Showing papers by "University of Milan published in 2003"
TL;DR: A solution to the bandit problem in which an adversary, rather than a well-behaved stochastic process, has complete control over the payoffs.
Abstract: In the multiarmed bandit problem, a gambler must decide which arm of K nonidentical slot machines to play in a sequence of trials so as to maximize his reward. This classical problem has received much attention because of the simple model it provides of the trade-off between exploration (trying out each arm to find the best one) and exploitation (playing the arm believed to give the best payoff). Past solutions for the bandit problem have almost always relied on assumptions about the statistics of the slot machines.
In this work, we make no statistical assumptions whatsoever about the nature of the process generating the payoffs of the slot machines. We give a solution to the bandit problem in which an adversary, rather than a well-behaved stochastic process, has complete control over the payoffs. In a sequence of T plays, we prove that the per-round payoff of our algorithm approaches that of the best arm at the rate O(T-1/2). We show by a matching lower bound that this is the best possible.
We also prove that our algorithm approaches the per-round payoff of any set of strategies at a similar rate: if the best strategy is chosen from a pool of N strategies, then our algorithm approaches the per-round payoff of the strategy at the rate O((log N1/2 T-1/2). Finally, we apply our results to the problem of playing an unknown repeated matrix game. We show that our algorithm approaches the minimax payoff of the unknown game at the rate O(T-1/2).
2,370 citations
TL;DR: The usage of protein CO groups as biomarkers of oxidative stress has some advantages in comparison with the measurement of other oxidation products because of the relative early formation and the relative stability of carbonylated proteins.
2,097 citations
TL;DR: The use of crystal engineering concepts has produced a variety of coordination networks, many of which exhibit novel and fascinating types of entanglements of individual motifs as mentioned in this paper, and the structures of a number of entangled polymeric networks reported in these years by many groups.
1,881 citations
TL;DR: The development of standardized protocols for RQ-PCR analysis of FG transcripts provides a milestone for molecular determination of MRD levels and is likely to prove invaluable to the management of patients entered into multicenter therapeutic trials.
Abstract: Detection of minimal residual disease (MRD) has proven to provide independent prognostic information for treatment stratification in several types of leukemias such as childhood acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and acute promyelocytc leukemia. This report focuses on the accurate quantitative measurement of fusion gene (FG) transcripts as can be applied in 35-45% of ALL and acute myeloid leukemia, and in more than 90% of CML. A total of 26 European university laboratories from 10 countries have collaborated to establish a standardized protocol for TaqMan-based real-time quantitative PCR (RQ-PCR) analysis of the main leukemia-associated FGs within the Europe Against Cancer EAC) program. Four phases were scheduled: (1) training, (2) optimization, (3) sensitivity testing and (4) patient sample testing. During our program, three quality control rounds on a large series of coded RNA samples were performed including a balanced randomized assay, which enabled final validation of the EAC primer and probe sets. The expression level of the nine major FG transcripts in a large series of stored diagnostic leukemia samples (n = 278) was evaluated. After normalization, no statistically significant difference in expression level was observed between bone marrow and peripheral blood on paired samples at diagnosis. However, RQ-PCR revealed marked differences in FG expression between transcripts in leukemic samples at diagnosis that could account for differential assay sensitivity. The development of standardized protocols for RQ-PCR analysis of FG transcripts provides a milestone for molecular determination of MRD levels. This is likely to prove invaluable to the management of patients entered into multicenter therapeutic trials.
1,450 citations
University of Turin1, Queen's University2, French Institute of Health and Medical Research3, University of Milan4, National Institutes of Health5, University of Bologna6, St Bartholomew's Hospital7, Université de Montréal8, University of Padua9, Northern General Hospital10, University of Virginia Health System11, University of Brescia12
TL;DR: The consensus statement on diagnostic criteria and the diagnosis and treatment of complications of this syndrome reached at the workshop is hereby summarized.
