A novel highly potent inhibitor of TMPRSS2-like proteases blocks SARS-... bioRxiv, 2021

Abstract The host cell serine protease TMPRSS2is an attractive therapeutic target for COVID-19 drug discovery. This protease activates theSpike protein of Severe Acute Respiratory SyndromeCoronavirus 2 (SARS...



pHLIP peptide targets nanogold particles to tumors PNAS, 2013

Abstract Progress in nanomedicine depends on the development of nanomaterials and targeted delivery methods. In this work, we describe a method for the preferential targeting of gold nanoparticles to a tumor in a mouse model. The method is based on the use of the pH Low Insertion Peptide (pHLIP), which targets various imaging agents to acidic tumors. We compare tumor targeting by nonfunctionalized nanogold particles with nanogold–pHLIP conjugates, where nanogold is covalently attached to the N terminus of pHLIP. Our most important fi...



LincRNA-immunity landscape analysis identifies EPIC1 as a regulator of... Science Advances, 2021

The ability of tumor cells to evade immune detection plays a critical role in tumor development. Although mechanisms of immune evasion have been characterized, understanding of how tumor cells avoid detection by the immune system and acquire resistance to immunotherapy remains incomplete. Utilizing Bio X Cell’s anti-mouse PD-1 (clone J43) antibody, researchers discovered that expression of the intergenic long noncoding RNA (lincRNA) EPIC1 helps cancer...



D614G Mutation Alters SARS-CoV-2 Spike Conformation and Enhances Prote... Cell Reports, 2021

In Brief: SARS-CoV-2 spike undergoes large conformational changes during cell fusion. Gobeil et al. identify a subdomain anchor that limits large motions in the receptor binding subunit of the pre-fusion spike from propagating to its fusion subunit. They demonstrate that theD614G mutation increases the rate off urin cleavage, which may impact infectivity. Jackson ImmunoResearch´s Peroxidase-AffiniPure Goat Anti-Human IgG, Fc gamma Fragment Specific JIM-109-035-098 was used...



ISG15-dependent activation of the sensor MDA5 is antagonized by the SA... Nature Microbiology, 2021

Abstract Activation of the RIG-I-like receptors, retinoic-acid inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5), establishes an antiviral state by upregulating interferon (IFN)-stimulated genes (ISGs). Among these is ISG15, the mechanistic roles of which in innate immunity still remain enigmatic. In the present study, we report that ISG15 conjugation is essential for antiviral IFN responses mediated by the viral RNA sensor MDA5. ISGylation of the caspase activation and recruitment domains of MDA5 promotes i...



A vaccine targeting mutant IDH1 in newly diagnosed glioma Nature, 2021

The availability of anti-IDH1 R132H antibody clone H09 (DNA-DIA-H09, Dianova, Germany) developed by the German Cancer Research Center (DKFZ) in Heidelberg has triggered fundamental advances for the 2016 WHO classification of CNS tumors (https://pubmed.ncbi.nlm.nih.gov/27157931/ ). IDH1 R132H IHC has been introduced as a backbone for differential diagnosis of glioma. Now, early in 2021 in the Journal Natur...



Zika virus NS3 protease induces bone morphogenetic protein-dependent b... Nature Microbiology, 2021

Abstract The most frequent fetal birth defect associated with prenatal Zika virus (ZIKV) infection is brain calcification, which in turn may potentially affect neurological development in infants. Understanding the mechanism could inform the development of potential therapies against prenatal ZIKV brain calcification. In perivascular cells, bone morphogenetic protein (BMP) is an osteogenic factor that undergoes maturation to activate osteogenesis and calcification. Here, we show that ZIKV infection of cultivated primary human brain pericyt...



Turning Cold Tumors Hot: The RANK Pathway as an Immune Modulator in Br... Nature Communications, 2021

Although immune checkpoint inhibitors have changed the treatment landscape for some cancers such as melanoma and non-small cell lung cancer, other tumor types often described as immunologically “cold” do not respond well to immunotherapy. Many breast tumors are cold with low immune infiltration and poor response to immune checkpoint blockade. Using Bio X Cell’s Anti-mouse RANKL (clone IK22/5) antibody, researc...



A new ketogenic formulation improves functional outcome and reduces ti... Theranostics, 2021

Abstract Rationale: Traumatic brain injury (TBI) leads to neurological impairment, with no satisfactory treatments available. Classical ketogenic diets (KD), which reduce reliance on carbohydrates and provide ketones as fuel, have neuroprotective potential, but their high fat content reduces compliance, and experimental evidence suggests they protect juvenile brain against TBI, but not adult brain, which would strongly limit their applicability in TBI. Methods: We designed a new-KD with a fat to...



SARS-CoV-2 D614G spike mutation increases entry efficiency with enhanc... Nature Communications, 2021

Abstract The causative agent of the COVID-19 pandemic, SARS-CoV-2, is steadily mutating during continuous transmission among humans. Such mutations can occur in the spike (S) protein that binds to the ACE2 receptor and is cleaved by TMPRSS2. However, whether S mutations affect SARS-CoV-2 cell entry remains unknown. Here, we show that naturally occurring S mutations can reduce or enhance cell entry via ACE2 and TMPRSS2. A SARS-CoV-2 S-pseudotyped lentivirus exhibits substantially lower entry than that of SARS-CoV S. Among S variants, the...