LEVELS OF IL-10 ALTER NF-KAPPA B ACTIVATION THROUGH REGULATION OF I KAPPA KINASE (IKK) IN BOTH HUMAN AND MOUSE CELL TYPES

2002 ◽  
Vol 30 (Supplement) ◽  
pp. A56
Author(s):  
Randall M Schwartz ◽  
Bin Zhao ◽  
Alvin G Denenberg ◽  
Thomas P Shanley
Keyword(s):  
Cell Types ◽  
Mouse Cell ◽  
Nf Kappa B ◽  
Human And Mouse

scholarly journals Conserved cell types with divergent features between human and mouse cortex

2018 ◽  
Author(s):  
Rebecca D Hodge ◽  
Trygve E Bakken ◽  
Jeremy A Miller ◽  
Kimberly A Smith ◽  
Eliza R Barkan ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Cognitive Abilities ◽  
Cell Types ◽  
Mouse Cell ◽  
Middle Temporal Gyrus ◽  
Cellular Architecture ◽  
Mouse Cortex ◽  
Single Nucleus ◽  
Species Specific ◽  
Human And Mouse

AbstractElucidating the cellular architecture of the human neocortex is central to understanding our cognitive abilities and susceptibility to disease. Here we applied single nucleus RNA-sequencing to perform a comprehensive analysis of cell types in the middle temporal gyrus of human cerebral cortex. We identify a highly diverse set of excitatory and inhibitory neuronal types that are mostly sparse, with excitatory types being less layer-restricted than expected. Comparison to a similar mouse cortex single cell RNA-sequencing dataset revealed a surprisingly well-conserved cellular architecture that enables matching of homologous types and predictions of human cell type properties. Despite this general conservation, we also find extensive differences between homologous human and mouse cell types, including dramatic alterations in proportions, laminar distributions, gene expression, and morphology. These species-specific features emphasize the importance of directly studying human brain.

scholarly journals An atlas of silencer elements for the human and mouse genomes

2018 ◽  
Author(s):  
Naresh Doni Jayavelu ◽  
Ajay Jajodia ◽  
Arpit Mishra ◽  
R. David Hawkins
Keyword(s):  
Cell Types ◽  
Regulatory Elements ◽  
Mouse Cell ◽  
Support Vector ◽  
General Strategy ◽  
Gene Promoters ◽  
Genome Wide ◽  
A Genome ◽  
Silencer Elements ◽  
Human And Mouse

ABSTRACTThe study of gene regulation is dominated by a focus on the control of gene activation or controlling an increase in the level of expression. Just as critical is the process of gene repression or silencing. Chromatin signatures have allowed for the global mapping of enhancer cis-regulatory elements, however, the identification of silencer elements by computational or experimental approaches in a genome-wide manner are lacking. We present a simple but powerful computational approach to identify putative silencers genome-wide. We used a series of consortia data to predict silencers in over 100 human and mouse cell or tissue types. We performed several analyses to determine if these elements exhibited characteristics expected of a silencers. Motif enrichment analyses on putative silencers determined that motifs belonging to known transcriptional repressors are enriched, as well as overlapping known transcription repressor binding sites. Leveraging promoter capture HiC data from several human and mouse cell types, we found that over 50% of putative silencer elements are interacting with gene promoters having very low to no expression. Next, to validate our silencer predictions, we quantified silencer activity using massively parallel reporter assays (MPRAs) on 7500 selected elements in K562 cells. We trained a support vector machine model classifier on MPRA data and used it to refine potential silencers in other cell types. We also show that similar to enhancer elements, silencer elements are enriched in disease-associated variants. Our results suggest a general strategy for genome-wide identification and characterization of silencer elements.

scholarly journals SACSANN: identifying sequence-based determinants of chromosomal compartments

