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1
Nguyen, Trung Duc, Yuan-I. Chen, Limin H. Chen, and Hsin-Chih Yeh. "Recent Advances in Single-Molecule Tracking and Imaging Techniques." Annual Review of Analytical Chemistry 16, no. 1 (June 14, 2023): 253–84. http://dx.doi.org/10.1146/annurev-anchem-091922-073057.
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Since the early 1990s, single-molecule detection in solution at room temperature has enabled direct observation of single biomolecules at work in real time and under physiological conditions, providing insights into complex biological systems that the traditional ensemble methods cannot offer. In particular, recent advances in single-molecule tracking techniques allow researchers to follow individual biomolecules in their native environments for a timescale of seconds to minutes, revealing not only the distinct pathways these biomolecules take for downstream signaling but also their roles in supporting life. In this review, we discuss various single-molecule tracking and imaging techniques developed to date, with an emphasis on advanced three-dimensional (3D) tracking systems that not only achieve ultrahigh spatiotemporal resolution but also provide sufficient working depths suitable for tracking single molecules in 3D tissue models. We then summarize the observables that can be extracted from the trajectory data. Methods to perform single-molecule clustering analysis and future directions are also discussed.
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Kataria, Meghna, and Hiroyuki Yamano. "Interplay between Phosphatases and the Anaphase-Promoting Complex/Cyclosome in Mitosis." Cells 8, no. 8 (August 2, 2019): 814. http://dx.doi.org/10.3390/cells8080814.
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Accurate division of cells into two daughters is a process that is vital to propagation of life. Protein phosphorylation and selective degradation have emerged as two important mechanisms safeguarding the delicate choreography of mitosis. Protein phosphatases catalyze dephosphorylation of thousands of sites on proteins, steering the cells through establishment of the mitotic phase and exit from it. A large E3 ubiquitin ligase, the anaphase-promoting complex/cyclosome (APC/C) becomes active during latter stages of mitosis through G1 and marks hundreds of proteins for destruction. Recent studies have revealed the complex interregulation between these two classes of enzymes. In this review, we highlight the direct and indirect mechanisms by which phosphatases and the APC/C mutually influence each other to ensure accurate spatiotemporal and orderly progression through mitosis, with a particular focus on recent insights and conceptual advances.
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HILLENBRAND, ULRICH, and J. LEO van HEMMEN. "Spatiotemporal adaptation through corticothalamic loops: A hypothesis." Visual Neuroscience 17, no. 1 (January 2000): 107–18. http://dx.doi.org/10.1017/s0952523800171111.
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The thalamus is the major gate to the cortex and its control over cortical responses is well established. Cortical feedback to the thalamus is, in turn, the anatomically dominant input to relay cells, yet its influence on thalamic processing has been difficult to interpret. For an understanding of complex sensory processing, detailed concepts of the corticothalamic interplay need yet to be established. Drawing on various physiological and anatomical data, we elaborate the novel hypothesis that the visual cortex controls the spatiotemporal structure of cortical receptive fields via feedback to the lateral geniculate nucleus. Furthermore, we present and analyze a model of corticogeniculate loops that implements this control, and exhibit its ability of object segmentation by statistical motion analysis in the visual field.
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Miller, R. A., and B. E. Britigan. "Role of oxidants in microbial pathophysiology." Clinical Microbiology Reviews 10, no. 1 (January 1997): 1–18. http://dx.doi.org/10.1128/cmr.10.1.1.
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Reactive oxidant species (superoxide, hydrogen peroxide, hydroxyl radical, hypohalous acid, and nitric oxide) are involved in many of the complex interactions between the invading microorganism and its host. Regardless of the source of these compounds or whether they are produced under normal conditions or those of oxidative stress, these oxidants exhibit a broad range of toxic effects to biomolecules that are essential for cell survival. Production of these oxidants by microorganisms enables them to have a survival advantage in their environment. Host oxidant production, especially by phagocytes, is a counteractive mechanism aimed at microbial killing. However, this mechanism may be contribute to a deleterious consequence of oxidant exposure, i.e., inflammatory tissue injury. Both the host and the microorganism have evolved complex adaptive mechanisms to deflect oxidant-mediated damage, including enzymatic and nonenzymatic oxidant-scavenging systems. This review discusses the formation of reactive oxidant species in vivo and how they mediate many of the processes involved in the complex interplay between microbial invasion and host defense.
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Das, N. S., S. T. Dheen, E. A. Ling, B. H. Bay, and D. K. Srinivasan. "Therapeutic Prospects in Preeclampsia - A Mini-Review." Current Medicinal Chemistry 26, no. 25 (October 16, 2019): 4786–98. http://dx.doi.org/10.2174/0929867326666190228115423.
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Background: Preeclapmsia (PE) is characterized by early onset symptoms such as elevated blood pressure, proteinuria and edema in the pregnant woman, and may result in seizures in the affected female. Currently, there are no therapeutic drugs available to treat this condition, but there are interventions to regulate the symptoms based on the gestational period of the fetus, although the largely favored option is delivery of the fetus and placenta. Objective: A search for biomolecules associated with PE was conducted so as to identify diagnostic markers and therapeutic leads. Results: The literature search resulted in the identification of biomolecules such as Corin and Placental Protein 13 (PP13), among others that are associated with PE. Thereby, giving an insight into the various mechanistic pathways involved in the causation of PE. However, it is also evident that PE cannot be solely attributed to any single mechanism but is due to an interplay of different factors that have led to the development of this disease condition. Conclusion: The identified biomarkers would ultimately help in understanding this complex disease and perhaps lead to the discovery of potential effective molecular targets for clinical trials, thereby providing a valuable therapeutic option for affected pregnant women.
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Zhang, Bing, Weijuan Huang, Sen Pei, Jinfeng Zeng, Wei Shen, Daoze Wang, Gang Wang, et al. "Mechanisms for the circulation of influenza A(H3N2) in China: A spatiotemporal modelling study." PLOS Pathogens 18, no. 12 (December 16, 2022): e1011046. http://dx.doi.org/10.1371/journal.ppat.1011046.
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Circulation of seasonal influenza is the product of complex interplay among multiple drivers, yet characterizing the underlying mechanism remains challenging. Leveraging the diverse seasonality of A(H3N2) virus and abundant climatic space across regions in China, we quantitatively investigated the relative importance of population susceptibility, climatic factors, and antigenic change on the dynamics of influenza A(H3N2) through an integrative modelling framework. Specifically, an absolute humidity driven multiscale transmission model was constructed for the 2013/2014, 2014/2015 and 2016/2017 influenza seasons that were dominated by influenza A(H3N2). We revealed the variable impact of absolute humidity on influenza transmission and differences in the occurring timing and magnitude of antigenic change for those three seasons. Overall, the initial population susceptibility, climatic factors, and antigenic change explained nearly 55% of variations in the dynamics of influenza A(H3N2). Specifically, the additional variation explained by the initial population susceptibility, climatic factors, and antigenic change were at 33%, 26%, and 48%, respectively. The vaccination program alone failed to fully eliminate the summer epidemics of influenza A(H3N2) and non-pharmacological interventions were needed to suppress the summer circulation. The quantitative understanding of the interplay among driving factors on the circulation of influenza A(H3N2) highlights the importance of simultaneous monitoring of fluctuations for related factors, which is crucial for precise and targeted prevention and control of seasonal influenza.
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Abbasi, Omid, Nadine Steingräber, Nikos Chalas, Daniel S. Kluger, and Joachim Gross. "Spatiotemporal dynamics characterise spectral connectivity profiles of continuous speaking and listening." PLOS Biology 21, no. 7 (July 21, 2023): e3002178. http://dx.doi.org/10.1371/journal.pbio.3002178.
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Speech production and perception are fundamental processes of human cognition that both rely on intricate processing mechanisms that are still poorly understood. Here, we study these processes by using magnetoencephalography (MEG) to comprehensively map connectivity of regional brain activity within the brain and to the speech envelope during continuous speaking and listening. Our results reveal not only a partly shared neural substrate for both processes but also a dissociation in space, delay, and frequency. Neural activity in motor and frontal areas is coupled to succeeding speech in delta band (1 to 3 Hz), whereas coupling in the theta range follows speech in temporal areas during speaking. Neural connectivity results showed a separation of bottom-up and top-down signalling in distinct frequency bands during speaking. Here, we show that frequency-specific connectivity channels for bottom-up and top-down signalling support continuous speaking and listening. These findings further shed light on the complex interplay between different brain regions involved in speech production and perception.
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Cowan, A. E., Y. Li, F. R. Morgan, D. E. Koppel, B. M. Slepchenko, L. M. Loew, and J. Schaff. "Using the Virtual Cell Simulation Environment for Extracting Quantitative Parameters from Live Cell Fluorescence Imaging Data." Microscopy Today 17, no. 6 (November 2009): 36–39. http://dx.doi.org/10.1017/s1551929509991039.
