Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates.

The COVID-19 pandemic represents a global challenge that has impacted and is expected to continue to impact the lives and health of people across the world for the foreseeable future. The rollout of vaccines has provided highly anticipated relief, but effective therapeutics are required to further reduce the risk and severity of infections. Monoclonal antibodies have been shown to be effective as therapeutics for SARS-CoV-2, but as new variants of concern (VoC) continue to emerge, their utility and use have waned due to limited or no efficacy against these variants.

Expanding the Malaria Antibody Toolkit: Development and Characterisation of RH5, CyRPA, and CSP Recombinant Human Monoclonal Antibodies.

Malaria, an infection caused by apicomplexan parasites of the genus , continues to exact a significant toll on public health with over 200 million cases world-wide, and annual deaths in excess of 600,000. Considerable progress has been made to reduce malaria burden in endemic countries in the last two decades. However, parasite and mosquito resistance to frontline chemotherapies and insecticides, respectively, highlights the continuing need for the development of safe and effective vaccines.

ACE2 Peptide Fragment Interaction with Different S1 Protein Sites.

Unlabelled: We study the effect of the peptide QAKTFLDKFNHEAEDLFYQ on the kinetics of the SARS-CoV-2 spike protein S1 binding to angiotensin-converting enzyme 2 (ACE2), with the aim to characterize the interaction mechanism of the SARS-CoV2 virus with its host cell. This peptide corresponds to the sequence 24-42 of the ACE2 α1 domain, which marks the binding site for the S1 protein. The kinetics of S1-ACE2 complex formation was measured in the presence of various concentrations of the peptide using bio-layer interferometry.

EPHA2 Polymorphisms in Estonian Patients with Age-Related Cataract.

Background: Ephrin receptors (Ephs) are tyrosine kinases that together with their ligands, ephrins, are considered important in cell-cell communication, especially during embryogenesis but also for epithelium homeostasis. Studies have demonstrated the involvement of mutations or common variants of the gene encoding Eph receptor A2 (EPHA2), in congenital cataract and in age-related cataract. This study investigated a number of disease-associated single nucleotide polymorphisms (SNPs) in EPHA2 in patients with age-related cataract.

Platelets store laminins 411/421 and 511/521 in compartments distinct from α- or dense granules and secrete these proteins via microvesicles.

Background: Blood platelets secrete upon activation of laminins 411/421 and 511/521, large adhesive proteins mainly found in the basement membranes of blood vessels and other tissues. At present, the subcellular localization and secretion mechanisms of platelet laminins are largely unknown.

Objectives: Our aim was to compare the subcellular localization of laminins 411/421 and 511/521 and specific granule markers in platelets.

Genetic variation of superoxide dismutases in patients with primary open-angle glaucoma.

Purpose: Oxidative stress has been described as an underlying pathogenetic mechanism in retinal ganglion cell apoptosis, which is a hallmark of primary open-angle glaucoma (POAG). Superoxide dismutases (SODs) are enzymes involved in the protection against oxidative stress by detoxification of superoxide. In this study, we investigated a number of disease-associated single nucleotide polymorphisms (SNPs) in the copper-zinc-containing SOD1 and SOD3, and in the manganese superoxide dismutase SOD2, in POAG patients.

Anti-cytokine autoantibodies suggest pathogenetic links with autoimmune regulator deficiency in humans and mice.

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is a recessive disorder resulting from mutations in the autoimmune regulator (AIRE). The patients' autoantibodies recognize not only multiple organ-specific targets, but also many type I interferons (IFNs) and most T helper type 17 (Th17) cell-associated cytokines, whose biological actions they neutralize in vitro. These anti-cytokine autoantibodies are highly disease-specific: otherwise, they have been found only in patients with thymomas, tumours of thymic epithelial cells that fail to express AIRE.

A novel monoclonal antibody to human laminin α5 chain strongly inhibits integrin-mediated cell adhesion and migration on laminins 511 and 521.

Laminins, a large family of αβγ heterotrimeric proteins mainly found in basement membranes, are strong promoters of adhesion and migration of multiple cell types, such as tumor and immune cells, via several integrin receptors. Among laminin α (LMα) chains, α5 displays the widest tissue distribution in adult life and is synthesized by most cell types. Here, we have generated and characterized five novel monoclonal antibodies (mAbs) to the human LMα5 chain to further study the biological relevance of α5 laminins, such as laminins 511 (α5β1γ1) and 521 (α5β2γ1).

