Role of the cerebellum in the visual guidance of movement

Mathematicians, control engineers and information technologists are beginning to take a greater interest in neuroscience. They are perhaps starting to realize that they may be able to learn a few tricks from nature with which to improve their machines. At the same time there is a good chance that neuroscientists will benefit from their input of fresh ideas and techniques with which to attack the problems of understanding neural processing. One area of the brain which seems particularly promising in these respects is the cerebellum.     

Aluminium in Alzheimer’s disease: are we still at a crossroad?

Aluminium, an environmentally abundant non-redox trivalent cation has long been implicated in the pathogenesis of Alzheimers disease (AD). However, the definite mechanism of aluminium toxicity in AD is not known. Evidence suggests that trace metal homeostasis plays a crucial role in the normal functioning of the brain, and any disturbance in it can exacerbate events associated with AD. The present paper reviews the scientific literature linking aluminium with AD. The focus is on aluminium levels in brain, region-specific and subcellular distribution, its relation to neurofibrillary tangles, amyloid beta, and other metals. A detailed mechanism of the role of aluminium in oxidative stress and cell death is highlighted. The importance of complex speciation chemistry of aluminium in relation to biology has been emphasized. The debatable role of aluminium in AD and the cross-talk between aluminium and genetic susceptibility are also discussed. Finally, it is concluded based on extensive literature that the neurotoxic effects of aluminium are beyond any doubt, and aluminium as a factor in AD cannot be discarded. However, whether aluminium is a sole factor in AD and whether it is a factor in all AD cases still needs to be understood.Received 22 July 2004; received after revision 3 September 2004; accepted 16 September 2004     

Hormone binding globulins undergo serpin conformational change in inflammation

A surprising recent finding is that thyroxine binding globulin (TBG) and cortisol binding globulin (CBG), are members of the serine protease inhibitor (serpin) superfamily. Apparently evolution has completely adapted the serpin structure for its new role in these proteins as a transport agent, as there is no evidence of any retained protease inhibitory activity. This drastic change in function raises the question as to why such a complex molecular framework has been selected for the relatively simple task of hormone transport? To function as inhibitors the serpins have a native stressed (S) conformation that makes them vulnerable to proteolytic cleavage, the cleavage being accompanied by an irreversible transition to a stable relaxed (R) form. We demonstrate here that TBG and CBG have retained the stressed native structure typical of the inhibitor members of the family and we provide evidence that the S-R transition has been adapted to allow altered hormone delivery at inflammatory sites.     

Seismology: speed and size of the Sumatra earthquake

Our seismological results reveal that Indonesia's devastating Sumatra-Andaman earthquake on 26 December 2004 was 2.5 times larger than initial reports suggested--second only to the 1960 Chilean earthquake in recorded magnitude. They indicate that it slowly released its energy by slip along a 1,200-km fault, generating a long rupture that contributed to the subsequent tsunami. Now that the entire rupture zone has slipped, the strain accumulated from the subduction of the Indian plate beneath the Burma microplate has been released, and there is no immediate danger of a similar tsunami being generated on this part of the plate boundary, although large earthquakes on segments to the south still present a threat.     

NF-kappaB functions as a tumour promoter in inflammation-associated cancer

The causes of sporadic human cancer are seldom recognized, but it is estimated that carcinogen exposure and chronic inflammation are two important underlying conditions for tumour development, the latter accounting for approximately 20% of human cancer. Whereas the causal relationship between carcinogen exposure and cancer has been intensely investigated, the molecular and cellular mechanisms linking chronic inflammation to tumorigenesis remain largely unresolved. We proposed that activation of the nuclear factor kappaB (NF-kappaB), a hallmark of inflammatory responses that is frequently detected in tumours, may constitute a missing link between inflammation and cancer. To test this hypothesis, we studied the Mdr2-knockout mouse strain, which spontaneously develops cholestatic hepatitis followed by hepatocellular carcinoma, a prototype of inflammation-associated cancer. We monitored hepatitis and cancer progression in Mdr2-knockout mice, and here we show that the inflammatory process triggers hepatocyte NF-kappaB through upregulation of tumour-necrosis factor-alpha (TNFalpha) in adjacent endothelial and inflammatory cells. Switching off NF-kappaB in mice from birth to seven months of age, using a hepatocyte-specific inducible IkappaB-super-repressor transgene, had no effect on the course of hepatitis, nor did it affect early phases of hepatocyte transformation. By contrast, suppressing NF-kappaB inhibition through anti-TNFalpha treatment or induction of IkappaB-super-repressor in later stages of tumour development resulted in apoptosis of transformed hepatocytes and failure to progress to hepatocellular carcinoma. Our studies thus indicate that NF-kappaB is essential for promoting inflammation-associated cancer, and is therefore a potential target for cancer prevention in chronic inflammatory diseases.     

Seismology: tectonic strain in plate interiors?

It is not fully understood how or why the inner areas of tectonic plates deform, leading to large, although infrequent, earthquakes. Smalley et al. offer a potential breakthrough by suggesting that surface deformation in the central United States accumulates at rates comparable to those across plate boundaries. However, we find no statistically significant deformation in three independent analyses of the data set used by Smalley et al., and conclude therefore that only the upper bounds of magnitude and repeat time for large earthquakes can be inferred at present.