Lactadherin Inhibits Secretory Phospholipase A2 Activity on Pre-Apoptotic Leukemia Cells

Secretory phospholipase A2 (sPLA2) is a critical component of insect and snake venoms and is secreted by mammalian leukocytes during inflammation. Elevated secretory PLA2 concentrations are associated with autoimmune diseases and septic shock. Many sPLA2’s do not bind to plasma membranes of quiescent cells but bind and digest phospholipids on the membranes of stimulated or apoptotic cells. The capacity of these phospholipases to digest membranes of stimulated or apoptotic cells correlates to the exposure of phosphatidylserine. In the present study, the ability of the phosphatidyl-L-serine-binding protein, lactadherin to inhibit phospholipase enzyme activity has been assessed. Inhibition of human secretory phospholipase A2-V on phospholipid vesicles exceeded 90%, whereas inhibition of Naja mossambica sPLA2 plateaued at 50–60%. Lactadherin inhibited 45% of activity of Naja mossambica sPLA2 and >70% of human secretory phospholipase A2-V on the membranes of human NB4 leukemia cells treated with calcium ionophore A23187. The data indicate that lactadherin may decrease inflammation by inhibiting sPLA2

What is the Source of Observed Annual Variations in Plasmaspheric Density?

Plasmaspheric densities have been observed previously to be higher in December than in June, with the ratio varying between 1.5 and 3.0 and with larger variations at lower L shells. In order to search for the cause of the observed annual variations, we have modeled plasmaspheric density, using a time-dependent hydrodynamic model. On an L = 2 field line with geomagnetic longitude equal to 300°, the modeled plasmaspheric densities were a factor of 1.5 times higher in December than in June. The modeled December to June density ratio was found to increase slightly with L shell, in contrast to observations; this discrepancy may be due to the fact that outer plasmaspheric flux tubes are never completely full. In addition, for an L = 2 field line with geomagnetic longitude equal to 120°, the modeled plasmaspheric density was higher in June than in December by a factor of about 1.2. Various numerical tests were also performed in order to examine the sensitivity of plasmaspheric density to various parameters. In particular, a large vertical neutral wind was applied in order to raise the O+ profile, which had the effect of raising plasmaspheric density by a factor of 6. This in conjunction with a theoretical analysis suggests that plasmaspheric density levels are very sensitive to O+ levels in the upper ionosphere. We conclude that annual variations in plasmaspheric density are due to similar variations in ionospheric O+

The Sirius Passet Lagerstätte of North Greenland—A geochemical window on early Cambrian low‐oxygen environments and ecosystems

The early Cambrian Sirius Passet fauna of northernmost Greenland (Cambrian Series 2, Stage 3) contains exceptionally preserved soft tissues that provide an important window to early animal evolution, while the surrounding sediment holds critical data on the palaeodepositional water‐column chemistry. The present study combines palaeontological data with a multiproxy geochemical approach based on samples collected in situ at high stratigraphic resolution from Sirius Passet. After careful consideration of chemical alterations during burial, our results demonstrate that fossil preservation and biodiversity show significant correlation with iron enrichments (FeHR/FeT), trace metal behaviour (V/Al), and changes in nitrogen cycling (δ15N). These data, together with Mo/Al and the preservation of organic carbon (TOC), are consistent with a water column that was transiently low in oxygen concentration, or even intermittently anoxic. When compared with the biogeochemical characteristics of modern oxygen minimum zones (OMZs), geochemical and palaeontological data collectively suggest that oxygen concentrations as low as 0.2–0.4 ml/L restricted bioturbation but not the development of a largely nektobenthic community of predators and scavengers. We envisage for the Sirius Passet biota a depositional setting where anoxic water column conditions developed and passed over the depositional site, possibly in association with sea‐level change, and where this early Cambrian biota was established in conditions with very low oxygen

Co-diversification of an intestinal Mycoplasma and its salmonid host

Understanding the evolutionary relationships between a host and its intestinal resident bacteria can transform how we understand adaptive phenotypic traits. The interplay between hosts and their resident bacteria inevitably affects the intestinal environment and, thereby, the living conditions of both the host and the microbiota. Thereby this co-existence likely influences the fitness of both bacteria and host. Whether this co-existence leads to evolutionary co-diversification in animals is largely unexplored, mainly due to the complexity of the environment and microbial communities and the often low host selection. We present the gut metagenome from wild Atlantic salmon (Salmo salar), a new wild organism model with an intestinal microbiota of low complexity and a well-described population structure, making it well-suited for investigating co-evolution. Our data reveal a strong host selection of a core gut microbiota dominated by a single Mycoplasma species. We found a clear co-diversification between the population structure of Atlantic salmon and nucleotide variability of the intestinal Mycoplasma populations conforming to expectations from co-evolution between host and resident bacteria. Our results show that the stable microbiota of Atlantic salmon has evolved with its salmonid host populations while potentially providing adaptive traits to the salmon host populations, including defence mechanisms, biosynthesis of essential amino acids, and metabolism of B vitamins. We highlight Atlantic salmon as a novel model for studying co-evolution between vertebrate hosts and their resident bacteria.publishedVersio

