Miracle-dz/UniFAR-FTUs huggingface dataset:
The Parkinson’s disease-associated gene ITPKB protects against α-synuclein aggregation by regulating ER-to-mitochondria calcium release

Significance Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease of aging, affecting approximately 10 million patients worldwide with no approved therapies to modify progression of disease. Further understanding of the cellular mechanisms contributing to the development of PD is necessary to discover therapies. Here, we characterize the role of a recently identified GWAS hit for sporadic PD, ITPKB, in the aggregation of α-synuclein, the primary pathological feature of disease. These results identify inhibition of inositol-1,4,5,-triphosphate (IP3)-mediated ER-to-mitochondria calcium release as a potential therapeutic approach for reducing neuropathology in PD. Inositol-1,4,5-triphosphate (IP3) kinase B (ITPKB) is a ubiquitously expressed lipid kinase that inactivates IP3, a secondary messenger that stimulates calcium release from the endoplasmic reticulum (ER). Genome-wide association studies have identified common variants in the ITPKB gene locus associated with reduced risk of sporadic Parkinson’s disease (PD). Here, we investigate whether ITPKB activity or expression level impacts PD phenotypes in cellular and animal models. In primary neurons, knockdown or pharmacological inhibition of ITPKB increased levels of phosphorylated, insoluble α-synuclein pathology following treatment with α-synuclein preformed fibrils (PFFs). Conversely, ITPKB overexpression reduced PFF-induced α-synuclein aggregation. We also demonstrate that ITPKB inhibition or knockdown increases intracellular calcium levels in neurons, leading to an accumulation of calcium in mitochondria that increases respiration and inhibits the initiation of autophagy, suggesting that ITPKB regulates α-synuclein pathology by inhibiting ER-to-mitochondria calcium transport. Furthermore, the effects of ITPKB on mitochondrial calcium and respiration were prevented by pretreatment with pharmacological inhibitors of the mitochondrial calcium uniporter complex, which was also sufficient to reduce α-synuclein pathology in PFF-treated neurons. Taken together, these results identify ITPKB as a negative regulator of α-synuclein aggregation and highlight modulation of ER-to-mitochondria calcium flux as a therapeutic strategy for the treatment of sporadic PD.
Transfer of information across repeated decisions in general and in obsessive–compulsive disorder

Significance Real-life decisions are often repeated. Whether considering taking a new job, or doing something mundane like checking if the stove is off, people frequently revisit decisions. This mode of behavior takes a particularly pathological form in obsessive–compulsive disorder (OCD). Surprisingly, little is known about how information is transferred across decisions, and whether and how such transfer is disrupted in OCD. Data from a repeated decision-making task and computational modeling revealed that different memory systems separately biased repeated decisions toward previous choices by changing how people weigh evidence. Transfer specifically driven by implicit memory was reduced in individuals with higher levels of OCD symptoms on top of other baseline decision-making deficits, offering computational insight into checking behavior. Real-life decisions are often repeated. Whether considering taking a job in a new city, or doing something mundane like checking if the stove is off, decisions are frequently revisited even if no new information is available. This mode of behavior takes a particularly pathological form in obsessive–compulsive disorder (OCD), which is marked by individuals’ redeliberating previously resolved decisions. Surprisingly, little is known about how information is transferred across decision episodes in such circumstances, and whether and how such transfer varies in OCD. In two experiments, data from a repeated decision-making task and computational modeling revealed that both implicit and explicit memories of previous decisions affected subsequent decisions by biasing the rate of evidence integration. Further, we replicated previous work demonstrating impairments in baseline decision-making as a function of self-reported OCD symptoms, and found that information transfer effects specifically due to implicit memory were reduced, offering computational insight into checking behavior.
ELF3 Overexpression as Prognostic Biomarker for Recurrence of Stage II Colorectal Cancer

Background/Aim: Adjuvant chemotherapy for high-risk Stage II colorectal cancer (CRC) is weakly recommended; however, no consensus exists on “high-risk” definition. Prognostic biomarker identification is important for selecting patients with poor prognosis who may benefit from adjuvant chemotherapy. Materials and Methods: Using Microarray data analyses, ELF3 was identified as a candidate gene highly expressed in Stage II CRC with distant recurrences. ELF3 mRNA expression in 168 Stage II CRC patients was subjected to quantitative RT-PCR analysis and ELF3 protein expression in 185 patients was quantified by immunohistochemical analysis. The relationship between mRNA and protein expression levels and patient characteristics were also investigated. Results: The overall recurrence rate and relapse-free survival were significantly poorer in the ELF3 high-expression than the low-expression group at the mRNA and protein levels. High ELF3 mRNA and protein expression levels were independent poor prognostic factors. Conclusion: High ELF3 expression was associated with recurrence of Stage II.
Astrocyte-secreted IL-33 mediates homeostatic synaptic plasticity in the adult hippocampus

