Search

The objective of this research is to assess the social awareness of Voluntary Termination of Pregnancy (VTP) in order to develop adequate information and training programmes. An observational study was carried out on a sample of individuals aged between 14 and 68. In social-aggregation areas 800 questionnaires were distributed, prior to the assurance of anonymity. 90.5% of the individuals asked to participate, answered the questionnaire. 21.2% of the sample was not aware of the existence of guidance centre in the Local Health Authorities and 25.7% of the Law that regulates VTP. Less than half of the interviewees (42.3%) considered VTP as an admissible choice in special circumstances, 11% consider it as a means of prevention of unwanted pregnancy and 55.35% do not know that a minor can have an abortion without the consent of her parents. 41.7% of the women interviewed would resort to VTP, while 12.2% have already resorted to it. The inclination to perform VTP has been drastically associated mainly with not being in a stable relationship, age, or being an atheist.

En 1724, un certain capitaine Charles Johnson publie a Londres A General History of the Robberies and Murders of the Most Notorious Pyrates and also their Policies, Discipline and Government. Chacun des dix-sept chapitres qui composent le volume raconte l’histoire d’un capitaine et de son equipage, parmi lesquels Rackham le Rouge et les femmes pirates, Mary Reed et Ann Bony, Edward Teach, plus connu sous le nom de Barbe noire, ou encore Henry Avery, devenu roi a Madagascar. Quatre ans plus t...

Pericentric heterochromatin (PCH) is a particular form of constitutive heterochromatin that is localized to both sides of centromeres and that forms silent compartments enriched in repressive marks. These genomic regions contain species-specific repetitive satellite DNA that differs in terms of nucleotide sequences and repeat lengths. In spite of this sequence diversity, PCH is involved in many biological phenomena that are conserved among species, including centromere function, the preservation of genome integrity, the suppression of spurious recombination during meiosis, and the organization of genomic silent compartments in the nucleus. PCH organization and maintenance of its repressive state is tightly regulated by a plethora of factors, including enzymes (e.g., DNA methyltransferases, histone deacetylases, and histone methyltransferases), DNA and histone methylation binding factors (e.g., MECP2 and HP1), chromatin remodeling proteins (e.g., ATRX and DAXX), and non-coding RNAs. This evidence helps us to understand how PCH organization is crucial for genome integrity. It then follows that alterations to the molecular signature of PCH might contribute to the onset of many genetic pathologies and to cancer progression. Here, we describe the most recent updates on the molecular mechanisms known to underlie PCH organization and function.

In his 1995 book, The Mangle of Practice, Andrew Pickering distinguished between representationalist and performative idioms in philosophy of science. While the former describes science as mainly a theoretical enterprise, the latter represents science as a collection of practices. The two perspectives outline two kinds of epistemologies presenting different philosophical concerns. In fact, in a scientific world where entities are not only thought or represented but touched, used, and transformed, the question about their existence does not really matter. What does matter though is to what extent we can extrapolate, from all our experimental material activities, the “real” working of the natural processes. In this chapter, drawing on Pickering's insights, we introduce a particular kind of performative epistemology fit for grasping how experimental biologists produce reliable knowledge. We argue that experimental biology can be mapped through four principal points: constrained action, standardization, epistemic “tightening,” and extrapolation. We show that each point presents its own proper problems, assumptions, and epistemic challenges. All together, the points define what we call the Epistemic Experimental Space (EES), i.e., the space in which experimental knowledge is produced, assessed, and validated. Without the pretention to be exhaustive, we also identify some of the main conditions making experimental knowledge in biology a highly consistent, reliable, and successful epistemic activity.

Resumen La relación entre organismos y maquinas es muy antigua. Hace más de un siglo, el filósofo e historiador francés Alfred Victor Espinas señalaba que ya para los griegos la inteligibilidad de lo orgánico suponía una comparación con el mundo de la técnica. Aristóteles, por ejemplo, equiparaba los órganos con los artefactos mecánicos para entender el movimiento de los animales. En el período moderno, Descartes, Borelli y otros mecanicistas defendieron la idea que los organismos eran maquinas. Hoy en día, no faltan filósofos y científicos que consideran al genoma como un programa informático y al cerebro como un computador. En este artículo, pretendo reconsiderar la relación entre organismos y maquinas a partir de propuesta de un autor todavía poco conocido: el filósofo y geógrafo alemán Ernst Kapp (1808-1896), unos de los padres fundadores de la Filosofía de la Técnica y la Tecnología. Rompiendo con una larga tradición filosófica, Kapp defiende la idea que las maquinas son, en realidad, “proyecciones orgánicas”. Los organismos no son máquinas, sino que, por el contrario, las maquinas son una imitación o reflejo del mundo orgánico. En primer lugar, aclararé la hipótesis de la proyección orgánica (así como sus alcances y límites), y, en segundo lugar, exploraré algunas de las consecuencias filosóficas de dicha hipótesis respecto al debate actual entre mecanicistas y anti-mecanicistas. Finalmente, defenderé la importancia de un acercamiento entre la Filosofía de la Tecnología y la Bio-filosofía para mejor entender el desarrollo de la Biología contemporánea.

