Open software for biologists: from famine to feast

Developing and deploying specialized computing systems for specific research communities is achievable, cost effective and has wide-ranging benefits.     

Effects of a Single Therapeutic Dose of Glycerol on Cerebral Metabolism in the Brains of Young Mice: Possible Increase in Brain Glucose Transport and Glucose Utilization

Abstract: This is a study of the effects of a single “therapeutic” dose of glycerol [2 g(22 mmol)/kg i.p.] on brain carbohydrate and energy metabolism in normal nursing weanling mice. Findings were correlated with brain water and electrolyte content and with metabolite changes in plasma, red blood cells, and liver. Plasma glycerol levels peaked at 21 mM 7.5 min after injection and returned to the control value, 0.16 mM, by 2 h. Plasma Na⁺ concentration decreased and plasma protein increased for as long as 2 h after injection. Although red blood cells were freely permeable to glycerol, there was no evidence for glycerol metabolism in these cells. Glycerol levels in liver paralleled those in plasma. Glycerol injection increased liver glucose concentration 23% and doubled hepatic glycerol-1-phosphate levels. Liver ATP levels were reduced 24% after glycerol injection. Brain water concentration was significantly reduced from 7.5 min to 30 min after glycerol injection; brain Na⁺ and K⁺ levels were unchanged. There was no evidence for glycerol entry into brain (the amount detected in brain tissue could be explained by the glycerol content in the blood of the brain). While plasma glucose increased 33%, brain glucose increased 87%. Concomitantly there were statistically significant increases in fructose-1,6-diphosphate, lactate, α-ketoglutarate, and malate levels. The disproportionately high brain glucose value suggests increased transport of glucose from the blood to the brain. Increases in fructose-1,6-diphosphate, lactate, α-ketoglutarate, and malate are compatible with an increased metabolic flux in the glycolytic pathway and Krebs citric acid cycle. As has been previously shown for urea and/or mannitol, these changes may result from the effects of the hyperosmolar glycerol solution on the blood-brain barrier and on cerebral glucose utilization. The sustained lowering of plasma Na⁺ concentration after a single “therapeutic” glycerol injection suggests a need for monitoring plasma Na⁺ levels in the clinical situation. Possible lowering of hepatic ATP levels by the use of glycerol in humans is another concern.     

Fluorescent 7-diethylaminocoumarin pyrrolobenzodiazepine conjugates: synthesis, DNA interaction, cytotoxicity and differential cellular localization

The pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are a class of DNA minor groove binding agents that react covalently with guanine bases, preferably at Pu-G-Pu sites. A series of three fluorescent PBD-coumarin conjugates with different linker architectures has been synthesized to probe correlations between DNA binding affinity, cellular localization and cytotoxicity. The results show that the linker structure plays a critical role for all three parameters.     

The infundibular balance organ in amphioxus larvae and related aspects of cerebral vesicle organization

Serial EM reconstructions were used to examine the organization and constituent cell types of the infundibular region of the cerebral vesicle (c.v.) in a 12.5-day larva of Branchiostoma floridae . The balance organ lies just in front of the infundibular cells and consists of 10 electron-dense cells with long, bulbous cilia, each surrounded by a ring of accessory cells. The ciliary bulb cells have axons that terminate in vesicle-filled swellings that lack identifiable synapses. The accessory cells have short basal processes that are minor contributors to the adjacent neuropile. Based on morphology, we suggest a mechanosensory function for the ciliary bulb cells, possibly related to balance or motion detection. Scattered cells of similar type are found elsewhere in the cerebral vesicle, along with a variety of other neurones with caudally projecting axons and varicosities, but few synapses. Instead, nonsynaptic, paracrine secretion appears to be the predominant mode of transmitter release in the neuropile and ventral tracts of the cerebral vesicle. The closest vertebrate homologue of this part of the amphioxus brain is arguably the limbic core of the caudal diencephalon and mesencephalon, including the homeostatic control centres of the hypothalamus. We postulate that this limbic core is an ancient structure traceable at least as far back in evolution as the common ancestor of amphioxus and vertebrates.     

Region-specific DNA methylation in the preimplantation embryo as a target for genomic plasticity

It has been long known that the unique genetic sequence each embryo inherits is not the sole determinant of phenotype. However, only recently have epigenetic modifications to DNA been implicated in providing potential developmental plasticity to the embryonic and fetal genome, with environmental influences directly altering the epigenetic modifications that contribute to tissue-specific gene regulation. Most is known about the potential environmental regulation of DNA methylation, epigenetic addition of methyl groups to cytosine residues in DNA that acts in the long-term silencing of affected sequences. While most attention has been paid to the methylation of imprinted gene sequences, in terms of developmental plasticity there are many more parts of the genome that are methylated and that could be affected. This review explores the distribution of cytosine methylation in the genome and discusses the potential effects of regional plasticity on subsequent development. Widening our consideration of potentially plastic regions is likely to greatly enhance our understanding of how individuals are shaped not only by DNA sequence, but by the environment in which pluripotent embryonic cells are transformed into the many cell types of the body.     

The transfer of glucose to steroids by chimpanzee liver microsomes.

Microsomal preparations from chimpanzee liver can transfer glucose from UDPglucose to the 17alpha-hydroxyl group of 17alpha-estradiol and of 17alpha-estradiol-3-glucuronide. A phenolic glucoside of estrone, but not of either 17alpha- or 17beta-estradiol is also formed. No formation of glucosides of p-nitrophenol, or of diethylstilbestrol was demonstrated. The specificity of glucosyl transfer in the chimpanzee is not identical to that in either the human, the rabbit, or the sheep.     

Effects of treatment for hypertension on cerebral haemorrhage and infarction.

One hundred and sixty nine patients admitted to hospital for stroke over 30 months were examined to see whether treating hypertension had influenced the incidence of cerebral haemorrhage and infarction. Seventy eight (46%) of them had normal blood pressure, 47 (28%) previously diagnosed hypertension for which they were receiving treatment, and 44 (26%) previously undiagnosed and untreated hypertension. Haemorrhagic stroke was commoner among patients with untreated hypertension, whereas infarction was commoner in patients with treated hypertension. Infarction and haemorrhage were equally prevalent in patients with normal blood pressure. Effective treatment in this population seemed to have had a substantially different impact on vascular disease, giving rise to cerebral haemorrhage as opposed to infarction. This is consistent with evidence from other studies that treatment for hypertension has little or no effect on the progression of atheroma.