TLR3 controls constitutive IFN-β antiviral immunity in human fibroblasts and cortical neurons

Human herpes simplex virus 1 (HSV-1) encephalitis can be caused by inborn errors of the TLR3 pathway, resulting in impairment of CNS cell-intrinsic antiviral immunity. Deficiencies of the TLR3 pathway impair cell-intrinsic immunity to vesicular stomatitis virus (VSV) and HSV-1 in fibroblasts, and to HSV-1 in cortical but not trigeminal neurons. The underlying molecular mechanism is thought to involve impaired IFN-α/β induction by the TLR3 recognition of dsRNA viral intermediates or by-products. However, we show here that human TLR3 controls constitutive levels of IFNB mRNA and secreted bioactive IFN-β protein, and thereby also controls constitutive mRNA levels for IFN-stimulated genes (ISGs) in fibroblasts. Tlr3-/- mouse embryonic fibroblasts also have lower basal ISG levels. Moreover, human TLR3 controls basal levels of IFN-β secretion and ISG mRNA in induced pluripotent stem cell-derived cortical neurons. Consistently, TLR3-deficient human fibroblasts and cortical neurons are vulnerable not only to both VSV and HSV-1, but also to several other families of viruses. The mechanism by which TLR3 restricts viral growth in human fibroblasts and cortical neurons in vitro and, by inference, by which the human CNS prevents infection by HSV-1 in vivo, is therefore based on the control of early viral infection by basal IFN-β immunity

Automatic events extraction in pre-stack seismic data based on edge detection in slant-stacked peak amplitude profiles

Events picking is one of the fundamental tasks in interpreting seismic data. To extract the correct travel-time of reflected waves, picking events in a wide range of source-receiver offsets is needed. Compared to post-stack seismic data, pre-stack seismic data has an accurate horizon and abundant travel-time, amplitude, and frequency while the waveform of post-stack data is damaged by normal move-out (NMO) applications. In this paper, we focus on automatic event extraction from pre-stack reflection seismic data. With the deep development of oil-gas exploration, the difficulty of petroleum exploration is being increased. Auto recognition and picking of seismic horizon is presented as the basis for oil-gas detection. There is a correspondence between the real geology horizon and events of seismic profiles. As a result, firstly, recognizing and tracing continuous events from real seismic records are needed to acquire significant horizon locations. Picking events is in this context the recognition and tracing of waves reflected from the same interfaces according to kinematics and dynamic characteristics of seismic waves. Current extraction algorithms are well able to trace these events of the seismic profile and are undergoing great development and utilization. In this paper, a method is proposed to pick travel-time and local continuous events based on edges obtained by slant-stacked peak amplitude section (SSPA). How to calculate the SSPA section is discussed in detail. The new method can improve the efficiency and accuracy without windowing and manual picking of seed points. The event curves obtained from both the synthetic layered model and field record have validated the high accuracy and efficiency of the proposed methodology

Single Endemic Genotype of Measles Virus Continuously Circulating in China for at Least 16 Years

The incidence of measles in China from 1991 to 2008 was reviewed, and the nucleotide sequences from 1507 measles viruses (MeV) isolated during 1993 to 2008 were phylogenetically analyzed. The results showed that measles epidemics peaked approximately every 3 to 5 years with the range of measles cases detected between 56,850 and 140,048 per year. The Chinese MeV strains represented three genotypes; 1501 H1, 1 H2 and 5 A. Genotype H1 was the predominant genotype throughout China continuously circulating for at least 16 years. Genotype H1 sequences could be divided into two distinct clusters, H1a and H1b. A 4.2% average nucleotide divergence was found between the H1a and H1b clusters, and the nucleotide sequence and predicted amino acid homologies of H1a viruses were 92.3%–100% and 84.7%–100%, H1b were 97.1%–100% and 95.3%–100%, respectively. Viruses from both clusters were distributed throughout China with no apparent geographic restriction and multiple co-circulating lineages were present in many provinces. Cluster H1a and H1b viruses were co-circulating during 1993 to 2005, while no H1b viruses were detected after 2005 and the transmission of that cluster has presumably been interrupted. Analysis of the nucleotide and predicted amino acid changes in the N proteins of H1a and H1b viruses showed no evidence of selective pressure. This study investigated the genotype and cluster distribution of MeV in China over a 16-year period to establish a genetic baseline before MeV elimination in Western Pacific Region (WPR). Continuous and extensive MeV surveillance and the ability to quickly identify imported cases of measles will become more critical as measles elimination goals are achieved in China in the near future. This is the first report that a single endemic genotype of measles virus has been found to be continuously circulating in one country for at least 16 years

SARS-CoV-2 brainstem encephalitis in human inherited DBR1 deficiency.

