scholarly journals Potential and Realized Impact of Astroglia Ca2 + Dynamics on Circuit Function and Behavior

2021 ◽  
Vol 15 ◽  
Author(s):  
Eunice Y. Lim ◽  
Liang Ye ◽  
Martin Paukert
Keyword(s):  
Behavioral Alterations ◽  
State Dependent ◽  
Wide Range ◽  
Intracellular Ca ◽  
Functional Consequences ◽  
Physiological Impact ◽  
Underlying Mechanisms ◽  
Circuit Function ◽  
And Behavior ◽  
Spontaneous Fluctuations

Astroglia display a wide range of spontaneous and behavioral state-dependent Ca2+ dynamics. During heightened vigilance, noradrenergic signaling leads to quasi-synchronous Ca2+ elevations encompassing soma and processes across the brain-wide astroglia network. Distinct from this vigilance-associated global Ca2+ rise are apparently spontaneous fluctuations within spatially restricted microdomains. Over the years, several strategies have been pursued to shed light on the physiological impact of these signals including deletion of endogenous ion channels or receptors and reduction of intracellular Ca2+ through buffering, extrusion or inhibition of release. Some experiments that revealed the most compelling behavioral alterations employed chemogenetic and optogenetic manipulations to modify astroglia Ca2+ signaling. However, there is considerable contrast between these findings and the comparatively modest effects of inhibiting endogenous sources of Ca2+. In this review, we describe the underlying mechanisms of various forms of astroglia Ca2+ signaling as well as the functional consequences of their inhibition. We then discuss how the effects of exogenous astroglia Ca2+ modification combined with our knowledge of physiological mechanisms of astroglia Ca2+ activation could guide further refinement of behavioral paradigms that will help elucidate the natural Ca2+-dependent function of astroglia.

Microfabrication research at the National Submicron Facility

1983 ◽  
Vol 41 ◽  
pp. 86-89
Author(s):  
E.D. Wolf
Keyword(s):  
Integrated Circuits ◽  
Particle Physics ◽  
High Speed ◽  
New Technology ◽  
High Energy ◽  
High Energy Particle ◽  
New Science ◽  
Wide Range ◽  
Intermediate Domain ◽  
Circuit Function

Most microelectronics devices and circuits operate faster, consume less power, execute more functions and cost less per circuit function when the feature-sizes internal to the devices and circuits are made smaller. This is part of the stimulus for the Very High-Speed Integrated Circuits (VHSIC) program. There is also a need for smaller, more sensitive sensors in a wide range of disciplines that includes electrochemistry, neurophysiology and ultra-high pressure solid state research. There is often fundamental new science (and sometimes new technology) to be revealed (and used) when a basic parameter such as size is extended to new dimensions, as is evident at the two extremes of smallness and largeness, high energy particle physics and cosmology, respectively. However, there is also a very important intermediate domain of size that spans from the diameter of a small cluster of atoms up to near one micrometer which may also have just as profound effects on society as “big” physics.

Tickets for the Inclusive Museum

2020 ◽  
pp. 390-406
Author(s):  
Magda Nikolaraizi ◽  
Charikleia Kanari ◽  
Marc Marschark
Keyword(s):  
Hard Of Hearing ◽  
Learning Experiences ◽  
Learning Needs ◽  
Participatory Learning ◽  
Maximum Benefit ◽  
Wide Range ◽  
The Right ◽  
Physical Features ◽  
And Behavior

In recent years, museums of various kinds have broadened their mission and made systematic efforts to develop a dynamic role in learning by offering a wide range of less formal experiences for individuals with diverse characteristics, including individuals who are deaf or hard-of-hearing (DHH). Despite the worthwhile efforts, in the case of DHH individuals, museums frequently neglect to consider their unique communication, cognitive, cultural, and learning characteristics, thus limiting their access and opportunities for fully experiencing what museums have to offer. This chapter examines the potential for creating accessible museum environments and methods that reflect an understanding of the diverse communication, cognitive, cultural, and learning needs of DHH visitors, all of which enhance their access and participation in the museum activities. The role of the physical features of museum spaces for the access and behavior of DHH visitors is emphasized, together with attention to exhibition methods and the communication and cognitive challenges that need to be considered so DHH visitors can get the maximum benefit. The chapter emphasizes the right of individuals who are DHH to nonformal learning and analyzes how museums could become more accessible to DHH individuals by designing, from the beginning, participatory learning experiences that address their diverse needs.

