De Sanctis Research Articles

Lipid mapping of colonic mucosa by cluster TOF-SIMS imaging and multivariate analysis in cftr knockout mice

The cftr knockout mouse model of cystic fibrosis (CF) shows intestinal obstruction; malabsorption and inflammation; and a fatty acid imbalance in intestinal mucosa. We performed a lipid mapping of colon sections from CF and control (WT) mice by cluster time of flight secondary-ion mass spectrometry (TOF-SIMS) imaging to localize lipid alterations. Data were processed either manually or by multivariate statistical methods. TOF-SIMS analysis showed a particular localization for cholesteryl sulfate at the epithelial border, C16:1 fatty acid in Lieberkühn glands, and C18:0 fatty acid in lamina propria and submucosa. Significant increases in vitamin E (vE) and C16:0 fatty acid in the epithelial border of CF colon were detected. Principal component analysis (PCA) and partitioning clustering allowed us to characterize different structural regions of colonic mucosa according to variations in C14:0, C16:0, C16:1, C18:0, C18:1, C18:2, C20:3, C20:4, and C22:6 fatty acids; phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol glycerolipids; cholesterol; vitamin E; and cholesteryl sulfate. PCA on spectra from Lieberkühn glands led to separation of CF and WT individuals. This study shows for the first time the spatial distribution of lipids in colonic mucosa and suggests TOF-SIMS plus multivariate analyses as a powerful tool to investigate disease-related tissue spatial lipid signatures.

Croce lettore di Giordano Bruno

Benedetto Croce was keen reader of the Italian works of Giordano Bruno when Giovanni Gentile published the Dialoghi metafisici e morali in 1907-1908. Just like his mentor Francesco De Sanctis, Croce sees Bruno as a great thinker and a great writer. What he attaches great value to above all is Bruno as philosopher deeply engaged in distinguishing between science and philosophy and combating the of the Renaissance. He used Bruno in his own fight against the Aristotelians of his age: the Neo-Kantians. In his interpretation of the Italian Renaissance as the age of rationalism, whose main thread was soon broken, Croce puts Bruno and Campanella among the «few scattered and scared apostles of the future» who continued to weave the thread of rationality, later taken up by Vico and Giannone and, finally, by the Italian Risorgimento, starting with the Neapolitan patriots of 1799. When he defined the Italian Renaissance as the historical age of the emersion of rationality and of true break the tradition, Croce made use of the fundamental intuition of Spaventa and of some of the latter’s disciples. They had stressed in the name of Bruno the sharp break between the Middle Ages and Renaissance philosophy while Croce here came closest to the philosopher from Nola, who had made trenchant critique of the biblical myth of the golden age.

La Franc‐maçonnerie et le droit à l’instruction: de l’Unité italienne jusqu’au début du XXème siècle

On the morrow of Italy’s unification, the new state found itself having to confront a long series of severe and important problems. Certainly one of these was illiteracy. This phenomenon was measured in very worrisome percentages, especially in several regions of the South. The first years of government were used to build a unitary system of education instead of the various organisational forms that had prevailed in the several pre‐unification states. The problem of education of the masses, starting from the basic elements of literacy, was confronted especially by politicians and intellectuals who belonged to (or were close to) freemasonry. It is believed that almost all the ministers who followed one after the other in public education were masons and that, particularly in the second half of the nineteenth century, Italian freemasonry took on a stronger and stronger role within the state and in political and cultural life. The social question and the education question were recurrent themes in these streams of thought. They were expressed particularly in the work and writings of Francesco De Sanctis, Pasquale Villari, and Michele Coppino. It was specifically the latter who, during his many appointments as minister of public education, not only conducted intense organisational and cultural activity, but also succeeded in bringing about passage in 1877 of a law that decreed compulsory elementary education up to the age of nine (10 years after his first attempt). The parliamentary debate over compulsory education, in part inspired by legislation in other European countries (sometimes referring to America too), was very wide‐ranging and stormy. The positions being argued were in fact contradictory and irreconcilable: on one hand, it was held that compulsory education would be a useless imposition on families in the countryside that could not economically do without the labour of their children; on the other hand, it was held that only compulsory education would open the road to literacy to the people and would convince them of its real benefits. All this should be read within a historical context characterised by a hostile, problem‐ridden process of separation between State and Church and by a strong contrast between religious and secular positions. Both sides expressed themselves in fact in terms of absolute opposition. And that had a direct impact on all educational subjects. This article demonstrates the contribution of masonic thought and the importance of the compulsory education law, inspired by the principle of equal access to education. This law, thanks to education being free of charge and to the expanding presence of schools, formed a turning point (and a point of discontinuity) in Italian education, improving the condition of the population in a real way, and preparing for the industrial development of the beginning of the twentieth century.

