Experience-dependent reshaping of body processing: from perception to clinical implications

Starting from the moment we come into the world, we are compelled to pay large attention to the body and its representation, which can be considered as a set of cognitive structures that have the function of tracing and coding our state (de Vignemont, 2010). However, we cannot consider body aside from its image, which can determine the way we emotionally perceive ourselves and other people as well as the way we experience the world. With a brief look to the body, we can identify a persons’ identity, thus catching distinctive elements such as her age or gender; further, by means of body posture and movements we can understand the affective state of others and appropriately shape our social interaction and communication. Several socially significant cues can be detected and provided through the body, but this thesis principally aims to increase the knowledge about how we perceive gender from bodily features and shape. Specifically, I report on a series of behavioral studies designed to investigate the influence of the visual experience on the detection of gender dimension, considering the contribution of brain networks which may also have a role in the development of mental disorders related to body misperception (i.e. Eating Disorders; ED). In the first chapter, I provide evidence for the interdependence of morphologic and dynamic cues in shaping gender judgment. By manipulating various characteristics of virtual-human body stimuli, the experiment I carried out demonstrates the association between stillness and femininity rating, addressing the evolutionary meaning of sexual selection and the influence of cultural norms (D’Argenio et al., 2020). In the second chapter, I present a study that seeks to define the relative role of parvo- and magnocellular visual streams in the identification of both morphologic and dynamic cues of the body. For these experiments, I used the differential tuning of the two streams to low- (LSF) and high-spatial frequencies (HSF) and I tested how the processing of body gender and postures is affected by filtering images to keep only the LSF or HSF (D’Argenio et al., submitted). The third chapter is dedicated to a series of experiments aimed at understanding how gender perception can be biased by the previous exposure to specific body models. I utilized a visual adaptation paradigm to investigate the mechanisms that drives the observers’ perception to a masculinity or femininity judgement (D’Argenio et al., 2021) and manipulates the spatial frequency content of the bodies in order to account for the contribution of parvo- and magnocellular system in in this process. In conclusion, in the last two chapters, I briefly report the preliminary results emerging from two visual adaptation studies. The first one, which is described in the fourth chapter, explored the role of cortical connections in body gender adaptation by means of Transcranial Magnetic Stimulation (TMS), with the aim to investigate neural correlates of dysfunctional body perception. The second represents the intent to explain, at least partially, body misperception disorders by applying adaptation paradigms to ED clinical population. Results were discussed in the fifth chapter.Starting from the moment we come into the world, we are compelled to pay large attention to the body and its representation, which can be considered as a set of cognitive structures that have the function of tracing and coding our state (de Vignemont, 2010). However, we cannot consider body aside from its image, which can determine the way we emotionally perceive ourselves and other people as well as the way we experience the world. With a brief look to the body, we can identify a persons’ identity, thus catching distinctive elements such as her age or gender; further, by means of body posture and movements we can understand the affective state of others and appropriately shape our social interaction and communication. Several socially significant cues can be detected and provided through the body, but this thesis principally aims to increase the knowledge about how we perceive gender from bodily features and shape. Specifically, I report on a series of behavioral studies designed to investigate the influence of the visual experience on the detection of gender dimension, considering the contribution of brain networks which may also have a role in the development of mental disorders related to body misperception (i.e. Eating Disorders; ED). In the first chapter, I provide evidence for the interdependence of morphologic and dynamic cues in shaping gender judgment. By manipulating various characteristics of virtual-human body stimuli, the experiment I carried out demonstrates the association between stillness and femininity rating, addressing the evolutionary meaning of sexual selection and the influence of cultural norms (D’Argenio et al., 2020). In the second chapter, I present a study that seeks to define the relative role of parvo- and magnocellular visual streams in the identification of both morphologic and dynamic cues of the body. For these experiments, I used the differential tuning of the two streams to low- (LSF) and high-spatial frequencies (HSF) and I tested how the processing of body gender and postures is affected by filtering images to keep only the LSF or HSF (D’Argenio et al., submitted). The third chapter is dedicated to a series of experiments aimed at understanding how gender perception can be biased by the previous exposure to specific body models. I utilized a visual adaptation paradigm to investigate the mechanisms that drives the observers’ perception to a masculinity or femininity judgement (D’Argenio et al., 2021) and manipulates the spatial frequency content of the bodies in order to account for the contribution of parvo- and magnocellular system in in this process. In conclusion, in the last two chapters, I briefly report the preliminary results emerging from two visual adaptation studies. The first one, which is described in the fourth chapter, explored the role of cortical connections in body gender adaptation by means of Transcranial Magnetic Stimulation (TMS), with the aim to investigate neural correlates of dysfunctional body perception. The second represents the intent to explain, at least partially, body misperception disorders by applying adaptation paradigms to ED clinical population. Results were discussed in the fifth chapter

The molecular analysis of BRCA1 and BRCA2: Next-generation sequencing supersedes conventional approaches

