Staphylococcus aureus is a major human pathogen, yet the immune factors that protect against infection remain elusive. High titers of opsonic IgG antibodies, achieved in preclinical animal immunization studies, have consistently failed to provide protection in humans. Here, we investigate antibody responses to the conserved S.
View Article and Find Full Text PDFAntibody-dependent complement activation plays a key role in the natural human immune response to infections. Currently, the understanding of which antibody-antigen combinations drive a potent complement response on bacteria is limited. Here, we develop an antigen-agnostic approach to stain and single-cell sort human IgG memory B cells recognizing intact bacterial cells, keeping surface antigens in their natural context.
View Article and Find Full Text PDFThe baubellum (os clitoridis) is a bone found in the clitoris of many female eutherian mammals and is homologous to the baculum in males. In contrast to the baculum, the baubellum has received very little attention regarding its morphological or interspecific diversity, or on hypotheses for its function. The presence of the baubellum in bears (Ursidae) has only been established and mentioned in the literature for the Ursus genus, and not for the other genera of bears.
View Article and Find Full Text PDFIntroduction: Implant infections caused by Staphylococcus aureus are responsible for high mortality and morbidity worldwide. Treatment of these infections can be difficult especially when bacterial biofilms are involved. In this study we investigate the potential of infrared photoimmunotherapy to eradicate staphylococcal infection in a mouse model.
View Article and Find Full Text PDFImmunoglobulin M (IgM) is an evolutionary conserved key component of humoral immunity, and the first antibody isotype to emerge during an immune response. IgM is a large (1 MDa), multimeric protein, for which both hexameric and pentameric structures have been described, the latter additionally containing a joining (J) chain. Using a combination of single-particle mass spectrometry and mass photometry, proteomics, and immunochemical assays, we here demonstrate that circulatory (serum) IgM exclusively exists as a complex of J-chain-containing pentamers covalently bound to the small (36 kDa) protein CD5 antigen-like (CD5L, also called apoptosis inhibitor of macrophage).
View Article and Find Full Text PDFAntibodies play a key role in the immune defence against Gram-negative bacteria. After binding to bacterial surface antigens, IgG and IgM can activate the complement system and trigger formation of lytic membrane attack complex (MAC) pores. Molecular studies to compare functional activity of antibodies on bacteria are hampered by the limited availability of well-defined antibodies against bacterial surface antigens.
View Article and Find Full Text PDFIntrauterine undernutrition in humans typically results in low birth weight ([small for gestational age] SGA) and delayed postnatal neuromotor maturation. Since SGA and intrauterine growth retardation are also common in domestic pigs, piglets are premised as models to study delayed motor development. Applied to the locomotor paradigm, however, questions emerge: (i) how to map the developmental time scale of the precocial model onto the altricial target species and (ii) how to distinguish size from maturation effects? Gait data were collected at self-selected voluntary walking speed during early development (0-96 hours postpartum; pp) for SGA- and normal ([appropriate for gestational age] AGA) piglets.
View Article and Find Full Text PDFLocomotor kinematics have been challenging inputs for automated diagnostic screening of livestock. Locomotion is a highly variable behavior, and influenced by subject characteristics (e.g.
View Article and Find Full Text PDFis the leading cause of community-acquired pneumonia and an important cause of childhood mortality. Despite the introduction of successful vaccines, the global spread of both non-vaccine serotypes and antibiotic-resistant strains reinforces the development of alternative therapies against this pathogen. One possible route is the development of monoclonal antibodies (mAbs) that induce killing of bacteria via the immune system.
View Article and Find Full Text PDFWe investigated how baboons transition from quadrupedal to bipedal walking without any significant interruption in their forward movement (i.e. transition 'on the fly').
View Article and Find Full Text PDFMed Sci Sports Exerc
November 2022
Purpose: Running with increased duty factors (DF) has been shown to effectively reduce external forces during running. In this study, we investigated whether running with increased DF (INCR) also reduces internal musculoskeletal loading measures, defined as peak muscle forces, muscle force impulses, and peak joint contact forces compared with a runners' preferred running pattern (PREF).
Method: Ten subjects were instructed to run with increased DF at 2.
IgG molecules are crucial for the human immune response against bacterial infections. IgGs can trigger phagocytosis by innate immune cells, like neutrophils. To do so, IgGs should bind to the bacterial surface via their variable Fab regions and interact with Fcγ receptors and complement C1 via the constant Fc domain.
View Article and Find Full Text PDFCentral line associated bloodstream infections (CLABSI) with are a major cause of morbidity in neonates, who have an increased risk of infection because of their immature immune system. As especially preterm neonates suffer from antibody deficiency, clinical studies into preventive therapies have thus far focused on antibody supplementation with pooled intravenous immunoglobulins from healthy donors (IVIG) but with little success. Here we study the potential of monoclonal antibodies (mAbs) against to induce phagocytic killing by human neutrophils.
View Article and Find Full Text PDFImplant-associated infections are difficult to treat because of biofilm formation. Bacteria in a biofilm are often insensitive to antibiotics and host immunity. Monoclonal antibodies (mAbs) could provide an alternative approach to improve the diagnosis and potential treatment of biofilm-related infections.
View Article and Find Full Text PDFComplement proteins can form membrane attack complex (MAC) pores that directly kill Gram-negative bacteria. MAC pores assemble by stepwise binding of C5b, C6, C7, C8 and finally C9, which can polymerize into a transmembrane ring of up to 18 C9 monomers. It is still unclear if the assembly of a polymeric-C9 ring is necessary to sufficiently damage the bacterial cell envelope to kill bacteria.
View Article and Find Full Text PDFPreterm infants frequently show neuromotor dysfunctions, but it is not clear how reduced gestational age at birth may induce developmental coordination disorders. Advancing postnatal age, not only post-conceptional age, may determine neuromuscular development, and early interventions in preterm newborns may improve their later motor skills. An animal model of preterm birth that allows early postnatal detection of movement patterns may help to investigate this hypothesis.
View Article and Find Full Text PDFPrimates exhibit unusual quadrupedal features (e.g. diagonal gaits, compliant walk) compared with other quadrupedal mammals.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
June 2021
Understanding how human complement proteins interact with human antibodies is important for the development of antibody therapies and understanding autoimmune diseases. At present, many groups use baby rabbit serum as a source of complement because, in contrast to human serum, it lacks preexisting antibodies. However, for characterization of human (monoclonal) antibodies, human serum would be a preferred source of complement.
View Article and Find Full Text PDFBMJ Open Sport Exerc Med
March 2021
Objectives: Recreational runners show a large interindividual variation in spatiotemporal characteristics. This research focused on slow runners and intended: (1) to document the variance in duty factor (DF) between runners in a real-life running setting and (2) examine whether the interindividual variation in DF and stride frequency (SF) relates to differences in external loading parameters between runners.
Methods: Spatiotemporal characteristics of 23 slow runners (ie, <2.
During the first half of the 20th century, extraordinary high jumping performances of East-African athletes were observed. These athletes used a specific native jumping style called Gusimbuka Urukiramende. Eye-witnesses believed that these performances could have been world-records and that these athletes could have competed at the Olympics.
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