Showing papers by "University of Udine published in 2005"

Postprandial Hyperglycemia and Diabetes Complications Is It Time to Treat

Abstract: Increasing evidence suggests that the postprandial state is a contributing factor to the development of atherosclerosis. In diabetes, the postprandial phase is characterized by a rapid and large increase in blood glucose levels, and the possibility that the postprandial "hyperglycemic spikes" may be relevant to the onset of cardiovascular complications has recently received much attention. Epidemiological studies and preliminary intervention studies have shown that postprandial hyperglycemia is a direct and independent risk factor for cardiovascular disease (CVD). Most of the cardiovascular risk factors are modified in the postprandial phase in diabetic subjects and directly affected by an acute increase of glycemia. The mechanisms through which acute hyperglycemia exerts its effects may be identified in the production of free radicals. This alarmingly suggestive body of evidence for a harmful effect of postprandial hyperglycemia on diabetes complications has been sufficient to influence guidelines from key professional scientific societies. Correcting the postprandial hyperglycemia may form part of the strategy for the prevention and management of CVDs in diabetes.

Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure

Abstract: In this study, we tested whether the human heart possesses a cardiac stem cell (CSC) pool that promotes regeneration after infarction. For this purpose, CSC growth and senescence were measured in 20 hearts with acute infarcts, 20 hearts with end-stage postinfarction cardiomyopathy, and 12 control hearts. CSC number increased markedly in acute and, to a lesser extent, in chronic infarcts. CSC growth correlated with the increase in telomerase-competent dividing CSCs from 1.5% in controls to 28% in acute infarcts and 14% in chronic infarcts. The CSC mitotic index increased 29-fold in acute and 14-fold in chronic infarcts. CSCs committed to the myocyte, smooth muscle, and endothelial cell lineages increased ≈85-fold in acute infarcts and ≈25-fold in chronic infarcts. However, p16INK4a-p53-positive senescent CSCs also increased and were 10%, 18%, and 40% in controls, acute infarcts, and chronic infarcts, respectively. Old CSCs had short telomeres and apoptosis involved 0.3%, 3.8%, and 9.6% of CSCs in controls, acute infarcts, and chronic infarcts, respectively. These variables reduced the number of functionally competent CSCs from ≈26,000/cm3 of viable myocardium in acute to ≈7,000/cm3 in chronic infarcts, respectively. In seven acute infarcts, foci of spontaneous myocardial regeneration that did not involve cell fusion were identified. In conclusion, the human heart possesses a CSC compartment, and CSC activation occurs in response to ischemic injury. The loss of functionally competent CSCs in chronic ischemic cardiomyopathy may underlie the progressive functional deterioration and the onset of terminal failure.

Gene duplication and exon shuffling by helitron-like transposons generate intraspecies diversity in maize

Abstract: We report a whole-genome comparison of gene content in allelic BAC contigs from two maize inbred lines. Genic content polymorphisms involve as many as 10,000 sequences and are mainly generated by DNA insertions. The termini of eight of the nine genic insertions that we analyzed shared the structural hallmarks of helitron rolling-circle transposons1,2,3. DNA segments defined by helitron termini contained multiple gene-derived fragments and had a structure typical of nonautonomous helitron-like transposons. Closely related insertions were found in multiple genomic locations. Some of these produced transcripts containing segments of different genes, supporting the idea that these transposition events have a role in exon shuffling and the evolution of new proteins. We identified putative autonomous helitron elements and found evidence for their transcription. Helitrons in maize seem to continually produce new nonautonomous elements responsible for the duplicative insertion of gene segments into new locations and for the unprecedented genic diversity. The maize genome is in constant flux, as transposable elements continue to change both the genic and nongenic fractions of the genome, profoundly affecting genetic diversity.