2020 ◽  
Author(s):  
Julie A Prost ◽  
Christopher JF Cameron ◽  
Mathieu Blanchette
Keyword(s):  
Machine Learning ◽  
Binding Sites ◽  
Genomic Organization ◽  
Genomic Sequence ◽  
Cell Types ◽  
Mouse Cell ◽  
Cell Type ◽  
3D Genome ◽  
Cell Type Specific ◽  
Human And Mouse

Genomic organization is critical for proper gene regulation and based on a hierarchical model, where chromosomes are segmented into megabase-sized, cell-type-specific transcriptionally active (A) and inactive (B) compartments. Here, we describe SACSANN, a machine learning pipeline consisting of stacked artificial neural networks that predicts compartment annotation solely from genomic sequence-based features such as predicted transcription factor binding sites and transposable elements. SACSANN provides accurate and cell-type specific compartment predictions, while identifying key genomic sequence determinants that associate with A/B compartments. Models are shown to be largely transferable across analogous human and mouse cell types. By enabling the study of chromosome compartmentalization in species for which no Hi-C data is available, SACSANN paves the way toward the study of 3D genome evolution. SACSANN is publicly available on GitHub: https://github.com/BlanchetteLab/SACSANN

scholarly journals A versatile system to record cell-cell interactions

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Rui Tang ◽  
Christopher W Murray ◽  
Ian L Linde ◽  
Nicholas J Kramer ◽  
Zhonglin Lyu ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
Cell Types ◽  
Mouse Cell ◽  
Cell Interactions ◽  
Physical Contact ◽  
Cell Labeling ◽  
Wide Range ◽  
Human And Mouse ◽  
Cell Cell

Cell-cell interactions influence all aspects of development, homeostasis, and disease. In cancer, interactions between cancer cells and stromal cells play a major role in nearly every step of carcinogenesis. Thus, the ability to record cell-cell interactions would facilitate mechanistic delineation of the role of the cancer microenvironment. Here, we describe GFP-based Touching Nexus (G-baToN) which relies upon nanobody-directed fluorescent protein transfer to enable sensitive and specific labeling of cells after cell-cell interactions. G-baToN is a generalizable system that enables physical contact-based labeling between various human and mouse cell types, including endothelial cell-pericyte, neuron-astrocyte, and diverse cancer-stromal cell pairs. A suite of orthogonal baToN tools enables reciprocal cell-cell labeling, interaction-dependent cargo transfer, and the identification of higher order cell-cell interactions across a wide range of cell types. The ability to track physically interacting cells with these simple and sensitive systems will greatly accelerate our understanding of the outputs of cell-cell interactions in cancer as well as across many biological processes.

Effect of elevated potassium on the ion content of mouse astrocytes and neurons

1992 ◽  
Vol 70 (S1) ◽  
pp. S263-S268 ◽  
Author(s):  
H. Steve White ◽  
Sien Yao Chow ◽  
Y. C. Yen-Chow ◽  
Dixon M. Woodbury
Keyword(s):  
Cortical Neurons ◽  
Cell Types ◽  
Mouse Cell ◽  
Ion Concentration ◽  
Cellular Heterogeneity ◽  
Resting Membrane Potential ◽  
Extracellular Potassium ◽  
Individual Response ◽  
Extracellular Potassium Concentration ◽  
The Brain

Potassium is tightly regulated within the extracellular compartment of the brain. Nonetheless, it can increase 3- to 4-fold during periods of intense seizure activity and 10- to 20-fold under certain pathological conditions such as spreading depression. Within the central nervous system, neurons and astrocytes are both affected by shifts in the extracellular concentration of potassium. Elevated potassium can lead to a redistribution of other ions (e.g., calcium, sodium, chloride, hydrogen, etc.) within the cellular compartment of the brain. Small shifts in the extracellular potassium concentration can markedly affect acid–base homeostasis, energy metabolism, and volume regulation of these two brain cells. Since normal neuronal function is tightly coupled to the ability of the surrounding glial cells to regulate ionic shifts within the brain and since both cell types can be affected by shifts in the extracellular potassium, it is important to characterize their individual response to an elevation of this ion. This review describes the results of side-by-side studies conducted on cortical neurons and astrocytes, which assessed the effect of elevated potassium on their resting membrane potential, intracellular volume, and their intracellular concentration of potassium, sodium, and chloride. The results obtained from these studies suggest that there exists a marked cellular heterogeneity between neurons and astrocytes in their response to an elevation in the extracellular potassium concentration.Key words: astrocytes, neurons, ion concentration, neuronal–glial interactions, mouse, cell culture.