Superoxide dismutase gene polymorphisms in patients with age-related cataract.

Background: Functional polymorphisms in genes encoding antioxidant enzymes may result in reduced enzyme activity and increased levels of reactive oxygen species, such as superoxide radicals, which in turn may contribute to increased risk of age-related disorders. Copper-zinc superoxide dismutases, SOD-1 and SOD-3, and manganese superoxide dismutase, SOD-2, are enzymes involved in the protection against oxidative stress and detoxification of superoxide. In this study, we investigated a number of disease-associated single nucleotide polymorphisms (SNPs) of SOD1, SOD2 and SOD3, in patients with age-related cataract.

Epitope of titin A-band-specific monoclonal antibody Tit1 5 H1.1 is highly conserved in several Fn3 domains of the titin molecule. Centriole staining in human, mouse and zebrafish cells.

Background: Previously we have reported on the development of a new mouse anti-titin monoclonal antibody, named MAb Titl 5 H1.1, using the synthetic peptide N-AVNKYGIGEPLESDSVVAK-C which corresponds to an amino acid sequence in the A-region of the titin molecule as immunogen. In the human skeletal muscles, MAb Titl 5 H1.

Ubiquitin carboxyl-terminal esterase L1 (UCHL1) S18Y polymorphism in patients with cataracts.

Background:  Cataract is characterized by light-scattering protein aggregates. The ubiquitin-proteasome system has been proposed a role in proteolytic removal of these protein aggregates. Ubiquitin carboxyl-terminal esterase L1 (UCHL1) is a de-ubiquitinating enzyme with important functions in recycling of ubiquitin.

Titin A-band-specific monoclonal antibody Tit1 5H1.1. Cellular Titin as a centriolar protein in non-muscle cells.

We report the development of a new mouse anti-titin monoclonal antibody, named MAb Tit1 5H1.1, using the synthetic peptide corresponding to an amino acid sequence in the A-band of the titin molecule as immunogen. In the human skeletal muscle, MAb Tit1 5H1.

New anti-Ku80 monoclonal antibody F10H2.B3 as a useful marker for dividing cells in culture.

We report on the development of a mouse monoclonal antibody (named F10H2.B3) using the native cellular fragments of human fetal neural stem cells as immunogens. Molecular analysis has shown that the target antigen of F10H2.

Functional characterization of fingers subdomain-specific monoclonal antibodies inhibiting the hepatitis C virus RNA-dependent RNA polymerase.

The hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp), encoded by nonstructural protein 5B (NS5B), is absolutely essential for the viral replication. Here we describe the development, characterization, and functional properties of the panel of monoclonal antibodies (mAbs) and specifically describe the mechanism of action of two mAbs inhibiting the NS5B RdRp activity. These mAbs recognize and bind to distinct linear epitopes in the fingers subdomain of NS5B.

DNA-PK contributes to the phosphorylation of AIRE: importance in transcriptional activity.

The autoimmune regulator (AIRE) protein is a key mediator of the central tolerance for tissue specific antigens and is involved in transcriptional control of many antigens in thymic medullary epithelial cells (mTEC). Mutations in the AIRE gene cause a rare disease named autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Here we report using GST pull-down assay, mass-spectrometry and co-immunoprecipitation that a heterotrimeric complex of DNA-Dependent Protein Kinase (DNA-PK), consisting of Ku70, Ku80 and DNA-PK catalytic subunit (DNA-PKcs), is a novel interaction partner for AIRE.

Variability in the kinesin light chain 1 gene may influence risk of age-related cataract.

Purpose: Kinesin-mediated cargo vesicle transport is fundamental to the maintenance of a proper lens fiber structure, which is essential for the transparency of the lens. Here, we test the hypothesis that the rs8702 polymorphism in the kinesin light chain 1 gene (KLC1), previously linked to Alzheimer disease (AD), may play a role in cataractogenesis.

