Thematic, Programmatic and Methodological Approaches of the Annual Publication

L'articolo presenta le linee teoriche, metodologiche e programmatiche dell'annuario Novecento Transnazionale, rivista accademica di respiro internazionale. Pubblicata annualmente in versione elettronica ad accesso aperto e sottoposta a double blind peer-review. Pubblica contributi di ambito comparatistico letterario, storico artistico e antropologico culturale. Il termine “transnazionale” indica che le forme culturali attuali della contemporaneità non possono essere associate alle dimensioni delle culture tradizionali basate su geografie e lingue specifiche. Il sapere transnazionale fonda il proprio interesse sui processi di delocalizzazione - e quindi - di transnazionalità delle espressioni culturali che i movimenti migratori e le nuove tecnologie della comunicazione hanno reso sempre più evidenti.The article offers a detailed presentation of the theoretical, methodological and thematic perspectives of the annual international academic journal "Transnational 20th Century. Literatures, Arts and Cultures". It is published yearly, open-access and uses double-blind review. Comparative literature, art history and cultural anthropology articles are published. The term “transnational” indicates that contemporary modern cultural structures cannot be related to those of traditional cultures founded on geographical and language-specific contexts. Transnational knowledge takes a special interest in the processes of delocalisation – and therefore in the transnationality of cultural expression, which has become increasingly evident as a result of migratory movements and new communication technologies

Carol Rama e l’animale: divenire donna e femminismo negli anni novanta

In 1996, television publicizes the news of a disease that affects cows, bringing them to death. This fact in a few days has a central place in the mass media information. Carol Rama, however, is interested by other aspects: the suffering and agony of the animal, the poses it takes, the obsessiveness of irrepressible movements. The animal and the woman, the madness of the cow and the individual state towards which Rama does not stop addressing, seem to be joining on a fragile threshold, without finding a balance and which remains in the condition of an identity oscillation. The contribution focuses on the presence of the animal in the work of Carol Rama and especially in the nineties, analyzing how the seduction for the disease of the animal reveals the gaze of a woman sensitive to many issues of the most recent feminist theories.Nel 1996 è la televisione a diffondere la notizia di una malattia che colpisce le mucche, portandole fino alla morte. Questo fatto in pochi giorni conquista un posto centrale nell’informazione. Carol Rama è tuttavia colpita da altri aspetti: la sofferenza e l’agonia dell’animale, le pose che assume, l’ossessività dei movimenti irrefrenabili. L’animale e la donna, la pazzia della mucca e lo stato individuale verso il quale Rama non smette di rivolgersi sembrano congiungersi su una soglia fragile, senza trovare un equilibrio e che resta nella condizione di un’oscillazione identitaria. Il contributo si sofferma sulla presenza dell’animale nell’opera di Carol Rama e soprattutto negli anni novanta, analizzando come la seduzione per la malattia dell’animale riveli lo sguardo di una donna sensibile a molte questioni proprie delle teorie femministe più recenti

Scrivere la storia dell’arte: metodologia e ricerca negli ultimi decenni

At the beginning of the new century the issue of art history and the methods to be used for research reopens many questions and determines the need for a critical review of historiography of the 20th century. Numerous initiatives demonstrate this need that many art historians in both Italian and international universities have felt in recent years. Art history departments, in their different denominations in Europe and other countries around the world, are concentrated on research and initiatives on the state of art history, on how to revise and question the strategies of its construction, and on the identification of documents and archival material considered its «sources». These problems involve work groups and differently oriented researches within which, however, it is possible to identify similar premises. On the one hand they address the issue on a theoretical and methodological level and on the other, focus on case studies regarding particular historical and philological aspects in order to put new hypotheses of study and research into practice. The essay focuses on these issues and looks at some of the basic segments in the most recent bibliography.All’inizio del nuovo secolo la questione della storia del’arte e dei metodi da utilizzare per la ricerca riapre molti interrogativi e determina la necessità di una revisione critica della storiografia del passato XX secolo. Molte iniziative dimostrano la necessità che molti storici dell’arte, nelle Università italiane ma anche internazionali avvertono in questi anni: i dipartimenti di storia dell’arte, nelle differenti denominazioni che hanno in Europa e in altri paesi del mondo, concentrano ricerche e iniziative sullo stato della storia dell’arte, su quanto sia necessario rivedere e interrogare le strategie della sua costruzione, nonché l’identificazione dei documenti e materiali d’archivio considerati le sue «fonti». Tali problemi coinvolgono gruppi di lavoro e ricerche differentemente orientati, all’interno dei quali è tuttavia possibile individuare premesse simili che da una parte affrontano la questione su un piano teorico e metodologico, dall’altro si concentrano su casi di studio, su particolari aspetti storici e filologici, per mettere in pratica, nuove ipotesi di studio e ricerca. Il saggio si sofferma su tali questioni e analizza alcuni passaggi fondamentali della bibliografia più recente