Abstract: In October 2002, a workshop was held in Ancona, Italy, to reach a Consensus on the management of Cushing's syndrome. The workshop was organized by the University of Ancona and sponsored by the Pituitary Society, the European Neuroendocrine Association, and the Italian Society of Endocrinology. Invited international participants included almost 50 leading endocrinologists with specific expertise in the management of Cushing's syndrome. The consensus statement on diagnostic criteria and the diagnosis and treatment of complications of this syndrome reached at the workshop is hereby summarized.
1,201 citations
TL;DR: The mitochondrial biogenesis induced by exposure to cold was markedly reduced in brown adipose tissue of endothelial nitric oxide synthase null-mutant (eNOS–/–) mice, which had a reduced metabolic rate and accelerated weight gain as compared to wild-type mice.
Abstract: Nitric oxide was found to trigger mitochondrial biogenesis in cells as diverse as brown adipocytes and 3T3-L1, U937, and HeLa cells. This effect of nitric oxide was dependent on guanosine 3',5'-monophosphate (cGMP) and was mediated by the induction of peroxisome proliferator-activated receptor gamma coactivator 1alpha, a master regulator of mitochondrial biogenesis. Moreover, the mitochondrial biogenesis induced by exposure to cold was markedly reduced in brown adipose tissue of endothelial nitric oxide synthase null-mutant (eNOS-/-) mice, which had a reduced metabolic rate and accelerated weight gain as compared to wild-type mice. Thus, a nitric oxide-cGMP-dependent pathway controls mitochondrial biogenesis and body energy balance.
1,177 citations
TL;DR: In this article, a model for the assembly of supermassive black holes (SMBHs) at the center of galaxies that trace their hierarchical buildup far up in the dark halo merger tree is presented.
Abstract: We assess models for the assembly of supermassive black holes (SMBHs) at the center of galaxies that trace their hierarchical buildup far up in the dark halo merger tree. Motivated by the recent discovery of luminous quasars around redshift z ≈ 6—suggesting a very early assembly epoch—and by numerical simulations of the fragmentation of primordial molecular clouds in cold dark matter (CDM) cosmogonies, we assume that the first seed black holes (BHs) had intermediate masses and formed in (mini)halos collapsing at z ~ 20 from high-σ density fluctuations. As these pregalactic holes become incorporated through a series of mergers into larger and larger halos, they sink to the center because of dynamical friction, accrete a fraction of the gas in the merger remnant to become supermassive, form a binary system, and eventually coalesce. The merger history of dark matter halos and associated BHs is followed by cosmological Monte Carlo realizations of the merger hierarchy from early times until the present in a ΛCDM cosmology. A simple model, where quasar activity is driven by major mergers and SMBHs accrete at the Eddington rate a mass that scales with the fifth power of the circular velocity of the host halo, is shown to reproduce the observed luminosity function of optically selected quasars in the redshift range 1 < z < 5. A scheme for describing the hardening of a BH binary in a stellar background with core formation due to mass ejection is applied, where the stellar cusp proportional to r-2 is promptly regenerated after every major merger event, replenishing the mass displaced by the binary. Triple BH interactions will inevitably take place at early times if the formation route for the assembly of SMBHs goes back to the very first generation of stars, and we follow them in our merger tree. The assumptions underlying our scenario lead to the prediction of a population of massive BHs wandering in galaxy halos and the intergalactic medium at the present epoch and contributing 10% to the total BH mass density, ρSMBH = 4 × 105 M☉ Mpc-3 (h = 0.7). The fraction of binary SMBHs in galaxy nuclei is on the order of 10% today, and it increases with redshift so that almost all massive nuclear BHs at early epochs are in binary systems. The fraction of binary quasars (both members brighter than 0.1L*) instead is less than 0.3% at all epochs. The nuclear SMBH occupation fraction is unity (0.6) at the present epoch if the first seed BHs were as numerous as the 3.5 σ (4 σ) density peaks at z = 20.
985 citations
TL;DR: It is concluded that wild-type huntingtin acts in the cytoplasm of neurons to regulate the availability of REST/NRSF to its nuclear NRSE-binding site and that this control is lost in the pathology of Huntington disease.
