In vivo experimental data on the mobility of hazardous chemical elements from clays

Conifers have long been recognized for their therapeutic potential in different disorders. Alkaloids, terpenes and polyphenols are the most abundant naturally occurring phytochemicals in these plants. Here, we provide an overview of the phytochemistry and related commercial products obtained from conifers. The pharmacological actions of different phytochemicals present in conifers against bacterial and fungal infections, cancer, diabetes and cardiovascular diseases are also reviewed. Data obtained from experimental and clinical studies performed to date clearly underline that such compounds exert promising antioxidant effects, being able to inhibit cell damage, cancer growth, inflammation and the onset of neurodegenerative diseases. Therefore, an attempt has been made with the intent to highlight the importance of conifer-derived extracts for pharmacological purposes, with the support of relevant in vitro and in vivo experimental data. In short, this review comprehends the information published to date related to conifers’ phytochemicals and illustrates their potential role as drugs.

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Development of a rabies virus-based retrograde tracer with high trans-monosynaptic efficiency by reshuffling glycoprotein

Molecular Brain ◽

10.1186/s13041-021-00821-7 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Fan Jia ◽

Li Li ◽

Haizhou Liu ◽

Pei Lv ◽

Xiangwei Shi ◽

...

Keyword(s):

Experimental Data ◽

Rabies Virus ◽

Oncolytic Virus ◽

Neural Circuits ◽

Bioinformatic Analysis ◽

Cell Engineering ◽

Bias Score ◽

Codon Pair Bias ◽

Codon Pair

AbstractRabies virus (RV) is the most widely used vector for mapping neural circuits. Previous studies have shown that the RV glycoprotein can be a target to improve the retrograde transsynaptic tracing efficiency. However, the current versions still label only a small portion of all presynaptic neurons. Here, we reshuffled the oG sequence, a chimeric glycoprotein, with positive codon pair bias score (CPBS) based on bioinformatic analysis of mouse codon pair bias, generating ooG, a further optimized glycoprotein. Our experimental data reveal that the ooG has a higher expression level than the oG in vivo, which significantly increases the tracing efficiency by up to 12.6 and 62.1-fold compared to oG and B19G, respectively. The new tool can be used for labeling neural circuits Therefore, the approach reported here provides a convenient, efficient and universal strategy to improve protein expression for various application scenarios such as trans-synaptic tracing efficiency, cell engineering, and vaccine and oncolytic virus designs.

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Exploring the effect of biological delays in kinetic models of influenza within a host or cell culture

10.32920/14639178 ◽

2021 ◽

Author(s):

Benjamin P Holder ◽

Catherine A. A. Beauchemin

Keyword(s):

Differential Equation ◽

Experimental Data ◽

Influenza Infection ◽

Biologically Relevant ◽

Differential Equation Models ◽

Viral Yield ◽

Infection Parameters ◽

Delay Differential

Background For a typical influenza infection in vivo, viral titers over time are characterized by 1–2 days of exponential growth followed by an exponential decay. This simple dynamic can be reproduced by a broad range of mathematical models which makes model selection and the extraction of biologically-relevant infection parameters from experimental data difficult. Results We analyze in vitro experimental data from the literature, specifically that of single-cycle viral yield experiments, to narrow the range of realistic models of infection. In particular, we demonstrate the viability of using a normal or lognormal distribution for the time a cell spends in a given infection state (e.g., the time spent by a newly infected cell in the latent state before it begins to produce virus), while exposing the shortcomings of ordinary differential equation models which implicitly utilize exponential distributions and delay-differential equation models with fixed-length delays. Conclusions By fitting published viral titer data from challenge experiments in human volunteers, we show that alternative models can lead to different estimates of the key infection parameters.

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A three-dimensional musculoskeletal model of the dog

10.1101/2020.07.16.205856 ◽

2020 ◽

Author(s):

Heiko Stark ◽

Martin S. Fischer ◽

Alexander Hunt ◽

Fletcher Young ◽

Roger Quinn ◽

...