Differentiation of two mouse cell lines is associated with hypomethylation of their genomes

1984 ◽  
Vol 4 (9) ◽  
pp. 1800-1806
Author(s):  
T H Bestor ◽  
S B Hellewell ◽  
V M Ingram
Keyword(s):  
Dna Methyltransferase ◽  
Cell Types ◽  
Mouse Cell ◽  
F9 Cells ◽  
Dna Restriction Fragments ◽  
Dna Restriction ◽  
F9 Embryonal Carcinoma Cells ◽  
Murine Erythroleukemia ◽  
Kinetics Of

Methyl-accepting assays and a sensitive method for labeling specific CpG sites have been used to show that the DNA of F9 embryonal carcinoma cells decreases in 5-methylcytosine content by ca. 9% during retinoic acid-induced differentiation, whereas the DNA of dimethyl sulfoxide-induced Friend murine erythroleukemia (MEL) cells loses ca. 3.8% of its methyl groups. These values correspond to the demethylation of 2.2 X 10(6) and 0.9 X 10(6) 5'-CpG-3' sites per haploid genome in differentiating F9 and MEL cells, respectively. Fluorography of DNA restriction fragments methylated in vitro and displayed on agarose gels showed that demethylation occurred throughout the genome. In uninduced F9 cells, the sequence TCGA tended to be more heavily methylated than did the sequence CCGG, whereas this tendency was reversed in MEL cells. The kinetics of in vitro DNA methylation reactions catalyzed by MEL cell DNA methyltransferase showed that substantial numbers of hemimethylated sites accumulate in the DNA of terminally differentiating F9 and MEL cells, implying that a partial loss of DNA-methylating activity may accompany terminal differentiation in these two cell types.

scholarly journals New insights into the phosphorylation of the threonine motif of the β1 integrin cytoplasmic domain

2022 ◽  
Vol 5 (4) ◽  
pp. e202101301
Author(s):  
Ralph T Böttcher ◽  
Nico Strohmeyer ◽  
Jonas Aretz ◽  
Reinhard Fässler
Keyword(s):  
Mass Spectrometry ◽  
Ligand Binding ◽  
Phosphorylation Site ◽  
Cell Spreading ◽  
Mouse Cell ◽  
Β1 Integrin ◽  
Β1 Integrins ◽  
Integrin Ligand ◽  
Human And Mouse ◽  
Major Phosphorylation Site

Integrins require an activation step before ligand binding and signaling that is mediated by talin and kindlin binding to the β integrin cytosolic domain (β-tail). Conflicting reports exist about the contribution of phosphorylation of a conserved threonine motif in the β1-tail (β1-pT788/pT789) to integrin activation. We show that widely used and commercially available antibodies against β1-pT788/pT789 integrin do not detect specific β1-pT788/pT789 integrin signals in immunoblots of several human and mouse cell lysates but bind bi-phosphorylated threonine residues in numerous proteins, which were identified by mass spectrometry experiments. Furthermore, we found that fibroblasts and epithelial cells expressing the phospho-mimicking β1-TT788/789DD integrin failed to activate β1 integrins and displayed reduced integrin ligand binding, adhesion initiation and cell spreading. These cellular defects are specifically caused by the inability of kindlin to bind β1-tail polypeptides carrying a phosphorylated threonine motif or phospho-mimicking TT788/789DD substitutions. Our findings indicate that the double-threonine motif in β1-class integrins is not a major phosphorylation site but if phosphorylated would curb integrin function.