Abstract: Huntingtin protein is mutated in Huntington disease. We previously reported that wild-type but not mutant huntingtin stimulates transcription of the gene encoding brain-derived neurotrophic factor (BDNF; ref. 2). Here we show that the neuron restrictive silencer element (NRSE) is the target of wild-type huntingtin activity on BDNF promoter II. Wild-type huntingtin inhibits the silencing activity of NRSE, increasing transcription of BDNF. We show that this effect occurs through cytoplasmic sequestering of repressor element-1 transcription factor/neuron restrictive silencer factor (REST/NRSF), the transcription factor that binds to NRSE. In contrast, aberrant accumulation of REST/NRSF in the nucleus is present in Huntington disease. We show that wild-type huntingtin coimmunoprecipitates with REST/NRSF and that less immunoprecipitated material is found in brain tissue with Huntington disease. We also report that wild-type huntingtin acts as a positive transcriptional regulator for other NRSE-containing genes involved in the maintenance of the neuronal phenotype. Consistently, loss of expression of NRSE-controlled neuronal genes is shown in cells, mice and human brain with Huntington disease. We conclude that wild-type huntingtin acts in the cytoplasm of neurons to regulate the availability of REST/NRSF to its nuclear NRSE-binding site and that this control is lost in the pathology of Huntington disease. These data identify a new mechanism by which mutation of huntingtin causes loss of transcription of neuronal genes.
914 citations
TL;DR: Rapid recent progress in the identification of carbonylated proteins should provide new diagnostic (possibly pre-symptomatic) biomarkers for oxidative damage, and yield basic information to aid the establishment an efficacious antioxidant therapy.
908 citations
TL;DR: It is described that oxygen availability is a determinant parameter in the setting of chemotactic responsiveness to stromal-derived factor 1 (CXCL12), and the Hyp–Hyp-inducible factor 1 α–CXCR4 pathway may regulate trafficking in and out of hypoxic tissue microenvironments.
Abstract: Cell adaptation to hypoxia (Hyp) requires activation of transcriptional programs that coordinate expression of genes involved in oxygen delivery (via angiogenesis) and metabolic adaptation (via glycolysis). Here, we describe that oxygen availability is a determinant parameter in the setting of chemotactic responsiveness to stromal-derived factor 1 (CXCL12). Low oxygen concentration induces high expression of the CXCL12 receptor, CXC receptor 4 (CXCR4), in different cell types (monocytes, monocyte-derived macrophages, tumor-associated macrophages, endothelial cells, and cancer cells), which is paralleled by increased chemotactic responsiveness to its specific ligand. CXCR4 induction by Hyp is dependent on both activation of the Hyp-inducible factor 1 alpha and transcript stabilization. In a relay multistep navigation process, the Hyp-Hyp-inducible factor 1 alpha-CXCR4 pathway may regulate trafficking in and out of hypoxic tissue microenvironments.
834 citations
TL;DR: Chemerin appears as a potent chemoattractant protein of a novel class, which requires proteolytic activation and is specific for APCs, and was shown to promote calcium mobilization and chemotaxis of immature DCs and macrophages in a ChemR23-dependent manner.
Abstract: Dendritic cells (DCs) and macrophages are professional antigen-presenting cells (APCs) that play key roles in both innate and adaptive immunity. ChemR23 is an orphan G protein-coupled receptor related to chemokine receptors, which is expressed specifically in these cell types. Here we present the characterization of chemerin, a novel chemoattractant protein, which acts through ChemR23 and is abundant in a diverse set of human inflammatory fluids. Chemerin is secreted as a precursor of low biological activity, which upon proteolytic cleavage of its COOH-terminal domain, is converted into a potent and highly specific agonist of ChemR23, the chemerin receptor. Activation of chemerin receptor results in intracellular calcium release, inhibition of cAMP accumulation, and phosphorylation of p42-p44 MAP kinases, through the Gi class of heterotrimeric G proteins. Chemerin is structurally and evolutionary related to the cathelicidin precursors (antibacterial peptides), cystatins (cysteine protease inhibitors), and kininogens. Chemerin was shown to promote calcium mobilization and chemotaxis of immature DCs and macrophages in a ChemR23-dependent manner. Therefore, chemerin appears as a potent chemoattractant protein of a novel class, which requires proteolytic activation and is specific for APCs.
