Miracle-dz/UniFAR-FTUs huggingface dataset:
Ganhos de força através de um programa de treinamento audiovisual com gerontes

Este trabalho investiga o desempenho e o coeficiente de ganho de adaptacao neural dentro de um programa de treinamento com idosos, utilizando um metodo de excitacao auditiva e visual atraves do aparelho eletronico computadorizado �ORION� (fabricado pela Mindplace). O tratamento dos dados envolveu estatistica inferencial para entendimento das relacoes causais (causa e efeito), nas quais se encontra baseado o corpo de hipoteses. Para tal inferencia utilizou-se o teste t de Student (comparacao de duas medias � pareado [intra] e nao pareado [inter]). Este resultado indica que devemos aceitar a Hipotese Nula, ou seja, nao existem diferencas significativas entre as medias Pre e Pos; portanto, a inferencia do experimento nao implicou em alteracoes significativas dos respectivos valores medios.
Hydrogen sulfide signaling in the gastrointestinal tract.

SIGNIFICANCE The current literature regarding the effects of the gaseous signal molecule hydrogen sulfide (H2S) in the gastrointestinal system is reviewed. Bacterial, host and pharmaceutical-derived H2S are all considered and presented according to the physiological or pathophysiological effects of the gaseous signal molecule. These subjects include the toxicology of intestinal H2S with emphasis on bacterial-derived H2S, especially from sulfate-reducing bacteria, the role of endogenous and exogenous H2S in intestinal inflammation, and the roles of H2S in gastrointestinal motility, secretion and nociception. RECENT ADVANCES While its pro- and anti-inflammatory, smooth muscle relaxant, prosecretory, and pro- and antinociceptive actions continue to remain the major effects of H2S in this system; recent findings have expanded the potential molecular targets for H2S in the gastrointestinal tract. CRITICAL ISSUES Numerous discrepancies remain in the literature, and definitive molecular targets in this system have not been supported by the use of competitive antagonism. FUTURE DIRECTIONS Future work will hopefully resolve discrepancies in the literature and identify molecular targets and mechanisms of action for H2S. It is clear from the current literature that the long-appreciated relationship between H2S and the gastrointestinal tract continues to be strong as we endeavor to unravel its mysteries.
Disulfide-containing high mobility group box-1 promotes N-methyl-D-aspartate receptor function and excitotoxicity by activating Toll-like receptor 4-dependent signaling in hippocampal neurons.

AIMS Using primary cultures of mouse hippocampal neurons, we studied the molecular and functional interactions between high mobility group box-1 (HMGB1) and the N-methyl-d-aspartate receptor (NMDAR), two proteins playing a key role in neuronal hyperexcitability. By measuring NMDA-induced calcium (Ca(2+)) increase in neuronal somata and neurotoxicity as functional read-out parameters, we explored the role of the redox state of HMGB1, the receptor involved, and the molecular signaling underlying its interactions with postsynaptic NMDAR. We also investigated whether HMGB1 redox state affects its proconvulsive effects in mice. RESULTS Nonoxidizable HMGB1 with a triple cysteine-to-serine replacement (3S-HMGB1) was ineffective on NMDA response. Conversely, the disulfide-containing form of HMGB1 dose dependently enhanced NMDA-induced Ca(2+) increase in neuronal cell bodies. This effect was prevented by BoxA, a competitive HMGB1 antagonist, and by Rhodobacter sphaeroides lipopolysaccharide (LPS-RS), a toll-like receptor 4 (TLR4) selective antagonist, and it was abrogated in neurons lacking TLR4 while persisting in the absence of receptor for advanced glycation end products (RAGE). TLR4 and NMDAR subunit 1 (NR1) and 2B (NR2B) were colocalized in neurons. Disulfide HMGB1 effect on NMDA-induced Ca(2+) influx was prevented by 3-O-methylsphingomyelin (3-O-MS) and 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo [3,4-d] pyrimidine, (PP2) selective inhibitors of neutral sphingomyelinase and Src-family Tyr kinases, respectively. Disulfide HMGB1, but not 3S-HMGB1, increased Tyr(1472) phosphorylation of the NR2B subunit of the NMDAR, which is known to increase Ca(2+) channel permeability. Similarly, disulfide HMGB1 increased NMDA-induced neuronal cell death in vitro and enhanced kainate-induced seizures in vivo. INNOVATION AND CONCLUSION We describe a novel molecular neuronal pathway activated by HMGB1 that could be targeted in vivo to prevent neurodegeneration and seizures mediated by excessive NMDARs stimulation.
Surface colonization by Azospirillum brasilense SM in the indole‐3‐acetic acid dependent growth improvement of sorghum

