Hyperbaric oxygen prevents early death caused by experimental cerebral malaria

Background

Cerebral malaria (CM) is a syndrome characterized by neurological signs, seizures and coma. Despite the fact that CM presents similarities with cerebral stroke, few studies have focused on new supportive therapies for the disease. Hyperbaric oxygen (HBO) therapy has been successfully used in patients with numerous brain disorders such as stroke, migraine and atherosclerosis.

Methodology/Principal Findings

C57BL/6 mice infected with Plasmodium berghei ANKA (PbA) were exposed to daily doses of HBO (100% O₂, 3.0 ATA, 1–2 h per day) in conditions well-tolerated by humans and animals, before or after parasite establishment. Cumulative survival analyses demonstrated that HBO therapy protected 50% of PbA-infected mice and delayed CM-specific neurological signs when administrated after patent parasitemia. Pressurized oxygen therapy reduced peripheral parasitemia, expression of TNF-α, IFN-γ and IL-10 mRNA levels and percentage of γδ and αβ CD4⁺ and CD8⁺ T lymphocytes sequestered in mice brains, thus resulting in a reduction of blood-brain barrier (BBB) dysfunction and hypothermia.

Conclusions/Significance

The data presented here is the first indication that HBO treatment could be used as supportive therapy, perhaps in association with neuroprotective drugs, to prevent CM clinical outcomes, including death.     

SnoRNA Snord116 (Pwcr1/MBII-85) deletion causes growth deficiency and hyperphagia in mice

Prader-Willi syndrome (PWS) is the leading genetic cause of obesity. After initial severe hypotonia, PWS children become hyperphagic and morbidly obese, if intake is not restricted. Short stature with abnormal growth hormone secretion, hypogonadism, cognitive impairment, anxiety and behavior problems are other features. PWS is caused by lack of expression of imprinted genes in a approximately 4 mb region of chromosome band 15q11.2. Our previous translocation studies predicted a major role for the C/D box small nucleolar RNA cluster SNORD116 (PWCR1/HBII-85) in PWS. To test this hypothesis, we created a approximately 150 kb deletion of the > 40 copies of Snord116 (Pwcr1/MBII-85) in C57BL/6 mice. Snord116del mice with paternally derived deletion lack expression of this snoRNA. They have early-onset postnatal growth deficiency, but normal fertility and lifespan. While pituitary structure and somatotrophs are normal, liver Igf1 mRNA is decreased. In cognitive and behavior tests, Snord116del mice are deficient in motor learning and have increased anxiety. Around three months of age, they develop hyperphagia, but stay lean on regular and high-fat diet. On reduced caloric intake, Snord116del mice maintain their weight better than wild-type littermates, excluding increased energy requirement as a cause of hyperphagia. Normal compensatory feeding after fasting, and ability to maintain body temperature in the cold indicate normal energy homeostasis regulation. Metabolic chamber studies reveal that Snord116del mice maintain energy homeostasis by altered fuel usage. Prolonged mealtime and increased circulating ghrelin indicate a defect in meal termination mechanism. Snord116del mice, the first snoRNA deletion animal model, reveal a novel role for a non-coding RNA in growth and feeding regulation.     

Galectin-4 controls intestinal inflammation by selective regulation of peripheral and mucosal T cell apoptosis and cell cycle

Galectin-4 is a carbohydrate-binding protein belonging to the galectin family. Here we provide novel evidence that galectin-4 is selectively expressed and secreted by intestinal epithelial cells and binds potently to activated peripheral and mucosal lamina propria T-cells at the CD3 epitope. The carbohydrate-dependent binding of galectin-4 at the CD3 epitope is fully functional and inhibited T cell activation, cycling and expansion. Galectin-4 induced apoptosis of activated peripheral and mucosal lamina propria T cells via calpain-, but not caspase-dependent, pathways. Providing further evidence for its important role in regulating T cell function, galectin-4 blockade by antisense oligonucleotides reduced TNF-alpha inhibitor induced T cell death. Furthermore, in T cells, galectin-4 reduced pro-inflammatory cytokine secretion including IL-17. In a model of experimental colitis, galectin-4 ameliorated mucosal inflammation, induced apoptosis of mucosal T-cells and decreased the secretion of pro-inflammatory cytokines. Our results show that galectin-4 plays a unique role in the intestine and assign a novel role of this protein in controlling intestinal inflammation by a selective induction of T cell apoptosis and cell cycle restriction. Conclusively, after defining its biological role, we propose Galectin-4 is a novel anti-inflammatory agent that could be therapeutically effective in diseases with a disturbed T cell expansion and apoptosis such as inflammatory bowel disease.     