TL;DR: Pulmonary vein ablation improves mortality, morbidity, and QoL as compared with medical therapy, paving the way for randomized trials to prospect a wider application of ablation therapy for AF.
TL;DR: In conclusion, prognosis of digestive bleeding in cirrhosis has much improved over the past 2 decades and accurate predictive rules are provided for early recognition of high‐risk patients.
TL;DR: The International Ascites Club, representing the spectrum of clinical practice from North America to Europe, have developed guidelines by consensus in the management of cirrhotic ascites from the early ascitic stage to the stage of refractory ascites.
TL;DR: This study provides a solid base for functional genomics studies into this important family of plant regulatory genes, including the poorly characterized group of M-type MADS-box proteins.
Abstract: MADS-box transcription factors are key regulators of several plant development processes Analysis of the complete Arabidopsis genome sequence revealed 107 genes encoding MADS-box proteins, of which 84% are of unknown function Here, we provide a complete overview of this family, describing the gene structure, gene expression, genome localization, protein motif organization, and phylogenetic relationship of each member We have divided this transcription factor family into five groups (named MIKC, Mα, Mβ, Mγ, and Mδ) based on the phylogenetic relationships of the conserved MADS-box domain This study provides a solid base for functional genomics studies into this important family of plant regulatory genes, including the poorly characterized group of M-type MADS-box proteins MADS-box genes also constitute an excellent system with which to study the evolution of complex gene families in higher plants
TL;DR: In this article, the epidermal growth factor and platelet-derived growth factor receptors are shown to be monoubiquitinated at multiple sites after their ligand-induced activation.
Abstract: Many cellular proteins are post-translationally modified by the addition of a single ubiquitin or a polyubiquitin chain1. Among these are receptor tyrosine kinases (RTKs), which undergo ligand-dependent ubiquitination2. The ubiquitination of RTKs has become recognized as an important signal for their endocytosis and degradation in the lysosome3; however, it is not clear whether ubiquitination itself is sufficient for this process or simply participates in its regulation. The issue is further complicated by the fact that RTKs are thought to be polyubiquitinated — a modification that is linked to protein degradation by the proteasome4. By contrast, monoubiquitination has been associated with diverse proteasome-independent cellular functions including intracellular protein movement5. Here we show that the epidermal growth factor and platelet-derived growth factor receptors are not polyubiquitinated but rather are monoubiquitinated at multiple sites after their ligand-induced activation. By using different biochemical and molecular genetics approaches, we show that a single ubiquitin is sufficient for both receptor internalization and degradation. Thus, monoubiquitination is the principal signal responsible for the movement of RTKs from the plasma membrane to the lysosome.
TL;DR: The CONVINCE trial did not demonstrate equivalence of a COER verapamil–based antihypertensive regimen compared with a regimen beginning with a diuretic or -blocker, and data indicate that the effectiveness of calcium-channel therapy in reducing cardiovascular disease is similar but not better than diuresis treatment.
Abstract: the HR was 1.15 (95% CI, 0.90-1.48); for fatal or nonfatal myocardial infarction, 0.82 (95% CI, 0.65-1.03); and for cardiovascular disease–related death, 1.09 (95% CI, 0.87-1.37). The HR was 1.05 (95% CI, 0.95-1.16) for any prespecified cardiovascular disease–related event and 1.08 (95% CI, 0.93-1.26) for all-cause mortality. Nonstroke hemorrhage was more common with participants in the COER-verapamil group (n=118) compared with the atenolol or hydrochlorothiazide group (n=79) (HR, 1.54 [95% CI, 1.16-2.04]; P=.003). More cardiovascular disease–related events occurred between 6 AM and noon in both the COER verapamil (99/277) and atenolol or hydrochlorothiazide (88/274) groups; HR, 1.15 (95% CI, 0.86-1.53). Conclusions The CONVINCE trial did not demonstrate equivalence of a COER verapamil–based antihypertensive regimen compared with a regimen beginning with a diuretic or -blocker. When considered in the context of other trials of calcium antagonists, these data indicate that the effectiveness of calcium-channel therapy in reducing cardiovascular disease is similar but not better than diuretic or -blocker treatment. JAMA. 2003;289:2073-2082 www.jama.com
TL;DR: Clinical features of the available cholinesterase inhibitors including their pharmacological properties, the evidence for switching from one agent to another, "head to head" studies, and the emerging evidence for the use of memantine in AD are reviewed.
