scholarly journals Deep Learning Decodes Multi-layered Roles of Polycomb Repressor Complex 2 During Mouse CNS Development

2021 ◽  
Author(s):  
Ariane Mora ◽  
Jonathan Rakar ◽  
Ignacio Monedero Cobeta ◽  
Behzad Yaghmaeian Salmani ◽  
Annika Starkenberg ◽  
...  
Keyword(s):  
Cns Development ◽  
Full Spectrum ◽  
Transcriptomic Response ◽  
Repressor Complex ◽  
Variate Analysis ◽  
Central Nervous Systems ◽  
Embryonic Cns ◽  
Spatio Temporal ◽  
Bioinformatics Workflow

A prominent aspect of most, if not all, central nervous systems (CNSs) is that anterior regions (brain) are larger than posterior ones (spinal cord). Studies in Drosophila and mouse have revealed that the Polycomb Repressor Complex 2 (PRC2) acts by several mechanisms to promote anterior CNS expansion. However, it is unclear if PRC2 acts directly and/or indirectly upon key downstream genes, what the full spectrum of PRC2 action is during embryonic CNS development and how PRC2 integrates with the epigenetic landscape. We removed PRC2 function from the developing mouse CNS, by mutating the key gene Eed, and generated spatio-temporal transcriptomic data. We developed a bioinformatics workflow that incorporates standard statistical analyses with machine learning to integrate the transcriptomic response to PRC2 inactivation with epigenetic information from ENCODE. This multi-variate analysis corroborates the central involvement of PRC2 in anterior CNS expansion, and reveals layered regulation via PRC2. These findings uncover a differential logic for the role of PRC2 upon functionally distinct gene categories that drive CNS anterior expansion. To support the analysis of emerging multi-modal datasets, we provide a novel bioinformatics package that can disentangle regulatory underpinnings of heterogeneous biological processes.

Conceptualizing and Measuring Affective and Cognitive Empathy

2020 ◽  
pp. 8-30
Author(s):  
Ross Buck ◽  
Zhan Xu
Keyword(s):  
Mental States ◽  
Cognitive Empathy ◽  
Emotional Empathy ◽  
Symbolic Communication ◽  
Current State ◽  
Communication Processes ◽  
Neuroscience Research ◽  
Emotion Displays ◽  
Central Nervous Systems

Individual differences in the ability to recognize emotion displays relate strongly to emotional intelligence, and emotional and social competence. However, there is a difference between the ability to judge the emotions of another person (i.e., emotional empathy) and the ability to take the perspective of another person, including making accurate appraisals, attributions, and inferences about the mental states of others (i.e., cognitive empathy). In this chapter, we review the concept of emotional empathy and the current state of the field, including emerging and converging evidence from neuroscience research that emotional and cognitive empathy involve doubly dissociable brain systems. We also discuss emerging literature on the physiological mechanisms underlying empathy in the peripheral and central nervous systems. We then distinguish spontaneous and symbolic communication processes to show how cognitive empathy emerges from emotional empathy during development. Development starts with the prelinguistic mutual contingent responsiveness of infant and caregiver yielding “raw” primary intersubjectivity, then secondary and tertiary intersubjectivity advances with increasing social experience, and finally cognitive empathic abilities expand in perspective taking and Theory of Mind (ToM) skills. We then present an Affect-Reason-Involvement (ARI) model to guide the conceptualization and measurement of emotional and cognitive empathy. We consider emotion correlation scores as a flexible and valid approach to empathy measurement, with implications for understanding the role of discrete emotions in decision making. Finally, we apply this reasoning to recent studies of the role of emotion and empathy in bullying.

scholarly journals The role of Extracellular Vesicles during CNS development

2021 ◽  
pp. 102124
Author(s):  
Nasim Bahram Sangani ◽  
Gomes. Ana Rita ◽  
Leopold M.G. Curfs ◽  
Chris P. Reutelingsperger
Keyword(s):  
Extracellular Vesicles ◽  
Cns Development

scholarly journals Structural variant detection in cancer genomes: computational challenges and perspectives for precision oncology