Delivery of biologics to the retinal pigment epithelium

Biologics are increasingly used in the treatment of ocular diseases such as age-related macular degeneration (AMD) that cannot be controlled with conventional small molecule drugs. AMD is a multifactorial eye disease that carries significant risk of morbidity and vision loss. In Finland and other western countries, AMD affects one in three people older than 75 years, and until the early 2000s no effective treatment was available for these patients. The marketing approval of anti-VEGF antibodies was a major breakthrough in the management of AMD; indeed these biologics effectively halt choroidal neovascularization and therefore prevent further vision loss in roughly half of the patients with wet AMD. Antibody therapy has been the most successful approach so far, however, other biological therapies such as gene therapy, cell therapy and other therapeutic proteins, may prove beneficial in the treatment of AMD and other vision threatening disorders. This thesis deals with the delivery of biologics, including DNA, cells, proteins and peptides, to the retinal pigment epithelium (RPE), which plays a central role in the development of AMD. Briefly, the main topics and results of this work are presented. New non-viral gene delivery candidates are usually screened for transfection efficiency and toxicity by reading out transgene expression levels relative to a reference formulation after in vitro transfection. The screening protocols, however, can be very different among laboratories, so that comparison of results is often difficult, if not impossible. Our aim was to develop a standardized protocol optimized for the transfection of retinal pigment epithelial cells in vitro. The developed screening protocol provides a relatively simple and reproducible procedure for the pre-selection of potential candidate reagents as non-viral gene delivery systems targeted to the retinal pigment epithelium. The ocular delivery of biologics remains a challenging task due to the barriers of the eye. Short cationic peptides, also known as cell-penetrating peptides (CPPs), have been successfully used as tools to introduce various biologics into cells due to their ability to translocate across the plasma membrane and deliver their cargoes intracellularly. In our work, we have explored the functionality of Tat peptide, one of the most widely studied CPPs. Our results indicate that it is not the sequence of Tat per se that dictates cell uptake, but the cationic charge of the peptide. Moreover no direct penetration was observed; instead all the peptides were endocytosed and, as it is often the case in non-viral gene delivery, ended their journey inside lysosomes. For this reason, we think that the use of Tat peptide for the delivery of biologics to the cytoplasm or nucleus of cells will probably not be very successful. Ocular stem cell therapy holds promise for the reconstruction of the degenerated RPE monolayer in AMD patients; in addition, engineered human RPE constructs may also provide a unique platform for drug discovery and toxicology. We have grown a functional RPE tissue in vitro by using human embryonic stem cells as cell source and the synthetic polymer polyimide as supporting scaffold for the growth and maturation of the cells. The epithelia acquired RPE-like properties, including characteristic RPE phenotype, expression of RPE markers, barrier and phagocytic function. The degeneration of RPE cells in dry AMD is caused by the aggregation of proteins inside RPE cells, and is currently untreatable. We have investigated the cytoprotective properties of heat shock protein 70 kDa (Hsp70) against oxidative damage and the feasibility of rhHsp70 protein therapy as a potential therapeutic approach for dry AMD. This work provides a novel therapeutic option for the treatment of RPE degeneration in AMD.Biologiset lääkkeet ovat uusi lääkeryhmä jotka valmistetaan elävistä organismeista, kuten mikro-organismeista sekä kasvi- ja eläinsoluista, bioteknologisin menetelmin. Biologisiin lääkkeisiin luetaan esimerkiksi proteiinit kuten vasta-aineet ja kasvutekijät, geneettinen materiaali ja soluterapia. Kuten kaikki