Search results for " polar"

Tetraspanin CD63 controls basolateral sorting of organic cation transporter 2 in renal proximal tubules.

2016

CD63 is a ubiquitously expressed member of the tetraspanin superfamily. Using a mating-based split-ubiquitin-yeast 2-hybrid system, pull-down experiments, total internal reflection fluorescence microscopy, Forster resonance energy transfer, and biotinylation assays, we found that CD63 interacts with human organic cation transporter 2 (hOCT2), which transports endogenous and exogenous substrates, such as neurotransmitters and drugs in several epithelial cells. CD63 overexpression affects cellular localization of hOCT2 expressed in human embryonic kidney (HEK)293 cells. Studies with CD63-knockout mice indicate that in renal proximal tubules, CD63 determines the insertion of the mouse ortholog…

Intercellular Connectivity and Multicellular Bioelectric Oscillations in Nonexcitable Cells: A Biophysical Model

2018

Bioelectricity is emerging as a crucial mechanism for signal transmission and processing from the single-cell level to multicellular domains. We explore theoretically the oscillatory dynamics that result from the coupling between the genetic and bioelectric descriptions of nonexcitable cells in multicellular ensembles, connecting the genetic prepatterns defined over the ensemble with the resulting spatio-temporal map of cell potentials. These prepatterns assume the existence of a small patch in the ensemble with locally low values of the genetic rate constants that produce a specific ion channel protein whose conductance promotes the cell-polarized state (inward-rectifying channel). In this…

Heterogeneity of biomaterial-induced multinucleated giant cells: Possible importance for the regeneration process?

2015

Biomaterial-associated multinucleated giant cells (BMGCs) have been found within the implantation beds of many different biomaterials. However, their exact differentiation and their involvement in the inflammatory and healing events of the foreign body response still remain mostly unclear. Silk fibroin (SF) scaffolds, which induces a tissue reaction involving both macrophages and BMGCs, was implanted in the subcutaneous connective tissue of four CD-1 mice for 15 days using an established subcutaneous implantation model. Analysis of macrophage polarization and BMGCs was performed by immunohistochemcial detection of pro- (cyclooxygenase-2 (COX-2), C-C chemokine receptor type 7 (CCR7), nuclear…

Cytoplasmic localization of the cell polarity factor scribble supports liver tumor formation and tumor cell invasiveness

2018

The loss of epithelial cell polarity plays an important role in the development and progression of liver cancer. However, the specific molecular mechanisms supporting tumor initiation and progression are poorly understood. In this study, transcriptome data and immunofluorescence stains of tissue samples derived from hepatocellular carcinoma (HCC) patients revealed that overexpression associated with cytoplasmic localization of the baso-lateral cell polarity complex protein Scribble (Scrib) correlated with poor prognosis of HCC patients. In comparison to HCC cells stably expressing wildtype Scrib (ScribWT), mutated Scrib with enforced cytoplasmic enrichment (ScribP305L) induced AKT signaling…

Th17 skewing in the GALT of a Crohn disease patient upon Lactobacillus rhamnosus GG consumption.

2015

We wish to report on a recent observation we made and that might represent a useful hint for the employment of the so called probiotics in the management of some pathological immune reactions of the gut. By analyzing GALT-associated T cells upon consumption of L. rhamnosus-GG, we obtained some hints that probiotics might have locoregional immunological effects mainly when administered in patients with IBDs rather than in individuals with non-inflamed gut mucosa.

Macrophage Factor Xa Signaling Promotes Cancer Immune Evasion

2018

Abstract Coagulation signaling through protease activated receptors (PARs) participates in inflammation and immunity. In cancer, tissue factor (TF) driven signaling via PAR2 promotes tumor progression, but effective pharmacological strategies to inhibit the PAR2 activating proteases for clinical anti-cancer benefit are currently unknown. To gain a better understanding of signaling by coagulation proteases, we generated PAR2 mouse strains with mutations that abolish canonical proteolysis by all proteases including FVIIa (PAR2 R38E) or create specific resistance to cleavage by the TF-FVIIa-Xa signaling complex (PAR2 G37I) that requires the endothelial cell protein C receptor (EPCR, Procr). As…

Transport of Amino Acids Across the Blood-Brain Barrier.

2020

The blood-brain-barrier (BBB), present in brain capillaries, constitutes an essential barrier mechanism for normal functioning and development of the brain. The presence of tight junctions between adjacent endothelial cells restricts permeability and movement of molecules between extracellular fluid and plasma. The protein complexes that control cell-cell attachment also polarize cellular membrane, so that it can be divided into luminal (blood-facing) and abluminal (brain) sides, and each solute that enters/leaves the brain must cross both membranes. Several amino acid (AA) transport systems with different distributions on both sides of the BBB have been described. In a broad sense, there a…

2021

Background: Immunomodulatory properties of bisphosphonates (BP) are suggested to contribute to the development of medication-associated osteonecrosis of the jaw (MRONJ). Furthermore, bisphosphonate-derived immune modulation might contribute to the anti-metastatic effect observed in breast cancer patients. Macrophages are potential candidates for the mediation of immunomodulatory effects of bisphosphonates. The study aimed to investigate the influence of bisphosphonates alone and in combination with surgical trauma on systemic macrophage polarization (M1 vs. M2) using an in vivo rat model. Methods: A total of 120 animals were divided into four groups. Groups 2 and 4 were treated with 8 × 40 …

Practicing logical reasoning through Drosophila segmentation gene mutants.

2021

Laboratory practical sessions are critical to scientific training in biology but usually fail to promote logical and hypothesis-driven reasoning and rely heavily on the teacher's instructions. This paper describes a 2-day laboratory practicum in which students prepare and analyze larval cuticle preparations of Drosophila segmentation gene mutant strains. Embryonic segmentation involves three major classes of genes according to their loss-of-function phenotypes: the establishment of broad regions by gap genes, the specification of the segments by the pair-rule genes, and the compartments within segments by the segment polarity genes. Students are asked to sort undefined segmentation mutants …

Rho resonance, timelike pion form factor, and implications for lattice studies of the hadronic vacuum polarization

2020

We study isospin-1 P-wave ππ scattering in lattice QCD with two flavors of O(a) improved Wilson fermions. For pion masses ranging from mπ=265 MeV to mπ=437 MeV, we determine the energy spectrum in the center-of-mass frame and in three moving frames. We obtain the scattering phase shifts using Lüscher’s finite-volume quantization condition. Fitting the dependence of the phase shifts on the scattering momentum to a Breit-Wigner form allows us to determine the corresponding ρ mass mρ and gρππ coupling. By combining the scattering phase shifts with the decay matrix element of the vector current, we calculate the timelike pion form factor, Fπ, and compare the results to the Gounaris-Sakurai repr…