Mutant Fam20c knock-in mice recapitulate both lethal and non-lethal human Raine Syndrome.

Background: Inactivation or mutations of FAM20C causes human Raine Syndrome, which manifests as lethal osteosclerosis bone dysplasia or non-lethal hypophosphatemia rickets. However, it is only hypophosphatemia rickets that was reported in the mice with Fam20c deletion or mutations. To further investigate the local and global impacts of Fam20c mutation, we constructed a knock-in allele carrying Fam20c mutation (D446N) found in the non-lethal Raine Syndrome.

Emergence of structures in neuronal network activities.

Nonlinear responses of individual neurons are both experimentally established and considered fundamental for the functioning of neuronal circuitry. Consequently, one may envisage the collective dynamics of large networks of neurons exhibiting a large repertoire of nonlinear behaviors. However, an ongoing and central challenge in the modeling of neural dynamics involves the trade-off between tractability and biological realism.

Transplantation of gasdermin pores by extracellular vesicles propagates pyroptosis to bystander cells.

Pyroptosis mediated by gasdermins (GSDMs) plays crucial roles in infection and inflammation. Pyroptosis triggers the release of inflammatory molecules, including damage-associated molecular patterns (DAMPs). However, the consequences of pyroptosis-especially beyond interleukin (IL)-1 cytokines and DAMPs-that govern inflammation are poorly defined.

Configuration of electrical synapses filters sensory information to drive behavioral choices.

Synaptic configurations underpin how the nervous system processes sensory information to produce a behavioral response. This is best understood for chemical synapses, and we know far less about how electrical synaptic configurations modulate sensory information processing and context-specific behaviors. We discovered that innexin 1 (INX-1), a gap junction protein that forms electrical synapses, is required to deploy context-specific behavioral strategies underlying thermotaxis behavior in C.

Anionic polysaccharides as delivery carriers for cancer therapy and theranostics: An overview of significance.

Recently, cancer therapy has witnessed remarkable advancements with a growing focus on precision medicine and targeted drug delivery strategies. The application of anionic polysaccharides has gained traction in various drug delivery systems. Anionic polysaccharides have emerged as promising delivery carriers in cancer therapy and theranostics, offering numerous advantages such as biocompatibility, low toxicity, and the ability to encapsulate and deliver therapeutic agents to tumor sites with high specificity.

A predictive language model for SARS-CoV-2 evolution.

Modeling and predicting mutations are critical for COVID-19 and similar pandemic preparedness. However, existing predictive models have yet to integrate the regularity and randomness of viral mutations with minimal data requirements. Here, we develop a non-demanding language model utilizing both regularity and randomness to predict candidate SARS-CoV-2 variants and mutations that might prevail.

Impact of Bindarit, a CCL2 Chemokine Synthesis Inhibitor, on Macrophage-Based Biofouling and Continuous Glucose Monitoring .

Continuous glucose monitoring (CGM) using implantable glucose sensors is a critical tool in the management of diabetes. Unfortunately, current commercial glucose sensors have limited performance and lifespans , considered to be due to sensor-induced tissue reactions (inflammation, fibrosis, and vessel regression). Previously, our laboratory utilized monocyte/macrophage (Mo/MQ) deficient and depleted mice to establish a causal relationship between Mo/MQ accumulation and inflammation in glucose sensor performance .

Optogenetically Induced Microtubule Acetylation Unveils the Molecular Dynamics of Actin-Microtubule Crosstalk in Directed Cell Migration.

Microtubule acetylation is implicated in regulating cell motility, yet its physiological role in directional migration and the underlying molecular mechanisms have remained unclear. This knowledge gap has persisted primarily due to a lack of tools capable of rapidly manipulating microtubule acetylation in actively migrating cells. To overcome this limitation and elucidate the causal relationship between microtubule acetylation and cell migration, we developed a novel optogenetic actuator, optoTAT, which enables precise and rapid induction of microtubule acetylation within minutes in live cells.

PITX2 expression and Neanderthal introgression in HS3ST3A1 contribute to variation in tooth dimensions in modern humans.

Dental morphology varies greatly throughout evolution, including in the human lineage, but little is known about the biology of this variation. Here, we use multiomics analyses to examine the genetics of variation in tooth crown dimensions. In a human cohort with mixed continental ancestry, we detected genome-wide significant associations at 18 genome regions.

Immune digital twins for complex human pathologies: applications, limitations, and challenges.

Digital twins represent a key technology for precision health. Medical digital twins consist of computational models that represent the health state of individual patients over time, enabling optimal therapeutics and forecasting patient prognosis. Many health conditions involve the immune system, so it is crucial to include its key features when designing medical digital twins.

The differential orbitofrontal activity and connectivity between atypical and typical major depressive disorder.

Objective: Atypical major depressive disorder (MDD) is a distinct subtype of MDD, characterized by increased appetite and/or weight gain, excessive sleep, leaden paralysis, and interpersonal rejection sensitivity. Delineating different neural circuits associated with atypical and typical MDD would better inform clinical personalized interventions.

Methods: Using resting-state fMRI, we investigated the voxel-level regional homogeneity (ReHo) and functional connectivity (FC) in 55 patients with atypical MDD, 51 patients with typical MDD, and 49 healthy controls (HCs).

Metabolic Chaos in Kidney Disease: Unraveling Energy Dysregulation.

Background: Acute kidney injury (AKI) and chronic kidney disease (CKD) share a fundamental disruption: metabolic dysfunction.

Methods: A literature review was performed to determine the metabolic changes that occur in AKI and CKD as well as potential therapeutic targets related to these changes.

Results: In AKI, increased energy demand in proximal tubular epithelial cells drives a shift from fatty acid oxidation (FAO) to glycolysis.

Interpreting CRISPR-Cas12a enzyme kinetics through free energy change of nucleic acids.

While CRISPR has revolutionized biotechnology, predicting CRISPR-Cas nuclease activity remains a challenge. Herein, through the trans-cleavage feature of CRISPR-Cas12a, we investigate the correlation between CRISPR enzyme kinetics and the free energy change of crRNA and DNA targets from their initial thermodynamic states to a presumed transition state before hybridization. By subjecting computationally designed CRISPR RNAs (crRNAs), we unravel a linear correlation between the trans-cleavage kinetics of Cas12a and the energy barrier for crRNA spacer and single-stranded DNA target unwinding.

Innovative spiral nerve conduits: Addressing nutrient transport and cellular activity for critical-sized nerve defects.

Large-gap nerve defects require nerve guide conduits (NGCs) for complete regeneration and muscle innervation. Many NGCs have been developed using various scaffold designs and tissue engineering strategies to promote axon regeneration. Still, most are tubular with inadequate pore sizes and lack surface cues for nutrient transport, cell attachment, and tissue infiltration.

CalDAG-GEFI acts as a guanine nucleotide exchange factor for LRRK2 to regulate LRRK2 function and neurodegeneration.

Mutations in are the most common genetic cause of Parkinson's disease (PD). LRRK2 protein contains two enzymatic domains: a GTPase (Roc-COR) and a kinase domain. Disease-causing mutations are found in both domains.

Genes Regulate Purkinje Cell Diversity in Cerebellar Development and Evolution.

Mammalian cerebellar development is thought to be influenced by distinct Purkinje cell (PC) subtypes. However, the degree of PC heterogeneity and the molecular drivers of this diversity have remained unclear, hindering efforts to manipulate PC diversification and assess its role in cerebellar development. Here, we demonstrate the critical role of genes in cerebellar development by regulating PC diversification.