Significance Synaptic plasticity in the hippocampus is important for learning and memory formation. In particular, homeostatic synaptic plasticity enables neurons to restore their activity levels in response to chronic neuronal activity changes. While astrocytes modulate synaptic functions via the secretion of factors, the underlying molecular mechanisms remain unclear. Here, we show that suppression of hippocampal neuronal activity increases cytokine IL-33 release from astrocytes in the CA1 region. Activation of IL-33 and its neuronal ST2 receptor complex promotes functional excitatory synapse formation. Moreover, IL-33/ST2 signaling is important for the neuronal activity blockade-induced increase of CA1 excitatory synapses in vivo and spatial memory formation. This study suggests that astrocyte-secreted IL-33 acts as a negative feedback control signal to regulate hippocampal homeostatic synaptic plasticity. Hippocampal synaptic plasticity is important for learning and memory formation. Homeostatic synaptic plasticity is a specific form of synaptic plasticity that is induced upon prolonged changes in neuronal activity to maintain network homeostasis. While astrocytes are important regulators of synaptic transmission and plasticity, it is largely unclear how they interact with neurons to regulate synaptic plasticity at the circuit level. Here, we show that neuronal activity blockade selectively increases the expression and secretion of IL-33 (interleukin-33) by astrocytes in the hippocampal cornu ammonis 1 (CA1) subregion. This IL-33 stimulates an increase in excitatory synapses and neurotransmission through the activation of neuronal IL-33 receptor complex and synaptic recruitment of the scaffold protein PSD-95. We found that acute administration of tetrodotoxin in hippocampal slices or inhibition of hippocampal CA1 excitatory neurons by optogenetic manipulation increases IL-33 expression in CA1 astrocytes. Furthermore, IL-33 administration in vivo promotes the formation of functional excitatory synapses in hippocampal CA1 neurons, whereas conditional knockout of IL-33 in CA1 astrocytes decreases the number of excitatory synapses therein. Importantly, blockade of IL-33 and its receptor signaling in vivo by intracerebroventricular administration of its decoy receptor inhibits homeostatic synaptic plasticity in CA1 pyramidal neurons and impairs spatial memory formation in mice. These results collectively reveal an important role of astrocytic IL-33 in mediating the negative-feedback signaling mechanism in homeostatic synaptic plasticity, providing insights into how astrocytes maintain hippocampal network homeostasis.
Drosophila melanogaster sex peptide regulates mated female midgut morphology and physiology

Significance We describe a role for the seminal fluid protein Sex Peptide (SP) in regulating the post-mating morphology and physiology of the female digestive tract. We show that females must receive SP to increase their midgut size following mating, a response that is important for female fecundity. Receiving SP is also important for post-mating changes in the expression of digestive enzyme and metabolic genes in the midgut. This is a significant step in our understanding of how female physiology shifts to cope with the metabolic demands of reproduction. Our study reveals another mechanism through which the male can alter female post-mating physiology to enhance reproductive output. Drosophila melanogaster females experience a large shift in energy homeostasis after mating to compensate for nutrient investment in egg production. To cope with this change in metabolism, mated females undergo widespread physiological and behavioral changes, including increased food intake and altered digestive processes. The mechanisms by which the female digestive system responds to mating remain poorly characterized. Here, we demonstrate that the seminal fluid protein Sex Peptide (SP) is a key modulator of female post-mating midgut growth and gene expression. SP is both necessary and sufficient to trigger post-mating midgut growth in females under normal nutrient conditions, and likely acting via its receptor, Sex Peptide Receptor (SPR). Moreover, SP is responsible for almost the totality of midgut transcriptomic changes following mating, including up-regulation of protein and lipid metabolism genes and down-regulation of carbohydrate metabolism genes. These changes in metabolism may help supply the female with the nutrients required to sustain egg production. Thus, we report a role for SP in altering female physiology to enhance reproductive output: Namely, SP triggers the switch from virgin to mated midgut state.
YES I CAN EXERCISE ADOPTION/ADHERENCE MODEL

Annotation Although other correlates of physical activity among youth have not been clearly established, a growing literature has suggested that social-cognitive factors such as attitudes, social norms and self-efficacy influence the decision to become physically active among youth. The “yes i can” builds on existing prominent theoretical models employed to study physical activity determinants and provides a curriculum design framework for the development of specific fitness education programs in schools and other educational settings.
Improvement of hand functions of spinal cord injury patients with electromyography-driven hand exoskeleton: A feasibility study

