect antifeedant. A conformational search using a Monte Carlo technique based on the RM1 semiempirical method was carried out in order to establish its preferred structure. The B3LYP/6-311++G(d,p), wB97XD/6-311++G(d,p), M06/6-311++G(d,p), M06-2X/6-311++G(d,p), and CAM-B3LYP/6-311++G(d,p) levels of theory were used to predict NMR chemical shifts. A Monte Carlo population-weighted average spectrum was produced based on the predicted Boltzmann contributions. In general, good agreement between experimental and theoretical data was obtained using both methods, and the (13)C NMR chemical shifts were predicted highly accurately. The geometry was optimized at the semiempirical level and used to calculate the NMR chemical shifts at the DFT level, and these shifts showed only minor deviations from those obtained following structural optimization at the DFT level, and incurred a much lower computational cost. The theoretical ultraviolet spectrum showed a maximum absorption peak that was mainly contributed by the tiglate group.

This study aimed to describe and compare ballet dancers' cardiorespiratory responses, muscle damage and oxidative stress levels during a ballet class (practice of isolated ballet exercises performed with barre/hand-rail support and across-the-floor movements to improve technical skills) and rehearsal (practice of ballet choreography involving technical-artistic skills to improve dancers' performance for shows). The 12 advanced female ballet dancers undertook three exercise sessions: maximum effort test, class and rehearsal. Heart rate (HR) and oxygen consumption (VO2) were continuously measured. Lactate was determined before 15 min and after class and rehearsal. Blood was sampled pre, post and 48 h after class and rehearsal for creatine kinase (CK), lipid peroxides (LPO) and glutathione analysis (GSSG/GSH). Class was of lower intensity than rehearsal as shown by VO2, HR and lactate values: VO2 (mL.kg(-1).min(-1)): 14.5±2.1 vs. 19.1±1.7 (p < 0.001); HR (bpm.min(-1)): 145.7±17.9 vs. 174.5±13.8 (p < 0.001); lactate (mmol.L(-1)): 4.2±1.1 vs. 5.5±2.7 (p = 0.049). CK (IU) increased following class and rehearsal, remaining high 48 h after: class (pre = 109.3±48.5; post = 144±60; 48 h = 117.2±64.6); rehearsal (pre = 78.6±52.1; post = 122±70.7; 48 h = 104.9±89.5). LPO (µM) increased from pre-class (1.27±0.19) to post-class (1.41±0.19) and went down after 48 h (1.20±0.22). No LPO time-course changes followed the rehearsal. GSSG/GSH decreased 48 h after class and rehearsal. Greater increases in LPO post-class suggest it promotes CK release by an oxidative membrane-damage mechanism. Physiological increases of LPO and CK in class indicate it prepares the dancers for exercise-induced oxidative stress and muscle damage during rehearsals. Ballet dancers' muscle damage and oxidative stress responses seem not to be dependent on exercise intensity based on VO2 responses.

The purpose of this study was to investigate the effect of different volumes of plyometric exercise (i.e., 100, 200, or 300 hurdle jumps) on acute strength and jump performance and on the acute hormonal and lactate responses in rugby players. Eleven young male elite rugby players (age, 23.5 ± 0.9 years; height, 173 ± 4.8 cm) volunteered for the study. Maximal isometric peak torque (PT), maximal rate of force development (RFD), squat jump (SJ), and drop jump (DJ) performance were assessed before and 5 minutes, 8 hours, and 24 hours after 100, 200, or 300 jumps. In addition, total testosterone (TT), cortisol (COR), and lactate were measured before and after the 3 different plyometric exercise volumes. There were significant decreases in the PT (p < 0.02) and maximal RFD (p < 0.001) 5 minutes, 8 hours, and 24 hours after 100, 200, and 300 jumps, with no differences between the exercise volumes. Additionally, there were significant decreases in the SJ (p < 0.001) and DJ (p < 0.01) performances 24 hours after 100, 200, and 300 jumps, with no differences between the exercise volumes. However, there were significant increases in the TT (p < 0.001), COR (p < 0.05), and lactate (p < 0.001) after 100, 200, and 300 jumps, with no differences between the exercise volumes. All plyometric exercise volumes (100, 200, and 300 jumps) resulted in similar neuromuscular, metabolic, and hormonal responses.

Physical and chemical adsorption of CO2 on ZnO surfaces were studied by means of two different implementations of periodic density functional theory. Adsorption energies were computed and compared to values in the literature. In particular, it was found that the calculated equilibrium structure and internuclear distances are in agreement with previous work. CO2 adsorption was analyzed by inspection of the density of states and electron localization function. Valence bands, band gap and final states of adsorbed CO2 were investigated and the effect of atomic displacements analyzed. The partial density of states (PDOS) of chemical adsorption of CO2 on the ZnO(0001) surface show that the p orbitals of CO2 were mixed with the ZnO valence band state appearing at the top of the valence band and in regions of low-energy conduction band.

