Characterisation of Death Receptor 3 dependent aortic changes during inflammatory arthritis

Murine collagen‐induced arthritis (mCIA) is characterized by decreased vascular constriction responses and increased MMP‐9. Here, we describe additional histological alterations within the aorta and surrounding perivascular adipose tissue (PVAT), study the role of PVAT in constriction response, and investigate the potential involvement of death receptor 3 (DR3). mCIA was induced in wild‐type (WT) and DR3−/− mice with nonimmunized, age‐matched controls. Vascular function was determined in isolated aortic rings ±PVAT, using isometric tension myography, in response to cumulative serotonin concentrations. Cellular expression of F4/80 (macrophages), Ly6G (neutrophils), DR3, and MMP‐9 was determined using immunohistochemistry. In WTs, arthritis‐induced vascular dysfunction was associated with increased F4/80+ macrophages and increased DR3 expression in the aorta and PVAT. MMP‐9 was also up‐regulated in PVAT, but did not correlate with alterations of PVAT intact constriction. DR3−/− mice inherently showed increased leukocyte numbers and MMP‐9 expression in the PVAT, but retained the same nonarthritic constriction response as DR3WT mice ±PVAT. Arthritic DR3−/− mice had a worsened constriction response than DR3WT and showed an influx of neutrophils to the aorta and PVAT. Macrophage numbers were also up‐regulated in DR3−/− PVAT. Despite this influx, PVAT intact DR3−/− constriction responses were restored to the same level as DR3WT. Impaired vascular constriction in inflammatory arthritis occurs independently of total MMP‐9 levels, but correlates with macrophage and neutrophil ingress. Ablating DR3 worsens the associated vasculature dysfunction, however, DR3−/− PVAT is able to protect the aorta against aberrant vasoconstriction caused in this model

Movie101: A New Movie Understanding Benchmark

To help the visually impaired enjoy movies, automatic movie narrating systems are expected to narrate accurate, coherent, and role-aware plots when there are no speaking lines of actors. Existing works benchmark this challenge as a normal video captioning task via some simplifications, such as removing role names and evaluating narrations with ngram-based metrics, which makes it difficult for automatic systems to meet the needs of real application scenarios. To narrow this gap, we construct a large-scale Chinese movie benchmark, named Movie101. Closer to real scenarios, the Movie Clip Narrating (MCN) task in our benchmark asks models to generate role-aware narration paragraphs for complete movie clips where no actors are speaking. External knowledge, such as role information and movie genres, is also provided for better movie understanding. Besides, we propose a new metric called Movie Narration Score (MNScore) for movie narrating evaluation, which achieves the best correlation with human evaluation. Our benchmark also supports the Temporal Narration Grounding (TNG) task to investigate clip localization given text descriptions. For both two tasks, our proposed methods well leverage external knowledge and outperform carefully designed baselines. The dataset and codes are released at https://github.com/yuezih/Movie101.Comment: Accepted to ACL 202

Deletion of the Notch ligand Jagged1 during cochlear maturation leads to inner hair cell defects and hearing loss

The mammalian cochlea is an exceptionally well-organized epithelium composed of hair cells, supporting cells, and innervating neurons. Loss or defects in any of these cell types, particularly the specialized sensory hair cells, leads to deafness. The Notch pathway is known to play a critical role in the decision to become either a hair cell or a supporting cell during embryogenesis; however, little is known about how Notch functions later during cochlear maturation. Uniquely amongst Notch ligands, Jagged1 (JAG1) is localized to supporting cells during cell fate acquisition and continues to be expressed into adulthood. Here, we demonstrate that JAG1 in maturing cochlear supporting cells is essential for normal cochlear function. Specifically, we show that deletion of JAG1 during cochlear maturation disrupts the inner hair cell pathway and leads to a type of deafness clinically similar to auditory neuropathy. Common pathologies associated with disruptions in inner hair cell function, including loss of hair cells, synapses, or auditory neurons, were not observed in JAG1 mutant cochleae. Instead, RNA-seq analysis of JAG1-deficient cochleae identified dysregulation of the Rho GTPase pathway, known to be involved in stereocilia development and maintenance. Interestingly, the overexpression of one of the altered genes, Diaph3, is responsible for autosomal dominant auditory neuropathy-1 (AUNA1) in humans and mice, and is associated with defects in the inner hair cell stereocilia. Strikingly, ultrastructural analyses of JAG1-deleted cochleae revealed stereocilia defects in inner hair cells, including fused and elongated bundles, that were similar to those stereocilia defects reported in AUNA1 mice. Taken together, these data indicate a novel role for Notch signaling in normal hearing development through maintaining stereocilia integrity of the inner hair cells during cochlear maturation

