Mechanisms by which Factor H protects from the alternative pathway of complement.

Chagas disease, a chronic disabling disease caused by the protozoan , has no standardized treatment or preventative vaccine. The infective trypomastigote form of is highly resistant to killing by the complement immune system. Factor H (FH), a negative regulator of the alternative pathway (AP) of complement on cell surfaces and in blood, contains 20 short consensus repeat domains.

Multilevel Community Engagement to Inform a Randomized Clinical Trial.

Objective: To explore how patients, community-based perinatal support professionals, and health system clinicians and staff perceived facilitators and barriers to implementation of a randomized clinical trial (RCT) designed to optimize Black maternal heart health.

Methods: This article describes the formative work that we believed needed to occur before the start of the Change of H.E.

Photothermal bleaching of nickel dithiolene for bright multi-colored 3D printed parts.

HP's Multi Jet Fusion is a powder bed fusion 3D printing technology that utilizes a carbon-based radiation absorber in combination with a near infrared (NIR) light source to facilitate the fusion of polymer powder in a layer-by-layer fashion to generate 3D parts. Most available carbon-based and NIR radiation absorbers have an intrinsic dark color, which as a result will only produce black/gray and dark colored parts. However, there are many applications that require variable color, including prosthetics, medical models, and indicators, among others.

Trauma-informed interprofessional education: Preliminary evaluation of building student capacity for system-wide collaboration.

Introduction: In urban areas, numerous barriers exist for children and families to access needed behavioral health care. Compounding the general deficit of behavioral health workers in the United States is lack of access to culturally responsive care. Additional challenges include inherent racism and oppression in our health and human service systems and siloed approaches to behavioral health care training and practice.

An optimized Factor H-Fc fusion protein against multidrug-resistant .

Novel therapeutics against the global threat of multidrug-resistant are urgently needed. Gonococci evade killing by complement by binding factor H (FH), a key inhibitor of the alternative pathway. FH comprises 20 short consensus repeat (SCR) domains organized as a single chain.

A Factor H-Fc fusion protein increases complement-mediated opsonophagocytosis and killing of community associated methicillin-resistant Staphylococcus aureus.

Staphylococcus aureus employs a multitude of immune-evasive tactics to circumvent host defenses including the complement system, a component of innate immunity central to controlling bacterial infections. With antibiotic resistance becoming increasingly common, there is a dire need for novel therapies. Previously, we have shown that S.

CD97 is associated with mitogenic pathway activation, metabolic reprogramming, and immune microenvironment changes in glioblastoma.

Glioblastoma (GBM) is the most common primary brain tumor with a median survival under two years. Using in silico and in vitro techniques, we demonstrate heterogeneous expression of CD97, a leukocyte adhesion marker, in human GBM. Beyond its previous demonstrated role in tumor invasion, we show that CD97 is also associated with upregulation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/Erk) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathways in GBM.

Development of Complement Factor H-Based Immunotherapeutic Molecules in Tobacco Plants Against Multidrug-Resistant .

Novel therapeutics against the global threat of multidrug-resistant are urgently needed. Gonococci possess several mechanisms to evade killing by human complement, including binding of factor H (FH), a key inhibitor of the alternative pathway. FH comprises 20 short consensus repeat (SCR) domains organized in a head-to-tail manner as a single chain.

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Single Domain Antibodies Are Potent Inhibitors of Low Density Lipoprotein Receptor Degradation.

Single domain antibodies (sdAbs) correspond to the antigen-binding domains of camelid antibodies. They have the same antigen-binding properties and specificity as monoclonal antibodies (mAbs) but are easier and cheaper to produce. We report here the development of sdAbs targeting human PCSK9 (proprotein convertase subtilisin/kexin type 9) as an alternative to anti-PCSK9 mAbs.

Anti-infective immunoadhesins from plants.

Immunoadhesins are recombinant proteins that combine the ligand-binding region of a receptor or adhesion molecule with immunoglobulin constant domains. All FDA-approved immunoadhesins are designed to modulate the interaction of a human receptor with its normal ligand, such as Etanercept (Enbrel(®) ), which interferes with the binding of tumour necrosis factor (TNF) to the TNF-alpha receptor and is used to treat inflammatory diseases such as rheumatoid arthritis. Like antibodies, immunoadhesins have long circulating half-lives, are readily purified by affinity-based methods and have the avidity advantages conferred by bivalency.

Equilibrium and kinetics of Sin Nombre hantavirus binding at DAF/CD55 functionalized bead surfaces.

Decay accelerating factor (DAF/CD55) is targeted by many pathogens for cell entry. It has been implicated as a co-receptor for hantaviruses. To examine the binding of hantaviruses to DAF, we describe the use of Protein G beads for binding human IgG Fc domain-functionalized DAF ((DAF)₂-Fc).

