Miracle-dz/UniFAR-FTUs huggingface dataset:
cDNA Cloning and Expression of the Cardiac Na+/Ca2+ Exchanger from Mozambique Tilapia (Oreochromis mossambicus) Reveal a Teleost Membrane Transporter with Mammalian Temperature Dependence*

The complete cDNA sequence of the tilapia cardiac Na+/Ca2+ exchanger (NCX-TL1.0) was determined. The 3.1-kb transcript encodes a protein 957 amino acids in length, with a predicted signal peptide cleaved at residue 31 and two potential N-glycosylation sites in the extracellular N terminus. Hydropathy analysis and sequence comparison predicted a mature protein with nine transmembrane-spanning segments, consistent with the structural topologies of other known mammalian and teleost NCX isoforms. Overall sequence comparison shows high identity to both trout NCX-TR1.0 (∼81%) and mammalian NCX1.1 (∼73%), and phylogenetic analyses confirmed its identity as a member of the NCX1 gene family, expressing exons A, C, D, and F in the alternative splice site. Sequence identity is even higher in the α-repeats, the exchanger inhibitory peptide (XIP) site, and Ca2+-binding domains, which is reflected in the functional and regulatory properties of tilapia NCX-TL1.0. When NCX-TL1.0 was expressed in Xenopus oocytes and the currents were measured in giant excised patches, they displayed both positive regulation by Ca2+ and Na+-dependent inactivation in a manner similar to trout NCX-TR1.0. However, tilapia NCX-TL1.0 exhibited a relatively high sensitivity to temperature compared with trout NCX-TR1.0. Whereas trout NCX-TR1.0 currents displayed activation energies of ∼7 kJ/mol, tilapia NCX-TL1.0 currents showed mammal-like temperature dependence, with peak and steady-state current activation energies of 53 ± 9 and 67 ± 21 kJ/mol, respectively. Using comparative sequence analysis, we highlighted 10 residue positions in the N-terminal domain of the NCX that, in combination, may confer exchanger temperature dependence through subtle changes in protein flexibility. Tilapia NCX-TL1.0 represents the first non-mammalian NCX to exhibit a mammalian temperature dependence phenotype and will prove to be a useful model in defining the interplay between molecular flexibility and stability in NCX function.
Leituras brasileiras sobre a Nova Ordem Internacional (1989-1991)

O objetivo desse artigo e analisar algumas das leituras brasileiras sobre a Nova Ordem Internacional, nocontexto das mudancassocio-politicasinternas e externas que se processavam. Essa analise foi feita a partir dos textos produzidos por tres personagens da historia da politica externa brasileira: CelsoLafer, Gelson Fonseca Junior e Rubens Ricupero. Atraves de seus textos pudemos identificar aresilienciade certos temas que sao caros ao pensamento social brasileiro do seculo XX, como a aspiracao por autonomia, o desejo deimplementacaode um projeto nacional e apercepcao do Brasil como pais que compartilha valores com o mundo ocidental.
Integrated vulnerability management system for enterprise networks

The number of vulnerabilities in enterprise networks has greatly increased recently as seen from frequent vulnerability reports from organizations, such as Microsoft and the CERT. Researchers in a number of organizations are currently working to develop and deploy frameworks to comprehensively manage these network vulnerabilities. This paper examines the existing attempts to solve this problem and the gaps in the existing methodologies. The paper presents our proposed integrated vulnerability management (IVM) framework based on open software standards.
Inheritance of hypoadrenocorticism in bearded collies.

OBJECTIVE To assess heritability and mode of inheritance for hypoadrenocorticism in Bearded Collies. ANIMALS 635 Bearded Collies. PROCEDURES Dogs were classified as affected by hypoadrenocorticism or unaffected. Phenotypic and pedigree data were analyzed. Heritability was estimated by use of Bayesian statistical methods. Regressive logistic models for complex segregation analyses were used to characterize mode of inheritance. RESULTS Hypoadrenocorticism was diagnosed in 60 (9.4%) dogs. Heritability of hypoadrenocorticism was estimated to be 0.76 with both sexes affected with equal probability. Evaluation of the pedigrees did not support a Mendelian autosomal dominant mode of inheritance. Evidence from the complex segregation analysis for a single locus of large effect on hypoadrenocorticism was not convincing. CONCLUSIONS AND CLINICAL RELEVANCE Hypoadrenocorticism in Bearded Collies is highly heritable. Although a precise genetic mechanism responsible for inheritance of the disorder remains undetermined, breeding decisions must include consideration of the genetic likelihood of passing on this deleterious disorder to offspring of affected dams and sires.
Prevalence and influence of hyperthyroidism on the long-term outcome of catheter ablation for drug-refractory atrial fibrillation.

