Search

Abstract Bradykinesia is defined as a “complex” of motor alterations including decreased movement amplitude and/or speed and tendency to reduce them with movement repetition (sequence effect). This study aimed at investigating the neural and kinematic correlates of bradykinesia during hand-tapping in people with Parkinson’s disease (pwPD) relative to healthy controls. Twenty-five pwPD and 25 age- and sex-matched healthy controls underwent brain functional MRI (fMRI) during a hand-tapping task: subjects alternatively opened and closed their right hand as fully and quickly as possible. Hand-tapping kinematic parameters were objectively measured during the fMRI task using an optical fibre glove. During the fMRI task, pwPD showed reduced hand-tapping amplitude (hypokinesia) and a greater sequence effect. PwPD relative to healthy controls showed a reduced activity of fronto-parietal areas, middle cingulum/supplementary motor area (SMA), parahippocampus, pallidum/thalamus and motor cerebellar areas. Moreover, pwPD showed an increased activity of brain cognitive areas such as superior temporal gyrus, posterior cingulum, and cerebellum crus I. The decreased activity of cerebellum IV–V–VI, vermis IV–V, inferior frontal gyrus, and cingulum/SMA correlated with hypokinesia and with the sequence effect. Interestingly, a reduced activity of areas involved in motor planning and timing correlated both with hypokinesia and with the sequence effect in pwPD. This study has the major strength of collecting objective motor parameters and brain activity simultaneously, providing a unique opportunity to investigate the neural correlates of the “bradykinesia complex”.

Despite the many potential applications of an accurate indoor positioning system (IPS), no universal, readily available system exists. Much of the IPS research to date has been based on the use of radio transmitters as positioning beacons. Visible light positioning (VLP) instead uses LED lights as beacons. Either cameras or photodiodes (PDs) can be used as VLP receivers, and position estimates are usually based on either the angle of arrival (AOA) or the strength of the received signal. Research on the use of AOA with photodiode receivers has so far been limited by the lack of a suitable compact receiver. The quadrature angular diversity aperture receiver (QADA) can fill this gap. In this paper, we describe a new QADA design that uses only three readily available parts: a quadrant photodiode, a 3D-printed aperture, and a programmable system on a chip (PSoC). Extensive experimental results demonstrate that this design provides accurate AOA estimates within a room-sized test chamber. The flexibility and programmability of the PSoC mean that other sensors can be supported by the same PSoC. This has the potential to allow the AOA estimates from the QADA to be combined with information from other sensors to form future powerful sensor-fusion systems requiring only one beacon.

El artículo propone un análisis de las estrategias institucionales participativas llevadas adelante por el Museo Provincial de Bellas Artes Emilio Caraffa (Córdoba, Argentina) y por el Museo Municipal de Bellas Artes Juan B. Castagnino (Rosario, Argentina), para delimitar qué perfiles organizacionales están promoviendo al poner en el centro de su dinámica a los públicos. Ello supone la necesidad de discutir no sólo sobre las distintas acepciones de la noción de participación, sino también, y esencialmente, distintas formas básicas de participación −recuperables en tácticas que devienen de aspectos generales y particulares− al convocar a los públicos. Se promueve, de este modo, revisar si los museos de arte están articulando lo artístico con lo social o, por el contrario, privilegian una de estas dimensiones.

Chimeric antigen receptor (CAR)-T cells have demonstrated clinical potential, but current receptors still need improvements to be successful against chronic HIV infection. In this study, we address some requirements of CAR motifs for strong surface expression of a novel anti-HIV CAR by evaluating important elements in the extracellular, hinge, and transmembrane (TM) domains. When combining a truncated CD4 extracellular domain and CD8α hinge/TM, the novel CAR did not express extracellularly but was detectable intracellularly. By shortening the CD8α hinge, CD4-CAR surface expression was partially recovered and addition of the LYC motif at the end of the CD8α TM fully recovered both intracellular and extracellular CAR expression. Mutation of LYC to TTA or TTC showed severe abrogation of CAR expression by flow cytometry and confocal microscopy. Additionally, we determined that CD4-CAR surface expression could be maximized by the removal of FQKAS motif at the junction of the extracellular domain and the hinge region. CD4-CAR surface expression also resulted in cytotoxic CAR T cell killing of HIV Env+ target cells. In this study, we identified elements that are crucial for optimal CAR surface expression, highlighting the need for structural analysis studies to establish fundamental guidelines of CAR designs.