Dominant-negative Effects of COL7A1 Mutations Can be Rescued by Controlled Overexpression of Normal Collagen VII

Dominant-negative interference by glycine substitution mutations in the COL7A1 gene causes dominant dystrophic epidermolysis bullosa (DDEB), a skin fragility disorder with mechanically induced blistering. Although qualitative and quantitative alterations of the COL7A1 gene product, collagen VII, underlie DDEB, the lack of direct correlation between mutations and the clinical phenotype has rendered DDEB less amenable to therapeutic targeting. To delineate the molecular mechanisms of DDEB, we used recombinant expression of wild-type (WT) and mutant collagen VII, which contained a naturally occurring COL7A1 mutation, G1776R, G2006D, or G2015E, for characterization of the triple helical molecules. The mutants were co-expressed with WT in equal amounts and could form heterotrimeric hybrid triple helices, as demonstrated by affinity purification and mass spectrometry. The thermal stability of the mutant molecules was strongly decreased, as evident in their sensitivity to trypsin digestion. The helix-to-coil transition, T(m), of the mutant molecules was 31-34 degrees C, and of WT collagen VII 41 degrees C. Co-expression of WT with G1776R- or G2006D-collagen VII resulted in partial intracellular retention of the collagen, and mutant collagen VII had reduced ability to support cell adhesion. Intriguingly, controlled overexpression of WT collagen VII gradually improved the thermal stability of the collective of collagen VII molecules. Co-expression in a ratio of 90% WT:10% mutant increased the T(m) to 41 degrees C for G1776R-collagen VII and to 39 degrees C for G2006D- and G2015E-collagen VII. Therefore, increasing the expression of WT collagen VII in the skin of patients with DDEB can be considered a valid therapeutic approach.

Lipidomic Analysis of Dynamic Eicosanoid Responses during the Induction and Resolution of Lyme Arthritis

Eicosanoids and other bioactive lipid mediators are indispensable regulators of biological processes, as demonstrated by the numerous inflammatory diseases resulting from their dysregulation, including cancer, hyperalgesia, atherosclerosis, and arthritis. Despite their importance, a robust strategy comparable with gene or protein array technology for comprehensively analyzing the eicosanoid metabolome has not been forthcoming. We have developed liquid chromatography-tandem mass spectrometry methodology that quantitatively and comprehensively analyzes the eicosanoid metabolome and utilized this approach to characterize eicosanoid production during experimental Lyme arthritis in mice infected with the bacterium Borrelia burgdorferi. Eicosanoids were extracted throughout infection from the joints of Lyme arthritis-resistant and -susceptible mice and subjected to lipidomic profiling. We identified temporal and quantitative differences between these mouse strains in the production of eicosanoids, which correlated with differences in arthritis development. The eicosanoid biosynthetic enzyme cyclooxygenase (COX)-2 has been implicated in the regulation of Lyme arthritis pathology, and subsequent lipidomic profiling of B. burgdorferi-infected COX-2(-/-) mice identified reductions not only in COX-2 products but, surprisingly, also significant off-target reductions in 5-lipoxygenase metabolites. Our results demonstrate the utility of a comprehensive lipidomic approach for identifying potential contributors to disease pathology and may facilitate the development of more precisely targeted treatment strategies.

