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Showing papers by "University of Siena published in 2004"


Journal ArticleDOI
TL;DR: A review of the research carried out by the Analysis Group at the Oxford Centre for Functional MRI of the Brain (FMRIB) on the development of new methodologies for the analysis of both structural and functional magnetic resonance imaging data.

12,097 citations


MonographDOI
TL;DR: In this article, the authors measure social norms and preferences using experimental games and find substantial variation among social groups in Bargaining and Public Goods Behavior in an Egalitarian Society of Hunter-Gatherers.
Abstract: 1. Introduction and Guide to the Volume 2. Overview and Synthesis 3. Measuring Social Norms and Preferences Using Experimental Games: A Guide for Social Sciences 4. Coalitional Effects on Reciprocal Fairness in the Ultimatum Game: A Case from the Ecuadorian Amazon 5. Comparative Experimental Evidence from Machiguenga, Mapuche, Huinca, and American Populations Shows Substantial Variation Among Social Groups in Bargaining and Public Goods Behavior 6. Dictators and Ultimatums in an Egalitarian Society of Hunter-Gatherers - the Hadza of Tanzania 7. Does Market Exposure Affect Economic Game Behavior? The Ultimatum Game and the Public Goods Game Among the Tsimane of Bolivia 8. Market Integration, Reciprocity, and Fairness in Rural Papua New Guinea: Results from a Two-Village Ultimatum Game Experiment 9. Ultimatum Game with an Ethnicity Manipulation: Results from Khovdiin Bulgan Sum, Mongolia 10. Kinship, Familiarity, and Trust: An Experimental Investigation 11. Community Structure, Mobility, and the Strength of Norms in an Africa Society: the Sangu of Tanzania 12. Market Integration and Fairness: Evidence from Ultimatum, Dictator, and Public Goods Experiments in East Africa 13. Economic Experiments to Examine Fairness and Cooperation among the Ache Indians of Paraguay 14. The Ultimatum Game, Fairness, and Cooperation among Big Game Hunters

1,361 citations


Journal ArticleDOI
TL;DR: An abnormally high interhemispheric inhibitory drive from M1intact hemisphere to M1lesioned hemisphere in the process of generation of a voluntary movement by the paretic hand is document, conceivable that this abnormality could adversely influence motor recovery in some patients with subcortical stroke.
Abstract: In patients with chronic stroke, the primary motor cortex of the intact hemisphere (M1(intact hemisphere)) may influence functional recovery, possibly through transcallosal effects exerted over M1 in the lesioned hemisphere (M1(lesioned hemisphere)). Here, we studied interhemispheric inhibition (IHI) between M1(intact hemisphere) and M1(lesioned hemisphere) in the process of generation of a voluntary movement by the paretic hand in patients with chronic subcortical stroke and in healthy volunteers. IHI was evaluated in both hands preceding the onset of unilateral voluntary index finger movements (paretic hand in patients, right hand in controls) in a simple reaction time paradigm. IHI at rest and shortly after the Go signal were comparable in patients and controls. Closer to movement onset, IHI targeting the moving index finger turned into facilitation in controls but remained deep in patients, a finding that correlated with poor motor performance. These results document an abnormally high interhemispheric inhibitory drive from M1(intact hemisphere) to M1(lesioned hemisphere) in the process of generation of a voluntary movement by the paretic hand. It is conceivable that this abnormality could adversely influence motor recovery in some patients with subcortical stroke, an interpretation consistent with models of interhemispheric competition in motor and sensory systems.

1,292 citations


Journal ArticleDOI
21 May 2004-Science
TL;DR: In this article, the authors characterized a subject's choices in terms of their anticipated and actual emotional impact, and found that normal subjects reported emotional responses consistent with counterfactual thinking; they chose to minimize future regret and learned from their emotional experience.
Abstract: Facing the consequence of a decision we made can trigger emotions like satisfaction, relief, or regret, which reflect our assessment of what was gained as compared to what would have been gained by making a different decision. These emotions are mediated by a cognitive process known as counterfactual thinking. By manipulating a simple gambling task, we characterized a subject's choices in terms of their anticipated and actual emotional impact. Normal subjects reported emotional responses consistent with counterfactual thinking; they chose to minimize future regret and learned from their emotional experience. Patients with orbitofrontal cortical lesions, however, did not report regret or anticipate negative consequences of their choices. The orbitofrontal cortex has a fundamental role in mediating the experience of regret.