Methyl-CpG binding protein 2 (MeCP2) is a multi-function factor involved in locus-specific transcriptional modulation and the regulation of genome architecture, e.g., pericentric heterochromatin (PCH) organization. MECP2 mutations are responsible for Rett syndrome (RTT), a devastating postnatal neurodevelopmental disorder, the pathogenetic mechanisms of which are still unknown. MeCP2, together with Alpha-thalassemia/mental retardation syndrome X-linked protein (ATRX), accumulates at chromocenters, which are repressive PCH domains. As with MECP2, mutations in ATRX cause ATR-X syndrome which is associated with severe intellectual disability. We exploited two murine embryonic stem cell lines, in which the expression of MeCP2 or ATRX is abolished. Through immunostaining, chromatin immunoprecipitation and western blot, we show that MeCP2 and ATRX are reciprocally dependent both for their expression and targeting to chromocenters. Moreover, ATRX plays a role in the accumulation of members of the heterochromatin protein 1 (HP1) family at PCH and, as MeCP2, modulates their expression. Furthermore, ATRX and HP1 targeting to chromocenters depends on an RNA component. 3D-DNA fluorescence in situ hybridization (FISH) highlighted, for the first time, a contribution of ATRX in MeCP2-mediated chromocenter clustering during neural differentiation. Overall, we provide a detailed dissection of the functional interplay between MeCP2 and ATRX in higher-order PCH organization in neurons. Our findings suggest molecular defects common to RTT and ATR-X syndrome, including an alteration in PCH.

Scholars have paid great attention to the neo-Darwinism of Ronald Fisher. He was one of the founding fathers of the modern synthesis and, not surprisingly, his writings and life have been widely scrutinized. However, less attention has been paid to his interests in the human sciences. In assessing Fisher’s uses of the human sciences in his seminal book the Genetical Theory of Natural Selection and elsewhere, the article shows how Fisher’s evolutionary thought was essentially eclectic when applied to the human context. In order to understand how evolution works among humans, Fisher made himself also a sociologist and historian. More than a eugenically minded Darwinist, Fisher was also a sophisticated scholar combining many disciplines without the ambition to reduce, simplistically, the human sciences to biology.

Neurological disorders can be associated with protein glycosylation abnormalities. Rett syndrome is a devastating genetic brain disorder, mainly caused by de novo loss-of-function mutations in the methylCpG binding protein 2 (MECP2) gene. Although its pathogenesis appears to be closely associated with a redox imbalance, no information on glycosylation is available. Glycoprotein detection strategies (i.e., lectin-blotting) were applied to identify target glycosylation changes in the whole brain of Mecp2 mutant murine models of the disease. Remarkable glycosylation pattern changes for a peculiar 50 kDa protein, i.e., the N-linked brain nucleotide pyrophosphatase-5 were evidenced, with decreased N-glycosylation in the presymptomatic and symptomatic mutant mice. Glycosylation changes were rescued by selected brain Mecp2 reactivation. Our findings indicate that there is a causal link between the amount of Mecp2 and the N-glycosylation of NPP-5. (C) 2015 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Huntington's disease is characterized by a complex and heterogeneous pathogenic profile. Studies have shown that disturbance in lipid homeostasis may represent a critical determinant in the progression of several neurodegenerative disorders. The recognition of perturbed lipid metabolism is only recently becoming evident in HD. In order to provide more insight into the nature of such a perturbation and into the effect its modulation may have in HD pathology, we investigated the metabolism of Sphingosine-1-phosphate (S1P), one of the most important bioactive lipids, in both animal models and patient samples. Here, we demonstrated that S1P metabolism is significantly disrupted in HD even at early stage of the disease and importantly, we revealed that such a dysfunction represents a common denominator among multiple disease models ranging from cells to humans through mouse models. Interestingly, the in vitro anti-apoptotic and the pro-survival actions seen after modulation of S1P-metabolizing enzymes allows this axis to emerge as a new druggable target and unfolds its promising therapeutic potential for the development of more effective and targeted interventions against this incurable condition.

El artículo explora algunos de los sentidos y usos de la historia en la filosofía de las ciencias. Se argumenta que la ausencia (o presencia) de la historia en las reflexiones filosóficas sobre la ciencia no depende de una falta de comunicación entre historiadores y filósofos, sino del contraste entre dos concepciones filosóficas del conocimiento radicalmente distintas. Por un lado, hay una concepción “idealista” que defiende un ideal de razón autónomo de cualquier elemento contingente que pueda orientar la cogitación científica. Por otro lado, hay una concepción “materialista” que es más atenta a las condiciones contextuales que posibilitan la ocurrencia de formas específicas de conocimientos. Las dos concepciones tienen historias distintas e interpretan la actividad científica en formas muy diferentes. La primera se enfoca en los aspectos teóricos de la ciencia y se orienta hacia un análisis conceptual de aquellas teorías científicas más exitosas en términos de coherencia, predicción y adecuación empírica (entre otros). La segunda es más orientada hacia la “praxis” científica y dirige su atención al conjunto de instrumentos, acciones, intereses y objetivos espacios que forjan formas situadas de conocimientos. También argumento que mientras la concepción “idealista” se aproxima a los ideales epistémicos de las Naturwissenschaften; la concepción “materialista” se acerca a los ideales metodológicos de las Geisteswissenschaften. Por lo tanto, mientras que en la primera concepción el saber histórico es accesorio, en la segunda este es indispensable. Concluyo sosteniendo que, si aceptamos la validez de dicha distinción, muchas de las dicotomías tradicionales que han caracterizado la filosofía de la ciencia hasta el momento – por ejemplo, externalismo versus internalismo o descubrimiento versus justificación – requieren una profunda revisión. The paper explores some of the meanings and uses of history in the philosophy of science. I argue that the absence (or presence) of history in the philosophical reflections of science does not depend from the lack of discussion between historians and philosophers. Rather, it follows from the clash between two radically different philosophical conceptions of knowledge. On the one hand, we have an “idealist” conception of knowledge, which defends a perspective of reason as autonomous from any contingent and particular element that might orient scientific cogitations. On the other hand, we have a “materialist” conception of knowledge, which is largely inclined towards the situated and contextual conditions making particular forms of knowledge possible. The two traditions have different histories and different understandings of science. The former is generally theory-centred and more focused over the analysis of successful scientific theories in terms of coherence, predictive power and empirical adequacy. The latter, instead, is mostly “praxis” centred and interested on how scientific practices, instruments, interests and goals shape particular forms of knowledge. I also argue that while the “idealist” conception of epistemology is closer to a Naturwissenschaften’s outlook; the “materialist” one fits more with a Geisteswissenschaften’s approach. Accordingly, while in the former case historical wisdom is auxiliary, in the latter case history is indispensable. I conclude that once we accept such distinction, many of the traditional dichotomies that have haunted philosophy of science so far– i.e. externalism or internalism, discovery or justification – need to be radically reframed.

