Engineering synthetic phosphorylation signaling networks in human cells.

Protein phosphorylation signaling networks have a central role in how cells sense and respond to their environment. We engineered artificial phosphorylation networks in which reversible enzymatic phosphorylation cycles were assembled from modular protein domain parts and wired together to create synthetic phosphorylation circuits in human cells. Our design scheme enabled model-guided tuning of circuit function and the ability to make diverse network connections; synthetic phosphorylation circuits can be coupled to upstream cell surface receptors to enable fast-timescale sensing of extracellular ligands, and downstream connections can regulate gene expression.

BCL2 Protein Progressively Declines during Robust CLL Clonal Expansion: Potential Impact on Venetoclax Clinical Efficacy and Insights on Mechanism.

CLL B cells express elevated pro-survival BCL2, and its selective inhibitor, venetoclax, significantly reduces leukemic cell load, leading to clinical remission. Nonetheless, relapses occur. This study evaluates the hypothesis that progressively diminished BCL2 protein in cycling CLL cells within patient lymph node niches contributes to relapse.

All1750 of Anabaena PCC 7120 encodes a novel NAD-dependent amine dehydrogenase having broad substrate range.

Native amine dehydrogenases (AmDHs) are rare and typically have narrow substrate specificity and low processivity. Therefore, they are often modified using protein engineering for industrial and pharmaceutical applications. This study presents identification and characterization of a novel native amine dehydrogenase (AmDH) encoding WD40 protein (All1750) from Anabaena PCC 7120.

Identifying waves of COVID-19 mortality using skew normal curves.

We propose a model for multiple waves of an epidemic that decomposes the health outcome of interest into the sum of scaled skew normal curves. When applied to daily COVID-19 mortality in six regions (Japan, Italy, Belgium, Ontario, Texas, and Peru), this model provides three notable results. First, when fit to data from early 2020 to May 31, 2022, the estimated skew normal curves substantially overlap with the dates of COVID-19 waves in Ontario and Belgium, as determined by their respective health authorities.

Plasma DNA Methylation-Based Biomarkers for MPNST Detection in Patients With Neurofibromatosis Type 1.

Malignant peripheral nerve sheath tumor (MPNST) development is characterized by an altered DNA methylation landscape, which presents a promising area for developing MPNST-specific biomarkers for screening patients with NF1. Genome-wide DNA methylation profiling of a cohort of 13 patients with MPNST (29 samples of tumor and adjacent neurofibroma tissues) and of NF1-MPNST cell lines was performed to identify and validate candidate MPNST-specific CpG sites (CpGs). A logistic regression prediction model was constructed to select MPNST-specific CpGs distinct from adjacent neurofibromas and normal tissues.