570 citations


Journal ArticleDOI
TL;DR: In conclusion, when measuring the bond strength of luted fiber posts, the push-out test appears to be more dependable than the microtensile technique.
Abstract: Aim of the study was to compare the trimming and non-trimming variants of the microtensile technique with the 'micro' push-out test in the ability to measure accurately the bond strength of fiber posts luted inside root canals. In 15 endodontically treated teeth (Group A), fiber posts were cemented with Excite DSC in combination with Variolink II (Ivoclar-Vivadent). In 15 roots RelyX Unicem (3M-ESPE) was used for fiber post luting (Group B). Within each group, the bond strength of cemented fiber posts was assessed with the trimming and non-trimming microtensile technique, as well as with the push-out test. The great number of premature failures (16.9% in Group A, 27.5% in Group B) and the finding of high standard deviation values make questionable the reliability of the trimming microtensile technique. With the non-trimming microtensile technique, only five sticks were obtained from a total of six roots. The remaining specimens failed prematurely during the cutting phase. With the push-out test no premature failure occurred, the variability of the data distribution was acceptable, and regional differences in bond strength among root levels could be assessed. Relatively low values of bond strength were, in general, recorded for luted fiber posts. In conclusion, when measuring the bond strength of luted fiber posts, the push-out test appears to be more dependable than the microtensile technique.

545 citations


Journal ArticleDOI
TL;DR: An overview of gonadal steroid modulation of pain and analgesia in animals and humans is presented to describe mechanisms by which males' and females' biology may differentially predispose them to pain and to analgesic effects of drugs and stress.

533 citations


Journal ArticleDOI
TL;DR: This work surveys current haptic systems and discusses some basic haptic-rendering algorithms, and describes the process by which desired sensory stimuli are imposed on the user to convey information about a virtual haptic object.
Abstract: Haptic rendering allows users to "feel" virtual objects in a simulated environment. We survey current haptic systems and discuss some basic haptic-rendering algorithms. In the past decade we've seen an enormous increase in interest in the science of haptics. Haptics broadly refers to touch interactions (physical contact) that occur for the purpose of perception or manipulation of objects. These interactions can be between a human hand and a real object; a robot end-effector and a real object; a human hand and a simulated object (via haptic interface devices); or a variety of combinations of human and machine interactions with real, remote, or virtual objects. Rendering refers to the process by which desired sensory stimuli are imposed on the user to convey information about a virtual haptic object.

469 citations


Journal ArticleDOI
TL;DR: This study confirms that MTC is not an infrequent finding among patients with thyroid nodules (nearly 1 in 250 patients) and allows the diagnosis and treatment of MTC at an earlier stage, resulting in a better outcome compared with MTC not detected by serum CT measurement.
Abstract: The survival rate of patients with medullary thyroid carcinoma (MTC) is significantly better in patients diagnosed and treated when the tumor is limited to the thyroid. In a pioneer study carried out in 1991, we demonstrated that routine measurement of serum calcitonin (CT) in nodular thyroid disease allowed the preoperative diagnosis of unsuspected sporadic MTC with better accuracy than routine fine needle aspiration cytology (FNAC). This finding has been confirmed in subsequent studies. In the present study we report the results of CT screening in 10,864 patients with thyroid nodular disease seen in the years 1991-1998 (group 1). We analyzed the prevalence of MTC and compared their outcomes with those of a historical group of patients (group 2) diagnosed before the introduction of CT screening (1970-1990). The prevalence of MTC found by CT screening in group 1 was 0.40% (44 patients). A positive CT test had a higher diagnostic sensitivity and specificity compared with FNAC. CT screening allowed the diagnosis of MTC at an earlier stage compared with group 2 (P = 0.004). Normalization of serum CT levels (undetectable) after surgery was more frequently observed in group 1. At the end of follow-up, complete remission was observed in 59% of group 1 and in 2.7% of group 2 (P = 0.0001). Our study confirms that MTC is not an infrequent finding among patients with thyroid nodules (nearly 1 in 250 patients). In addition, screening thyroid nodules with serum CT measurement allows the diagnosis and treatment of MTC at an earlier stage, resulting in a better outcome compared with MTC not detected by serum CT measurement. One of the reasons for this finding is that increasing the preoperative diagnostic accuracy of MTC prompts the surgeon to perform a more radical and possibly curative treatment. On this basis, routine measurement of basal serum CT levels should be considered an integral part of the diagnostic evaluation of thyroid nodules.

