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I'd fallen asleep reading, and when I woke up, the house was dark. I opened my eyes with a calm not my own: I knew exactly what I had to [...]

Abstract Supersymmetric, magnetically charged (and possibly accelerating) black holes in AdS4 that uplift on Sasaki-Einstein manifolds Y 7 to M-theory have a dual matrix model description. The matrix model in turn arises by localization of the 3d N $$ \mathcal{N} $$ = 2 SCFTs, dual to the AdS4 vacuum, on the black hole horizon geometry, which is a Riemann surface Σ g (or a spindle Σ). We identify the imaginary part t of the continuously distributed eigenvalues in the matrix model, and their density function ρ(t), with natural geometric quantities associated with the M-theory circle action U(1) M on the near-horizon geometry AdS2 × Y 9, the internal space Y 9 being a Y 7 fibration over Σ g (or Σ). Moreover, we argue that the points where ρ ′ (t) is discontinuous match with the classical action of BPS probe M2-branes wrapping AdS2 and the M-theory circle. We illustrate our findings with the ABJM and ADHM theories, whose duals have Y 7 = S 7/ℤ k , and some of their flavoured variants corresponding to other toric Y 7.

Abstract Background Spinal Muscular Atrophy (SMA) is an autosomal-recessive neuromuscular disease affecting children. It is caused by the mutation or deletion of the survival motor neuron 1 (SMN1) gene resulting in lower motor neuron (MN) degeneration followed by motor impairment, progressive skeletal muscle paralysis and respiratory failure. In addition to the already existing therapies, a possible combinatorial strategy could be represented by the use of adipose-derived mesenchymal stem cells (ASCs) that can be obtained easily and in large amounts from adipose tissue. Their efficacy seems to be correlated to their paracrine activity and the production of soluble factors released through extracellular vesicles (EVs). EVs are important mediators of intercellular communication with a diameter between 30 and 100 nm. Their use in other neurodegenerative disorders showed a neuroprotective effect thanks to the release of their content, especially proteins, miRNAs and mRNAs. Methods In this study, we evaluated the effect of EVs isolated from ASCs (ASC-EVs) in the SMNΔ7 mice, a severe SMA model. With this purpose, we performed two administrations of ASC-EVs (0.5 µg) in SMA pups via intracerebroventricular injections at post-natal day 3 (P3) and P6. We then assessed the treatment efficacy by behavioural test from P2 to P10 and histological analyses at P10. Results The results showed positive effects of ASC-EVs on the disease progression, with improved motor performance and a significant delay in spinal MN degeneration of treated animals. ASC-EVs could also reduce the apoptotic activation (cleaved Caspase-3) and modulate the neuroinflammation with an observed decreased glial activation in lumbar spinal cord, while at peripheral level ASC-EVs could only partially limit the muscular atrophy and fiber denervation. Conclusions Our results could encourage the use of ASC-EVs as a therapeutic combinatorial treatment for SMA, bypassing the controversial use of stem cells.

Patients with anorexia nervosa (AN) typically hold altered beliefs about their body that they struggle to update, including global, prospective beliefs about their ability to know and regulate their body and particularly their interoceptive states. While clinical questionnaire studies have provided ample evidence on the role of such beliefs in the onset, maintenance, and treatment of AN, psychophysical studies have typically focused on perceptual and ‘local’ beliefs. Across two experiments, we examined how women at the acute AN (N = 86) and post-acute AN state (N = 87), compared to matched healthy controls (N = 180) formed and updated their self-efficacy beliefs retrospectively (Experiment 1) and prospectively (Experiment 2) about their heartbeat counting abilities in an adapted heartbeat counting task. As preregistered, while AN patients did not differ from controls in interoceptive accuracy per se, they hold and maintain ‘pessimistic’ interoceptive, metacognitive self-efficacy beliefs after performance. Modelling using a simplified computational Bayesian learning framework showed that neither local evidence from performance, nor retrospective beliefs following that performance (that themselves were suboptimally updated) seem to be sufficient to counter and update pessimistic, self-efficacy beliefs in AN. AN patients showed lower learning rates than controls, revealing a tendency to base their posterior beliefs more on prior beliefs rather than prediction errors in both retrospective and prospective belief updating. Further explorations showed that while these differences in both explicit beliefs, and the latent mechanisms of belief updating, were not explained by general cognitive flexibility differences, they were explained by negative mood comorbidity, even after the acute stage of illness.