Abstract Background Multiple sclerosis (MS) is a neuroinflammatory disease in which pregnancy leads to a temporary amelioration in disease activity as indicated by the profound decrease in relapses rate during the 3rd trimester of pregnancy. CD4+ and CD8+ T cells are implicated in MS pathogenesis as being key regulators of inflammation and brain lesion formation. Although Tcells are prime candidates for the pregnancy-associated improvement of MS, the precise mechanisms are yet unclear, and in particular, a deep characterization of the epigenetic and transcriptomic events that occur in peripheral T cells during pregnancy in MS is lacking. Methods Women with MS and healthy controls were longitudinally sampled before, during (1st, 2nd and 3rd trimesters) and after pregnancy. DNA methylation array and RNA sequencing were performed on paired CD4+ and CD8+ T cells samples. Differential analysis and network-based approaches were used to analyze the global dynamics of epigenetic and transcriptomic changes. Results Both DNA methylation and RNA sequencing revealed a prominent regulation, mostly peaking in the 3rd trimester and reversing post-partum, thus mirroring the clinical course with improvement followed by a worsening in disease activity. This rebound pattern was found to represent a general adaptation of the maternal immune system, with only minor differences between MS and controls. By using a network-based approach, we highlighted several genes at the core of this pregnancy-induced regulation, which were found to be enriched for genes and pathways previously reported to be involved in MS. Moreover, these pathways were enriched for in vitro stimulated genes and pregnancy hormones targets. Conclusion This study represents, to our knowledge, the first in-depth investigation of the methylation and expression changes in peripheral CD4+ and CD8+ T cells during pregnancy in MS. Our findings indicate that pregnancy induces profound changes in peripheral T cells, in both MS and healthy controls, which are associated with the modulation of inflammation and MS activity.

Background and aims: Functional motor disorders (FMD) present a prevalent, yet misunderstood spectrum of neurological conditions characterized by abnormal movements (i.e., functional limb weakness, tremor, dystonia, gait impairments), leading to substantial disability and diminished quality of life. Despite their high prevalence, FMD often face delayed diagnosis and inadequate treatment, resulting in significant social and economic burdens. The old concept of psychological factors as the primary cause (conversion disorder) has been abandoned due to the need for more evidence about their causal role. According to a predictive coding account, the emerging idea is that symptoms and disability may depend on dysfunctions of a specific neural system integrating interoception, exteroception, and motor control. Consequently, symptoms are construed as perceptions of the body's state. Besides the main pathophysiological features (abnormal attentional focus, beliefs/expectations, and sense of agency), the lived experience of symptoms and their resulting disability may depend on an altered integration at the neural level of interoception, exteroception, and motor control. Methods and materials: Our proposal aims to elucidate the pathophysiological mechanisms of FMD through a three-stage research approach. Initially, a large cohort study will collect behavioral, neurophysiological, and MRI biomarkers from patients with FMD and healthy controls, employing eXplainable Artificial Intelligence (XAI) to develop a diagnostic algorithm. Subsequently, validation will occur using patients with organic motor disorders. Finally, the algorithm's prognostic value will be explored post-rehabilitation in one subgroup of patients with FMD. Results: Data collection for the present study started in May 2023, and by May 2025, data collection will conclude. Discussion: Our approach seeks to enhance early diagnosis and prognostication, improve FMD management, and reduce associated disability and socio-economic costs by identifying disease-specific biomarkers. Trial registration: This trial was registered in clinicaltrials.gov (NCT06328790). [ABSTRACT FROM AUTHOR]