465 citations


Journal ArticleDOI
TL;DR: A brief historical overview of the development of the concepts and theories of energy quality, and net energy that were the precursors to emergy is given in this paper, where the authors provide some insights into the types of processes and systems that have been evaluated using emergy methods.

431 citations


Journal ArticleDOI
TL;DR: It is found that real networks are always either correlated or anticorrelated, and that networks of the same type display similar values of the reciprocity.
Abstract: We address the problem of link reciprocity, the nonrandom presence of two mutual links between pairs of vertices. We propose a new measure of reciprocity that allows the ordering of networks according to their actual degree of correlation between mutual links. We find that real networks are always either correlated or anticorrelated, and that networks of the same type (economic, social, cellular, financial, ecological, etc.) display similar values of the reciprocity. The observed patterns are not reproduced by current models. This leads us to introduce a more general framework where mutual links occur with a conditional connection probability. In some of the studied networks we discuss the form of the conditional connection probability and the size dependence of the reciprocity.

421 citations


Journal ArticleDOI
TL;DR: This paper considers the scheduling problems arising when two agents, each with a set of nonpreemptive jobs, compete to perform their respective jobs on a common processing resource, and addresses the complexity of various problems.
Abstract: We consider the scheduling problems arising when two agents, each with a set of nonpreemptive jobs, compete to perform their respective jobs on a common processing resource. Each agent wants to minimize a certain objective function, which depends on the completion times of its jobs only. The objective functions we consider in this paper are maximum of regular functions (associated with each job), number of late jobs, and total weighted completion times. We obtain different scenarios, depending on the objective function of each agent, and on the structure of the processing system (single machine or shop). For each scenario, we address the complexity of various problems, namely, finding the optimal solution for one agent with a constraint on the other agent's cost function, finding single nondominated schedules (i.e., such that a better schedule for one of the two agents necessarily results in a worse schedule for the other agent), and generating all nondominated schedules.

Journal ArticleDOI
TL;DR: This paper provides algorithms based on mixed-integer linear or quadratic programming which are guaranteed to converge to a global optimum of hybrid dynamical systems, and suggests a way of trading off between optimality and complexity by using a change detection approach.


Journal ArticleDOI
TL;DR: It is concluded that induction of DKK1 contributes to the pathological cascade triggered by β-amyloid and is critically involved in the process of tau phosphorylation.
Abstract: We used primary cultures of cortical neurons to examine the relationship between β-amyloid toxicity and hyperphosphorylation of the tau protein, the biochemical substrate for neurofibrillary tangles of Alzheimer's brain. Exposure of the cultures to β-amyloid peptide (βAP) induced the expression of the secreted glycoprotein Dickkopf-1 (DKK1). DKK1 negatively modulates the canonical Wnt signaling pathway, thus activating the tau-phosphorylating enzyme glycogen synthase kinase-3β. DKK1 was induced at late times after βAP exposure, and its expression was dependent on the tumor suppressing protein p53. The antisense induced knock-down of DKK1 attenuated neuronal apoptosis but nearly abolished the increase in tau phosphorylation in βAP-treated neurons. DKK1 was also expressed by degenerating neurons in the brain from Alzheimer's patients, where it colocalized with neurofibrillary tangles and distrophic neurites. We conclude that induction of DKK1 contributes to the pathological cascade triggered by β-amyloid and is critically involved in the process of tau phosphorylation.