Abstract Background Accurate and sensitive detection of BRCA 1/2 germ-line mutations is crucial for the clinical management of women affected by breast cancer, for prevention and, notably, also for the identification of at-risk healthy relatives. The most widely used methods for BRCA1 / 2 molecular analysis are Sanger sequencing, and denaturing high performance liquid chromatography (dHPLC) followed by the Sanger method. However, recent findings suggest that next-generation sequencing (NGS)-based approaches may be an efficient tool for diagnostic purposes. In this context, we evaluated the effectiveness of NGS for BRCA gene analysis compared with dHPLC/Sanger sequencing. Methods Seventy women were screened for BRCA1/2 mutations by both dHPLC/Sanger sequencing and NGS, and the data were analyzed using a bioinformatic pipeline. Results Sequence data analysis showed that NGS is more sensitive in detecting BRCA 1/2 variants than the conventional procedure, namely, dHPLC/Sanger. Conclusion Next-generation sequencing is more sensitive, faster, easier to use and less expensive than the conventional Sanger method. Consequently, it is a reliable procedure for the routine molecular screening of the BRCA 1/2 genes

Experience-dependent reshaping of body gender perception

Protracted exposure to specific stimuli causes biased visual aftereffects at both low- and high-level dimensions of a stimulus. Recently, it has been proposed that alterations of these aftereffects could play a role in body misperceptions. However, since previous studies have mainly addressed manipulations of body size, the relative contribution of low-level retinotopic and/or high-level object-based mechanisms is yet to be understood. In three experiments, we investigated visual aftereffects for body-gender perception, testing for the tuning of visual aftereffects across different characters and orientation. We found that exposure to a distinctively female (or male) body makes androgynous bodies appear as more masculine (or feminine) and that these aftereffects were not specific for the individual characteristics of the adapting body (Exp.1). Furthermore, exposure to only upright bodies (Exp.2) biased the perception of upright, but not of inverted bodies, while exposure to both upright and inverted bodies (Exp.3) biased perception for both. Finally, participants' sensitivity to body aftereffects was lower in individuals with greater communication deficits and deeper internalization of a male gender role. Overall, our data reveals the orientation-, but not identity-tuning of body-gender aftereffects and points to the association between alterations of the malleability of body gender perception and social deficits

Disturbi alimentari e neuroscienze: la rappresentazione del corpo

La societ\ue0 odierna rivolge sempre maggiore attenzione al corpo e alla sua rappresentazione e tale fenomeno viene indubbiamente enfatizzato dalla realt\ue0 mediatica dell\u2019immagine nella quale siamo immersi. Ci\uf2 rende il corpo un\u2019icona che si impone fortemente su tutte le altre caratteristiche psicologiche e di personalit\ue0 dell\u2019individuo, spesso con risultati negativi. Non a caso diversi studi hanno messo in luce come le sensazioni negative riguardanti l\u2019inadeguatezza del proprio corpo siano correlate allo sviluppo dei disturbi della nutrizione e dell\u2019alimentazione (Stice, Shaw, 2002), a loro volta associati a problemi fisici e psicologici a lungo termine (Wagner et al., 2006; Mascolo et al., 2012) nonch\ue9 al pi\uf9 alto tasso di mortalit\ue0 tra i disturbi psichiatrici (Smink, van Hoeken, Hoek, 2012). \uc8 ormai evidente che l\u2019origine e il decorso dei disturbi alimentari (DA) abbiano un\u2019eziologia multifattoriale e che, accanto ai pi\uf9 noti fattori psicologici, evolutivi, biologici e socioculturali, debbano essere presi in considerazione alcuni aspetti pi\uf9 prettamente cognitivi, tra i quali la rappresentazione del corpo

Apple polyphenol extracts prevent aspirin-induced damage to the rat gastric mucosa

Aspirin causes gastroduodenal ulcers and complications. Food bioactive compounds could exert beneficial effects in the gastrointestinal tract. We evaluated whether apple polyphenol extract (APE) reduced aspirin-induced injury to the rat gastric mucosa. Rats were treated with APE (104 M catechin equivalent) before oral aspirin (200 mg/kg). Cyclo-oxygenase-2 (COX-2), transforming growth factor-α (TGFα) and heparin-binding epidermal-growth-factor-like growth factor (HB-EGF) mRNA and protein expression were assessed by RT-PCR and Western blot analysis, respectively; malondialdehyde (MDA) was determined by HPLC; gastric secretion was evaluated in pylorus-ligated rats. APE decreased acute and chronic aspirin injury both macroscopically and microscopically (approximately 50% decrease in lesion score; P < 0. 05). Aspirin up-regulated mRNA and protein expression of COX-2 and HB-EGF, but not of TGFα APE reduced aspirin-induced mRNA and protein over-expression of COX-2 and HB-EGF; aspirin significantly increased gastric MDA and this effect was counteracted by APE pre-treatment. APE did not significantly affect gastric acid secretion. In conclusion, APE reduces aspirin-induced gastric injury independently of acid inhibition. We speculate that APE might be of therapeutic use in the prophylaxis of aspirin-related gastropathy

DNA sequence capture and high-throughput sequencing technology: a novel approach to identify a large number of hypertrophic cardiomyopathy-causing genes