Abstract: Alzheimer's disease (AD) is the most common neurodegenerative disorder and the most prevalent cause of dementia with ageing. Pharmacological treatment of AD is based on the use of acetylcholinesterase inhibitors, which have beneficial effects on cognitive, functional, and behavioural symptoms of the disease, but their role in AD pathogenesis is unknown. Other pharmacological therapies are becoming available--including the recently approved drug memantine, an NMDA channel blocker indicated for advanced AD. Here, we review clinical features of the available cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) including their pharmacological properties, the evidence for switching from one agent to another, "head to head" studies, and the emerging evidence for the use of memantine in AD. New therapeutic approaches--including those more closely targeted to the pathogenesis of the disease--will also be reviewed. These potentially disease modifying treatments include amyloid-beta-peptide vaccination, secretase inhibitors, cholesterol-lowering drugs, metal chelators, and anti-inflammatory agents.
TL;DR: Sgs1 and its associated topoisomerase Top3 remove double Holliday junction intermediates from a crossover-producing repair pathway, thereby reducing crossovers and Srs2 promotes the noncrossover synthesis-dependent strand-annealing pathway, apparently by regulating Rad51 binding during strand exchange.
TL;DR: In this paper, the electron density distribution in transition metal carbonyl clusters has been analyzed using the quantum theory of atoms in molecules and experimental determinations of electron density in metal-caroline clusters.
TL;DR: The interpretation of RQ-PCR MRD data needs standardized criteria and reporting of MRDData needs international uniformity, and several European networks have now been established and common guidelines for data analysis and for reporting ofMRD data are being developed.
Abstract: Detection of minimal residual disease (MRD) has prognostic value in many hematologic malignancies, including acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia, non-Hodgkin's lymphoma, and multiple myeloma. Quantitative MRD data can be obtained with real-time quantitative PCR (RQ-PCR) analysis of immunoglobulin and T-cell receptor gene rearrangements, breakpoint fusion regions of chromosome aberrations, fusion-gene transcripts, aberrant genes, or aberrantly expressed genes, their application being dependent on the type of disease. RQ-PCR analysis can be performed with SYBR Green I, hydrolysis (TaqMan) probes, or hybridization (LightCycler) probes, as detection system in several RQ-PCR instruments. Dependent on the type of MRD-PCR target, different types of oligonucleotides can be used for specific detection, such as an allele-specific oligonucleotide (ASO) probe, an ASO forward primer, an ASO reverse primer, or germline probe and primers. To assess the quantity and quality of the RNA/DNA, one or more control genes must be included. Finally, the interpretation of RQ-PCR MRD data needs standardized criteria and reporting of MRD data needs international uniformity. Several European networks have now been established and common guidelines for data analysis and for reporting of MRD data are being developed. These networks also include standardization of technology as well as regular quality control rounds, both being essential for the introduction of RQ-PCR-based MRD detection in multicenter clinical treatment protocols.
TL;DR: It is suggested that a significant proportion of patients with angiographically documented coronary artery disease have erectile dysfunction and that this latter condition may become evident prior to angina symptoms in almost 70% of cases.
TL;DR: Data demonstrate that C activation is fundamental for rituximab therapeutic activity in vivo, suggesting that its activity is T cell independent.
