Miracle-dz/UniFAR-FTUs huggingface dataset:
The Cyanide-Resistant Oxidase: To Inhibit or Not to Inhibit, That Is the Question

In recent years, there have been considerable advances in the characterization of the cyanide-resistant alternative pathway associated with plant respiration. The pathway consists of a single enzyme, a cyanide-resistant quinol oxidase called the AO, that shunts electrons off the cyanide-sensitive Cyt pathway at the level of the ubiquinone pool and reduces oxygen to water with no conservation of energy (for recent reviews, see Day et al., 1995; Siedow and Umbach, 1995; Wagner and Krab, 1995). cDNA and gene sequences for the AO from several species have been reported (Day et al., 1995), which has led to some understanding of the structural features of the oxidase (Day et al., 1995; Siedow and Umbach, 1995). Studying the partitioning of electron flow between the alternative and Cyt pathways using isolated mitochondria, Bahr and Bonner (1973) found that low concentrations of Cyt pathway inhibitors such as cyanide or antimycin diverted electrons onto the alternative pathway. However, specific inhibition of the AO, using compounds such as SHAM, did not divert electrons onto the Cyt pathway. These results suggested that electron flow through the alternative pathway took place only when electron transfer through the Cyt pathway was either at or near saturation. The validity of the Bahr-Bonner, or electron overflow, paradigm has been debated within the plant respiration community (Laties, 1982; Lambers, 1985). Most experimental evidence was consistent with the paradigm, and simultaneous measurement of oxygen uptake and ubiquinone redox poise qualitatively confirmed the Bahr-Bonner model (Dry et al., 1989). During succinate oxidation by isolated mitochondria, AO activity appeared only when the ubiquinone pool was more than 40 to 50% reduced, whereas the activity of the main pathway increased as a linear function of reduced ubiquinone at levels well below those needed for significant AO activity. The general acceptance of the electron overflow paradigm had several consequences. First, regulation of the alternative pathway through an electron overflow mechanism culminated in the proposal that the AO acted primarily in an "energy overflow" capacity (Lambers, 1985). The alternative pathway was envisioned as being active when the cytoplasm contained excess reducing equivalents and/or had a high adenylate charge (i.e. ATPADP ratio). The latter circumstance, in particular, will restrict electron flow through the Cyt pathway. Shunting electrons onto the alternative pathway allows continued operation of glycolysis and the TCA cycle, providing carbon skeletons and oxidation of excess carbohydrate, among other possibilities (Lambers, 1985). Second, acceptance of the electron overflow paradigm led to the use of AO inhibitors to quantify alternative pathway activity during respiration by intact plant tissues (Laties, 1982; Lambers, 1985). Any Question
Frailty is associated with objectively assessed sedentary behaviour patterns in older adults: Evidence from the Toledo Study for Healthy Aging (TSHA)

Objective The aim of this study was to examine the association of sedentary behaviour patterns with frailty in older people. Setting Clinical setting. Design Cross-sectional, observational study. Participants and measurements A triaxial accelerometer was used in a subsample from the Toledo Study for Healthy Aging (519 participants, 67–97 years) to assess several sedentary behaviour patterns including sedentary time per day, the number and duration (min) of breaks in sedentary time per day, and the proportion of the day spent in sedentary bouts of 10 minutes or more. Frailty was assessed using the Frailty Trait Scale (FTS). Regression analysis was used to ascertain the associations between sedentary behaviour patterns and frailty. Results Sedentary time per day and the proportion of the day spent in sedentary bouts of 10 minutes or more, were positively associated with frailty in the study sample. Conversely, the time spent in breaks in sedentary time was negatively associated with frailty. Conclusion In summary, breaking up sedentary time and time spent in sedentary behaviour are associated with frailty in older people.
Comparison of suppressive potency between prednisolone and prednisolone sodium succinate against mitogen‐induced blastogenesis of human peripheral blood mononuclear cells in‐vitro