The key to improving plant productivity is successful bacterial‐plant interaction in the rhizosphere that can be maintained in the environment. The results presented here confirm Azospirillum brasilense strain SM as a competent plant growth promoting bacterium over mid‐ and long‐term associations with sorghum. This study establishes that plant growth can be directly correlated with the associated bacterium's indole‐3‐acetic acid (IAA) production capability as IAA over‐expressing variants, SMp30 and SMΔi3‐6 fared better than the wild type strain. The auxin antagonist, p‐chlorophenoxy isobutyric acid confirmed the role of bacterial IAA in plant growth promotion and verified the presence of larger amount of IAA available to the seeds on inoculation with IAA over‐expressing mutants. Microscopic analysis identified the bacterial association at root tips, root‐shoot junction and elongation zone and their surface colonizing nature. Scanning electron microscopy identified larger number of root hairs and extensive exopolysaccharide covering in comparison to untreated ones. In addition, vibroid‐shaped Azospirilla attached by means of fibrillar material were dispersed along the elongation zone. The notable difference with IAA over‐expressing variants was enhanced number of root hairs. Thus, the variant strains may be more efficient surface colonizers of the sorghum root and used as superior bio‐inoculants for improving plant productivity. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The Use of a Ceramic Surfaced Oxidized Zirconium Implant in Total Knee Replacement

This article reports on the 5-year follow-up of total knee replacement using a ceramic surfaced zirconium femoral component (Oxinium). Laboratory testing had indicated that the material, when articulated against both non-cross-linked and cross-linked ultrahigh-molecular-weight polyethylene, resulted in lower abrasive and adhesive wear than did a cobalt-chrome implant. There were no complications attributable to the material, and the clinical results at 5 years, as evaluated by the Knee Society rating system, were excellent.
Harnessing experience-dependent plasticity for CNS repair and regeneration

The 7th World Congress of Neurorehabilitation was held from 16–19 May, 2012, in Melbourne, Australia. Melbourne produced the largest attendance of any meeting thus far for this biennial congress of the World Federation of Neurorehabilitation. The congress provided a diverse range of presentations, from environmental interventions in animal models of brain disorders, to new techniques for rehabilitation and clinical trials. While stroke, traumatic brain injury and spinal cord injury featured prominently, there were also many other presentations on rehabilitation for neurodegenerative diseases and other neurological disorders. Here, we focus on a selection of novel findings reported at this congress.
Downregulation of TRAP1 sensitizes glioblastoma cells to temozolomide chemotherapy through regulating metabolic reprogramming

Cancer cells preferentially use aerobic glycolysis to support growth, a metabolic alteration commonly referred to as the ‘Warburg effect. ’ Here, we show that the tumor necrosis factor receptor-associated protein 1 (TRAP1) is crucial for the Warburg effect in human glioblastoma multiforme (GBM). In contrast to normal brain, GBMs show increased TRAP1 expression. We used both GBM cell lines and neurospheres derived from human GBM specimens to examine the effects of Knockdown of TRAP1 on GBM cell lines and glioma stem cells. We also used a neurosphere recovery assay that measured neurosphere formation at three time points to assess the capacity of the culture to repopulate after knockdown of TRAP1. Our results showed that knockdown of TRAP1 strongly decreased GBM cell proliferation and migration, inhibited neurosphere recovery, secondary neurosphere formation, and enhanced the therapeutic effect of temozolomide in neurosphere cultures. In GBM, knockdown of TRAP1 appeared to inhibit tumor growth and migration through its regulatory effects on metabolic reprogramming.
Changes in the expression of voltage-gated sodium channels Nav1.3, Nav1.7, Nav1.8, and Nav1.9 in rat trigeminal ganglia following chronic constriction injury

Voltage-gated sodium channels (VGSCs), especially the tetrodotoxin-sensitive Nav1.3 and Nav1.7, and the tetrodotoxin-resistant Nav1.8 and Nav1.9, have been implicated in acute and chronic neuropathic pain. The aim of this study was to investigate the expression of VGSC Nav1.3, Nav1.7, Nav1.8, and Nav1.9 after nerve injury and their roles in the development of trigeminal neuralgia (TN). We used the infraorbital nerve-chronic constriction injury model of TN in the rat. The time course of changes in the mechanical pain threshold was examined. In addition, real-time PCR and double immunofluorescence staining of VGSC &agr; subunits were used to evaluate messenger RNA and protein expression, respectively, in the trigeminal ganglion. Behavioral tests showed that the mechanical pain threshold decreased significantly 4–42 days after surgery and reached the lowest observed value by day 12. Compared with sham-operated controls, we found that trigeminal ganglion in rats subjected to an infraorbital nerve-chronic constriction injury showed upregulation of Nav1.3 and downregulation of Nav1.7, Nav1.8, and Nav1.9 messenger RNA and protein levels. Our findings suggest that VGSC may participate in the regulation of TN.
Oxidative modulation of K+ channels in the central nervous system in neurodegenerative diseases and aging.