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Rapid advances in fluorescence probe and imaging technologies now provide easily accessible tools for biologists to perform highly detailed analysis of molecular interactions in living cells. However it can be difficult to extract accurate parameters from these experiments because of the complex interplay of diffusion-reaction events with the morphology of the cell. As a result, only a small fraction of the available spatiotemporal information is utilized, and in many cases analysis remains at a qualitative level. The Virtual Cell (VCell, http://vcell.org) simulation environment is uniquely suited to analyzing these types of fluorescence imaging experiments because it is designed to solve reaction-diffusion equations within any given geometry [1]
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Ruhl, C. J., R. E. Abercrombie, K. D. Smith, and I. Zaliapin. "Complex spatiotemporal evolution of the 2008 M w 4.9 Mogul earthquake swarm (Reno, Nevada): Interplay of fluid and faulting." Journal of Geophysical Research: Solid Earth 121, no. 11 (November 2016): 8196–216. http://dx.doi.org/10.1002/2016jb013399.
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Chen, Lijun, and Shangjing Jiang. "Spatiotemporal Polyrhythm Characteristics of Public Bicycle Mobility in Urban Chronotopes Context." ISPRS International Journal of Geo-Information 11, no. 1 (December 28, 2021): 6. http://dx.doi.org/10.3390/ijgi11010006.
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Cycling rhythm performance is the result of a complex interplay between active travel demand and cycling network supply. Most studies focused on bicycle flow, but little attention has been paid to cycling rhythm changes for public bicycles. Full sample data of origin–destination enables an efficient description of network-wide cycling mobility efficiency in urban public bicycle systems. In this paper, we show how the spatiotemporal characteristics of cycling speed reveal the performance of cycling rhythms. The inference method of riding speed estimation is proposed with an unknown cycling path. The significant inconsistency of docking stations in cycling rhythm was unraveled by the source–sink relationship comparison. The asymmetry of the cycling rhythm on the path is manifested as the rhythm difference among paths and bidirectional inconsistency. We found that cycling rhythm has a temporal multilayer and spatial mismatch, which shows the inflection points of the cycling rhythm where the travel behavioral preference changes and the exact road segments with different rhythms. This finding suggests that a well-designed cycling environment and occupation-residential function should be considered in active transport demand management and urban planning to help induce active travel behavior decisions.
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Wirth, Corina, and Hans-R. Lüscher. "Spatiotemporal Evolution of Excitation and Inhibition in the Rat Barrel Cortex Investigated With Multielectrode Arrays." Journal of Neurophysiology 91, no. 4 (April 2004): 1635–47. http://dx.doi.org/10.1152/jn.00950.2003.
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We investigated the spatiotemporal evolution of activity in the rat barrel cortex using multielectrode arrays (MEAs). In acute brain slices, field potentials were recorded simultaneously from 60 electrodes with high spatial and temporal resolution. This new technique allowed us to map functionally discrete barrels and to observe the interplay between the excitatory and inhibitory network. The local field potentials (LFPs) were elicited by focal electrical stimulation in layer 4 (L4). Excitation recorded in a single barrel was first confined to the stimulated barrel and subsequently spread in a columnar manner to layer 2/3 (L2/3). This excitation in L4 and lower L2/3 was followed by inhibition curtailing excitation to a short period lasting only ∼2 ms. In the uppermost layer, a long-lasting (∼10 ms), laterally spreading band of excitation remained active. Blockade of GABAA-receptors resulted in a long-lasting and diffuse activation of L4 and lower L2/3 and abolition of activation of the upper L2/3. Thus inhibition not only shaped the spatial-temporal map of excitation in L4 and lower L2/3 but also resulted indirectly in an excitatory action in the superficial layers. Stimulation in L6 revealed a feedforward inhibition to L4 and subsequently an excitatory L6-L4-L6 loop. The complex interplay between excitation and inhibition opens two spatial windows of excitation in the infra- and supragranular layers. They may prepare the L5 pyramidal neuron for associating top-down input from other cortical regions with bottom-up input from the whisker pad to generate behaviorally relevant output.
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Munaron, Luca. "A Tridimensional Model of Proangiogenic Calcium Signals in Endothelial Cells." Open Biology Journal 2, no. 1 (October 20, 2009): 114–29. http://dx.doi.org/10.2174/1874196700902010114.
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Angiogenic factors, including bFGF and VEGF, induce cytosolic calcium (Cac) increases in endothelial cells, critically involved in angiogenesis progression. At low agonist concentrations, Cac elevation is mainly due to calcium entry controlled by a complex interplay between two intracellular messengers, arachidonic acid (AA) and nitric oxide (NO), released upon stimulation with proangiogenic factors: they trigger spatially localized calcium signals restricted to the cell periphery, and such a spatiotemporal pattern could contribute to the specificity of cellular responses. Based on experimental measurements, here we provide the first quantitative spatiotemporal 3D modeling of proangiogenic calcium events in endothelial cells using Virtual Cell framework. The main aims were to validate previously proposed signaling pathways and to suggest new experimental protocols. The most relevant conclusions are: 1. The interplay between AA and NO, previously proposed to be responsible for VEGF/bFGF-dependent calcium entry in endothelial cells, triggers peripheral calcium signals that reproduce the experimental measurements; 2. Spatial restriction is not an artefact due to the calcium-sensitive dye; 3. Channels clusterization in thin lamellipodia plays a key role in the generation of the peripheral-restricted proangiogenic calcium signals; 4. A model containing two distinct channels, named AAAC and NOAC, respectively activated by AA or NO, explains the basic properties of proangiogenic calcium signals. This could be considered an ‘open model’ containing the simplest conditions leading to a satisfactory reproduction of the experimental results: it should be implemented in order to make it more complete and to maximize physical and biochemical constraints.
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Özturan, Doğancan, Tunç Morova, and Nathan A. Lack. "Androgen Receptor-Mediated Transcription in Prostate Cancer." Cells 11, no. 5 (March 5, 2022): 898. http://dx.doi.org/10.3390/cells11050898.
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Androgen receptor (AR)-mediated transcription is critical in almost all stages of prostate cancer (PCa) growth and differentiation. This process involves a complex interplay of coregulatory proteins, chromatin remodeling complexes, and other transcription factors that work with AR at cis-regulatory enhancer regions to induce the spatiotemporal transcription of target genes. This enhancer-driven mechanism is remarkably dynamic and undergoes significant alterations during PCa progression. In this review, we discuss the AR mechanism of action in PCa with a focus on how cis-regulatory elements modulate gene expression. We explore emerging evidence of genetic variants that can impact AR regulatory regions and alter gene transcription in PCa. Finally, we highlight several outstanding questions and discuss potential mechanisms of this critical transcription factor.
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Li, Chao, Meng Cheng, Maoyan Zhu, and Timothy W. Lyons. "Heterogeneous and dynamic marine shelf oxygenation and coupled early animal evolution." Emerging Topics in Life Sciences 2, no. 2 (June 29, 2018): 279–88. http://dx.doi.org/10.1042/etls20170157.
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It is generally agreed that early diversification of animals and significant rise of atmospheric and oceanic oxygen (O2) levels occurred in the Ediacaran (635–541 million years ago, Ma) and early Cambrian (ca. 541–509 Ma). The strength and nature of their relationship, however, remain unclear and debated. A recent wave of paleoredox research — with a particular focus on the fossiliferous sections in South China — demonstrates high spatial heterogeneity of oceanic O2 (redox) conditions and dynamic marine shelf oxygenation in a dominantly anoxic ocean during the Ediacaran and early Cambrian. This pattern shows a general spatiotemporal coupling to early animal evolution. We attribute dynamic shelf oxygenation to a complex interplay among the evolving atmosphere, continents, oceans, and biosphere during a critical period in Earth history. Our review supports the idea of a complex coevolution between increasing O2 levels and early diversification of animals, although additional work is required to fully delineate the timing and patterns of this coevolution and the mechanistic underpinnings.
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Frank, Lawrence R., Vitaly L. Galinsky, Leigh Orf, and Joshua Wurman. "Dynamic Multiscale Modes of Severe Storm Structure Detected in Mobile Doppler Radar Data by Entropy Field Decomposition." Journal of the Atmospheric Sciences 75, no. 3 (February 20, 2018): 709–30. http://dx.doi.org/10.1175/jas-d-17-0117.1.
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Abstract The detection of complex spatially and temporally varying coherent structures in data from highly nonlinear and non-Gaussian systems is a challenging problem in a wide range of scientific disciplines. This is the case in the analysis of Doppler on Wheels (DOW) mobile Doppler radar (MDR) data where the goal is to detect rapidly evolving coherent storm structures that reflect the complex interplay of nonlinear dynamical processes. Estimating and quantifying such structures from the noisy and relatively sparsely sampled MDR data poses a difficult inverse problem for which traditional analysis methods such as expert and subjective pattern recognition, thresholding, and contouring choices can be difficult. In this paper the authors investigate the application of a recently developed objective method for the analysis of spatiotemporal data called the entropy field decomposition (EFD) to the problem of the analysis of MDR data in tornadic supercells. The EFD method is based on a field theoretic reformulation of Bayesian probability theory that incorporates prior information from the coupling structure within the data to automatically detect multivariate spatiotemporal modes. The method is first applied to data from a numerically simulated tornadic supercell in order to validate the method’s ability to detect and quantify known storm-scale features. It is then applied to actual MDR data collected during the evolution of a tornadic supercell—data that have been analyzed previously by experts. The authors demonstrate the ability of the EFD method to detect spatiotemporal features currently believed to be related to tornadogenesis. This new method has the potential to provide improved and objective analysis/detection with increased sensitivity to nonlinear and non-Gaussian spatially and temporally coherent features related to tornadogenesis and thus offers the potential to aid in the study, prediction, and warnings of tornadoes.