BACKGROUND Hyperthyroidism is usually regarded as a reversible cause of atrial fibrillation (AF); however, one-third of patients remain in AF despite euthyroid restoration. We hypothesized that a significant number of AF patients with hyperthyroidism (Hyperthyroid-AF) as well as those without (Non-thyroid-AF) would benefit from catheter ablation of AF (AF ablation). This study aimed to clarify the prevalence of hyperthyroidism in candidates for AF ablation and to compare the long-term outcome of AF ablation between the Hyperthyroid-AF and Non-thyroid-AF groups. METHODS AND RESULTS This study enrolled 337 consecutive patients with AF who underwent a first AF ablation that mainly involved extensive encircling pulmonary vein isolation. Sixteen (4.7%) patients had hyperthyroidism; the remaining 321 (95.3%) did not. In the Hyperthyroid-AF patients, a euthyroid state had been restored for at least 3 months before the ablation. During a mean follow-up period of 4±1 years after ablation, AF recurred in 7 patients (44%) with Hyperthyroid-AF and in 139 patients (43%) with Non-thyroid-AF (P=0.91 by the log-rank test). In the multivariate Cox regression models, the presence of hyperthyroidism was not associated with a higher risk of AF recurrence (hazard ratio, 0.87; 95% confidence interval, 0.40-1.88; P=0.73). CONCLUSIONS In the AF ablation candidates without structural heart disease, hyperthyroidism was not rare. After euthyroid restoration on pharmacological treatment, hyperthyroidism was not associated with a higher risk of AF recurrence.
Species Variability in Platelet and other Cellular Responsiveness to Thrombin Receptor-derived Peptides

Summary The aggregation of platelets from a variety of animal species in response to thrombin receptor-derived activating peptides was evaluated. A series of 14-(SFLLRNPNDKYEPF), 7-(SFLLRNP-NH2), 6-(SFLLRN-HN2) or 5-(SFLLR-NH2) residue peptides, the structures of which were based on the deduced amino acid sequence of the human thrombin receptor, promoted full aggregation of platelets in plasma from humans, African Green and Rhesus monkeys, baboons and guinea pigs at 4-50 μM depending on the peptide used. Platelets in plasma from rabbit, dog, pig, and hamster underwent a shape change but failed to aggregate in response to these peptides over 3 log units of peptide up to 800 μM, despite being fully responsive to human thrombin. However, because the receptor peptides induced shape change in the platelets from these non-aggregating species, they apparently can activate some of the intracellular signaling system(s) usually initiated by thrombin in these platelets. In contrast, platelets from rats did not undergo shape change or aggregate in response to the peptides. A 7-residue receptor-derived peptide based on the deduced amino acid sequence of the clone of the hamster thrombin receptor (SFFLRNP-N2) was nearly as efficacious as the corresponding human receptor-derived 7-residue peptide to promote aggregation of human platelets. However, the hamster peptide could not promote aggregation of hamster platelets in plasma at up to 800 μM peptide, while a shape change response was elicited. Platelets from rats, rabbits and pigs also did not aggregate in response to this peptide derived from the hamster thrombin receptor, but all species except the rat underwent a shape change. Longer 17-residue peptides derived from the sequences of the hamster or mouse thrombin receptors elicited aggregation of human platelets but no aggregation of the hamster platelets. In contrast, the human 14- and 5-residue and the hamster 7-residue thrombin receptor-derived peptides promoted mitogenesis of CCL39 cells, a hamster fibroblast cell line. Finally, the human 6-residue thrombin receptor-derived peptide promoted contraction of normal and de-endothelialized canine coronary artery rings, despite having no pro-aggregatory effect on canine platelets. Taken together, these results demonstrate that the thrombin receptor-derived peptides are able to mimic many, but not all, of the activating effect of thrombin in different tissues from multiple species. The heterogeneity of responsiveness to these peptides should be taken into account in future experiments designed to elucidate the mechanism of thrombin stimulation of platelets and other cells.
Visualization of the Higgs Interaction in the Standard Model and Beyond the Standard Model Physics