Proteins as biomarkers of oxidative/nitrosative stress in diseases: The contribution of redox proteomics

Abstract: I. Introduction 00 II. Reactive Oxygen and Nitrogen Species 00 III. Biological Markers of Oxidative/Nitrosative Stress 00 IV. Oxidative/Nitrosative Stress and Protein Modifications 00 A. Oxidative/Nitrosative Modification of Protein Thiols 00 B. Oxidative/Nitrosative Modification of Tyrosine 00 C. Oxidative Modification of Methionine 00 D. Protein Carbonylation 00 E. Oxidative Modification of Histidine and Tryptophan 00 V. MS Approaches for the Molecular Characterization of Oxidatively/Nitrosatively Modified Proteins 00 A. Analysis of Oxidized/Nitrosated Products of Protein Thiols 00 B. Analysis of Oxidized/Nitrated Products of Tyrosine Residues 00 C. Analysis of Oxidized Products of Methionine Residues 00 D. Analysis of Protein Carbonylation Products 00 E. Analysis of Oxidized Products of Tryptophan Residues 00 F. Analysis of Oxidized Products of Histidine Residues 00 VI. Proteomic Strategies for the Identification of ROS/RNS Targets in Complex Protein Mixtures 00 VII. Selected Human Diseases Associated with Oxidative/Nitrosative Stress 00 A. Acute (Adult) Respiratory Distress Syndrome 00 B. Alzheimer's Disease 00 C. Amyotrophic Lateral Sclerosis 00 D. Asthma 00 E. Atherosclerosis 00 F. Chronic Obstructive Pulmonary Diseases 00 G. Diabetes Mellitus 00 H. HIV Infection 00 I. Preeclampsia 00 J. Rheumatoid Arthritis 00 K. Transmissible Spongiform Encephalopathies 00 VIII. Oxidatively Modified Proteins in Human Diseases 00 IX. Concluding Remarks and Future Perspectives 00 Acknowledgments 00 Abbreviations 00 References 00 Reactive oxygen species (ROS) and reactive nitrogen species (RNS) contribute to the pathogenesis and/or progression of several human diseases. Proteins are important molecular signposts of oxidative/nitrosative damage. However, it is generally unresolved whether the presence of oxidatively/nitrosatively modified proteins has a causal role or simply reflects secondary epiphenomena. Only direct identification and characterization of the modified protein(s) in a given pathophysiological condition can decipher the potential roles played by ROS/RNS-induced protein modifications. During the last few years, mass spectrometry (MS)-based technologies have contributed in a significant way to foster a better understanding of disease processes. The study of oxidative/nitrosative modifications, investigated by redox proteomics, is contributing to establish a relationship between pathological hallmarks of disease and protein structural and functional abnormalities. MS-based technologies promise a contribution in a new era of molecular medicine, especially in the discovery of diagnostic biomarkers of oxidative/nitrosative stress, enabling early detection of diseases. Indeed, identification and characterization of oxidatively/nitrosatively modified proteins in human diseases has just begun. © 2004 Wiley Periodicals, Inc., Mass Spec Rev

The Role of Cathelicidins in the Innate Host Defenses of Mammals

Abstract: The cathelicidin peptides comprise one of several families of antimicrobial peptides that are found in neutrophils and epithelia as components of the early host defenses of mammals against infection. All cathelicidin family members are synthesized and stored in cells as two-domain proteins. These are split on demand to produce a cathelin protein and an antimicrobial peptide. Accumulating evidence indicates that both the cathelin portion and the C-terminal peptide exert biological activities connected with host protection. This review presents an overview of the structure and biology of cathelicidins and discusses recent progress in cathelicidin research with emphasis on the functional properties and role in host defense of the human cathelicidin hCAP18/LL-37. Although investigators initially concentrated their attention on antibiotic activity, it is becoming clear now that LL-37 is a multifunctional molecule that may mediate various host responses, and thus represents an essential component of the innate immune system in humans.