Despite the many potential applications of an accurate indoor positioning system (IPS), no universal, readily available system exists. Much of the IPS research to date has been based on the use of radio transmitters as positioning beacons. Visible light positioning (VLP) instead uses LED lights as beacons. Either cameras or photodiodes (PDs) can be used as VLP receivers, and position estimates are usually based on either the angle of arrival (AOA) or the strength of the received signal. Research on the use of AOA with photodiode receivers has so far been limited by the lack of a suitable compact receiver. The quadrature angular diversity aperture receiver (QADA) can fill this gap. In this paper, we describe a new QADA design that uses only three readily available parts: a quadrant photodiode, a 3D-printed aperture, and a programmable system on a chip (PSoC). Extensive experimental results demonstrate that this design provides accurate AOA estimates within a room-sized test chamber. The flexibility and programmability of the PSoC mean that other sensors can be supported by the same PSoC. This has the potential to allow the AOA estimates from the QADA to be combined with information from other sensors to form future powerful sensor-fusion systems requiring only one beacon. [ABSTRACT FROM AUTHOR]

Background: Isolated rapid eye movement sleep behavioral disorder (iRBD) can precede neurodegenerative diseases. There is an urgent need for biomarkers to aid early intervention and neuroprotection. Objective: The aim is to assess quantitative motor, cognitive, and brain magnetic resonance imaging (MRI) characteristics in iRBD patients. Methods: Thirty‐eight polysomnography‐confirmed iRBD patients and 28 age‐ and sex‐matched healthy controls underwent clinical, cognitive, and motor functional evaluations, along with brain MRI. Motor tasks included nine‐hole peg test, five‐times‐sit‐to‐stand test, timed‐up‐and‐go test, and 4‐meter walking test with and without cognitive dual task. Quantitative spatiotemporal gait parameters were obtained using an optoelectronic system. Brain MRI analysis included functional connectivity (FC) of the main resting‐state networks, gray matter (GM) volume using voxel‐based morphometry, cortical thickness, and deep GM and brainstem volumes using FMRIB's Integrated Registration and Segmentation Tool and FreeSurfer. Results: iRBD patients relative to healthy subjects exhibited a poorer performance during the nine‐hole peg test and five‐times‐sit‐to‐stand test, and greater asymmetry of arm‐swing amplitude and stride length variability during dual‐task gait. Dual task significantly worsened the walking performance of iRBD patients more than healthy controls. iRBD patients exhibited nonmotor symptoms, and memory, abstract reasoning, and visuospatial deficits. iRBD patients exhibited decreased FC of pallidum and putamen within the basal ganglia network and occipital and temporal areas within the visuo‐associative network, and a reduced volume of the supramarginal gyrus. Brain functional alterations correlated with gait changes. Conclusions: Subtle motor and nonmotor alterations were identified in iRBD patients, alongside brain structural and functional MRI changes. These findings may represent early signs of neurodegeneration and contribute to the development of predictive models for progression to parkinsonism. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Este trabajo aborda algunos aspectos de la dimensión social y política del museo en la actualidad, a partir de la articulación de distintas perspectivas vinculadas con las políticas de los bienes comunes, la sociomuseología y la museología participativa. Este cruce teórico permitió diseñar un escenario o un subescenario -según qué lectura se pondere- político-museológico en el que, consideramos, existe una apuesta por una diferenciación de los modelos tradicionales.

Two analogous 2-D Hofmann-type frameworks, which incorporate the novel ligand N-(pyridin-4-yl)benzamide (benpy) [FeII(benpy)2M(CN)4]·2H2O (M = Pd (Pd(benpy)) and Pt (Pt(benpy))) are reported. The benpy ligand was explored to facilitate spin-crossover (SCO) cooperativity via amide group hydrogen bonding. Structural analyses of the 2-D Hofmann frameworks revealed benpy-guest hydrogen bonding and benpy-benpy aromatic contacts. Both analogues exhibited single-step hysteretic spin-crossover (SCO) transitions, with the metal-cyanide linker (M = Pd or Pt) impacting the SCO spin-state transition temperature and hysteresis loop width (Pd(benpy): T½↓↑: 201, 218 K, ∆T: 17 K and Pt(benpy): T½↓↑: 206, 226 K, ∆T: 20 K). The parallel structural and SCO changes over the high-spin to low-spin transition were investigated using variable-temperature, single-crystal, and powder X-ray diffraction, Raman spectroscopy, and differential scanning calorimetry. These studies indicated that the ligand–guest interactions facilitated by the amide group acted to support the cooperative spin-state transitions displayed by these two Hofmann-type frameworks, providing further insight into cooperativity and structure–property relationships.