Introduction Neurofilmology is a young and evolving research field, at the intersection between neuroscience and movie experiences, that explores how the brain processes and responds to visual storytelling. It involves examining the cognitive and emotional effects of movies on viewers, including social cognition and perspective-taking aspects. However, up to date, these studies have focused only on the neurotypical population, hence constituting a considerable gap in the literature with respect to individuals with neuroatypical functioning. Objectives Aim of this study was to investigate the experience of film viewing and its correlates in individuals with a diagnosis of Autism Spectrum Disorders (ASD). Methods 30 neurotypical individuals and 30 individuals with ASD without intellectual disabilities were asked to observe 12 short video clips of 3 seconds length, showing an agent grasping an object from a table, and filmed with three different camera techniques: Still, Steadycam, Zoom; for each clip, they were asked to respond to six question on a Visual Analogue Scale (0-100) designed to investigate participants’ potential feeling of involvement with the observed scene, their comfort with the different filming conditions, and their estimation of the ecological plausibility of the different types of camera movements. Results Participants felt more involved watching videos filmed with a Steadycam, with respect to the Zoom and Still condition. Within the neurotypical group participants felt more comfortable when the camera was in motion (both Steadycam and Zoom condition) compared to the Still condition; no differences were found between conditions in the ASD group, as if they felt equally comfortable in every condition administered, regardless the filming technique. Conclusions First, our results reinforce prior findings regarding the influence of different camera techniques on neurotypical individuals. Second, they add to the existing literature suggesting that individuals with ASD may exhibit differences in their subjective experiences related to empathizing with characters and immersing themselves as actors when the camera replicates naturalistic movements, resulting in a diminished overall fulfillment in the movie-watching process. Disclosure of Interest None Declared

En el presente trabajo analizo un corpus de obras de la realizadora argentina Albertina Carri. Propongo poner en diálogo su último largometraje documental Cuatreros (2016) junto a la pieza Punto Impropio (2020) y Restos (2010) con la lectura performática titulada El affaire Velázquez (2013) y la instalación Investigación del cuatrerismo (2015). Estas realizaciones están construidas a partir de documentos tomados de distintos acervos. Pueden entenderse como un diálogo en ausencia que la directora intenta con su padre­madre desaparecidos por la última dictadura cívico-militar. Estas propuestas, además, son un intento de repensar la herencia o legado de sus progenitores partiendo desde los despojos. Allí asoma una forma de montaje desviado sobre los archivos construyendo otro tipo de narrativas intermediales que proponen repensar los vínculos íntimos y familiares. This paper analyses a corpus of works by Argentine filmmaker Albertina Carri. I propose to put into dialogue her latest documentary Cuatreros (2016) together with the piece Punto Impropio (2020) and Restos (2010) using the performative lecture El affaire Velázquez (2013) and the installation Investigación del cuatrerismo (2015). These works are constructed from documents taken from different collections. They can be understood as a dialogue in absence that the director attempts with her parents, who were disappeared during the last civil-military dictatorship in Argentina. These proposals are also attempts to rethink the inheritance or legacy of her parents based on the remains. Somehow, there emerges a form of deflected montage on the archives, constructing another type of intermedial narrative that proposes to rethink intimate and family ties.

Abstract Background Huntington’s disease (HD) is a motor and cognitive neurodegenerative disorder due to prominent loss of striatal medium spiny neurons (MSNs). Cell replacement using human embryonic stem cells (hESCs) derivatives may offer new therapeutic opportunities to replace degenerated neurons and repair damaged circuits. Methods With the aim to develop effective cell replacement for HD, we assessed the long-term therapeutic value of hESC-derived striatal progenitors by grafting the cells into the striatum of a preclinical model of HD [i.e., adult immunodeficient rats in which the striatum was lesioned by monolateral injection of quinolinic acid (QA)]. We examined the survival, maturation, self-organization and integration of the graft as well as its impact on lesion-dependent motor alterations up to 6 months post-graft. Moreover, we tested whether exposing a cohort of QA-lesioned animals to environmental enrichment (EE) could improve graft integration and function. Results Human striatal progenitors survived up to 6 months after transplantation and showed morphological and neurochemical features typical of human MSNs. Donor-derived interneurons were also detected. Grafts wired in both local and long-range striatal circuits, formed domains suggestive of distinct ganglionic eminence territories and displayed emerging striosome features. Moreover, over time grafts improved complex motor performances affected by QA. EE selectively increased cell differentiation into MSN phenotype and promoted host-to-graft connectivity. However, when combined to the graft, the EE paradigm used in this study was insufficient to produce an additive effect on task execution. Conclusions The data support the long-term therapeutic potential of ESC-derived human striatal progenitor grafts for the replacement of degenerated striatal neurons in HD and suggest that EE can effectively accelerate the maturation and promote the integration of human striatal cells.

