scholarly journals Quantifying the dynamics of hematopoiesis by in vivo IdU pulse-chase, mass cytometry and mathematical modeling

2019 ◽  
Author(s):  
Amir Erez ◽  
Ratnadeep Mukherjee ◽  
Alexandre Day ◽  
Pankaj Mehta ◽  
Grégoire Altan-Bonnet
Keyword(s):  
Mathematical Modeling ◽  
Direct Detection ◽  
Binary Classification ◽  
Mouse Strains ◽  
Mass Cytometry ◽  
Experimental Conditions ◽  
Minimal Impact ◽  
Wide Range

AbstractWe present a new method to directly quantify the dynamics of differentiation of multiple cellular subsets in unperturbed mice. We combine a pulse-chase protocol of IdU injections with subsequent analysis by mass cytometry (CyTOF), and mathematical modeling of the IdU dynamics. Measurements by CyTOF allow for a wide range of cells to be analyzed at once, due to the availability of a large staining panel without the complication of fluorescence spill-over. These are also compatible with direct detection of integrated iodine signal, with minimal impact on immunophenotyping based on surface markers. Mathematical modeling beyond a binary classification of surface marker abundance allows for a continuum of cellular states as the cells transition from one state to another. Thus, we present a complete and robust method for directly quantifying differentiation at the systemic level, allowing for system-wide comparisons between different mouse strains and/or experimental conditions.

scholarly journals Amyloid Beta: Multiple Mechanisms of Toxicity and Only Some Protective Effects?

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Paul Carrillo-Mora ◽  
Rogelio Luna ◽  
Laura Colín-Barenque
Keyword(s):  
Amyloid Beta ◽  
Protective Effects ◽  
Protective Mechanisms ◽  
Experimental Conditions ◽  
Mechanisms Of Toxicity ◽  
Mitochondrial Alterations ◽  
Physiological Properties ◽  
Wide Range

Amyloid beta (Aβ) is a peptide of 39–43 amino acids found in large amounts and forming deposits in the brain tissue of patients with Alzheimer’s disease (AD). For this reason, it has been implicated in the pathophysiology of damage observed in this type of dementia. However, the role of Aβin the pathophysiology of AD is not yet precisely understood. Aβhas been experimentally shown to have a wide range of toxic mechanismsin vivoandin vitro, such as excitotoxicity, mitochondrial alterations, synaptic dysfunction, altered calcium homeostasis, oxidative stress, and so forth. In contrast, Aβhas also shown some interesting neuroprotective and physiological properties under certain experimental conditions, suggesting that both physiological and pathological roles of Aβmay depend on several factors. In this paper, we reviewed both toxic and protective mechanisms of Aβto further explore what their potential roles could be in the pathophysiology of AD. The complete understanding of such apparently opposed effects will also be an important guide for the therapeutic efforts coming in the future.

In Vivo Behavior of Bioactive Glass-Based Hybrids in Animal Models For Bone Regeneration

2020 ◽  
Author(s):  
Shal N
Keyword(s):  
Bioactive Glass ◽  
Bone Regeneration ◽  
Bone Repair ◽  
Weight Bearing ◽  
Chemical Properties ◽  
Experimental Conditions ◽  
Wide Range ◽  
The Matrix ◽  
Hybrid Biomaterials

This review presents the recent advances and the current state-of-the-art of bioactive glass-based hybrid biomaterials for bone regeneration. Hybrid materials comprise two (or more) constituents at the nanometre scale, in which typically, one constituent is organic and functions as the matrix phase and the other constituent is inorganic and behaves as the filler phase. Such materials, thereby, more closely resemble natural bio-nanocomposites such as bone. Various glass compositions in combination with a wide range of natural and synthetic polymers have been evaluated in vivo under experimental conditions ranging from unloaded critical-sized defects to mechanically-loaded, weight-bearing sites with highly favourable outcomes. Additional possibilities include controlled release of anti-osteoporotic drugs, ions, antibiotics, pro-angiogenic substances and pro-osteogenic substances. Histological and morphological evaluations suggest the formation of new, highly vascularised bone that displays signs of remodelling over time. With the possibility to tailor the mechanical and chemical properties through careful selection of individual components, as well as the overall geometry (from mesoporous particles and micro-/nanospheres to 3D scaffolds and coatings) through innovative manufacturing processes, such biomaterials present exciting new avenues for bone repair and regeneration.

