Il balletto a Leningrado tra avanguardia e ideologia

La tesi di dottorato dal titolo Il balletto a Leningrado tra avanguardia e ideologia si pone come intento quello di analizzare il passaggio dal clima russo rivoluzionario degli anni Venti del Novecento al periodo dell’ideologia stalinista, prendendo come oggetto specifico il genere teatrale del balletto nella sua intersezione con le altre arti e impostando come delimitazione geografica la città di San Pietroburgo-Leningrado, già culla del balletto zarista. Prendendo come base gli spunti offerti dalla recente letteratura scientifica internazionale, la ricerca mira innanzitutto a inquadrare l’attività coreografica di Fedor Lopuchov e gli influssi che quest’ultimo recepì dal musicologo Boris Asaf’ev e dall’artista Aleksandr Benois. Diviene pertanto chiaro come l’eredità del “sinfonismo” di Petipa fu da Lopuchov riletta sotto la lente delle più recenti conquiste dell’Avanguardia. Inoltre, attraverso l’esplorazione del rapporto tra La danzasinfonia di Lopuchov e la sua restante produzione coreografica, ci si comincia a interrogare sulla reale natura dei due rami dell’arte coreografica (la “danza pura” e la “danza drammatica”) sviluppando le idee racchiuse dalla studiosa Christina Ezrahi nel suo recente testo Swans of the Kremlin (University of Pittsburgh Press, 2012) attraverso il confronto con la produzione letteraria, teatrale, musicale e visiva delle Avanguardie russe oltre che con gli scritti dello stesso Lopuchov. La parte centrale della tesi si focalizza come già anticipato sul passaggio dal clima rivoluzionario all’ideologia del realismo socialista. Di fondamentale importanza diviene qui rintracciare le ragioni della costituzione del paradigma del drambalet (“balletto drammatico”), riflettendo in parallelo sulla revisione dei balletti classici in epoca sovietica. Traendo spunto da fonti diverse, di cui la più rilevante è la trascrizione conservata nell’archivio CGALI di una discussione avvenuta in seno al Dipartimento di Teoria del Teatro e della Musica dell’Accademia Statale di Scienze delle Arti in congiunzione con l’Unione dei Compositori Sovietici, si comprenderà in ultima analisi come il drambalet non fosse altro che una rivisitazione dell’eredità coreografica del maître de ballet francese Marius Petipa. La parte conclusiva della tesi si sposta infine all’epoca del “disgelo” sovietico per osservare il modo in cui il modello del balletto classico accademico e quello del drambalet confluirono in un’unica forma, dando vita al fenomeno del “nuovo sinfonismo coreografico”. Il dilemma cui tenta di rispondere la produzione coreografica dell’epoca del “disgelo” si muove tra il polo dello sviluppo della pantomima in stretta unione con la musica (obiettivo perseguito dal coreografo Jakobson nello spettacolo Spartacus attraverso l’ideazione di una particolare “plastica coreografica”) e il polo della liberazione della danza pura di derivazione sinfonica, arricchita però dalle lezioni sovietiche (obiettivo perseguito dal coreografo Jurij Grigorovič, allievo di Fedor Lopuchov, nello spettacolo Il fiore di pietra). In sintesi, entrambe le strade erano valide, ma se si preferì il linguaggio più astratto della danza classica fu soprattutto perché in essa non si vide più solo una componente ornamentale, ma un elemento atto ad “esprimere” l’interiorità e l’essenza del personaggio. Come aveva affermato in campo teatrale il regista Mejerchol’d, era la marionetta con i suoi gesti espressivi, con il gesto inventato, con il movimento convenzionale a creare la realtà e a dar vita alla maschera, in un processo dall’esteriore all’interiore che accomunava il Dottor Dappertutto all’ultimo Stanislavskij, quello delle azioni fisiche. Attraverso Grigorovič trionfava dunque la rilettura del balletto tradizionale à la Petipa offerta inizialmente da Lopuchov tramite la vicinanza con l’Avanguardia, ma ora rimodulata attraverso le lezioni del realismo socialista

Designing fast-dissolving orodispersible films of amphotericin B for oropharyngeal candidiasis