Inherited deficiency of the RNA lariat-debranching enzyme 1 (DBR1) is a rare etiology of brainstem viral encephalitis. The cellular basis of disease and the range of viral predisposition are unclear. We report inherited DBR1 deficiency in a 14-year-old boy who suffered from isolated SARS-CoV-2 brainstem encephalitis. The patient is homozygous for a previously reported hypomorphic and pathogenic DBR1 variant (I120T). Consistently, DBR1 I120T/I120T fibroblasts from affected individuals from this and another unrelated kindred have similarly low levels of DBR1 protein and high levels of RNA lariats. DBR1 I120T/I120T human pluripotent stem cell (hPSC)-derived hindbrain neurons are highly susceptible to SARS-CoV-2 infection. Exogenous WT DBR1 expression in DBR1 I120T/I120T fibroblasts and hindbrain neurons rescued the RNA lariat accumulation phenotype. Moreover, expression of exogenous RNA lariats, mimicking DBR1 deficiency, increased the susceptibility of WT hindbrain neurons to SARS-CoV-2 infection. Inborn errors of DBR1 impair hindbrain neuron-intrinsic antiviral immunity, predisposing to viral infections of the brainstem, including that by SARS-CoV-2

Roles of Cyclic GMP-AMP Synthase in Immune Defense Against Retroviruses and Autoimmunity

The presence of DNA in the cytosol is known to trigger robust innate immunity. Cyclic GMP-AMP synthase (cGAS) is the sensor of cytosolic DNA and activation of cGAS initiates cytokine production. Here we show cGAS plays essential roles in immune defense against retroviruses as well as in autoimmune diseases caused by self-DNA. HIV infection abrogates adaptive immunity by the depletion of CD4 T cells. However, innate immune defense mechanisms against HIV are largely unknown. We show that pseudotyped HIV can infect human and mouse cell lines, leading to the production of interferons (IFN) and other antiviral cytokines. Activation of innate immunity by HIV requires viral cDNA synthesis but not cDNA integration. Furthermore, retrotranscribed HIV cDNA is sensed by the cytosolic DNA sensor cGAS, which then produces the second messenger 2'3'-cyclic GMP-AMP (cGAMP) to activate the adaptor STING. Importantly, wild-type HIV also triggers cGAMP production in human primary macrophages, underscoring the key role of cGAS in HIV sensing. Moreover, cytosolic sensing of other retroviruses such as murine leukemia virus and simian immunodeficiency virus also depends on cGAS. cGAS is important for the immune response against retroviruses, however, overactive cGAS causes autoimmunity. TREX1 is a cytosolic DNase which clears mislocalized DNA in the cytosol. Loss-of-function mutations in TREX1 cause the human disease Aicardi-Goutières syndrome (AGS). AGS manifests with abnormal type I IFN production and inflammation in multiple organs. Trex1-/- mice exhibit autoimmune and inflammatory phenotypes that are associated with elevated expression of IFN-induced genes (ISGs). Here we show that genetic ablation of cGAS in Trex1-/- mice eliminates all detectable pathological and molecular phenotypes, including ISG induction, autoantibody production, aberrant T-cell activation, and lethality. Similarly, deletion of cGAS in mice lacking DNaseII, a lysosomal enzyme that digests DNA, rescues the lethal autoimmune phenotype of the DNaseII-/- mice. Also, polyarthritis in DNaseII-/- Ifnar1-/- mice is dependent on cGAS. These results improve our understanding of immune detection of HIV and provide cGAMP as a new adjuvant for developing HIV vaccines. Moreover, our results suggest that inhibition of cGAS may lead to new treatments of some human autoimmune diseases caused by self-DNA