Neural development is accomplished by differentiation events leading to metabolic reprogramming. Glycosphingolipid metabolism is reprogrammed during neural development with a switch from globo‐ to ganglio‐series glycosphingolipid production. Failure to execute this glycosphingolipid switch leads to neurodevelopmental disorders in humans, indicating that glycosphingolipids are key players in this process. Nevertheless, both the molecular mechanisms that control the glycosphingolipid switch and its function in neurodevelopment are poorly understood. Here, we describe a self‐contained circuit that controls glycosphingolipid reprogramming and neural differentiation. We find that globo‐series glycosphingolipids repress the epigenetic regulator of neuronal gene expression AUTS2. AUTS2 in turn binds and activates the promoter of the first and rate‐limiting ganglioside‐producing enzyme GM3 synthase, thus fostering the synthesis of gangliosides. By this mechanism, the globo–AUTS2 axis controls glycosphingolipid reprogramming and neural gene expression during neural differentiation, which involves this circuit in neurodevelopment and its defects in neuropathology.

In this article we argue that the classical—linear and bottom-up directed—models of causation in biology, and the “proximate/ultimate” dichotomy, are inappropriate to capture the complexity inherent to biological processes. We introduce a new notion of “multilevel causation” where old dichotomies such as proximate/ultimate and bottom-up/top-down are reinterpreted within a multilevel, web-like, approach. In briefly reviewing some recent work on complexity, EvoDevo, carcinogenesis, autocatalysis, comparative genomics, animal regeneration, phenotypic plasticity, and niche construction, we will argue that such reinterpretation is a necessary step for the advancement of the “Extended Synthesis.”

Hypoxia plays a crucial role in the angiogenic switch, modulating a large set of genes mainly through the activation of hypoxia-inducible factor (HIF) transcriptional complex. Endothelial cells play a central role in new vessels formation and express placental growth factor (PlGF), a member of vascular endothelial growth factor (VEGF) family, mainly involved in pathological angiogenesis. Despite several observations suggest a hypoxia-mediated positive modulation of PlGF, the molecular mechanism governing this regulation has not been fully elucidated. We decided to investigate if epigenetic modifications are involved in hypoxia-induced PlGF expression. We report that PlGF expression was induced in cultured human and mouse endothelial cells exposed to hypoxia (1% O 2), although DNA methylation at the Plgf CpG-island remains unchanged. Remarkably, robust hyperacetylation of histones H3 and H4 was observed in the second intron of Plgf, where hypoxia responsive elements (HREs), never described before, are located. HIF-1?, but not HIF-2?, binds to identified HREs. Noteworthy, only HIF-1? silencing fully inhibited PlGF upregulation. These results formally demonstrate a direct involvement of HIF-1? in the upregulation of PlGF expression in hypoxia through chromatin remodeling of HREs sites. Therefore, PlGF may be considered one of the putative targets of anti-HIF therapeutic applications.

ArgumentD’Arcy Thompson has often been portrayed as a loner. His science of form has frequently been labeled anachronistic, idiosyncratic, and unconnected to his contemporary biology. This article aims to challenge this interpretation. Thompson's representation as a loner did not lie in the idiosyncrasies of his science, but in our own historiography. Through the use of unedited archival sources, this study shows that Thompson's biology was well-connected to an international research program – a program mainly shared by developmental biologists, physiologists, and morphologists. In addition, this article also aims to propose a new interpretation of Thompson'sOn Growth and Form. Drawing on his private correspondence and published sources, the paper re-contextualizes the contents and conclusions of Thompson's seminal work. We will see that Thompson defended a particular kind of organismal biology. The bio-science he supported stemmed not only from Aristotle's zoology or Pythagorean mathematics, but had many allies among twentieth-century naturalists.

In 1903, the Scripps Marine Association was founded in La Jolla, San Diego. It was rechristened the Scripps Institution of Oceanography two decades later. Today it is one of the largest marine research institutions in the world. The present study aims to reconstruct the history of this institution during the first years of its existence, the life of its first director, W. E. Ritter, and the cultural and scientific background of both. In particular, through the use of archival sources and unpublished materials, the essay reports on Ritter’s dream to import a form of holistic biology from Europe to southern California. This biology, which Ritter termed “organismal,” had to challenge reductionist and mechanist approaches to life sciences, including Weismann’s and Mendelian’s theories of heredity, both considered ideologically biased, politically dangerous, and scientifically flawed. Ritter believed that his new biology had to be grounded in a pluralist approach where laboratory and field investigations went hand in hand. In addition, the new biology had to support a progressivist political agenda whereby biological studies were linked with the political progress and the democratization of California and the United States. Despite its ambitions, Ritter’s research program was rapidly forgotten after the 1930s. In the conclusion, the article explores a few possible hypotheses explaining why this happened.

Blood-brain barrier (BBB) breakdown, due to the concomitant disruption of the tight junctions (TJs), normally required for the maintenance of BBB function, and to the altered transport of molecules between blood and brain and vice-versa, has been suggested to significantly contribute to the development and progression of different brain disorders including Huntington’s disease (HD). Although the detrimental consequence the BBB breakdown may have in the clinical settings, the timing of its alteration remains elusive for many neurodegenerative diseases. In this study we demonstrate for the first time that BBB disruption in HD is not confined to established symptoms, but occurs early in the disease progression. Despite the obvious signs of impaired BBB permeability were only detectable in concomitance with the onset of the disease, signs of deranged TJs integrity occur precociously in the disease and precede the onset of overt symptoms. To our perspective this finding may add a new dimension to the horizons of pathological mechanisms underlying this devastating disease, however much remains to be elucidated for understanding how specific BBB drug targets can be approached in the future.

