scholarly journals Chronophotopharmacology: towards chronotherapy with high spatio-temporal precision

2020 ◽  
Author(s):  
◽  
Dusan Kolarski
Keyword(s):  
Temporal Precision ◽  
Spatio Temporal

Elucidating cyclic AMP signaling in subcellular domains with optogenetic tools and fluorescent biosensors

2019 ◽  
Vol 47 (6) ◽  
pp. 1733-1747 ◽  
Author(s):  
Christina Klausen ◽  
Fabian Kaiser ◽  
Birthe Stüven ◽  
Jan N. Hansen ◽  
Dagmar Wachten
Keyword(s):  
Cyclic Amp ◽  
Adenosine Monophosphate ◽  
Adenylyl Cyclases ◽  
Temporal Precision ◽  
Fluorescent Biosensors ◽  
Subcellular Domains ◽  
Spatio Temporal ◽  
Hydrolysis Of ◽  
Shed Light ◽  
Cyclic Amp Signaling

The second messenger 3′,5′-cyclic nucleoside adenosine monophosphate (cAMP) plays a key role in signal transduction across prokaryotes and eukaryotes. Cyclic AMP signaling is compartmentalized into microdomains to fulfil specific functions. To define the function of cAMP within these microdomains, signaling needs to be analyzed with spatio-temporal precision. To this end, optogenetic approaches and genetically encoded fluorescent biosensors are particularly well suited. Synthesis and hydrolysis of cAMP can be directly manipulated by photoactivated adenylyl cyclases (PACs) and light-regulated phosphodiesterases (PDEs), respectively. In addition, many biosensors have been designed to spatially and temporarily resolve cAMP dynamics in the cell. This review provides an overview about optogenetic tools and biosensors to shed light on the subcellular organization of cAMP signaling.

Phonological disorders and spatio‐temporal precision of stop consonant gestures

1998 ◽  
Vol 104 (3) ◽  
pp. 1853-1853
Author(s):  
Jan Edwards ◽  
Marios Fourakis ◽  
Mary Beckman ◽  
Pauline Welby ◽  
Ying Xu
Keyword(s):  
Stop Consonant ◽  
Temporal Precision ◽  
Phonological Disorders ◽  
Spatio Temporal

scholarly journals Epigenetic regulation of retinal development

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Reza Raeisossadati ◽  
Merari F. R. Ferrari ◽  
Alexandre Hiroaki Kihara ◽  
Issam AlDiri ◽  
Jeffrey M. Gross
Keyword(s):  
Cell Fate ◽  
Epigenetic Regulation ◽  
Developmental Disorders ◽  
Retinal Development ◽  
Treatment Strategies ◽  
Temporal Precision ◽  
Numerous Cell ◽  
Spatio Temporal ◽  
Novel Treatment Strategies ◽  
Retinal Pathologies

AbstractIn the developing vertebrate retina, retinal progenitor cells (RPCs) proliferate and give rise to terminally differentiated neurons with exquisite spatio-temporal precision. Lineage commitment, fate determination and terminal differentiation are controlled by intricate crosstalk between the genome and epigenome. Indeed, epigenetic regulation plays pivotal roles in numerous cell fate specification and differentiation events in the retina. Moreover, aberrant chromatin structure can contribute to developmental disorders and retinal pathologies. In this review, we highlight recent advances in our understanding of epigenetic regulation in the retina. We also provide insight into several aspects of epigenetic-related regulation that should be investigated in future studies of retinal development and disease. Importantly, focusing on these mechanisms could contribute to the development of novel treatment strategies targeting a variety of retinal disorders.

scholarly journals Bursty Expression Enhances Reliability of Messaging in Gene Networks

2020 ◽  
Author(s):  
Leonardo R. Gama ◽  
Guilherme Giovanini ◽  
Gábor Balázsi ◽  
Alexandre F. Ramos
Keyword(s):  
Transcription Factors ◽  
Mutual Information ◽  
Gene Networks ◽  
Gene Network ◽  
The State ◽  
Expression Levels ◽  
Temporal Precision ◽  
Spatio Temporal ◽  
Steady State Solutions ◽  
Slow Switching