We use visualization to investigate the Higgs Interaction in the Standard Model and Beyond the Standard Model Physics. The Higgs discovery at the Large Hadron Collider has allowed for a precise determination of the Higgs Potential. We visualize this potential and the Higgs interactions with the fermions of the Standard Model as well as beyond standard model such as interactions with Dark matter and heavy neutrinos. We animate these potentials with respect to energy and temperature (different energies and temperatures per frame) to see how the potential changes shape as one moves up in energy or temperature.
Inhibition of Histone Deacetylase 6 Acetylates and Disrupts the Chaperone Function of Heat Shock Protein 90

The hydroxamic acid (HAA) analogue pan-histone deacetylase (HDAC) inhibitors (HDIs) LAQ824 and LBH589 have been shown to induce acetylation and inhibit the ATP binding and chaperone function of heat shock protein (HSP) 90. This promotes the polyubiquitylation and degradation of the pro-growth and pro-survival client proteins Bcr-Abl, mutant FLT-3, c-Raf, and AKT in human leukemia cells. HDAC6 is a member of the class IIB HDACs. It is predominantly cytosolic, microtubule-associated α-tubulin deacetylase that is also known to promote aggresome inclusion of the misfolded polyubiquitylated proteins. Here we demonstrate that in the Bcr-abl oncogene expressing human leukemia K562 cells, HDAC6 can be co-immunoprecipitated with HSP90, and the knock-down of HDAC6 by its siRNA induced the acetylation of HSP90 and α-tubulin. Depletion of HDAC6 levels also inhibited the binding of HSP90 to ATP, reduced the chaperone association of HSP90 with its client proteins, e.g. Bcr-Abl, and induced polyubiquitylation and partial depletion of Bcr-Abl. Conversely, the ectopic overexpression of HDAC6 inhibited LAQ824-induced acetylation of HSP90 and α-tubulin and reduced LAQ824-mediated depletion of Bcr-Abl, AKT, and c-Raf. Collectively, these findings indicate that HDAC6 is also an HSP90 deacetylase. Targeted inhibition of HDAC6 leads to acetylation of HSP90 and disruption of its chaperone function, resulting in polyubiquitylation and depletion of pro-growth and pro-survival HSP90 client proteins including Bcr-Abl. Depletion of HDAC6 sensitized human leukemia cells to HAA-HDIs and proteasome inhibitors.
Antibacterial activity of Omani honey alone and in combination with gentamicin.

OBJECTIVE To investigate the anti-Staphylococcal activity of Omani honey, gentamicin and combination of the 2. METHODS This study was conducted in the Laboratories of the Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, Sultanate of Oman in 2004. Thirty honey samples from different parts of Oman were investigated for their activity against Staphylococcus aureus, using an agar well diffusion technique. The honey sample giving the best anti-staphylococcal activity was selected and further investigated for the killing rate on its own and in combination with gentamicin using tube dilution technique. RESULTS Marked variations in the antibacterial activity of the different honey samples were observed. Thirteen of the Omani honey samples (43%) showed excellent anti Staphylococcus aureus activity. The best of the excellent honey samples (OH26), at a concentration of 50%, showed killing rate of 38% of Staphylococcus aureus at 30 minutes and 45% at one hour. Gentamicin (at 4 microg/ml) killed 70% and 88% while the rate of killing for the combination of honey and gentamicin was superior with 92% and 93% killing in the same duration. CONCLUSION Omani honey, in-vitro, possess anti-Staphylococcus aureus activity, which enhances gentamicin activity by 22% in the early phases of interaction.
A Sensitive Method for Detecting EGFR Mutations in Non-small Cell Lung Cancer Samples with Few Tumor Cells

