On a Minimal Model for Hemodynamics and Metabolism of Lactate: Application to Low Grade Glioma and Therapeutic Strategies

WHO II low grade glioma evolves inevitably to anaplastic transformation. Magnetic resonance imaging is a good non-invasive way to watch it, by hemodynamic and metabolic modifications, thanks to multinuclear spectroscopy ¹H/³¹P. In this work we study a multi-scale minimal model of hemodynamics and metabolism applied to the study of gliomas. This mathematical analysis leads us to a fast-slow system. The control of the position of the stationary point brings to the concept of domain of viability. Starting from this system, the equations bring to light the parameters that push glioma cells out of their domain of viability. Four fundamental factors are highlighted. The first two are cerebral blood flow and the rate of lactate transport through monocarboxylate transporters, which must be reduced in order to push glioma out of its domain of viability. Another factor is the intra arterial lactate, which must be increased. The last factor is pH, indeed a decrease of intra cellular pH could interfere with glioma growth. These reflections suggest that these four parameters could lead to new therapeutic strategies for the management of low grade gliomas.     

Expression of Measles Virus V Protein Is Associated with Pathogenicity and Control of Viral RNA Synthesis

Nonstructural proteins encoded by measles virus (MV) include the V protein which is translated from an edited P mRNA. V protein is not associated with intracellular or released viral particles and has recently been found to be dispensable for MV propagation in cell culture (H. Schneider, K. Kaelin, and M. A. Billeter, Virology 227:314–322, 1997). Using recombinant MVs (strain Edmonston [ED]) genetically engineered to overexpress V protein (ED-V+) or to be deficient for V protein (ED-V−), we found that in the absence of V both MV-specific proteins and RNAs accumulated to levels higher than those in the parental MV molecular clone (ED-tag), whereas MV-specific gene expression was strongly attenuated in human U-87 glioblastomas cells after infection with ED-V+. The titers of virus released from these cells 48 h after infection with either V mutant virus were lower than those from cells infected with ED-tag. Similarly, significantly reduced titers of infectious virus were reisolated from lung tissue of cotton rats (Sigmodon hispidus) after intranasal infection with both editing mutants compared to titers isolated from ED-tag-infected animals. In cell culture, expression of V protein led to a redistribution of MV N protein in doubly transfected Cos-7 cells, indicating that these proteins form heterologous complexes. This interaction was further confirmed by using a two-hybrid approach with both proteins expressed as Gal4 or VP16 fusion products. Moreover, V protein efficiently competed complexes formed between MV N and P proteins. These findings indicate that V protein acts to balance accumulation of viral gene products in cell culture, and this may be dependent on its interaction with MV N protein. Furthermore, expression of V protein may contribute to viral pathogenicity in vivo.     

Progress in understanding the biosynthesis of amylose

The storage of glucose in insoluble granules is a distinctive feature of plant cells. Biosynthesis of amylose, the minor low molecular mass fraction of starch occurs from ADP-glucose. This takes place within the polysaccharide matrix through the action of granule-bound starch synthase, the major protein associated with the granule. Recently, amylose has been successfully synthesized in vitro from purified granules. Two models have been proposed to explain the mechanism of amylose synthesis in plants. The first calls for priming of synthesis through small-size malto-oligosaccharides. The second suggests that glucans are extended by granule-bound starch synthase from a high molecular mass primer present within the granule. This extension is terminated through cleavage to produce amylose. This process is subsequently repeated to give several rounds of amylose synthesis.     

The distribution of the Hb Constant Spring gene in Southeast Asian populations

Summary The distribution of the hemoglobin Constant Spring (Hb CS) gene in eight populations in Southeast Asia (including Assam) was determined using oligonucleotide hybridization. Hb CS was absent in two Assamese populations with a high prevalence of Hb E. The Hb CS gene frequency was 0.033 in northern Thailand and near 0.01 in central Thailand and Cambodia. High frequencies, between 0.05 and 0.06, were observed in northeastern Thailand. The present data and a similar study in Laotians suggest that the Lao-speaking populations of the Mekong River basin in northeastern Thailand and Laos have the highest frequencies of the Hb CS gene in Southeast Asia.     