SIGNIFICANCE Oxidative stress and damage are well-established components of neurodegenerative diseases, contributing to neuronal death during disease progression. Here, we consider key K(+) channels as target proteins that can undergo oxidative modulation, describe what is understood about how this influences disease progression, and consider regulation of these channels by gasotransmitters as a means of cellular protection. RECENT ADVANCES Oxidative regulation of the delayed rectifier Kv2.1 and the Ca(2+)- and voltage-sensitive BK channel are established, but recent studies contest how their redox sensitivity contributes to altered excitability, progression of neurodegenerative diseases, and healthy aging. CRITICAL ISSUES Both Kv2.1 and BK channels have recently been established as target proteins for regulation by the gasotransmitters carbon monoxide and hydrogen sulfide. Establishing the molecular basis of such regulation, and exactly how this influences excitability and vulnerability to apoptotic cell death will determine whether such regulation can be exploited for therapeutic benefit. FUTURE DIRECTIONS Developing a more comprehensive picture of the oxidative modulation of K(+) channels (and, indeed, other ion channels) within the central nervous system in health and disease will enable us to better understand processes associated with healthy aging as well as distinct processes underlying progression of neurodegenerative diseases. Advances in the growing understanding of how gasotransmitters can regulate ion channels, including redox-sensitive K(+) channels, are a research priority for this field, and will establish their usefulness in design of future approaches for the treatment of such diseases.
Glutathione S-Transferase P-Mediated Protein S-Glutathionylation of Resident Endoplasmic Reticulum Proteins Influences Sensitivity to Drug-Induced Unfolded Protein Response.

AIMS S-glutathionylation of cysteine residues, catalyzed by glutathione S-transferase Pi (GSTP), alters structure/function characteristics of certain targeted proteins. Our goal is to characterize how S-glutathionylation of proteins within the endoplasmic reticulum (ER) impact cell sensitivity to ER-stress inducing drugs. RESULTS We identify GSTP to be an ER-resident protein where it demonstrates both chaperone and catalytic functions. Redox based proteomic analyses identified a cluster of proteins cooperatively involved in the regulation of ER stress (immunoglobulin heavy chain-binding protein [BiP], protein disulfide isomerase [PDI], calnexin, calreticulin, endoplasmin, sarco/endoplasmic reticulum Ca2+-ATPase [SERCA]) that individually co-immunoprecipitated with GSTP (implying protein complex formation) and were subject to reactive oxygen species (ROS) induced S-glutathionylation. S-glutathionylation of each of these six proteins was attenuated in cells (liver, embryo fibroblasts or bone marrow dendritic) from mice lacking GSTP (Gstp1/p2-/-) compared to wild type (Gstp1/p2+/+). Moreover, Gstp1/p2-/- cells were significantly more sensitive to the cytotoxic effects of the ER-stress inducing drugs, thapsigargin (7-fold) and tunicamycin (2-fold). INNOVATION Within the family of GST isozymes, GSTP has been ascribed the broadest range of catalytic and chaperone functions. Now, for the first time, we identify it as an ER resident protein that catalyzes S-glutathionylation of critical ER proteins within this organelle. Of note, this can provide a nexus for linkage of redox based signaling and pathways that regulate the unfolded protein response (UPR). This has novel importance in determining how some drugs kill cancer cells. CONCLUSIONS Contextually, these results provide mechanistic evidence that GSTP can exert redox regulation in the oxidative ER environment and indicate that, within the ER, GSTP influences the cellular consequences of the UPR through S-glutathionylation of a series of key interrelated proteins. Antioxid. Redox Signal. 26, 247-261.
An Endothelial Hsp70-TLR4 Axis Limits Nox3 Expression and Protects Against Oxidant Injury in Lungs.

