Human neutrophils, subjected to stimulation under different conditions (phorbol myristate acetate, opsonized zymosan, formylmethionyl-leucinephenylalanine, nonopsonized staphylococci), produced a factor (denoted as clumping factor, or CF) with a capacity for highly selective clumping and opsonization of staphylococci. Out of 68 strains of different species of staphylococci, only a single strains (S.epidermidis) was sensitive of CF. CF negative staphylococci were capable of inducing the release of CF by neutrophils, but were not bound by this factor. Extracts, obtained by the mechanical destruction of neutrophils (sonication, repeated freezing and thawing), had no clumping activity. CF had a mol. wt. exceeding 100 kD, was positively charged and disintegrated at 100 degrees C. The capacity of S.epidermidis 178 M for binding CF completely disappeared after the treatment of bacteria with pronase and partially disappeared after boiling and treatment with trypsin and periodate. Neuraminidase and heating at 80 degrees C produced no effect. These data are the first demonstration of highly selective (strain-specific) interaction between secretory products of neutrophils and bacteria.
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Plant Dis
January 2025
USDA-ARS North Central Agricultural Research Laboratory, Brookings, South Dakota, United States;
Soilborne diseases are persistent problems in soybean production. Long-term crop rotation can contribute to soilborne disease management. However, the response of soilborne pathogens to crop rotation is inconsistent, and rotation efficacy is highly variable.
View Article and Find Full Text PDFACS Nano
January 2025
Department of Bioengineering, University of Washington, Seattle, Washington 98195-5061, United States.
The recent development of modular universal chimeric antigen receptor (CAR) T-cell platforms that use bifunctional adaptor intermediates to redirect engineered T-cell effector function has greatly expanded the capabilities of adoptive T-cell therapy, enabling safer and more comprehensive cancer treatment. However, universal CAR receptor systems rely on unstable transient recognition of tag-coupled intermediates for T-cell activation, and the array of targeting intermediates has been limited to antibodies and small molecules. Addressing these shortcomings, we engineered universal CAR T-cell receptors that can be covalently modified with synthetic biomaterials by accelerated SpyCatcher003-SpyTag003 chemistry for cancer-cell targeting.
View Article and Find Full Text PDFJ Clin Oncol
January 2025
Children's Hospital of Philadelphia/University of Pennsylvania, Philadelphia, PA.
Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor with efficacy in children with TRK fusion tumors. We evaluated patient outcomes after elective discontinuation of larotrectinib in the absence of disease progression in a protocol-defined wait-and-see subset analysis of eligible patients where treatment resumption with larotrectinib was allowed if disease progressed. We also assessed the safety and efficacy of larotrectinib in all pediatric patients with sarcoma.
View Article and Find Full Text PDFJ Med Chem
January 2025
Pharmaron Beijing Co., Ltd., 6 Taihe Road, BDA, Beijing 100176, P. R. China.
Despite recent advances in the inhibition of EGFR (epidermal growth factor receptor), there remains a clinical need for new EGFR Exon20 insertion (Ex20Ins) inhibitors that spare EGFR WT. Herein, we report the discovery and optimization of two chemical series leading to ether and biaryl as potent, selective, and brain-penetrant inhibitors of Ex20Ins mutants. Building on our earlier discovery of alkyne which allowed access to CNS property space for an Ex20Ins inhibitor, we utilized structure-based design to move to lower lipophilicity and lower CL compounds while maintaining a WT selectivity margin.
View Article and Find Full Text PDFPLoS Negl Trop Dis
January 2025
Department of Pathology, Center for Global Health and Disease, Case Western Reserve University, Cleveland, Ohio, United States of America.
Background: WHO recommends two annual rounds of mass drug administration (MDA) with ivermectin, diethylcarbamazine, and albendazole (IDA) for lymphatic filariasis (LF) elimination in treatment naïve areas that are not co-endemic for onchocerciasis such as Papua New Guinea (PNG). Whether two rounds of MDA are necessary or sufficient and the optimal sampling strategies and endpoints for stopping MDA remain undefined.
Methods And Findings: Two cross-sectional studies were conducted at baseline (N = 49 clusters or villages) and 12 months after mass drug administration (MDA) with IDA (N = 47 villages) to assess lymphatic filariasis (LF) by circulating filarial antigenemia (CFA) and microfilariae (Mf).
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