Abstract: Rituximab is an anti-CD20 chimeric mAb effective for the treatment of B-NHL. It can lyse lymphoma cells in vitro through both C- and Ab-dependent cellular cytotoxicity. The mechanism of action of rituximab in vivo is however still unclear. We have set up a new in vivo model in nonimmunodeficient mice by stable transduction of the human CD20 cDNA in the murine lymphoma line EL4. Animals injected i.v. with the EL4-CD20(+) lymphoma cells died within 30 days with evident liver, spleen, and bone marrow involvement, confirmed by immunohistochemistry and PCR analysis. A single injection of rituximab or the murine anti-CD20 Ab 1F5, given i.p. 1 day after the tumor, cured 100% of the animals. Indeed, at week 4 after tumor cell inoculation, CD20(+) cells were undetectable in all organs analyzed in rituximab-treated animals, as determined by immunohistochemistry and PCR. Rituximab had no direct effect on tumor growth in vitro. Depletion of either NK cells or neutrophils or both in tumor-injected animals did not affect the therapeutic activity of the drug. Similarly, rituximab was able to eradicate tumor cells in athymic nude mice, suggesting that its activity is T cell independent. In contrast, the protective activity of rituximab or the 1F5 Ab was completely abolished in syngeneic knockout animals lacking C1q, the first component of the classical pathway of C (C1qa(-/-)). These data demonstrate that C activation is fundamental for rituximab therapeutic activity in vivo.
TL;DR: A selective overview of how recent investigations of visual neglect are beginning to elucidate the underlying structure of spatial processes and mental representations is provided.
TL;DR: In patients with chronic renal failure who are undergoing percutaneous coronary interventions, periprocedural hemofiltration given in an ICU setting appears to be effective in preventing the deterioration of renal function due to contrast-agent-induced nephropathy and is associated with improved in-hospital and long-term outcomes.
Abstract: background Nephropathy induced by exposure to radiocontrast agents, a possible complication of percutaneous coronary interventions, is associated with significant in-hospital and longterm morbidity and mortality. Patients with preexisting renal failure are at particularly high risk. We investigated the role of hemofiltration, as compared with isotonic-saline hydration, in preventing contrast-agent–induced nephropathy in patients with renal failure. methods We studied 114 consecutive patients with chronic renal failure (serum creatinine concentration, >2 mg per deciliter [176.8 µmol per liter]) who were undergoing coronary interventions. We randomly assigned them to either hemofiltration in an intensive care unit (ICU) (58 patients, with a mean [ ± SD] serum creatinine concentration of 3.0 ± 1.0 mg per deciliter [265.2 ± 88.4 µmol per liter]) or isotonic-saline hydration at a rate of 1 ml per kilogram of body weight per hour given in a step-down unit (56 patients, with a mean serum creatinine concentration of 3.1 ± 1.0 mg per deciliter [274.0 ± 88.4 µmol per liter]). Hemofiltration (fluid replacement rate, 1000 ml per hour without weight loss) and saline hydration were initiated 4 to 8 hours before the coronary intervention and were continued for 18 to 24 hours after the procedure was completed. results An increase in the serum creatinine concentration of more than 25 percent from the baseline value after the coronary intervention occurred less frequently among the patients in the hemofiltration group than among the control patients (5 percent vs. 50 percent, P<0.001). Temporary renal-replacement therapy (hemodialysis or hemofiltration) was required in 25 percent of the control patients and in 3 percent of the patients in the hemofiltration group. The rate of in-hospital events was 9 percent in the hemofiltration group and 52 percent in the control group (P<0.001). In-hospital mortality was 2 percent in the hemofiltration group and 14 percent in the control group (P=0.02), and the cumulative one-year mortality was 10 percent and 30 percent, respectively (P=0.01). conclusions In patients with chronic renal failure who are undergoing percutaneous coronary interventions, periprocedural hemofiltration given in an ICU setting appears to be effective in preventing the deterioration of renal function due to contrast-agent–induced nephropathy and is associated with improved in-hospital and long-term outcomes.
TL;DR: It is shown that recombinant human EPO markedly reduces astrocyte activation and the recruitment of leukocytes and microglia into an infarction produced by middle cerebral artery occlusion in rats, suggesting that rhEPO attenuates ischemia-induced inflammation by reducing neuronal death rather than by direct effects upon EPO-R–expressing inflammatory cells.