Rett Syndrome (RTT), which affects approximately 1:10.000 live births, is a X-linked pervasive neuro-developmental disorder which is caused, in the vast majority of cases, by a sporadic mutation in the Methyl-CpG-binding protein-2 (MeCP2) gene. This is a transcriptional activator/repressor with presumed pleiotropic activities. The broad tissue expression of MeCP2 suggests that it may be involved in several metabolic pathways, but the molecular mechanisms which provoke the onset and progression of the syndrome are largely unknown. In this paper, we report that primary fibroblasts that have been isolated from RTT patients display a defective formation of autophagosomes under conditions of nutrient starvation and that the mature Red Blood Cells of some RTT patients retain mitochondria. Moreover, we provide evidence regarding the accumulation of the p62/SQSTM1 protein and ubiquitin-aggregated structures in the cerebellum of Mecp2 knockout mouse model (Mecp2−/y) during transition from the non-symptomatic to the symptomatic stage of the disease. Hence, we propose that a defective autophagy could be involved in the RTT clinical phenotype, which introduces new molecular perspectives in the pathogenesis of the syndrome.

In 1915, the German physiologist Jacques Loeb published a paper titled “Mechanistic Science and Metaphysical Romance.” In that article, Loeb lamented that scientific research was still infected by a “romantic” approach. Despite the triumphal achievements of the sciences based on mechanistic precepts, romantic and mystical speculations abounded. Life science, Loeb added, was besieged by mysticism, vitalism, and irrationalism. “Romantic” evolutionists indulged in unsupported theories and untested conjectures. But who were these twentieth-century “romantics” really? In this chapter, it will be argued that, contrarily to Loeb’s rhetoric, such a “romantic” community was not always constituted by irrational and mystical cranks. Rather, it was often composed of reflective scientists criticizing the overoptimism of the neo-Darwinian agenda and the unwarranted ambitions of the mechanistic (physicalist) approaches to biology. The chapter has three aims: First, to outline the main ideas of the early twentieth-century organicist agenda, with particular emphasis on evolutionary and developmental biology. Second, to briefly present the background and works of a few representative figures involved in the international community of organismal biology from the 1920s onward. Third, to show that aside from the neo-Darwinian synthesis, these scholars proposed an alternative synthesis between the 1920s and 1950s, a biological synthesis aiming to link studies on evolutionary and developmental biology within an organismal framework. The points of convergence and divergence between the two syntheses will be assessed. Then, the question of whether or not they were two incommensurable alternatives will be addressed.

UCP2 maps nearby the lod score peak of STR1-stroke QTL in the SHRSP rat strain. We explored the potential contribution of UCP2 to the high-salt diet (JD)-dependent increased stroke susceptibility of SHRSP. Male SHRSP, SHRSR, two reciprocal SHRSR/SHRSP-STR1/QTL stroke congenic lines received JD for 4 weeks to detect brain UCP2 gene/protein modulation as compared with regular diet (RD). Brains were also analyzed for NF-κB protein expression, oxidative stress level and UCP2-targeted microRNAs expression level. Next, based on knowledge that fenofibrate and Brassica Oleracea (BO) stimulate UCP2 expression through PPARα activation, we monitored stroke occurrence in SHRSP receiving JD plus fenofibrate versus vehicle, JD plus BO juice versus BO juice plus PPARα inhibitor. Brain UCP2 expression was markedly reduced by JD in SHRSP and in the (SHRsr.SHRsp-(D1Rat134-Mt1pa)) congenic line, whereas NF-κB expression and oxidative stress level increased. The opposite phenomenon was observed in the SHRSR and in the (SHRsp.SHRsr-(D1Rat134-Mt1pa)) reciprocal congenic line. Interestingly, the UCP2-targeted rno-microRNA-503 was significantly upregulated in SHRSP and decreased in SHRSR upon JD, with consistent changes in the two reciprocal congenic lines. Both fenofibrate and BO significantly decreased brain microRNA-503 level, upregulated UCP2 expression and protected SHRSP from stroke occurrence. In vitro overexpression of microRNA-503 in endothelial cells suppressed UCP2 expression and led to a significant increase of cell mortality with decreased cell viability. Brain UCP2 downregulation is a determinant of increased stroke predisposition in high-salt-fed SHRSP. In this context, UCP2 can be modulated by both pharmacological and nutraceutical agents. The microRNA-503 significantly contributes to mediate brain UCP2 downregulation in JD-fed SHRSP.

Genetic determinism is nowadays largely questioned and widely criticized. However, if we look at the history of biology in the last one hundred years, we realize that genetic determinism has always been controversial. Why, then, did it acquire such relevance in the past despite facing longstanding criticism? Through the analysis of some of the ambitious expectations of future scientific applications, this article explores the possibility that part of the historical success of genetic determinism lies in the powerful rhetorical strategies that have connected the germinal matter with alluring bio-technological visions. Indeed, in drawing on the recent perspectives of "expectation studies" in science and technology, it will be shown that there has been an interesting historical relationship between reductionist notions of the gene as a hereditary unit, coded information or functional DNA segment, and startling prophecies of what controlling such an entity might achieve. It will also be suggested that the well-known promissory nature of genomics is far older than the emergence of biotechnology in the 1970s. At least from the time of the bio-utopias predicted by J.B.S. Haldane and J. S. Huxley, the gene has often been surrounded by what I call the "rhetoric of futurity": a promissory rhetoric that, despite momentous changes in the life sciences throughout the 20th century, has remained relatively consistent over time.