PROTEOLYTIC ENZYMES AND EXPERIMENTAL DEMYELINATION IN THE RAT AND MONKEY

Abstract— Visible lesions from monkeys with acute experimental allergic encephalomyelitis (EAE) induced by injection of purified myelin basic protein were assayed for acid proteinase, for a neutral proteinase at pH 6·5, and one lesion was measured for cathepsin A. Acid proteinase was increased to 152–176 per cent of levels in normal-appearing brain areas, neutral proteinase increased to 220–258 per cent, and the one lesion assayed for cathepsin A was 840 per cent of control. These enzymes were measured in the brain stem of Lewis rats with acute EAE as a result of basic protein injection and compared to Freund's adjuvant-injected controls. Acid proteinase was increased significantly to an average level of 128 per cent of control, the increase in neutral proteinase was not significant, and cathepsin A levels were 258 per cent of control, a highly significant increase. The rise in cathepsin A levels was not seen until the onset of paralytic symptoms. The brain stem of Wistar rats treated with whole spinal cord which show EAE in a milder form than the Lewis rat did not contain significantly higher enzyme levels than the control. The increases in acid proteinase and cathepsin A in brain stems were compared to levels of these enzymes in lymph nodes of EAE, Freund's adjuvant-injected controls and uninjected controls. The level of acid proteinase of lymph nodes/g protein did not change appreciably in the course of EAE development in the Lewis and Wistar rats and was about 3–4 times the activity in the brain stem. The cathepsin A in the inguinal lymph nodes of Wistar and Lewis rats injected with whole spinal cord in Freund's adjuvant increases to a level 2× that of the lymph nodes of the uninjected control. The cathepsin A levels in these activated lymph nodes was 6–8 × that of the control brain stem. The lymph nodes of Lewis and Wistar rats injected with Freund's adjuvant alone showed the same increase in cathepsin A as those from rats injected with spinal cord. The brain stem of rats undergoing severe demyelination as a result of chronic administration of triethyl tin did not show the enzyme increases. These results are compatible with the theory that proteolytic enzyme increases in EAE (and probably multiple sclerosis) are due to the invasion of mononuclear cells, some of which are probably lymphocytes. Whether or not these enzymes participate in the actual dissolution of myelin is unknown.     

Continuous rearing of the aster leafhopper, Macrosteles fascifrons, on a chemically defined diet

A holidic diet for feeding the aster leafhopper, Macrosteles fascifrons, was formulated. The amino acids, B-vitamins, and sucrose are less concentrated than in aphid diets. Cholesterol, at 5 mg/ml, is required for the last ecdysis. Although leafhoppers reared on this diet have poorer survival and shorter life span than those reared on plants, they produce more progeny. Leafhoppers reared on this diet have completed the ninth generation and the culture is still thriving.     

Fluctuations in human serum lipoproteins during the normal menstrual cycle

1. Lipoproteins were measured in sera from 11 young women having a similar environment and diet. Sera were obtained at weekly intervals over a 12-week period. The values of the lipoproteins during periods in the normal ovulatory cycle were compared to assess their relation to reported hormone concentrations in blood. 2. Only the 4–0s_f (HDL₂) (d 1·125 sodium chloride) fraction changed significantly; it increased at ovulation in ten of the 11 subjects and fell as menstruation approached. 3. There was greater variability in most of the low-density rather than the high-density lipoproteins within individuals. The lipoprotein class most characteristic for an individual was the 4–0s_f or HDL₂ fraction.     

Electroencephalographic Patterns in Chronic Pain: A Systematic Review of the Literature

The main objective of this study is to review and summarize recent findings on electroencephalographic patterns in individuals with chronic pain. We also discuss recent advances in the use of quantitative Electroencephalography (qEEG) for the assessment of pathophysiology and biopsychosocial factors involved in its maintenance over time. Data collection took place from February 2014 to July 2015 in PubMed, SciELO and PEDro databases. Data from cross-sectional studies and longitudinal studies, as well as clinical trials involving chronic pain participants were incorporated into the final analysis. Our primary findings related to chronic pain were an increase of theta and alpha EEG power at rest, and a decrease in the amplitude of evoked potentials after sensory stimulation and cognitive tasks. This review suggests that qEEG could be considered as a simple and objective tool for the study of brain mechanisms involved in chronic pain, as well as for identifying the specific characteristics of chronic pain condition. In addition, results show that qEEG probably is a relevant outcome measure for assessing changes in therapeutic studies.     

NF-κB in the regulation of epithelial homeostasis and inflammation

The IκB kinase/NF-κB signaling pathway has been implicated in the pathogenesis of several inflammatory diseases. Increased activation of NF-κB is often detected in both immune and non-immune cells in tissues affected by chronic inflammation, where it is believed to exert detrimental functions by inducing the expression of proinflammatory mediators that orchestrate and sustain the inflammatory response and cause tissue damage. Thus, increased NF-κB activation is considered an important pathogenic factor in many acute and chronic inflammatory disorders, raising hopes that NF-κB inhibitors could be effective for the treatment of inflammatory diseases. However, ample evidence has accumulated that NF-κB inhibition can also be harmful for the organism, and in some cases trigger the development of inflammation and disease. These findings suggested that NF-κB signaling has important functions for the maintenance of physiological immune homeostasis and for the prevention of inflammatory diseases in many tissues. This beneficial function of NF-κB has been predominantly observed in epithelial cells, indicating that NF-κB signaling has a particularly important role for the maintenance of immune homeostasis in epithelial tissues. It seems therefore that NF-κB displays two faces in chronic inflammation: on the one hand increased and sustained NF-κB activation induces inflammation and tissue damage, but on the other hand inhibition of NF-κB signaling can also disturb immune homeostasis, triggering inflammation and disease. Here, we discuss the mechanisms that control these apparently opposing functions of NF-κB signaling, focusing particularly on the role of NF-κB in the regulation of immune homeostasis and inflammation in the intestine and the skin.