scholarly journals Enhanced VWF biosynthesis and elevated plasma VWF due to a natural variant in the murine Vwf gene

Blood ◽  
2006 ◽  
Vol 108 (9) ◽  
pp. 3061-3067 ◽  
Author(s):  
Heidi L. Lemmerhirt ◽  
Jordan A. Shavit ◽  
Gallia G. Levy ◽  
Suzanne M. Cole ◽  
Jeffrey C. Long ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Inbred Mice ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
Genetic Modifiers ◽  
Wide Range ◽  
Natural Variant ◽  
Vitro Analysis

Abstract Both genetic and environmental influences contribute to the wide variation in plasma von Willebrand factor (VWF) levels observed in humans. Inbred mouse strains also have highly variable plasma VWF levels, providing a convenient model in which to study genetic modifiers of VWF. Previously, we identified a major modifier of VWF levels in the mouse (Mvwf1) as a regulatory mutation in murine Galgt2. We now report the identification of an additional murine VWF modifier (Mvwf2). Mvwf2 accounts for approximately 16% of the 8-fold plasma VWF variation (or ∼ 25% of the genetic variation) observed between the A/J and CASA/RkJ strains and maps to the murine Vwf gene itself. Twenty SNPs were identified within the coding regions of the A/J and CASA/RkJ Vwf alleles, and in vitro analysis of recombinant VWF demonstrated that a single SNP (+7970G>A) and the associated nonsynonymous amino acid change (R2657Q) confers a significant increase in VWF biosynthesis from the CASA/RkJ Vwf allele. This change appears to represent a unique gain of function that likely explains the mechanism of Mvwf2 in vivo. The identification of a natural Vwf gene variant among inbred mice affecting biosynthesis suggests that similar genetic variation may contribute to the wide range of VWF levels observed in humans.

scholarly journals EyeBallGUI: A Tool for Visual Inspection and Binary Marking of Multi-channel Bio-signals

2017 ◽  
Author(s):  
Kieran S. Mohr ◽  
Bahman Nasseroleslami ◽  
Parameswaran M. Iyer ◽  
Orla Hardiman ◽  
Edmund C. Lalor
Keyword(s):  
Visual Inspection ◽  
Binary Classification ◽  
Analysis Tool ◽  
Data Retention ◽  
Wide Range ◽  
Sample Data ◽  
Electroencephalogram Eeg ◽  
Free Open Source ◽  
Selection Of

AbstractA wide range of studies in human neuroscience rely on the analysis of electrophysiological bio-signals such as electroencephalogram (EEG) where customized data analysis may require supervised artefact rejection, binary marking through visual inspection, selection of noise and artefact samples for pre-processing algorithms, and selection of clinically-relevant signal segments in neurological conditions. Nevertheless, the existing preprocessing tools do not provide the needed flexibility to handle such tasks efficiently. We therefore developed a free open-source Graphical User Interface (GUI), EyeBallGUI, that allows visualization and flexible, manual marking (binary classification) of multi-channel bio-signal data. EyeBallGUI, developed for MATLAB®, allows the user to interactively and accurately inspect and mark multi-channel digitized data with no restriction on marking periods of data in subsets of channels (a restriction in place in existing tools). The new tool facilitates precise, manual marking of bio-signals by allowing any desired segment of data to be marked in any subset of channels. It is therefore of utility in circumstances where such flexibility is essential. The developed GUI is an auxiliary analysis tool that shall facilitate neural signal (pre-)processing applications where it is desirable to perform accurate supervised artefact rejection, flexible data marking for increased data retention yield, extraction of specific signal segments by expert users from sample data, or labeling of data for clinical and scientific research purposes.

scholarly journals Patient Derived Models to Study Head and Neck Cancer Radiation Response

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 419 ◽  
Author(s):  
Pippa F. Cosper ◽  
Lindsey Abel ◽  
Yong-Syu Lee ◽  
Cristina Paz ◽  
Saakshi Kaushik ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Animal Studies ◽  
Model Systems ◽  
Mouse Strains ◽  
In Vivo Model ◽  
Cancer Therapies ◽  
Wide Range