Journal ArticleDOI
TL;DR: It is found that the power-law distributed gross domestic product can be successfully identified with the hidden variable determining the topology of the world trade web: all previously studied properties up to third-order correlation structure are found to be in excellent agreement with the predictions of the model.
Abstract: Among the proposed network models, the hidden variable (or good get richer) one is particularly interesting, even if an explicit empirical test of its hypotheses has not yet been performed on a real network. Here we provide the first empirical test of this mechanism on the world trade web, the network defined by the trade relationships between world countries. We find that the power-law distributed gross domestic product can be successfully identified with the hidden variable (or fitness) determining the topology of the world trade web: all previously studied properties up to third-order correlation structure (degree distribution, degree correlations, and hierarchy) are found to be in excellent agreement with the predictions of the model. The choice of the connection probability is such that all realizations of the network with the same degree sequence are equiprobable.

Journal ArticleDOI
TL;DR: Long-term followup of patients from the ELNT confirms that, in lupus nephritis, a remission-inducing regimen of low-dose IV CYC followed by AZA achieves clinical results comparable with those obtained with a high-dose regimen.
Abstract: OBJECTIVE: In the Euro-Lupus Nephritis Trial (ELNT), 90 patients with lupus nephritis were randomly assigned to a high-dose intravenous cyclophosphamide (IV CYC) regimen (6 monthly pulses and 2 quarterly pulses with escalating doses) or a low-dose IV CYC regimen (6 pulses of 500 mg given at intervals of 2 weeks), each of which was followed by azathioprine (AZA). After a median followup of 41 months, a difference in efficacy between the 2 regimens was not observed. The present analysis was undertaken to extend the followup and to identify prognostic factors. METHODS: Renal function was prospectively assessed quarterly in all 90 patients except 5 who were lost to followup. Survival curves were derived using the Kaplan-Meier method. RESULTS: After a median followup of 73 months, there was no significant difference in the cumulative probability of end-stage renal disease or doubling of the serum creatinine level in patients who received the low-dose IV CYC regimen versus those who received the high-dose regimen. At long-term followup, 18 patients (8 receiving low-dose and 10 receiving high-dose treatment) had developed permanent renal impairment and were classified as having poor long-term renal outcome. We demonstrated by multivariate analysis that early response to therapy at 6 months (defined as a decrease in serum creatinine level and proteinuria <1 g/24 hours) was the best predictor of good long-term renal outcome. CONCLUSION: Long-term followup of patients from the ELNT confirms that, in lupus nephritis, a remission-inducing regimen of low-dose IV CYC followed by AZA achieves clinical results comparable with those obtained with a high-dose regimen. Early response to therapy is predictive of good long-term renal outcome.

Journal ArticleDOI
TL;DR: It can be concluded that for some products, aging of composites in water leads to color instability and opacity variation.

Journal ArticleDOI
TL;DR: In this article, the authors discuss different methods to assign the responsibility for Greenhouse gas (GHG) emissions: the geographical approach, based on the IPCC guidelines for GHG inventory; the consumer responsibility approach based on a Ecological Footprint methodology; the Carbon Emission Added (CEA) approach that adopts the Embodied Energy-Emergy Analysis method.

Journal ArticleDOI
TL;DR: increasing evidence of functional changes resulting from this modification, and the growing number of proteins shown to be S‐glutathionylated both in vitro and in vivo support this contention, and confirm this as an attractive area of research.
Abstract: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play an integral role in the modulation of several physiological functions but can also be potentially destructive if produced in excessive amounts. Protein cysteinyl thiols appear especially sensitive to ROS/RNS attack. Experimental evidence started to accumulate recently, documenting that S-glutathionylation occurs in a number of physiologically relevant situations, where it can produce discrete modulatory effects on protein function. The increasing evidence of functional changes resulting from this modification, and the growing number of proteins shown to be S-glutathionylated both in vitro and in vivo support this contention, and confirm this as an attractive area of research. S-glutathionylated proteins are now actively investigated with reference to problems of biological interest and as possible biomarkers of human diseases associated with oxidative/nitrosative stress.