Background: Detection of epidermal growth factor receptor (EGFR) mutations in advanced non-small cell lung cancer (NSCLC) patients has relied on DNA purification from biopsies, amplification, and sequencing. However, the number of tumor cells in a sample is often insufficient for EGFR assessment. Methods: We prospectively screened 1380 NSCLC patients for EGFR mutations but found that 268 were not evaluable because of insufficient tumor tissue. We therefore developed and validated a method of detecting EGFR mutations in these samples. Tumor cells were microdissected into polymerase chain reaction buffer and amplified. EGFR mutations were detected by length analysis of fluorescently labeled polymerase chain reaction products and TaqMan assay. Results: We determined EGFR status in 217 (81%) of the 268 primary NSCLC samples not evaluable in our original study—fresh and paraffin-embedded with less than 150 cells. Exon 19 deletions were detected in 11.5% of patients and exon 21 L858R mutations in 5.5%. In addition, the exon 20 T790M mutation was detected in 6 of 15 (40%) patients at the time of progression to erlotinib. The primary, sensitive mutation was present in all tumor cells, whereas the T790M mutation was absent in some groups. Conclusions: The method presented here eliminates the need for DNA purification and allows for detection of EGFR mutations in samples containing as few as eight cancer cells.
Targeted Disruption of the Osteoblast/Osteocyte Factor 45 Gene (OF45) Results in Increased Bone Formation and Bone Mass*

We have previously described osteoblast/osteocyte factor 45 (OF45), a novel bone-specific extracellular matrix protein, and demonstrated that its expression is tightly linked to mineralization and bone formation. In this report, we have cloned and characterized the mouse OF45 cDNA and genomic region. Mouse OF45 (also called MEPE) was similar to its rat orthologue in that its expression was increased during mineralization in osteoblast cultures and the protein was highly expressed within the osteocytes that are imbedded within bone. To further determine the role of OF45 in bone metabolism, we generated a targeted mouse line deficient in this protein. Ablation ofOF45 resulted in increased bone mass. In fact, disruption of only a single allele of OF45 caused significantly increased bone mass. In addition, knockout mice were resistant to aging-associated trabecular bone loss. Cancellous bone histomorphometry revealed that the increased bone mass was the result of increased osteoblast number and osteoblast activity with unaltered osteoclast number and osteoclast surface in knockout animals. Consistent with the bone histomorphometric results, we also determined thatOF45 knockout osteoblasts produced significantly more mineralized nodules in ex vivo cell cultures than did wild type osteoblasts. Osteoclastogenesis and bone resorption in ex vivo cultures was unaffected by OF45 mutation. We conclude that OF45 plays an inhibitory role in bone formation in mouse.
All in the Family: Family Folklore, Objectivity and Self-Censorship

This past Thanksgiving, my mother died. I spent the holiday taking plastic garbage bags of her clothing to the Salvation Army. I also went through her jewel-boxes, her drawers, her cedar chest. In doing this, I uncovered remnants of my mother's life, pieces of her that brought back memories. My sister and I sat on her bed, pulling necklaces out of a box, asking each other questions like: "Do you remember when she used to wear this with that long brown dress? " We found old photographs of our parents and grandparents. We found mimeographed sheets bearing family trees. It was a time to remember, to exchange shared memories of family history. It was a time rife with folklore, but it wasn't a time to collect folklore. And then I found it: a simple photocopied sheet of paper. I burst out laughing. I had just stood in the hospital a few days ago and watched her die. But here I was in her dining room sifting through pieces of her life, and what I found made me laugh until I almost cried. The paper I held was an informational sheet on sustaining grapes-Miraculous Sustaining Grapes For the Latter Time, no less-put out by a group called "Mary's Helpers" in Elmhurst, Illinois. I was doing something no folklorist should admit that they ever do. I was laughing like hell at my mother's beliefs. And to compound this cardinal sin of folkloric objectivity, I am now putting it down on paper. True, at the time, I didn't think I would ever use this information myself. My interests in folklore lay within the sphere of Judaism; I had no intention of ever
Ionising radiation and cancer risks: What have we learned from epidemiology?

Purpose: Epidemiologic studies of persons exposed to ionising radiation offer a wealth of information on cancer risks in humans. The Life Span Study cohort of Japanese A-bomb survivors, a large cohort that includes all ages and both sexes with a wide range of well-characterised doses, is the primary resource for estimating carcinogenic risks from low linear energy transfer external exposure. Extensive data on persons exposed for therapeutic or diagnostic medical reasons offer the opportunity to study fractionated exposure, risks at high therapeutic doses, and risks of site-specific cancers in non-Japanese populations. Studies of persons exposed for occupational and environmental reasons allow a direct evaluation of exposure at low doses and dose rates, and also provide information on different types of radiation such as radon and iodine-131. This article summarises the findings from these studies with emphasis on studies with well-characterised doses. Conclusions: Epidemiologic studies provide the necessary data for quantifying cancer risks as a function of dose and for setting radiation protection standards. Leukaemia and most solid cancers have been linked with radiation. Most solid cancer data are reasonably well described by linear-dose response functions although there may be a downturn in risks at very high doses. Persons exposed early in life have especially high relative risks for many cancers, and radiation-related risk of solid cancers appears to persist throughout life.
Effects of obstructive sleep apnea on endothelin-1 and blood pressure.

