Miracle-dz/UniFAR-FTUs huggingface dataset:
The psychosis susceptibility gene ZNF 804 A is associated with less impaired 1 cognitive performance in schizophrenia . 2 3

The psychosis susceptibility gene ZNF804A is associated with less impaired 1 cognitive performance in schizophrenia. 2 3 James T.R. Walters MRCPsych, B.M. , Aiden Corvin MRCPsych. , Ph.D., Hywel Williams 4 Ph.D., Milan Dragovic Ph.D., Emma M Quinn M.Sc., Róisín Judge B.A., Daniel J. Smith 5 M.D. , Nadine Norton Ph.D., Ina Giegling Ph.D., Annette M. Hartmann Ph.D., Hans-Jürgen 6 Möller M.D., Pierandrea Muglia M.D., Valentina Moskvina Ph.D., Therese O’Donoghue 7 M.Sc., Bharti Morar Ph.D., Matthew Cooper M.Sc., David Chandler Ph.D., Assen 8 Jablensky M.D., Ph.D., Michael Gill MRCPsych. , M.D. , Michael J. Owen FRCPsych, 9 Ph.D., Luba Kaladjieva M.D., Ph.D., Derek W. Morris Ph.D., Michael C. O’Donovan 10 FRCPsych, Ph.D., Dan Rujescu M.D., Gary Donohoe D.Clin. Psych, Ph.D. 11 12 Affiliations 13 1 MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological 14 Medicine and Neurology, School of Medicine, Cardiff University, Heath Park, Cardiff, UK. 15 2 Neuropsychiatric Genetics Research Group, Dept of Psychiatry & Institute of Molecular 16 Medicine, Trinity College Dublin, Ireland. 17 3 Molecular and Clinical Neurobiology, Ludwig-Maximilians-University, Munich, Germany. 18 4 Department of Psychiatry, Ludwig-Maximilians-University, Munich, Germany. 19 5 Medical Genetics, GlaxoSmithKline R&D, Verona, Italy. 20 6 Trinity Institute of Neuroscience, Trinity College, Dublin. 21 7 Centre for Medical Research/Western Australian Institute for Medical Research, The 22 University of Western Australia, Perth, Australia. 23 8 Centre for Clinical Research in Neuropsychiatry, The University of Western Australia, Perth, 24 Australia. 25 9 Centre for Genetic Epidemiology and Biostatistics, University of Western Australia, Perth, 26 Australia. 27 28 29 30 Address for correspondence 31 Dr. Gary Donohoe. 32 Neuropsychiatric Genetics Research Group, 33 Dept of Psychiatry, 34 Trinity Health Sciences Building, 35 St. James’s Hospital, 36 Dublin 8. 37 Telephone 38 +353 1 896 2467 39 Fax 40 +353 1 896 3405 41 E-mail 42 Gary.Donohoe@tcd.ie 43 44 Word count: 4699 45 Number of Tables: 3 Number of Figures: 1 46 47
Nebivolol in the treatment of chronic heart failure

Nebivolol is a highly selective beta1-adrenergic blocker that also enhances nitric oxide bioavailability via the L-arginine-nitric oxide pathway, leading to vasodilation and decreased peripheral vascular resistance. It is marketed in Europe for the treatment of hypertension and heart failure and is currently being reviewed for use in the US by the Food and Drug Administration. Nebivolol appears to be well tolerated with an adverse event profile that is at least similar, if not better, than that of other beta-adrenergic blockers. Studies suggest that long-term therapy with nebivolol improves left ventricular function, exercise capacity, and clinical endpoints of death and cardiovascular hospital admissions in patients with stable heart failure. To date, it is one of the only beta-adrenergic blockers that have been exclusively studied in elderly patients. Additionally, the unique mechanism of action of nebivolol makes it a promising agent for treatment of chronic heart failure in high-risk patient populations, such as African Americans. This article will review the pharmacologic and pharmacokinetic properties of nebivolol as well as clinical studies assessing its efficacy for the treatment of heart failure.
A New Approach to Indian Philosophy and Personality – A Study

