How does a cell locate the source of molecular guidance cues from within a concentration gradient? We present a computational approach to recover the source from the absorbed fluxes at narrow receptor windows located on the surface of the cell. In the limit of fast binding, we solve the steady-state diffusion equation using an asymptotic approach and hybrid stochastic-analytical simulations. We show that the sensitivity to the gradient direction decays too rapidly to enable long-distance sensing. We illustrate how this constraint can be alleviated when triangulating the source with an increasing number of receptor windows and quantify the susceptibility of this process to flux perturbations.
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http://dx.doi.org/10.1103/PhysRevLett.125.148102 | DOI Listing |
Int J Mol Sci
December 2024
Department of OB/GYN and REI (UniKiD), Medical Faculty and University Hospital Duesseldorf, Heinrich Heine University Duesseldorf, 40255 Duesseldorf, Germany.
To date, very little is known about how apoptosis and autophagy affect human endometrial stromal cells (ESCs), particularly how these processes might determine the depth of implantation in humans. Before investigating how apoptosis and autophagy might modulate the implantation process in an infertile population, it is necessary to clarify how these processes are regulated in healthy individuals. This study examined the protein expression related to apoptosis and autophagy in primary ESCs from fertile women, particularly in the context of decidualization and embryo contact, using Western blot analysis.
View Article and Find Full Text PDFJ Hepatol
January 2025
Department of Surgery, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong, Shatin, Hong Kong, China. Electronic address:
Background & Aims: The ubiquitin receptor ADRM1/Rpn13 governs the specificity of eukaryotic protein degradation. By SMRT sequencing, we first discovered a novel spliced variant of ADRM1 with a skipped exon 9, termed ADRM1-ΔEx9, in human hepatocellular carcinoma (HCC). This study aimed to elucidate this novel ubiquitin receptor's underlying biology and clinical implications in HCC.
View Article and Find Full Text PDFFront Neurol
December 2024
NextGen Precision Health, University of Missouri, Columbia, MO, United States.
In Periodic Paralysis (PP), a rare inherited condition caused by mutation in skeletal muscle ion channels, the phenotype changes with age, transitioning from the episodic attacks of weakness that give the condition its name, to a more degenerative phenotype of permanent progressive weakness and myopathy. This leads to disability and reduced quality of life. Neither the cause of this phenotype transition, nor why it occurs around the age of 40 is known.
View Article and Find Full Text PDFJ Neuroimmune Pharmacol
January 2025
Pharmacology and Toxicology Department, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
Empagliflozin (EMPA) is one of the sodium/glucose cotransporter 2 (SGLT2) inhibitors that has been recently approved for the treatment of diabetes mellitus type II. Recently, EMPA has shown protective effects in different neurological disorders, besides its antidiabetic activity. Kindling is a relevant model to study epilepsy and neuroplasticity.
View Article and Find Full Text PDFT cell receptor (TCR) mimics offer a promising platform for tumor-specific targeting of peptide-MHC in cancer immunotherapy. Here, we designed a α-helical TCR mimic (TCRm) specific for the NY-ESO-1 peptide presented by HLA-A 02, achieving high on-target specificity with nanomolar affinity (K = 9.5 nM).
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