Publications by authors named "S E P Bruzzone"

164 Publications

Applying Spike-density component analysis for high-accuracy auditory event-related potentials in children.

Clin Neurophysiol 2021 Aug 29;132(8):1887-1896. Epub 2021 May 29.

Center for Music in the Brain, Department of Clinical Medicine, Aarhus University and Royal Academy of Music, Aarhus/Aalborg, Universitetsbyen 3, 8000 Aarhus C, Denmark; Department of Education, Psychology, Communication, University of Bari Aldo Moro, Italy.

Objective: Overlapping neurophysiological signals are the main obstacle preventing from using cortical auditory event-related potentials (AEPs) in clinical settings. Children AEPs are particularly affected by this problem, as their cerebral cortex is still maturing. To overcome this problem, we applied a new version of Spike-density Component Analysis (SCA), an analysis method recently developed, to isolate with high accuracy the neural components of auditory responses of 8-year-old children.

Methods: Electroencephalography was used with 33 children to record AEPs to auditory stimuli varying in spectrotemporal features. Three different analysis approaches were adopted: the standard AEP analysis procedure, SCA with template-match (SCA-TM), and SCA with half-split average consistency (SCA-HSAC).

Results: SCA-HSAC most successfully allowed the extraction of AEPs for each child, revealing that the most consistent components were P1 and N2. An immature N1 component was also detected.

Conclusion: Superior accuracy in isolating neural components at the individual level was demonstrated for SCA-HSAC over other SCA approaches even for children AEPs.

Significance: Reliable methods of extraction of neurophysiological signals at the individual level are crucial for the application of cortical AEPs for routine diagnostic exams in clinical settings both in children and adults.
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http://dx.doi.org/10.1016/j.clinph.2021.05.007DOI Listing
August 2021

Nampt controls skeletal muscle development by maintaining Ca homeostasis and mitochondrial integrity.

Mol Metab 2021 Jun 11;53:101271. Epub 2021 Jun 11.

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address:

Objective: NAD is a co-factor and substrate for enzymes maintaining energy homeostasis. Nicotinamide phosphoribosyltransferase (NAMPT) controls NAD synthesis, and in skeletal muscle, NAD is essential for muscle integrity. However, the underlying molecular mechanisms by which NAD synthesis affects muscle health remain poorly understood. Thus, the objective of the current study was to delineate the role of NAMPT-mediated NAD biosynthesis in skeletal muscle development and function.

Methods: To determine the role of Nampt in muscle development and function, we generated skeletal muscle-specific Nampt KO (SMNKO) mice. We performed a comprehensive phenotypic characterization of the SMNKO mice, including metabolic measurements, histological examinations, and RNA sequencing analyses of skeletal muscle from SMNKO mice and WT littermates.

Results: SMNKO mice were smaller, with phenotypic changes in skeletal muscle, including reduced fiber area and increased number of centralized nuclei. The majority of SMNKO mice died prematurely. Transcriptomic analysis identified that the gene encoding the mitochondrial permeability transition pore (mPTP) regulator Cyclophilin D (Ppif) was upregulated in skeletal muscle of SMNKO mice from 2 weeks of age, with associated increased sensitivity of mitochondria to the Ca-stimulated mPTP opening. Treatment of SMNKO mice with the Cyclophilin D inhibitor, Cyclosporine A, increased membrane integrity, decreased the number of centralized nuclei, and increased survival.

Conclusions: Our study demonstrates that NAMPT is crucial for maintaining cellular Ca homeostasis and skeletal muscle development, which is vital for juvenile survival.
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http://dx.doi.org/10.1016/j.molmet.2021.101271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259345PMC
June 2021

Association between extreme ambient temperatures and general indistinct and work-related road crashes. A nationwide study in Italy.

Accid Anal Prev 2021 Jun 6;155:106110. Epub 2021 Apr 6.

Occupational and Environmental Medicine, Epidemiology and Hygiene Department, Italian Workers' Compensation Authority (INAIL), Monte Porzio Catone, RM, Italy.

Despite the relevance of road crashes and their impact on social and health care costs, the effects of extreme temperatures on road crashes risk have been scarcely investigated, particularly for those occurring in occupational activities. A nationwide epidemiological study was carried out to estimate the risk of general indistinct and work-related road crashes related with extreme temperatures and to identify crash and occupation parameters mostly involved. Data about road crashes, resulting in death or injury, occurring during years 2013-2015 in Italy, were collected from the National Institute of Statistics, for general indistinct road crashes, and from the compensation claim applications registered by the national workers' compensation authority, for work-related ones. Time series of hourly temperature were derived from the results provided by the meteorological model WRF applied at a national domain with 5 km resolution. To consider the different spatial-temporal characteristics of the two road crashes archives, the association with extreme temperatures was estimated by means of a case-crossover time-stratified approach using conditional logistic regression analysis, and a time-series analysis, using over-dispersed Poisson generalized linear regression model, for general indistinct and work-related datasets respectively. The analyses were controlled for other covariates and confounding variables (including precipitation). Non-linearity and lag effects were considered by using a distributed lag non-linear model. Relative risks were calculated for increment from 75th to 99th percentiles (hot) and from 25 to first percentile (cold) of temperature. Results for general indistinct crashes show a positive association with hot temperature (RR = 1.12, 95 % CI: 1.09-1.16) and a negative one for cold (RR = 0.93, 95 % CI: 0.91-0.96), while for work-related crashes a positive association was found for both hot and cold (RR = 1.06 (95 % CI: 1.01-1.11) and RR = 1.10 (95 % CI: 1.05-1.16). The use of motorcycles, the location of accident (urban vs out of town), presence of crossroads, as well as occupational factors like the use of a vehicle on duty were all found to produce higher risks of road crashes during extreme temperatures. Mitigation and prevention measures are needed to limit social and health care costs.
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http://dx.doi.org/10.1016/j.aap.2021.106110DOI Listing
June 2021