Grape pomace, the main by-product of wine process, shows high potential for the development of functional foods, being a natural source of bioactive compounds and dietary fiber. Thus, the present study proposes the development of five potential functional biscuits. The five formulations were achieved by varying the Tannat grape pomace powder (TGP, 10–20% w/w total wet dough) and sweetener sucralose (2–4% w/w total wet dough) content through a factorial design with central points. TGP microbiological and pesticides analysis were performed as a food safety requirement. Identification of bioactive compounds by HPLC-DAD-MS, in vitro bioactivity (total phenol content, antioxidant by ABTS and ORAC-FL, antidiabetic and antiobesity by inhibition of α-glucosidase and pancreatic lipase, respectively) and sensory properties of the biscuits were evaluated. TGP microbiological and pesticides showed values within food safety criteria. Sensory profiles of TGP biscuits were obtained, showing biscuits with 20% TGP good sensory quality (7.3, scale 1–9) in a cluster of 37 out of 101 consumers. TGP addition in biscuits had a significant (p < 0.05) effect on total phenolic content (0.893–1.858 mg GAE/g biscuit) and bioactive properties when compared to controls: 11.467–50.491 and 4.342–50.912 μmol TE/g biscuit for ABTS and ORAC-FL, respectively; inhibition of α-glucosidase and pancreatic lipase, IC50 35.572–64.268 and 7.197–47.135 mg/mL, respectively. HPLC-DAD-MS results showed all the identified phenolic compounds in 20/4% biscuit (TGP/sucralose%) were degraded during baking. Malvidin-3-O-(6′-p-coumaroyl) glucoside, (+)-catechin, malvidin-3-O-glucoside, and (−)-epicatechin were the main phenolic compounds (in descendent order of content) found. The bioactive properties could be attributed to the remaining phenolic compounds in the biscuits. In conclusion, TGP biscuits seemed to be a promising functional food with potential for ameliorating oxidative stress, glucose and fatty acids levels with good sensory quality.

In this work we will analyze three recent pieces by the film director, producer and screenwriter Albertina Carri. We will give particular attention to works made from film archives and personal documents. To do so, we will focus on two of the pieces that were part of the installation Operación fracaso y el sonido recobrado (2015) presented at the Museo del Parque de la Memoria: Punto Impropio (2015) and Investigación del cuatrerismo (2015), putting them in dialogue with the later feature film Cuatreros (2016). We will investigate the archive reappropriation strategies developed to write her personal story, marked by the kidnapping and subsequent disappearance of her father and mother during the last military dictatorship. We will explore the ways in which Carri wonders about the workings of memory, and whether it is possible to reconstruct a story solely based on the testimonies or memories of those years. Finally, we aim to give an account of how these images return to the present, now accompanied by a political power capable of constructing a new narrative about a past marked by horror.

Abstract During physiological aging, iron accumulates in the brain with a preferential distribution in regions that are more vulnerable to age-dependent neurodegeneration such as the cerebral cortex and hippocampus. In the brain of aged wild-type mice, alteration of the Brain Blood Barrier integrity, together with a marked inflammatory and oxidative state lead to increased permeability and deregulation of brain-iron homeostasis. In this context, we found that iron accumulation drives Hepcidin upregulation in the brain and the inhibition of the iron exporter Ferroportin1. We also observed the transcription and the increase of NCOA4 levels in the aged brain together with the increase of light-chain enriched ferritin heteropolymers, more efficient as iron chelators. Interestingly, in cerebral cortex and hippocampus, Ferroportin1 is mainly expressed by astrocytes, while the iron storage protein ferritin light-chain by neurons. This differential distribution suggests that astrocytes mediate iron shuttling in the nervous tissue and that neurons are unable to metabolize it. Our findings highlight for the first time that Hepcidin/Ferroportin1 axis and NCOA4 are directly involved in iron metabolism in mice brain during physiological aging as a response to a higher brain iron influx.