Hypertrophic cardiomyopathy (HCM) is the most frequent genetic cardiovascular disease worldwide and is an important cause of heart failure-related disability in young people. To date, more than 20 different genes have been identified and the number is increasing. We evaluted a novel approach to identify causative mutations in a large number of HCM-related and candidate genes. Four HCM patients previously analysed by DHPLC/Sanger sequencing for causative mutations in 8 sarcomeric genes were enrolled in this study. Overall, 234 genes were selected for array on the chip, and a custom sequence capture array was designed for target enrichment of all coding regions. The size of our target was 3,908,196 bp. Each DNA sample was enriched using one custom array, and then sequenced in two runs by the GS FLX System. We obtained an average of 164 Mb/sample, which is equivalent to 503,775 sequencing reads/sample with an average read length of 325.6 bp. Sequence and data analysis were performed using the Roche/454 gsMapper software. High confidence variants were blasted against the SNP database to distinguish between known and unknown variants. We found 7864 different variants, of which 6725 were intronic, 424 intergenic and 715 exonic. About 31% of these variants were novel and 56 novel variants were in 35 HCM related genes. In all patients, we confirmed the mutations and polymorphisms previously identified in them with the DHPLC/Sanger approach. The simultaneous analysis of a vocabulary of genes so to increase sensitivity for the molecular diagnosis may in turn increase the information for those patients in whom traditional screening was not adequate. With this new technology it may be possible to identify mutations in genes that, also acting as phenotype modifiers, could be responsible for clinical variability thereby explaining the pathogenetic mechanism underlying HCM development. Consequently, by reducing time and costs and increasing the sensitivity of molecular testing, routine HCM molecular diagnostics could be implemented also to obtain a model readily applicable to other genetic diseases

DNA Sequence Capture and Next-Generation Sequencing for the Molecular Diagnosis of Genetic Cardiomyopathies

Hypertrophic cardiomyopathy is a relatively frequent disease with a prevalence of 0.2% worldwide and a remarkable genetic heterogeneity, with more than 30 causative genes reported to date. Current PCR-based strategies are inadequate for genomic investigations involving many candidate genes. Here, we report a next-generation sequencing procedure associated with DNA sequence capture that is able to sequence 202 cardiomyopathy-related genes simultaneously. We developed a complementary data analysis pipeline to select and prioritize genetic variants. The overall procedure can screen a large number of target genes simultaneously, thereby potentially revealing new disease-causing and modifier genes. By using this procedure, we analyzed hypertrophic cardiomyopathy patients in a shorter time and at a lower cost than with current procedures. The specificity of the next-generation sequencing-based procedure is at least as good as other techniques routinely used for mutation searching, and the sensitivity is much better. Analysis of the results showed some novel variants potentially involved in the pathogenesis of hypertrophic cardiomyopathy: a missense mutation in MYH7 and a nonsense variant in INS-IGF2 (patient 1), a splicing variant in MYBPC3 and an indel/frameshift variant in KCNQ1 (patient 2), and two concomitant variations in CACNA1C (patient 3). Sequencing of DNA from the three patients within a pool allowed detection of most variants identified in each individual patient, indicating that this approach is a feasible and cost-effective procedure

DNA Sequence Capture and High Throughput Sequencing Technology: a Novel Approach to Identify a Large Number of Hypertrophic Cardiomyopathy-causing Genes

Hypertrophic cardiomyopathy (HCM) is the most frequent genetic cardiovascular disease worldwide and is an important cause of heart failure-related disability in young people. To date, more than 20 different genes have been identified and the number is increasing. We evaluted a novel approach to identify causative mutations in a large number of HCM-related and candidate genes. Four HCM patients previously analysed by DHPLC/Sanger sequencing for causative mutations in 8 sarcomeric genes were enrolled in this study. Overall, 234 genes were selected for array on the chip, and a custom sequence capture array was designed for target enrichment of all coding regions. The size of our target was 3,908,196 bp. Each DNA sample was enriched using one custom array, and then sequenced in two runs by the GS FLX System. We obtained an average of 164 Mb/sample, which is equivalent to 503,775 sequencing reads/sample with an average read length of 325.6 bp. Sequence and data analysis were performed using the Roche/454 gsMapper software. High confidence variants were blasted against the SNP database to distinguish between known and unknown variants. We found 7864 different variants, of which 6725 were intronic, 424 intergenic and 715 exonic. About 31% of these variants were novel and 56 novel variants were in 35 HCM related genes. In all patients, we confirmed the mutations and polymorphisms previously identified in them with the DHPLC/Sanger approach. The simultaneous analysis of a vocabulary of genes so to increase sensitivity for the molecular diagnosis may in turn increase the information for those patients in whom traditional screening was not adequate. With this new technology it may be possible to identify mutations in genes that, also acting as phenotype modifiers, could be responsible for clinical variability thereby explaining the pathogenetic mechanism underlying HCM development. Consequently, by reducing time and costs and increasing the sensitivity of molecular testing, routine HCM molecular diagnostics could be implemented also to obtain a model readily applicable to other genetic diseases