scholarly journals Drivers of Infectious Disease Seasonality: Potential Implications for COVID-19

2021 ◽  
pp. 074873042098732
Author(s):  
N. Kronfeld-Schor ◽  
T. J. Stevenson ◽  
S. Nickbakhsh ◽  
E. S. Schernhammer ◽  
X. C. Dopico ◽  
...  
Keyword(s):  
Infectious Disease ◽  
Infectious Diseases ◽  
Multidisciplinary Approach ◽  
Preliminary Assessment ◽  
Epidemiological Evidence ◽  
Wide Range ◽  
Human Coronaviruses ◽  
Induced Changes ◽  
And Behavior ◽  
Timing Phase

Not 1 year has passed since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). Since its emergence, great uncertainty has surrounded the potential for COVID-19 to establish as a seasonally recurrent disease. Many infectious diseases, including endemic human coronaviruses, vary across the year. They show a wide range of seasonal waveforms, timing (phase), and amplitudes, which differ depending on the geographical region. Drivers of such patterns are predominantly studied from an epidemiological perspective with a focus on weather and behavior, but complementary insights emerge from physiological studies of seasonality in animals, including humans. Thus, we take a multidisciplinary approach to integrate knowledge from usually distinct fields. First, we review epidemiological evidence of environmental and behavioral drivers of infectious disease seasonality. Subsequently, we take a chronobiological perspective and discuss within-host changes that may affect susceptibility, morbidity, and mortality from infectious diseases. Based on photoperiodic, circannual, and comparative human data, we not only identify promising future avenues but also highlight the need for further studies in animal models. Our preliminary assessment is that host immune seasonality warrants evaluation alongside weather and human behavior as factors that may contribute to COVID-19 seasonality, and that the relative importance of these drivers requires further investigation. A major challenge to predicting seasonality of infectious diseases are rapid, human-induced changes in the hitherto predictable seasonality of our planet, whose influence we review in a final outlook section. We conclude that a proactive multidisciplinary approach is warranted to predict, mitigate, and prevent seasonal infectious diseases in our complex, changing human-earth system.

scholarly journals Zebrafish Models to Study New Pathways in Tauopathies

2021 ◽  
Vol 22 (9) ◽  
pp. 4626
Author(s):  
Clément Barbereau ◽  
Nicolas Cubedo ◽  
Tangui Maurice ◽  
Mireille Rossel
Keyword(s):  
Cognitive Deficits ◽  
Tau Protein ◽  
Common Point ◽  
Transgenic Models ◽  
Synaptic Loss ◽  
Wide Range ◽  
Transgenic Lines ◽  
Functional Consequences ◽  
The Common

Tauopathies represent a vast family of neurodegenerative diseases, the most well-known of which is Alzheimer’s disease. The symptoms observed in patients include cognitive deficits and locomotor problems and can lead ultimately to dementia. The common point found in all these pathologies is the accumulation in neural and/or glial cells of abnormal forms of Tau protein, leading to its aggregation and neurofibrillary tangles. Zebrafish transgenic models have been generated with different overexpression strategies of human Tau protein. These transgenic lines have made it possible to highlight Tau interacting factors or factors which may limit the neurotoxicity induced by mutations and hyperphosphorylation of the Tau protein in neurons. Several studies have tested neuroprotective pharmacological approaches. On few-days-old larvae, modulation of various signaling or degradation pathways reversed the deleterious effects of Tau mutations, mainly hTauP301L and hTauA152T. Live imaging and live tracking techniques as well as behavioral follow-up enable the analysis of the wide range of Tau-related phenotypes from synaptic loss to cognitive functional consequences.

scholarly journals Cellular Heterogeneity–Adjusted cLonal Methylation (CHALM) improves prediction of gene expression

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jianfeng Xu ◽  
Jiejun Shi ◽  
Xiaodong Cui ◽  
Ya Cui ◽  
Jingyi Jessica Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cellular Heterogeneity ◽  
Biological Functions ◽  
Global Correlation ◽  
Differentially Methylated Genes ◽  
Promoter Dna Methylation ◽  
Functional Consequences ◽  
Promoter Dna ◽  
Underlying Mechanisms

AbstractPromoter DNA methylation is a well-established mechanism of transcription repression, though its global correlation with gene expression is weak. This weak correlation can be attributed to the failure of current methylation quantification methods to consider the heterogeneity among sequenced bulk cells. Here, we introduce Cell Heterogeneity–Adjusted cLonal Methylation (CHALM) as a methylation quantification method. CHALM improves understanding of the functional consequences of DNA methylation, including its correlations with gene expression and H3K4me3. When applied to different methylation datasets, the CHALM method enables detection of differentially methylated genes that exhibit distinct biological functions supporting underlying mechanisms.