Atomistic modelling of all dislocations and twins in HCP and BCC Ti

Ti exhibits complex plastic deformation controlled by active dislocation and twinning systems. Understandings on dislocation cores and twin interfaces are currently not complete or quantitative, despite extensive experimental and simulation studies. Here, we determine all the core and twin interface properties in both HCP and BCC Ti using a Deep Potential (DP) and DFT. We determine the core structures, critical resolved shear stresses and mobilities of , , dislocations in HCP and /2 dislocations in BCC Ti. The slip consists of slow core migration on pyramidal-I planes and fast migration on prism-planes, and is kinetically limited by cross-slips among them. This behaviour is consistent with "locking-unlocking" phenomena in TEM and is likely an intrinsic property. Large-scale DFT calculations provide a peek at the screw core and glide behaviour, which is further quantified using DP-Ti. The screw is unstable on pyramidal-II planes. The mixed is nearly sessile on pyramidal-I planes, consistent with observations of long dislocations in this orientation. The edge and mixed are unstable against a pyramidal-to-basal (PB) transition and become sessile at high temperatures, corroborate the difficulties in -axis compression of Ti. Finally, in BCC Ti, the /2 screw has a degenerate core with average glide on {112} planes; the /2 edge and mixed dislocations have non-dissociated cores on {110} planes. This work paints a self-consistent, complete picture on all dislocations in Ti, rationalises previous experimental observations and points to future HRTEM examinations of unusual dislocations such as the mixed and PB transformed cores

Death receptor 3 regulates distinct pathological attributes of acute versus chronic murine allergic lung inflammation

The Death Receptor 3 (DR3)/Tumour Necrosis Factor-like cytokine 1A (TL1A) axis stimulates effector T cells and type 2 innate lymphocytes (ILC2) that trigger cytokine release and drive disease pathology in several inflammatory and autoimmune diseases, including murine models of acute allergic lung inflammation (ALI). The aim of this study was to elucidate the role of DR3 in chronic ALI compared to acute ALI, using mice genetically deficient in the DR3 gene (DR3ko). Results showed DR3 expression in the lungs of wild-type mice was up-regulated following induction of acute ALI and this increased expression was maintained in chronic disease. DR3ko mice were resistant to cellular accumulation within the alveolar passages in acute, but not chronic ALI. However, DR3ko mice displayed reduced immuno-histopathology and goblet cell hyperplasia; hallmarks of the asthmatic phenotype; in chronic, but not acute ALI. These data suggest DR3 is a potential therapeutic target, involved in temporally distinct aspects of ALI progression and pathogenesis

Death receptor 3 (TNFRSF25) increases mineral apposition by osteoblasts and region specific new bone formation in the axial skeleton of male DBA/1 mice

Fraser L. Collins and this work were funded by an Arthritis Research UK PhD studentship (Grant Code: 18598) awarded to Anwen S. Williams, Eddie C. Y. Wang, and Michael D. Stone. Eddie C. Y. Wang was additionally funded by MRC Project Grant G0901119. Funding for open access was kindly provided by Cardiff University.Peer reviewedPublisher PD

Sensing User's Activity, Channel, and Location with Near-Field Extra-Large-Scale MIMO

This paper proposes a grant-free massive access scheme based on the millimeter wave (mmWave) extra-large-scale multiple-input multiple-output (XL-MIMO) to support massive Internet-of-Things (IoT) devices with low latency, high data rate, and high localization accuracy in the upcoming sixth-generation (6G) networks. The XL-MIMO consists of multiple antenna subarrays that are widely spaced over the service area to ensure line-of-sight (LoS) transmissions. First, we establish the XL-MIMO-based massive access model considering the near-field spatial non-stationary (SNS) property. Then, by exploiting the block sparsity of subarrays and the SNS property, we propose a structured block orthogonal matching pursuit algorithm for efficient active user detection (AUD) and channel estimation (CE). Furthermore, different sensing matrices are applied in different pilot subcarriers for exploiting the diversity gains. Additionally, a multi-subarray collaborative localization algorithm is designed for localization. In particular, the angle of arrival (AoA) and time difference of arrival (TDoA) of the LoS links between active users and related subarrays are extracted from the estimated XL-MIMO channels, and then the coordinates of active users are acquired by jointly utilizing the AoAs and TDoAs. Simulation results show that the proposed algorithms outperform existing algorithms in terms of AUD and CE performance and can achieve centimeter-level localization accuracy.Comment: Submitted to IEEE Transactions on Communications, Major revision. Codes will be open to all on https://gaozhen16.github.io/ soo