Chimeric antigen receptor (CAR)-T cells have demonstrated clinical potential, but current receptors still need improvements to be successful against chronic HIV infection. In this study, we address some requirements of CAR motifs for strong surface expression of a novel anti-HIV CAR by evaluating important elements in the extracellular, hinge, and transmembrane (TM) domains. When combining a truncated CD4 extracellular domain and CD8α hinge/TM, the novel CAR did not express extracellularly but was detectable intracellularly. By shortening the CD8α hinge, CD4-CAR surface expression was partially recovered and addition of the LYC motif at the end of the CD8α TM fully recovered both intracellular and extracellular CAR expression. Mutation of LYC to TTA or TTC showed severe abrogation of CAR expression by flow cytometry and confocal microscopy. Additionally, we determined that CD4-CAR surface expression could be maximized by the removal of FQKAS motif at the junction of the extracellular domain and the hinge region. CD4-CAR surface expression also resulted in cytotoxic CAR T cell killing of HIV Env+ target cells. In this study, we identified elements that are crucial for optimal CAR surface expression, highlighting the need for structural analysis studies to establish fundamental guidelines of CAR designs. [ABSTRACT FROM AUTHOR]

Summary: In this article we use high-throughput epigenomics, transcriptomics, and proteomics data to construct fine-graded models of the “protein-coding units” gathering all transcript isoforms and chromatin accessibility peaks associated with more than 4000 genes in humans. Each protein-coding unit has the structure of a directed acyclic graph (DAG) and can be represented as a Bayesian network. The factorization of the joint probability distribution induced by the DAGs imposes a number of conditional independence relationships among the variables forming a protein-coding unit, corresponding to the missing edges in the DAGs. We show that a large fraction of these conditional independencies are indeed verified by the data. Factors driving this verification appear to be the structural and functional annotation of the transcript isoforms, as well as a notion of structural balance (or frustration-free) of the corresponding sample correlation graph, which naturally leads to reduction of correlation (and hence to independence) upon conditioning.

Here, Fahlberg et al. describe the cellular immune response during acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates. The study identifies associations of monocytes and macrophage subtypes in lungs with disease outcome, IL-6 and IL-10 ratio in plasma, and viral replication in bronchial brushes.

Saber quiénes son sus visitantes es una de las principales tareas de los museos en la actualidad, en la medida en que fluctúan entre ajustarse a las imposiciones del sistema capitalista y convertirse en instituciones democráticas y participativas. No obstante, este aspecto resulta aun más dificultoso en los museos de arte, en virtud de los atributos particulares de su estructura y actores. El presente trabajo tiene como objetivo aproximar algunos criterios que permitan conocer quiénes son los visitantes de los museos de arte creados en Argentina desde el inicio del nuevo milenio. Dada la magnitud del desafío, se procura, con el foco puesto en un caso particular, trazar algunos lineamientos sostenidos en los enfoques teórico-críticos aplicados a la museología y en los estudios de públicos. En cuanto a lo metodológico, se recurrió a un estudio de visitantes que apeló a orientaciones cuantitativas y cualitativas, realizado en el Museo de Arte de Tigre durante 2017, centrado en los públicos del fin de semana. Se considera que, al indagar los rasgos singulares de esta entidad patrimonial, pueden identificarse algunos indicios que permitan comenzar a trazar un perfil, tanto general como específico, de los visitantes de los museos de arte.