Bhagvad Gita is considered as a marvelous literature in the Indian context. Over the centuries, several authors have explored various dimensions of Bhagvad Gita ranging from philosophy, spirituality, politics, economics, sociology, culture, literature, language, poetry, and others. However, human behaviour does not seem to be a popular subject of analysis from the Bhagvad Gita. The author has explored Triguna theory which provides lessons for understanding personality as a dimension of human behaviouran attempt has also been made to understand the dynamics of Gunas that is Sattva, Rajas and Tamas.The Gunas inherited by an individual are liable to change due to physical, psychological and social influences and the behavior of an individual, both overt and covert is determined by the prakriti (Personality) operating at that time. As prakriti governs the perception, cognition, motivation and values of an individual, it also influences well-being. The author feel that a deep understanding in this area could go a long way in human development, which could help in understanding the relation between personalityand behaviour in the Indian context.
Origins of afferents to visual suprageniculate nucleus of the cat

Small iontophoretic ejections of horseradish peroxidase (HRP) were made from recording‐multibarrel micropipette assemblies in areas of the cat's suprageniculate nucleus (SGn) that contained visually responsive neurones. The sources of afferents of the SGn were determined by locating the labeled cell bodies of neurones that were presumed to send their axons to the area of the SGn containing the light‐sensitive cells. The greatest concentration of labeled cell bodies was found in the granular insular cortex and the adjacent area of agranular insula. Most cells projecting to SGn from these areas were distributed in the middle and lower laminae. A second intensely labeled region was found in stratum opticum and stratum griseum intermediate of the superior colliculus. Other areas containing labeled cells that were distributed with intermediate density included the ventral thalamic nuclear complex (basal, medial, and lateral divisions), periaqueductal gray (PAG), zona incerta, and pretectal nuclei (posterior, medial, and anterior divisions). Sparsely labeled sites included the fields of Forel, substantia nigra (pars reticulata), peri‐insular cortex, superior colliculus (profundum), lateral suprasylvian cortex (posterolateral lateral suprasylvian, PLLS and posteromedial lateral suprasylvian, PMLS), anterior ectosylvian cortex, thalamic reticular complex, nucleus of the optic tract, basal part of the ventromedial hypothalamic nucleus, and the pontine reticular nucleus (oralis) and adjacent reticular formation. Together with previous electrophysiological and neuroanatomical studies, the findings suggest that the SGn provides an integrating link between limbic structures and certain modalities of sensory information.
Circulating tumor cells in metastatic breast cancer: the need for a standardized approach.

Gradilone et al. [1] recently published a study addressing the prognostic and predictive value of circulating tumor cells (CTCs) in metastatic breast cancer (MBC) and its relation to drug resistance molecular profile and stemness markers. We know that CTCs are highly relevant to the study of the biology of the metastatic process. The detection and enumeration of CTCs has been shown to be a useful tool in predicting response and clinical outcome of the treatment of MBC patients. Current evidence suggests that patients with elevated CTCs levels (5 CTCs/7.5 ml of blood) have shorter progression-free survival (PFS) and overall survival [2, 3]. Moreover, it has been shown that elevated CTC values any time in the clinical course of MBC patients is indicative of impending disease and hence CTCs monitoring is proposed as a possibly better prognostic tool compared with functional imaging [3, 4]. In the present study, the authors defined patients with positive CTCs as those having at least one EpCAM-positive cell isolated by CELLection Dynabeads (CD452, CK8+, CK20+) [1], differing from previous studies that count and dichotomized CTCs levels (<5 or ‡5) [2–4]. While Gradilone et al. demonstrated a shorter PFS for patients with positive CTCs expression, they added some controversy on the exact definition of CTC positivity. Although the drug resistance profile predicted a poor response to chemotherapy, the results were obtained in a population treated with different regimens. It would have been of value to know details of the chemotherapy used, whether single agent or combination. Furthermore, 50% of patients were known to be HER2 positive but were not offered antiHER2-targeted therapy. It also would have been interesting to provide information regarding the breast cancer molecular classification, considering that it has recently been shown to correlate with CTCs dissemination [5]. All these factors along with the small sample size and lack of a control group should be taken into consideration when interpreting these data. Currently, the Southwest Oncology Group (SWOG) is addressing, in a prospective randomized trial, the issue of treatment decision based on CTCs blood levels. This study will determine, among women with MBC and elevated CTCs, the value of an immediate change of therapy versus waiting until classic clinic–radiological evidence of progressive disease. Both SWOG and the present study are interesting steps toward therapy individualization. However, one important issue remains open: what treatment should be chosen when CTCs levels rise, and how could this molecular chemosensitivity profile be used? Hence, we could interrogate ourselves regarding the real importance of learning about the CTCs biocharacteristics, molecular portrait of the most relevant signaling pathways and their drug resistance profiles. It would, indeed, help us to overcome the aggressiveness of metastatic disease in the era of personalized medicine.
Acute and Chronic Cardiovascular Effects of Doxorubicin in the Dog: The Cardiovascular Pharmacology of Drug‐Induced Histamine Release