Electronic and vibrational properties of different single-walled carbon nanotubes (SWNTs) interacting with a CO2 molecule are investigated through the use of density functional theory (DFT) calculations and the discrete variable representation (DVR) method, respectively. We observed a considerable geometry difference between pristine and doped nanotubes. Consequently, a greater binding energy between the former type of nanotubes and the adsorbing molecule is achieved, a fact that finds experimental support and leads us to consider cobalt-doped nanotubes as promising candidates for chemical sensors. From the vibrational point of view, we note that the zigzag chirality tends to present higher values of vibrational frequencies for most of the states considered regardless of the nanotubes being doped or not. The potential energy curves (PECs) for the interactions between CO2 and all of the considered nanotubes together with spectroscopic constants are provided, and the reliability of the performed calculations makes the data a useful source of comparison for future works.

Cardiac resynchronization therapy (CRT) using a biventricular pacemaker is an invasive and expensive treatment option for left ventricular mechanical dyssynchrony (LVMD). The CRT candidate selection is a crucial issue due to the unreliability of the current standard CRT indicators. Real-time three-dimensional (3-D) echocardiography (RT3DE) provides four-dimensional (4-D) (3-D+time) information about the LV and is suitable for LVMD assessment. In this article, the complex left ventricle (LV) shape and motion of 50 RT3DE datasets are represented by novel 4-D descriptors - 4-D sphericity, volume and shape, from which novel indices were derived by principal component analysis (PCA) and subsequently analyzed by a support vector machine (SVM) classifier to assess their capability of LVMD characterization and CRT outcome prediction. These novel indices outperformed clinical indices and have promising capabilities in disease characterization and great potential in CRT outcome prediction. To enable efficient quantitative RT3DE analysis, a segmentation method was developed to combine the powers of active shape models and optimal graph search. Various aspects of the method were designed to handle varying RT3DE image quality among datasets and LV segments. An application with graphical user interface was developed to provide the user with simple and intuitive control. The developed method was robust to inter-observer variability and produced very good accuracy - 3.2±1.1 mm absolute surface positioning error, <1 mm mean signed error and <5% mean volume difference. The computer method's classification performance was compared with the independent standard, showing that the 4-D shape modal indices were not only the most capable of all tested options when employed for disease characterization but also the least sensitive to segmentation imperfections., (Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Paraquat (PQ), a cationic nonselective bipyridyl herbicide, has been used as neurotoxicant to modulate Parkinson's disease in laboratory settings. Other compounds like rotenone (ROT), a pesticide, and 1-methyl-4-phenylpyridinium ion (MPP(+)) have been widely used as neurotoxicants. We compared the toxicity of these three neurotoxicants using differentiated dopaminergic SH-SY5Y human cells, aiming to elucidate their differential effects. PQ-induced neurotoxicity was shown to be concentration and time dependent, being mitochondrial dysfunction followed by neuronal death. On the other hand, cells exposure to MPP(+) induced mitochondrial dysfunction, but not cellular lyses. Meanwhile, ROT promoted both mitochondrial dysfunction and neuronal death, revealing a biphasic pattern. To further elucidate PQ neurotoxic mechanism, several protective agents were used. SH-SY5Y cells pretreatment with tiron (TIR) and 2-hydroxybenzoic acid sodium salt (NaSAL), both antioxidants, and N ω -nitro-L-arginine methyl ester hydrochloride (L-NAME), a nitric oxide synthase inhibitor, partially protected against PQ-induced cell injury. Additionally, 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenyl-propyl)piperazine (GBR 12909), a dopamine transporter inhibitor, and cycloheximide (CHX), a protein synthesis inhibitor, also partially protected against PQ-induced cell injury. In conclusion, we demonstrated that PQ, MPP(+), and ROT exerted differential toxic effects on dopaminergic cells. PQ neurotoxicity occurred through exacerbated oxidative stress, with involvement of uptake through the dopamine transporter and protein synthesis.

The purpose of this study was to examine the influence of the intrasession sequencing of concurrent strength and aerobic training on the acute testosterone (TT) and cortisol (COR) responses. Ten recreationally strength-trained young men (23.5 ± 0.9 years) performed 2 exercise interventions: aerobic-strength (AS) and strength-aerobic (SA), which consisted of 30 minutes of aerobic exercise on a cycle ergometer at 75% of maximal heart rate and 3 sets of 8 repetitions at 75% of 1 repetition maximum (1RM) in 4 strength exercises. Maximal heart rate was determined using a maximal incremental test on a cycle ergometer. Blood samples were collected before, between exercise modalities, and immediately after the concurrent training sessions to determine basal and acute total TT and COR concentrations. There were significant increases in TT after the first modality in both exercise orders (p < 0.05). However, the TT level remained significantly higher than the resting levels after the second exercise modality only in the AS (p < 0.05) which resulted in a significant higher relative total change after the complete concurrent training session compared with SA (p < 0.05). Regarding COR, there were significant increases after the first modality in both AS and SA orders (p < 0.05), but the COR returned to resting levels after the second modality in both AS and SA interventions. During AS and SA, the change observed after the first modality performance was greater than that after the second in both hormones. The present results suggest that the TT response is optimized after the AS order, whereas both AS and SA produced similar hormonal levels at all time points. However, it is important to state that the present results should be applied only when short duration and moderate intensity aerobic training is performed.