Care, Cure and Training of the Body According to Italian Medicine of the Nineteenth Century

Sometime in the latter half of the nineteenth century, the idea that progress in science and technology would lead to solutions for, or at least control over, human ills had reached Italy as a result of positivism. The Parliament of the new Kingdom of Italy, formed in 1861, worked, among other things, towards increasing the processes of modernisation and industrialisation that were already ongoing in northern and central Italy. This was done to combat the backwardness of the poorer regions in the south and towards augmenting the size and quality of the newly created Italian army so that it could compete on an equal footing with the powerful nations of Europe. In the same period, the government was legislating in favour of public education to fight the great problem of illiteracy, upgrade the teaching classes, improve existing schools and procure the funds needed for social hygiene and care of the body as factors in the physical and moral regeneration of the race. A campaign to increase physical education for both sexes in schools was successfully begun by the then Education Minister, Francesco De Sanctis, who made this subject obligatory by law throughout the nation in 1878. Much has already been said of the Italian doctors of the time who were strongly in favour of gymnastics, traditional games and/or modern sports, as well as other hygienic and recreational physical activities for people of all ages; suffice to mention the ‘apostle of Italian sport', Dr. Angelo Mosso (1846–1910), and the ‘father of Italian gymnastics', Dr. Emilio Baumann (1843–1917). However, not enough has been said about the support for these same activities offered by another famous doctor from the same period, Paolo Mantegazza (1830–1910), on whom the first part of the essay will focus. The latter part will propose a comparative consideration of the works of Mantegazza, Baumann and Mosso, showing similarities but also notable differences in their personality and philosophical approach.

Resurrecting Dante's Florence: Figural Realism in the Decameron and the Esposizioni

Resurrecting Dante's Florence:Figural Realism in the Decameron and the Esposizioni Kristina Marie Olson Much of Boccaccio's work is heavilyinfluenced by Dante, and near the end ofhis life he both wrote a treatise celebratingDante and delivered a set of lecturescommenting in detail on the first twenty-eight[sic] cantos of the Inferno. Yet theDecameron is an implicitly anti-Dantean work. —Norton Anthology of World Literature So reads the introductory matter to selections from the Decameron in the Norton Anthology to World Literature,2 which, after offering preliminary evidence of the relation between these two works (the Decameron's division into one-hundred tales; the pedigree of "prencipe Galeotto" from Inferno V), summarily dismisses any sustained similarities between the two works in favor of a rhetorical opposition. As incorrect as this classification may seem, the critical tradition of Italian studies forged this rhetoric before any misgivings within the marketplace of World Literature. At the end of the nineteenth century, Francesco de Sanctis called the Decameron the "nuova Commedia, non la 'divina,' ma la 'terrestre' Commedia."3 Much later, Erich Auerbach made claims about [End Page 45] Boccaccio's realism and the historical content of the Decameron4 that were eventually challenged by the work of Vittore Branca:5 Il capolavoro del Boccaccio, invece, proprio perché appare nei suoi aspetti più costituzionali e più validi come la tipica "commedia dell'uomo" rappresenta attraverso i paradigmi canonici alla visione cristiana e scolastica della vita e insieme come una vasta e multiforme epopea della società medievale italiana colta e ritratta nel suo autunno splendido e lussureggiante, non si oppone alla Divina Commedia ma in qualche modo le si affianca e quasi la completa. (Branca 29) But despite Branca's efforts, a relative lack of formal and historical comparative analysis of these two capolavori continues to exist. Though Carlo Delcorno established that Boccaccio was familiar with Dante's works by 1350, and echoes of Dante's verse have been discerned in the Elegia di madonna Fiammetta, the Caccia di Diana, the Amorosa visione and the Corbaccio,6 studies of Dante's presence in the Decameron have truly emerged in the late twentieth century with the work of Bettinzoli, Hollander, and Kirkham.7 Yet the presence of nearly verbatim passages in the Decameron and the Esposizioni requires us, I believe, to reconsider the nature of the influence of the Commedia on the [End Page 46] Decameron and the chronological terms of Boccaccio's engagement with Dante's work. Appearing in Decameron I.8, VI.9, and IX.8 and in the text of the later Esposizioni, these "autocitations" not only imply that Boccaccio kept the Commedia in mind while writing the Decameron, but that he himself intended that certain of the hundred novelle be read as a "gloss" of Dante's poem.8 Interestingly enough, it is one of Boccaccio's works that explicitly bears witness to his deep knowledge of the Commedia as a source for textual analogues to the Decameron. The collection of Boccaccio's incomplete public lectures on Inferno I to XVII, commonly called the Comento but referred to by Giorgio Padoan as the Esposizioni sopra la Comedia di Dante (October 1373–January 1374), often enters into the margins of work on Boccaccio as dantista but have seldom solicited the exclusive treatments such as those mentioned.9 The Esposizioni, the first lectura Dantis offered to the people of Florence in the church of Santo Stefano in Badia, most conspicuously demonstrates Boccaccio's close reading of Dante's text, though it is an unfinished work (and most likely not the exact content of the public lectures). To consider these autocitations in the Decameron and the Esposizioni within their Dantean cornice and their interpretation of the changes in Florentine society depicted in the Commedia, a view of Boccaccio as storyteller, chronicler and social commentator emerges, one that should lead to further reconsiderations of his classification in respect to his formidable processor. While the almost verbatim nature of these passages is often noted by Giorgio Padoan in his edition of the Esposizioni, and certain critics have also noted parallels between these texts, no one has ventured to interpret their...