Clinically, both prednisolone and prednisolone sodium succinate are widely used as immunosuppressive agents for the treatment of various allergic disorders. However, whether prednisolone sodium succinate itself has immunosuppressive or anti‐inflammatory effects is unclear, and prednisolone sodium succinate may exhibit its efficacy only after hydrolytic conversion to prednisolone in‐vivo. If this is the case, the impairment of prednisolone sodium succinate conversion to prednisolone in some clinical conditions may attenuate the efficacy of prednisolone sodium succinate. We therefore compared the pharmacological efficacy of prednisolone with that of prednisolone sodium succinate in‐vitro using human peripheral blood mononuclear cells (PBMCs). PBMCs were obtained from 5 healthy subjects and 1 patient with pneumonia. The cells were incubated in the presence of concanavalin A and the cell growth was estimated by 3‐(4,5‐dimethyl thiazo‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) assay. Both prednisolone and prednisolone sodium succinate dose‐dependently suppressed PBMC blastogenesis. Mean (s.d.) prednisolone and prednisolone sodium succinate IC50 (concentration of drug that gave 50% inhibition of cell growth) values were 580.0 (1037.9) and 3237.1 (4627.3) nm, respectively. The ratio of prednisolone IC50/prednisolone sodium succinate IC50 ranged from 0.005 to 0.230. Thus, prednisolone sodium succinate potency was markedly lower than that of prednisolone. After incubation of PBMCs with 100 μm prednisolone sodium succinate, 22.7–42.9 μm prednisolone was liberated into the culture medium, as determined by HPLC. The ratio of prednisolone liberation from prednisolone sodium succinate was not affected by the presence of fetal bovine serum or PBMC, or both, in the culture medium. These results suggested that the PBMC‐suppressive effects of prednisolone sodium succinate might be due, at least partially, to prednisolone liberated from prednisolone sodium succinate into the culture medium. Prednisolone sodium succinate can be converted to prednisolone in the absence of serum or PBMCs, but the ratio of this conversion was very slow (t£frac12; > 4 days). Therefore, impairment of the enzymatic conversion of prednisolone sodium succinate to prednisolone in some pathological conditions such as liver diseases may result in attenuation of the clinical efficacy of prednisolone sodium succinate.
μ opioid receptor gene as a candidate for the study of obsessive compulsive disorder with and without tics

Obsessive compulsive disorder (OCD) is a complex psychiatric disease characterized by recurring obsessions or compulsions that cause significant distress to the patient. The etiology of this disorder remains largely unknown, although a genetic component has been suggested. Many candidates genes have been evaluated based on a possible serotoninergic and dopaminergic brain dysfunction. We postulate the μ opioid receptor (MOR) gene as a candidate because some observations support a role of the opioid system in OCD. The opioid antagonist, naloxone, rapidly exacerbates OCD symptoms and the opioid agonist, tramadol, was reported to be effective in the treatment of some patients. We studied two single nucleotide polymorphisms (C17T and A118G) in 51 trios with OCD. Genotyping was analyzed with transmission desequilibrium test (TDT). The allelic variant +17T of the C17T polymorphism had a low frequency (1%) in our population that did not allow for statistic analysis. However, for the allelic variant +G of the A118G polymorphism we were able to performed statistical comparisons. Our results showed a trend toward significance (χ2 McNemar = 3.6, P = 0.065) for TDT in patients with comorbid tics. It is an interesting finding that should be tested in a larger sample of OCD patients with tics. © 2004 Wiley‐Liss, Inc.
Effects of Nimodipine and Magnesium Sulfate on Endogenous Antioxidant Levels in Brain Tissue After Experimental Head Trauma

To examine the effects of calcium antagonists nimodipine and magnesium sulfate (MgSO4) on tissue endogenous antioxidant levels, the authors studied superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels in rabbit brain 1 hour after experimental head trauma. Forty New Zealand rabbits were anesthetized and randomly divided into four groups. Group 1 (n = 10) was the sham operated group. Group 2 (n = 10), the control group, received head trauma and no treatment. Group 3 (n = 10) received head trauma and intravenous (IV) 2 &mgr;gr/kg nimodipine. Group 4 (n = 10) received head trauma and IV 100 mg/kg MgSO4. Head trauma was delivered by performing a craniectomy over the right hemisphere and dropping a weight of 20 g from a height of 40 cm. In the right (traumatized) hemisphere, SOD and GPx decreased by 57.60% ± 9.60% and 72.93% ± 5.51% respectively from sham values. Magnesium sulfate, but not nimodipine, reduced the magnitude of decrease of SOD and GPx to 19.43% ± 7.15% and 39.01% ± 7.92% respectively from sham values. In the left (nontraumatized) hemisphere, MgSO4 increased SOD to 42.43% ± 24.76% above sham values. The authors conclude that MgSO4 treatment inhibited the decrease in SOD and GPx levels in experimental brain injury.
Tuberculous Pericardial Effusions in Children