This paper has three principal aims: first, through a detailed analysis of the hypotheses and assumptions underlying Weismann's and Morgan's disagreement on the nature of animal regeneration, it seeks to readdress the imbalance in coverage of their discussion, providing, at the same time, a fascinating case-study for those interested in general issues related to controversies in science. Second, contrary to Morgan's beliefs according to which Weismann employed a speculative and unempirical method of scientific investigation, the article shows that Weismann performed experiments, made observations and proposed 'undogmatic' theories open to refutation. Third, through the reconstruction of Weismann's and Morgan's disagreement, this study illustrates how biology, during the very late nineteenth and early twentieth centuries, was undergoing important changes. I argue that this controversy clearly and convincingly demonstrates how some important epistemic assumptions became increasingly problematic for some members of the younger generations of biologists. At the end of my discussion I will also argue that Weismann and Morgan both had strong well-grounded arguments supporting their conclusions; for this reason I suggest a few factors ("taken-for-granted" beliefs or assumptions) that could explain why their disagreement was doomed to remain unresolved. In particular, I will analyze their diverse explicative interests, their different theoretical concerns and their distinct use of the available evidence.

PurposeThis paper aims to consider the influence of imprisonment on the health of prisoners with the HIV virus or AIDS and their perceptions of their quality of life.Design/methodology/approachThis is a qualitative study involving adult male prisoners in three Italian prisons. A total of 19 individual semi‐structured interviews were conducted.FindingsLife in prison for HIV positive detainees is experienced as a kind of “double burden,” due to the connection between the loss of freedom and the limitations imposed by their health status. The experience of being ill and sick in prison results in the prisoner exhibiting fatalism towards the future, having a sense of alienation and marginalisation as well as being afraid of the consequences of living with HIV or AIDS.Social implicationsPrison can be considered as a “total institution” where prisoners are cut off from every role except the negative one of a prisoner deprived of freedom, and this situation greatly contributes to apathy and reinforces the inmates' antisocial behaviour.Originality/valueThis paper gives a voice to the needs and views of Italian prisoners who are HIV positive or who have AIDS and presents these in the context of the international situation.

Background: Several international studies, confirmed in Italy too, show a hard presence of socio-relational problems inside the celiac population. Methods: Qualitative study involving persons with celiac disease and their families. 25 individual semi-structured interviews were conducted in three Italian regions. Results: Problems of management of social life for celiac persons are experienced, specially in the fields of: school, work, travels and life outside the home. Conclusion: Chronic illness is a “biographical disruption” [1] and the whole society has to be invested to fight the burden of celiac persons in their possibility of access to public life.

Objective Rett syndrome (RTT) is a neurological disorder and a leading cause of mental retardation in females. It is caused by mutations in methyl-CpG-binding protein 2 (MeCP2) gene and more rarely in cyclin-dependent kinase-like 5 (CDKL5) and forkhead box protein G1 (FOXG1) genes. Increased oxidative stress (OS) has been documented in MeCP2-RTT patients. Here, we evaluated the levels of 4-hydroxynonenal plasma protein adducts (4HNE-PAs) in MeCP2-, CDKL5-, and FOXG1-RTT and in their clinical variants. Design and methods 4HNE-PAs were determined by Western blot in plasma from healthy subjects and RTT patients. Results 4HNE-PAs levels were increased in MeCP2- and CDKL5-related RTT but not in FOXG1-related RTT. Conclusion These results showed that OS is present in RTT clinical variants and could play a key role in RTT pathogenesis. Under the OS point of view FOXG1-related RTT appears to be distinct from the MeCP2/CDKL5, suggesting a distinct mechanism involved in its pathogenesis.

In this paper I propose a new interpretation of the British evolutionary synthesis. The synthetic work of J. B. S. Haldane, R. A. Fisher and J. S. Huxley was characterized by both an integration of Mendelism and Darwinism and the unification of different biological subdisciplines within a coherent framework. But it must also be seen as a bold and synthetic Darwinian program in which the biosciences served as a utopian blueprint for the progress of civilization. Describing the futuristic visions of these three scientists in their synthetic heydays, I show that, despite a number of important divergences, their biopolitical ideals could be biased toward a controlled and regimented utopian society. Their common ideals entailed a social order where liberal and democratic principles were partially or totally suspended in favor of bioscientific control and planning for the future. Finally, I will argue that the original redefinition of Darwinism that modern synthesizers proposed is a significant historical example of how Darwinism has been used and adapted in different contexts. The lesson I draw from this account is a venerable one: that, whenever we wish to define Darwinism, we need to recognize not only its scientific content and achievements but expose the other traditions and ideologies it may have supported.

Despite declarations about health and social inequalities by the World Health Organization (WHO) and the Italian Constitution, the Italian penitentiary health system often does not meet the needs of the prisoners. This article summarizes the findings concerning contextual and structural reasons for these deficiencies (in part as reported by a prisoner rights association) and describes an Italian Ministry of Justice project to promote health by creating homogeneous groups of comorbidity for epidemiological study. Data and analysis on certain pathologies in the prison population are presented with special regard to addictions, hepatitis C virus, and cardiovascular problems. One etiological hypothesis focuses on the factors of promiscuity, excessive smoking, sedentary life, and stress. The conclusion is that prisoner health is a problem not only of inmates but for society.

The compensation of the different level of transcripts of X-linked genes in male and female mammals is achieved through X chromosome inactivation, a complex process that differentially regulates the sex chromosomes of female cells. This mechanism has been dissected at evolutionary, genetic and molecular levels: here, we discuss some of the latest examples that illustrate better these intricate connections, focusing particularly on the emerging role of spatial and three-dimensional chromatin arrangements in the building of this special chromosome, the inactive X chromosome.