Chastity Models in the Legenda Aurea and in the Sermones de Sanctis of Jacobus de Voragine

The Sermones de sanctis of Jacobus de Voragine is not an independent text but the last written link of a communicative chain that starts with the holy figurae of the Legenda aurea and is completed with a final speech from a preacher to his audience. Chastity is represented in this hagiographical material, which is closely connected to the most important saints of the Dominican calendar, through absolute models that are removed from everyday experience: these models need to be interpreted by a preacher's spoken words and to be illustrated with a choice of exempla to reach laypeople effectively.

Escape from the dark forest: the experimentalist standpoint of Sante De Sanctis' psychology of dreams

Sante De Sanctis (1862—1935), a pioneer of psychology in Rome at the end of the 19th century, applied methods from the expanding field of experimental psychology to the study of dreams, which was considered one of the leading ways to gain an understanding of normal and pathological psychic life. Taking inspiration from several traditions, De Sanctis proposed a study that anticipated a scientific program that also differentiated between contemporary psychoanalytical interpretations according to which previous dream psychology was considered a 'dark forest'. On the contrary, the multi-faceted methodology that he adopted for the study of an, until then, marginal phenomenon of the 'new' psychology, represented an element of originality that also included the elaboration of a psycho-physiological theory of dreams. Although the Italian psychologist's work on dreams was characterized by these important methodological changes, it disappeared from the references of those who contributed to the foundation of modern dreaming psychology after the Second World War. The present article places De Sanctis' psychology of dreams in its scientific context and singles out its originality while also analyzing the reasons for its marginalization.