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Ianthe A. E. M. van Belzen ◽  
Alexander Schönhuth ◽  
Patrick Kemmeren ◽  
Jayne Y. Hehir-Kwa
Keyword(s):  
Intratumor Heterogeneity ◽  
Precision Oncology ◽  
Single Nucleotide Variants ◽  
Full Spectrum ◽  
Single Nucleotide ◽  
Sequencing Technologies ◽  
Cancer Genomes ◽  
Genomic Aberrations

AbstractCancer is generally characterized by acquired genomic aberrations in a broad spectrum of types and sizes, ranging from single nucleotide variants to structural variants (SVs). At least 30% of cancers have a known pathogenic SV used in diagnosis or treatment stratification. However, research into the role of SVs in cancer has been limited due to difficulties in detection. Biological and computational challenges confound SV detection in cancer samples, including intratumor heterogeneity, polyploidy, and distinguishing tumor-specific SVs from germline and somatic variants present in healthy cells. Classification of tumor-specific SVs is challenging due to inconsistencies in detected breakpoints, derived variant types and biological complexity of some rearrangements. Full-spectrum SV detection with high recall and precision requires integration of multiple algorithms and sequencing technologies to rescue variants that are difficult to resolve through individual methods. Here, we explore current strategies for integrating SV callsets and to enable the use of tumor-specific SVs in precision oncology.

Dissecting the Role of Thyrotropin in the DNA Damage Response in Human Thyrocytes after 131I, γ Radiation and H2O2

2019 ◽  
Vol 105 (3) ◽  
pp. 839-853
Author(s):  
Aglaia Kyrilli ◽  
David Gacquer ◽  
Vincent Detours ◽  
Anne Lefort ◽  
Frédéric Libert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Iodide Uptake ◽  
Transcriptomic Response ◽  
Uptake Inhibition ◽  
Γ Radiation ◽  
Damage Response

Abstract Background The early molecular events in human thyrocytes after 131I exposure have not yet been unravelled. Therefore, we investigated the role of TSH in the 131I-induced DNA damage response and gene expression in primary cultured human thyrocytes. Methods Following exposure of thyrocytes, in the presence or absence of TSH, to 131I (β radiation), γ radiation (3 Gy), and hydrogen peroxide (H2O2), we assessed DNA damage, proliferation, and cell-cycle status. We conducted RNA sequencing to profile gene expression after each type of exposure and evaluated the influence of TSH on each transcriptomic response. Results Overall, the thyrocyte responses following exposure to β or γ radiation and to H2O2 were similar. However, TSH increased 131I-induced DNA damage, an effect partially diminished after iodide uptake inhibition. Specifically, TSH increased the number of DNA double-strand breaks in nonexposed thyrocytes and thus predisposed them to greater damage following 131I exposure. This effect most likely occurred via Gα q cascade and a rise in intracellular reactive oxygen species (ROS) levels. β and γ radiation prolonged thyroid cell-cycle arrest to a similar extent without sign of apoptosis. The gene expression profiles of thyrocytes exposed to β/γ radiation or H2O2 were overlapping. Modulations in genes involved in inflammatory response, apoptosis, and proliferation were observed. TSH increased the number and intensity of modulation of differentially expressed genes after 131I exposure. Conclusions TSH specifically increased 131I-induced DNA damage probably via a rise in ROS levels and produced a more prominent transcriptomic response after exposure to 131I.

scholarly journals Mitochondria, Oxidative Stress, cAMP Signalling and Apoptosis: A Crossroads in Lymphocytes of Multiple Sclerosis, a Possible Role of Nutraceutics

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 21
Author(s):  
Anna Signorile ◽  
Anna Ferretta ◽  
Maddalena Ruggieri ◽  
Damiano Paolicelli ◽  
Paolo Lattanzio ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Multiple Sclerosis ◽  
T Lymphocytes ◽  
Main Role ◽  
Apoptosis Resistance ◽  
Nutraceutical Compounds ◽  
Camp Pathway ◽  
Central Nervous Systems ◽  
Genetic And Environmental Factors