Journal ArticleDOI
TL;DR: In this article, the geographical origin of ice core dust (ICD) in cold periods has been investigated at both sites through 87Sr/86Sr versus 143Nd/144Nd isotopic tracers.

Journal ArticleDOI
TL;DR: A general 'metal index' for drinking water, which takes into account possible additive effects of N heavy metals on the human health that helps to quickly evaluate the overall quality of drinking waters, is introduced in this paper as MI=?(i=1,N)[C(i)/(MAC)(i)].

Journal ArticleDOI
TL;DR: Assessing whether SMN2 gene expression can be increased by 4-phenylbutyrate suggested that the compound, owing also to its favorable pharmacological properties, could be a good candidate for the treatment of SMA.
Abstract: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease, characterized by degeneration of the anterior horn cells of the spinal cord. SMA presents with a highly variable phenotype ranging from very severe to mild (type I-III). No cure for SMA is available at present. All forms of SMA are caused by homozygous loss of the functional survival motor neuron (SMN1) gene. However, all patients have one or more copies of the SMN2 gene, nearly identical to SMN1. Both genes encode the SMN protein but the level produced by SMN2 is insufficient to protect from disease. Increasing SMN2 gene expression could be of considerable therapeutic importance. The aim of this study was to assess whether SMN2 gene expression can be increased by 4-phenylbutyrate (PBA). Fibroblast cell cultures from 16 SMA patients affected by different clinical severities were treated with PBA, and full-length SMN2 transcripts were measured by real-time PCR. In all cell cultures, except one, PBA treatment caused an increase in full-length SMN2 transcripts, ranging from 50 to 160% in type I and from 80 to 400% in type II and III cultures. PBA was found also effective in enhancing SMN protein levels and the number of SMN-containing nuclear structures (gems). These data show that SMN expression is considerably increased by PBA, and suggest that the compound, owing also to its favorable pharmacological properties, could be a good candidate for the treatment of SMA.

Journal ArticleDOI
TL;DR: Early treatment with interferon beta-1a is effective in reducing conversion to clinically definite multiple sclerosis and in slowing progressive loss of brain tissue in patients with clinically isolated syndromes, suggesting that inflammatory and neurodegenerative processes are, at least partly, dissociated from the earliest clinical stage of multiple sclerosis onwards.

Journal ArticleDOI
TL;DR: In this paper, the authors investigate the contribution of within-group cultural affinity to the ability of parochial groups to cooperate in social dilemmas, in which the losses incurred by not trading with outsiders are offset by an enhanced ability to enforce informal contracts by fostering trust among insiders.
Abstract: Decentralized groups such as close knit residential neighborhoods and ethnically linked businesses often achieve high levels of cooperation while engaging in exclusionary practices that we call parochialism. We investigate the contribution of within-group cultural affinity to the ability of parochial groups to cooperate in social dilemmas. We analyze parochial networks in which the losses incurred by not trading with outsiders are offset by an enhanced ability to enforce informal contracts by fostering trust among insiders. We show that there is a range of degrees of parochialism for which parochial networks can coexist with an anonymous market offering unrestricted trading opportunities.

