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Antimicrobial peptides (AMPs) are major components of the innate immune defense. Accumulating evidence suggests that the antibacterial activity of many AMPs is dependent on the formation of amyloid-like fibrils. To identify novel fibril forming AMPs, we generated a spleen-derived peptide library and screened it for the presence of amyloidogenic peptides. This approach led to the identification of a C-terminal 32-mer fragment of alpha-hemoglobin, termed HBA(111-142). The non-fibrillar peptide has membranolytic activity against various bacterial species, while the HBA(111-142) fibrils aggregated bacteria to promote their phagocytotic clearance. Further, HBA(111-142) fibrils selectively inhibited measles and herpes viruses (HSV-1, HSV-2, HCMV), but not SARS-CoV-2, ZIKV and IAV. HBA(111-142) is released from its precursor by ubiquitous aspartic proteases under acidic conditions characteristic at sites of infection and inflammation. Thus, HBA(111-142) is an amyloidogenic AMP that may specifically be generated from a highly abundant precursor during bacterial or viral infection and may play an important role in innate antimicrobial immune responses., (© 2023. The Author(s).)

Microglia, the brain's resident immune cells, exhibit constitutive expression of the ionized calcium binding adaptor molecule 1 (IBA1), a cytoplasmic protein with actin and calcium-binding functions involved in membrane ruffling. Microglia are long-lived cells that exhibit a senescent morphology (dystrophy) with aging, which may be indicative of cell dysfunction. It has been reported that dystrophy of IBA1-positive microglia is exacerbated in obese humans. Our own preliminary studies of microglia in the medial temporal lobe of obese subjects have revealed another microglial abnormality, which is the loss of IBA1 immunoreactivity that can create large areas in the brain seemingly devoid of all microglial cells. Here, we systematically compared microglial appearance in human hippocampi derived from obese individuals compared to controls (n obese  = 33, n non-obese  = 30). In both groups, we found areas that were negative for IBA1, but contained P2YR12 and glutathione-peroxidase 1 (GPX)-positive microglia. The number and extent of IBA1-negative regions was increased in obese cases. Since some cases of non-obese individuals also exhibited loss of IBA-1 immunoreactivity, we searched for possible confounders and found that hepatic dysfunction strongly impacts the distribution of microglial cells: By computational analysis of scanned IBA1-stained sections, we detected increased Mean Empty Space distances (p = 0.016) and IBA1-negative areas (p = 0.090) which were independent from the cause of liver dysfunction, but also from aging. Thus, we report on a novel type of microglia pathological change, i.e. localized loss of IBA1 that is linked, at least in part, to obesity and hepatic dysfunction., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Measurement of the migration of the acetabular component following total hip replacement seems to be a useful method of early detection of aseptic loosening. The methods used so far for migration analysis are either too time-consuming or too elaborate in terms of the technical equipment required, and are therefore not suitable for use in day-to-day clinical practice. Analysis software based on the methods described by Nunn and Sutherland was developed with the aid of digitized conventional radiographs of the pelvis. It allows a planar migration measurement including cup inclination following manual marking of only five reference points on a computer screen. A correction for projection enlargement and rotational malpositioning of the patient is performed. All results are stored in a data bank and automatically compared with those recorded at previous follow-ups. Five different acetabular cups were analysed by a conventional and by a digital method for calculation of intra-observer variability. The standard deviation (SD) for horizontal and vertical migration was 0.2-0.4 mm and that for inclination angle 0.8-1.4 degrees with digital evaluation. For manual measurement the SD was 0.4-0.8 mm for migration and 0.8-1.2 degrees for inclination. A pelvis phantom was measured in nine different positions (neutral, 5 degrees and 10 degrees cranial and caudal inclination, 5 degrees and 10 degrees rotation to each side). Four different acetabular cup design were examined, each of which yielded a series of nine measurements. Within these series the SD for biplanar distances varied between 0.1 mm and 1.2 mm and for inclination between 1.1 degree and 2.3 degrees. Intra-observer variability was negligible.(ABSTRACT TRUNCATED AT 250 WORDS)