Less input same output: simplified approach for population size assessment in Lepidoptera

With the aim of creating a simplified sampling scheme that would retain the accuracy of standard mark–release–recapture (MRR) sampling, but at a greatly reduced cost, we analysed 23 capture–recapture data sets from spatially closed populations of six Lepidoptera species according to the constrained Cormack–Jolly–Seber models. Subsequently the relationships between the estimates of population parameters were investigated in order to develop a regression equation that would enable us to calculate seasonal population size without sampling the population throughout the entire flight period. The proportion of individuals flying at peak population was highly variable (CV=0.39), but the variation decreased considerably (CV=0.14) after different life span and flight period length were accounted for. Over 90% of the variance of this proportion was explained by the life span:flight period length ratio. Simulations of hypothetical sampling schemes proved that schemes covering the second and third quarter of the flight period performed much better than those restricted to the second quarter only. The accuracy of seasonal population size estimated with the regression equation developed was comparable for intensive schemes (daily sampling) and non-intensive ones (sampling once in 2 or 3 days). We propose a simplified method of surveying butterfly populations that should be based on checking the presence of flying adults at the beginning and end of the flight period to assess its length, and MRR sampling covering its middle part, with intervals between capture days corresponding to the average life span of investigated butterflies.     

Stamping Vital Cells—a Force-Based Ligand Receptor Assay

Gaining information about receptor profiles on cells, and subsequently finding the most efficient ligands for these signaling receptors, remain challenging tasks in stem cell and cancer research as well as drug development. We introduce a live-cell method with great potential in both screening for surface receptors and analysing binding forces of different ligands. The technique is based on the molecular force assay, a parallel-format, high-throughput experiment on a single-molecule level. On human red blood cells, we demonstrate the detection of the interaction of N-acetyl-α-D-galactosaminyl residues with the lectin helix pomatia agglutinine and of the CD47 receptor with its antibody. The measurements are performed under nearly physiological conditions and still provide a highly specific binding signal. Moreover, with a detailed comparative force analysis on two cell types with different morphology, we show that our method even allows the determination of a DNA force equivalent for the interaction of the CD47 receptor and its antibody.     

Aggregation and Sedimentation of Thalassiosira weissflogii (diatom) in a Warmer and More Acidified Future Ocean

Increasing Transparent Exopolymer Particle (TEP) formation during diatom blooms as a result of elevated temperature and pCO₂ have been suggested to result in enhanced aggregation and carbon flux, therewith potentially increasing the sequestration of carbon by the ocean. We present experimental results on TEP and aggregate formation by Thalassiosira weissflogii (diatom) in the presence or absence of bacteria under two temperature and three pCO₂ scenarios. During the aggregation phase of the experiment TEP formation was elevated at the higher temperature (20°C vs. 15°C), as predicted. However, in contrast to expectations based on the established relationship between TEP and aggregation, aggregation rates and sinking velocity of aggregates were depressed in warmer treatments, especially under ocean acidification conditions. If our experimental findings can be extrapolated to natural conditions, they would imply a reduction in carbon flux and potentially reduced carbon sequestration after diatom blooms in the future ocean.     

Field Studies on the African Fruit Bat Epomophorus wahlbergi (Sundevall), with Special Reference to Male Calling

Social interactions, site attachment and group cohesion were studied in a free-living colony of Epomophorus fruit bats. Daily activities in an undisturbed colony were recorded. Special attention was paid to the peculiar calling behaviour of courting ♂♂ during the night. Structure and repetition rate of their sounds were analyzed in the laboratory. A special mode of acoustic interaction was found and related to the observed spacing out of calling ♂♂ By following feeding animals in the field and by analysis of their faeces we found that besides fruits they eat special leaves which afford steroidal sapogenins.