An improved deadbeat control for UPS using disturbance observers

Abstract: A digital control technique for the inverter stage of uninterruptible power supplies is proposed, which is based on a predictive regulator on both output voltage and inductor current. Its aim is to achieve a deadbeat dynamic response for the controlled variables (output voltage and inverter current). Besides the linear state feedback which allocates system poles at the origin so as to achieve deadbeat response for all state variables, the use of a disturbance observer for the estimation of the load current and of any other source of errors (such as dead-times, parameter, and model mismatches) is investigated. The proposed solution is able to guarantee a fast dynamic response and also a precise compensation of any source of unpredictable disturbance. Moreover, with a proper design of observer parameters, it is possible to reduce control sensitivity to model uncertainties, parameter mismatches, and noise on sensed variables, which usually characterizes existing deadbeat control techniques. Finally, the control algorithm is quite simple and requires only the measurements of the output voltage and inductor current. Experimental results on a single-phase 2 kVA prototype show the effectiveness of the proposed approach.

The intracellular localization of APE1/Ref-1: more than a passive phenomenon?

Abstract: Human apurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/Ref-1) is a perfect paradigm of the functional complexity of a biological macromolecule. First, it plays a crucial role, by both redox-dependent and –independent mechanisms, as a transcriptional coactivator for different transcription factors, either ubiquitous (i.e., AP-1, Egr-1, NF-κB, p53, HIF) or tissue-specific (i.e., PEBP-2, Pax-5 and -8, TTF-1), in controlling different cellular processes such as apoptosis, proliferation, and differentiation. Second, it acts, as an apurinic/apyrimidinic endonuclease, during the second step of the DNA base excision repair pathway, which is responsible for the repair of cellular alkylation and oxidative DNA damages. Third, it controls the intracellular reactive oxygen species production by negatively regulating the activity of the Ras-related GTPase Rac1. Despite these known functions of APE1/Ref-1, information is still scanty about the molecular mechanisms responsible for the coordinated contro...

Sprint running: a new energetic approach

Abstract: The speed of the initial 30 m of an all-out run from a stationary start on a flat track was determined for 12 medium level male sprinters by means of a radar device. The peak speed of 9.46+/-0.19 m s(-1) (mean +/- s.d.) was attained after about 5 s, the highest forward acceleration (a(f)), attained immediately after the start, amounting to 6.42+/-0.61 m s(-2). During acceleration, the runner's body (assumed to coincide with the segment joining the centre of mass and the point of contact foot terrain) must lean forward, as compared to constant speed running, by an angle alpha = arctang/a(f) (g = acceleration of gravity). The complement (90-alpha) is the angle, with respect to the horizontal, by which the terrain should be tilted upwards to bring the runner's body to a position identical to that of constant speed running. Therefore, accelerated running is similar to running at constant speed up an ;equivalent slope' ES = tan(90-alpha). Maximum ES was 0.643+/-0.059. Knowledge of ES allowed us to estimate the energy cost of sprint running (C(sr), J kg(-1) m(-1)) from literature data on the energy cost measured during uphill running at constant speed. Peak Csr was 43.8+/-10.4 J kg(-1) m(-1); its average over the acceleration phase (30 m) was 10.7+/-0.59 J kg(-1) m(-1), as compared with 3.8 for running at constant speed on flat terrain. The corresponding metabolic powers (in W kg(-1)) amounted to 91.9+/-20.5 (peak) and 61.0+/-4.7 (mean).

