164 research outputs found
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An Aquaporin 3-Notch1 Axis in Keratinocyte Differentiation and Inflammation
Aquaporin 3 (AQP3) is an aquaglyceroporin which transports water, glycerol and small solutes across the plasma membrane. Its functions are not limited to fluid transport but also involve the regulation of cell proliferation, migration, skin hydration, wound healing and tumorigenesis. While AQP3 has been reported to play an important role in keratinocyte proliferation, its role in differentiation remains controversial. Our study demonstrated that the expression of AQP3 was regulated during differentiation and that it participated in keratinocyte differentiation control. We further revealed that AQP3 was a transcriptional target of Notch signaling, a critical pathway regulating keratinocyte differentiation and tumor suppression, and it regulated differentiation through a reciprocal negative feedback loop with Notch1. When the expression level of AQP3 was elevated, impaired barrier integrity and increased pro-inflammatory cytokine production ensued, mimicking the pathological conditions in Notch deficient mice and in atopic dermatitis. Dysregulation of AQP3 and Notch receptors has been reported in several skin diseases, including skin cancer. Our discovery of the novel AQP3-Notch1 axis may provide insight into epidermal homeostasis control and possible translational applications, including its potential use as a biomarker for molecular diagnosis in environmental studies
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Increased gene copy number of DEFA1/DEFA3 worsens sepsis by inducing endothelial pyroptosis.
Sepsis claims an estimated 30 million episodes and 6 million deaths per year, and treatment options are rather limited. Human neutrophil peptides 1-3 (HNP1-3) are the most abundant neutrophil granule proteins but their neutrophil content varies because of unusually extensive gene copy number polymorphism. A genetic association study found that increased copy number of the HNP-encoding gene DEFA1/DEFA3 is a risk factor for organ dysfunction during sepsis development. However, direct experimental evidence demonstrating that these risk alleles are pathogenic for sepsis is lacking because the genes are present only in some primates and humans. Here, we generate DEFA1/DEFA3 transgenic mice with neutrophil-specific expression of the peptides. We show that mice with high copy number of DEFA1/DEFA3 genes have more severe sepsis-related vital organ damage and mortality than mice with low copy number of DEFA1/DEFA3 or wild-type mice, resulting from more severe endothelial barrier dysfunction and endothelial cell pyroptosis after sepsis challenge. Mechanistically, HNP-1 induces endothelial cell pyroptosis via P2X7 receptor-mediating canonical caspase-1 activation in a NLRP3 inflammasome-dependent manner. Based on these findings, we engineered a monoclonal antibody against HNP-1 to block the interaction with P2X7 and found that the blocking antibody protected mice carrying high copy number of DEFA1/DEFA3 from lethal sepsis. We thus demonstrate that DEFA1/DEFA3 copy number variation strongly modulates sepsis development in vivo and explore a paradigm for the precision treatment of sepsis tailored by individual genetic information
UGG: Unified Generative Grasping
Dexterous grasping aims to produce diverse grasping postures with a high
grasping success rate. Regression-based methods that directly predict grasping
parameters given the object may achieve a high success rate but often lack
diversity. Generation-based methods that generate grasping postures conditioned
on the object can often produce diverse grasping, but they are insufficient for
high grasping success due to lack of discriminative information. To mitigate,
we introduce a unified diffusion-based dexterous grasp generation model, dubbed
the name UGG, which operates within the object point cloud and hand parameter
spaces. Our all-transformer architecture unifies the information from the
object, the hand, and the contacts, introducing a novel representation of
contact points for improved contact modeling. The flexibility and quality of
our model enable the integration of a lightweight discriminator, benefiting
from simulated discriminative data, which pushes for a high success rate while
preserving high diversity. Beyond grasp generation, our model can also generate
objects based on hand information, offering valuable insights into object
design and studying how the generative model perceives objects. Our model
achieves state-of-the-art dexterous grasping on the large-scale DexGraspNet
dataset while facilitating human-centric object design, marking a significant
advancement in dexterous grasping research. Our project page is
https://jiaxin-lu.github.io/ugg/ .Comment: 17 pages, 14 figure
Point Defects and Localized Excitons in 2D WSe2
Identifying the point defects in 2D materials is important for many
applications. Recent studies have proposed that W vacancies are the predominant
point defect in 2D WSe2, in contrast to theoretical studies, which predict that
chalcogen vacancies are the most likely intrinsic point defects in transition
metal dichalcogenide semiconductors. We show using first principles
calculations, scanning tunneling microscopy (STM) and scanning transmission
electron microscopy experiments, that W vacancies are not present in our
CVD-grown 2D WSe2. We predict that O-passivated Se vacancies (O_Se) and O
interstitials (Oins) are present in 2D WSe2, because of facile O2 dissociation
at Se vacancies, or due to the presence of WO3 precursors in CVD growth. These
defects give STM images in good agreement with experiment. The optical
properties of point defects in 2D WSe2 are important because single photon
emission (SPE) from 2D WSe2 has been observed experimentally. While strain
gradients funnel the exciton in real space, point defects are necessary for the
localization of the exciton at length scales that enable photons to be emitted
one at a time. Using state-of-the-art GW-Bethe-Salpeter-equation calculations,
we predict that only Oins defects give localized excitons within the energy
range of SPE in previous experiments, making them a likely source of previously
observed SPE. No other point defects (O_Se, Se vacancies, W vacancies and Se_W
antisites) give localized excitons in the same energy range. Our predictions
suggest ways to realize SPE in related 2D materials and point experimentalists
toward other energy ranges for SPE in 2D WSe2
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