The human cellular prion protein (PrP(C)) is a glycosylphosphatidylinositol (GPI) anchored membrane glycoprotein with two N-glycosylation sites at residues 181 and 197. This protein migrates in several bands by Western blot analysis (WB). Interestingly, PNGase F treatment of human brain homogenates prior to the WB, which is known to remove the N-glycosylations, unexpectedly gives rise to two dominant bands, which are now known as C-terminal (C1) and N-terminal (N1) fragments. This resembles the β-amyloid precursor protein (APP) in Alzheimer disease (AD), which can be physiologically processed by α-, β-, and γ-secretases. The processing of APP has been extensively studied, while the identity of the cellular proteases involved in the proteolysis of PrP(C) and their possible role in prion biology has remained limited and controversial. Nevertheless, there is a strong correlation between the neurotoxicity caused by prion proteins and the blockade of their normal proteolysis. For example, expression of non-cleavable PrP(C) mutants in transgenic mice generates neurotoxicity, even in the absence of infectious prions, suggesting that PrP(C) proteolysis is physiologically and pathologically important. As many mouse models of prion diseases have recently been developed and the knowledge about the proteases responsible for the PrP(C) proteolysis is accumulating, we examine the historical experimental evidence and highlight recent studies that shed new light on this issue.

The differentiation of follicular dendritic cells (FDC) is essential to the remarkable microanatomic plasticity of lymphoid follicles. Here we show that FDC arise from ubiquitous perivascular precursors (preFDC) expressing platelet-derived growth factor receptor β (PDGFRβ). PDGFRβ-Cre-driven reporter gene recombination resulted in FDC labeling, whereas conditional ablation of PDGFRβ(+)-derived cells abolished FDC, indicating that FDC originate from PDGFRβ(+) cells. Lymphotoxin-α-overexpressing prion protein (PrP)(+) kidneys developed PrP(+) FDC after transplantation into PrP(-) mice, confirming that preFDC exist outside lymphoid organs. Adipose tissue-derived PDGFRβ(+) stromal-vascular cells responded to FDC maturation factors and, when transplanted into lymphotoxin β receptor (LTβR)(-) kidney capsules, differentiated into Mfge8(+)CD21/35(+)FcγRIIβ(+)PrP(+) FDC capable of trapping immune complexes and recruiting B cells. Spleens of lymphocyte-deficient mice contained perivascular PDGFRβ(+) FDC precursors whose expansion required both lymphoid tissue inducer (LTi) cells and lymphotoxin. The ubiquity of preFDC and their strategic location at blood vessels may explain the de novo generation of organized lymphoid tissue at sites of lymphocytic inflammation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

This study compared rectal temperature (Tre), heat sensation and sweating between obese and non-obese boys during cycling in the heat. Participants (aged 12-15 years) were 17 obese and 16 non-obese (BMI=29.4±4.3 and 16.8±1.7 kg · m⁻², respectively) boys. They cycled for 30-min (50-55% VO(2peak)) in a climatic chamber (35°C, 45% RH) and Tre, heat sensation and sweat volume were monitored. From the start to the end of cycling, Tre was similar between the obese (37.4±0.3-37.8±0.3°C) and non-obese (37.3±0.2-37.9±0.2°C) groups. Heat sensation was higher in the obese group from the start (3.6±2.7 vs. 1.3±1.4 cm; P=0.008) to the end (7.6±2 vs. 5.2±2.2 cm; P=0.003) of cycling. Sweat volume corrected by body surface area was similar between the obese (200±123 mL · m⁻²) and non-obese (212±80 mL · m⁻²) groups. Initial and final HR were similar in both groups, and RPE was higher in the obese group at 25th (P=0.040) and 30th (P=0.019) min. In conclusion, the obese pubescent participants presented similar Tre and sweating volume, but higher heat sensation while cycling in the heat., (© Georg Thieme Verlag KG Stuttgart · New York.)

For the first time in the literature, rigorous time-independent quantum scattering formalism was applied, by means of the ABC program, to the H + Li(2) → LiH + Li reaction. The state-to-state probabilities as a function of the total energy have been computed at zero total angular momentum (J = 0) allowing us to evaluate the effect of vibrational/rotational excitation on the reaction promotion/inhibition, the energetic distribution of products, and the temperature dependence of the J-shifting thermal rate coefficients.