Abstract We have developed a one-of-a-kind hand exoskeleton, called Maestro, which can power finger movements of those surviving severe disabilities to complete daily tasks using compliant joints. In this paper, we present results from an electromyography (EMG) control strategy conducted with spinal cord injury (SCI) patients (C5, C6, and C7) in which the subjects completed daily tasks controlling Maestro with EMG signals from their forearm muscles. With its compliant actuation and its degrees of freedom that match the natural finger movements, Maestro is capable of helping the subjects grasp and manipulate a variety of daily objects (more than 15 from a standardized set). To generate control commands for Maestro, an artificial neural network algorithm was implemented along with a probabilistic control approach to classify and deliver four hand poses robustly with three EMG signals measured from the forearm and palm. Increase in the scores of a standardized test, called the Sollerman hand function test, and enhancement in different aspects of grasping such as strength shows feasibility that Maestro can be capable of improving the hand function of SCI subjects.
Women and Rural Revolt in India

Women's major productive role (outside of the home) in agriculture and the crucial part which women play in peasant revolts have been more or less ignored by social scientists. In this paper an attempt is made to analyse the interconnections between class and sexual oppression, and between women's movements and class struggle, in rural India: with class structure, the nature of society, and the development of social movements looked at from the viewpoint of women themselves. With the use of two key concepts, work participation and mode of production, it is argued that in India, increasingly during the last decade, capitalism has developed in the countryside, and that, with the changing social relations of production, there has emerged a mass‐based and militant women's movement, whose objective basis has been the militancy of women of the rural poor. This is illustrated for a variety of Indian states, but especially for the state of Maharashtra.
Crenças e emoções no cotidiano de uma professora de língua inglesa: uma pesquisa sociocultural

A partir do momento em que o ensino-aprendizagem de lingua inglesa (LI) passou a ser compreendido atraves da perspectiva sociocultural (LANTOLF 2000, 2010; LANTOLF; THORNE, 2006; VYGOTSKY, 1978, 1986), houve uma ressignificacao na formacao docente onde as experiencias de vida dos professores passaram a ser valorizadas. (ABRAHAO, 2010). Tendo em conta este cenario, a trajetoria percorrida pelo profissional, suas crencas e emocoes tornaram-se relevantes para a compreensao de sua pratica docente. Para o desenvolvimento desta pesquisa, optou-se por realizar um estudo qualitativo etnografico envolvendo uma investigacao narrativa. A pesquisa, desenvolvida entre julho e novembro de 2018, conta com a participacao de uma professora de LI de uma escola particular em uma cidade no interior do Rio Grande do Sul. O objetivo deste estudo e investigar reflexivamente as perspectivas da professora participante a respeito de sua trajetoria de ensino-aprendizagem de LI, e as percepcoes sobre sua pratica docente, mapeando as crencas e emocoes que permeiam a sua historia profissional. Para a coleta dos dados, foram utilizadas entrevistas narrativas semiestruturadas, gravacoes em audio, observacoes de aulas, gravacoes em video, diarios de campo, notas de campo, autoscopias, e um encontro- fechamento. Os dados foram triangulados e analisados a partir do desenvolvimento de um Marco de Referencia. (MICCOLI, 2014). Os resultados do estudo revelaram que, a partir da reflexao, a professora participante revisitou suas emocoes, percebeu e reformulou crencas, e passou por um processo de autoconhecimento.
Long Lasting Memories, una plataforma TIC integrada contra el deterioro cognitivo relacionado con la edad: estudio de usabilidad

En Europa la poblacion mayor de 65 anos se esta incrementando y seguira aumentando en las proximas decadas. Las consecuencias de este cambio demografico plantea dificultades para dar respuesta a las necesidades de atencion de este grupo poblacional. La integracion de nuevas tecnologias ofrece la posibilidad de intervenir a mayor escala. En el campo de la investigacion psicogeriatrica se ha producido en los ultimos anos un gran desarrollo de la tecnologia de software con el objetivo de mejorar la calidad de vida de las personas mayores, asi como prevenir el deterioro cognitivo asociado al envejecimiento. Sin embargo, las personas mayores no tienen experiencia en el uso de las TIC y muchas de estas tecnologias no han sido desarrolladas para ser utilizadas por las personas mayores, ademas un numero escaso de esas aplicaciones han sido analizadas en terminos de su usabilidad en poblacion mayor con y sin deterioro cognitivo. Esta tesis doctoral se enmarca dentro del campo de la usabilidad y experiencia de usuario. El objetivo general de esta tesis es analizar la usabilidad de una plataforma de entrenamiento fisico y cognitivo en poblacion mayor espanola con y sin deterioro cognitivo asi como en los profesionales encargados de la intervencion. La tesis se estructura en una primera parte de contextualizacion teorica, justificacion, objetivos y metodo y una segunda parte de resultados con datos cualitativos y cuantitativos, su discusion y conclusiones. En cuanto a las conclusiones de esta tesis doctoral cabe resaltar la importancia que los resultados del estudio de usabilidad del programa Long Lasting Memories tienen, ya que hasta la fecha no hemos encontrado otros estudios en poblacion espanola que evaluen la usabilidad y experiencia de usuario de un programa de entrenamiento fisico y cognitivo por medio de nuevas tecnologias en poblacion mayor con y sin deterioro cognitivo. De este modo la presente investigacion genera un marco que permite advertir las necesidades de usabilidad de este grupo poblacional.
Association Between Obstructive Sleep Apnea, Its Treatment, and Alzheimer's Disease: Systematic Mini-Review