Evolution of DNA Sequence Nonhomologies among Maize Inbreds

Abstract: Allelic chromosomal regions totaling more than 2.8 Mb and located on maize (Zea mays) chromosomes 1L, 2S, 7L, and 9S have been sequenced and compared over distances of 100 to 350 kb between the two maize inbred lines Mo17 and B73. The alleles contain extended regions of nonhomology. On average, more than 50% of the compared sequence is noncolinear, mainly because of the insertion of large numbers of long terminal repeat (LTR)-retrotransposons. Only 27 LTR-retroelements are shared between alleles, whereas 62 are allele specific. The insertion of LTR-retrotransposons into the maize genome is statistically more recent for nonshared than shared ones. Most surprisingly, more than one-third of the genes (27/72) are absent in one of the inbreds at the loci examined. Such nonshared genes usually appear to be truncated and form clusters in which they are oriented in the same direction. However, the nonshared genome segments are gene-poor, relative to regions shared by both inbreds, with up to 12-fold difference in gene density. By contrast, miniature inverted terminal repeats (MITEs) occur at a similar frequency in the shared and nonshared fractions. Many times, MITES are present in an identical position in both LTRs of a retroelement, indicating that their insertion occurred before the replication of the retroelement in question. Maize ESTs and/or maize massively parallel signature sequencing tags were identified for the majority of the nonshared genes or homologs of them. In contrast with shared genes, which are usually conserved in gene order and location relative to rice (Oryza sativa), nonshared genes violate the maize colinearity with rice. Based on this, insertion by a yet unknown mechanism, rather than deletion events, seems to be the origin of the nonshared genes. The intergenic space between conserved genes is enlarged up to sixfold in maize compared with rice. Frequently, retroelement insertions create a different sequence environment adjacent to conserved genes.

Antimicrobial therapy in critically ill patients: a review of pathophysiological conditions responsible for altered disposition and pharmacokinetic variability

Abstract: Antimicrobials are among the most important and commonly prescribed drugs in the management of critically ill patients. Selecting the appropriate antimicrobial at the commencement of therapy, both in terms of spectrum of activity and dose and frequency of administration according to concentration or time dependency, is mandatory in this setting. Despite appropriate standard dosage regimens, failure of the antimicrobial treatment may occur because of the inability of the antimicrobial to achieve adequate concentrations at the infection site through alterations in its pharmacokinetics due to underlying pathophysiological conditions. According to the intrinsic chemicophysical properties of antimicrobials, hydrophilic antimicrobials (β-lactams, aminoglycosides, glycopeptides) have to be considered at much higher risk of inter- and intraindividual pharmacokinetic variations than lipophilic antimicrobials (macrolides, fluoroquinolones, tetracyclines, chloramphenicol, rifampicin [rifampin]) in critically ill patients, with significant frequent fluctuations of plasma concentrations that may require significant dosage adjustments. For example, underexposure may occur because of increased volume of distribution (as a result of oedema in sepsis and trauma, pleural effusion, ascites, mediastinitis, fluid therapy or indwelling post-surgical drainage) and/or enhanced renal clearance (as a result of burns, drug abuse, hyperdynamic conditions during sepsis, acute leukaemia or use of haemodynamically active drugs). On the other hand, overexposure may occur because of a drop in renal clearance caused by renal impairment. Care with all these factors whenever choosing an antimicrobial may substantially improve the outcome of antimicrobial therapy in critically ill patients. However, since these situations may often coexist in the same patient and pharmacokinetic variability may be unpredictable, the antimicrobial policy may further benefit from real-time application of therapeutic drug monitoring, since this practice, by tailoring exposure to the individual patient, may consequently be helpful both in improving the outcome of antimicrobial therapy and in containing the spread of resistance in the hospital setting.

Effect of Atorvastatin and Irbesartan, Alone and in Combination, on Postprandial Endothelial Dysfunction, Oxidative Stress, and Inflammation in Type 2 Diabetic Patients

Abstract: Background— Postprandial hypertriglyceridemia and hyperglycemia are considered risk factors for cardiovascular disease. Evidence suggests that postprandial hypertriglyceridemia and hyperglycemia induce endothelial dysfunction and inflammation through oxidative stress. Statins and angiotensin type 1 receptor blockers have been shown to reduce oxidative stress and inflammation, improving endothelial function. Methods and Results— Twenty type 2 diabetic patients ate 3 different test meals: a high-fat meal, 75 g glucose alone, and a high-fat meal plus glucose. Glycemia, triglyceridemia, endothelial function, nitrotyrosine, C-reactive protein, intercellular adhesion molecule-1, and interleukin-6 were assayed during the tests. Subsequently, diabetics took atorvastatin 40 mg/d, irbesartan 300 mg/d, both, or placebo for 1 week. The 3 tests were performed again between 5 and 7 days after the start of each treatment. High-fat load and glucose alone produced a decrease in endothelial function and increases in nitrot...