We evaluated the acute hemodynamic effects of doxorubicin in the open-chest dog. Doxorubicin at doses of 1–4 mg/kg administered over 2 min produced profound hemodynamic changes that were similar to those produced by histamine. These changes persisted despite administering the drug as a slow infusion. Histamine release in peripheral tissues was documented by a marked increase in venous histamine levels following doxorubicin administration. The heart extracted histamine during a period when arterial levels were increased, as indicated by consistently low coronary sinus/aortic ratios. Secondary catecholamine release occurred in response to histamine and histamine-mediated hemodynamic effects. Immunoreactive prostaglandins E and F were increased in coronary sinus blood beginning 30 min after the initiation of a continuous infusion of doxorubicin, and increased slowly thereafter. H1- and H2-receptor blockade with diphenhydramine and cimetidine prevented the early (2–30 min postinfusion) effects of doxorubicin, and combined his taminergic and adrenergic blockade prevented the late effects. A dose of doxorubicin (1 mg/kg) that released histamine and catecholamines produced primary cardiac effects acutely and a cardiomyopathy when administered chronically. The release of vasoactive substances could be part of the pathogenetic mechanism of anthracycline cardiomyopathy.
Selenium suppressed hydrogen peroxide‐induced vascular smooth muscle cells calcification through inhibiting oxidative stress and ERK activation

Atherosclerosis is frequently associated with vascular calcification. Increasing evidences underline that the essential micronutrient selenium may prevent atherosclerosis, but the role of selenium in vascular calcification remains unknown. In this study, we assessed the effect of sodium selenite (Na2SeO3) on H2O2‐enhanced vascular smooth muscle cells (VSMCs) calcification and examined the involvement of extracellular signal‐regulated kinase (ERK) signaling pathway. Hydrogen peroxide enhanced vascular calcification by inducing osteoblastic differentiation of VSMCs, as showed by up‐regulating the mRNA expression of type I collagen, osteocalcin, and Runx2, a key transcription factor for osteoblastic differentiation, increasing alkaline phosphatase activity, and calcium deposition. These effects of H2O2 were suppressed by pretreatment of the cells with selenite (0.1–1 µM) for 24 h. In addition, H2O2 activated the phosphorylation of ERK1/2 and inhibition of H2O2‐activated ERK signaling by MEK inhibitor PD98059 blocked the effect of H2O2 on osteoblastic differentiation of VSMCs. Furthermore, H2O2 induced oxidative stress in calcifying VSMCs, as evidenced by the increase of intracellular reactive oxygen species production and malondialdehyde level, and the decrease of total protein thiols content and the activity of antioxidant selenoenzyme glutathione peroxidases. Selenite pretreatment also attenuated H2O2‐induced oxidative stress and ERK activation. These results suggested that selenite suppressed H2O2‐enhanced osteoblastic differentiation and calcification of VSMCs through inhibiting oxidative stress and ERK activation, indicating a potential preventive role for selenium in vascular calcification. J. Cell. Biochem. 111: 1556–1564, 2010. © 2010 Wiley‐Liss, Inc.
Learning in the Santa Fe Bar Problem

