Humanization of Pan-HLA-DR mAb 44H10 Hinges on Critical Residues in the Antibody Framework.

Reducing the immunogenicity of animal-derived monoclonal antibodies (mAbs) for use in humans is critical to maximize therapeutic effectiveness and preclude potential adverse events. While traditional humanization methods have primarily focused on grafting antibody Complementarity-Determining Regions (CDRs) on homologous human antibody scaffolds, framework regions can also play essential roles in antigen binding. Here, we describe the humanization of the pan-HLA-DR mAb 44H10, a murine antibody displaying significant involvement of the framework region in antigen binding.

Tryptophan residues in TDP-43 and SOD1 modulate the cross-seeding and toxicity of SOD1.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of motor neurons. Neuronal superoxide dismutase-1 (SOD1) inclusion bodies are characteristic of familial ALS with SOD1 mutations, while a hallmark of sporadic ALS is inclusions containing aggregated WT TAR DNA-binding protein 43 (TDP-43). We show here that co-expression of mutant or WT TDP-43 with SOD1 leads to misfolding of endogenous SOD1 and aggregation of SOD1 reporter protein SOD1-GFP in human cell cultures and promotes synergistic axonopathy in zebrafish.

Glycosylated nanoparticle-based PfCSP vaccine confers long-lasting antibody responses and sterile protection in mouse malaria model.

The development of an effective and durable vaccine remains a central goal in the fight against malaria. Circumsporozoite protein (CSP) is the major surface protein of sporozoites and the target of the only licensed Plasmodium falciparum (Pf) malaria vaccine, RTS,S/AS01. However, vaccine efficacy is low and short-lived, highlighting the need for a second-generation vaccine with superior efficacy and durability.

Engineering pan-HIV-1 neutralization potency through multispecific antibody avidity.

Deep mining of B cell repertoires of HIV-1-infected individuals has resulted in the isolation of dozens of HIV-1 broadly neutralizing antibodies (bNAbs). Yet, it remains uncertain whether any such bNAbs alone are sufficiently broad and potent to deploy therapeutically. Here, we engineered HIV-1 bNAbs for their combination on a single multispecific and avid molecule via direct genetic fusion of their Fab fragments to the human apoferritin light chain.

Feasibility and Added Value of Fetal DTI Tractography in the Evaluation of an Isolated Short Corpus Callosum: Preliminary Results.

Background And Purpose: Prognosis of isolated short corpus callosum is challenging. Our aim was to assess whether fetal DTI tractography can distinguish callosal dysplasia from variants of normal callosal development in fetuses with an isolated short corpus callosum.

Materials And Methods: This was a retrospective study of 37 cases referred for fetal DTI at 30.

Multivalency transforms SARS-CoV-2 antibodies into ultrapotent neutralizers.

SARS-CoV-2, the virus responsible for COVID-19, has caused a global pandemic. Antibodies can be powerful biotherapeutics to fight viral infections. Here, we use the human apoferritin protomer as a modular subunit to drive oligomerization of antibody fragments and transform antibodies targeting SARS-CoV-2 into exceptionally potent neutralizers.

Trends in Performance and Opportunities for Improvement on a Composite Measure of Acute Myocardial Infarction Care.

Background Despite improvements on individual process of care measures for acute myocardial infarction (AMI), little is known about performance on a composite measure of AMI care that assesses the delivery of many components of high-quality AMI care. We sought to examine trends in patient- and hospital-level performance on a composite defect-free care measure, identify disparities in the performance across sociodemographic groups, and identify opportunities to further improve quality and outcomes. Methods and Results We calculated the proportion of patients in the National Cardiovascular Data Registry-Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines (now known as the Chest Pain - Myocardial Infarction Registry) between January 1, 2010, and December 31, 2017, receiving defect-free AMI care including guideline-recommended pharmacotherapy, timely provision of medical and reperfusion therapy, assessment of ventricular function, referral to cardiac rehabilitation, and smoking cessation counseling for patients with AMI.

ACSL1 Is Associated With Fetal Programming of Insulin Sensitivity and Cellular Lipid Content.

Individuals who are born small for gestational age (SGA) have a risk to develop various metabolic diseases during their life course. The biological memory of the prenatal state of growth restricted individuals may be reflected in epigenetic alterations in stem cell populations. Mesenchymal stem cells (MSCs) from the Wharton's jelly of umbilical cord tissue are multipotent, and we generated primary umbilical cord MSC isolates from SGA and normal neonates, which were subsequently differentiated into adipocytes.

Cleavage strongly influences whether soluble HIV-1 envelope glycoprotein trimers adopt a native-like conformation.

We compare the antigenicity and conformation of soluble, cleaved vs. uncleaved envelope glycoprotein (Env gp)140 trimers from the subtype A HIV type 1 (HIV-1) strain BG505. The impact of gp120-gp41 cleavage on trimer structure, in the presence or absence of trimer-stabilizing modifications (i.

Pre-Main-Sequence Star Candidates in the Bar of the Large Magellanic Cloud.

Candidate pre-main-sequence stars were observed in the bar of the Large Magellanic Cloud during the search for dark matter in the galactic halo. Seven blue stars of apparent visual magnitude 15 to 17 had irregular photometric variations and hydrogen emission lines in their optical spectra, which suggested that these stars are pre-main-sequence stars of about 10 solar masses. These stars are slightly more massive and definitely more luminous than are Herbig AeBe pre-main-sequence stars in our own galaxy.

Neuron specificity of the neurofilament light promoter in transgenic mice requires the presence of DNA unwinding elements.

Three reporter genes, the chloramphenicol acetyltransferase (CAT), the lacZ, and the intronless NF-L DNA, were used to test the activity of the proximal promoter region (-292 bp) of the human neurofilament light (hNF-L) gene in transgenic mice. Surprisingly, the hNF-L/CAT construct was highly sensitive to position effect, and its expression was found at low levels in several tissues of adult transgenic mice (Beaudet, L., Charron, G.