AIMS Oxidants play a critical role in the pathogenesis of acute lung injury (ALI). Nox3 is a novel member of the NADPH oxidase (Nox) family of oxidant-generating enzymes, which our laboratory had previously identified to be induced in the lungs of TLR4(-/-) mice. However, the physiologic role of Nox3 induction in lungs and its precise relationship to TLR4 are unknown. Furthermore, the cell compartment involved and the signaling mechanisms of Nox3 induction are unknown. RESULTS We identified that Nox3 is regulated by heat shock protein 70 (Hsp70) signaling via a TLR4-Trif-signal transducer and activator of transcription 3 (Stat3) pathway and that Nox3 induction leads to increased oxidant injury and death in mice and lung endothelial cells. We generated Nox3(-/-)/TLR4(-/-) double knockout mice, endothelial-targeting lentiviral silencing constructs, and endothelial-targeted Stat3(-/-) mice to specifically demonstrate that Nox3 induction is responsible for the pro-oxidant, proapoptotic phenotype of TLR4(-/-) mice. We also show that an endothelial Hsp70-TLR4-Trif-Stat3 axis is required to suppress deleterious Nox3 induction. INNOVATION To date, a physiologic role for Nox3 in oxidant-induced ALI has not been identified. In addition, we generated unique double knockout mice and endothelial-targeted lentiviral silencing constructs to specifically demonstrate the role of a TLR4 signaling pathway in regulating pro-oxidant generation. CONCLUSIONS We identified an endothelial TLR4-Trif antioxidant pathway that leads to the inhibition of a novel NADPH oxidase, Nox3, in lungs and lung endothelial cells. We also identified the role of a TLR4 ligand, Hsp70, in suppressing Nox3 in basal and pro-oxidant conditions. These studies identify potentially new therapeutic targets in oxidant-induced ALI. Antioxid. Redox Signal. 24, 991-1012.
Irrelevant visual stimuli improve auditory task performance

Multisensory behavioral benefits generally occur when one modality provides improved or disambiguating information to another. Here, we show benefits when no information is apparently provided. Participants performed an auditory frequency discrimination task in which auditory stimuli were paired with uninformative visual stimuli. Visual–auditory stimulus onset asynchrony was varied between −10 ms (sound first) to 80 ms without compromising perceptual simultaneity. In most stimulus onset asynchrony conditions, response times to audiovisual pairs were significantly shorter than auditory-alone controls. This suggests a general processing advantage for multisensory stimuli over unisensory stimuli, even when only one modality is informative. Response times were shortest with an auditory delay of 65 ms, indicating an audiovisual ‘perceptual optimum’ that may be related to processing simultaneity.
Alterations in regional blood flow during positive end-expiratory pressure ventilation.

: PEEP improves the gas-exchange abnormalities that accompany adult respiratory distress syndrome (ARDS). However, since PEEP decreases cardiac output, it may also alter regional blood flow and therefore, substrate delivery to specific organs. To test this hypothesis, radiolabeled 15-mu microspheres were used to directly quantify the effects of mechanical ventilation with PEEP on regional blood flow to individual organs in animals. Mechanical ventilation alone produced a -21.2 +/- 3.6% and a -28.1 +/- 5.2% decrease in cardiac output at 30 and 60 min, respectively. The addition of 14 cm H2O PEEP resulted in little further reduction in cardiac output at 30 and 60 min (-28 +/- 2.3% and -36.4 +/- 4.9%, respectively). However, 25 cm H2O PEEP reduced markedly (p less than .01) cardiac output (-59.2 +/- 6.1% at 30 min and -55.1 +/- 4.0% at 60 min). Although blood flows to the kidney and brain were maintained, decreases in cardiac output were invariably accompanied by proportional decreases in blood flow to the heart. Intravascular volume expansion with saline (20 ml/kg) during 14 cm H2O PEEP significantly improved cardiac output (3.23 +/- 0.34 to 4.22 +/- 0.13 L/min; p less than .01) and proportionately increased blood flow to several regional vascular beds, including the heart. These data suggest that PEEP decreases cardiac output to produce reversible alterations in blood flow to a number of regional vascular beds. These PEEP-induced alterations in regional blood flow may have important implications for the development of multiple-organ failure in ARDS patients.
Carbon Monoxide Potentiation of L-Type Ca2+ Channel Activity Increases HIF-1α-Independent VEGF Expression via an AMPKα/SIRT1-Mediated PGC-1α/ERRα Axis.