Patient-derived model systems are important tools for studying novel anti-cancer therapies. Patient-derived xenografts (PDXs) have gained favor over the last 10 years as newer mouse strains have improved the success rate of establishing PDXs from patient biopsies. PDXs can be engrafted from head and neck cancer (HNC) samples across a wide range of cancer stages, retain the genetic features of their human source, and can be treated with both chemotherapy and radiation, allowing for clinically relevant studies. Not only do PDXs allow for the study of patient tissues in an in vivo model, they can also provide a renewable source of cancer cells for organoid cultures. Herein, we review the uses of HNC patient-derived models for radiation research, including approaches to establishing both orthotopic and heterotopic PDXs, approaches and potential pitfalls to delivering chemotherapy and radiation to these animal models, biological advantages and limitations, and alternatives to animal studies that still use patient-derived tissues.

scholarly journals Quantifying the Dynamics of Hematopoiesis by In Vivo IdU Pulse‐Chase, Mass Cytometry, and Mathematical Modeling

2019 ◽  
Vol 95 (10) ◽  
pp. 1075-1084
Author(s):  
Amir Erez ◽  
Ratnadeep Mukherjee ◽  
Grégoire Altan‐Bonnet
Keyword(s):  
Mathematical Modeling ◽  
Mass Cytometry

scholarly journals TePhe, a tellurium-containing phenylalanine mimic, allows monitoring of protein synthesis in vivo with mass cytometry

2019 ◽  
Vol 116 (17) ◽  
pp. 8155-8160 ◽  
Author(s):  
Jay Bassan ◽  
Lisa M. Willis ◽  
Ravi N. Vellanki ◽  
Alan Nguyen ◽  
Landon J. Edgar ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Direct Detection ◽  
Aromatic Amino Acids ◽  
Protein Synthesis Inhibitor ◽  
Mass Cytometry ◽  
Synthesis Inhibitor ◽  
Molecular Specificity ◽  
Noncanonical Amino Acid

Protein synthesis is central to maintaining cellular homeostasis and its study is critical to understanding the function and dysfunction of eukaryotic systems. Here we report L-2-tellurienylalanine (TePhe) as a noncanonical amino acid for direct measurement of protein synthesis. TePhe is synthetically accessible, nontoxic, stable under biological conditions, and the tellurium atom allows its direct detection with mass cytometry, without postexperiment labeling. TePhe labeling is competitive with phenylalanine but not other large and aromatic amino acids, demonstrating its molecular specificity as a phenylalanine mimic; labeling is also abrogated in vitro and in vivo by the protein synthesis inhibitor cycloheximide, validating TePhe as a translation reporter. In vivo, imaging mass cytometry with TePhe visualizes translation dynamics in the mouse gut, brain, and tumor. The strong performance of TePhe as a probe for protein synthesis, coupled with the operational simplicity of its use, suggests TePhe could become a broadly applied molecule for measuring translation in vitro and in vivo.

scholarly journals Patient Derived Models to Study Head and Neck Cancer Radiation Response

2020 ◽  
Author(s):  
Pippa F. Cosper ◽  
Lindsey Abel ◽  
Yong-Syu Lee ◽  
Cristina Paz ◽  
Saakshi Kaushik ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Animal Studies ◽  
Model Systems ◽  
Mouse Strains ◽  
In Vivo Model ◽  
Cancer Therapies ◽  
Wide Range

Patient derived model systems are important tools for studying novel anti-cancer therapies. Patient derived xenografts (PDXs) have gained favor over the last 10 years as newer mouse strains have improved the success rate of establishing PDXs from patient biopsies. PDXs can be engrafted from head and neck cancer (HNC) samples across a wide range of cancer stages, retain the genetic features of their human source, and can be treated with both chemotherapy and radiation, allowing for clinically relevant studies. Not only do PDXs allow for study of patient tissues in an in vivo model, they can also provide a renewable source of cancer cells for organoid cultures. Herein, we review the uses of HNC patient derived models for radiation research including approaches to establishing both orthotopic and heterotopic PDXs, approaches and potential pitfalls to delivering chemotherapy and radiation to these animal models, biological advantages and limitations, and alternatives to animal studies that still use patient-derived tissues.