Current data on tuberculous pericardial effusion in children are limited. In this study, the cases of 30 children with tuberculous pericardial effusion were reviewed retrospectively. The prevalence of human immunodeficiency virus and of culture-confirmed tuberculosis was high. Chest radiography provided lower diagnostic sensitivity than sonography but detected all large and complicated effusions. Outcomes were generally good, and residual complications were mainly due to comorbidity.
Fate and Fear: Risk and its Consequences in Africa

We review the evidence on risk and its consequences in Africa. We argue that too much attention has been given to the risk management and coping mechanisms used by households, and not enough on its implications and the scope for interventions. Much of the empirical work on risk in developing countries has also focused largely on the short-run implications, and has ignored the long-run. Risk and shocks have important long-run implications for growth and poverty, and distinguishing risk from shocks adds further insights. A few key missing dimensions in the work on risk and its consequences in Africa are also explored. First, microeconomic research on risk has limited itself to work on risks that are `easy` to analyze, such as weather shocks. These risks are still dominating the life of many of the poor, dependent on agricultural production, but these risks are not necessarily central to the growth and poverty tragedy in Africa: which is driven by the lack of African and foreign investment in Africa. In particular, the risks related to poorly functioning markets and economic and political institutions have been underresearched by microeconomists, often leaving the initiative to macroeconomic research. A few examples are offered that appear to start tackling these questions. Finally, research on risk and its implications has to embrace more seriously the experimental and behavioural literature. The research frameworks used in most work on risk and its implications are based on shaky behavioural foundations, building on the expected utility framework - but testing these foundations in the environments where risk really matters, such as the poorest settings of Africa, has largely been lacking, limiting our understanding of whether they matter.
Language and Nature

I would like to discuss an approach to the mind that considers language and similar phenomena to be elements of the natural world, to be studied by ordinary methods of empirical inquiry. I will be using the terms "mind" and "mental" here with no metaphysical import. Thus I understand "mental" to be on a par with "chemical", "optical", or "electrical". Certain phenomena, events, processes and states are informally called "chemical" etc., but no metaphysical divide is suggested thereby. The terms are used to select certain aspects of the world as a focus of inquiry. We do not seek to determine the true criterion of the chemical, or the mark of the electrical, or the boundaries of the optical. I will use "mental" the same way, with something like ordinary coverage, but no deeper implications. By "mind" I just mean the mental aspects of the world, with no more interest in sharpening the boundaries or finding a criterion than in other cases. I'll use the terms "linguistic" and "language" in much the same way. We focus attention on aspects of the world that fall under this informal rubric, and try to understand them better. In the course of doing so we may-and apparently do-develop a concept that more or less resembles the informal notion of "language", and. postulate that such objects are among the things in the world, alongside of complex molecules, electrical fields, the human visual system, and so on. A naturalistic approach to linguistic and mental aspects of the world seeks to construct intelligible explanatory theories, taking as "real" what we are led to posit in this quest, and hoping for eventual unification with the "core" natural sciences: unification, not necessarily reduction. Largescale reduction is rare in the history of the sciences. Commonly the more "fundamental" science has had to undergo radical revision for unification to proceed. The case of chemistry and physics is a recent example;
Usefulness of a New Radiofrequency Thermal Balloon Catheter for Pulmonary Vein Isolation:

Introduction: A rapidly firing or triggered ectopic focus located within a pulmonary vein (PV) or close to the PV ostium could induce atrial fibrillation (AF). The aim of this study was to evaluate the efficacy and safety of a radiofrequency thermal balloon catheter for isolation of the PV from the left atrium (LA).
Efeitos biológicos in vitro de agentes físicos utilizados em fisioterapia