X chromosome inactivation (XCI) is the phenomenon by which mammals compensate for dosage of X-linked genes in females (XX) versus males (XY). XCI patterns can be random or show extreme skewing, and can modify the mode of inheritance of X-driven phenotypes, which contributes to the variability of human pathologies. Recent findings have shown reversibility of the XCI process, which has opened new avenues in the approaches used for the treatment of X-linked diseases.

High individual variability in follicular recruitment and hence in the number of embryos produced is a major factor limiting the application of reproductive technologies in buffalo. Therefore, the identification of reliable markers to select embryo donors is critical to enroll buffaloes in embryo production programs. Better understanding of factors involved in follicular growth is also necessary to improve the response to superovulation in this species. The aim of this work was thus to determine the anti-Mullerian hormone (AMH) concentration in follicular fluid (FF) recovered from different size follicles and evaluate the mRNA expression profiles of development-related (AMHR2, CYP19A1, FSHR, and LHR) and apoptosis-related genes (TP53INP1 and CASP3) in the corresponding granulosa cells (GCs) in buffalo. Another objective was to evaluate whether the AMH concentration in FF and gene expression of GCs is associated with the antral follicular count. Ovaries were collected at the slaughterhouse, and all follicles were counted and classified as small (3-5 mm), medium (5-8 mm), and large (>8 mm). Follicular fluid was recovered for AMH determination, and the mRNA expression of AMHR2, FSHR, LHR, CYP19A1, TP53INP1, and CASP3 was analyzed in GCs. The AMH concentration in FF decreased (P < 0.01) at increasing follicular diameter. The mRNA expression of AMHR2 and FSHR was higher (P < 0.05) in small follicles, whereas that of LHR and CYP19A1 was higher (P < 0.05) in large follicles. The intrafollicular AMH concentration was positively correlated with the antral follicular count (r = 031; P < 0.05). Interestingly, good donors (>12 follicles) had a higher (P < 0.05) concentration of AMH and AMHR2 levels in small follicles and higher (P < 0.05) LHR levels in large follicles than bad donors (

Chromosome territory (CT) organization and chromatin condensation have been linked to gene expression. Although individual genes can be transcribed from inside CTs, some regions that have constitutively high expression or are coordinately activated loop out from CTs and decondense. The relationship between epigenetic marks, such as DNA methylation, and higher-order chromatin structures is largely unexplored. DNMT3B mutations in immunodeficiency centromeric instability facial anomalies (ICF) syndrome result in loss of DNA methylation at particular sites, including CpG islands on the inactive X chromosome (Xi). This allows the specific effects of DNA methylation on CTs to be examined. Using fluorescence in situ hybridization, we reveal a differential organization of the human pseudoautosomal region (PAR)2 between the CTs of the X and Y in normal males and the active X (Xa) and the Xi in females. There is also a more condensed chromatin structure on Xi compared with Xa in this region. PAR2 genes are relocalized toward the outside of the Y and Xi CTs in ICF, and on the Xi, we show that this can extend to genes distant from the site of DNA hypomethylation itself. This reorganization is not simply a reflection of the transcriptional activation of the relocalized genes. This report of altered CT organization in a human genetic disease illustrates that DNA hypomethylation at restricted sites in the genome can lead to more extensive changes in nuclear organization away from the original site of epigenetic change.

Rett syndrome (RTT, MIM 312750) is a rare and orphan progressive neurodevelopmental disorder affecting girls almost exclusively, with a frequency of 1/15,000 live births of girls. The disease is characterized by a period of 6 to 18 months of apparently normal neurodevelopment, followed by early neurological regression, with a progressive loss of acquired cognitive, social, and motor skills. RTT is known to be caused in 95% of the cases by sporadic de novo loss-of-function mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene encoding methyl-CpG binding protein 2 (MeCP2), a nuclear protein able to regulate gene expression. Despite almost two decades of research into the functions and role of MeCP2, little is known about the mechanisms leading from MECP2 mutation to the disease. Oxidative stress (OS) is involved in the pathogenic mechanisms of several neurodevelopmental and neurodegenerative disorders, although in many cases it is not clear whether OS is a cause or a consequence of the pathology. Fairly recently, the presence of a systemic OS has been demonstrated in RTT patients with a strong correlation with the patients' clinical status. The link between MECP2 mutation and the redox imbalance found in RTT is not clear. Animal studies have suggested a possible direct correlation between Mecp2 mutation and increased OS levels. In addition, the restoration of Mecp2 function in astrocytes significantly improves the developmental outcome of Mecp2-null mice and reexpression of Mecp2 gene in the brain of null mice restored oxidative damage, suggesting that Mecp2 loss of function can be involved in oxidative brain damage. Starting from the evidence that oxidative damage in the brain of Mecp2-null mice precedes the onset of symptoms, we evaluated whether, based on the current literature, the dysfunctions described in RTT could be a consequence or, in contrast, could be caused by OS. We also analyzed whether therapies that at least partially treated some RTT symptoms can play a role in defense against OS. At this stage we can propose that OS could be one of the main causes of the dysfunctions observed in RTT. In addition, the major part of the therapies recommended to alleviate RTT symptoms have been shown to interfere with oxidative homeostasis, suggesting that MeCP2 could somehow be involved in the protection of the brain from OS.

DNA methylation is an epigenetic repressor mark for transcription dynamically regulated in neurons. We analyzed visual experience regulation of DNA methylation in mice and its involvement in ocular dominance plasticity of the developing visual cortex. Monocular deprivation modulated the expression of factors controlling DNA methylation and exerted opposite effects on DNA methylation and hydroxymethylation in specific plasticity genes. Inhibition of DNA methyltrasferase (DNMT) blocked molecular and functional effects of monocular deprivation, partially reversing the monocular deprivation transcriptional program.

