Pumpless platform for high-throughput dynamic multicellular culture and chemosensitivity evaluation.
AuthorsChen Z, He S, Zilberberg J, Lee W,
JournalLab Chip
PubMed ID30547180
'We report here a novel pumpless, 96-well plate-based platform for high-throughput dynamic multicellular culture and chemosensitivity evaluation. A gravity-driven flow strategy was developed to generate and sustain the flow rate of culture medium within 10% in the platform''s 20 culture chambers. The ability of the platform to generate and sustain ... More
Microscopy-Based Automated Live Cell Screening for Small Molecules That Affect Ciliation.
'The primary monocilium, or cilium, is a single antenna-like organelle that protrudes from the surface of most mammalian cell types, and serves as a signaling hub. Mutations of cilia-associated genes result in severe genetic disorders termed ciliopathies. Among these, the most common is autosomal dominant polycystic kidney disease (ADPKD); less ... More
In Vitro Screening Platforms for Identifying Autophagy Modulators in Mammalian Cells.
AuthorsSeranova E, Ward C, Chipara M, Rosenstock TR, Sarkar S,
JournalMethods Mol Biol
PubMed ID30610712
'Autophagy is a vital homeostatic pathway essential for cellular survival and human health. It primarily functions as an intracellular degradation process for the turnover of aggregation-prone proteins and unwanted organelles. Dysregulation of autophagy underlying diverse human diseases reduces cell viability, whereas stimulation of autophagy is cytoprotective in a number of ... More
Epigenetic regulation of diabetogenic adipose morphology.
AuthorsKerr AG, Sinha I, Dadvar S, Arner P, Dahlman I,
JournalMol Metab
PubMed ID31031182
'Hypertrophic white adipose tissue (WAT) morphology is associated with insulin resistance and type 2 diabetes. The mechanisms governing hyperplastic versus hypertrophic WAT expansion are poorly understood. We assessed if epigenetic modifications in adipocytes are associated with hypertrophic adipose morphology. A subset of genes with differentially methylated CpG-sites (DMS) in the ... More
The effect of rho kinase inhibition on morphological and electrophysiological maturity in iPSC-derived neurons.
AuthorsHarbom LJ, Rudisill TL, Michel N, Litwa KA, Beenhakker MP, McConnell MJ,
JournalCell Tissue Res
PubMed ID30406823
'Induced pluripotent stem cell (iPSC)-derived neurons permit the study of neurogenesis and neurological disease in a human setting. However, the electrophysiological properties of iPSC-derived neurons are consistent with those observed in immature cortical neurons, including a high membrane resistance depolarized resting membrane potential and immature firing properties, limiting their use ... More
Glucocorticoids delay RAF-induced senescence promoted by EGR1.
'Expression of hyperactive RAF kinases, such as the oncogenic B-RAF-V600E mutant, in normal human cells triggers a proliferative arrest that blocks tumor formation. We discovered that glucocorticoids delayed the entry into senescence induced by B-RAF-V600E in human fibroblasts, and allowed senescence bypass when the cells were regularly passaged, but that ... More
High content screening for drug discovery from traditional Chinese medicine.
AuthorsWang J, Wu MY, Tan JQ, Li M, Lu JH,
JournalChin Med
PubMed ID30858873
'Traditional Chinese medicine (TCM) represents the crystallization of Chinese wisdom and civilization. It has been valued as the renewable source for the discovery of novel drugs, owing to its long-term proved efficacy in human diseases and abundant biologically active components pools. To dissect the mystery of TCM, modern technologies such ... More
Vesicular Stomatitis Virus-Based Vaccines Provide Cross-Protection against Andes and Sin Nombre Viruses.
AuthorsWarner BM, Stein DR, Jangra RK, Slough MM, Sroga P, Sloan A, Frost KL, Booth S, Chandran K, Safronetz D,
JournalViruses
PubMed ID31337019
Andes virus (ANDV) and Sin Nombre virus (SNV) are the main causative agents responsible for hantavirus cardiopulmonary syndrome (HCPS) in the Americas. HCPS is a severe respiratory disease with a high fatality rate for which there are no approved therapeutics or vaccines available. Some vaccine approaches for HCPS have been ... More
Coupling caging and proteomics on the European flounder (Platichthys flesus) to assess the estuarine water quality at micro scale.
Estuaries are important areas highly vulnerable to anthropogenic pollutions. Therefore, the assessment of estuarine water quality is a major ecological issue. In this study, we sampled juveniles of the European flounder in the ... More
A Novel Small Molecule Supports the Survival of Cultured Dopamine Neurons and May Restore the Dopaminergic Innervation of the Brain in the MPTP Mouse Model of Parkinson's Disease.
We previously showed that monoterpenoid (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol 1 alleviates motor manifestations of Parkinson's disease in animal models. In the present study, we designed and synthesized monoepoxides of (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol 1 and evaluated their biological activity in the MPTP mouse model of Parkinson's disease. We also assessed the ability of these compounds to ... More
A Hyperstabilizing Mutation in the Base of the Ebola Virus Glycoprotein Acts at Multiple Steps To Abrogate Viral Entry.
Ebola virus (EBOV) causes highly lethal disease outbreaks against which no FDA-approved countermeasures are available. Although many host factors exploited by EBOV for cell entry have been identified, including host cell surface phosphatidylserine receptors, endosomal cysteine proteases, and the lysosomal cholesterol trafficking protein NPC1, key questions remain. Specifically, late entry ... More
Round optimization for improved discovery of native bispecific antibodies.
AuthorsGueneau F, Ravn U, Fischer N,
JournalMethods
PubMed ID30448477
The assembly of bispecific antibodies (bsAb) that retain the structure of a standard IgG can be challenging as the correct pairing of the different heavy and light chains has to be ensured while unwanted side products kept to a minimum. The use of antibodies sharing a common chain facilitates assembly ... More
High-Content Screening for Cryptosporidium Drug Discovery.
AuthorsLove MS, McNamara CW,
JournalMethods Mol Biol
PubMed ID31452169
High-content screening (HCS) is a cell-based type of phenotypic screening that combines multiple simultaneous readouts with a high level of throughput. A particular benefit of this form of screening for drug discovery is the ability to perform the interrogation in a biologically relevant system. This approach has greatly advanced the ... More