Closure to “Bearing Capacity of Piled Rafts on Soft Clay Soils” by Luca de Sanctis and Alessandro Mandolini

Closure to “Bearing Capacity of Piled Rafts on Soft Clay Soils” by Luca de Sanctis and Alessandro Mandolini

Discussion of “Bearing Capacity of Piled Rafts on Soft Clay Soils” by Luca de Sanctis and Alessandro Mandolini

Discussion of “Bearing Capacity of Piled Rafts on Soft Clay Soils” by Luca de Sanctis and Alessandro Mandolini

Lentiviral-mediated GATA-3 RNAi Decreases Allergic Airway Inflammation and Hyperresponsiveness

GATA-3 is the key transcriptional factor for Th2 commitment in T cells and is strongly associated with asthma and allergic disease. We studied the silencing of the GATA-3 gene expression using RNA interference (RNAi) delivered by a lentiviral vector, to evaluate the therapeutic role of GATA-3 short hairpin RNAs (shRNAs) in a murine model of asthma. Mice were sensitized with OVA and instilled intratracheally (IT) with GATA-3 shRNAs lentiviral vector (Lenti-si-GATA-3) once, 48 hours before challenge. After three challenges with the OVA antigen, the mice were assessed for airway hyperresponsiveness (AHR) and inflammation. With infection of Lenti-si-GATA-3 in EL-4 cells, GATA-3 gene expression was abrogated and downstream Th2 cytokines, such as interleukin-4 (IL-4) and IL-5, were also significantly inhibited. IT delivery of Lenti-si-GATA-3 in OVA-immunized mice resulted in a strong inhibition of local GATA-3 gene expression. Treatment with Lenti-si-GATA-3 successfully alleviated OVA-induced airway eosinophilia and Th2 cytokine release. While evaluating AHR by means of enhanced pause (Penh) and pulmonary resistance (R(L)) using body plethysmography, it was found that the administration of Lenti-si-GATA-3 had significantly decreased AHR in OVA-immunized mice. These results suggest that inhibition of GATA-3 gene expression by shRNAs lentiviral vectors strongly attenuates antigen-induced airway inflammation and hyper-responsiveness in mice.

Diet and Primordial Prevention of Cardiovascular Disease in Children and Adolescents

It is now clear that the process of atherosclerosis begins in childhood. A series of pathology studies, starting with autopsy examination of young soldiers killed in combat in the Korean War1 and the war in Vietnam2 to more recent studies such as the Pathobiologic Determinants of Atherosclerosis in Youth (PDAY) study3 and the Bogalusa study,4,5 have demonstrated that fatty streaks in the aorta and coronary arteries develop early in life and that even the more advanced and more concerning fibrous plaques are present in a proportion of adolescents and young adults. The PDAY and Bogalusa studies also have demonstrated that the traditional risk factors such as high body mass index, high blood pressure, and dyslipidemia are strongly associated with the presence and extent of arterial lesions.3,4 The Bogalusa cohort also has demonstrated that the presence of multiple risk factors is associated with an even higher risk for atherosclerotic lesions.5 Article p 1032 It is also well known that atherosclerotic cardiovascular disease is the most common cause of death in developed countries.6 Not uncommonly, the first clinical episode related to atherosclerosis is sudden cardiac death.7 Taken together, these data argue very strongly for the prevention of atherosclerosis and for prevention efforts to begin early in life. This might best be labeled primordial prevention because it is aimed at the prevention of development of risk factors in the first place. However, pediatric prevention of cardiovascular …

Mast Cell-restricted Tryptases: Structure and Function in Inflammation and Pathogen Defense

Mast cells (MCs) are highly specialized immune cells present in mammals and in lower organisms that predate the development of adaptive immunity. The strong evolutionary pressure to retain MCs for >500 million years suggests critical roles for these cells in our survival. In support of this conclusion, no human has been identified to date that lacks MCs, despite the adverse roles of MCs in systemic anaphylaxis and varied inflammatory disorders. MCs express numerous lineage-restricted neutral proteases, and four members of the chromosome 17A3.3 family of tryptases are preferentially expressed in mouse MCs. The anatomical location of MCs at host-environment interfaces has raised the possibility that some of these enzymes are evolutionally conserved because they are needed for combating infectious organisms. Here we review recent insights into the structure and function of MC tryptases in inflammation and host defense against bacteria and other infectious organisms.