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Litwin, Piotr, Beata Zybura, and Paweł Motyka. "Tactile information counteracts the attenuation of rubber hand illusion attributable to increased visuo-proprioceptive divergence." PLOS ONE 15, no. 12 (December 30, 2020): e0244594. http://dx.doi.org/10.1371/journal.pone.0244594.
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Sense of body ownership is an immediate and distinct experience of one’s body as belonging to oneself. While it is well-recognized that ownership feelings emerge from the integration of visual and somatosensory signals, the principles upon which they are integrated are still intensely debated. Here, we used the rubber hand illusion (RHI) to examine how the interplay of visual, tactile, and proprioceptive signals is governed depending on their spatiotemporal properties. For this purpose, the RHI was elicited in different conditions varying with respect to the extent of visuo-proprioceptive divergence (i.e., the distance between the real and fake hands) and differing in terms of the availability and spatiotemporal complexity of tactile stimulation (none, simple, or complex). We expected that the attenuating effect of distance on illusion strength will be more pronounced in the absence of touch (when proprioception gains relatively higher importance) and absent in the presence of complex tactile signals. Additionally, we hypothesized that participants with greater proprioceptive acuity—assessed using an elbow joint position discrimination task—will be less susceptible to the illusion, but only under the conditions of limited tactile stimulation. In line with our prediction, RHI was attenuated at the farthest distance only when tactile information was absent or simplified, but the attenuation was effectively prevented by the use of complex tactile stimulation—in this case, RHI was comparably vivid at both distances. However, passive proprioceptive acuity was not related to RHI strength in either of the conditions. The results indicate that complex-structured tactile signals can override the influence of proprioceptive signals in body attribution processes. These findings extend our understanding of body ownership by showing that it is primarily determined by informative cues from the most relevant sensory domains, rather than mere accumulation of multisensory evidence.
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Mentkowski, Kyle I., Lindsey M. Euscher, Akshar Patel, B. Rita Alevriadou, and Jennifer K. Lang. "Monocyte recruitment and fate specification after myocardial infarction." American Journal of Physiology-Cell Physiology 319, no. 5 (November 1, 2020): C797—C806. http://dx.doi.org/10.1152/ajpcell.00330.2020.
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Monocytes are critical mediators of the inflammatory response following myocardial infarction (MI) and ischemia-reperfusion injury. They are involved in both initiation and resolution of inflammation and play an integral role in cardiac repair. The antagonistic nature of their function is dependent on their subset heterogeneity and biphasic response following injury. New advancements in single-cell transcriptomics and mass cytometry have allowed us to identify smaller, transcriptionally distinct clusters that may have functional relevance in disease and homeostasis. Additionally, recent insights into the spatiotemporal dynamics of monocytes following ischemic injury and their subsequent interactions with the endothelium and other immune cells reveal a complex interplay between monocytes and the cardiac milieu. In this review, we highlight recent findings on monocyte functional heterogeneity, present new mechanistic insight into monocyte recruitment and fate specification following MI, and discuss promising therapeutic avenues targeting monocytes for the treatment of ischemic heart disease.
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Dharmadana, Durga, Nicholas P. Reynolds, Charlotte E. Conn, and Céline Valéry. "Molecular interactions of amyloid nanofibrils with biological aggregation modifiers: implications for cytotoxicity mechanisms and biomaterial design." Interface Focus 7, no. 4 (June 16, 2017): 20160160. http://dx.doi.org/10.1098/rsfs.2016.0160.
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Amyloid nanofibrils are ubiquitous biological protein fibrous aggregates, with a wide range of either toxic or beneficial activities that are relevant to human disease and normal biology. Protein amyloid fibrillization occurs via nucleated polymerization, through non-covalent interactions. As such, protein nanofibril formation is based on a complex interplay between kinetic and thermodynamic factors. The process entails metastable oligomeric species and a highly thermodynamically favoured end state. The kinetics, and the reaction pathway itself, can be influenced by third party moieties, either molecules or surfaces. Specifically, in the biological context, different classes of biomolecules are known to act as catalysts, inhibitors or modifiers of the generic protein fibrillization process. The biological aggregation modifiers reviewed here include lipid membranes of varying composition, glycosaminoglycans and metal ions, with a final word on xenobiotic compounds. The corresponding molecular interactions are critically analysed and placed in the context of the mechanisms of cytotoxicity of the amyloids involved in diverse pathologies and the non-toxicity of functional amyloids (at least towards their biological host). Finally, the utilization of this knowledge towards the design of bio-inspired and biocompatible nanomaterials is explored.
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Gessner, Isabel, and Ines Neundorf. "Nanoparticles Modified with Cell-Penetrating Peptides: Conjugation Mechanisms, Physicochemical Properties, and Application in Cancer Diagnosis and Therapy." International Journal of Molecular Sciences 21, no. 7 (April 6, 2020): 2536. http://dx.doi.org/10.3390/ijms21072536.
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Based on their tunable physicochemical properties and the possibility of producing cell-specific platforms through surface modification with functional biomolecules, nanoparticles (NPs) represent highly promising tools for biomedical applications. To improve their potential under physiological conditions and to enhance their cellular uptake, combinations with cell-penetrating peptides (CPPs) represent a valuable strategy. CPPs are often cationic peptide sequences that are able to translocate across biological membranes and to carry attached cargos inside cells and have thus been recognized as versatile tools for drug delivery. Nevertheless, the conjugation of CPP to NP surfaces is dependent on many properties from both individual components, and further insight into this complex interplay is needed to allow for the fabrication of highly stable but functional vectors. Since CPPs per se are nonselective and enter nearly all cells likewise, additional decoration of NPs with homing devices, such as tumor-homing peptides, enables the design of multifunctional platforms for the targeted delivery of chemotherapeutic drugs. In this review, we have updated the recent advances in the field of CPP-NPs, focusing on synthesis strategies, elucidating the influence of different physicochemical properties, as well as their application in cancer research.
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Becker, Alyssa L., and Arup K. Indra. "Oxidative Stress in Melanoma: Beneficial Antioxidant and Pro-Oxidant Therapeutic Strategies." Cancers 15, no. 11 (June 2, 2023): 3038. http://dx.doi.org/10.3390/cancers15113038.
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Cutaneous melanoma ranks as the fifth most common cancer in the United States and represents one of the deadliest forms of skin cancer. While recent advances in systemic targeted therapies and immunotherapies have positively impacted melanoma survival, the survival rate of stage IV melanoma remains at a meager 32%. Unfortunately, tumor resistance can impede the effectiveness of these treatments. Oxidative stress is a pivotal player in all stages of melanoma progression, with a somewhat paradoxical function that promotes tumor initiation but hinders vertical growth and metastasis in later disease. As melanoma progresses, it employs adaptive mechanisms to lessen oxidative stress in the tumor environment. Redox metabolic rewiring has been implicated in acquired resistance to BRAF/MEK inhibitors. A promising approach to enhance the response to therapy involves boosting intracellular ROS production using active biomolecules or targeting enzymes that regulate oxidative stress. The complex interplay between oxidative stress, redox homeostasis, and melanomagenesis can also be leveraged in a preventive context. The purpose of this review is to provide an overview of oxidative stress in melanoma, and how the antioxidant system may be manipulated in a therapeutic context for improved efficacy and survival.
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Guimarães, Paulo R. "The Structure of Ecological Networks Across Levels of Organization." Annual Review of Ecology, Evolution, and Systematics 51, no. 1 (November 2, 2020): 433–60. http://dx.doi.org/10.1146/annurev-ecolsys-012220-120819.
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Interactions connect the units of ecological systems, forming networks. Individual-based networks characterize variation in niches among individuals within populations. These individual-based networks merge with each other, forming species-based networks and food webs that describe the architecture of ecological communities. Networks at broader spatiotemporal scales portray the structure of ecological interactions across landscapes and over macroevolutionary time. Here, I review the patterns observed in ecological networks across multiple levels of biological organization. A fundamental challenge is to understand the amount of interdependence as we move from individual-based networks to species-based networks and beyond. Despite the uneven distribution of studies, regularities in network structure emerge across scales due to the fundamental architectural patterns shared by complex networks and the interplay between traits and numerical effects. I illustrate the integration of these organizational scales by exploring the consequences of the emergence of highly connected species for network structures across scales.
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Gaire, Janak, Valentina Supper, Darrice Montgomery, and Chelsey S. Simmons. "Spiny mice (Acomys) cells fail to engraft in NOD scid gamma." PLOS ONE 18, no. 5 (May 19, 2023): e0286000. http://dx.doi.org/10.1371/journal.pone.0286000.
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Immune cells and stromal cells regulate wound healing and regeneration through complex activation patterns with spatiotemporal variation. The scarless regeneration of Spiny mice (Acomys species) is no exception; differential activation of immune and stromal cell populations seems to play a role in its remarkable regenerative capacity. To elucidate the role and interplay of Acomys immune cells in mammalian regeneration, we sought to create Acomys-Mus chimeras by transplanting bone marrow (BM) from Acomys into NOD Scid Gamma (NSG), a severely immunodeficient mouse line often used in creating humanized mice. Here, we report that Acomys BM cells fail to reconstitute and differentiate when transferred to irradiated NSG adults and neonates. In addition, we did not detect the presence of donor cells nor observe the onset of Graft versus Host Disease (GvHD)-like pathology, even after transplanting Acomys splenocytes in Acomys-Mus chimeras suggesting early graft failure. Overall, these results demonstrate the adoptive transfer of Acomys BM alone is not sufficient to establish Acomys hematopoietic system in NSG mouse.