OBJECTIVE To evaluate blood pressure and humoral vasoconstrictor responses to recurrent episodes of obstructive sleep apnea and the effects of therapy by means of continuous positive airway pressure. PATIENTS AND METHODS We prospectively evaluated overnight changes in hemodynamics, oxygen saturation, the apnea-hypopnea index, circulating endothelin-1, norepinephrine and plasma renin activity in 22 patients with severe obstructive sleep apnea before and after successful therapy using continuous positive airway pressure therapy (three measurements). Measurements of endothelin-1 and blood pressure were also obtained on three occasions, at similar times, in 12 healthy control subjects without sleep disturbances. RESULTS Mean arterial pressure and endothelin-1 concentrations increased significantly after 4 h of untreated obstructive sleep apnea, and decreased after 5 h of continuous positive airway pressure. Changes in endothelin-1 levels were correlated with changes in mean arterial pressure (r = 0.44, P < 0.02) and with changes in oxygen saturation (r = 0.37, P < 0.05). Norepinephrine levels and plasma renin activity did not change significantly in patients with obstructive sleep apnea, and were not correlated with changes in blood pressure or oxygen saturation. In controls, blood pressure measurements at similar times during the night showed changes directionally opposite to that seen in obstructive sleep apnea, while endothelin-1 levels remained unchanged. CONCLUSIONS Sleep apnea elicits increases in blood pressure and endothelin-1, with reductions in both after treatment. Vasoconstrictor and mitogenic effects of endothelin-1 may be implicated in increased cardiovascular risk in patients with obstructive sleep apnea.
Space Microbiology

SUMMARY The responses of microorganisms (viruses, bacterial cells, bacterial and fungal spores, and lichens) to selected factors of space (microgravity, galactic cosmic radiation, solar UV radiation, and space vacuum) were determined in space and laboratory simulation experiments. In general, microorganisms tend to thrive in the space flight environment in terms of enhanced growth parameters and a demonstrated ability to proliferate in the presence of normally inhibitory levels of antibiotics. The mechanisms responsible for the observed biological responses, however, are not yet fully understood. A hypothesized interaction of microgravity with radiation-induced DNA repair processes was experimentally refuted. The survival of microorganisms in outer space was investigated to tackle questions on the upper boundary of the biosphere and on the likelihood of interplanetary transport of microorganisms. It was found that extraterrestrial solar UV radiation was the most deleterious factor of space. Among all organisms tested, only lichens (Rhizocarpon geographicum and Xanthoria elegans) maintained full viability after 2 weeks in outer space, whereas all other test systems were inactivated by orders of magnitude. Using optical filters and spores of Bacillus subtilis as a biological UV dosimeter, it was found that the current ozone layer reduces the biological effectiveness of solar UV by 3 orders of magnitude. If shielded against solar UV, spores of B. subtilis were capable of surviving in space for up to 6 years, especially if embedded in clay or meteorite powder (artificial meteorites). The data support the likelihood of interplanetary transfer of microorganisms within meteorites, the so-called lithopanspermia hypothesis.
Auxin gradient is crucial for the maintenance of root distal stem cell identity in Arabidopsis

The plant hormone auxin plays a critical role in the maintenance of root stem cell niches in Arabidopsis. We have recently reported that WUSCHEL-RELATED HOMEOBOX 5 (WOX5) transcription factor modulates free auxin production in the quiescent center (QC) of the root and its expression is inhibited in a feedback-dependent manner by canonical auxin signaling that involves indole-3-acetic acid 17 (IAA17) auxin response repressor. WOX5-IAA17 feedback circuit assures the maintenance of auxin response maximum in the root tip and thereby contributes to the maintenance of distal stem cell (DSC) populations. Here, we provide evidence to show that an optimal auxin maximum in QC guided auxin signaling gradient in root tips is crucial for maintaining root DSC identity.