O uso de radiobiocomplexos marcados com 99mtecnecio tem contribuido para avancos em Ciencias da Saude. Na marcacao desses radiobiocomplexos utiliza-se o redutor cloreto estanoso (SnCl2). Efeitos citotoxicos e genotoxicos do SnCl2 tem sido descritos. Atraves de modelos experimentais em nivel molecular, celular e sistemico estas alteracoes podem ser avaliadas. Entre os novos agentes fisicos sugeridos para a pratica da Fisioterapia Dermato-Funcional, ha os que sao de natureza eletromagnetica (campos eletromagneticos pulsados, a radiofrequencia e a luz intensa pulsada) e os de natureza mecânica (ondas sonicas). A literatura a respeito dos agentes fisicos gera duvidas quanto aos seus efeitos. Seu uso correto e importante nao so para proteger a saude publica, mas tambem para justificar niveis de exposicao que resultem em efeitos biologicos significativos. Dessa forma, o objetivo desse estudo e verificar os possiveis efeitos destes agentes fisicos em plasmidios bacterianos e em culturas bacterianas na presenca e na ausencia de cloreto estanoso e na marcacao de elementos sanguineos com o 99mtecnecio. Sangue de ratos Wistar foi exposto as fontes citadas e a marcacao de celulas sanguineas com 99mtecnecio foi realizada. Culturas de E. coli AB1157 e amostras DNA plasmidial tambem foram expostas aos agentes fisicos. As consequencias biologicas associadas a esses agentes nao foram capazes de interferir em algumas propriedades dos constituintes sanguineos, nem na sobrevivencia de E. coli ou na mobilidade eletroforetica do DNA plasmidial. O carater multidisciplinar ficou claro neste estudo desde a interacao entre o Setor de Medicina Nuclear da UERJ e o Laboratorio de Agentes Fisicos da Universidade Maimonides na Argentina ate a uniao entre um orientador (biomedico e fisioterapeuta) e uma orientanda (fisioterapeuta), contando com colaboradores da area de Fisica e Biologia, possibilitando novas ideias e perspectivas, agregando o conhecimento de diferentes areas
Evaluation of Epidermal Growth Factor Receptor (EGFR) by Chromogenic In Situ: Hybridization (CISH™) and Immunohistochemistry (IHC) in Archival Gliomas Using Bright-Field Microscopy

Overexpression of EGFR secondary to EGFR gene amplification is a common feature in primary malignant gliomas. To correctly assess EGFR protein and gene level as possible prognostic and predictive markers in gliomas, straightforward assays, which can be used routinely in the pathology laboratory to evaluate EGFR status, becomes critical. EGFR gene amplification and chromosome 7 aneuploidy was detected in 34 formalin-fixed, paraffin-embedded benign and malignant gliomas by chromogenic in situ hybridization (CISH™) using digoxigenin-labeled EGFR and biotin-labeled chromosome 7 centromeric probes. The results were evaluated by bright-field microscopy under a 40× objective lens. EGFR protein level was detected by immunohistochemistry (IHC) using monoclonal antibody 31G7. Five cases, 3 astrocytoma grade III (33%) and 2 glioblastoma multiforme (GBM) (33%), had EGFR amplification displayed as diaminobenzidine-stained multiple dots suggesting the pattern of double-minute chromosomes. Chromosome 7 polysomy was found in 68% gliomas, 100% GBM, 67% astrocytoma grade III, 42% astrocytoma grade II, 50% astrocytoma grade I, 100% ependymoma, and the 1 case of mixed glioma III. High expression of EGFR protein was present in 62% gliomas and displayed membrane and cytoplasmic staining. All tumors with EGFR gene amplification showed EGFR high expression. High expression of EGFR without gene amplification was observed in all grades of gliomas. Simultaneous detection of EGFR gene copies or chromosome 7 centromere signals along with tissue morphology allows us to compare CISH™ results easily with IHC results. Our results show that CISH™ is an objective, practical, and accurate assay to screen for EGFR gene status in gliomas.
The impact of Computer-assisted Test Interpretation on Physician Decision Making