lääkkeet, biologiset lääkkeet toimivat vuorovaikutussuhteessa ruumiin kanssa tuottaen terapeuttisen lopputuloksen. Kuitenkin kun niitä verrataan pienimolekyylisiin lääkkeisiin kuten aspiriiniin, biologiset lääkkeet ovat huomattavasti suurempia ja monimutkaisempia, mikä tekee niiden toimittamisesta vaikutusalueelle huomattavasti haastavampaa ja vaikeampaa. Huolimatta näistä vaikeuksista biologisten lääkkeiden käyttö ihmisen sairauksien hoidossa on kasvanut nopeasti ja siitä hyötyvät jo nyt miljoonat potilaat ympäri maailman. Silmäpohjan ikärappeuma (age-related macular degeneration, AMD) on näkökykyä tuhoava sairaus joka on suurin sokeutumisen aiheuttaja länsimaiden ikääntyvässä väestössä. Suomessa AMD todetaan yhdellä kolmesta yli 75-vuotiaasta ja näkökyvyn menetys on pysyvä. Kuitenkin viimeisen kymmenen vuoden aikana on kyetty kehittämään uusi biologinen hoito joka kykenee pysäyttämään taudin etenemisen joillakin potilailla jotka kärsivät AMD:n kosteasta muodosta. Kostean AMD:n tyypillisenä tuntomerkkinä on uusien verisuonien kasvaminen silmän takaosaan, mikä tuhoaa verkkokalvon rakenteen ja aiheuttaa nopeasti näkökyvyn menettämisen. Biologiset lääkkeet joita käytetään kostean AMD:n hoitoon estävät uusien verisuonien kasvun ja pitävät näin silmän terveenä. Valitettavasti tämä hoitomuoto ei tehoa suurimpaan osaan AMD-potilaista, ja lisäksi jotta biologiset lääkkeet saadaan toimitettua vaikutusalueelleen silmän takaosaan tarvitaan kuukausittaisia injektioita. Tämän takia on tarpeen kehittää uusia teknologioita, jotka mahdollistavat paremman, helpomman ja potilasystävällisemmän AMD-hoidon biologisilla lääkkeillä. Tämä väitöskirja tutkii uusia tapoja toimittaa biologisia lääkkeitä kuten geneettistä materiaalia, peptidejä, proteiineja ja soluja verkkokalvon pigmenttiepiteeliin (RPE). RPE on yhden solun paksuinen kalvo silmän takaosassa, jolla on tärkeä tehtävä verkkokalvon terveyden ja toimintakyvyn ylläpitämisessä. Itse asiassa juuri RPE:n toiminnan häiriö ja tuhoutuminen katsotaan olevan AMD:n aiheuttaja. Ensimmäinen tutkittu menetelmä oli terapeuttisen geenimateriaalin toimittaminen RPE:hen. Ensin kehitettiin ja optimoitiin standardoitu protokolla toistettavissa olevan ja korkeatasoisen geenisiirteen toimittamiseksi verkkokalvon pigmenttiepiteeliin. Seuraavaksi protokollaa käytettiin erityyppisten geneettisten materiaalien ja DNA-siirteiden tutkimiseen. Lisäksi tutkimme Tat-peptidiä, jota käytetään yleisesti biologisten lääkkeiden kantoainena. Kuitenkin tuloksemme osoittavat ettei Tat-peptidi mahdollisesti ole kovinkaan lupaava kantoaine biologisten lääkkeiden toimittamiseen RPE:hen, johtuen sen epäsuotuisista ominaisuuksista. Toinen menetelmämme oli RPE:n uudelleenkonstruointi käyttäen kantasoluja ja synteettisestä kalvosta muodostetua kehikkoa joka auttaa oikean rakenteen muodostamisessa kudokselle, samaan tapaan kun rakennettaessa esimerkiksi taloa. Tässä tutkimuksessa onnistuimme luomaan toimivan RPE-kerroksen jota voidaan tulevaisuudessa käyttää korvaamaan AMD-potilaiden sairastunut RPE, sekä myös uusien RPE-solujen terveyttä parantavien lääkkeiden testaukseen in vitro. Kolmantena menetelmänä oli lämpöshokkiproteiini 70:n (Hsp70) toimittaminen RPE:hen. Olemme osoittaneet että Hsp70 edesauttaa RPE-solujen pysymistä terveinä ja suojaa niitä vaurioitumiselta. Tämä on uusi hoitostrategia joka toivottavasti tulee auttamaan AMD:hen liittyvän RPE-solukadon ehkäisemisessä

Madness and Modernity: The Drawings of Antonin Artaud from 1944 to 1946

Antonin Artaud, words, drawings, and the extreme and traumatic condition of an individual who pushed back the boundaries of history, of his own time, in Europe’s darkest days. Such is my scope in the pages that follow. This essay examines the drawings produced by Artaud between 1944 and 1946. They offer a particularly helpful starting point for a series of reflections on, on the one hand, a concept of identity that had emerged and re-emerged with a new critical awareness following the close of the Second World War, and on the other, how – leaving behind a modernism in which the cracks were clearly showing – it is from madness and suffering that the contemporary notion of the individual is reborn