Influence of Polypropylene Fiber in Strength of Foamed Concrete

2012 ◽  
Vol 488-489 ◽  
pp. 253-257 ◽  
Author(s):  
Josef Hadipramana ◽  
Abdul Aziz Abdul Samad ◽  
Zi Jun Zhao ◽  
Noridah Mohammad ◽  
W. Wirdawati
Keyword(s):  
Tensile Strength ◽  
Mechanical Test ◽  
Polypropylene Fiber ◽  
High Density ◽  
Splitting Tensile Strength ◽  
Normal Concrete ◽  
Wide Range ◽  
Foamed Concrete ◽  
Strength Result ◽  
And Behavior

Foamed concrete is material that can be used in wide range of constructions and produced in high density. This investigation examined effect of chopped Polypropylene Fiber (PF) that mixed into admixture concerning strength of foamed concrete high density. Mechanical test were performed to measure effect of PF on improving compressive and splitting tensile strength. Result indicate that PF significantly improving compressive strength and behavior of PF where drawn into foamed concrete similarly with normal concrete. The fibrillated PF has been occurred and reduced the micro crack of matrix and prevented propagation crack growth. The presence of PF improved splitting tensile strength was not significantly. Influence of porous of foamed concrete is considered. Scanning Electron Microscope (SEM) exhibits condition microstructure of foamed concrete reinforced PF that alter microstructure, especially interfacial bonding due to PF presence.

Brain plasticity in response to short-term exposure to corticosterone in larval amphibians

2021 ◽  
Author(s):  
Elizabeth S. Cha ◽  
Madison T. Uhrin ◽  
Sara J McClelland ◽  
Sarah Woodley
Keyword(s):  
Neural Development ◽  
Brain Plasticity ◽  
Leopard Frog ◽  
Brain Morphology ◽  
Vertebrate Brain ◽  
Larval Amphibians ◽  
Short Term Exposure ◽  
Functional Consequences ◽  
And Behavior ◽  
Brain Shape

Exposure to stressors and elevation of glucocorticoid hormones such as corticosterone (CORT) has widespread effects on vertebrate brain development. Previous studies have shown that exposure to environmental stressors alters larval amphibian brain morphology and behavior, yet the effects of CORT on amphibian neural development are still unknown. We exposed prometamorphic Northern Leopard Frog (Lithobates pipiens (Schreber, 1782)) tadpoles for 7 days to a concentration of exogenous CORT (45.56 g/L ) that produced physiologically-relevant increases in plasma CORT. This brief exposure to CORT, relatively late in development, resulted in a significantly larger diencephalon width (relative to body mass) when compared to controls. Although we were unable to detect changes in behavior or body morphology, our results indicate that brain shape is modulated by exposure to CORT. More studies are needed to better understand what accounts for the CORT-induced change in brain shape as well as the functional consequences of these changes.

A high-power PCCM LED driver based on GaN eHEMT with hybrid dimming modes

Circuit World ◽  
2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Xixian Lin ◽  
Yuming Zhang ◽  
Yimeng Zhang ◽  
Guangjian Rong
Keyword(s):  
Printed Circuit Board ◽  
Pulse Width Modulation ◽  
Circuit Board ◽  
Switching Frequency ◽  
Led Driver ◽  
Power Circuit ◽  
Content Type ◽  
Wide Range ◽  
Circuit Function ◽  
Pwm Dimming