La pandemia que afecta al mundo, desde el 2020, aceleró la posibilidad de convertir al museo en un facilitador de interacciones con y desde los públicos/destinatarios. En este sentido, la comunicación mediatizada se convierte en una posibilidad viable para comprender este cambio de paradigma al que aspiran este tipo de institución cultural. Se apela, de este modo, a un enfoque interdisciplinar que atiende a una articulación entre el estudio de los museos y del marketing digital, bajo la mirada general de la comunicación mediatizada. Puntualmente, aquí, no abocaremos a analizar cuatro tipos de contenidos digitales presentes en las plataformas de los museos, con el propósito de delimitar sus rasgos en el presente y el tipo de relación que establecen con los públicos/destinatarios al proyectarse desde las tecnologías digitales.

On September 6, 2017, Hurricane Irma, a Category 5 storm packing winds of 185 miles per hour skirted the northern coast of Puerto Rico, leaving 1 million residents without electrical power. Schools were closed for 5 days, but a major calamity was narrowly avoided. Overall, residents were grateful for their good fortune, but the same could not be said for the islands of Antigua and Barbuda, where the storm destroyed 90% of the buildings and left 50% of the population homeless. Two weeks later, hurricane Maria ravaged Puerto Rico with wind gusts of 150 miles per hour and widespread flooding. Maria was the strongest hurricane to strike the island in 80 years. One hundred percent of the island was without electricity; water from the ocean and swollen rivers inundated many communities; many roads were impassible due to downed trees; and a number of bridges were washed away, preventing access to residents who desperately needed basic supplies required for survival. Five days after Maria slammed Puerto Rico, author Frank J. Zenere, school psychologist and chair of the crisis management program in the Miami-Dade County Public Schools, and an Emeritus of the National Emergency Assistance Team was contacted by a clinical psychologist he met 2 months earlier at a training. The psychologist worked closely with a mental health professional on the island, who serves as an advisor to the Secretary of Education of Puerto Rico. This connection led to a conference call to discuss their concerns, identify needs and available resources, and plan for the reopening of schools. Near the end of an hour-long dialogue, Zenere volunteered to go to the island to provide further consultation, assist in providing technical assistance, conduct training for school mental health professionals, and offer recommendations for preparing to meet the short and long-term needs of students, their families, teachers, and support staff. Zenere writes that he believes following a natural disaster, immediate attention should be focused upon meeting the needs of the population including food, water, and shelter. After that the next important step in the recovery process is the reopening of schools. This article details Zenere's journey through the seven days he was there as he helped set the foundation for recovery efforts following this devastating natural disaster. He shares his thoughts on recovery assistance based on his experiences with numerous other natural disasters around the globe.

Las lógicas y prácticas que establece el modelo museístico contemporáneo implican diferentes transformaciones, entre ellas, destacamos la nueva relación que se impulsa con los visitantes. Estamos ante un cambio en el proceso comunicativo emisor-receptor que reconstruye la relación museales-visitantes. Para dar cuenta de ello, en un primer momento, realizaremos una breve introducción de los estudios de recepción identificando al museo como medio masivo, y su posible consumo por parte de los visitantes. Luego, nos detendremos en los aportes de los estudios de visitantes como una herramienta valida para generar acciones de diálogo con sus destinatarios o proyectarse como espacios-servicios. Para, finalmente analizar este fenómeno desde los museos argentinos, e identificar cómo están pensando sus visitantes.

El modelo museístico contemporáneo establece una lógica de disciplinamiento vinculado a múltiples ofertas de experiencias, de entretenimiento, de consumo y de diálogo. En este esquema, los gustos, los intereses y las necesidades de los visitantes se vuelven fundamentales para que el museo se reconfigure ante los desafíos del sistema capitalista. La discusión del presente texto, abordará las contrariedades que presentan los museos de arte argentinos al generar instancias de indagación sobre sus públicos. Para ello, el trabajo procura desentrañar el nuevo vínculo que se establece con los visitantes desde un contexto determinado y una tipología específica, lo que ayuda a comprender la dinámica que adquieren estos establecimientos en la contemporaneidad. En líneas generales, se apela a un cruce de contenidos sustentados en los enfoques teóricos críticos aplicados a la museología y los estudios de visitantes y, en lo específico, se aportan datos analíticos sobre la utilización los estudios de visitantes en los museos de arte argentinos. Además, se recurre al estudio de casos múltiples al describir algunos estudios que permiten reconocer instancias de diálogo en la dinámica museal.