Amphotericin B possesses high activity against Candida spp. with low risk of resistance. However, Amphotericin B's high molecular weight compared to other antifungal drugs, such as miconazole and clotrimazole, and poor water solubility hampers its efficacy at the physiological conditions of the oropharyngeal cavity (saliva pH, limited volume for dissolution) and thereby limits its clinical use in oropharyngeal candidiasis. We have prepared fast-dissolving orodispersible films with high loading (1% w/w) using solvent casting that enables amphotericin B to remain solubilised in saliva in equilibrium between the monomeric and dimeric states, and able to produce a local antifungal effect. Optimisation of the amphotericin B-loaded orodispersible films was achieved by quality by design studies combining dextran and/or maltodextrin as dextrose-derived-polymer film formers with cellulose-derived film formers (hydroxypropylmethyl/hydroxypropyl cellulose in a 1:4 weight ratio), sorbitol for taste masking, microcrystalline cellulose (Avicel 200) or microcrystalline cellulose-carboxymethylcellulose sodium (Avicel CL-611) for enhancing the mechanical strength of the film, and polyethylene glycol 400 and glycerol (1:1 w/w) as plasticizers. The optimised amphotericin B orodispersible films (containing 1% AmB, 25% dextran, 25% maltodextrin, 5% sorbitol, 10% Avicel 200, 10% polyethylene glycol 400, 10% glycerol, 3% hydroxypropylmethyl cellulose acetate succinate, 12% hydroxypropyl cellulose) possessed a fast disintegration time (60 ± 3 s), quick release in artificial saliva (>80% in 10 min), high burst strength (2190 mN mm) and high efficacy against several Candida spp. (C. albicans, C. parapsilosis and C. krusei) (>15 mm inhibition halo). Amphotericin B orodispersible films are stable for two weeks at room temperature (25° C) and up to 1 year in the fridge. Although further toxicological and in vivo efficacy studies are required, this novel Amphotericin B orodispersible films is a promising, physicochemically stable formulation with potential wide application in clinical practice, especially for immunocompromised patients suffering from oropharyngeal candidiasis

Unraveling the degradation mechanism in FIrpic based Blue OLEDs: II. Trap and detect molecules at the interfaces

The impact of organic light emitting diodes (OLEDs) in modern life is witnessed by their wide employment in full-color, energy-saving, flat panel displays and smart-screens; a bright future is likewise expected in the field of solid state lighting. Cyclometalated iridium complexes are the most used phosphorescent emitters in OLEDs due to their widely tunable photophysical properties and their versatile synthesis. Blue-emitting OLEDs, suffer from intrinsic instability issues hampering their long term stability. Backed by computational studies, in this work we studied the sky-blue emitter FIrpic in both ex-situ and in-situ degradation experiments combining complementary, mutually independent, experiments including chemical metathesis reactions, in liquid phase and solid state, thermal and spectroscopic studies and LC-MS investigations. We developed a straightforward protocol to evaluate the degradation pathways in iridium complexes, finding that FIrpic degrades through the loss of the picolinate ancillary ligand. The resulting iridium fragment was than efficiently trapped "in-situ" as BPhen derivative 1. This process is found to be well mirrored when a suitably engineered, FIrpic-based, OLED is operated and aged. In this paper we (i) describe how it is possible to effectively study OLED materials with a small set of readily accessible experiments and (ii) evidence the central role of host matrix in trapping experiments.Comment: 13 pages, 6 figure

A Holocene tephra layer within coastal aeolian deposits north of Caleta Olivia (Santa Cruz Province, Argentina)

