Repression of Germline RNAi Pathways in Somatic Cells by Retinoblastoma Pathway Chromatin Complexes

The retinoblastoma (Rb) tumor suppressor acts with a number of chromatin cofactors in a wide range of species to suppress cell proliferation. The Caenorhabditis elegans retinoblastoma gene and many of these cofactors, called synMuv B genes, were identified in genetic screens for cell lineage defects caused by growth factor misexpression. Mutations in many synMuv B genes, including lin-35/Rb, also cause somatic misexpression of the germline RNA processing P granules and enhanced RNAi. We show here that multiple small RNA components, including a set of germline-specific Argonaute genes, are misexpressed in the soma of many synMuv B mutant animals, revealing one node for enhanced RNAi. Distinct classes of synMuv B mutants differ in the subcellular architecture of their misexpressed P granules, their profile of misexpressed small RNA and P granule genes, as well as their enhancement of RNAi and the related silencing of transgenes. These differences define three classes of synMuv B genes, representing three chromatin complexes: a LIN-35/Rb-containing DRM core complex, a SUMO-recruited Mec complex, and a synMuv B heterochromatin complex, suggesting that intersecting chromatin pathways regulate the repression of small RNA and P granule genes in the soma and the potency of RNAi. Consistent with this, the DRM complex and the synMuv B heterochromatin complex were genetically additive and displayed distinct antagonistic interactions with the MES-4 histone methyltransferase and the MRG-1 chromodomain protein, two germline chromatin regulators required for the synMuv phenotype and the somatic misexpression of P granule components. Thus intersecting synMuv B chromatin pathways conspire with synMuv B suppressor chromatin factors to regulate the expression of small RNA pathway genes, which enables heightened RNAi response. Regulation of small RNA pathway genes by human retinoblastoma may also underlie its role as a tumor suppressor gene

ActionPrompt: Action-Guided 3D Human Pose Estimation With Text and Pose Prompting

Recent 2D-to-3D human pose estimation (HPE) utilizes temporal consistency across sequences to alleviate the depth ambiguity problem but ignore the action related prior knowledge hidden in the pose sequence. In this paper, we propose a plug-and-play module named Action Prompt Module (APM) that effectively mines different kinds of action clues for 3D HPE. The highlight is that, the mining scheme of APM can be widely adapted to different frameworks and bring consistent benefits. Specifically, we first present a novel Action-related Text Prompt module (ATP) that directly embeds action labels and transfers the rich language information in the label to the pose sequence. Besides, we further introduce Action-specific Pose Prompt module (APP) to mine the position-aware pose pattern of each action, and exploit the correlation between the mined patterns and input pose sequence for further pose refinement. Experiments show that APM can improve the performance of most video-based 2D-to-3D HPE frameworks by a large margin.Comment: 6 pages, 4 figures, 2023ICM

Modified Technique of Pancreaticogastrostomy for Soft Pancreas with Two Continuous Hemstitch Sutures: A Single-Center Prospective Study

Postoperative pancreatic fistula (POPF) remains a persistent problem after pancreaticoduodenectomy (PD), especially in the presence of a soft, nonfibrotic pancreas. To reduce the risk of POPF, pancreaticogastrostomy (PG) is an optional reconstruction technique for surgeons after PD. This study presents a new technique of PG for a soft, nonfibrotic pancreas with double-binding continuous hemstitch sutures and evaluates its safety and reliability. From January 2011 to June 2012, 92 cases of patients with periampullary malignancy with a soft pancreas underwent this technique. A modified technique of PG was performed with two continuous hemstitch sutures placed in the mucosal and seromuscular layers of the posterior gastric wall, respectively. Then the morbidity and mortality was calculated. This technique was applied in 92 patients after PD all with soft pancreas. The median time for the anastomosis was 12 min (range, 8–24). Operative mortality was zero, and morbidity was 16.3 % (n = 15), including hemorrhage (n = 2), biliary fistula (n = 2), pulmonary infection (n = 1), delayed gastric emptying (DGE; n = 5, 5.4 %), abdominal abscess (n = 3, one caused by PF), and POPF (n = 2, 2.2 %). Two patients developed a pancreatic fistula (one type A and one type B) classified according to the International Study Group on Pancreatic Fistula. The described technique is a simple and safe reconstruction procedure after PD, especially for patients with a soft and fragile pancreas. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11605-013-2183-8) contains supplementary material, which is available to authorized users

The role of the transcription factor Rbpj in the development of dorsal root ganglia

<p>Abstract</p> <p>Background</p> <p>The dorsal root ganglion (DRG) is composed of well-characterized populations of sensory neurons and glia derived from a common pool of neural crest stem cells (NCCs), and is a good system to study the mechanisms of neurogenesis and gliogenesis. Notch signaling is known to play important roles in DRG development, but the full scope of Notch functions in mammalian DRG development remains poorly understood.</p> <p>Results</p> <p>In the present study, we used <it>Wnt1-Cre </it>to conditionally inactivate the transcription factor Rbpj, a critical integrator of activation signals from all Notch receptors, in NCCs and their derived cells. Deletion of <it>Rbpj </it>caused the up-regulation of <it>NeuroD1 </it>and precocious neurogenesis in DRG early development but led to an eventual deficit of sensory neurons at later stages, due to reduced cell proliferation and abnormal cell death. In addition, gliogenesis was delayed initially, but a near-complete loss of glia was observed finally in <it>Rbpj</it>-deficient DRG. Furthermore, we found P75 and Sox10, which are normally expressed exclusively in neuronal and glial progenitors of the DRG after the NCCs have completed their migration, were co-expressed in many cells of the DRG of <it>Rbpj </it>conditional knock-out mice.</p> <p>Conclusions</p> <p>Our data indicate that Rbpj-mediated canonical Notch signaling inhibits DRG neuronal differentiation, possibly by regulating <it>NeuroD1 </it>expression, and is required for DRG gliogenesis <it>in vivo</it>.</p

Pose-Oriented Transformer with Uncertainty-Guided Refinement for 2D-to-3D Human Pose Estimation

There has been a recent surge of interest in introducing transformers to 3D human pose estimation (HPE) due to their powerful capabilities in modeling long-term dependencies. However, existing transformer-based methods treat body joints as equally important inputs and ignore the prior knowledge of human skeleton topology in the self-attention mechanism. To tackle this issue, in this paper, we propose a Pose-Oriented Transformer (POT) with uncertainty guided refinement for 3D HPE. Specifically, we first develop novel pose-oriented self-attention mechanism and distance-related position embedding for POT to explicitly exploit the human skeleton topology. The pose-oriented self-attention mechanism explicitly models the topological interactions between body joints, whereas the distance-related position embedding encodes the distance of joints to the root joint to distinguish groups of joints with different difficulties in regression. Furthermore, we present an Uncertainty-Guided Refinement Network (UGRN) to refine pose predictions from POT, especially for the difficult joints, by considering the estimated uncertainty of each joint with uncertainty-guided sampling strategy and self-attention mechanism. Extensive experiments demonstrate that our method significantly outperforms the state-of-the-art methods with reduced model parameters on 3D HPE benchmarks such as Human3.6M and MPI-INF-3DHPComment: accepted by AAAI202