AIMS The heme oxygenase-1 (HO-1)/carbon monoxide (CO) pathway induced in astrocytes after ischemic brain injury promotes vascular endothelial growth factor (VEGF) expression to maintain and repair neurovascular function. Although HO-1-derived CO has been shown to induce hypoxia-inducible factor-1α (HIF-1α)-dependent VEGF expression, the underlying mechanism independent of HIF-1α remains to be elucidated. RESULTS HO-1 and VEGF were coexpressed in astrocytes of ischemic mouse brain tissues. Experiments with specific siRNAs and pharmacological activators/inhibitors of various target genes demonstrated that astrocytes pre-exposed to the CO-releasing compound, CORM-2, or transfected with HO-1 increased HIF-1α-independent VEGF expression via sequential activation of the following signal cascades; Ca2+/calmodulin-dependent protein kinase kinase β-mediated AMP-activated protein kinase (AMPK)α activation, AMPKα-induced increases in nicotinamide phosphoribosyltransferase (NAMPT) expression and cellular NAD+ level, sirtuin 1 (SIRT1)-dependent peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) stabilization and activation, and PGC-1α/estrogen-related receptor (ERR)α-mediated VEGF expression. All of these sequential events were blocked by an L-type voltage-gated Ca2+ channel inhibitor and Ca2+ chelators, but not by other Ca2+ channel inhibitors. INNOVATION HO-1-derived CO elicits Ca2+ influx by activating L-type Ca2+ channels, which is a key player in HIF-1α-independent VEGF expression by activating the AMPKα-NAMPT-SIRT1-PGC-1α/ERRα pathway. CONCLUSION Our results provide new mechanistic insight into the possible role for L-type Ca2+ channels in HO-1/CO-induced angiogenesis. Antioxid. Redox Signal. 27, 21-36.
FMRI/ERP of musical syntax: comparison of melodies and unstructured note sequences

To date, the neural correlates of musical syntax processing have been investigated mainly by means of paradigms in which isolated chords are made incongruent with the harmonic context. Here, we present results obtained contrasting unfamiliar one-part piano melodies with unstructured note sequences, comparable in pitch and rhythm but devoid of any syntactic structure. This paradigm indexes a superset of the cognitive functions involved in processing of harmonic rules. Using functional magnetic resonance imaging, differential activation of a bilateral cortical network comprising the inferior frontal gyrus, superior temporal gyrus and premotor cortex was found. Using event-related potentials, the N2 evoked by each note in melodies was found to have longer latency and a more frontal distribution than that evoked in unstructured sequences.
Brain potentials and repetition effects during encoding and retrieval of words

Using event-related potentials (ERPs), this study utilized a study-test paradigm to investigate the existence of a common mechanism underlying repeated learning effects during encoding and retrieval. Results showed repeated learning effects occurred in both encoding and retrieval. The effect of encoding, however, appeared earlier and lasted longer than that of retrieval. Furthermore, the effect of implicit retrieval appeared earlier than that of explicit retrieval. The main scalp distributions of the repetition effects related to both encoding and retrieval occurred at parietal and central sites. Both ERP repetition effects manifested significantly larger and positive-going ERP response of repeated words compared with the words' first appearance. The ERP repetition effects support the hypothesis that there is common learning-related automatic processing during encoding and retrieval.
Silver nanoparticles from Pilimelia columellifera subsp. pallida SL19 strain demonstrated antifungal activity against fungi causing superficial mycoses

In this study, we present the in vitro antifungal activity of silver nanoparticles (AgNPs) synthesized from acidophilic actinobacterium Pilimelia columellifera subsp. pallida SL19 strain, alone and in combination with antibiotics viz., amphotericin B, fluconazole, and ketoconazole against pathogenic fungi, namely Candida albicans, Malassezia furfur, and Trichophyton erinacei. The minimum inhibitory concentration (MIC) and minimum biocidal concentration (MBC) of AgNPs against test fungi were evaluated. The fractional inhibitory concentration (FIC) index was determined to estimate antifungal activity of AgNPs combined with antibiotics. Antifungal activity of AgNPs varied among the tested fungal strains. M. furfur was found to be most sensitive to biogenic silver nanoparticles, followed by C. albicans and T. erinacei. The lowest MIC of AgNPs was noticed against M. furfur (16 μg ml−1). Synergistic effect was observed on C. albicans when AgNP were combined with amphotericin B and ketoconazole and on M. furfur with fluconazole and ketoconazole (FIC index of 0.5). Cytotoxic effect of AgNPs on HeLa and 3T3 cell lines was evaluated. The IC50 values were found to be 55 and 25 μg ml−1, respectively. The present study indicates that silver nanoparticles from P. columellifera subsp. pallida SL19 strain have antifungal activity, both alone and in combination with antibiotics, and offer a valuable contribution to nanomedicine.