Keyword(s):

Experimental Data ◽

Body Size ◽

Degrees Of Freedom ◽

Inverse Dynamics ◽

Musculoskeletal Model ◽

Muscle Synergy ◽

Locomotor System ◽

Wide Range ◽

Joint Load

AbstractDogs are an interesting object of investigation because of the wide range of body size, body mass, and physique. In the last several years, the number of clinical and biomechanical studies on dog locomotion has increased. However, the relationship between body structure and joint load during locomotion, as well as between joint load and degenerative diseases of the locomotor system (e.g. dysplasia), are not sufficiently understood. In vivo measurements/records of joint forces and loads or deep/small muscles are complex, invasive, and sometimes ethically questionable. The use of detailed musculoskeletal models may help in filling that knowledge gap. We describe here the methods we used to create a detailed musculoskeletal model with 84 degrees of freedom and 134 muscles. Our model has three key-features: Three-dimensionality, scalability, and modularity. We tested the validity of the model by identifying forelimb muscle synergies of a beagle at walk. We used inverse dynamics and static optimization to estimate muscle activations based on experimental data. We identified three muscle synergy groups by using hierarchical clustering. Predicted activation patterns exhibited good agreement with experimental data for most of the forelimb muscles. We expect that our model will speed up the analysis of how body size, physique, agility, and disease influence joint neuronal control and loading in dog locomotion.

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Regulation of lamin properties and functions: does phosphorylation do it all?

Open Biology ◽

10.1098/rsob.150094 ◽

2015 ◽

Vol 5 (11) ◽

pp. 150094 ◽

Cited By ~ 32

Author(s):

Magdalena Machowska ◽

Katarzyna Piekarowicz ◽

Ryszard Rzepecki

Keyword(s):

Gene Expression ◽

Experimental Data ◽

Chromatin Structure ◽

In Silico ◽

Building Blocks ◽

Model Organisms ◽

Intracellular Signalling Pathway ◽

Evolutionarily Conserved ◽

Structure Regulation

The main functions of lamins are their mechanical and structural roles as major building blocks of the karyoskeleton. They are also involved in chromatin structure regulation, gene expression, intracellular signalling pathway modulation and development. All essential lamin functions seem to depend on their capacity for assembly or disassembly after the receipt of specific signals, and after specific, selective and precisely regulated interactions through their various domains. Reversible phosphorylation of lamins is crucial for their functions, so it is important to understand how lamin polymerization and interactions are modulated, and which sequences may undergo such modifications. This review combines experimental data with results of our in silico analyses focused on lamin phosphorylation in model organisms to show the presence of evolutionarily conserved sequences and to indicate specific in vivo phosphorylations that affect particular functions.

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The Role of Dimensionality in Understanding Granuloma Formation

Computation ◽

10.3390/computation6040058 ◽

2018 ◽

Vol 6 (4) ◽

pp. 58 ◽

Cited By ~ 5

Author(s):

Simeone Marino ◽

Caitlin Hult ◽

Paul Wolberg ◽

Jennifer Linderman ◽

Denise Kirschner

Keyword(s):

Experimental Data ◽

Large Scale ◽

Bacterial Load ◽

Computational Cost ◽

Granuloma Formation ◽

In Silico Studies ◽

Cellular Recruitment ◽

2D And 3D

Within the first 2–3 months of a Mycobacterium tuberculosis (Mtb) infection, 2–4 mm spherical structures called granulomas develop in the lungs of the infected hosts. These are the hallmark of tuberculosis (TB) infection in humans and non-human primates. A cascade of immunological events occurs in the first 3 months of granuloma formation that likely shapes the outcome of the infection. Understanding the main mechanisms driving granuloma development and function is key to generating treatments and vaccines. In vitro, in vivo, and in silico studies have been performed in the past decades to address the complexity of granuloma dynamics. This study builds on our previous 2D spatio-temporal hybrid computational model of granuloma formation in TB (GranSim) and presents for the first time a more realistic 3D implementation. We use uncertainty and sensitivity analysis techniques to calibrate the new 3D resolution to non-human primate (NHP) experimental data on bacterial levels per granuloma during the first 100 days post infection. Due to the large computational cost associated with running a 3D agent-based model, our major goal is to assess to what extent 2D and 3D simulations differ in predictions for TB granulomas and what can be learned in the context of 3D that is missed in 2D. Our findings suggest that in terms of major mechanisms driving bacterial burden, 2D and 3D models return very similar results. For example, Mtb growth rates and molecular regulation mechanisms are very important both in 2D and 3D, as are cellular movement and modulation of cell recruitment. The main difference we found was that the 3D model is less affected by crowding when cellular recruitment and movement of cells are increased. Overall, we conclude that the use of a 2D resolution in GranSim is warranted when large scale pilot runs are to be performed and if the goal is to determine major mechanisms driving infection outcome (e.g., bacterial load). To comprehensively compare the roles of model dimensionality, further tests and experimental data will be needed to expand our conclusions to molecular scale dynamics and multi-scale resolutions.