The Mast Cell-restricted Tryptase mMCP-6 Has a Critical Immunoprotective Role in Bacterial Infections

Although it has been shown that mast cell-deficient mice have diminished innate immune responses against bacteria, the most important immunoprotective factors secreted from activated mast cells have not been identified. Mouse mast cell protease 6 is a tetramer-forming tryptase. This serine protease is abundant in the secretory granules and is exocytosed upon bacterial challenge. Here we have described the generation of a mast cell protease-6-null mouse. Our discovery that mice lacking this neutral protease cannot efficiently clear Klebsiella pneumoniae from their peritoneal cavities reveals an essential role for this serine protease, and presumably its human ortholog, in innate immunity.

Skin Metastases from Anaplastic Thyroid Carcinoma

ThyroidVol. 16, No. 5 Images in ThyroidologySkin Metastases from Anaplastic Thyroid CarcinomaMarco Capezzone, Paolo Giannasio, Domenico De Sanctis, Pasquale Bellitti, Pasquale Vena, Eugenia Morabito, and Rocco BrunoMarco CapezzoneSearch for more papers by this author, Paolo GiannasioSearch for more papers by this author, Domenico De SanctisSearch for more papers by this author, Pasquale BellittiSearch for more papers by this author, Pasquale VenaSearch for more papers by this author, Eugenia MorabitoSearch for more papers by this author, and Rocco BrunoSearch for more papers by this authorPublished Online:6 Jun 2006https://doi.org/10.1089/thy.2006.16.513AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail "Skin Metastases from Anaplastic Thyroid Carcinoma." , 16(5), pp. 513–514FiguresReferencesRelatedDetailsCited byCutaneous Metastasis of Head and Neck Malignancy1 January 2015 | International Journal of Head and Neck Surgery, Vol. 6, No. 2American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer Robert C. Smallridge, Kenneth B. Ain, Sylvia L. Asa, Keith C. Bible, James D. Brierley, Kenneth D. Burman, Electron Kebebew, Nancy Y. Lee, Yuri E. Nikiforov, M. Sara Rosenthal, Manisha H. Shah, Ashok R. Shaha, and R. Michael Tuttle for the American Thyroid Association Anaplastic Thyroid Cancer Guidelines Taskforce6 November 2012 | Thyroid, Vol. 22, No. 11Thyroid Cancer and the SkinF-18 FDG PET/CT Imaging of a Subcutaneous Scalp Metastasis From Primary Carcinoma of the ThyroidClinical Nuclear Medicine, Vol. 32, No. 2 Volume 16Issue 5May 2006 InformationCopyright 2006, Mary Ann Liebert, Inc.To cite this article:Marco Capezzone, Paolo Giannasio, Domenico De Sanctis, Pasquale Bellitti, Pasquale Vena, Eugenia Morabito, and Rocco Bruno.Skin Metastases from Anaplastic Thyroid Carcinoma.Thyroid.May 2006.513-514.http://doi.org/10.1089/thy.2006.16.513Published in Volume: 16 Issue 5: June 6, 2006PDF download

Un témoin précoce de la réception du « Manipulus florum » au début du XIVe siècle : le recueil de sermons du dominicain Guillaume de Sauqueville

The Dominican Guillaume de Sauqueville, active in Paris in the later years of the reign of Philip the Fair, left a collection of one hundred and eight sermons 'de tempore’ and 'de sanctis’. An analysis of his work reveals features typical of the art of preaching as it was then understood. Each sermon is based on an excerpt of the Scriptures, subjected to divisions and distinctions, and supported by a wealth of scriptural, liturgical and patristic quotations. The main interest of the writings of Guillaume de Sauqueville lies in the fact that much of their subject matter was borrowed fromthe Manipulus florum, an anthology of authoritative quotations compiled by Thomas of Ireland in 1306, as a thorough comparison makes apparent. Yet, however often this anthology may have been used by Guillaume, it was far from being his only source: the textual competence one would expect from a preacher is also quite perceptible in his work. One of his sermons, delivered on St. Hippolytus’ day, is published as an appendix to illustrate the manner in which Guillaume put his sources to use.