Multiple sclerosis (MS) is a complex inflammatory and neurodegenerative chronic disease that involves the immune and central nervous systems (CNS). The pathogenesis involves the loss of blood–brain barrier integrity, resulting in the invasion of lymphocytes into the CNS with consequent tissue damage. The MS etiology is probably a combination of immunological, genetic, and environmental factors. It has been proposed that T lymphocytes have a main role in the onset and propagation of MS, leading to the inflammation of white matter and myelin sheath destruction. Cyclic AMP (cAMP), mitochondrial dysfunction, and oxidative stress exert a role in the alteration of T lymphocytes homeostasis and are involved in the apoptosis resistance of immune cells with the consequent development of autoimmune diseases. The defective apoptosis of autoreactive lymphocytes in patients with MS, allows these cells to perpetuate, within the CNS, a continuous cycle of inflammation. In this review, we discuss the involvement in MS of cAMP pathway, mitochondria, reactive oxygen species (ROS), apoptosis, and their interaction in the alteration of T lymphocytes homeostasis. In addition, we discuss a series of nutraceutical compounds that could influence these aspects.

scholarly journals Microglia control small vessel calcification via TREM2

2021 ◽  
Vol 7 (9) ◽  
pp. eabc4898
Author(s):  
Yvette Zarb ◽  
Sucheta Sridhar ◽  
Sina Nassiri ◽  
Sebastian Guido Utz ◽  
Johanna Schaffenrath ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mouse Model ◽  
Vascular Calcification ◽  
Neurovascular Unit ◽  
Small Vessel ◽  
Vascular Pathology ◽  
Cns Development ◽  
Brain Calcification

Microglia participate in central nervous system (CNS) development and homeostasis and are often implicated in modulating disease processes. However, less is known about the role of microglia in the biology of the neurovascular unit (NVU). In particular, data are scant on whether microglia are involved in CNS vascular pathology. In this study, we use a mouse model of primary familial brain calcification, Pdgfbret/ret, to investigate the role of microglia in calcification of the NVU. We report that microglia enclosing vessel calcifications, coined calcification-associated microglia, display a distinct activation phenotype. Pharmacological ablation of microglia with the CSF1R inhibitor PLX5622 leads to aggravated vessel calcification. Mechanistically, we show that microglia require functional TREM2 for controlling vascular calcification. Our results demonstrate that microglial activity in the setting of pathological vascular calcification is beneficial. In addition, we identify a previously unrecognized function of microglia in halting the expansion of vascular calcification.

scholarly journals The Role of Spatio-Temporal Information to Govern the COVID-19 Pandemic: A European Perspective

2021 ◽  
Vol 10 (3) ◽  
pp. 166
Author(s):  
Hartmut Müller ◽  
Marije Louwsma
Keyword(s):  
European Union ◽  
Spatial Distribution ◽  
Spatial Information ◽  
National Level ◽  
Temporal Information ◽  
The European Union ◽  
Member States ◽  
Heavy Burden ◽  
Spatio Temporal

The Covid-19 pandemic put a heavy burden on member states in the European Union. To govern the pandemic, having access to reliable geo-information is key for monitoring the spatial distribution of the outbreak over time. This study aims to analyze the role of spatio-temporal information in governing the pandemic in the European Union and its member states. The European Nomenclature of Territorial Units for Statistics (NUTS) system and selected national dashboards from member states were assessed to analyze which spatio-temporal information was used, how the information was visualized and whether this changed over the course of the pandemic. Initially, member states focused on their own jurisdiction by creating national dashboards to monitor the pandemic. Information between member states was not aligned. Producing reliable data and timeliness reporting was problematic, just like selecting indictors to monitor the spatial distribution and intensity of the outbreak. Over the course of the pandemic, with more knowledge about the virus and its characteristics, interventions of member states to govern the outbreak were better aligned at the European level. However, further integration and alignment of public health data, statistical data and spatio-temporal data could provide even better information for governments and actors involved in managing the outbreak, both at national and supra-national level. The Infrastructure for Spatial Information in Europe (INSPIRE) initiative and the NUTS system provide a framework to guide future integration and extension of existing systems.

