Identification of genotype 4 Hepatitis E virus binding proteins on swine liver cells

Hepatitis E virus (HEV) is a zoonotic pathogen of which several species of animal were reported as reservoirs. Swine stands out as the major reservoir for HEV infection in humans, as suggested by the close genetic relationship of swine and human virus and cross-species infection of HEV. Up to now, the mechanism of cross-species infection of HEV from swine to humans is still unclear. This study sought to identify receptor element for genotype 4 HEV on swine liver cells using the viral overlay protein binding assay (VOPBA) technique and Mass Spectrometry fingerprinting. A single virus binding band with natural molecular weight about 55 kDa was observed, and mass spectrometry revealed that this virus binding band contained 31 different proteins. Infection inhibition assay suggested that this 55 kDa protein could prevent HEV from infecting its susceptible A549 cell line, which was further confirmed by the HEV genome detecting in the inoculated cells. Further research should be performed to elucidate the accurate receptor of HEV on the swine liver cells

Electrochemical Monitoring of ROS/RNS Homeostasis Within Individual Phagolysosomes Inside Single Macrophages

International audienceReactive Oxygen/Nitrogen Species (ROS/RNS) produced by macrophages inside their phagolysosomes are closely related to immunity and inflammation by being involved in the removal of pathogens, altered cells, etc. The existence of a homeostatic mechanism regulating the ROS/RNS amounts inside phagolysosomes has been invoked to account for the efficiency of this crucial process but this could never be unambiguously documented. In this work, intracellular electrochemical analysis with platinized nanowires electrodes (Pt-NWEs) allowed monitoring ROS/RNS effluxes with sub-millisecond resolution from individual phagolysosomes randomly impacting onto the electrode inserted inside a living macrophage. This evidenced for the first time that the consumption of ROS/RNS by their oxidation at the nanoelectrode surface stimulates the production of significant ROS/RNS amounts inside phagolysosomes. These results established the existence of the long-time postulated ROS/RNS homeostasis and allowed quantifying its kinetics and efficiency. ROS/RNS concentrations may then be maintained at sufficiently high levels for sustaining proper pathogen digestion rates without endangering the macrophage internal structures

MADNet: Maximizing Addressee Deduction Expectation for Multi-Party Conversation Generation

Modeling multi-party conversations (MPCs) with graph neural networks has been proven effective at capturing complicated and graphical information flows. However, existing methods rely heavily on the necessary addressee labels and can only be applied to an ideal setting where each utterance must be tagged with an addressee label. To study the scarcity of addressee labels which is a common issue in MPCs, we propose MADNet that maximizes addressee deduction expectation in heterogeneous graph neural networks for MPC generation. Given an MPC with a few addressee labels missing, existing methods fail to build a consecutively connected conversation graph, but only a few separate conversation fragments instead. To ensure message passing between these conversation fragments, four additional types of latent edges are designed to complete a fully-connected graph. Besides, to optimize the edge-type-dependent message passing for those utterances without addressee labels, an Expectation-Maximization-based method that iteratively generates silver addressee labels (E step), and optimizes the quality of generated responses (M step), is designed. Experimental results on two Ubuntu IRC channel benchmarks show that MADNet outperforms various baseline models on the task of MPC generation, especially under the more common and challenging setting where part of addressee labels are missing.Comment: Accepted by EMNLP 2023. arXiv admin note: text overlap with arXiv:2203.0850

Detection of differentially expressed genes between Erhualian and Large White placentas on day 75 and 90 of gestation

<p>Abstract</p> <p>Background</p> <p>Placental efficiency is strongly associated with litter size, fetal weight and prenatal mortality. Together with its rapid growth during late gestation, the Large White pig breed shows a significant increase in placental size and weight, but this does not occur in the highly prolific Chinese pig breeds. To understand the molecular basis of placental development during late gestation in Chinese indigenous and Western breeds with different placental efficiency, female placental samples were collected from six pregnant Erhualian gilts at gestation day 75 (E75) and day 90 (E90) and from six pregnant Large White gilts at gestation day 75 (L75) and day 90 (L90). Two female placentas from one sow were used to extract RNA and then pooled in equal volumes. Twelve pooled samples were hybridized to the porcine Affymetrix GeneChip.</p> <p>Results</p> <p>A total of 226 and 577 transcripts were detected that were differentially expressed between E75 and L75 and between E90 and L90 (p < 0.01, q < 0.2), respectively. Gene Ontology (GO) analysis revealed that these genes belong to the class of genes that participate in angiogenesis and development. Real-time RT-PCR confirmed the differential expression of eight selected genes. Significant differential expression of five genes in the <it>VEGF </it>pathway was also detected between the breeds. A search of chromosomal location revealed that 44 differentially expressed genes located to QTL regions related to reproduction. Differential expression of six candidate imprinted genes was also confirmed. Three of the six genes (<it>PLAGL1</it>, <it>DIRAS3</it>, and <it>SLC38A4</it>) showed monoallelic expression in the porcine placenta.</p> <p>Conclusion</p> <p>Our study detected many genes that showed differential expression between placentas of two divergent breed of pigs, and confirmed the imprinting of three genes. These findings help to elucidate the genetic control of placental efficiency and improve the understanding of placental development.</p

