B Cells Influence Encephalitogenic T Cell Frequency to Myelin Oligodendrocyte Glycoprotein (MOG)38-49 during Full-length MOG Protein-Induced Demyelinating Disease.

Although T cells are encephalitogenic during demyelinating disease, B cell-depleting therapies are a successful treatment for patients with multiple sclerosis. Murine models of demyelinating disease utilizing myelin epitopes, such as myelin oligodendrocyte glycoprotein (MOG)35-55, induce a robust CD4 T cell response but mitigate the contribution of pathological B cells. This limits their efficacy for investigating how B cell depletion affects T cells.

Diphtheria toxin-derived, anti-PD-1 immunotoxin, a potent and practical tool to selectively deplete PD-1 cells.

Programmed death-1 (PD-1), an immune checkpoint receptor, is expressed on activated lymphocytes, macrophages, and some types of tumor cells. While PD-1 cells have been implicated in outcomes of cancer immunity, autoimmunity, and chronic infections, the exact roles of these cells in various physiological and pathological processes remain elusive. Molecules that target and deplete PD-1 cells would be instrumental in defining the roles unambiguously.

Clinical characteristics and management of coexistent cardiomyopathy in patients with bicuspid aortic valve.

Background: Bicuspid aortic valve (BAV) is the most common congenital heart disease. However, the prevalence, clinical characteristics, and current management of BAV associated with inherited cardiomyopathy, including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and left ventricular noncompaction (LVNC) have not been well described.

Methods: Consecutive patients diagnosed with BAV at a large tertiary cardiovascular referral center between 2009 and 2018 were retrospectively assessed for HCM, DCM, and LVNC based on clinical and echocardiographic criteria.

A Phase-Coded Sequence Design Method for Active Sonar.

Phase-coded sequences are widely studied as the transmitted signals of active sonars. Recently, several design methods have been developed to generate phased-coded sequences satisfying specific aperiodic or periodic autocorrelation sidelobe level metrics. In this paper, based on the majorization-minimization strategy and the squared iterative acceleration scheme, we propose a method to generate sequences with the periodic weighted integrated sidelobe level metric.

Frontline Science: Cxxc5 expression alters cell cycle and myeloid differentiation of mouse hematopoietic stem and progenitor cells.

CXXC5 is a member of the CXXC-type zinc finger epigenetic regulators. Various hematopoietic and nonhematopoietic roles have been assigned to CXXC5. In the present study, the role of Cxxc5 in myelopoiesis was studied using overexpression and short hairpin RNA-mediated knockdown in mouse early stem and progenitor cells defined as Lineage Sca-1 c-Kit (LSK) cells.

HLA-DM catalytically enhances peptide dissociation by sensing peptide-MHC class II interactions throughout the peptide-binding cleft.

Human leukocyte antigen-DM (HLA-DM) is an integral component of the major histocompatibility complex class II (MHCII) antigen-processing and -presentation pathway. HLA-DM shapes the immune system by differentially catalyzing peptide exchange on MHCII molecules, thereby editing the peptide-MHCII (pMHCII) repertoire by imposing a bias on the foreign and self-derived peptide cargos that are presented on the cell surface for immune surveillance and tolerance induction by CD4 T cells. To better understand DM selectivity, here we developed a real-time fluorescence anisotropy assay to delineate the pMHCII intrinsic stability, DM-binding affinity, and catalytic turnover, independent kinetic parameters of HLA-DM enzymatic activity.

Optimal Waveform Design Using Frequency-Modulated Pulse Trains for Active Sonar.

Frequency-modulated pulse trains can be applied in active sonar systems to improve the performance of conventional transmitted waveforms. Recently, two pulse trains have been widely researched as the transmitted waveforms for active sonars. The LFM-Costas pulse train was formed by modulating the linear frequency-modulated (LFM) waveform via the Costas sequence to remove the Doppler ambiguity of LFM pulses.

Depletion of PD-1-positive cells ameliorates autoimmune disease.