The Rhetorical Case: Its Roman Precedent and the Current Debate

1989 ◽  
Vol 19 (3) ◽  
pp. 203-226 ◽  
Author(s):  
Michael Mendelson
Keyword(s):  
Problem Solving ◽  
Technical Writing ◽  
Current Debate ◽  
Case Study Method ◽  
Full Spectrum ◽  
Problem Solving Skills ◽  
Early Case ◽  
New Phase

Because of the recent emphasis on rhetorical context in business and technical writing (BTW) instruction, the problem-solving case has become a staple in BTW classrooms. However, a number of critics have voiced concerns about the use of the rhetorical case. These concerns recall an ancient debate among Roman rhetoricians over an early case-study method called declamation. For contemporary theorists, the debate over case study revolves around its value as a stimulant to problem-solving skills, its ability to imitate the realistic circumstances of professional BTW, and its emphasis on persona and audience along with its deemphasis of the teacher. A full spectrum of arguments on these and other issues in the case-study debate indicates that the discipline is entering a new phase in its deliberations over the role of problem-solving and pragmatics in the BTW classroom.

scholarly journals From Loschmidt daemons to time-reversed waves

2016 ◽  
Vol 374 (2069) ◽  
pp. 20150156 ◽  
Author(s):  
Mathias Fink
Keyword(s):  
Wave Propagation ◽  
Time Reversal ◽  
Degrees Of Freedom ◽  
Point Of View ◽  
Propagation Time ◽  
Reversal Invariance ◽  
Spatial Boundary ◽  
Dual Approaches ◽  
Spatio Temporal

Time-reversal invariance can be exploited in wave physics to control wave propagation in complex media. Because time and space play a similar role in wave propagation, time-reversed waves can be obtained by manipulating spatial boundaries or by manipulating time boundaries. The two dual approaches will be discussed in this paper. The first approach uses ‘time-reversal mirrors’ with a wave manipulation along a spatial boundary sampled by a finite number of antennas. Related to this method, the role of the spatio-temporal degrees of freedom of the wavefield will be emphasized. In a second approach, waves are manipulated from a time boundary and we show that ‘instantaneous time mirrors’, mimicking the Loschmidt point of view, simultaneously acting in the entire space at once can also radiate time-reversed waves.

scholarly journals Prediction limits of mobile phone activity modelling

2017 ◽  
Vol 4 (2) ◽  
pp. 160900 ◽  
Author(s):  
Dániel Kondor ◽  
Sebastian Grauwin ◽  
Zsófia Kallus ◽  
István Gódor ◽  
Stanislav Sobolevsky ◽  
...  
Keyword(s):  
Mobile Phone ◽  
Spatial Scales ◽  
Urban Environments ◽  
Full Spectrum ◽  
Left Behind ◽  
Social Events ◽  
Prediction Limits ◽  
Spatio Temporal ◽  
City Structure ◽  
The City

Thanks to their widespread usage, mobile devices have become one of the main sensors of human behaviour and digital traces left behind can be used as a proxy to study urban environments. Exploring the nature of the spatio-temporal patterns of mobile phone activity could thus be a crucial step towards understanding the full spectrum of human activities. Using 10 months of mobile phone records from Greater London resolved in both space and time, we investigate the regularity of human telecommunication activity on urban scales. We evaluate several options for decomposing activity timelines into typical and residual patterns, accounting for the strong periodic and seasonal components. We carry out our analysis on various spatial scales, showing that regularity increases as we look at aggregated activity in larger spatial units with more activity in them. We examine the statistical properties of the residuals and show that it can be explained by noise and specific outliers. Also, we look at sources of deviations from the general trends, which we find to be explainable based on knowledge of the city structure and places of attractions. We show examples how some of the outliers can be related to external factors such as specific social events.

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