El presente trabajo tiene como objetivo delinear y articular diferentes abordajes de la exposición que permiten problematizar los modos de exhibir el arte en la contemporaneidad. Dada la magnitud del desafío, se procura trazar algunos lineamientos desde el cruce de los Estudios Visuales con los enfoques teórico-críticos aplicados a la museología. Se propone una metodología cualitativa que parte de la museología de la idea (García Blanco, 1999) y se la amplía a partir de los giros temáticos de lo global (Guasch, 2016) y la noción de constelación (Benjamin, 2005; Didi-Huberman, 2008, 2011). Con esta articulación buscamos caracterizar y comparar estas propuestas museográficas que coexisten en una trama compleja y se contaminan entre sí. Si bien tenemos en claro que cada caso se pronuncia de manera específica, esta aproximación busca explorar los rasgos generales de la convivencia de estos modos de exhibir y los desafíos del tiempo presente, tomando en cuenta tanto la expansión de los límites del sistema del arte, como las incumbencias y los problemas disciplinares que allí se mixturan.

A fines del siglo XX, se instaura un tipo de museo que se nombra como tardocapitalista o global, el cual presenta una nueva estructura en la que la caracterización y acciones de sus directivos resultan clave para interpretarla. El rol de estos actores ya no solo les demanda saberes sobre el acervo, sino la capacidad de promover acciones vinculadas con lo empresarial, lo cual puede leerse al articular diferentes enfoques teórico-críticos aplicados a la museología. A fin de exponer algunas especificidades de dichos rasgos, se realiza un breve señalamiento de ciertas acciones llevadas adelante por sus directores en dos museos argentinos de arte, entre fines de la década del noventa y principios del siglo XXI: el Museo de Arte Contemporáneo de Bahía Blanca (Buenos Aires) y el Museo de Arte Contemporáneo de Rosario (Santa Fe).

Los museos producen mensajes para legitimar y desarrollar un relato sobre su colección a través de sus espacios expositivos, actividades educativas, eventos masivos, publicaciones, entre otras opciones. En la actualidad, las piezas gráficas o editoriales se convierten en herramientas que permiten acercarse a las prácticas comunicacionales que operan en este tipo de institución cultural. Por ello, el presente trabajo tiene por objetivo desentrañar algunas transformaciones que se producen en este tipo de dispositivo en el modelo museístico contemporáneo. Esta exploración articula enfoques teóricos críticos museológicos y estudios de lo comunicacional. En este entrecruzamiento se busca, primeramente, trabajar el uso de este tipo de dispositivos, luego, definir algunos rasgos significativos que cobran las publicaciones en la actualidad a partir de los cruces entre comercial-experiencia-TIC, para confluir en un posible ejemplo de este tipo de propuesta llevada adelante por el museo argentino Castagnino+macro.

Complex eukaryotic promoters normally contain multiple cis-regulatory sequences for different transcription factors (TFs). The binding patterns of the TFs to these sites, as well as the way the TFs interact with each other and with the RNA polymerase (RNAp), lead to combinatorial problems rarely understood in detail, especially under varying epigenetic conditions. The aim of this paper is to build a model describing how the main regulatory cluster of the olfactory receptor Or59b drives transcription of this gene in Drosophila. The cluster-driven expression of this gene is represented as the equilibrium probability of RNAp being bound to the promoter region, using a statistical thermodynamic approach. The RNAp equilibrium probability is computed in terms of the occupancy probabilities of the single TFs of the cluster to the corresponding binding sites, and of the interaction rules among TFs and RNAp, using experimental data of Or59b expression to tune the model parameters. The model reproduces correctly the changes in RNAp binding probability induced by various mutation of specific sites and epigenetic modifications. Some of its predictions have also been validated in novel experiments.