Journal ArticleDOI
TL;DR: The molecular genetic study of the BRAF gene showed the presence of a missense thymine to adenine transversion at nucleotide 1796, resulting in the V599E substitution, in 24 of 60 PTCs (40%), none of six follicular adenomas, and none of five follicular carcinomas or one anaplastic carcinoma.
Abstract: Activating mutations of BRAF have been identified in a variety of human cancers, most notably melanomas and papillary thyroid carcinomas (PTCs). The aim of the present study was to disclose the role of BRAF mutations in thyroid carcinoma development. Seventy-two thyroid tumors, including 60 PTCs, six follicular adenomas, five follicular carcinomas, and one anaplastic carcinoma, were studied. BRAF mutation screening focused on exon 15 and exon 11 of the gene by single-stranded conformational polymorphism and sequence analysis. Search of RET/PTC expression was conducted with the RT-PCR technique. The molecular genetic study of the BRAF gene showed the presence of a missense thymine to adenine transversion at nucleotide 1796, resulting in the V599E substitution, in 24 of 60 PTCs (40%), none of six follicular adenomas, and none of five follicular carcinomas or one anaplastic carcinoma. Moreover, nine of 60 PTCs (15%) presented RET/PTC expression. A genetico-clinical association analysis showed a statistically...

Journal ArticleDOI
Velio Bocci1
TL;DR: The aim of this review is to indicate that a wrong dogma and several misconceptions thwart progress: in reality, properly performed ozone therapy, carried out by expert physicians, can be very useful when orthodox medicine appears inadequate.
Abstract: Ozone is an intrinsically toxic gas and its hazardous employment has led to a poor consideration of ozone therapy. The aim of this review is to indicate that a wrong dogma and several misconceptions thwart progress: in reality, properly performed ozone therapy, carried out by expert physicians, can be very useful when orthodox medicine appears inadequate. The unbelievable versatility of ozone therapy is due to the cascade of ozone-derived compounds able to act on several targets leading to a multifactorial correction of a pathological state. During the past decade, contrary to all expectations, it has been demonstrated that the judicious application of ozone in chronic infectious diseases, vasculopathies, orthopedics and even dentistry has yielded such striking results that it is deplorable that the medical establishment continues to ignore ozone therapy.

Journal ArticleDOI
TL;DR: It is shown that the Rh environment is more similar to the “gas phase” than to the solution environment and that the mechanism of the ∼30 kcal·mol-1 photon energy storage observed for Rh is not consistent with a model based exclusively on the change of the electrostatic interaction of the chromophore with the protein/counterion environment.
Abstract: We demonstrate that a "brute force" quantum chemical calculation based on an ab initio multiconfigurational second order perturbation theory approach implemented in a quantum mechanics/molecular mechanics strategy can be applied to the investigation of the excited state of the visual pigment rhodopsin (Rh) with a computational error <5 kcal.mol(-1). As a consequence, the simulation of the absorption and fluorescence of Rh and its retinal chromophore in solution allows for a nearly quantitative analysis of the factors determining the properties of the protein environment. More specifically, we demonstrate that the Rh environment is more similar to the "gas phase" than to the solution environment and that the so-called "opsin shift" originates from the inability of the solvent to effectively "shield" the chromophore from its counterion. The same strategy is used to investigate three transient structures involved in the photoisomerization of Rh under the assumption that the protein cavity does not change shape during the reaction. Accordingly, the analysis of the initially relaxed excited-state structure, the conical intersection driving the excited-state decay, and the primary isolable bathorhodopsin intermediate supports a mechanism where the photoisomerization coordinate involves a "motion" reminiscent of the so-called bicycle-pedal reaction coordinate. Most importantly, it is shown that the mechanism of the approximately 30 kcal.mol(-1) photon energy storage observed for Rh is not consistent with a model based exclusively on the change of the electrostatic interaction of the chromophore with the protein/counterion environment.