Targeted suppression of autoimmune diseases without collateral suppression of normal immunity remains an elusive yet clinically important goal. Targeted blockade of programmed-cell-death-protein-1 (PD-1)-an immune checkpoint factor expressed by activated T cells and B cells-is an efficacious therapy for potentiating immune activation against tumours. Here we show that an immunotoxin consisting of an anti-PD-1 single-chain variable fragment, an albumin-binding domain and Pseudomonas exotoxin targeting PD-1-expressing cells, selectively recognizes and induces the killing of the cells.

Association between vitamin D receptor BsmI polymorphism and bone mineral density in pediatric patients: A meta-analysis and systematic review of observational studies.

Background: Vitamin D and the vitamin D receptor (VDR) are important in the metabolic processes that affect bone mineral density (BMD). However, the effect of VDR BsmI polymorphism on BMD in pediatric patients is still unclear.

Methods: Eligible studies were identified from the following electronic databases: PubMed, Embase, the Cochrane Library, and the Chinese CNKI and Wanfang databases before October 1, 2016.

Peptidomic analysis of type 1 diabetes associated HLA-DQ molecules and the impact of HLA-DM on peptide repertoire editing.

HLA-DM and class II associated invariant chain (Ii) are key cofactors in the MHC class II (MHCII) antigen processing pathway. We used tandem mass spectrometry sequencing to directly interrogate the global impact of DM and Ii on the repertoire of MHCII-bound peptides in human embryonic kidney 293T cells expressing HLA-DQ molecules in the absence or presence of these cofactors. We found that Ii and DM have a major impact on the repertoire of peptides presented by DQ1 and DQ6, with the caveat that this technology is not quantitative.

Type 1 diabetes associated HLA-DQ2 and DQ8 molecules are relatively resistant to HLA-DM mediated release of invariant chain-derived CLIP peptides.

HLA-DM is essential for editing peptides bound to MHC class II, thus influencing the repertoire of peptides mediating selection and activation of CD4(+) T cells. Individuals expressing HLA-DQ2 or DQ8, and DQ2/8 trans-dimers, have elevated risk for type 1 diabetes (T1D). Cells coexpressing DM with these DQ molecules were observed to express elevated levels of CLIP (Class II associated invariant chain peptide).

Structural Characteristics of HLA-DQ that May Impact DM Editing and Susceptibility to Type-1 Diabetes.

Autoreactive CD4+ T cells initiate the chronic autoimmune disease Type-1 diabetes (T1D), in which multiple environmental and genetic factors are involved. The association of HLA, especially the DR-DQ loci, with risk for T1D is well documented. However, the molecular mechanisms are poorly understood.

Cutting edge: HLA-DM functions through a mechanism that does not require specific conserved hydrogen bonds in class II MHC-peptide complexes.

HLA-DM catalyzes peptide dissociation and exchange in class II MHC molecules through a mechanism that has been proposed to involve the disruption of specific components of the conserved hydrogen bond network in MHC-peptide complexes. HLA-DR1 molecules with alanine substitutions at each of the six conserved H- bonding positions were expressed in cells, and susceptibility to DM catalytic activity was evaluated by measuring the release of CLIP. The mutants alphaN62A, alphaN69A, alphaR76A, and betaH81A DR1 were fully susceptible to DM-mediated CLIP release, and betaN82A resulted in spontaneous release of CLIP.

[The study of pancreas three-dimensional reconstruction based on the Virtual Chinese Human-Female No 1].

Objective: To study the three-dimensional (3D) reconstruction and 3D visualization of the pancreas and create anatomy of the digitalized visual pancreas so as to construct a concrete basis for virtual operation and surgical operation on pancreas.

Methods: The digital imaging data of pancreas, duodenum, common bile duct, arteries and veins were obtained from the Virtual Chinese Human-Female 1 (VCH-F1) and processed using ACDSee and Photoshop so as to reconstruct 3D pancreas digitally and realize 3D visualization of pancreas.

Results: We successfully 3D reconstructed and visualized the pancreas and the peri-pancreatic structures: the duodenum, the common bile duct, the inferior vena cava, the portal vein vessels, the aorta, the ceoliac trunk vessels.