AbstractThe promoter state of a gene and its expression levels are modulated by the amounts of transcription factors interacting with its regulatory regions. Hence, one may interpret a gene network as a communicating system in which the state of the promoter of a gene (the source) is communicated by the amounts of transcription factors that it expresses (the message) to modulate the state of the promoter and expression levels of another gene (the receptor). The reliability of the gene network dynamics can be quantified by the Shannon’s entropy of the message and the mutual information between the message and the promoter state. Here we consider a stochastic model for a binary gene and use its exact steady state solutions to calculate the entropy and mutual information. We show that a slow switching promoter having long and equally standing ON and OFF states maximizes the mutual information and reduces entropy. That is a bursty regime generating a high variance message governed by a bimodal probability distribution with peaks of the same height. Our results indicate that Shannon’s theory can be a powerful framework for understanding how bursty gene expression conciliates with the striking spatio-temporal precision exhibited in pattern formation of developing organisms.

scholarly journals Light-Inducible Spatio-Temporal Control of TLR4 and NF-κB-Gluc Reporter in Human Pancreatic Cell Line

2021 ◽  
Vol 22 (17) ◽  
pp. 9232
Author(s):  
Anna Stierschneider ◽  
Petra Grünstäudl ◽  
Katrin Colleselli ◽  
Josef Atzler ◽  
Christian T. Klein ◽  
...  
Keyword(s):  
Cell Line ◽  
Molecular Mechanisms ◽  
Cell Attachment ◽  
Light Exposure ◽  
Ground Level ◽  
Time Resolved ◽  
Pancreatic Cell ◽  
Temporal Precision ◽  
Tumorigenesis And Progression ◽  
Spatio Temporal

Augmented Toll-like receptor 4 (TLR4) expression was found in nearly 70% of patients with pancreatic adenocarcinoma, which is correlated with increased tumorigenesis and progression. In this study, we engineered a new light-oxygen-voltage-sensing (LOV) domain-based optogenetic cell line (opto-TLR4 PANC-1) that enables time-resolved activation of the NF-κB and extracellular-signal regulated kinases (ERK)1/2 signalling pathway upon blue light-sensitive homodimerisation of the TLR4-LOV fusion protein. Continuous stimulation with light indicated strong p65 and ERK1/2 phosphorylation even after 24 h, whereas brief light exposure peaked at 8 h and reached the ground level 24 h post-illumination. The cell line further allows a voltage-dependent TLR4 activation, which can be continuously monitored, turned on by light or off in the dark. Using this cell line, we performed different phenotypic cell-based assays with 2D and 3D cultures, with the aim of controlling cellular activity with spatial and temporal precision. Light exposure enhanced cell attachment, the formation and extension of invadopodia, and cell migration in 3D spheroid cultures, but no significant changes in proliferation or viability could be detected. We conclude that the opto-TLR4 PANC-1 cell line is an ideal tool for investigating the underlying molecular mechanisms of TLR4, thereby providing strategies for new therapeutic options.

scholarly journals Evolution of primate protomusicality via locomotion

2020 ◽  
Author(s):  
David M. Schruth ◽  
Christopher N. Templeton ◽  
Darryl J. Holman ◽  
Eric A. Smith
Keyword(s):  
Regression Analysis ◽  
Locomotor Activity ◽  
Primate Species ◽  
Temporal Precision ◽  
Branching Points ◽  
Calling Patterns ◽  
Spatio Temporal

AbstractAnimals communicate acoustically to report location and identity to conspecifics. More complex patterning of calls can also function as displays to potential mates and as territorial advertisement. Music and song are terms often reserved only for humans and birds, but elements of both forms of acoustic display are also found in non-human primates. While theories on proximate functions abound, ultimate drivers of specific call structures are less well understood. We hypothesized that spatio-temporal precision in landing during perilous arboreal locomotion favored the evolution of musical calling in early primates—vastly preceding the origin of more music-like behavior in hominoids and subsequent emergence of music in later hominids. We test this locomotion based hypothesis on the origins of proto-musicality using spectrographic depictions of vocal repertoires of modern day primates and corresponding estimates of locomotor activity. Phylogenetically controlled regression analysis of 54 primate species reveals that arboreal locomotion and monogamy are robust influences on complex calling patterns while controlling for other socioecological variables. Given that these findings rest primarily upon a handful of deep branching points in the primate tree, we conclude that this coevolution likely occurred very slowly, occupying on the order of tens of millions of years.

scholarly journals Optogenetic stimulation of Gs-signaling in the heart with high spatio-temporal precision