Furfurylamines from biomass: Transaminase catalysed upgrading of furfurals

Furfural is recognised as an attractive platform molecule for the production of solvents, plastics, resins and fuel additives. Furfurylamines have many applications as monomers in biopolymer synthesis and for the preparation of pharmacologically active compounds, although preparation via traditional synthetic routes is not straightforward due to by-product formation and sensitivity of the furan ring to reductive conditions. In this work transaminases (TAms) have been investigated as a mild sustainable method for the amination of furfural and derivatives to access furfurylamines. Preliminary screening with a recently reported colorimetric assay highlighted that a range of furfurals were readily accepted by several transaminases and the use of different amine donors was then investigated. Multistep synthetic routes were required to synthesise furfurylamine derivatives for use as analytical standards, highlighting the benefits of using a one step biocatalytic route. To demonstrate the potential of using TAms for the production of furfurals, the amination of selected compounds was then investigated on a preparative scale

Direct Conversion of Hydrazones to Amines using Transaminases

Transaminase enzymes (TAms) have been widely used for the amination of aldehydes and ketones, often resulting in optically pure products. In this work, transaminases were directly reacted with hydrazones in a novel approach to form amine products. Several substrates were investigated, including those with furan and phenyl moieties. It was determined that the amine yields increased when an additional electrophile was added to the reaction mixture, suggesting that they can sequester the hydrazine released in the reaction. Pyridoxal 5’-phosphate (PLP), a cofactor for transaminases, and polyethylene glycol (PEG)-aldehydes were both found to increase the yield of amine formed. Notably, the amination of (S)-(−)-1-amino-2-(methoxymethyl)pyrrolidine (SAMP) hydrazones gave promising results as a method to form chiral β-substituted amines in good yield

Aminopolyols from Carbohydrates: Amination of Sugars and Sugar‐Derived Tetrahydrofurans with Transaminases

Carbohydrates are the major component of biomass and have unique potential as a sustainable source of building blocks for chemicals, materials, and biofuels because of their low cost, ready availability, and stereochemical diversity. With a view to upgrading carbohydrates to access valuable nitrogen‐containing sugar‐like compounds such as aminopolyols, biocatalytic aminations using transaminase enzymes (TAms) have been investigated as a sustainable alternative to traditional synthetic strategies. Demonstrated here is the reaction of TAms with sugar‐derived tetrahydrofuran (THF) aldehydes, obtained from the regioselective dehydration of biomass‐derived sugars, to provide access to cyclic aminodiols in high yields. In a preliminary study we have also established the direct transamination of sugars to give acyclic aminopolyols. Notably, the reaction of the ketose d‐fructose proceeds with complete stereoselectivity to yield valuable aminosugars in high purity

One-pot, two-step transaminase and transketolase synthesis of L-gluco-heptulose from L-arabinose

The use of biocatalysis for the synthesis of high value added chemical building blocks derived from biomass is becoming an increasingly important application for future sustainable technologies. The synthesis of a higher value chemical from L-arabinose, the predominant monosaccharide obtained from sugar beet pulp, is demonstrated here via a transketolase and transaminase coupled reaction. Thermostable transketolases derived from Deinococcus geothermalis and Dei nococcus radiodurans catalysed the synthesis of L-gluco-heptulose from L-arabinose and β-hydroxypyruvate at elevated temperatures with high conversions. β-Hydroxypyruvate, a commercially expensive compound used in the transketolase reaction, was generated in situ from L-serine and α-ketoglutaric acid via a thermostable transaminase, also from Deinococcus geothermalis. The two steps were investigated and implemented in a one-pot system for the sustainable and efficient production of L-gluco-heptulose

Stereoselective synthesis of cis-1,3-dimethyltetrahydroisoquinolines: formal synthesis of naphthylisoquinoline alkaloids

Starting from tricyclic lactam 2, which is easily accessible by cyclocondensation of -oxoester 1 with (R)-phenylglycinol, a three-step synthetic route to enantiopure 1-substituted tetrahydroisoquinolines, including 1-alkyl-, 1-aryl-, and 1-benzyl- tetrahydroisoquinoline alkaloids as well as the tricyclic alkaloid (-)-crispine A, has been developed. The key step is a stereoselective -amidoalkylation reaction using the appropriate Grignard reagent