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Wang, Weiqiang, and Rui Zhang. "Interplay of Active Stress and Driven Flow in Self-Assembled, Tumbling Active Nematics." Crystals 11, no. 9 (September 4, 2021): 1071. http://dx.doi.org/10.3390/cryst11091071.
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Lyotropic chromonic liquid crystals (LCLCs) are a special type of hierarchical material in which self-assembled molecular aggregates are responsible for the formation of liquid crystal phases. Thanks to its unusual material properties and bio compatibility, it has found wide applications including the formation of active nematic liquid crystals. Recent experiments have uncovered tumbling character of certain LCLCs. However, how tumbling behavior modifies structure and flow in driven and active nematics is poorly understood. Here, we rely on continuum simulation to study the interplay of extensile active stress and externally driven flow in a flow-tumbling nematic with a low twist modulus to mimic nematic LCLCs. We find that a spontaneous transverse flow can be developed in a flow-tumbling active nematic confined to a hybrid alignment cell when it is in log-rolling mode at sufficiently high activities. The orientation of the total spontaneous flow is tunable by tuning the active stress. We further show that activity can suppress pressure-driven flow of a flow-tumbling nematic in a planar-anchoring cell but can also promote a transition of the director field under a pressure gradient in a homeotropic-anchoring cell. Remarkably, we demonstrate that the frequency of unsteady director dynamics in a tumbling nematic under Couette flow is invariant against active stress when below a threshold activity but exhibits a discontinuous increase when above the threshold at which a complex, periodic spatiotemporal director pattern emerges. Taken together, our simulations reveal qualitative differences between flow-tumbling and flow-aligning active nematics and suggest potential applications of tumbling nematics in microfluidics.
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Kim, Kyra, and James Heiss. "Methods in Capturing the Spatiotemporal Dynamics of Flow and Biogeochemical Reactivity in Sandy Beach Aquifers: A Review." Water 13, no. 6 (March 13, 2021): 782. http://dx.doi.org/10.3390/w13060782.
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Sandy beach aquifers are complex hydrological and biogeochemical systems where fresh groundwater and seawater mix. The extent of the intertidal mixing zone and the rates of circulating flows within beaches are a primary control on porewater chemistry and microbiology of the intertidal subsurface. Interplay between the hydrological and biogeochemical processes at these land-sea transition zones moderate fluxes of chemicals, particulates, heavy metals, and biota across the aquifer-ocean interface, affecting coastal water quality and nutrient loads to marine ecosystems. Thus, it is important to characterize hydrological and biogeochemical processes in beach aquifers when estimating material fluxes to the ocean. This can be achieved through a suite of cross-disciplinary measurements of beach groundwater flow and chemistry. In this review, we present measurement approaches that have been developed and employed to characterize the physical (geology, topography, subsurface hydrology) and biogeochemical (solute and particulate distributions, reaction rates) properties of and processes occurring within sandy intertidal aquifers. As applied to beach systems, we discuss vibracoring, sample collection, laboratory experiments, variable-density considerations, instrument construction, and sensor technologies. We discuss advantages and limitations of typical hydrologic field sampling methods when used to investigate beach aquifers and provide a measurement framework for researchers seeking to sample and collect data from these systems.
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Sajadimajd, Soraya, and Mozafar Khazaei. "Oxidative Stress and Cancer: The Role of Nrf2." Current Cancer Drug Targets 18, no. 6 (June 11, 2018): 538–57. http://dx.doi.org/10.2174/1568009617666171002144228.
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Oxidative stress due to imbalance between ROS production and detoxification plays a pivotal role in determining cell fate. In response to the excessive ROS, apoptotic signaling pathway is activated to promote normal cell death. However, through deregulation of biomolecules, high amount of ROS promotes carcinogenesis in cells with defective signaling factors. In this line, NRF2 appears to be as a master regulator, which protects cells from oxidative and electrophilic stress. Nrf2 is an intracellular transcription factor that regulates the expression of a number of genes to encode anti-oxidative enzymes, detoxifying factors, anti-apoptotic proteins and drug transporters. Under normal condition, Nrf2 is commonly degraded in cytoplasm by interaction with Keap1 inhibitor as an adaptor for ubiquitination factors. However, high amount of ROS activates tyrosine kinases to dissociate Nrf2: Keap1 complex, nuclear import of Nrf2 and coordinated activation of cytoprotective gene expression. Nevertheless, deregulation of Nrf2 and/or Keap1 due to mutation and activated upstream oncogenes is associated with nuclear accumulation and constitutive activation of Nrf2 to protect cells from apoptosis and induce proliferation, metastasis and chemoresistance. Owning to the interplay of ROS and Nrf2 signaling pathways with carcinogenesis, Nrf2 modulation seems to be important in the personalization of cancer therapy.
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Perrella, Fulvio, Federico Coppola, Nadia Rega, and Alessio Petrone. "An Expedited Route to Optical and Electronic Properties at Finite Temperature via Unsupervised Learning." Molecules 28, no. 8 (April 12, 2023): 3411. http://dx.doi.org/10.3390/molecules28083411.
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Electronic properties and absorption spectra are the grounds to investigate molecular electronic states and their interactions with the environment. Modeling and computations are required for the molecular understanding and design strategies of photo-active materials and sensors. However, the interpretation of such properties demands expensive computations and dealing with the interplay of electronic excited states with the conformational freedom of the chromophores in complex matrices (i.e., solvents, biomolecules, crystals) at finite temperature. Computational protocols combining time dependent density functional theory and ab initio molecular dynamics (MD) have become very powerful in this field, although they require still a large number of computations for a detailed reproduction of electronic properties, such as band shapes. Besides the ongoing research in more traditional computational chemistry fields, data analysis and machine learning methods have been increasingly employed as complementary approaches for efficient data exploration, prediction and model development, starting from the data resulting from MD simulations and electronic structure calculations. In this work, dataset reduction capabilities by unsupervised clustering techniques applied to MD trajectories are proposed and tested for the ab initio modeling of electronic absorption spectra of two challenging case studies: a non-covalent charge-transfer dimer and a ruthenium complex in solution at room temperature. The K-medoids clustering technique is applied and is proven to be able to reduce by ∼100 times the total cost of excited state calculations on an MD sampling with no loss in the accuracy and it also provides an easier understanding of the representative structures (medoids) to be analyzed on the molecular scale.
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Fatoux-Ardore, Marie, Franck Peysselon, Anthony Weiss, Patrick Bastien, Francine Pratlong, and Sylvie Ricard-Blum. "Large-Scale Investigation of Leishmania Interaction Networks with Host Extracellular Matrix by Surface Plasmon Resonance Imaging." Infection and Immunity 82, no. 2 (November 25, 2013): 594–606. http://dx.doi.org/10.1128/iai.01146-13.
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ABSTRACTWe have set up an assay to study the interactions of live pathogens with their hosts by using protein and glycosaminoglycan arrays probed by surface plasmon resonance imaging. We have used this assay to characterize the interactions ofLeishmaniapromastigotes with ∼70 mammalian host biomolecules (extracellular proteins, glycosaminoglycans, growth factors, cell surface receptors). We have identified, in total, 27 new partners (23 proteins, 4 glycosaminoglycans) of procyclic promastigotes of sixLeishmaniaspecies and 18 partners (15 proteins, 3 glycosaminoglycans) of three species of stationary-phase promastigotes for all the strains tested. The diversity of the interaction repertoires ofLeishmaniaparasites reflects their dynamic and complex interplay with their mammalian hosts, which depends mostly on the species and strains ofLeishmania. Stationary-phaseLeishmaniaparasites target extracellular matrix proteins and glycosaminoglycans, which are highly connected in the extracellular interaction network. Heparin and heparan sulfate bind to mostLeishmaniastrains tested, and 6-O-sulfate groups play a crucial role in these interactions. NumerousLeishmaniastrains bind to tropoelastin, and some strains are even able to degrade it. Several strains interact with collagen VI, which is expressed by macrophages. MostLeishmaniapromastigotes interact with several regulators of angiogenesis, including antiangiogenic factors (endostatin, anastellin) and proangiogenic factors (ECM-1, VEGF, and TEM8 [also known as anthrax toxin receptor 1]), which are regulated by hypoxia. Since hypoxia modulates the infection of macrophages by the parasites, these interactions might influence the infection of host cells byLeishmania.
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Cloete, Karen J., Žiga Šmit, and Alessandra Gianoncelli. "Multidimensional Profiling of Human Body Hairs Using Qualitative and Semi-Quantitative Approaches with SR-XRF, ATR-FTIR, DSC, and SEM-EDX." International Journal of Molecular Sciences 24, no. 4 (February 19, 2023): 4166. http://dx.doi.org/10.3390/ijms24044166.