This paper investigates learning in the Santa Fe (El Farol) bar problem (sfbp). It is argued that rationality together with belief-based learning (e.g., Bayesian updating) yields unstable behavior in this game. More specifically, two conditions normally sufficient for convergence to Nash equilibrium, namely rationality and predictivity, are shown to be incompatible. Low-rationality learning algorithms, however, converge to the symmetric Nash equilibrium in sfbp. Although it is fair, this equilibrium is suboptimal—the expected utility of the collective is near zero. This paper therefore proposes a simple modification to sfbp, whereby agents that attend the bar are charged an entry fee that is divided equally among those agents who do not attend the bar. In this modified scenario, low-rationality algorithms, which once again learn Nash equilibrium strategies, approximate Pareto-optimal behavior: individual rationality coincides with collective rationality.
Nuclear fusion occurs during mating in Candida albicans and is dependent on the KAR3 gene

It is now well established that mating can occur between diploid a and α cells of Candida albicans. There is, however, controversy over when, and with what efficiency, nuclear fusion follows cell fusion to create stable tetraploid a/α cells. In this study, we have analysed the mating process between C. albicans strains using both cytological and genetic approaches. Using strains derived from SC5314, we used a number of techniques, including time‐lapse microscopy, to demonstrate that efficient nuclear fusion occurs in the zygote before formation of the first daughter cell. Consistent with these observations, zygotes micromanipulated from mating mixes gave rise to mononuclear tetraploid cells, even when no selection for successful mating was applied to them. Mating between different clinical isolates of C. albicans revealed that while all isolates could undergo nuclear fusion, the efficiency of nuclear fusion varied in different crosses. We also show that nuclear fusion in C. albicans requires the Kar3 microtubule motor protein. Deletion of the CaKAR3 gene from both mating partners had little or no effect on zygote formation but reduced the formation of stable tetraploids more than 600‐fold, as determined by quantitative mating assays. These findings demonstrate that nuclear fusion is an active process that can occur in C. albicans at high frequency to produce stable, mononucleate mating products.
[Elective coronary angioplasty in total absence of heart surgery].

BACKGROUND One-hundred consecutive procedures of elective coronary angioplasty were attempted in 95 patients, in the absence of any surgical stand-by. All patients had angina and/or signs of inducible ischemia. METHODS All patients and attending physicians were informed that no surgical coverage was available, and gave their consent. The choice was made on the basis of the estimate, on clinical and angiographic grounds, of the consequences of vessel occlusion, of the possible help offered by percutaneous bail-out techniques, and of the applicability of surgical stand-by. RESULTS A primary success was achieved in 92 cases: in 5 cases a Palmaz-Schatz stent was implanted. In 6 cases the procedure was unsuccessful, with no complications. Two patients sustained a myocardial infarction without new Q-waves. No patient died, nor underwent cardiac surgery within 1 month of discharge. CONCLUSIONS Our initial experience suggests that, in the absence of surgical stand-by, elective coronary angioplasty can be performed in selected patients at an acceptable risk.
Exploiting Natural Dynamics in the Control of a Planar Bipedal Walking Robot

Natural dynamics can be exploited in the control of bipedal walking robots: the swing leg can swing freely once started; a kneecap can be used to prevent the leg from inverting; and a compliant ankle can be used to naturally transfer the center of pressure along the foot and help in toe off. Each of these mechanisms helps make control easier to achieve and results in motion that is smooth and natural looking. We describe a simple control algorithm using these natural mechanisms which requires very little computation. The necessary sensing consists of joint angles and velocities, body pitch and angular velocity, and ground reaction forces. Using this simple algorithm, we have controlled a seven link planar bipedal robot, called Spring Flamingo, to walk. Video, photographs, and more information on Spring Flamingo can be found at http://www.leglab. ai.mit. edu
Clonal involvement of eosinophils in therapy‐related myelodysplastic syndrome with eosinophilia, translocation t(1;7) and lung cancer

We report a therapy‐related MDS (RAEB) patient with eosinophilia, unbalanced translocation der(7)t(1;7) (q12;q22) and lung cancer. We observed no increase in cytokine levels in serum or in the conditioned medium (CM) of peripheral T cells cultured with or without IL‐2. When bone marrow (BM) cells were cultured with GM‐CSF, IL‐3 and SCF in a semisolid system, the colonies were exclusively eosinophilic. Cytogenetic analysis of the colony cells identified the same chromosome abnormality in all metaphases to that of BM cells. Suspension and clonogenic colony assay of BM cells cultured with various cytokines showed predominant eosinophilic growth and differentiation with GM‐CSF, but not with the other cytokines examined. These findings, together with mild morphological abnormalities of eosinophils, indicate clonal involvement of eosinophils in the myelodysplastic syndrome (MDS) clone, and that the eosinophilia was derived from the neoplastic clone with the translocation and was not associated with the patient’s lung cancer.
Seasonal Plasticity of Precise Spike Timing in the Avian Auditory System