Microfiltration of raw milk for production of high-purity milk fat globule membrane material

peer-reviewedCommercial ingredients containing milk fat globule membrane (MFGM) material are currently isolated from heavily processed dairy streams. The aim of this study was to achieve a more gentle isolation of MFGM material by means of ceramic dia-microfiltration of raw whole milk to separate fat globules from casein micelles and whey proteins prior to MFGM extraction. A pilot-scale experiment with 1.4 μm pore size (membrane surface area 1.05 m2) resulted in an optimal outcome of low permeation of fat (2.5% permeation) and high permeation of proteins (97% permeation). This yielded an MFGM isolate with 7% w/w polar lipids and 30% w/w proteins, where contamination of non-MFGM proteins was only 25% of total protein content. Furthermore, mild pasteurization (72 °C, 15 s) introduced either before or after microfiltration had no impact on filtration efficiency or MFGM yield and composition. The work describes an industrially relevant production method for a less-processed MFGM material of high purity with potential for further separation and valorisation of protein-rich permeate streams.Innovationsfonde

Genetic Factors Underlie Stability of Obsessive–Compulsive Symptoms

The contribution of genetic and environmental factors to the stability of obsessive-compulsive (OC) symptoms has not yet been established in adult population based samples. We obtained the Young Adult Self Report Obsessive-Compulsive Subscale in mono- and dizygotic twins from the population-based Netherlands Twin Register in 1991, 1995 and 1997 and the Padua Inventory Revised Abbreviated in 2002. Stability of OC symptoms was analyzed as a function of genetic and environmental components. Heritability of OC behavior was around 40% at each time-point, independent of the instrument used. OC behavior was moderately stable with correlations ranging between r = .2 (for 11-year intervals), .4 (for 4-5 year intervals) and .6 (for 2 year intervals). Genetic correlations across time were higher, varying between .4 and .9, indicating that the stability of OC symptoms is mainly due to stable genetic factors. This study showed a moderate heritability and stability for OC behavior in adults. Genetic stability across time is high

Pharmacokinetics of the phosphatidylserine tracers 99m Tc-lactadherin and 99m Tc-annexin V in pigs

Abstract Background: Phosphatidylserine (PS) is a phospholipid normally located in the inner leaflet of the cell membrane. PS is translocated from the inner to the outer leaflet of the plasma membrane during the early stages of apoptosis and in necrosis. In cell and animal studies, reversible PS externalisation to the outer membrane leaflet has been observed in viable cells. Hence, PS markers have been proposed as markers of both reversibly and irreversibly damaged cells. The purpose of this experimental study in pigs was to investigate the kinetics of the newly introduced PS marker technetium-99m-labelled lactadherin ( 99m Tc-lactadherin) in comparison with the well-known PS trace

Definition of the σW regulon of Bacillus subtilis in the absence of stress

Bacteria employ extracytoplasmic function (ECF) sigma factors for their responses to environmental stresses. Despite intensive research, the molecular dissection of ECF sigma factor regulons has remained a major challenge due to overlaps in the ECF sigma factor-regulated genes and the stimuli that activate the different ECF sigma factors. Here we have employed tiling arrays to single out the ECF σW regulon of the Gram-positive bacterium Bacillus subtilis from the overlapping ECF σX, σY, and σM regulons. For this purpose, we profiled the transcriptome of a B. subtilis sigW mutant under non-stress conditions to select candidate genes that are strictly σW-regulated. Under these conditions, σW exhibits a basal level of activity. Subsequently, we verified the σW-dependency of candidate genes by comparing their transcript profiles to transcriptome data obtained with the parental B. subtilis strain 168 grown under 104 different conditions, including relevant stress conditions, such as salt shock. In addition, we investigated the transcriptomes of rasP or prsW mutant strains that lack the proteases involved in the degradation of the σW anti-sigma factor RsiW and subsequent activation of the σW-regulon. Taken together, our studies identify 89 genes as being strictly σW-regulated, including several genes for non-coding RNAs. The effects of rasP or prsW mutations on the expression of σW-dependent genes were relatively mild, which implies that σW-dependent transcription under non-stress conditions is not strictly related to RasP and PrsW. Lastly, we show that the pleiotropic phenotype of rasP mutant cells, which have defects in competence development, protein secretion and membrane protein production, is not mirrored in the transcript profile of these cells. This implies that RasP is not only important for transcriptional regulation via σW, but that this membrane protease also exerts other important post-transcriptional regulatory functions