Síndrome de De Sanctis-Cacchione

We present a male patient with photosensitivity since the earliest months of his life, and pigmented macules in exposed areas, some showing clinical atypia, which increased in number over time. Molecular biology studies detected an alteration in DNA repair ability, so xeroderma pigmentosum was diagnosed. Shortly after birth, low weight, microcephaly and psychomotor retardation had been observed, but the cause was not established. The patient progressively showed neurological disorders that included perceptive deafness, hyporeflexia and areflexia, as well as choreoathetotic movements. Therefore, we felt that the patient's symptoms fit De Sanctis- Cacchione syndrome.

Inducible Nitric-oxide Synthase and NO Donor Induce Insulin Receptor Substrate-1 Degradation in Skeletal Muscle Cells

Chronic inflammation plays an important role in insulin resistance. Inducible nitric-oxide synthase (iNOS), a mediator of inflammation, has been implicated in many human diseases including insulin resistance. However, the molecular mechanisms by which iNOS mediates insulin resistance remain largely unknown. Here we demonstrate that exposure to NO donor or iNOS transfection reduced insulin receptor substrate (IRS)-1 protein expression without altering the mRNA level in cultured skeletal muscle cells. NO donor increased IRS-1 ubiquitination, and proteasome inhibitors blocked NO donor-induced reduction in IRS-1 expression in cultured skeletal muscle cells. The effect of NO donor on IRS-1 expression was cGMP-independent and accentuated by concomitant oxidative stress, suggesting an involvement of nitrosative stress. Inhibitors for phosphatidylinositol-3 kinase, mammalian target of rapamycin, and c-Jun amino-terminal kinase failed to block NO donor-induced IRS-1 reduction, whereas these inhibitors prevented insulin-stimulated IRS-1 decrease. Moreover iNOS expression was increased in skeletal muscle of diabetic (ob/ob) mice compared with lean wild-type mice. iNOS gene disruption or treatment with iNOS inhibitor ameliorated depressed IRS-1 expression in skeletal muscle of diabetic (ob/ob) mice. These findings indicate that iNOS reduces IRS-1 expression in skeletal muscle via proteasome-mediated degradation and thereby may contribute to obesity-related insulin resistance.

Signs, Wonders, Miracles: Supporting the Faith in Medieval Rome

Judging by the quantity of surviving texts – whethervitaeor saints’ lives,libelli miraculorumor narratives of miracles for public reading in church, lectionaries or collections of liturgical readings,inventionesandtranslationesor accounts of relics found and later moved to a new location, popular receptivity to signs, wonders and miracles had reached a high point by the turn of the twelfth century. Whilst ordinary laypeople remained fascinated by supernatural phenomena, intellectuals were already beginning to challenge the preternatural in a process described by Chenu as the ‘desacralizing’ of nature. In the first book of his treatise,De Sanctis et eorum pignoribus(c.1120), Guibert, Abbot of Nogent, had contrasted the credulity of the faithful towards pseudo-miracles with the growing unease experienced by many scholars at inadequate written evidence for the authentication of relics. Andrew of Saint-Victor (d.1175), in an exposition on the literal interpretation of Scripture, found himself arguing for a natural explanation of events before any recourse to the miraculous. In the School of Pastoral Theology at Paris, Master Peter the Chanter (d.1197) vehemently criticized trial by ordeal as a flagrant tempting of God whereby a supposedly miraculous intervention was allowed to intrude into the regular legalistic operation of the courts. In the years immediately following the Chanter’s death, his former students, led by Pope Innocent III (1198–1216) and like-minded clerical associates, developed a significant agenda, emphasizing rationality and record keeping to sustain the faith of the Church within a new and more firmly pastoral context.