Brain predictive coding processes are associated to COMT gene Val158Met polymorphism.

Neuroimage 2021 06 11;233:117954. Epub 2021 Mar 11.

Center for Music in the Brain, Department of Clinical Medicine, Aarhus University & The Royal Academy of Music Aarhus/Aalborg, Denmark; Department of Education, Psychology, Communication, University of Bari Aldo Moro, Italy.

Predicting events in the ever-changing environment is a fundamental survival function intrinsic to the physiology of sensory systems, whose efficiency varies among the population. Even though it is established that a major source of such variations is genetic heritage, there are no studies tracking down auditory predicting processes to genetic mutations. Thus, we examined the neurophysiological responses to deviant stimuli recorded with magnetoencephalography (MEG) in 108 healthy participants carrying different variants of Val158Met single-nucleotide polymorphism (SNP) within the catechol-O-methyltransferase (COMT) gene, responsible for the majority of catecholamines degradation in the prefrontal cortex. Our results showed significant amplitude enhancement of prediction error responses originating from the inferior frontal gyrus, superior and middle temporal cortices in heterozygous genotype carriers (Val/Met) vs homozygous (Val/Val and Met/Met) carriers. Integrating neurophysiology and genetics, this study shows how the neural mechanisms underlying optimal deviant detection vary according to the gene-determined cathecolamine levels in the brain.
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http://dx.doi.org/10.1016/j.neuroimage.2021.117954DOI Listing
June 2021

SIRT6 enhances oxidative phosphorylation in breast cancer and promotes mammary tumorigenesis in mice.

Cancer Metab 2021 Jan 22;9(1). Epub 2021 Jan 22.

Department of Internal Medicine and Medical Specialties (DIMI), University of Genoa, V.le Benedetto XV 6, 16132, Genoa, Italy.

Background: Sirtuin 6 (SIRT6) is a NAD-dependent deacetylase with key roles in cell metabolism. High SIRT6 expression is associated with adverse prognosis in breast cancer (BC) patients. However, the mechanisms through which SIRT6 exerts its pro-oncogenic effects in BC remain unclear. Here, we sought to define the role of SIRT6 in BC cell metabolism and in mouse polyoma middle T antigen (PyMT)-driven mammary tumors.

Methods: We evaluated the effect of a heterozygous deletion of Sirt6 on tumor latency and survival of mouse mammary tumor virus (MMTV)-PyMT mice. The effect of SIRT6 silencing on human BC cell growth was assessed in MDA-MB-231 xenografts. We also analyzed the effect of Sirt6 heterozygous deletion, of SIRT6 silencing, and of the overexpression of either wild-type (WT) or catalytically inactive (H133Y) SIRT6 on BC cell pyruvate dehydrogenase (PDH) expression and activity and oxidative phosphorylation (OXPHOS), including respiratory complex activity, ATP/AMP ratio, AMPK activation, and intracellular calcium concentration.

Results: The heterozygous Sirt6 deletion extended tumor latency and mouse survival in the MMTV-PyMT mouse BC model, while SIRT6 silencing slowed the growth of MDA-MB-231 BC cell xenografts. WT, but not catalytically inactive, SIRT6 enhanced PDH expression and activity, OXPHOS, and ATP/AMP ratio in MDA-MB-231 and MCF7 BC cells. Opposite effects were obtained by SIRT6 silencing, which also blunted the expression of genes encoding for respiratory chain proteins, such as UQCRFS1, COX5B, NDUFB8, and UQCRC2, and increased AMPK activation in BC cells. In addition, SIRT6 overexpression increased, while SIRT6 silencing reduced, intracellular calcium concentration in MDA-MB-231 cells. Consistent with these findings, the heterozygous Sirt6 deletion reduced the expression of OXPHOS-related genes, the activity of respiratory complexes, and the ATP/AMP ratio in tumors isolated from MMTV-PyMT mice.

Conclusions: Via its enzymatic activity, SIRT6 enhances PDH expression and activity, OXPHOS, ATP/AMP ratio, and intracellular calcium concentration, while reducing AMPK activation, in BC cells. Thus, overall, SIRT6 inhibition appears as a viable strategy for preventing or treating BC.
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http://dx.doi.org/10.1186/s40170-021-00240-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821730PMC
January 2021
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