Journal ArticleDOI
TL;DR: Findings identify promoter methylation as directly responsible for the intratumoral heterogeneity of therapeutic CTA in melanoma and foresee the use of 5-AZA-dCyd to overcome the limitations set by their intratumor heterogeneous expression to CTA-based vaccine therapy.
Abstract: Cancer/testis antigens (CTA) are suitable targets for immunotherapy of human malignancies, and clinical trials are mainly focusing on MAGE-A3. However, the heterogeneous intratumor expression of CTA may hamper the effectiveness of CTA-directed vaccination through the emergence of CTA-negative neoplastic clones. We investigated the intratumor heterogeneity of CTA in human melanoma and the underlying molecular mechanism(s) at clonal level using 14 single cell clones generated from the melanoma lesion Mel 313. Reverse transcription-PCR revealed a highly heterogeneous expression of MAGE-A1, -A2, -A3, -A4, -A6, GAGE 1-6, SSX 1-5, and PRAME among melanoma clones. Only nine clones expressed MAGE-A3 and competitive reverse transcription-PCR identified relative differences in the number of mRNA molecules of up to 130-fold between clones 5 and 14. This clonal heterogeneity of MAGE-A3 expression correlated with the methylation status of specific CpG dinucleotides in MAGE-A3 promoter: i.e., hypomethylated CpG dinucleotides at positions -321, -151, -19, -16, -5, -2, +21, and +42 were found in clones expressing high but not low levels of MAGE-A3. Supporting the role of DNA methylation in generating the intratumor heterogeneity of CTA, the DNA hypomethylating agent 5-aza-2'-deoxycytidine (5-AZA-dCyd) invariably induced their expression in all CTA-negative clones. Furthermore, 5-AZA-dCyd-treatment reduced to 6 folds the differential expression of MAGE-A3 between clones 5 and 14, which became recognized to a similar extent by T cells specific for a MAGE-A-encoded peptide. These findings identify promoter methylation as directly responsible for the intratumoral heterogeneity of therapeutic CTA in melanoma and foresee the use of 5-AZA-dCyd to overcome the limitations set by their intratumor heterogeneous expression to CTA-based vaccine therapy.

Journal ArticleDOI
TL;DR: In this article, a combination of homozygosity mapping, integration of physical and functional genomic data sets, and mutational screening was used to identify GenBank D83198 as the gene responsible for EE.
Abstract: Ethylmalonic encephalopathy (EE) is a devastating infantile metabolic disorder affecting the brain, gastrointestinal tract, and peripheral vessels. High levels of ethylmalonic acid are detected in the body fluids, and cytochrome c oxidase activity is decreased in skeletal muscle. By use of a combination of homozygosity mapping, integration of physical and functional genomic data sets, and mutational screening, we identified GenBank D83198 as the gene responsible for EE. We also demonstrated that the D83198 protein product is targeted to mitochondria and internalized into the matrix after energy-dependent cleavage of a short leader peptide. The gene had previously been known as "HSCO" (for hepatoma subtracted clone one). However, given its role in EE, the name of the gene has been changed to "ETHE1." The severe consequences of its malfunctioning indicate an important role of the ETHE1 gene product in mitochondrial homeostasis and energy metabolism.

Journal ArticleDOI
TL;DR: The transient interference produced by repetitive transcranial magnetic stimulation is compared to show that the neural correlates of retrieval modify along aging, suggesting that the bilateral engagement of the DLPFC has a compensatory role on the elders' episodic memory performance.
Abstract: Neuroimaging findings suggest that the lateralization of prefrontal cortex activation associated with episodic memory performance is reduced by aging. It is still a matter of debate whether this loss of asymmetry during encoding and retrieval reflects compensatory mechanisms or de-differentiation processes. We addressed this issue by the transient interference produced by repetitive transcranial magnetic stimulation (rTMS), which directly assesses causal relationships between performance and stimulated regions. We compared the effects of rTMS (a rapid-rate train occurring simultaneously to the presentation of memoranda) applied to the left or right dorsolateral prefrontal cortex (DLPFC) on visuospatial recognition memory in 66 healthy subjects divided in two classes of age ( 50 years). In young subjects, rTMS of the right DLPFC interfered with retrieval more than left DLPFC stimulation. The asymmetry of the effect progressively vanished with aging, as indicated by bilateral interference effects on recognition performance. Conversely, the predominance of left DLPFC effect during encoding was not abolished in elders, thus probing its causal role for encoding along the life span. Findings confirm that the neural correlates of retrieval modify along aging, suggesting that the bilateral engagement of the DLPFC has a compensatory role on the elders' episodic memory performance.