SARS-CoV-2 Accessory Protein ORF8 Decreases Antibody-Dependent Cellular Cytotoxicity

Viruses use many different strategies to evade host immune responses. In the case of SARS-CoV-2, its Spike mutates rapidly to escape from neutralizing antibodies. In addition to this strategy, ORF8, a small accessory protein encoded by SARS-CoV-2, helps immune evasion by reducing the susceptibility of SARS-CoV-2-infected cells to the cytotoxic CD8+ T cell response. Interestingly, among all accessory proteins, ORF8 is rapidly evolving and a deletion in this protein has been linked to milder disease. Here, we studied the effect of ORF8 on peripheral blood mononuclear cells (PBMC). Specifically, we found that ORF8 can bind monocytes as well as NK cells. Strikingly, ORF8 binds CD16a (FcγRIIIA) with nanomolar affinity and decreases the overall level of CD16 at the surface of monocytes and, to a lesser extent, NK cells. This decrease significantly reduces the capacity of PBMCs and particularly monocytes to mediate antibody-dependent cellular cytotoxicity (ADCC). Overall, our data identifies a new immune-evasion activity used by SARS-CoV-2 to escape humoral responses.     

Quantitative glycoproteomics of high-density lipoproteins

In this work, we developed a targeted glycoproteomic method to monitor the site-specific glycoprofiles and quantities of the most abundant HDL-associated proteins using Orbitrap LC-MS for (glyco)peptide target discovery and QqQ LC-MS for quantitative analysis. We conducted a pilot study using the workflow to determine whether HDL protein glycoprofiles are altered in healthy human participants in response to dietary glycan supplementation.

The optimized HDL glycoproteomics method was sensitive enough to detect the effects of dietary supplements on HDL protein glycoprofiles even in a small sample size.     

Paradoxical brain embolism shadowing massive pulmonary embolism

Patent foramen ovale is frequently observed in the general population. In case of massive pulmonary embolism, the sudden increase in the right heart cavity's pressure may cause a right-to-left shunting across this foramen, which could be associated with conflicting outcomes. Herein, we report a case of reversible cardiac arrest preceded by seizures, and followed by hemodynamic stability without any vasopressor. A brain CT-scan showed a limited ischemic stroke. Initial echocardiographic assessment revealed an acute cor pulmonale and a right-to-left intracardiac shunt across a large patent foramen ovale, suggesting the diagnosis of massive pulmonary embolism that was lately confirmed by a multidetector CT-angiography. Anticoagulation therapy was rapidly complicated by a hemorrhagic transformation of the ischemic stroke leading to a fatal outcome. This case illustrates the double-edged circulatory effect of shunting across a patent foramen ovale in case of massive pulmonary embolism: it may have limited circulatory failure but caused in the meanwhile a fatal paradoxical brain embolism.     

The genetics of platelet count and volume in humans

The last decade has witnessed an explosion in the depth, variety, and amount of human genetic data that can be generated. This revolution in technical and analytical capacities has enabled the genetic investigation of human traits and disease in thousands to now millions of participants. Investigators have taken advantage of these advancements to gain insight into platelet biology and the platelet’s role in human disease. To do so, large human genetics studies have examined the association of genetic variation with two quantitative traits measured in many population and patient based cohorts: platelet count (PLT) and mean platelet volume (MPV). This article will review the many human genetic strategies—ranging from genome-wide association study (GWAS), Exomechip, whole exome sequencing (WES), to whole genome sequencing (WGS)—employed to identify genes and variants that contribute to platelet traits. Additionally, we will discuss how these investigations have examined and interpreted the functional implications of these newly identified genetic factors and whether they also impart risk to human disease. The depth and size of genetic, phenotypic, and other -omic data are primed to continue their growth in the coming years and provide unprecedented opportunities to gain critical insights into platelet biology and how platelets contribute to disease.     

Primary vertebral osteosarcoma: Five cases

Primary vertebral osteosarcoma is a rare type of osteosarcoma, differing from the appendicular forms by an incidence peak occurring at a higher age and a poorer prognosis, due to the difficulties of the surgical treatment. We present five cases of histologically proven primary vertebral osteosarcomas followed in our institution between 2004 and 2012. They allow to illustrate some essential radiologic features, useful to evoke this rare entity.     

Rinderpest Virus Sequestration and Use in Posteradication Era

After the 2011 declaration of rinderpest disease eradication, we surveyed 150 countries about rinderpest virus stocks. Forty-four laboratories in 35 countries held laboratory-attenuated strains, field strains, or diagnostic samples. Vaccine and reagent production and laboratory experiments continued. Rigorous standards are necessary to ensure that stocks are kept under safe conditions.     

Leukocyte and Platelet-Rich Fibrin Have Same Effect as Blood Clot in the 3-Dimensional Alveolar Ridge Preservation. A Split-Mouth Randomized Clinical Trial

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Crystal structure and functional mapping of human ASMT,the last enzyme of the melatonin synthesis pathway

Abstract: Melatonin is a synchronizer of many physiological processes. Abnormal melatonin signaling is associated with human disorders related to sleep, metabolism, and neurodevelopment. Here, we present the X‐ray crystal structure of human N‐acetyl serotonin methyltransferase (ASMT), the last enzyme of the melatonin biosynthesis pathway. The polypeptide chain of ASMT consists of a C‐terminal domain, which is typical of other SAM‐dependent O‐methyltransferases, and an N‐terminal domain, which intertwines several helices with another monomer to form the physiologically active dimer. Using radioenzymology, we analyzed 20 nonsynonymous variants identified through the 1000 genomes project and in patients with neuropsychiatric disorders. We found that the majority of these mutations reduced or abolished ASMT activity including one relatively frequent polymorphism in the Han Chinese population (N17K, rs17149149). Overall, we estimate that the allelic frequency of ASMT deleterious mutations ranges from 0.66% in Europe to 2.97% in Asia. Mapping of the variants on to the 3‐dimensional structure clarifies why some are harmful and provides a structural basis for understanding melatonin deficiency in humans.