Three-Dimensional Reconstruction of Light Field Based on Phase Similarity

Light field imaging plays an increasingly important role in the field of three-dimensional (3D) reconstruction because of its ability to quickly obtain four-dimensional information (angle and space) of the scene. In this paper, a 3D reconstruction method of light field based on phase similarity is proposed to increase the accuracy of depth estimation and the scope of applicability of epipolar plane image (EPI). The calibration method of the light field camera was used to obtain the relationship between disparity and depth, and the projector calibration was removed to make the experimental procedure more flexible. Then, the disparity estimation algorithm based on phase similarity was designed to effectively improve the reliability and accuracy of disparity calculation, in which the phase information was used instead of the structure tensor, and the morphological processing method was used to denoise and optimize the disparity map. Finally, 3D reconstruction of the light field was realized by combining disparity information with the calibrated relationship. The experimental results showed that the reconstruction standard deviation of the two objects was 0.3179 mm and 0.3865 mm compared with the ground truth of the measured objects, respectively. Compared with the traditional EPI method, our method can not only make EPI perform well in a single scene or blurred texture situations but also maintain good reconstruction accuracy

Seismic forward and inverse simulation in a tight reservoir model of loess plateau region

To find out the seismic wave field propagation principles in loess plateau near surface of the Ordos Basin and the seismic response characteristics of tight oil reservoirs, this study established a geological-geophysical model under the real conditions of ground surface of loess plateau, and launched full elastic seismic wave equation forward modeling and pre-stack elastic seismic inversion study. Comparison of modeling and real seismic data shows that, the loose and wavy loess plateau surface is the main reason for causing the problems of seismic static correction and interference wave. Tomographic static correction method with the constraint of traces near shot point can effectively solve the problem of seismic static correction in the loess plateau and enhance seismic imaging accuracy, S-wave impedance obtained from pre-stack seismic inversion can identify sandstone effectively, and Poisson's ratio can identify oil-bearing reservoirs. The seismic forward and inverse simulation and rock physical analysis provide a solid theoretical and experimental basis for the seismic prediction of tight oil reservoir, and have worked well in the oil exploration and development in the loess plateau of the Ordos Basin. Key words: loess plateau surface, tight reservoir, wave equation forward simulation, tomographic inversion static correction, pre-stack elastic inversio

Detection and Characterization of Metastatic Cancer Cells in the Mesogastrium of Gastric Cancer Patients.

Gastric cancer is the second leading cause of cancer death worldwide. Here, we propose a novel type of tumor metastasis designated as Metastasis V in gastric cancer. Metastasis V is defined as the appearance of cancer cells in the mesogastrium with perigastric adipose tissue. To detect its incidence and characterize its clinic pathological features, large cross sectional tissue analysis of mesogastrium from 74 patients were used. Metastasis V was detected in 1 of 40 (2.5%) patients with early gastric cancer, 8 of 34 (24%) patients with advanced gastric cancer. The mean distance of Metastasis V from gastric wall was approximately 2.6 cm. Metastasis V was closely associated with tumor invasion depth, along with a number of positive lymph node metastasis. The prognosis of patients with Metastasis V was significantly (P<0.05) worse than those with tumor cell-free mesogastrium. These findings indicate that by using whole-sectional analysis, Metastasis V can be detected in the mesogastrium of gastric cancer patients, and also suggests that it may be a risk factor for patient survival after radical surgery

Finite Element Investigation of a Novel Cold-Formed Steel Shear Wall

In this paper, a novel corrugated steel sheet central sheathed cold-formed steel (CCS-CFS) shear wall is proposed. This shear wall can address the problems of low shear strength and ductility in conventional cold-formed steel (CFS) shear walls caused by screw connection failure and eccentric sheet arrangement. A numerical simulation method for the novel shear wall was developed and verified through cyclic loading test results of two full-size shear wall specimens. Parameter analysis was then conducted to investigate the effects of screw spacing, sheet thickness ratio, and aspect ratio on the seismic performance of these shear walls, accompanied by design recommendations. The results indicated that this innovative shear wall configuration can effectively resolve the connection failure between the frame and the sheet. Furthermore, the CCS-CFS shear wall can effectively improve shear strength, energy dissipation capacity, and ductility. The developed numerical simulation method can accurately capture the hysteretic properties and failure modes of shear walls. In addition, it can address the shortcomings in conventional models that neglect the mixed hardening characteristic of steel and metal damage criteria, resulting in inaccurate simulation results and unrealistic buckling modes. The principal failure modes observed in the novel shear wall were identified as the plastic buckling of corrugated steel sheathing and the distortional buckling of the end stud. Reducing the screw spacing has a limited impact on its shear strength. It is recommended that the sheet thickness ratio of the CCS-CFS shear wall should be greater than 2.0, while the aspect ratio can be relaxed to 10:4