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Philipp Makowka ◽  
Tobias Bruegmann ◽  
Vanessa Dusend ◽  
Daniela Malan ◽  
Thomas Beiert ◽  
...  
Keyword(s):  
Temporal Precision ◽  
Optogenetic Stimulation ◽  
Spatio Temporal ◽  
Stimulation Of

scholarly journals Binary Expression Enhances Reliability of Messaging in Gene Networks

Entropy ◽  
2020 ◽  
Vol 22 (4) ◽  
pp. 479
Author(s):  
Leonardo R. Gama ◽  
Guilherme Giovanini ◽  
Gábor Balázsi ◽  
Alexandre F. Ramos
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Mutual Information ◽  
Gene Networks ◽  
Gene Network ◽  
The State ◽  
Expression Levels ◽  
Temporal Precision ◽  
Spatio Temporal ◽  
Steady State Solutions

The promoter state of a gene and its expression levels are modulated by the amounts of transcription factors interacting with its regulatory regions. Hence, one may interpret a gene network as a communicating system in which the state of the promoter of a gene (the source) is communicated by the amounts of transcription factors that it expresses (the message) to modulate the state of the promoter and expression levels of another gene (the receptor). The reliability of the gene network dynamics can be quantified by Shannon’s entropy of the message and the mutual information between the message and the promoter state. Here we consider a stochastic model for a binary gene and use its exact steady state solutions to calculate the entropy and mutual information. We show that a slow switching promoter with long and equally standing ON and OFF states maximizes the mutual information and reduces entropy. That is a binary gene expression regime generating a high variance message governed by a bimodal probability distribution with peaks of the same height. Our results indicate that Shannon’s theory can be a powerful framework for understanding how bursty gene expression conciliates with the striking spatio-temporal precision exhibited in pattern formation of developing organisms.

Spatio-temporal constraints of the tidal wave theory

1997 ◽  
Vol 20 (2) ◽  
pp. 264-265
Author(s):  
Cornelius Schwarz
Keyword(s):  
Purkinje Cell ◽  
Input Sequence ◽  
Wave Theory ◽  
Tidal Wave ◽  
Minimal Distance ◽  
Temporal Precision ◽  
Tidal Waves ◽  
Temporal And Spatial ◽  
Spatio Temporal ◽  
Cortical Inputs

The tidal-wave theory is inspired by the particular morphology of the cerebellar cortex. It elegantly attributes function to the anisotropy of the cerebellar wiring and the geometry of Purkinje cell dendrites. In this commentary, physiological considerations are used to elaborate temporal and spatial constraints of the tidal-wave theory. It is shown, first, that limitations of temporal precision in the cortical inputs to the mammalian cerebellum delimit the spatial resolution of an input sequence (i.e., the minimal distance along the parallel fibers which can detect sequential input) to the range of a millimeter at best. Second, temporal characteristics of Purkinje cell postsynaptic potentials are argued to predict a distance of at least several millimeters along the parallel fiber beam in order to generate a sequence in the cerebellar output. It is concluded that the implementation of tidal waves as a general principle of cerebellar function is questionable as there exist cerebelli too small to match these constraints.

scholarly journals Activation and Delivery of Tetrazine-Responsive Bioorthogonal Prodrugs

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5640 ◽  
Author(s):  
Yayue Wang ◽  
Chang Zhang ◽  
Haoxing Wu ◽  
Ping Feng
Keyword(s):  
Great Promise ◽  
Attractive Alternative ◽  
Bioorthogonal Chemistry ◽  
Cleavage Reaction ◽  
Trigger Factors ◽  
Temporal Precision ◽  
Bioorthogonal Reactions ◽  
Factors Associated ◽  
Spatio Temporal ◽  
Target Effects

Prodrugs, which remain inert until they are activated under appropriate conditions at the target site, have emerged as an attractive alternative to drugs that lack selectivity and show off-target effects. Prodrugs have traditionally been activated by enzymes, pH or other trigger factors associated with the disease. In recent years, bioorthogonal chemistry has allowed the creation of prodrugs that can be chemically activated with spatio-temporal precision. In particular, tetrazine-responsive bioorthogonal reactions can rapidly activate prodrugs with excellent biocompatibility. This review summarized the recent development of tetrazine bioorthogonal cleavage reaction and great promise for prodrug systems.

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