The cathelicidins--structure, function and evolution.

Abstract: The cathelicidin family of host defense peptides includes a group of cationic and usually amphipathic peptides that display a variety of activities related to host defense functions, among which the most acknowledged is a direct antimicrobial activity against various microbial pathogens. All members of this family are synthesized as precursors characterized by an N-terminal cathelin-like domain which is relatively well conserved also in evolutionary distant vertebrates. By contrast, the C-terminal region, which carries the active peptide, appears to be a focus for genetic mechanisms that have selectively generated a considerable sequence diversity. This process is particularly striking in Cetartiodactyls, where repeated gene duplication events and subsequent divergence have produced an array of distinct family members. The corresponding mature cathelicidin peptides are considerably diverse in length, amino acid sequence and structure, variously adopting alpha-helical, elongated or beta-hairpin conformations. The diverse nature of these peptides may account for distinct functions and for a diverse spectrum of activity and/or antimicrobial potency.

Torque-ripple reduction in PM synchronous motor drives using repetitive current control

Abstract: The paper deals with the torque-ripple reduction in a permanent magnet synchronous motor (PMSM) drive with distorted back electromotive force. A smooth torque is obtained by tracking a modified current reference which is periodic over one-sixth of the electrical time period in the synchronous reference frame. An accurate tracking involves, however, very high current loop bandwidth, which is usually not achievable with conventional linear controllers. In order to improve current tracking in the presence of periodic reference signals and disturbances, the paper proposes the application of repetitive techniques to the current control in a field-oriented PMSM drive, where the q-axis current reference has been modified to achieve constant torque. The paper investigates the advantages and pitfalls of the method, through a mathematical analysis and an experimental validation obtained on a laboratory prototype. Particular emphasis is placed on the adjustments that have been specifically studied to enhance the overall system performance.

Ambient Intelligence: A New Multidisciplinary Paradigm

Abstract: Ambient intelligence (AmI) is a new multidisciplinary paradigm rooted in the ideas of NormanAuthor of the Invisible Computer [32]. and Ubiquitous Computing. AmI fosters novel anthropomorphic human–machine models of interaction. In AmI, technologies are deployed to make computers disappear in the background, while the human user moves into the foreground in complete control of the augmented environment. AmI is a user-centric paradigm, it supports a variety of artificial intelligence methods and works pervasively, nonintrusively, and transparently to aid the user. AmI supports and promotes interdisciplinary research encompassing the technological, scientific and artistic fields creating a virtual support for embedded and distributed intelligence.

The renin–angiotensin–aldosterone system, glucose metabolism and diabetes

Abstract: In diabetes mellitus (DM), the circulating renin–angiotensin system (RAS) is suppressed, but the renal tissue RAS is activated. Hyperglycemia increases tissue angiotensin II (Ang II), which induces oxidative stress, endothelial damage and disease pathology including vasoconstriction, thrombosis, inflammation and vascular remodeling. In early DM, the type 1 Ang II (AT 1 ) receptor is upregulated but the type 2 Ang II (AT 2 ) receptor is downregulated. This imbalance can predispose the individual to tissue damage. Hyperglycemia also increases the production of aldosterone, which has an unknown contribution to tissue damage. The insulin resistance state is associated with upregulation of the AT 1 receptor and an increase in oxygen free radicals in endothelial tissue caused by activation of NAD(P)H oxidase. Treatment with an AT 1 receptor blocker normalizes oxidase activity and improves endothelial function. An understanding of the tissue renin–angiotensin–aldosterone system, which is a crucial factor in the progression of tissue damage in DM, is imperative for protection against tissue damage in this chronic disease.

