CD47 Receptor Globally Regulates Metabolic Pathways That Control Resistance to Ionizing Radiation

Modulating tissue responses to stress is an important therapeutic objective. Oxidative and genotoxic stresses caused by ionizing radiation are detrimental to healthy tissues but beneficial for treatment of cancer. CD47 is a signaling receptor for thrombospondin-1 and an attractive therapeutic target because blocking CD47 signaling protects normal tissues while sensitizing tumors to ionizing radiation. Here we utilized a metabolomic approach to define molecular mechanisms underlying this radioprotective activity. CD47-deficient cells and cd47-null mice exhibited global advantages in preserving metabolite levels after irradiation. Metabolic pathways required for controlling oxidative stress and mediating DNA repair were enhanced. Some cellular energetics pathways differed basally in CD47-deficient cells, and the global declines in the glycolytic and tricarboxylic acid cycle metabolites characteristic of normal cell and tissue responses to irradiation were prevented in the absence of CD47. Thus, CD47 mediates signaling from the extracellular matrix that coordinately regulates basal metabolism and cytoprotective responses to radiation injury.     

Esterase Polymorphism in Meloidogyne konaensis

The continual detection of a slow (I1) esterase band in greenhouse cultures of Meloidogyne konaensis isolated from the field led to a hypothesis that the nematode may be polymorphic for esterase. A survey of coffee fields demonstrated at least four esterase phenotypes were present in Meloidogyne recovered. An F1 phenotype predominated (60% of the females), but an I1 phenotype was also common (30% of samples). A series of greenhouse and laboratory experiments were undertaken to understand this polymorphism. Esterase phenotype was not affected by development at 22º, 25º, or 33 ºC on tomato. Two different esterase phenotypes (I1 and F1-I1) were detected after M. konaensis was grown on tomato for several generations, even in single-egg-mass lines derived from an F1 female. Three isolates of M. konaensis differing in esterase phenotype (F1, I1, and F1-I1) did not differ morphologically but did differ in their parasitic ability. Only the F1 isolate parasitized Coffea arabica. The F1-I1 isolate had greater reproduction on Lycopersicon esculentum and Cucumis sativus than either the I1 or F1 isolate. The mechanism of the development of the polymorphism has yet to be determined. However, the F1 esterase may be useful as a marker for future research on parasitism of coffee by M. konaensis.     

Revisiting the Great American Biotic Interchange through analyses of amphitropical bees

The Great American Biotic Interchange (GABI) is zoogeographic event characterized by the exchange of taxa between North and South America, typically associated with the rise of the Isthmus of Panama in the late Pliocene. Recent geologic evidence suggests the connections between North and South America may be much older, and that the interchange of organisms between the two continents could have therefore happened much earlier than 3 Ma. Most of the research investigating the GABI has come from tropical vertebrate taxa; little work has been done on invertebrates or on non‐tropical species. To investigate how the GABI shaped the distribution of arid‐adapted species, particularly those with amphitropical distributions (i.e. taxa found in South and North American xeric regions yet absent from the tropics), we examine the historical biogeography of the bee genus Diadasia using a hypothesis of Diadasia phylogenetic relationships. Nuclear and mitochondrial genetic loci are used to reconstruct a phylogeny of Diadasia, which is then used to estimate divergence dates and reconstruct ancestral area relationships. Our analyses suggest the divergence between North and South American Diadasia species occurred between 20.5 and 15 Ma, long before the formation of the Isthmus of Panama. This study is the first to show a Miocene connection for an amphitropically‐distributed insect group. It suggests that the biotic connection between continents is more complicated than previously thought and may have initiated long before the late Pliocene.     

Evaluation of GABA Production and Probiotic Activities of Enterococcus faecium BS5

Probiotics and Antimicrobial Proteins - Gamma-aminobutyric acid (GABA) is a principal inhibitory neurotransmitter in the central nervous system and is produced by irreversible decarboxylation of...     

Artificial gravity as a multi-system countermeasure: effects on cognitive function

The Space Flight Cognitive Assessment Tool for Windows (WinSCAT) is used on the International Space Station to evaluate cognitive functioning after physical insult or trauma. The current study uses WinSCAT to assess cognitive functioning in a space flight analog (bed rest) environment where intermittent artificial gravity (AG) is being tested as a countermeasure. Fifteen male subjects (8 treatment, 7 control), who participated in 21 days of 6 degree head-down tilt bed rest, were assessed during the acclimatization phase, bed rest phase, and recovery phase. Individual differences were found within both the treatment and control groups. The treatment group accounted for more off-nominal WinSCAT scores than the control group. The length of time spent in bed rest was not associated with a change in cognitive function. Individual differences in underlying cognitive ability and motivation level are other possible explanations for the current findings.     

Investigation of the terminal P4 domain in a series of D-phenylglycinamide-based factor Xa inhibitors

Several P4 domain derivatives of the general d-phenylglycinamide-based scaffold (2) were synthesized and evaluated for their ability to bind to the serine protease factor Xa. Some of the more potent compounds were evaluated for their anticoagulant effects in vitro. A select subset containing various P1 indole constructs was further evaluated for their pharmacokinetic properties after oral administration to rats.     

Effects of retinoic acid on the development of liver fibrosis produced by carbon tetrachloride in mice

The role of retinoic acid (RA) in liver fibrogenesis was previously studied in cultured hepatic stellate cells (HSCs). RA suppresses the expression of alpha2(I) collagen by means of the activities of specific nuclear receptors RARalpha, RXRbeta and their coregulators. In this study, the effects of RA in fibrogenesis were examined in carbon tetrachloride (CCl4) induced liver fibrosis in mice. Mice were treated with CCl4 or RA and CCl4, along side control groups, for 12weeks. RA reduced the amount of histologically detectable fibrosis produced by CCl4. This was accompanied by a attenuation of the CCl4 induced increase in alpha2(I) collagen mRNA and a lower (2-fold versus 3-fold) increase in liver hydroxyproline. Furthermore, RA reduced the levels of 3-nitrotyrosine (3-NT) protein adducts and thiobarbituric acid (TBA) reactive substance (TBARS) in the liver, which are formed as results of oxidative stress induced by CCl4 treatment. These in vivo findings support our previous in vitro studies in cultured HSC of the inhibitory effect of RA on type I collagen expression. The data also provide evidence that RA reduces CCl4 induced oxidative stress in liver, suggesting that the anti-fibrotic role of RA is not limited to the inhibition of type I collagen expression.