Purpose The purpose of this study is to design a more flexible and larger range of the dimming circuit that achieves the independence of multiple LED strings drive and can time-multiplex the power circuit. Design/methodology/approach The state-space method is used to model the BUCK circuit working in Pseudo continuous conduction mode, analyze the frequency characteristics of the system transfer function and design the compensation network. Build a simulation platform on the Orcad PSPICE platform and verify the function of the designed circuit through the simulation results. Use Altium Designer 16 to draw the printed circuit board, complete the welding of various components and use the oscilloscope, direct current (DC) power supply and a signal generator to verify the circuit function. Findings A prototype of the proposed LED driver is fabricated and tested. The measurement results show that the switching frequency can be increased to 1 MHz, Power inductance is 2.2 µH, which is smaller than current research. The dimming ratio can be set from 10% to 100%. The proposed LED driver can output more than 48 W and achieve a peak conversion efficiency of 91%. Originality/value The proposed LED driver adopts pulse width modulation (PWM) dimming at a lower dimming ratio and adopts DC dimming at a larger dimming ratio to realize switching PWM dimming to analog dimming. The control strategy can be more precise and have a wide range of dimming.

Comparisons of voltage-gated sodium channel structures with open and closed gates and implications for state-dependent drug design

2018 ◽  
Vol 46 (6) ◽  
pp. 1567-1575 ◽  
Author(s):  
Giulia Montini ◽  
Jennifer Booker ◽  
Altin Sula ◽  
B.A. Wallace
Keyword(s):  
Drug Design ◽  
Sodium Channels ◽  
Rational Drug Design ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
State Dependent ◽  
Rational Drug ◽  
Sequence Homologies ◽  
Arcobacter Butzleri ◽  
Functional Consequences

Voltage-gated sodium channels (Navs) are responsible for the initiation of the action potential in excitable cells. Several prokaryotic sodium channels, most notably NavMs from Magnetococcus marinus and NavAb from Arcobacter butzleri, have been shown to be good models for human sodium channels based on their sequence homologies and high levels of functional similarities, including ion flux, and functional consequences of critical mutations. The complete full-length crystal structures of these prokaryotic sodium channels captured in different functional states have now revealed the molecular natures of changes associated with the gating process. These include the structures of the intracellular gate, the selectivity filter, the voltage sensors, the intra-membrane fenestrations, and the transmembrane (TM) pore. Here we have identified for the first time how changes in the fenestrations in the hydrophobic TM region associated with the opening of the intracellular gate could modulate the state-dependent ingress and binding of drugs in the TM cavity, in a way that could be exploited for rational drug design.

scholarly journals Functional consequences of the first reported mutations of the proto-oncogene PTTG1IP/PBF

2017 ◽  
Vol 24 (9) ◽  
pp. 459-474 ◽  
Author(s):  
W Imruetaicharoenchoke ◽  
A Fletcher ◽  
W Lu ◽  
R J Watkins ◽  
B Modasia ◽  
...  
Keyword(s):  
Colony Formation ◽  
Human Cancer ◽  
Soft Agar ◽  
Cellular Migration ◽  
3T3 Fibroblasts ◽  
Wide Range ◽  
Functional Consequences ◽  
Altered Cell ◽  
Proliferation Assays ◽  
Nih 3T3

Pituitary tumor-transforming gene 1-binding factor (PTTG1IP; PBF) is a multifunctional glycoprotein, which is overexpressed in a wide range of tumours, and significantly associated with poorer oncological outcomes, such as early tumour recurrence, distant metastasis, extramural vascular invasion and decreased disease-specific survival. PBF transforms NIH 3T3 fibroblasts and induces tumours in nude mice, while mice harbouring transgenic thyroidal PBF expression show hyperplasia and macrofollicular lesions. Our assumption that PBF becomes an oncogene purely through increased expression has been challenged by the recent report of mutations in PBF within the Catalogue of Somatic Mutations in Cancer (COSMIC) database. We therefore sought to determine whether the first 10 PBF missense substitutions in human cancer might be oncogenic. Anisomycin half-life studies revealed that most mutations were associated with reduced protein stability compared to wild-type (WT) PBF. Proliferation assays narrowed our interest to two mutational events which significantly altered cell turnover: C51R and R140W. C51R was mainly confined to the endoplasmic reticulum while R140W was apparent in the Golgi apparatus. Both C51R and R140W lost the capacity to induce cellular migration and significantly reduced cell invasion. Colony formation and soft agar assays demonstrated that, in contrast to WT PBF, both mutants were unable to elicit significant colony formation or anchorage-independent growth. However, C51R and R140W retained the ability to repress radioiodide uptake, a functional hallmark of PBF. Our data reveal new insight into PBF function and confirm that, rather than being oncogenic, mutations in PBF are likely to be passenger effects, with overexpression of PBF the more important aetiological event in human cancer.

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