Culture-dependent and -independent methods to investigate the microbial ecology of Italian fermented sausages.

Abstract: In this study, the microbial ecology of three naturally fermented sausages produced in northeast Italy was studied by culture-dependent and -independent methods. By plating analysis, the predominance of lactic acid bacteria populations was pointed out, as well as the importance of coagulase-negative cocci. Also in the case of one fermentation, the fecal enterocci reached significant counts, highlighting their contribution to the particular transformation process. Yeast counts were higher than the detection limit (> 100 CFU/g) in only one fermented sausage. Analysis of the denaturing gradient gel electrophoresis (DGGE) patterns and sequencing of the bands allowed profiling of the microbial populations present in the sausages during fermentation. The bacterial ecology was mainly characterized by the stable presence of Lactobacillus curvatus and Lactobacillus sakei, but Lactobacillus paracasei was also repeatedly detected. An important piece of evidence was the presence of Lactococcus garvieae, which clearly contributed in two fermentations. Several species of Staphylococcus were also detected. Regarding other bacterial groups, Bacillus sp., Ruminococcus sp., and Macrococcus caseolyticus were also identified at the beginning of the transformations. In addition, yeast species belonging to Debaryomyces hansenii, several Candida species, and Willopsis saturnus were observed in the DGGE gels. Finally, cluster analysis of the bacterial and yeast DGGE profiles highlighted the uniqueness of the fermentation processes studied.

A voxel based morphometry study on mild cognitive impairment.

Abstract: Background: Mild cognitive impairment (MCI) is the most widely used concept in classifying cognitive impairment in the elderly who do not fulfil the criteria for dementia. MCI is considered to confer an increased risk of progressing to dementia and most often Alzheimer's disease (AD). Various approaches such as imaging of the brain have been applied to predict the conversion of MCI to dementia. A number of volumetric magnetic resonance imaging (MRI) studies have detected atrophy of the medial temporal lobe in subjects with MCI, but for the other cerebral regions the results have been inconsistent. Objective: To study the pattern of brain atrophy in MCI. Methods: Thirty two controls and 51 individuals with MCI deriving from population based cohorts were studied by MRI using voxel based morphometry. The threshold of t maps was set at p<0.001. Results: Individuals with MCI had significant unilateral atrophy in the medial temporal lobe on the right side. Less extensive atrophy was found elsewhere—for example, in the temporal lobe, left superior parietal lobule, left anterior cingulate gyrus, and bilaterally in the thalami. Conclusions: The MRI findings in MCI resemble those seen in early AD.

Ruthenium(II) terdentate CNN complexes: superlative catalysts for the hydrogen-transfer reduction of ketones by reversible insertion of a carbonyl group into the Ru-H bond.

Abstract: Geringe Katalysatormengen und kurze Reaktionsdauer genugen zur quantitativen Reduktion von Ketonen durch 2-Propanol und den Komplex [RuX(CNN)(dppb)] (siehe Struktur; X=H, Cl), dessen dreizahniger Ligand sich von 6-(4-Methylphenyl)-2-pyridylmethylamin ableitet. Die Reduktion scheint uber eine reversible Insertion des Substrats in die Ru-H-Bindung zu verlaufen, bei der ein RutheniumII)-alkoxid entsteht. dppb=Ph2P(CH2)4PPh2.