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This study aimed to assess the potential of a multidimensional approach to differentiate body hairs based on their physico-chemical properties and whether body hairs can replace the use of scalp hair in studies linked to forensic and systemic intoxication. This is the first case report controlling for confounding variables to explore the utility of multidimensional profiling of body hair using synchrotron synchrotron microbeam X-ray fluorescence (SR-XRF) for longitudinal and hair morphological region mapping) and benchtop methods, including attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) (complemented with chemometrics analysis), energy dispersive X-ray analysis (EDX) (complemented with heatmap analysis), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) analysis (complemented by descriptive statistics) to profile different body hairs in terms of their elemental, biochemical, thermal, and cuticle properties. This multidimensional approach provided supportive information to emphasize the intricate and rather complex interplay between the organization and levels of elements and biomolecules within the crystalline and amorphous matrix of different body hairs responsible for the differences in physico-chemical properties between body hairs that are predominantly affected by the growth rate, follicle or apocrine gland activity, and external factors such as cosmetic use and exposure to environmental xenobiotics. The data from this study may have important implications for forensic science, toxicology and systemic intoxication, or other studies involving hair as a research matrix.
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Torok, Justin, Pedro D. Maia, Parul Verma, Christopher Mezias, and Ashish Raj. "Emergence of directional bias in tau deposition from axonal transport dynamics." PLOS Computational Biology 17, no. 7 (July 27, 2021): e1009258. http://dx.doi.org/10.1371/journal.pcbi.1009258.
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Defects in axonal transport may partly underpin the differences between the observed pathophysiology of Alzheimer’s disease (AD) and that of other non-amyloidogenic tauopathies. Particularly, pathological tau variants may have molecular properties that dysregulate motor proteins responsible for the anterograde-directed transport of tau in a disease-specific fashion. Here we develop the first computational model of tau-modified axonal transport that produces directional biases in the spread of tau pathology. We simulated the spatiotemporal profiles of soluble and insoluble tau species in a multicompartment, two-neuron system using biologically plausible parameters and time scales. Changes in the balance of tau transport feedback parameters can elicit anterograde and retrograde biases in the distributions of soluble and insoluble tau between compartments in the system. Aggregation and fragmentation parameters can also perturb this balance, suggesting a complex interplay between these distinct molecular processes. Critically, we show that the model faithfully recreates the characteristic network spread biases in both AD-like and non-AD-like mouse tauopathy models. Tau transport feedback may therefore help link microscopic differences in tau conformational states and the resulting variety in clinical presentations.
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Albert, Noémi. "“A Multitude of Drops.” David Mitchell’s Cloud Atlas and the Subject between Space and Time." Acta Universitatis Sapientiae, Philologica 11, no. 1 (November 1, 2019): 49–63. http://dx.doi.org/10.2478/ausp-2019-0004.
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Abstract David Mitchell’s Cloud Atlas (2004) presents its readers with a “borderless world.” This borderlessness concerns space and time, with complex and interweaving spatiotemporal planes. In this fictional world, the subject will serve as an entity that brings together disparate spatialities and temporalities through an intricate symbolic web that connects the subject’s body to the world it inhabits. Numerous versions of past, present, and future run in parallel, the actual and the virtual coexist, and the text folds upon itself. The novel operates a constant state of liminality, a state that will be embodied by the subject. Seemingly in a paradoxical way, the multiple liminal states identifiable in the novel convey the ultimate sense of borderlessness. It is exactly the work’s heterogeneity, its jumps through time and space, its interrupted chapter structure that lend it a special unity and coherence that erases both geographical and temporal borders. The novel’s structure goes into thematic depths and creates a bridge, a constant interplay between form and content, captured in the metaphor of the concertina. Consequently, Cloud Atlas creates a constantly shifting world where the only fixed entity is the subject and its comet-shaped birthmark.
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Fink, Charles C., Boris Slepchenko, Ion I. Moraru, James Schaff, James Watras, and Leslie M. Loew. "Morphological Control of Inositol-1,4,5-Trisphosphate–Dependent Signals." Journal of Cell Biology 147, no. 5 (November 29, 1999): 929–36. http://dx.doi.org/10.1083/jcb.147.5.929.
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Inositol-1,4,5-trisphosphate (InsP3)-mediated calcium signals represent an important mechanism for transmitting external stimuli to the cell. However, information about intracellular spatial patterns of InsP3 itself is not generally available. In particular, it has not been determined how the interplay of InsP3 generation, diffusion, and degradation within complex cellular geometries can control the patterns of InsP3 signaling. Here, we explore the spatial and temporal characteristics of [InsP3]cyt during a bradykinin-induced calcium wave in a neuroblastoma cell. This is achieved by using a unique image-based computer modeling system, Virtual Cell, to integrate experimental data on the rates and spatial distributions of the key molecular components of the process. We conclude that the characteristic calcium dynamics requires rapid, high-amplitude production of [InsP3]cyt in the neurite. This requisite InsP3 spatiotemporal profile is provided, in turn, as an intrinsic consequence of the cell's morphology, demonstrating how geometry can locally and dramatically intensify cytosolic signals that originate at the plasma membrane. In addition, the model predicts, and experiments confirm, that stimulation of just the neurite, but not the soma or growth cone, is sufficient to generate a calcium response throughout the cell.
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Rathjens, Hendrik, Jens Kiesel, Michael Winchell, Jeffrey Arnold, and Robin Sur. "Technical note: Extending the SWAT model to transport chemicals through tile and groundwater flow." Hydrology and Earth System Sciences 27, no. 1 (January 9, 2023): 159–67. http://dx.doi.org/10.5194/hess-27-159-2023.
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Abstract. The Soil and Water Assessment Tool (SWAT) is frequently used to simulate the transport of water-soluble chemicals in the environment such as pesticides and their metabolites originating from agricultural applications. However, the model does not simulate the transport of chemicals through subsurface tile drains and groundwater. This limitation is particularly significant in lowland regions and when simulating stable chemicals that can leach into and accumulate in groundwater. To fill this gap, the publicly available SWAT code was modified to complement the simulation of chemicals by adding transport capabilities through tile and groundwater flow. The extended model was tested in two agricultural catchments with a typically used pesticide and one of its metabolites. Results show that the transport of the pesticide is mainly governed by surface runoff and that shallow surface tile flow contributions can be significant. Metabolite concentrations in streamflow are, however, driven by a complex spatiotemporal interplay of all surface and subsurface transport components. This highlights the advantages of applying the modified code in catchment-scale environmental exposure studies and for developing best management practices or mitigation strategies. The new code is made available as an electronic supplement to this technical note.
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Goddard, Erin, Samuel G. Solomon, and Thomas A. Carlson. "Dynamic population codes of multiplexed stimulus features in primate area MT." Journal of Neurophysiology 118, no. 1 (July 1, 2017): 203–18. http://dx.doi.org/10.1152/jn.00954.2016.
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The middle-temporal area (MT) of primate visual cortex is critical in the analysis of visual motion. Single-unit studies suggest that the response dynamics of neurons within area MT depend on stimulus features, but how these dynamics emerge at the population level, and how feature representations interact, is not clear. Here, we used multivariate classification analysis to study how stimulus features are represented in the spiking activity of populations of neurons in area MT of marmoset monkey. Using representational similarity analysis we distinguished the emerging representations of moving grating and dot field stimuli. We show that representations of stimulus orientation, spatial frequency, and speed are evident near the onset of the population response, while the representation of stimulus direction is slower to emerge and sustained throughout the stimulus-evoked response. We further found a spatiotemporal asymmetry in the emergence of direction representations. Representations for high spatial frequencies and low temporal frequencies are initially orientation dependent, while those for high temporal frequencies and low spatial frequencies are more sensitive to motion direction. Our analyses reveal a complex interplay of feature representations in area MT population response that may explain the stimulus-dependent dynamics of motion vision. NEW & NOTEWORTHY Simultaneous multielectrode recordings can measure population-level codes that previously were only inferred from single-electrode recordings. However, many multielectrode recordings are analyzed using univariate single-electrode analysis approaches, which fail to fully utilize the population-level information. Here, we overcome these limitations by applying multivariate pattern classification analysis and representational similarity analysis to large-scale recordings from middle-temporal area (MT) in marmoset monkeys. Our analyses reveal a dynamic interplay of feature representations in area MT population response.
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Rosés, Raquel, Cristina Kadar, Charlotte Gerritsen, and Chris Rouly. "Simulating Offender Mobility: Modeling Activity Nodes from Large-Scale Human Activity Data." Journal of Artificial Intelligence Research 68 (July 9, 2020): 541–70. http://dx.doi.org/10.1613/jair.1.11831.
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In recent years, simulation techniques have been applied to investigate the spatiotemporal dynamics of crime. Researchers have instantiated mobile offenders in agent-based simulations for theory testing, experimenting with crime prevention strategies, and exploring crime prediction techniques, despite facing challenges due to the complex dynamics of crime and the lack of detailed information about offender mobility. This paper presents a simulation model to explore offender mobility, focusing on the interplay between the agent's awareness space and activity nodes. The simulation generates patterns of individual mobility aiming to cumulatively match crime patterns. To instantiate a realistic urban environment, we use open data to simulate the urban structure, location-based social networks data to represent activity nodes as a proxy for human activity, and taxi trip data as a proxy for human movement between regions of the city. We analyze and systematically compare 35 different mobility strategies and demonstrate the benefits of using large-scale human activity data to simulate offender mobility. The strategies combining taxi trip data or historic crime data with popular activity nodes perform best compared to other strategies, especially for robbery. Our approach provides a basis for building agent-based crime simulations that infer offender mobility in urban areas from real-world data.