In this paper we illustrate the stratigraphy, geochronology, and geochemistry (major, minor, trace elements and Sr-isotopes) of a Holocene tephra layer found within coastal sedimentary deposits north of Caleta Olivia (Santa Cruz Province, Argentina). The stratigraphic succession comprises beach deposits with basal erosive surface resting on the local substrate (“Formación Patagonia”) followed by a poorly developed paleosoil. The paleosoil is covered by a lenticular fine grained (Mdφ: 5.2, 0.027 mm), well sorted (σφ: 1.2) volcanic ash layer and aeolian sands. The geochemical composition of shard fragments points to an origin from the Hudson volcano, located in the southern Andes, ca. 400 km to the west. The geochemistry, Sr-isotopes and the radiometric constraints (younger than the age of the underlying marine layer dated at ca. 4,100 a cal BP) further allow correlating this tephra with the so-called H2 eruption (ca. 3,900 a cal BP). This finding is of interest owing to the poor preservation potential of tephra within the Late Holocene sedimentary deposits of the Atlantic coast of Patagonia and represents the first finding of H2 eruption in this area, improving our knowledge of the dispersion of the fine-grained distal deposit of the Hudson volcanic explosive activity, thus allowing a better estimate of the eruptive dynamics and the risks associated with the Hudson volcano

Clinical expression of facioscapulohumeral muscular dystrophy in carriers of 1-3 D4Z4 reduced alleles: Experience of the FSHD Italian National Registry

OBJECTIVES: Facioscapulohumeral muscular dystrophy type 1 (FSHD1) has been genetically linked to reduced numbers ( 64 8) of D4Z4 repeats at 4q35. Particularly severe FSHD cases, characterised by an infantile onset and presence of additional extra-muscular features, have been associated with the shortest D4Z4 reduced alleles with 1-3 repeats (1-3 DRA). We searched for signs of perinatal onset and evaluated disease outcome through the systematic collection of clinical and anamnestic records of de novo and familial index cases and their relatives, carrying 1-3 DRA. SETTING: Italy. PARTICIPANTS: 66 index cases and 33 relatives carrying 1-3 DRA. OUTCOMES: The clinical examination was performed using the standardised FSHD evaluation form with validated inter-rater reliability. To investigate the earliest signs of disease, we designed the Infantile Anamnestic Questionnaire (IAQ). Comparison of age at onset was performed using the non-parametric Wilcoxon rank-sum or Kruskal-Wallis test. Comparison of the FSHD score was performed using a general linear model and Wald test. Kaplan-Meier survival analysis was used to estimate the age-specific cumulative motor impairment risk. RESULTS: No patients had perinatal onset. Among index cases, 36 (54.5%) showed the first signs by 10 years of age. The large majority of patients with early disease onset (26 out of 36, 72.2%) were de novo; whereas the majority of patients with disease onset after 10 years of age were familial (16, 53.3%). Comparison of the disease severity outcome between index cases with age at onset before and over 10 years of age, failed to detect statistical significance (Wald test p value=0.064). Of 61 index cases, only 17 (27.9%) presented extra-muscular conditions. Relatives carrying 1-3 DRA showed a large clinical variability ranging from healthy subjects, to patients with severe motor impairment. CONCLUSIONS: The size of the D4Z4 allele is not always predictive of severe clinical outcome. The high degree of clinical variability suggests that additional factors contribute to the phenotype complexity

Functional Implications of Human-Specific Changes in Great Ape microRNAs

microRNAs are crucial post-transcriptional regulators of gene expression involved in a wide range of biological processes. Although microRNAs are highly conserved among species, the functional implications of existing lineage-specific changes and their role in determining differences between humans and other great apes have not been specifically addressed. We analyzed the recent evolutionary history of 1,595 human microRNAs by looking at their intra-and inter-species variation in great apes using high-coverage sequenced genomes of 82 individuals including gorillas, orangutans, bonobos, chimpanzees and humans. We explored the strength of purifying selection among microRNA regions and found that the seed and mature regions are under similar and stronger constraint than the precursor region. We further constructed a comprehensive catalogue of microRNA species-specific nucleotide substitutions among great apes and, for the first time, investigated the biological relevance that human-specific changes in microRNAs may have had in great ape evolution. Expression and functional analyses of four microRNAs (miR-299-3p, miR-503-3p, miR508-3p and miR-541-3p) revealed that lineage-specific nucleotide substitutions and changes in the length of these microRNAs alter their expression as well as the repertoires of target genes and regulatory networks. We suggest that the studied molecular changes could have modified crucial microRNA functions shaping phenotypes that, ultimately, became human-specific. Our work provides a frame to study the impact that regulatory changes may have in the recent evolution of our species.Peer reviewe