Este artículo tiene como objetivo analizar la evolución que presenta la normativa legal, con sus posteriores reglamentaciones, en Uruguay y países de la región (Argentina, Brasil, Chile, Perú y Colombia); también se analizarán algunas de las principales plataformas de financiamiento colectivo, para visualizar su impacto y evolución. Para ello se propone analizar bibliografía especializada en la temática de los últimos diez años, estudiar y comparar la normativa vigente en el área y finalmente indagar en tres de las plataformas principales que hay activas en estos países, así como también a qué tipo de crowdfunding se dedican. Este análisis se realiza con el objetivo de indagar si es una opción de financiamiento posible y activa en Uruguay y en los países de la región, su impacto en la economía y actividades de los promotores. En conclusión, es una opción viable en muchos países. En Uruguay su inicio es lento, con poca proyección a futuro, y escasa cantidad de ofertas. Se visualiza la importancia de seguir ahondando en estos medios de financiación, y su impacto en la economía.

Fourteen quinolizidine derivatives, structurally related to the alkaloids lupinine and cytisine and previously studied for other pharmacological purposes, were presently tested for antiarrhythmic, and other cardiovascular effects on isolated guinea pig heart tissues in comparison to well-established reference drugs. According to their structures, the tested compounds are assembled into three subsets: (a) N-(quinolizidinyl-alkyl)-benzamides; (b) 2-(benzotriazol-2-yl)methyl-1-(quinolizidinyl)alkyl-benzimidazoles; (c) N-substituted cytisines. All compounds but two displayed antiarrhythmic activity that was potent for compounds 4, 1, 6, and 5 (in ascending order). The last compound (N-(3,4,5-trimethoxybenzoyl)aminohomolupinane) was outstanding, exhibiting a nanomolar potency (EC50 = 0.017 µM) for the increase in the threshold of ac-arrhythmia. The tested compounds shared strong negative inotropic activity; however, this does not compromise the value of their antiarrhythmic action. On the other hand, only moderate or modest negative chronotropic and vasorelaxant activities were commonly observed. Compound 5, which has high antiarrhythmic potency, a favorable cardiovascular profile, and is devoid of antihypertensive activity in spontaneously hypertensive rats, represents a lead worthy of further investigation.

In the field of neurodegenerative pathologies, the platforms for disease modelling based on patient-derived induced pluripotent stem cells (iPSCs) represent a valuable molecular diagnostic/prognostic tool. Indeed, they paved the way for the in vitro recapitulation of the pathological mechanisms underlying neurodegeneration and for characterizing the molecular heterogeneity of disease manifestations, also enabling drug screening approaches for new therapeutic candidates. A major challenge is related to the choice and optimization of the morpho-functional study designs in human iPSC-derived neurons to deeply detail the cell phenotypes as markers of neurodegeneration. In recent years, the specific combination of high-throughput screening with subcellular resolution microscopy for cell-based high-content imaging (HCI) screening allowed in-depth analyses of cell morphology and neurite trafficking in iPSC-derived neuronal cells by using specific cutting-edge microscopes and automated computational assays. The present work aims to describe the main recent protocols and advances achieved with the HCI analysis in iPSC-based modelling of neurodegenerative diseases, highlighting technical and bioinformatics tips and tricks for further uses and research. To this end, microscopy requirements and the latest computational pipelines to analyze imaging data will be explored, while also providing an overview of the available open-source high-throughput automated platforms.

Grape pomaces have a wide and diverse antioxidant phenolics composition. Six Uruguayan red grape pomaces were evaluated in their phenolics composition, antioxidant capacity, and anti-inflammatory properties. Not only radical scavenging methods as DPPH· and ABTS·+ were employed but also ORAC and FRAP analyses were applied to assess the antioxidant potency of the extracts. The antioxidant reactivity of all extracts against hydroxyl radicals was assessed with ESR. The phenol profile of the most bioactive extract was analyzed by HPLC-MS, and a set of 57 structures were determined. To investigate the potential anti-inflammatory activity of the extracts, Nuclear Factor kappa-B (NF-κB) modulation was evaluated in the human colon cancer reporter cell line (HT-29-NF-κB-hrGFP). Our results suggest that Tannat grapes pomaces have higher phenolic content and antioxidant capacity compared to Cabernet Franc. These extracts inhibited TNF-alpha mediated NF-κB activation and IL-8 production when added to reporter cells. A molecular docking study was carried out to rationalize the experimental results allowing us to propose the proactive interaction between the NF-κB, the grape extracts phenols, and their putative anti-inflammatory bioactivity. The present findings show that red grape pomace constitutes a sustainable source of phenolic compounds, which may be valuable for pharmaceutical, cosmetic, and food industry applications.