Vertebrate audition is a dynamic process, capable of exhibiting both short- and long-term adaptations to varying listening conditions. Precise spike timing has long been known to play an important role in auditory encoding, but its role in sensory plasticity remains largely unexplored. We addressed this issue in Gambel's white-crowned sparrow (Zonotrichia leucophrys gambelii), a songbird that shows pronounced seasonal fluctuations in circulating levels of sex-steroid hormones, which are known to be potent neuromodulators of auditory function. We recorded extracellular single-unit activity in the auditory forebrain of males and females under different breeding conditions and used a computational approach to explore two potential strategies for the neural discrimination of sound level: one based on spike counts and one based on spike timing reliability. We report that breeding condition has robust sex-specific effects on spike timing. Specifically, in females, breeding condition increases the proportion of cells that rely solely on spike timing information and increases the temporal resolution required for optimal intensity encoding. Furthermore, in a functionally distinct subset of cells that are particularly well suited for amplitude encoding, female breeding condition enhances spike timing-based discrimination accuracy. No effects of breeding condition were observed in males. Our results suggest that high-resolution temporal discharge patterns may provide a plastic neural substrate for sensory coding.
Characterization of the Physical Interaction of Gli Proteins with SUFU Proteins*

The Hedgehog signaling pathway is involved in both development and cancer induction in a wide range of organisms. The end point of the Hedgehog signal-transduction cascade is the Gli/Ci, zinc-finger transcription factors. Proteins such as Fused, Suppressor of fused (SUFU), Costal-2, and protein kinase A are essential for regulation of Gli/Ci processing, activity, and localization. Coimmunoprecipitation and Far Western assays, coupled with truncation analysis and mutagenesis have been used to define the region of interaction between Gli proteins and SUFU. We identify a novel motif SYGH in Gli/Ci family proteins, which is required for the interaction with SUFU. Mutational studies revealed that Gly122 and His123 are crucial for binding to SUFU, suggesting the importance of hydrophobicity for the correct binding conformation. Functional analysis revealed that the activity of GLI transcription factors with mutations in this motif is no longer suppressed by co-expression of SUFU. Moreover, we have found that a C-terminal 19-amino acid deletion in SUFU (Δ465) is sufficient to abrogate interaction with GLI1. Interestingly, this SUFU mutant localizes in the nucleus, most probably because it is not efficiently sequestered in the cytoplasm. Taken together, we identified a novel motif in the Gli/Ci family of proteins that is essential both for protein-protein interaction with SUFU and for functional repression of GLI1 by SUFU.
Translation and cultural adaptation of a specific instrument for measuring asthma control and asthma status: the Asthma Control and Communication Instrument

ABSTRACT Objective: To translate the Asthma Control and Communication Instrument (ACCI) to Portuguese and adapt it for use in Brazil. Methods: The ACCI was translated to Portuguese and adapted for use in Brazil in accordance with internationally accepted guidelines. The protocol included the following steps: permission and rights of use granted by the original author; translation of the ACCI from English to Portuguese; reconciliation; back-translation; review and harmonization of the back-translation; approval from the original author; review of the Portuguese version of the ACCI by an expert panel; cognitive debriefing (the clarity, understandability, and acceptability of the translated version being tested in a sample of the target population); and reconciliation and preparation of the final version. Results: During the cognitive debriefing process, 41 asthma patients meeting the inclusion criteria completed the ACCI and evaluated the clarity of the questions/statements. The clarity index for all ACCI items was > 0.9, meaning that all items were considered to be clear. Conclusions: The ACCI was successfully translated to Portuguese and culturally adapted for use in Brazil, the translated version maintaining the psychometric properties of the original version. The ACCI can be used in clinical practice because it is easy to understand and easily applied.