The landscape of expression and alternative splicing variation across human traits

Understanding the consequences of individual transcriptome variation is fundamental to deciphering human biology and disease. We implement a statistical framework to quantify the contributions of 21 individual traits as drivers of gene expression and alternative splicing variation across 46 human tissues and 781 individuals from the Genotype-Tissue Expression project. We demonstrate that ancestry, sex, age, and BMI make additive and tissue-specific contributions to expression variability, whereas interactions are rare. Variation in splicing is dominated by ancestry and is under genetic control in most tissues, with ribosomal proteins showing a strong enrichment of tissue-shared splicing events. Our analyses reveal a systemic contribution of types 1 and 2 diabetes to tissue transcriptome variation with the strongest signal in the nerve, where histopathology image analysis identifies novel genes related to diabetic neuropathy. Our multi-tissue and multi-trait approach provides an extensive characterization of the main drivers of human transcriptome variation in health and disease.This study was funded by the HumTranscriptom project with reference PID2019-107937GA-I00. R.G.-P. was supported by a Juan de la Cierva fellowship (FJC2020-044119-I) funded by MCIN/AEI/10.13039/501100011033 and ‘‘European Union NextGenerationEU/PRTR.’’ J.M.R. was supported by a predoctoral fellowship from ‘‘la Caixa’’ Foundation (ID 100010434) with code LCF/BQ/DR22/11950022. A.R.-C. was supported by a Formación Personal Investigador (FPI) fellowship (PRE2019-090193) funded by MCIN/AEI. R.C.-G. was supported by an FPI fellowship (PRE2020-092510) funded by MCIN/AEI. M.M. was supported by a Ramon y Cajal fellowship (RYC-2017-22249).Peer ReviewedPostprint (published version

Sustained release from injectable composite gels loaded with silver nanowires designed to combat bacterial resistance in bone regeneration applications

One-dimensional nanostructures, such as silver nanowires (AgNWs), have attracted considerable attention owing to their outstanding electrical, thermal and antimicrobial properties. However, their application in the prevention of infections linked to bone tissue regeneration intervention has not yet been explored. Here we report on the development of an innovative scaffold prepared from chitosan, composite hydroxyapatite and AgNWs (CS-HACS-AgNWs) having both bioactive and antibacterial properties. In vitro results highlighted the antibacterial potential of AgNWs against both gram-positive and gram-negative bacteria. The CS-HACS-AgNWs composite scaffold demonstrated suitable Ca/P deposition, improved gel strength, reduced gelation time, and sustained Ag+ release within therapeutic concentrations. Antibacterial studies showed that the composite formulation was capable of inhibiting bacterial growth in suspension, and able to completely prevent biofilm formation on the scaffold in the presence of resistant strains. The hydrogels were also shown to be biocompatible, allowing cell proliferation. In summary, the developed CS-HACS-AgNWs composite hydrogels demonstrated significant potential as a scaffold material to be employed in bone regenerative medicine, as they present enhanced mechanical strength combined with the ability to allow calcium salts deposition, while efficiently decreasing the risk of infections. The results presented justify further investigations into the potential clinical applications of these materials

Una capa de tefra holocena intercalada en los depósitos eólicos costeros ubicados al norte de Caleta Olivia (Provincia de Santa Cruz, Argentina)