scholarly journals Endomicroscopy Image Recognition using Ensemble Neural network with Contrast Limited Adaptive Histogram Equalisation

2020 ◽  
Vol 9 (4) ◽  
pp. 44-49
Keyword(s):  
Neural Network ◽  
Binary Classification ◽  
Histogram Equalization ◽  
Poor Quality ◽  
Generalization Error ◽  
Adaptive Histogram Equalization ◽  
Ensemble Neural Network ◽  
Small Tool

Endomicroscopy is a small tool used for cancer diagnosis, this enables in-vivo imaging at microscopic resolution closely to histology image during endoscopic procedures and captured image within the dataset has high imaging quality resulting in an inequality between moral and poor-quality images. There's no clear demonstration of the artifacts in an endomicroscopy producer. During this proposed method, the ensemble neural network (ENN) approach models to scale back the variance of predictions and reduce generalization error with contrast limited adaptive histogram equalization (CLAHE) algorithm were used to recover the image pixel balancing. Binary classification of accuracy 98.79% has been achieved.

scholarly journals Development and assessment of the performance of a shared ventilatory system that uses clinically available components to individualize tidal volumes

2020 ◽  
Author(s):  
David M. Hannon ◽  
Tim Jones ◽  
Jack Conolly ◽  
Conor Judge ◽  
Talha Iqbal ◽  
...  
Keyword(s):  
Invasive Mechanical Ventilation ◽  
Ventilation System ◽  
List Type ◽  
Test Lung ◽  
Minimal Impact ◽  
Wide Range ◽  
The Impact ◽  
Ventilator Settings

AbstractObjectivesTo develop and assess the performance of a system for shared ventilation that uses clinically available components to individualize tidal volumes under a variety of clinically relevant conditions.DesignEvaluation and in vitro validation study.SettingVentilator shortage during the SARS-CoV-2 global pandemic.ParticipantsThe design and validation team consisted of intensive care physicians, bioengineers, computer programmers, and representatives from the medtech sector.MethodsUsing standard clinical components, a system of shared ventilation consisting of two ventilatory limbs was assembled and connected to a single ventilator. Individual monitors for each circuit were developed using widely available equipment and open source software. System performance was determined under 2 sets of conditions. First, the effect of altering ventilator settings (Inspiratory Pressure, Respiratory rate, I:E ratio) on the tidal volumes delivered to each lung circuit was determined. Second, the impact of altering the compliance and resistance in one simulated lung circuit on the tidal volumes delivered to that lung and the second lung circuit was determined. All measurements at each setting were repeated three times to determine the variability in the system.ResultsThe system permitted accurate and reproducible titration of tidal volumes to each ‘lung circuit’ over a wide range of ventilator settings and simulated lung conditions. Alteration of ventilator inspiratory pressures stepwise from 4-20cm H2O, of respiratory rates from 6-20 breaths/minute and I:E ratio from 1:1 to 1:4 resulted in near identical tidal volumes delivered under each set of conditions to each simulated ‘lung’. Stepwise alteration of compliance and resistance in one ‘test’ lung circuit resulted in reproducible alterations in tidal volume to the ‘test’ lung, with little change to tidal volumes in the ‘control’ lung (a change of only 6% is noted). All tidal volumes delivered were highly reproducible upon repetition.ConclusionsWe demonstrate the reliability of a simple shared ventilation system assembled using commonly available clinical components that allows individual titration of tidal volumes. This system may be useful as a temporary strategy of last resort where the numbers of patients requiring invasive mechanical ventilation exceeds supply of ventilators.Article SummaryStrengths and limitations of this studyThis solution provides the ability to safely and robustly ventilate two patients simultaneously while allowing differing tidal volumes in each limb.The designed solution uses equipment readily available in most hospitals.Accurate and reproducible titration of tidal volumes to each ‘lung’ was possible over a wide range of ventilator settings.Alteration of one simulated ‘lung’ conditions had minimal impact on the tidal volumes delivered to the unaffected lungThe system relies on patients being sedated and paralysed.We have not yet tested this solution in vivo, on COVID-19 patients.

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