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De Groef, Lies, Manuel Salinas-Navarro, Griet Van Imschoot, Claude Libert, Roosmarijn E. Vandenbroucke, and Lieve Moons. "Decreased TNF Levels and Improved Retinal Ganglion Cell Survival in MMP-2 Null Mice Suggest a Role for MMP-2 as TNF Sheddase." Mediators of Inflammation 2015 (2015): 1–13. http://dx.doi.org/10.1155/2015/108617.
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Matrix metalloproteinases (MMPs) have been designated as both friend and foe in the central nervous system (CNS): while being involved in many neurodegenerative and neuroinflammatory diseases, their actions appear to be indispensable to a healthy CNS. Pathological conditions in the CNS are therefore often related to imbalanced MMP activities and disturbances of the complex MMP-dependent protease network. Likewise, in the retina, various studies in animal models and human patients suggested MMPs to be involved in glaucoma. In this study, we sought to determine the spatiotemporal expression profile of MMP-2 in the excitotoxic retina and to unravel its role during glaucoma pathogenesis. We reveal that intravitreal NMDA injection induces MMP-2 expression to be upregulated in the Müller glia. Moreover, MMP-2 null mice display attenuated retinal ganglion cell death upon excitotoxic insult to the retina, which is accompanied by normal glial reactivity, yet reduced TNF levels. Hence, we propose a novelin vivofunction for MMP-2, as an activating sheddase of tumor necrosis factor (TNF). Given the pivotal role of TNF as a proinflammatory cytokine and neurodegeneration-exacerbating mediator, these findings generate important novel insights into the pathological processes contributing to glaucomatous neurodegeneration and into the interplay of neuroinflammation and neurodegeneration in the CNS.
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Willoughby, D., and D. M. F. Cooper. "Use of single-cell imaging techniques to assess the regulation of cAMP dynamics." Biochemical Society Transactions 34, no. 4 (July 21, 2006): 468–71. http://dx.doi.org/10.1042/bst0340468.
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cAMP is a ubiquitous intracellular signalling molecule that can regulate a wide array of cellular processes. The diversity of action of this second messenger owes much to the localized generation, action and hydrolysis of cAMP within discrete subcellular regions. Further signalling specificity can be achieved by the ability of cells to modulate the frequency or incidence of such cAMP signals. Here, we discuss the use of two cAMP biosensors that measure real-time cAMP changes in the single cell, to address the mechanisms underlying the generation of dynamic cAMP signals. The first method monitors sub-plasmalemmal cAMP changes using mutant cyclic nucleotide-gated channels and identifies an AKAP (A-kinase-anchoring protein)–protein kinase A–PDE4 (phosphodiesterase-4) signalling complex that is central to the generation of dynamic cAMP transients in this region of the cell. The second study uses a fluorescence resonance energy transfer-based cAMP probe, based on Epac1 (exchange protein directly activated by cAMP 1), to examine interplay between Ca2+ and cAMP signals. This study demonstrates real-time oscillations in cAMP driven by a Ca2+-stimulated AC (adenylate cyclase) (AC8) and subsequent PDE4 activity. These studies, using two very different single-cell cAMP probes, broaden our understanding of the specific spatiotemporal characteristics of agonist-evoked cAMP signals in a model cell system.
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Papanicolaou, Natali, and Alessandro Bonetti. "The New Frontier of Functional Genomics: From Chromatin Architecture and Noncoding RNAs to Therapeutic Targets." SLAS DISCOVERY: Advancing the Science of Drug Discovery 25, no. 6 (June 2, 2020): 568–80. http://dx.doi.org/10.1177/2472555220926158.
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Common diseases are complex, multifactorial disorders whose pathogenesis is influenced by the interplay of genetic predisposition and environmental factors. Genome-wide association studies have interrogated genetic polymorphisms across genomes of individuals to test associations between genotype and susceptibility to specific disorders, providing insights into the genetic architecture of several complex disorders. However, genetic variants associated with the susceptibility to common diseases are often located in noncoding regions of the genome, such as tissue-specific enhancers or long noncoding RNAs, suggesting that regulatory elements might play a relevant role in human diseases. Enhancers are cis-regulatory genomic sequences that act in concert with promoters to regulate gene expression in a precise spatiotemporal manner. They can be located at a considerable distance from their cognate target promoters, increasing the difficulty of their identification. Genomes are organized in domains of chromatin folding, namely topologically associating domains (TADs). Identification of enhancer–promoter interactions within TADs has revealed principles of cell-type specificity across several organisms and tissues. The vast majority of mammalian genomes are pervasively transcribed, accounting for a previously unappreciated complexity of the noncoding RNA fraction. Particularly, long noncoding RNAs have emerged as key players for the establishment of chromatin architecture and regulation of gene expression. In this perspective, we describe the new advances in the fields of transcriptomics and genome organization, focusing on the role of noncoding genomic variants in the predisposition of common diseases. Finally, we propose a new framework for the identification of the next generation of pharmacological targets for common human diseases.
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Kang, Byungho, and Orencio Duran Vinent. "The Application of CNN-Based Image Segmentation for Tracking Coastal Erosion and Post-Storm Recovery." Remote Sensing 15, no. 14 (July 11, 2023): 3485. http://dx.doi.org/10.3390/rs15143485.
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Coastal erosion due to extreme events can cause significant damage to coastal communities and deplete beaches. Post-storm beach recovery is a crucial natural process that rebuilds coastal morphology and reintroduces eroded sediment to the subaerial beach. However, monitoring the beach recovery, which occurs at various spatiotemporal scales, presents a significant challenge. This is due to, firstly, the complex interplay between factors such as storm-induced erosion, sediment availability, local topography, and wave and wind-driven sand transport; secondly, the complex morphology of coastal areas, where water, sand, debris and vegetation co-exists dynamically; and, finally, the challenging weather conditions affecting the long-term small-scale data acquisition needed to monitor the recovery process. This complexity hinders our understanding and effective management of coastal vulnerability and resilience. In this study, we apply Convolutional Neural Networks (CNN)-based semantic segmentation to high-resolution complex beach imagery. This model efficiently distinguishes between various features indicative of coastal processes, including sand texture, water content, debris, and vegetation with a mean precision of 95.1% and mean Intersection of Union (IOU) of 86.7%. Furthermore, we propose a new method to quantify false positives and negatives that allows a reliable estimation of the model’s uncertainty in the absence of a ground truth to validate the model predictions. This method is particularly effective in scenarios where the boundaries between classes are not clearly defined. We also discuss how to identify blurry beach images in advance of semantic segmentation prediction, as our model is less effective at predicting this type of image. By examining how different beach regions evolve over time through time series analysis, we discovered that rare events of wind-driven (aeolian) sand transport seem to play a crucial role in promoting the vertical growth of beaches and thus driving the beach recovery process.
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Canning, Anna Rose, Peer Fietzek, Gregor Rehder, and Arne Körtzinger. "Technical note: Seamless gas measurements across the land–ocean aquatic continuum – corrections and evaluation of sensor data for CO<sub>2</sub>, CH<sub>4</sub> and O<sub>2</sub> from field deployments in contrasting environments." Biogeosciences 18, no. 4 (February 23, 2021): 1351–73. http://dx.doi.org/10.5194/bg-18-1351-2021.
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Abstract. The ocean and inland waters are two separate regimes, with concentrations in greenhouse gases differing on orders of magnitude between them. Together, they create the land–ocean aquatic continuum (LOAC), which comprises itself largely of areas with little to no data with regards to understanding the global carbon system. Reasons for this include remote and inaccessible sample locations, often tedious methods that require collection of water samples and subsequent analysis in the lab, and the complex interplay of biological, physical and chemical processes. This has led to large inconsistencies, increasing errors and has inevitably lead to potentially false upscaling. A set-up of multiple pre-existing oceanographic sensors allowing for highly detailed and accurate measurements was successfully deployed in oceanic to remote inland regions over extreme concentration ranges. The set-up consists of four sensors simultaneously measuring pCO2, pCH4 (both flow-through, membrane-based non-dispersive infrared (NDIR) or tunable diode laser absorption spectroscopy (TDLAS) sensors), O2 and a thermosalinograph at high resolution from the same water source. The flexibility of the system allowed for deployment from freshwater to open ocean conditions on varying vessel sizes, where we managed to capture day–night cycles, repeat transects and also delineate small-scale variability. Our work demonstrates the need for increased spatiotemporal monitoring and shows a way of homogenizing methods and data streams in the ocean and limnic realms.
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Mosconi, Enrico Maria, Andrea Colantoni, Filippo Gambella, Eva Cudlinová, Luca Salvati, and Jesús Rodrigo-Comino. "Revisiting the Environmental Kuznets Curve: The Spatial Interaction between Economy and Territory." Economies 8, no. 3 (September 14, 2020): 74. http://dx.doi.org/10.3390/economies8030074.