Methods: Patients with nuclear (n=76), cortical (n=154), posterior subcapsular (n=117), and mixed (n=148) cataract as well as 183 controls were analyzed for the KLC1 rs8702 polymorphism using the dynamic allele-specific hybridization (DASH) technique.

Methylenetetrahydrofolate reductase genetic polymorphisms in patients with primary open-angle glaucoma.

Purpose: Hyperhomocysteinemia has been found in patients with primary open-angle glaucoma. The purpose of the present study was to determine if hyperhomocysteinemia-associated polymorphisms of the methylenetetrahydrofolate reductase gene (MTHFR) are overrepresented in primary open-angle glaucoma.

Methods: Patients with primary open-angle glaucoma (n = 243) and controls (n = 187) were analyzed for the MTHFR 677 C > T and 1298 A > C polymorphisms using minisequencing technique.

Apolipoprotein E polymorphisms in patients with primary open-angle glaucoma.

Purpose: To investigate apolipoprotein E (APOE) polymorphisms, which are known to influence the risk of Alzheimer disease (AD), in patients with primary open-angle glaucoma (POAG).

Design: Retrospective case-control association study.

Methods: Patients with POAG (n = 242) and controls (n = 187) were analyzed for the APOE epsilon 2/epsilon 3/epsilon 4 polymorphisms using minisequencing technique.

Methylenetetrahydrofolate reductase genetic polymorphisms in patients with cataract.

Purpose: Hyperhomocysteinemia is commonly associated with polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene. The level of homocysteine can be lowered by dietary intake of folate. A protective effect of folate supplementation has been reported against cataract.

An endothelial laminin isoform, laminin 8 (alpha4beta1gamma1), is secreted by blood neutrophils, promotes neutrophil migration and extravasation, and protects neutrophils from apoptosis.

During extravasation, neutrophils migrate through the perivascular basement membrane (BM), a specialized extracellular matrix rich in laminins. Laminins 8 (LN-8) (alpha4beta1gamma1) and 10 (LN-10) (alpha5beta1gamma1) are major components of the endothelial BM, but expression, recognition, and use of these laminin isoforms by neutrophils are poorly understood. In the present study, we provide evidence, using a panel of novel monoclonal antibodies against human laminin alpha4 (LNalpha4) chain, that neutrophils contain and secrete LN-8, and that this endogenous laminin contributes to chemoattractant-induced, alphaMbeta2-integrin-dependent neutrophil migration through albumin-coated filters.

Eye lens crystallins: a component of intraocular pseudoexfoliative material.

Feeding experimental animals (19 pigs) with surplus sucrose and salt (NaCl) caused cataractous changes in lens tissue and triggered the formation of pseudoexfoliative material on the lens capsule. In the control animals (15 pigs) pseudoexfoliative material was absent. The avidin-biotin complex immunohistochemical method was applied to the pseudoexfoliative material obtained from 15 porcine experimental precataractous lenses and 1 spontaneously cataractous eye and revealed crystallins as a component of the intraocular pseudoexfoliative material.

CYP2D6, GST-M1 and GST-T1 enzymes: expression in parathyroid gland and association with the parathyroid hormone concentration during early renal replacement therapy.

Aims: The purpose of this research was to characterize CYP2D6, GST-M1 and GST-T1 enzyme expression in human parathyroid tissue, and to determine whether or not there is any association between deficiencies in these enzymes and serum parathyroid hormone concentrations in patients with end-stage renal disease.

Methods: Surgical human parathyroid tissue was obtained and evaluated by immunohistochemistry for cellular localization of CYP2D6, GST-M1 and GST-T1 and colocalization of CYP2D6 with parathyroid hormone. Blood samples were collected from 328 Caucasian patients with end-stage renal disease for genetic testing of CYP2D6*3, *4, *5, *6, *7 and GST-M1*0 and GST-T1*0 alleles.

Dietary sugar and salt represent real risk factors for cataract development.

Dietary sugar and salt represent etiological risk factors of human cataract. To verify etiological data on the basis of histological findings, 9 pigs with a body weight of 40 kg, 3 months of age, in groups of 3 were continuously fed with 5% of refined dietary sugar (sucrose - C(12)H(22)O(11)), 0.5% of salt (NaCl) and a sugar-salt mixture (2.