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The Dynamics of Bone Mineral in Some Vertebrates

Zeitschrift für Naturforschung C ◽

10.1515/znc-1986-0413 ◽

1986 ◽

Vol 41 (4) ◽

pp. 468-471 ◽

Cited By ~ 19

Author(s):

F. C. M. Driessens ◽

R. M. H. Verbeeck

Keyword(s):

Experimental Data ◽

Bone Mineral ◽

Bone Development ◽

Precursor Phase

In the literature octocalcium phosphate as well as brushite have been proposed as the precursor phase for bone mineral in the higher vertebrates. In this study it is shown that the situation is more complex. A sodium and carbonate containing apatite (NCCA) and a magnesium whitlockite (MWH) are present from the beginning of mineralization together with octocalcium phosphate. Upon further bone development the NCCA and the MWH phase are deposited in amounts proportional to the amount of mineral deposited. However, the octocalcium phosphate is transformed slowly in a heavily carbonated defective hydroxyapatite. From the available experimental data it can be derived that the time of this transformation is smaller than four weeks under in vivo conditions.

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Anisotropic residual stresses in arteries

Journal of The Royal Society Interface ◽

10.1098/rsif.2019.0029 ◽

2019 ◽

Vol 16 (151) ◽

pp. 20190029 ◽

Cited By ~ 4

Author(s):

Taisiya Sigaeva ◽

Gerhard Sommer ◽

Gerhard A. Holzapfel ◽

Elena S. Di Martino

Keyword(s):

Experimental Data ◽

Residual Stresses ◽

Abdominal Aorta ◽

Strain Energy Function ◽

Opening Angle ◽

Link Type ◽

Residual Deformations ◽

Angle Method ◽

The Individual

The paper provides a deepened insight into the role of anisotropy in the analysis of residual stresses in arteries. Residual deformations are modelled following Holzapfel and Ogden (Holzapfel and Ogden 2010, J. R. Soc. Interface 7 , 787–799. ( doi:10.1098/rsif.2009.0357 )), which is based on extensive experimental data on human abdominal aortas (Holzapfel et al. 2007, Ann. Biomed. Eng. 35 , 530–545. ( doi:10.1007/s10439-006-9252-z )) and accounts for both circumferential and axial residual deformations of the individual layers of arteries—intima, media and adventitia. Each layer exhibits distinctive nonlinear and anisotropic mechanical behaviour originating from its unique microstructure; therefore, we use the most general form of strain-energy function (Holzapfel et al. 2015, J. R. Soc. Interface 12 , 20150188. ( doi:10.1098/rsif.2015.0188 )) to derive residual stresses for each layer individually. Finally, the systematic experimental data (Niestrawska et al. 2016, J. R. Soc. Interface 13 , 20160620. ( doi:10.1098/rsif.2016.0620 )) on both mechanical and structural properties of the different layers of the human abdominal aorta facilitate our discussion on (i) the importance of anisotropy in modelling residual stresses; (ii) the variability of residual stresses within the same class of tissue, the abdominal aorta; (iii) the limitations of conventional opening angle method to account for complex residual deformations; and (iv) the effect of residual stresses on the loaded configuration of the aorta mimicking in vivo conditions.

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Electro-osmotic flow enhancement in carbon nanotube membranes

Philosophical Transactions of The Royal Society A Mathematical Physical and Engineering Sciences ◽

10.1098/rsta.2015.0268 ◽

2016 ◽

Vol 374 (2060) ◽

pp. 20150268 ◽

Cited By ~ 7

Author(s):

Davide Mattia ◽

Hannah Leese ◽

Francesco Calabrò

Keyword(s):

Experimental Data ◽

Carbon Nanotube ◽

Osmotic Flow ◽

Nanotube Membranes ◽

Wide Range ◽

Simplifying Assumptions ◽

Carbon Nanotube Membranes ◽

Simplified Solution ◽

Electro Osmotic Flow

In this work, experimental evidence of the presence of electro-osmotic flow (EOF) in carbon nanotube membranes with diameters close to or in the region of electrical double layer overlap is presented for two different electrolytes for the first time. No EOF in this region should be present according to the simplified theoretical framework commonly used for EOF in micrometre-sized channels. The simplifying assumptions concern primarily the electrolyte charge density structure, based on the Poisson–Boltzmann (P-B) equation. Here, a numerical analysis of the solutions for the simplified case and for the nonlinear and the linearized P-B equations is compared with experimental data. Results show that the simplified solution produces a significant deviation from experimental data, whereas the linearized solution of the P-B equation can be adopted with little error compared with the full P-B case. This work opens the way to using electro-osmotic pumping in a wide range of applications, from membrane-based ultrafiltration and nanofiltration (as a more efficient alternative to mechanical pumping at the nanoscale) to further miniaturization of lab-on-a-chip devices at the nanoscale for in vivo implantation.

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