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A complex interplay of socio-ecological drivers of change exists at the different spatiotemporal scales affecting environmental degradation. This is a key issue worldwide and needs to be understood to develop efficient management solutions. One of the most applied theories in the regional analysis is the U-shaped relationship between environmental degradation and the level of income in a given economic system or Environmental Kuznets Curve (EKC). Specifically, the EKC hypothesis underlines the (potentially positive) role of formal responses to environmental degradation grounded on government policies that are usually more ambitious in wealthier economic systems. However, there is a lack of knowledge on the role of space in EKC, arguing that spatial variability in the environment–income relationship may indicate additional targets for integrated socio–environmental policies. We hypothesize that a spatially differentiated response to environmental degradation could better adapt to differentiated local contexts. Therefore, to achieve this goal, we present a multi-scale investigation of degradation processes at the local level, providing a refined knowledge of the environment–economy linkages considering more traditional, cross-country and cross-region exercises. Our results demonstrated that—together with temporal, sectoral, and institutional aspects—space and, consequently, the related analysis’ spatial scales, are significant dimensions in ecological economics, whose investigation requires improvements in data collection and dedicated statistical approaches.
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Tlili, S., J. Yin, J. F. Rupprecht, M. A. Mendieta-Serrano, G. Weissbart, N. Verma, X. Teng, Y. Toyama, J. Prost, and T. E. Saunders. "Shaping the zebrafish myotome by intertissue friction and active stress." Proceedings of the National Academy of Sciences 116, no. 51 (November 26, 2019): 25430–39. http://dx.doi.org/10.1073/pnas.1900819116.
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Organ formation is an inherently biophysical process, requiring large-scale tissue deformations. Yet, understanding how complex organ shape emerges during development remains a major challenge. During zebrafish embryogenesis, large muscle segments, called myotomes, acquire a characteristic chevron morphology, which is believed to aid swimming. Myotome shape can be altered by perturbing muscle cell differentiation or the interaction between myotomes and surrounding tissues during morphogenesis. To disentangle the mechanisms contributing to shape formation of the myotome, we combine single-cell resolution live imaging with quantitative image analysis and theoretical modeling. We find that, soon after segmentation from the presomitic mesoderm, the future myotome spreads across the underlying tissues. The mechanical coupling between the future myotome and the surrounding tissues appears to spatially vary, effectively resulting in spatially heterogeneous friction. Using a vertex model combined with experimental validation, we show that the interplay of tissue spreading and friction is sufficient to drive the initial phase of chevron shape formation. However, local anisotropic stresses, generated during muscle cell differentiation, are necessary to reach the acute angle of the chevron in wild-type embryos. Finally, tissue plasticity is required for formation and maintenance of the chevron shape, which is mediated by orientated cellular rearrangements. Our work sheds light on how a spatiotemporal sequence of local cellular events can have a nonlocal and irreversible mechanical impact at the tissue scale, leading to robust organ shaping.
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Dentith, Jennifer E., Ruza F. Ivanovic, Lauren J. Gregoire, Julia C. Tindall, and Laura F. Robinson. "Simulating stable carbon isotopes in the ocean component of the FAMOUS general circulation model with MOSES1 (XOAVI)." Geoscientific Model Development 13, no. 8 (August 7, 2020): 3529–52. http://dx.doi.org/10.5194/gmd-13-3529-2020.
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Abstract. Ocean circulation and the marine carbon cycle can be indirectly inferred from stable and radiogenic carbon isotope ratios (δ13C and Δ14C, respectively), measured directly in the water column, or recorded in geological archives such as sedimentary microfossils and corals. However, interpreting these records is non-trivial because they reflect a complex interplay between physical and biogeochemical processes. By directly simulating multiple isotopic tracer fields within numerical models, we can improve our understanding of the processes that control large-scale isotope distributions and interpolate the spatiotemporal gaps in both modern and palaeo datasets. We have added the stable isotope 13C to the ocean component of the FAMOUS coupled atmosphere–ocean general circulation model, which is a valuable tool for simulating complex feedbacks between different Earth system processes on decadal to multi-millennial timescales. We tested three different biological fractionation parameterisations to account for the uncertainty associated with equilibrium fractionation during photosynthesis and used sensitivity experiments to quantify the effects of fractionation during air–sea gas exchange and primary productivity on the simulated δ13CDIC distributions. Following a 10 000-year pre-industrial spin-up, we simulated the Suess effect (the isotopic imprint of anthropogenic fossil fuel burning) to assess the performance of the model in replicating modern observations. Our implementation captures the large-scale structure and range of δ13CDIC observations in the surface ocean, but the simulated values are too high at all depths, which we infer is due to biases in the biological pump. In the first instance, the new 13C tracer will therefore be useful for recalibrating both the physical and biogeochemical components of FAMOUS.
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Chakraborty, Trisha, Debashish Das, Rafiq Hamdi, Ansar Khan, and Dev Niyogi. "Large-Scale Urban Heating and Pollution Domes over the Indian Subcontinent." Remote Sensing 15, no. 10 (May 22, 2023): 2681. http://dx.doi.org/10.3390/rs15102681.
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The unique geographical diversity and rapid urbanization across the Indian subcontinent give rise to large-scale spatiotemporal variations in urban heating and air emissions. The complex relationship between geophysical parameters and anthropogenic activity is vital in understanding the urban environment. This study analyses the characteristics of heating events using aerosol optical depth (AOD) level variability, across 43 urban agglomerations (UAs) with populations of a million or more, along with 13 industrial districts (IDs), and 14 biosphere reserves (BRs) in the Indian sub-continent. Pre-monsoon average surface heating was highest in the urban areas of the western (42 °C), central (41.9 °C), and southern parts (40 °C) of the Indian subcontinent. High concentration of AOD in the eastern part of the Indo-Gangetic Plain including the megacity: Kolkata (decadal average 0.708) was noted relative to other UAs over time. The statistically significant negative correlation (−0.51) between land surface temperature (LST) and AOD in urban areas during pre-monsoon time illustrates how aerosol loading impacts the surface radiation and has a net effect of reducing surface temperatures. Notable interannual variability was noted with, the pre-monsoon LST dropping in 2020 across most of the selected urban regions (approx. 89% urban clusters) while it was high in 2019 (for approx. 92% urban clusters) in the pre-monsoon season. The results indicate complex variability and correlations between LST and urban aerosol at large scales across the Indian subcontinent. These large-scale observations suggest a need for more in-depth analysis at city scales to understand the interplay and combined variability between physical and anthropogenic atmospheric parameters in mesoscale and microscale climates.
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Canepa, Federico, Massimiliano Burlando, Horia Hangan, and Djordje Romanic. "Experimental Investigation of the Near-Surface Flow Dynamics in Downburst-like Impinging Jets Immersed in ABL-like Winds." Atmosphere 13, no. 4 (April 13, 2022): 621. http://dx.doi.org/10.3390/atmos13040621.
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Downburst winds are strong downdrafts of cold air that embed into the atmospheric boundary layer (ABL) and produce intense horizontal outflow upon impingement on the ground. They are highly transient and three-dimensional extreme wind phenomena with a limited spatiotemporal structure that often makes the anemometric measurements in nature inadequate for reconstructing their complex flow fields. In the framework of the project THUNDERR, an experimental campaign on downburst outflows has been carried out at the WindEEE Dome at Western University, Canada. The present study analyzes the three-dimensional interaction between downburst (DB) outflows produced as large-scale impinging jets and ABL winds. Most experimental, numerical and analytical models in the literature neglect this flow interplay or treat it in an oversimplistic manner through a vector superposition. We found that the generated near-surface outflow is asymmetric, and a high-intensity wind zone develops at the interface between DB and ABL winds. The time variability of the leading edge of the outflow was investigated by synchronizing all wind measurements across the testing chamber. The three-dimensional flow structure was studied using a refined grid of Cobra probes that sampled the flow at high frequencies. The passage of the primary vortex produced a significant decrease in the height of maximum radial wind speed, predominantly in the ABL-streamwise direction. The turbulence intensity was the highest in the region where DB propagates into oppositely directed ABL winds.
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Atasoy, Selen, Gustavo Deco, Morten L. Kringelbach, and Joel Pearson. "Harmonic Brain Modes: A Unifying Framework for Linking Space and Time in Brain Dynamics." Neuroscientist 24, no. 3 (September 1, 2017): 277–93. http://dx.doi.org/10.1177/1073858417728032.
Full textAbstract:
A fundamental characteristic of spontaneous brain activity is coherent oscillations covering a wide range of frequencies. Interestingly, these temporal oscillations are highly correlated among spatially distributed cortical areas forming structured correlation patterns known as the resting state networks, although the brain is never truly at “rest.” Here, we introduce the concept of harmonic brain modes—fundamental building blocks of complex spatiotemporal patterns of neural activity. We define these elementary harmonic brain modes as harmonic modes of structural connectivity; that is, connectome harmonics, yielding fully synchronous neural activity patterns with different frequency oscillations emerging on and constrained by the particular structure of the brain. Hence, this particular definition implicitly links the hitherto poorly understood dimensions of space and time in brain dynamics and its underlying anatomy. Further we show how harmonic brain modes can explain the relationship between neurophysiological, temporal, and network-level changes in the brain across different mental states ( wakefulness, sleep, anesthesia, psychedelic). Notably, when decoded as activation of connectome harmonics, spatial and temporal characteristics of neural activity naturally emerge from the interplay between excitation and inhibition and this critical relation fits the spatial, temporal, and neurophysiological changes associated with different mental states. Thus, the introduced framework of harmonic brain modes not only establishes a relation between the spatial structure of correlation patterns and temporal oscillations (linking space and time in brain dynamics), but also enables a new dimension of tools for understanding fundamental principles underlying brain dynamics in different states of consciousness.