In this paper we illustrate the stratigraphy, geochronology, and geochemistry (major, minor, trace elements and Sr-isotopes) of a Holocene tephra layer found within coastal sedimentary deposits north of Caleta Olivia (Santa Cruz Province, Argentina). The stratigraphic succession comprises beach deposits with basal erosive surface resting on the local substrate (“Formacion Patagonia”) followed by a poorly developed paleosoil. The paleosoil is covered by a lenticular fine-grained (Mdφ: 5.2, 0.027 mm), well sorted (σφ: 1.2) volcanic ash layer and aeolian sands. The geochemical composition of shard fragments points to an origin from the Hudson volcano, located in the southern Andes, ca. 400 km to the west. The geochemistry, Sr-isotopes and the radiometric constraints (younger than the age of the underlying marine layer dated at ca. 4,100 a cal BP) further allow correlating this tephra with the so-called H2 eruption (ca. 3,900 a cal BP). This finding is of interest owing to the poor preservation potential of tephra within the Late Holocene sedimentary deposits of the Atlantic coast of Patagonia and represents the first finding of H2 eruption in this area, improving our knowledge of the dispersion of the fine-grained distal deposit of the Hudson volcanic explosive activity, thus allowing a better estimate of the eruptive dynamics and the risks associated with the Hudson volcano.Este artículo aborda la estratigrafía, geocronología y geoquímica (elementos mayoritarios, minoritarios, trazas e isótopos de Sr) de un nivel de tefra holocena que forma parte de una secuencia de sedimentos costeros ubicados al norte de Caleta Olivia (provincia de Santa Cruz, Argentina). La secuencia comprende depósitos sedimentarios que se disponen sobre una superficie basal erosiva que suprayace al sustrato local (“Formación Patagonia”), y continúa esta secuencia con un paleosuelo de escaso desarrollo. El paleosuelo está cubierto por una capa lenticular de cenizas volcánicas de grano fino (Mdφ: 5,2, 0,027 mm), bien seleccionada (σφ: 1,2) y arenas eólicas. La composición geoquímica de los shards indica que esta tefra se originó en el volcán Hudson, ubicado en los Andes del sur, a aproximadamente 400 km hacia el oeste. La geoquímica, los isótopos de Sr y las restricciones radiométricas (más joven que la edad de la capa marina que la subyace, fechada en aproximadamente 4.100 a cal AP) permiten correlacionar esta tefra con la denominada erupción H2 de dicho volcán (ocurrida aproximadamente 3.900 a cal AP). Este hallazgo es de interés debido al escaso potencial de preservación de los depósitos de tefra dentro de las secuencias sedimentarias costeras del Holoceno Tardío, en la costa atlántica de Patagonia y representa el primer hallazgo del evento eruptivo H2 en esta área, lo cual contribuye a mejorar el conocimiento sobre la dispersión de la tefra generada por la actividad volcánica explosiva del volcán Hudson, lo que permite una mejor estimación de la dinámica eruptiva y los riesgos asociados con este volcán.Centro de Estudios Integrales de la Dinámica Exógen

CFH and CFHR Copy Number Variations in C3 Glomerulopathy and Immune Complex-Mediated Membranoproliferative Glomerulonephritis

C3 Glomerulopathy (C3G) and Immune Complex-Mediated Membranoproliferative glomerulonephritis (IC-MPGN) are rare diseases characterized by glomerular deposition of C3 caused by dysregulation of the alternative pathway (AP) of complement. In approximately 20% of affected patients, dysregulation is driven by pathogenic variants in the two components of the AP C3 convertase, complement C3 (C3) and Factor B (CFB), or in complement Factor H (CFH) and Factor I (CFI), two genes that encode complement regulators. Copy number variations (CNVs) involving the CFH-related genes (CFHRs) that give rise to hybrid FHR proteins also have been described in a few C3G patients but not in IC-MPGN patients. In this study, we used multiplex ligation-dependent probe amplification (MLPA) to study the genomic architecture of the CFH-CFHR region and characterize CNVs in a large cohort of patients with C3G (n = 103) and IC-MPGN (n = 96) compared to healthy controls (n = 100). We identified new/rare CNVs resulting in structural variants (SVs) in 5 C3G and 2 IC-MPGN patients. Using long-read single molecule real-time sequencing (SMRT), we detected the breakpoints of three SVs. The identified SVs included: 1) a deletion of the entire CFH in one patient with IC-MPGN; 2) an increased number of CFHR4 copies in one IC-MPGN and three C3G patients; 3) a deletion from CFHR3-intron 3 to CFHR3-3′UTR (CFHR34–6Δ) that results in a FHR3-FHR1 hybrid protein in a C3G patient; and 4) a CFHR31–5-CFHR410 hybrid gene in a C3G patient. This work highlights the contribution of CFH-CFHR CNVs to the pathogenesis of both C3G and IC-MPGN