6-Shogaol,an active constituent of ginger,attenuates neuroinflammation and cognitive deficits in animal models of dementia

Recently, increased attention has been directed towards medicinal extracts as potential new drug candidates for dementia. Ginger has long been used as an important ingredient in cooking and traditional herbal medicine. In particular, ginger has been known to have disease-modifying effects in Alzheimer's disease (AD). However, there is no evidence of which constituents of ginger exhibit therapeutic effects against AD. A growing number of experimental studies suggest that 6-shogaol, a bioactive component of ginger, may play an important role as a memory-enhancing and anti-oxidant agent against neurological diseases. 6-Shogaol has also recently been shown to have anti-neuroinflammatory effects in lipopolysaccharide (LPS)-treated astrocytes and animal models of Parkinson’s disease, LPS-induced inflammation and transient global ischemia. However, it is still unknown whether 6-shogaol has anti-inflammatory effects against oligomeric forms of the Aβ (AβO) in animal brains. Furthermore, the effects of 6-shogaol against memory impairment in dementia models are also yet to be investigated. In this study, we found that administration of 6-shogaol significantly reduced microgliosis and astrogliosis in intrahippocampal AβO-injected mice, ameliorated AβO and scopolamine-induced memory impairment, and elevated NGF levels and pre- and post-synaptic marker in the hippocampus. All these results suggest that 6-shogaol may play a role in inhibiting glial cell activation and reducing memory impairment in animal models of dementia.     

Spinal cord injury increases iron levels: catalytic production of hydroxyl radicals

This study used a weight drop impact injury model to explore the role of iron and the reality of iron-catalyzed hydroxyl radical ((*)OH) formation in secondary spinal cord injury (SCI). The time course of total extracellular iron was measured following SCI by microcannula sampling and atomic absorption spectrophotometry analysis. Immediately following SCI, the total iron concentration increased from an undetectable level to an average of 1.32 microM. The time course of SCI-induced (*)OH-generating catalytic activity in the cord was obtained by determining the ability of tissue homogenate to convert hydrogen peroxide to (*)OH and then measuring 2,3-dihydroxybenzoic acid, a hydroxylation product of salicylate. The concentration of 2,3-DHBA quickly and significantly increased (p <.001) and returned to sham level (p = 1) by 30 min post-SCI. Desferrioxamine (80 and 800 mg/kg body weight) significantly (p <.001) reduced the catalytic activity, suggesting that iron is the major contributor of the activity. Administering FeCl(3) (100 microM)/EDTA (0.5 mM) in ACSF into the cord through a dialysis fiber significantly increased SCI-induced (*)OH production in the extracellular space, demonstrating that Fe(3+) can catalyze (*)OH production in vivo. Our results support that iron-catalyzed (*)OH formation plays a role in the early stage of secondary SCI.     

Conserved substrate binding by chaperones in the bacterial periplasm and the mitochondrial intermembrane space

Mitochondria were derived from intracellular bacteria and the mitochondrial intermembrane space is topologically equivalent to the bacterial periplasm. Both compartments contain ATP-independent chaperones involved in the transport of hydrophobic membrane proteins. The mitochondrial TIM (translocase of the mitochondrial inner membrane) 10 complex and the periplasmic chaperone SurA were examined in terms of evolutionary relation, structural similarity, substrate binding specificity and their function in transporting polypeptides for insertion into membranes. The two chaperones are evolutionarily unrelated; structurally, they are also distinct both in their characteristics, as determined by SAXS (small-angle X-ray scattering), and in pairwise structural comparison using the distance matrix alignment (DALILite server). Despite their structural differences, SurA and the TIM10 complex share a common binding specificity in Pepscan assays of substrate proteins. Comprehensive analysis of the binding on a total of 1407 immobilized 13-mer peptides revealed that the TIM10 complex, like SurA, does not bind hydrophobic peptides generally, but that both chaperones display selectivity for peptides rich in aromatic residues and with net positive charge. This common binding specificity was not sufficient for SurA to completely replace TIM10 in yeast cells in vivo. In yeast cells lacking TIM10, when SurA is targeted to the intermembrane space of mitochondria, it binds translocating substrate proteins, but fails to completely transfer the substrate to the translocase in the mitochondrial inner membrane. We suggest that SurA was incapable of presenting substrates effectively to the primitive TOM (translocase of the mitochondrial outer membrane) and TIM complexes in early mitochondria, and was replaced by the more effective small Tim chaperone.     