Recombinant anthrax toxin receptor-Fc fusion proteins produced in plants protect rabbits against inhalational anthrax.

Inhalational anthrax, a zoonotic disease caused by the inhalation of Bacillus anthracis spores, has a ∼50% fatality rate even when treated with antibiotics. Pathogenesis is dependent on the activity of two toxic noncovalent complexes: edema toxin (EdTx) and lethal toxin (LeTx). Protective antigen (PA), an essential component of both complexes, binds with high affinity to the major receptor mediating the lethality of anthrax toxin in vivo, capillary morphogenesis protein 2 (CMG2).

Secretory IgA antibodies from plants.

Secretory IgA (SIgA) is the antibody type produced in both mammals and birds that protects the body from infection at mucosal surfaces. While monoclonal IgG antibodies, particularly those against tumor antigens, have received a great deal of attention, both scientific and commercial, as immunotherapeutic agents, the potential of SIgA antibodies has only recently begun to be exploited. Part of the reason for this is that SIgA production in vivo normally requires the cooperation of two different cell types, and single animal cell systems for monoclonal SIgA production are inefficient.

Clinical trial of a plant-derived antibody on recolonization of mutans streptococci.

Objective: This double-blinded, placebo-controlled clinical trial tested the safety and efficacy of a topical secretory IgA antibody manufactured in tobacco plants (plantibody) in preventing recolonization of mutans streptococci (MS) in human plaque as measured by whole stimulated saliva samples.

Methods: Following a 9-day antimicrobial treatment with chlorhexidine (CHX), 56 eligible adults (enrollment salivary MS > or = 10(4) CFU/ml; no current caries) were randomized equally to a group receiving 0, 2, 4, or 6 topical applications of plantibody followed by 6, 4, 2, or 0 applications of placebo, respectively, over a 3-week period.

Results: Among the 54 subjects who completed the trial, the CHX regimen eliminated salivary MS in 69%.

Production of secretory IgA antibodies in plants.

Functional antibodies produced in tobacco plants were first reported over a decade ago (1989). The basic protocol used to generate these 'plantibodies' involved the independent cloning of H and L chain antibody genes in Agrobacterium tumefaciens vectors, the transformation of plant tissue in vitro with the recombinant bacterium, the reconstitution of whole plants expressing individual chains, and their sexual cross. In a 'Mendelian' fashion, a fully assembled and functional antibody was recovered from plant tissue in some double-transgenic plants.

Medical molecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants.

The use of plants for medicinal purposes dates back thousands of years but genetic engineering of plants to produce desired biopharmaceuticals is much more recent. As the demand for biopharmaceuticals is expected to increase, it would be wise to ensure that they will be available in significantly larger amounts, on a cost-effective basis. Currently, the cost of biopharmaceuticals limits their availability.

Oxygen regulation of a nodule-located carbonic anhydrase in alfalfa.

Control of the permeability to oxygen is critical for the function of symbiotic nitrogen fixation in legume nodules. The inner cortex (IC) seems to be a primary site for this regulation. In alfalfa (Medicago sativa) nodules, expression of the Msca1 gene encoding a carbonic anhydrase (CA) was previously found to be restricted to the IC.

Production of antibodies in transgenic plants.

Plants offer a cost-effective bioreactor to produce antibodies of diverse types. Recent studies demonstrate that secretory IgA, the predominant antibody isotype of the mucosal immune system, can be made in large quantities in plants. CaroRx, the lead SIgA antibody being developed by Planet Biotechnology Inc.

Effects of oxygen on nodule physiology and expression of nodulins in alfalfa.

Early nodulin 2 (ENOD2) transcripts and protein are specifically found in the inner cortex of legume nodules, a location that coincides with the site of a barrier to O2 diffusion. The extracellular glycoprotein that binds the monoclonal antibody MAC236 has also been localized to this site. Thus, it has been proposed that these proteins function in the regulation of nodule permeability to O2 diffusion.

Characterization of a recombinant plant monoclonal secretory antibody and preventive immunotherapy in humans.

A functional comparison was made between a monoclonal secretory antibody generated in transgenic plants and its parent murine IgG antibody.The affinity constants of both antibodies for a Streptococcus mutans adhesion protein were similar. However the secretory antibody had a higher functional affinity due to its dimeric structure.

The ribosomal protein P0 of soybean (Glycine max L. Merr.) has antigenic cross-reactivity to soybean seed lectin.

Soybean (Glycine max L. Merr.) mutants lacking the ability to produce the lectin normally found in soybean seeds (SBL) are designated Le-.

Stress activation of a bean hydroxyproline-rich glycoprotein promoter is superimposed on a pattern of tissue-specific developmental expression.

The HRGP4.1 gene, which encodes a cell wall hydroxyproline-rich glycoprotein, was isolated from a genomic library of bean (Phaseolus vulgaris L.).