This research investigated the effect of computer-assisted test interpretation (CATI) on physicians' readings of electrocardiograms (ECGs). The authors used an experimental method based on direct observations of 22 cardiologists, each reading 80 ECGs, for a total of 1,760 (of which 1,745 were used in the study). There were 40 sets of clini cally-matched pairs of ECGs, one with CATI and one without. Reading time was ob served and interpretation accuracy was measured by criterion-referenced aggregate scoring. To control for potential biases, the findings were subjected to multivariate analyses using ordinary least-squares regressions. The impact of CATI on cardiolo gists' readings of ECGs is demonstrably beneficial: the main empirical conclusion of this study is that, compared with conventional interpretation, the use of computer- assisted interpretation of ECGs cuts physician time by an average of 28% and signif icantly improves the concordance of the physician's interpretation with the expert benchmark, without increasing the false-positive rate. Moreover, CATI is the most ac curate and saves the most time when the ECGs have many unambiguous diagnoses. Given that computers alone cannot perform the task of cardiovascular diagnosis, and that cardiologists' ECG interpretations are greatly enhanced by ubiquitous CATI tech nology, it appears that the best approach is one that combines person and machine. Key words: electrocardiogram interpretation; computer-assisted test interpretation; physician decision making; diagnostic concordance; technology utilization. (Med Decis Making 1997;17:80-86)
Birds Generally Carry a Small Repertoire of Bitter Taste Receptor Genes

As they belong to the most species-rich class of tetrapod vertebrates, birds have long been believed to possess an inferior taste system. However, the bitter taste is fundamental in birds to recognize dietary toxins (which are typically bitter) in potential food sources. To characterize the evolution of avian bitter taste receptor genes (Tas2rs) and to test whether dietary toxins have shaped the repertoire size of avian Tas2rs, we examined 48 genomes representing all but 3 avian orders. The total number of Tas2r genes was found to range from 1 in the domestic pigeon to 12 in the bar-tailed trogon, with an average of 4, which suggested that a much smaller Tas2r gene repertoire exists in birds than in other vertebrates. Furthermore, we uncovered a positive correlation between the number of putatively functional Tas2rs and the abundance of potential toxins in avian diets. Because plant products contain more toxins than animal tissues and insects release poisonous defensive secretions, we hypothesized that herbivorous and insectivorous birds may demand more functional Tas2rs than carnivorous birds feeding on noninsect animals. Our analyses appear to support this hypothesis and highlight the critical role of taste perception in birds.
The Souls of Black Folk

The voices of African-American thinkers were often systematically and arbitrarily excluded from philosophical discourse for several reasons. The first, and more sinister of these, is similar to the exclusion of women's voices. The legacy of racism, like that of sexism, is now recognized to have been a blight up on the academy for centuries and lost in that rejection were the voices of some very sophisticated, very creative, and potentially very critical voices. The second reason is related to the path academic philosophy took in the 20th century.
Blockade of the RhoA-JNK-c-Jun-MMP2 Cascade by Atorvastatin Reduces Osteosarcoma Cell Invasion*

Osteosarcoma is characterized by a high malignant and metastatic potential, which points to the need for new therapeutic strategies to prevent cell metastasis. In this study, we show that statin-induced HMG-CoA reductase inhibition reduces cell migration and invasion in human and murine osteosarcoma cells, independently of the genotype. The statin-induced reduction of cell migration and invasion was independent of induction of apoptosis and was geranylgeranylpyrophosphate-dependent. The statin reduced matrix metalloproteinase (MMP) 2, 9, and 14 and TIMP2 expression or activity in invading cells. Forced expression of MMP2 and MMP14 overcame the inhibitory effect of the statin on cell invasion, suggesting a role for these MMPs in invasive potential. We also investigated the mechanisms involved in the reduced MMP2 activity and cell invasion. Inhibition of JNK, but not ERK1/2 signaling, reduced MMP2 activity. Pharmacological or constitutive activation of JNK overcame the reduced MMP2 activity and cell invasion induced by the statin. The statin decreased JNK phosphorylation and c-Jun nuclear translocation, suggesting that HMG-CoA reductase inhibition targets the JNK-c-Jun signaling pathway. We showed that mevalonate or geranylgeranylpyrophosphate treatment prevented the statin-induced reduction in JNK phosphorylation, MMP2 activity, and cell invasion. Forced expression of a constitutively active form of RhoA increased JNK phosphorylation and overcame the inhibitory effect of atorvastatin on MMP2 activity and cell invasion. The data establish a link between RhoA, JNK, c-Jun, and MMP2 activity that is functionally involved in the reduction in osteosarcoma cell invasion by the statin. This suggests a novel strategy targeting RhoA-JNK-c-Jun signaling to reduce osteosarcoma cell tumorigenesis.