A novel PKC-regulated mechanism controls CD44 ezrin association and directional cell motility

The dynamic assembly and disassembly of membrane cytoskeleton junctional complexes is critical in cell migration. Here we describe a novel phosphorylation mechanism that regulates the hyaluronan receptor CD44. In resting cells, CD44 is constitutively phosphorylated at a single serine residue, Ser325. After protein kinase C is activated, a switch in phosphorylation results in CD44 being phosphorylated solely at an alternative residue, Ser291. Using fluorescence resonance energy transfer (FRET) monitored by fluorescence lifetime imaging microscopy (FLIM) and chemotaxis assays we show that phosphorylation of Ser291 modulates the interaction between CD44 and the cytoskeletal linker protein ezrin in vivo, and that this phosphorylation is critical for CD44-dependent directional cell motility.     

Effect of maternal serum on viability and function of early human placental explants

Summary Fetal bovine serum (FBS) is frequently used to supplement chemically defined media such as Ham’s F10 when studying placental explant cultures. However in vitro production of hormones is usually declining by the 2nd or 3rd day and is short-lived (7 to 10 days). In this study we explored the use of human maternal serum (HMS) from early gestation as the medium supplement to Ham’s F10. Early placental hormone production was compared using two concentrations of FBS and HMS. On Day 3 of incubation, progesterone production in 10% HMS was 12-fold increased over that in 10% FBS, estradiol production was increased 10-fold, and βhCG production more than 3-fold. When the serum concentrations were increased to 40%, the results in all cases were similar to those at 10%. Preliminary characterization studies revealed that the stimulatory activity of HMS is heat-labile, neither extractable into organic solvent (diethyl ether) nor dialyzable, suggesting that it is protein in nature. In a long-term incubation, compared with FBS (7 days), HMS permitted survival of culture up to 30 days, judged both histologically and biochemically. We conclude that HMS provides substance(s), probably protein in nature, not present in FBS or non-pregnant human serum, which are important for human placental viability and function in vivo.     

Effects of cystic fibrosis serum on the rat parotid gland

Summary Injections of serum from human patients with cystic fibrosis into adult rats caused pronounced structural modifications and increased mitotic rate in the parotid gland. Mitotic rate was increased from a low level of 0.02/1,000 acinar cells in parotid glands of adult rats to 6.5/1,000 acinar cells after 2 or 3 days of serum injection. At the light and electron microscopic levels, significant acinar cell atrophy and degranulation were observed. Cellular necrosis, and increases in quantity of lysosome-like dense bodies, mast cells, and macrophages were also detected. These changes are suggestive of tissue response to injurious foreign protein. Furthermore, the fact that normal sera pronounced the same kind of effects (but greatly reduced in extent) strengthens the view that these effects result from the immunologic response of the host organ to foreign antigen. Since, however, the responses of the rat parotid to cystic fibrosis serum were considerably more marked than those elicited by normal serum, the rat parotid may thus have potential usefulness in assaying for the presence of human cystic fibrosis factor.This work was supported in part by U.S.P.H.S. Grant DE 02110The authors wish to thank Dr. Alexander Spock, Cystic Fibrosis Center, Duke University Medical Center, Durham, North Carolina, and Dr. Ralph Tiller, Children's Hospital, University of Alabama Medical Center, for generously supplying blood from patients with cystic fibrosis. The authors also want to thank Dr. A. Siegel, Department of Pathology, University of Alabama Medical Center, and Mr. R. Siegel, for determinations of serum catecholamine levels     

Parasites do not adapt to elevated temperature,as evidenced from experimental evolution of a phytoplankton–fungus system

Global warming is predicted to impact the prevalence and severity of infectious diseases. However, empirical data supporting this statement usually stem from experiments in which parasite fitness and disease outcome are measured directly after temperature increase. This might exclude the possibility of parasite adaptation. To incorporate the adaptive response of parasites into predictions of disease severity in a warmer world, we undertook an experimental evolution assay in which a fungal parasite of phytoplankton was maintained at elevated or control temperatures for six months, corresponding to 100–200 parasite generations. Host cultures were maintained at the respective temperatures and provided as substrate, but were not under parasite pressure. A reciprocal infection experiment conducted after six-month serial passages revealed no evidence of parasite adaptation. In fact, parasite fitness at elevated temperatures was inferior in parasite populations reared at elevated temperatures compared with those maintained under control temperature. However, this effect was reversed after parasites were returned to control temperatures for a few (approx. 10) generations. The absence of parasite adaptation to elevated temperatures suggests that, in phytoplankton–fungus systems, disease outcome under global warming will be largely determined by both host and parasite thermal ecology.     

Observed Antibody Space: A diverse database of cleaned,annotated, and translated unpaired and paired antibody sequences

The antibody repertoires of individuals and groups have been used to explore disease states, understand vaccine responses, and drive therapeutic development. The arrival of B‐cell receptor repertoire sequencing has enabled researchers to get a snapshot of these antibody repertoires, and as more data are generated, increasingly in‐depth studies are possible. However, most publicly available data only exist as raw FASTQ files, making the data hard to access, process, and compare. The Observed Antibody Space (OAS) database was created in 2018 to offer clean, annotated, and translated repertoire data. In this paper, we describe an update to OAS that has been driven by the increasing volume of data and the appearance of paired (VH/VL) sequence data. OAS is now accessible via a new web server, with standardized search parameters and a new sequence‐based search option. The new database provides both nucleotides and amino acids for every sequence, with additional sequence annotations to make the data Minimal Information about Adaptive Immune Receptor Repertoire compliant, and comments on potential problems with the sequence. OAS now contains 25 new studies, including severe acute respiratory syndrome coronavirus 2 data and paired sequencing data. The new database is accessible at http://opig.stats.ox.ac.uk/webapps/oas/, and all data are freely available for download.     

Fracture patterns at the Medieval Leper Hospital in Chichester

Humans are constantly at risk of bone fractures, not only when threatened by personal violence, but also by the challenge of daily living. Because fractures are a cross-cultural phenomenon and are one of the more commonly observed skeletal lesions in archaeological collections, their presence provides a unique opportunity to compare living conditions, and thereby assess fracture risk in coexisting cultures. This study analyzed long bone fracture patterns of 212 sexed adults from the medieval leper hospital of St. James and St. Mary Magdalene in Chichester, England. The comparison of this hospital sample to other British medieval skeletal samples examined the level of health manifest in fracture etiology. The fracture frequency for this sample was 15.1%, with males accounting for 85.4% of the fractures. The fracture frequencies from the samples not affiliated with hospitals ranged from 3.3 to 5.6%. Because medieval urban lifestyle was notoriously difficult due to inadequate sanitation and living conditions, the overall health of the population at large was inferior, placing all at similar fracture risk. Therefore, more specific complications associated with the fractures were examined. Osseous modifications of the skeletons due to lepromatous leprosy were associated with 28% of individuals sustaining fractures. However, persons with the milder tuberculoid leprosy do not exhibit skeletal lesions, but are more prone to accident due to the earlier loss of sensory perception and visual impairment. It is argued that the presence of leprosy is underestimated in archaeological populations and may be a major contributing factor to the prevalence of fracture resulting from accidental falls. Am J Phys Anthropol 105:43–55, 1998. © 1998 Wiley-Liss, Inc.