Angiogenesis-promoting macromolecules reduce adverse remodeling and preserve cardiac function in rodents following myocardial infarctions, yet repeatedly fail to translate across length scales in humans. Through mass transport studies in human and swine myocardium, we found that dense, anisotropic myocardial fibers limit therapeutic diffusion and convection to millimeter scales for existing approaches including bolus intramyocardial injections, […]
TorchLIMIX: GPU-accelerated multivariate genome-wideassociation studies
We introduce TorchLIMIX, a GPU-accelerated PyTorch implementation of the LIMIX multivariate genome-wide association study pipeline. By leveraging batched GPU linear algebra, TorchLIMIX achieves speedups of up to two orders of magnitude over the original CPU-based implementation while maintaining numerically equivalent results and full concordance of significantly associated loci. In simulation studies, replacing the default initialization […]
A Bio-inspired Synthetic Gene Circuit
Salinity exerts a major constraint on global crop production while seawater intrusion impacts coastal aquifers and surface waters. Using a blueprint from nature, we produced highly salt tolerant Arabidopsis and rice. Endodermal-like barriers, duplicated to the root epidermis and distally expanded to protect sensitive regions, provide salt tolerance to 600 mM NaCl, levels comparable to […]
Dynamic CTCF bridges drive genome organization
Human CCCTC-binding factor (CTCF) is a crucial factor in genome organization, regulating chromatin looping and gene expression. The loop extrusion model (LEM) designates cohesin as the sole active player and limits CTCF to a passive barrier, though emerging evidence suggests a more dynamic role. Using complementary single-molecule techniques, combining dual- and quad-trap optical tweezers, fluorescence […]
Nanoscale Organization of Membrane Tension during Neutrophil Extracellular Trap Formation Revealed by Fluorescence Lifetime Imaging
Cells continuously generate and respond to mechanical forces across compartments, with the plasma membrane acting as a nanoscale interface for sensing and transmitting tension. How intracellular forces are translated into membrane tension during dynamic processes such as neutrophil extracellular trap (NET) formation remains unclear. Here, we combine the mechanosensitive fluorescent probe Flipper-TR with fluorescence lifetime […]
TolC is required for a Mixed-Linkage β-Glucan (MLG) biosynthesis: Engineering bacteria for MLG overproduction
Mixed-linkage beta-glucans (MLGs) are emerging as promising biopolymers with significant biotechnological potential due to their unique structural and rheological properties. In rhizobia, MLG biosynthesis is controlled by the second messenger cyclic di-GMP (c-di-GMP) and mediated by the bicistronic operon bgsBA. However, the full composition of the biosynthetic machinery and strategies for enhanced production remain incompletely […]
Novel mouse reporter models for the detection of genome editing events in vivo
With the expansion of therapeutic gene editing technology, small animal models provide essential platforms to evaluate the function of these new approaches in vivo. As part of the Somatic Cell Genome Editing (SCGE) Consortium, we developed next-generation murine reporters that overcome current model limitations and broaden detectable in vivo editing outcomes. These include two mouse […]
Copper transport is required for metabolism and persistence of Toxoplasma gondii
Copper is a conserved cofactor, required for aerobic mitochondrial respiration and other cellular processes. Pathogens acquire copper from their hosts, however the mechanisms of uptake and role of copper within divergent eukaryotes is not well understood. Here, using genetic and metabolic approaches we identify and validate the two copper transporters of Toxoplasma gondii, and we […]
TorchLIMIX: GPU-accelerated multivariate genome-wideassociation studies
We introduce TorchLIMIX, a GPU-accelerated PyTorch implementation of the LIMIX multivariate genome-wide association study pipeline. By leveraging batched GPU linear algebra, TorchLIMIX achieves speedups of up to two orders of magnitude over the original CPU-based implementation while maintaining numerically equivalent results and full concordance of significantly associated loci. In simulation studies, replacing the default initialization […]
Cycles upon cycles – Temperature Scaling of Medaka Development
How organisms develop in dynamic environmental conditions is a fundamental question. We asked how day-night temperature cycles impact embryonic axis elongation and segmentation, itself a cyclic process linked to the segmentation clock, using the Japanese rice fish, Medaka. We developed an unbiased dimensional reduction approach, based on Singular Value Decomposition (SVD), to reliably identify the […]
Evidence for an Organometallic Species Formed in the ArsL Reaction
The radical S-adenosylmethionine (SAM) superfamily comprises over 800,000 unique sequences of enzymes that catalyze more than 100 distinct reactions. Canonical radical SAM (RS) enzymes are composed of a full or partial triose phosphate isomerase fold and contain a highly conserved CX3CX2C motif. The cysteines in the conserved motif ligate an [Fe4S4] cluster used in the […]
Multi-point convective delivery overcomes mass transport barriers for myocardial therapeutics
Angiogenesis-promoting macromolecules reduce adverse remodeling and preserve cardiac function in rodents following myocardial infarctions, yet repeatedly fail to translate across length scales in humans. Through mass transport studies in human and swine myocardium, we found that dense, anisotropic myocardial fibers limit therapeutic diffusion and convection to millimeter scales for existing approaches including bolus intramyocardial injections, […]