A textbook history of animal behaviour

The history of animal behaviour research over the last 50 years has been marked by a decline in traditional ethology and an increase in the prominence of behavioural ecology. Here I examine these changes in the discipline of animal behaviour during the past 50 years as reflected in specialized behaviour textbooks and introductory textbooks for general biology courses. Prior to 1975, all the behaviour texts devoted far more coverage to ethological research on the proximate causes of behaviour than to research on the adaptive value of behavioural traits. After 1975, ultimate questions about adaptation received much more attention than they had previously. The change took place because of events in the mid-1960s, including W. D. Hamilton's solution to the evolutionary puzzle of altruism and the group selection debate involving V. C. Wynne-Edwards, G. C. Williams and D. Lack. The effect of these events was to encourage researchers to use sound adaptationist theory untainted by species-benefit thinking. The theory helped identify many new questions about the adaptive value of behavioural traits, stimulating workers to give as much weight to these issues as had previously been devoted to research into the physiology and development of behaviour. Although pure ethological research appeared to decline after 1975, in fact the major proximate concerns of ethology were simply taken on by cell biologists and neurophysiologists who used tools not available to the classic ethologist. The result was the development of neuroethology, which has flourished over the years. However, classic (pre-1975) ethological research still receives considerable coverage in many introductory biology textbooks, possibly because of the weight given these studies by W. T. Keeton in his influential textbook. None the less, ever since the 1980s, most biology textbooks have also discussed some of the fruits of adaptationist theory, especially Hamilton's explanation for altruism, thereby providing a more balanced treatment of proximate and ultimate issues than was once the case. Copyright 2003 The Association for the Study of Animal Behaviour. Published by Elsevier Science Ltd. All rights reserved.     

Two soluble glycosyltransferases glycosylate less efficiently in vivo than their membrane bound counterparts

Many Golgi glycosyltransferases are type II membrane proteins which are cleaved to produce soluble forms that are released from cells. Cho and Cummings recently reported that a soluble form of alpha1, 3- galactosyltransferase was comparable to its membrane bound counterpart in its ability to galactosylate newly synthesized glycoproteins (Cho,S.K. and Cummings,R.D. (1997) J. Biol. Chem., 272, 13622-13628). To test the generality of their findings, we compared the activities of the full length and soluble forms of two such glycosyltransferases, ss1,4 N-Acetylgalactosaminyltransferase (GM2/GD2/ GA2 synthase; GalNAcT) and beta galactoside alpha2,6 sialyltransferase (alpha2,6-ST; ST6Gal I), for production of their glycoconjugate products in vivo . Unlike the full length form of GalNAcT which produced ganglioside GM2 in transfected cells, soluble GalNAcT did not produce detectable GM2 in vivo even though it possessed in vitro GalNAcT activity comparable to that of full length GalNAcT. When compared with cells expressing full length alpha2,6-ST, cells expressing a soluble form of alpha2,6-ST contained 3-fold higher alpha2,6-ST mRNA levels and secreted 7-fold greater alpha2,6-ST activity as measured in vitro , but in striking contrast contained 2- to 4-fold less of the alpha2,6-linked sialic acid moiety in cellular glycoproteins in vivo . In summary these results suggest that unlike alpha1,3-galactosyltransferase the soluble forms of these two glycosyltransferases are less efficient at glycosylation of membrane proteins and lipids in vivo than their membrane bound counterparts.      

Use of the allogeneic TCR repertoire to enhance anti-tumor immunity

It is well established that antigen-specific T lymphocytes can inhibit tumor growth in humans and in mice, leading to complete tumor elimination in some cases. However, in many cases T cell immunity is unable to successfully control tumor progression. Since tumors are derived from normal tissues, most antigens are shared with normal tissues, although expression levels are usually elevated in malignant cells. Nevertheless, low-level expression in normal cells can be sufficient to render autologous T cells tolerant and thus unable to mount effective immune responses against tumors. Here, we review how allogeneic T cells can be used to isolate T cells that effectively recognise and kill tumor cells, but not normal cells with low level of antigen expression. The TCR of allogeneic T cells can be introduced into patient T cells to equip them with anti-tumor specificity that may not be present in the autologous T cell repertoire.     

Preliminary evaluation of non-native rainbow trout (Oncorhynchus mykiss) impact on the Cederberg ghost frog (Heleophryne depressa) in South Africa’s Cape Fold Ecoregion

We evaluated the impact of non-native rainbow trout Oncorhynchus mykiss on a population of endemic Cedarberg ghost frog Heleophryne depressa in the upper Krom River (Olifants-Doring River Catchment, Cape Fold Ecoregion). We compared H. depressa abundance (using kick-sampling and underwater video analysis) and environmental conditions between sites above and below a waterfall that marks the upper distribution limit of O. mykiss. Heleophryne depressa abundance was significantly greater above the waterfall than that below it, and, because there was no significant difference in measured environmental variables, O. mykiss presence is identified as the most likely explanation for the observed decrease in H. depressa abundance.