scholarly journals Comparing the electrophysiology and morphology of human and mouse layer 2/3 pyramidal neurons with Bayesian networks

2020 ◽  
Author(s):  
Bojan Mihaljević ◽  
Pedro Larrañaga ◽  
Concha Bielza
Keyword(s):  
Bayesian Networks ◽  
Probabilistic Reasoning ◽  
Pyramidal Neurons ◽  
Temporal Cortex ◽  
Input Resistance ◽  
Cell Types ◽  
Dendritic Arbor ◽  
Basal Dendrites ◽  
Morphological Variables ◽  
Human And Mouse

ABSTRACTPyramidal neurons are the most common neurons in the cerebral cortex. Understanding how they differ between species is a key challenge in neuroscience. We compared human temporal cortex and mouse visual cortex pyramidal neurons from the Allen Cell Types Database in terms of their electrophysiology and basal dendrites’ morphology. We found that, among other differences, human pyramidal neurons had a higher threshold voltage, a lower input resistance, and a larger basal dendritic arbor. We learned Gaussian Bayesian networks from the data in order to identify correlations and conditional independencies between the variables and compare them between the species. We found strong correlations between electrophysiological and morphological variables in both species. One result is that, in human cells, dendritic arbor width had the strongest effect on input resistance after accounting for the remaining variables. Electrophysiological variables were correlated, in both species, even with morphological variables that are not directly related to dendritic arbor size or diameter, such as mean bifurcation angle and mean branch tortuosity. Contrary to previous results, cortical depth was correlated with both electrophysiological and morphological variables, and its effect on electrophysiological could not be explained in terms of the morphological variables. Overall, the correlations among the variables differed strikingly between human and mouse neurons. Besides identifying correlations and conditional independencies, the learned Bayesian networks might be useful for probabilistic reasoning regarding the morphology and electrophysiology of pyramidal neurons.

scholarly journals Nanoemulsions as Delivery Systems for Poly-Chemotherapy Aiming at Melanoma Treatment

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1198
Author(s):  
Chiara Dianzani ◽  
Chiara Monge ◽  
Gianluca Miglio ◽  
Loredana Serpe ◽  
Katia Martina ◽  
...  
Keyword(s):  
Mouse Cell ◽  
Advanced Melanoma ◽  
In Vivo Studies ◽  
Cell Models ◽  
Tumour Angiogenesis ◽  
Investigation Methods ◽  
Melanoma Treatment ◽  
Human And Mouse

Aims: Advanced melanoma is characterized by poor outcome. Despite the number of treatments having been increased over the last decade, current pharmacological strategies are only partially effective. Therefore, the improvement of the current systemic therapy is worthy of investigation. Methods: a nanotechnology-based poly-chemotherapy was tested at preclinical level. Temozolomide, rapamycin, and bevacizumab were co-loaded as injectable nanoemulsions for total parenteral nutrition (Intralipid®), due to suitable devices, and preliminarily tested in vitro on human and mouse cell models and in vivo on the B16-F10 melanoma mouse model. Results: Drug combination was efficiently loaded in the liquid lipid matrix of Intralipid®, including bevacizumab monoclonal antibody, leading to a fast internalization in tumour cells. An increased cytotoxicity towards melanoma cells, as well as an improved inhibition of tumour relapse, migration, and angiogenesis were demonstrated in cell models for the Intralipid®-loaded drug combinations. In preliminary in vivo studies, the proposed approach was able to reduce tumour growth significantly, compared to controls. A relevant efficacy towards tumour angiogenesis and mitotic index was determined and immune response was involved. Conclusions: In these preliminary studies, Intralipid® proved to be a safe and versatile poly-chemotherapy delivery system for advanced melanoma treatment, by acting on multiple mechanisms.

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