Rett syndrome (RTT; OMIM 312750) is an X-linked dominant neurological disorder, which affects mostly females. It is associated with mutations of the MECP2 gene, codifying for a methyl-CpG DNA binding protein of the MBDs family, sharing the common Methyl Binding Domain. MeCP2 binds single methylated CpG pair and brings transcriptional silencing to the substrate DNA templates. However, around 5-10% of clinically well defined RTT patients do not show any mutations in this gene. Several hypotheses have been postulated to clarify the remaining unexplained RTT cases. We pointed our attention on Kaiso gene. This gene is localized in the Xq23 region and codifies for a protein acting as a methyl-CpG binding protein by using three zinc-finger domains: for this reason it is not strictly related to the MBD family of proteins, even if it may repress transcription of methylated genes as well. To investigate the potential association of Kaiso disfunction with pathogenesis of Rett syndrome, we approached the analysis at two different levels. Primarily, we performed an itemized murine brain expression analysis of Kaiso gene. Expression data and localization made it an excellent candidate as additional causative gene for MECP2 negative, classical RTT patients. On the bases of this data a detailed mutational analysis of 44 patients from Spanish, UK, and Italian archives has been performed to the coding region of Kaiso. No mutation was found while a very frequent polymorphism was identified and characterized. Our study suggests that this gene is not implicated in the RTT molecular pathogenesis, but additional analyses are needed to exclude it as causative gene for X-linked mental retardation disorders.

Maintenance of X-inactivation is achieved through a combination of different repressive mechanisms, thus perpetuating the silencing message through many cell generations. The second human X-Y pseudoautosomal region 2 (PAR2) is a useful model to explore the features and internal relationships of the epigenetic circuits involved in this phenomenon. Recently, we demonstrated that DNA methylation plays an essential role for the maintenance of X- and Y-inactivation of the PAR2 gene SYBL1; here we report that the silencing of the second repressed PAR2 gene, SPRY3, appears to be independent of DNA methylation. In contrast to SYBL1, the inactive X and Y alleles of SPRY3 are not reactivated in cells treated with a DNA methylation inhibitor and in cells from ICF (immunodeficiency, centromeric instability, facial anomalies) syndrome patients, which have mutations in the DNA methyltransferase gene DNMT3B. SPRY3 X- and Y-inactivation is associated with a differential enrichment of repressive histone modifications and the recruitment of Polycomb 2 group proteins compared to the active X allele. Another major factor in SPRY3 repression is late replication; the inactive X and Y alleles of SPRY3 have delayed replication relative to the active X allele, even in ICF syndrome cells where the closely linked SYBL1 gene is reactivated and advanced in replication. The relatively stable maintenance of SPRY3 silencing compared with SYBL1 suggests that genes without CpG islands may be less prone to reactivation than previously thought and that genes with CpG islands require promoter methylation as an additional layer of repression.

A long path, initiated more than 40 years ago, has led to a deeper understanding of the complexity of gene regulation in eukaryotic genomes. In addition to genetic mechanisms, the imbalance in the epigenetic control of gene expression may profoundly alter the finely tuned machinery leading to gene regulation. Here, we review the impact of the studies on DNA methylation, the "primadonna" in the epigenetic scenario, on the understanding of basic phenomena, such as X inactivation and genomic imprinting. The effect of deregulation of DNA methylation on human health, will be also discussed. Finally, an attempt to predict future directions of this rapidly evolving field has been proposed, with the certainty that, fortunately, science is always better than predictions.

Background Bovine papillomaviruses (BPVs) types 1 and 2 are the only known papillomaviruses able to jump the species. In fact, BPVs 1/2 induce neoplasia in their natural bovine host but infection is also associated to neoplastic skin lesions in equids termed sarcoids. The equine sarcoid is considered to be the most common equine cutaneous tumour worldwide for which no effective therapy is available. Very little is known about the molecular mechanisms underlying tumourigenesis, although genes contributing to sarcoid development have been identified. Several studies associate the development of cancer to the loss of function of a number of oncosuppressor genes. In this study the putative role of O6-methylguanine-DNA methyltrasferase (MGMT) was investigated for sarcoids. The expression of the oncosuppressor protein was assessed in normal and sarcoid cells and tissues. In addition, the DNA methylation profile was analysed to assess the role of epigenetic mechanism in regulation of MGMT expression. Results A group of 15 equine sarcoids and two primary sarcoid cell lines (fibroblasts) were analyzed for the expression of MGMT protein by immunohistochemistry, immunofluorescence and Western blotting techniques. The sarcoid cell line EqSO4b and the tumour samples showed a reduction or absence of MGMT expression. To investigate the causes of deregulated MGMT expression, ten samples were analyzed for the DNA methylation profile of the CpG island associated to the MGMT promoter. The analysis of 73 CpGs encompassing the region of interest showed in 1 out of 10 (10%) sarcoids a pronouncedly altered methylation profile when compared to the control epidermal sample. Similarily the EqSO4b cell line showed an altered MGMT methylation pattern in comparison to normal fibroblasts. Conclusion As previously demonstrated for the oncosuppressor gene FHIT, analysis of MGMT expression in sarcoid tissues and a sarcoid-derived fibroblast cell line further suggests that oncosuppressor silencing may be also involved in BPV-induced equine tumours. Abnormal DNA methylation seems to be one of the possible molecular mechanisms involved in the alteration of MGMT expression. Further studies are required to address other basic molecular mechanisms involved in reduced MGMT expression. This study underlines the possible role of DNA methylation in oncosuppressor inactivation in equine sarcoids.