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Costa, M., K. N. Dodds, L. Wiklendt, N. J. Spencer, S. J. H. Brookes, and P. G. Dinning. "Neurogenic and myogenic motor activity in the colon of the guinea pig, mouse, rabbit, and rat." American Journal of Physiology-Gastrointestinal and Liver Physiology 305, no. 10 (November 15, 2013): G749—G759. http://dx.doi.org/10.1152/ajpgi.00227.2013.
Full textAbstract:
Gastrointestinal motility involves interactions between myogenic and neurogenic processes intrinsic to the gut wall. We have compared the presence of propagating myogenic contractions of the isolated colon in four experimental animals (guinea pig, mouse, rabbit, and rat), following blockade of enteric neural activity. Isolated colonic preparations were distended with fluid, with the anal end either closed or open. Spatiotemporal maps of changes in diameter were constructed from video recordings. Distension-induced peristaltic contractions were abolished by tetrodotoxin (TTX; 0.6 μM) in all animal species. Subsequent addition of carbachol (0.1–1 μM) did not evoke myogenic motor patterns in the mouse or guinea pig, although some activity was observed in rabbit and rat colon. These myogenic contractions propagated both orally and anally and differed from neurogenic propagating contractions in their frequency, extent of propagation, and polarity. Niflumic acid (300 μM), used to block myogenic activity, also blocked neural peristalsis and thus cannot be used to discriminate between these mechanisms. In all species, except the mouse colon, small myogenic “ripple” contractions were revealed in TTX, but in both rat and rabbit an additional, higher-frequency ripple-type contraction was superimposed. Following blockade of enteric nerve function, a muscarinic agonist can evoke propulsive myogenic peristaltic contractions in isolated rabbit and rat colon, but not in guinea pig or mouse colon. Marked differences between species exist in the ability of myogenic mechanisms to propel luminal content, but in all species there is normally a complex interplay between neurogenic and myogenic processes.
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Corniani, Giulia, Miguel A. Casal, Stefano Panzeri, and Hannes P. Saal. "Population coding strategies in human tactile afferents." PLOS Computational Biology 18, no. 12 (December 7, 2022): e1010763. http://dx.doi.org/10.1371/journal.pcbi.1010763.
Full textAbstract:
Sensory information is conveyed by populations of neurons, and coding strategies cannot always be deduced when considering individual neurons. Moreover, information coding depends on the number of neurons available and on the composition of the population when multiple classes with different response properties are available. Here, we study population coding in human tactile afferents by employing a recently developed simulator of mechanoreceptor firing activity. First, we highlight the interplay of afferents within each class. We demonstrate that the optimal afferent density to convey maximal information depends on both the tactile feature under consideration and the afferent class. Second, we find that information is spread across different classes for all tactile features and that each class encodes both redundant and complementary information with respect to the other afferent classes. Specifically, combining information from multiple afferent classes improves information transmission and is often more efficient than increasing the density of afferents from the same class. Finally, we examine the importance of temporal and spatial contributions, respectively, to the joint spatiotemporal code. On average, destroying temporal information is more destructive than removing spatial information, but the importance of either depends on the stimulus feature analysed. Overall, our results suggest that both optimal afferent innervation densities and the composition of the population depend in complex ways on the tactile features in question, potentially accounting for the variety in which tactile peripheral populations are assembled in different regions across the body.
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Joshi, Lalit Mohan, Lung-Chih Tsai, and Shin-Yi Su. "Wavenumber-4 Structure in COSMIC-2 Observations: Vertical Plane Perspective." Remote Sensing 15, no. 8 (April 17, 2023): 2105. http://dx.doi.org/10.3390/rs15082105.
Full textAbstract:
High-rate radio occultation (RO) in COSMIC-2 (FORMOSAT7) enables us to investigate the finer details of the ionosphere owing to the measurements being made at a significantly high spatiotemporal resolution, which was unthinkable a decade ago. In the vertical plane, local-time ionospheric wavenumber-4 (WN4) structures display tilted phase-fronts over the equatorial ionization anomaly (EIA) belt. The longitudinal extent of a tilted WN4 phase-front approximates the zonal wavelength of nonmigrating DE3 tide in the local-time frame of reference, i.e., ~900. The WN4-filtered (residual) component indicates a greater tilt (when visible), with a larger longitudinal extent of a wavenumber structure in the vertical plane. The WN4 structure over the EIA crest region is found to be out of phase (in phase) with respect to that over the EIA trough region during daytime (nighttime), which also depended on the altitude under consideration. Intriguingly, above 400 km, the WN4 structures in the EIA crest and trough regions are seen to be in phase with each other at all local times. The phenomenon of the “longitudinal co-location” of WN4 over the EIA crest and trough regions at altitudes above ~400 km at all local times remains unexplained. Results also highlight that the formation of WN4 is governed by a complex interplay of direct forcing of nonmigrating tides and the zonal electric field whose characteristics within the EIA belt vary drastically with latitude and altitude under consideration.
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Lombardi, Aniello, Peter Jedlicka, Heiko Luhmann, and Werner Kilb. "Interactions between Membrane Resistance, GABA-A Receptor Properties, Bicarbonate Dynamics and Cl−-Transport Shape Activity-Dependent Changes of Intracellular Cl− Concentration." International Journal of Molecular Sciences 20, no. 6 (March 20, 2019): 1416. http://dx.doi.org/10.3390/ijms20061416.
Full textAbstract:
The effects of ionotropic γ-aminobutyric acid receptor (GABA-A, GABAA) activation depends critically on the Cl−-gradient across neuronal membranes. Previous studies demonstrated that the intracellular Cl−-concentration ([Cl−]i) is not stable but shows a considerable amount of activity-dependent plasticity. To characterize how membrane properties and different molecules that are directly or indirectly involved in GABAergic synaptic transmission affect GABA-induced [Cl−]i changes, we performed compartmental modeling in the NEURON environment. These simulations demonstrate that GABA-induced [Cl−]i changes decrease at higher membrane resistance, revealing a sigmoidal dependency between both parameters. Increase in GABAergic conductivity enhances [Cl−]i with a logarithmic dependency, while increasing the decay time of GABAA receptors leads to a nearly linear enhancement of the [Cl−]i changes. Implementing physiological levels of HCO3−-conductivity to GABAA receptors enhances the [Cl−]i changes over a wide range of [Cl−]i, but this effect depends on the stability of the HCO3− gradient and the intracellular pH. Finally, these simulations show that pure diffusional Cl−-elimination from dendrites is slow and that a high activity of Cl−-transport is required to improve the spatiotemporal restriction of GABA-induced [Cl−]i changes. In summary, these simulations revealed a complex interplay between several key factors that influence GABA-induced [Cl]i changes. The results suggest that some of these factors, including high resting [Cl−]i, high input resistance, slow decay time of GABAA receptors and dynamic HCO3− gradient, are specifically adapted in early postnatal neurons to facilitate limited activity-dependent [Cl−]i decreases.
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Mahul-Mellier, Anne-Laure, Johannes Burtscher, Niran Maharjan, Laura Weerens, Marie Croisier, Fabien Kuttler, Marion Leleu, Graham W. Knott, and Hilal A. Lashuel. "The process of Lewy body formation, rather than simply α-synuclein fibrillization, is one of the major drivers of neurodegeneration." Proceedings of the National Academy of Sciences 117, no. 9 (February 19, 2020): 4971–82. http://dx.doi.org/10.1073/pnas.1913904117.
Full textAbstract:
Parkinson’s disease (PD) is characterized by the accumulation of misfolded and aggregated α-synuclein (α-syn) into intraneuronal inclusions named Lewy bodies (LBs). Although it is widely believed that α-syn plays a central role in the pathogenesis of PD, the processes that govern α-syn fibrillization and LB formation remain poorly understood. In this work, we sought to dissect the spatiotemporal events involved in the biogenesis of the LBs at the genetic, molecular, biochemical, structural, and cellular levels. Toward this goal, we further developed a seeding-based model of α-syn fibrillization to generate a neuronal model that reproduces the key events leading to LB formation, including seeding, fibrillization, and the formation of inclusions that recapitulate many of the biochemical, structural, and organizational features of bona fide LBs. Using an integrative omics, biochemical and imaging approach, we dissected the molecular events associated with the different stages of LB formation and their contribution to neuronal dysfunction and degeneration. In addition, we demonstrate that LB formation involves a complex interplay between α-syn fibrillization, posttranslational modifications, and interactions between α-syn aggregates and membranous organelles, including mitochondria, the autophagosome, and endolysosome. Finally, we show that the process of LB formation, rather than simply fibril formation, is one of the major drivers of neurodegeneration through disruption of cellular functions and inducing mitochondria damage and deficits, and synaptic dysfunctions. We believe that this model represents a powerful platform to further investigate the mechanisms of LB formation and clearance and to screen and evaluate therapeutics targeting α-syn aggregation and LB formation.