6-Methyl-2-p-tolyl-4-[3-(trifluoro­meth­yl)phen­yl]pyridazin-3(2H)-one

In the title mol­ecule, C19H15F3N2O, the benzene rings of the tolyl and trifluoro­methyl­phenyl groups form dihedral angles of 64.1 (2) and 38.5 (2)°, respectively, with the pyridazine ring. The CF3 group is disordered over two orientations, with site-occupancy factors of ca 0.56 and 0.44

A role of brassinosteroids in early fruit development in cucumber

Brassinosteroids (BRs) are essential for many biological processes in plants, however, little is known about their roles in early fruit development. To address this, BR levels were manipulated through the application of exogenous BRs (24-epibrassinolide, EBR) or a BR biosynthesis inhibitor (brassinazole, Brz) and their effects on early fruit development, cell division, and expression of cyclin and cyclin-dependent kinases (CDKs) genes were examined in two cucumber cultivars that differ in parthenocarpic capacity. The application of EBR induced parthenocarpic growth accompanied by active cell division in Jinchun No. 4, a cultivar without parthenocarpic capacity, whereas Brz treatment inhibited fruit set and, subsequently, fruit growth in Jinchun No. 2, a cultivar with natural parthenocarpic capacity, and this inhibitory effect could be rescued by the application of EBR. RT-PCR analysis showed both pollination and EBR induced expression of cell cycle-related genes (CycA, CycB, CycD3;1, CycD3;2, and CDKB) after anthesis. cDNA sequences for CsCycD3;1 and CsCycD3;2 were isolated through PCR amplification. Both CsCycD3;1 and CsCycD3;2 transcripts were up-regulated by EBR treatment and pollination but strongly repressed by Brz treatment. Meanwhile, BR6ox1 and SMT transcripts, two genes involved in BR synthesis, exhibited feedback regulation. These results strongly suggest that BRs play an important role during early fruit development in cucumber

Identification of FKBP10 prognostic value in lung adenocarcinoma patients with surgical resection of brain metastases: A retrospective single-institution cohort study

Objective: To explore the expression levels and clinical value of FKBP10 in lung adenocarcinoma brain metastases. Design: A retrospective single-institution cohort study. Patients: The perioperative records of&nbsp;71&nbsp;patients with lung adenocarcinoma brain metastases who underwent surgical resection at the authors’ institution between November&nbsp;2012 and June&nbsp;2019 were retrospectively analyzed. Methods: The authors evaluated FKBP10 expression levels using immunohistochemistry in tissue arrays of these patients. Kaplan-Meier survival curves were constructed, and a Cox proportional hazards regression model was used to identify independent prognostic biomarkers. A public database was used to detect FKBP10 expression and its clinical value in primary lung adenocarcinoma. Results: The authors found that the FKBP10 protein was selectively expressed in lung adenocarcinoma brain metastases. Survival analysis showed that FKBP10 expression (p&nbsp;=&nbsp;0.02, HR&nbsp;=&nbsp;2.472, 95%&nbsp;CI&nbsp;[1.156, 5.289]), target therapy (p &lt; 0.01, HR&nbsp;=&nbsp;0.186, 95%&nbsp;CI [0.073, 0.477]), and radiotherapy (p&nbsp;=&nbsp;0.006, HR&nbsp;=&nbsp;0.330, 95%&nbsp;CI&nbsp;[0.149, 0.731]) were independent prognostic factors for survival in lung adenocarcinoma patients with brain metastases. The authors also detected FKBP10 expression in primary lung adenocarcinoma using a public database, found that FKBP10 is also selectively expressed in primary lung adenocarcinoma, and affects the overall survival and disease-free survival of patients. Limitations: The number of enrolled patients was relatively small and patients’ treatment options varied. Conclusions: A combination of surgical resection, adjuvant radiotherapy, and precise target therapy may benefit the survival of selected patients with lung adenocarcinoma brain metastases. FKBP10 is a novel biomarker for lung adenocarcinoma brain metastases, which is closely associated with survival time and may serve as a potential therapeutic target