Mapping With a Few Plants: Using Selective Mapping for Microsatellite Saturation of the Prunus Reference Map

Abstract: The concept of selective (or bin) mapping is used here for the first time, using as an example the Prunus reference map constructed with an almond × peach F2 population. On the basis of this map, a set of six plants that jointly defined 65 possible different genotypes for the codominant markers mapped on it was selected. Sixty-three of these joint genotypes corresponded to a single chromosomal region (a bin) of the Prunus genome, and the two remaining corresponded to two bins each. The 67 bins defined by these six plants had a 7.8-cM average length and a maximum individual length of 24.7 cM. Using a unit of analysis composed of these six plants, their F1 hybrid parent, and one of the parents of the hybrid, we mapped 264 microsatellite (or simple-sequence repeat, SSR) markers from 401 different microsatellite primer pairs. Bin mapping proved to be a fast and economic strategy that could be used for further map saturation, the addition of valuable markers (such as those based on microsatellites or ESTs), and giving a wider scope to, and a more efficient use of, reference mapping populations.

Flavonoids and Breast Cancer Risk in Italy

Abstract: Few epidemiologic studies have investigated the potential relation between flavonoids and breast cancer risk. We have applied recently published data on the composition of foods and beverages in terms of six principal classes of flavonoids (i.e., flavanones, flavan-3-ols, flavonols, flavones, anthocyanidines, and isoflavones) on dietary information collected in a large-case control study of breast cancer conducted in Italy between 1991 and 1994. The study included 2,569 women with incident, histologically confirmed breast cancer, and 2,588 hospital controls. Odds ratios (OR) and 95% confidence intervals were estimated by multiple logistic regression models. After allowance for major confounding factors and energy intake, a reduced risk of breast cancer was found for increasing intake of flavones (OR, 0.81, for the highest versus the lowest quintile; P-trend, 0.02), and flavonols (OR, 0.80; P-trend, 0.06). No significant association was found for other flavonoids, including flavanones (OR, 0.95), flavan-3-ols (OR, 0.86), anthocyanidins (OR, 1.09), as well as for isoflavones (OR, 1.05). The findings of this large study of an inverse association between flavones and breast cancer risk confirm the results of a Greek study.

Photon events with missing energy in e(+)e(-) collisions at root s=130 to 209 GeV

Abstract: The production of single- and multi-photon events has been studied in the reaction e+e- -> gamma (gamma) + invisible particles. The data collected with the DELPHI detector during the years 1999 and 2000 at centre-of-mass energies between 191 GeV and 209 GeV was combined with earlier data to search for phenomena beyond the Standard Model. The measured number of light neutrino families was consistent with three and the absence of an excess of events beyond that predicted by the Standard Model processes was used to set limits on new physics. Both model-independent searches and searches for new processes predicted by supersymmetric and extra-dimensional models have been made. Limits on new non-standard model interactions between neutrinos and electrons were also determined.

Structural correlates of early and late onset Alzheimer's disease: voxel based morphometric study.

Abstract: Objective: To examine the brain structural correlates of age at onset in patients with Alzheimer’s disease. Methods: We studied nine patients with early onset (age ⩽65 years), nine with late onset (age >65) Alzheimer’s disease (EOAD and LOAD, respectively) of mild-moderate severity, and 26 controls who were stratified into younger (YC, age ⩽65, n = 9) and older (OC, age >65, n = 17) subjects. The patients were closely matched for clinical severity: 3/2/3/1 patients had clinical dementia rating of 0.5/1/2/3, respectively, in both the groups. High resolution magnetic resonance images of the brain of the EOAD and YC groups and the LOAD and OC groups were compared on a voxel by voxel basis with statistical parametric mapping to detect areas specifically atrophic. Results: The patients with EOAD showed greater neocortical atrophy at the temporoparietal junction while the patients with LOAD showed greater hippocampal atrophy. The results could not be accounted for by the apolipoprotein E genotype. Conclusions: Since genetic factors are believed to play a relevant pathogenetic role in EOAD and environmental factors in LOAD, genetic and environmental factors may differentially predispose the neocortical and limbic areas to the development of Alzheimer’s neuropathology.