Abstract: Ischemic brain injury resulting from stroke arises from primary neuronal losses and by inflammatory responses. Previous studies suggest that erythropoietin (EPO) attenuates both processes. Although EPO is clearly antiapoptotic for neurons after experimental stroke, it is unknown whether EPO also directly modulates EPO receptor (EPO-R)–expressing glia, microglia, and other inflammatory cells. In these experiments, we show that recombinant human EPO (rhEPO; 5,000 U/kg body weight, i.p.) markedly reduces astrocyte activation and the recruitment of leukocytes and microglia into an infarction produced by middle cerebral artery occlusion in rats. In addition, ischemia-induced production of the proinflammatory cytokines tumor necrosis factor, interleukin 6, and monocyte chemoattractant protein 1 concentration is reduced by >50% after rhEPO administration. Similar results were also observed in mixed neuronal-glial cocultures exposed to the neuronal-selective toxin trimethyl tin. In contrast, rhEPO did not inhibit cytokine production by astrocyte cultures exposed to neuronal homogenates or modulate the response of human peripheral blood mononuclear cells, rat glial cells, or the brain to lipopolysaccharide. These findings suggest that rhEPO attenuates ischemia-induced inflammation by reducing neuronal death rather than by direct effects upon EPO-R–expressing inflammatory cells.
TL;DR: It is established that α6β2* nAChRs are functional and sensitive to α-conotoxin MII inhibition, and somato-dendritic (nonα6)α4β2- nA ChRs most likely contribute to nicotine reinforcement.
Abstract: Nicotinic acetylcholine receptors (nAChRs) expressed by dopaminergic (DA) neurons have long been considered as potential therapeutic targets for the treatment of several neuropsychiatric diseases, including nicotine and cocaine addiction or Parkinson9s disease. However, DA neurons express mRNAs coding for most, if not all, neuronal nAChR subunits, and the subunit composition of functional nAChRs has been difficult to establish. Immunoprecipitation experiments performed on mouse striatal extracts allowed us to identify three main types of heteromeric nAChRs (α4β2 * , α6β2 * , and α4α6β2 * ) in DA terminal fields. The functional relevance of these subtypes was then examined by studying nicotine-induced DA release in striatal synaptosomes and recording ACh-elicited currents in DA neurons fromα4, α6, α4α6, and β2 knock-out mice. Our results establish that α6β2 * nAChRs are functional and sensitive to α-conotoxin MII inhibition. These receptors are mainly located on DA terminals and consistently do not contribute to DA release induced by systemic nicotine administration, as evidenced by in vivo microdialysis. In contrast, (nonα6)α4β2 * nAChRs represent the majority of functional heteromeric nAChRs on DA neuronal soma. Thus, whereas a combination of α6β2 * and α4β2 * nAChRs may mediate the endogenous cholinergic modulation of DA release at the terminal level, somato-dendritic (nonα6)α4β2 * nAChRs most likely contribute to nicotine reinforcement.
TL;DR: In this paper, the authors observed a narrow state near 2.32 GeV/c(2) in the inclusive D(+)(s)pi(0) invariant mass distribution from e(+)e(-) annihilation data at energies near 10.6 GeV.
Abstract: We have observed a narrow state near 2.32 GeV/c(2) in the inclusive D(+)(s)pi(0) invariant mass distribution from e(+)e(-) annihilation data at energies near 10.6 GeV. The observed width is consistent with the experimental resolution. The small intrinsic width and the quantum numbers of the final state indicate that the decay violates isospin conservation. The state has natural spin-parity and the low mass suggests a J(P)=0(+) assignment. The data sample corresponds to an integrated luminosity of 91 fb(-1) recorded by the BABAR detector at the SLAC PEP-II asymmetric-energy e(+)e(-) storage ring.
TL;DR: It is reported that, besides the described basal ATP release facilitated by exposure to calcium-free medium, astrocytes release purine under conditions of elevated calcium, and the activation of metabotropic glutamate receptors, which strongly evokes glutamate release, was only slightly effective in promoting purine secretion.
TL;DR: Scalp DC might represent a non-invasive simple and valuable potential treatment for psychiatric and neurologic diseases with changes in brain excitability or focally abnormal function.