The human X and Y chromosomes differ in size, morphology, and gene content, the X being large and gene rich and the Y being small and heterochromatic. They do not pair at male meiosis except within small, homologous, “pseudoautosomal” regions (PARs) (Vogt et al. 1997). PARs lie at either extremity of the human sex chromosomes (Cooke et al. 1985). The 2.6-Mb PAR region 1 (PAR1), at the tip of the short arm (Xp-YpPAR) contains 13 genes (Rappold 1993; Gianfrancesco et al. 2001b), and is required for pairing of the X and Y chromosomes at male meiosis. The 320-kb PAR region 2 (PAR2) at the end of the long arms (Xq-YqPAR) (Freije et al. 1992) shows a much lower frequency of pairing and recombination than PAR1 and is not necessary for fertility (Kvaloy et al. 1994; Li and Hamer 1995; Kuhl et al. 2001). The first two genes to be mapped to the PAR2 were SYBL1 (synaptobrevin-like protein 1) and IL9R (interleukin 9 receptor). Recently, the entire human PAR2 was sequenced and found to contain two other genes HSPRY3 (homolog to Drosophila sprouty 3) and CXYorf1, as well as a number of fragmentary pseudogenes (Ciccodicola et al. 2000). The order of the genes from centromere to telomere is HSPRY3, SYBL1, IL9R, and CXYorf1. HSPRY3 and SYBL1 lie within the proximal 100 kb, while IL9R and CXYorf1 are close together in the GC-rich distal 35 kb. HSPRY3 and SYBL1 both map to the X, but not the Y, in primate and the mouse. IL9R maps to the X in primate but is autosomal in mouse (Kermouni et al. 1995; D'Esposito et al. 1997; Vermeesch et al. 1997; Matarazzo et al. 1999; Ciccodicola et al. 2000) (Table ​(Table1).1). HSPRY3 and SYBL1are both inactive on the Y and are subject to X inactivation in humans. In contrast, IL9R and CXYorf1 are expressed from the Y and are not subject to X inactivation (Huber et al. 1999; Ciccodicola et al. 2000). Table 1. Map Position of PAR2 Genes in Different Mammalian Species The presence of these four genes on the X but not the Y in primate and mouse indicated that the region was transferred to the Y during the last few million years, perhaps via an illegitimate LINE sequence recombination between the X and Y (Kvaloy et al. 1994). The absence of IL9R from the mouse X and the dichotomy in expression patterns between proximal and distal pairs of PAR2 genes led to the hypothesis that the regions containing them were added independently to the X chromosome during eutherian evolution. Ciccodicola et al. (2000) suggested a division into Zone 1 (HSPRY3 and SYBL1) and a later added Zone 2 (IL9R and CXYorf1) possibly obtained by three independent events. As a result, there are differences in base composition, recombination, and transcription that define operationally the two PAR2 zones. We tested this hypothesis by comparing the location of homologs of PAR2 genes in two eutherian mammals that diverged from humans 60–70 million years ago (Mya) and in a distantly related marsupial mammal, which diverged independently from the eutherian lineage 130 Mya (Kumar and Hedges 1998). Comparative mapping of human X-borne genes in distantly related mammals can distinguish genes that were a part of the ancient mammalian X, and have been important in establishing the origin of the human PAR1. Mapping human X-borne genes in marsupial and monotreme mammals, which diverged from the eutherian lineage 130 and 170 Mya, respectively, have defined a conserved region (XCR) shared by the X chromosome in all three extant mammals, and a region (XAR) recently added to the eutherian X, but still autosomal in marsupials and monotremes (Graves 1995; Graves et al. 1998). The eutherian Y is also composed of a conserved (YCR) and an added region (YAR) that contains most of the ubiquitously expressed genes (Waters et al. 2001). The demonstration that cloned marsupial homologs of human PAR1 genes colocalize with other genes on human Xp (Toder and Graves 1998) implied that PAR1 is part of the large region added to the eutherian X and Y after the divergence of marsupials (130 Mya) but before the eutherian radiation (80 Mya). To examine the origin of PAR2, we therefore cloned and mapped all four human PAR2 genes in a model marsupial species, Macropus eugenii (the tammar wallaby). We also cloned and mapped two PAR2 genes in Felis cattus (the domestic cat) and Lemur catta (the lemur). If the human PAR2 region originated as part of the conserved region present on the X in all mammals, we would expect the human PAR2 genes to map to the X also in marsupials. If PAR2 represents part of the same addition as PAR1, we would expect PAR2 genes to map with PAR1 genes on tammar 5p, and if PAR2 represents an independent addition, they will map on other autosomes. Our results further clarify PAR2 evolution, implying that most of PAR2 was independently added to the eutherian X and rearranged in at least four separate events and before it was transposed to the Y.

Background: Brain dead patients are the main source of organs for transplants. Brain death causes changes in peripheral organs. We define modifications of gene expression in specific pathways occurring in donor livers and their influence on gene expression profile of livers after transplant. Methods: We compared gene expression profile of both deceased donor livers and transplanted livers to gene expression data of liver tissue, retrieved from Array Express database, used as control. All expression data were obtained by microarray analysis. Results: The expression of about 33,000 genes has been compared in liver samples from three groups: deceased donor livers, transplanted livers two hours after reperfusion, and control livers. We found that about 900 genes are dysregulated in deceased donor versus control livers. Up-regulated genes are mainly involved in apoptosis, immune response and inflammation. Down-regulated genes are mostly involved in metabolism and electron transport. We also re-evaluated a group of genes that in a previous study were found dysregulated in transplanted livers when compared to donor livers. Most of these genes, but not all, were dysregulated also when compared to control livers. Moreover 317 additional genes, dysregulated after liver transplant, were identified in this study; they were undetectable in the previous study because they had the same dysregulation both in donor and in transplanted livers. Conclusions: Understanding molecular mechanisms that in the donor compromise graft function is crucial in order to discriminate between basal graft damages and ischemia-reperfusion injuries and therefore to identify therapeutic targets aiming to improve liver transplantation performances.