Obstructive sleep apnea (OSA) and Alzheimer's disease (AD) are common in the elderly population. Obstructive sleep apnea that may cause significant changes in the cerebrospinal fluid β-amyloid and T-tau and/or P-tau protein levels is often identified as a risk factor for development of AD. Although the underlying mechanisms of AD are still not fully understood, a hypothesis associating OSA with AD has been already proposed. In this systematic mini-review, we first discuss the recent findings supporting the association of OSA with an increased risk of AD and then provide evidence suggesting the positive effect of OSA treatment on a reduced risk of AD.
Psychological and Cognitive Aspects of Ageing: The Importance of Driving on Senior Living

This research aims to understand the psychological, the social and cognitive aspects of ageing and assess the relevance of driving a personal automobile to seniors. We know that biological ageing is an inescapable fact, but is there also a psychological and a cognitive ageing? If so, is it related to getting older or to other factors? How relevant is continuing to drive to seniors, and how can the activity influence psychological and cognitive types of their ageing and self well-being? To answer these questions, we study several authors and concepts about mental health, development of ageing and their relationship to driving. We also explore psychological and cognitive changes associated with ageing, the principal behavioural changes of healthy senior people (with normal cognitive function) and MCI (mild cognitive impairment), as well as how driving inhibition can induce and affect psychological and cognitive characteristics. We conclude that low mental functioning is caused by a set of biological, psychological and social factors, connected in turn to environmental factors. The slowdown of cognitive activities and performances in seniors is not inevitably accompanied by a decrease in intellectual capacity, low sensory acuity, or slowing psychomotor skills. Other factors should be considered—such as health status, limitations, anxiety, lack of interest, motivation and attitudes. The loss of cognitive abilities and the prevalence of mild cognitive impairment increase with age and are a growing concern, especially among seniors who drive cars. However, we still lack specific evidence based on tests and criteria—in particular, on psychological and cognitive domains—to assess senior drivers actually at risk. It is important to establish a base of evidence to allow objective risk determination. The safest senior drivers should continue driving for as long as possible, thereby contributing to their mental health, independence and quality of life.
OPC structures for maskshops qualification for the CMOS65nm and CMOS45nm nodes

Several qualification stages are required for new maskshop tools, first step is done by the maskshop internally. Taking a new writer for example, the maskshop will review the basic factory and site acceptance tests, including CD uniformity, CD linearity, local CD errors and registration errors. The second step is to have dedicated OPC (Optical Proximity Correction) structures from the wafer fab. These dedicated OPC structures will be measured by the maskshop to get a reticle CD metrology trend line. With this trend line, we can: - ensure the stability at reticle level of the maskshop processes - put in place a matching procedure to guarantee the same OPC signature at reticle level in case of any internal maskshop process change or new maskshop evaluation. Changes that require qualification could be process changes for capacity reasons, like introducing a new writer or a new manufacturing line, or for capability reasons, like a new process (new developer tool for example) introduction. Most advanced levels will have dedicated OPC structures. Also dedicated maskshop processes will be monitored with these specific OPC structures. In this paper, we will follow in detail the different reticle CD measurements of dedicated OPC structures for the three advanced logic levels of the 65nm node: poly level, contact level and metal level. The related maskshop's processes are - for poly: eaPSM 193nm with a nega CAR (Chemically Amplified Resist) process for Clear Field L/S (Lines & Space) reticles - for contact: eaPSM 193nm with a posi CAR process for Dark Field Holes reticles - for metal1: eaPSM 193nm with a posi CAR process for Dark Field L/S reticles. For all these structures, CD linearity, CD through pitch, length effects, and pattern density effects will be monitored. To average the metrology errors, the structures are placed twice on the reticle. The first part of this paper will describe the different OPC structures. These OPC structures are close to the DRM (Design Rule Manual) of the dedicated levels to be monitored. The second part of the paper will describe the matching procedure to ensure the same OPC signature at reticle level. We will give an example of an internal maskshop matching exercise, which could be needed when we switched from an already qualified 50 KeV tool to a new 50 KeV tool. The second example is the same matching exercise of our 65nm OPC structures, but with two different maskshops. The last part of the paper will show first results on dedicated OPC structures for the 45nm node.