Trak1 mutation disrupts GABA(A) receptor homeostasis in hypertonic mice

Hypertonia, which results from motor pathway defects in the central nervous system (CNS), is observed in numerous neurological conditions, including cerebral palsy, stroke, spinal cord injury, stiff-person syndrome, spastic paraplegia, dystonia and Parkinson disease. Mice with mutation in the hypertonic (hyrt) gene exhibit severe hypertonia as their primary symptom. Here we show that hyrt mutant mice have much lower levels of gamma-aminobutyric acid type A (GABA(A)) receptors in their CNS, particularly the lower motor neurons, than do wild-type mice, indicating that the hypertonicity of the mutants is likely to be caused by deficits in GABA-mediated motor neuron inhibition. We cloned the responsible gene, trafficking protein, kinesin binding 1 (Trak1), and showed that its protein product interacts with GABA(A) receptors. Our data implicate Trak1 as a crucial regulator of GABA(A) receptor homeostasis and underscore the importance of hyrt mice as a model for studying the molecular etiology of hypertonia associated with human neurological diseases.     

The use of complexes of lymphocyte antigens with antibody as immunogens for the preparation of antilymphocytic sera

Résumé Des complexes antigène-anticorps préparées par réaction du sérum antilymphocytaire (ALS) avec des lymphocytes ou avec des broyats lymphocytaires furent injectées aux lapins. Les ALS obtenu ainsi des lapins furent immunodépresseurs. Cette technique peut être utilisée pour obtenir des ALS plus specifique et moins toxique.

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Acknowlegments. We are indebted to our colleagues in the ALS Project Group of these Laboratories for much help and advice.     

Elevation of hepatic tyrosine 2-oxoglutarate aminotransferase in rats by 4-pentynoic acid,a hypoglycemic agent

Zusammenfassung 4-Pentinsäure, ein hypoglykämisches Mittel, vermehrte Leber-Tyrosinaminotransferase in intakten, nicht aber in adrenalektomierten Ratten.     

Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice

Minocycline mediates neuroprotection in experimental models of neurodegeneration. It inhibits the activity of caspase-1, caspase-3, inducible form of nitric oxide synthetase (iNOS) and p38 mitogen-activated protein kinase (MAPK). Although minocycline does not directly inhibit these enzymes, the effects may result from interference with upstream mechanisms resulting in their secondary activation. Because the above-mentioned factors are important in amyotrophic lateral sclerosis (ALS), we tested minocycline in mice with ALS. Here we report that minocycline delays disease onset and extends survival in ALS mice. Given the broad efficacy of minocycline, understanding its mechanisms of action is of great importance. We find that minocycline inhibits mitochondrial permeability-transition-mediated cytochrome c release. Minocycline-mediated inhibition of cytochrome c release is demonstrated in vivo, in cells, and in isolated mitochondria. Understanding the mechanism of action of minocycline will assist in the development and testing of more powerful and effective analogues. Because of the safety record of minocycline, and its ability to penetrate the blood-brain barrier, this drug may be a novel therapy for ALS.     

Biodiversity and biogeography of phages in modern stromatolites and thrombolites

Viruses, and more particularly phages (viruses that infect bacteria), represent one of the most abundant living entities in aquatic and terrestrial environments. The biogeography of phages has only recently been investigated and so far reveals a cosmopolitan distribution of phage genetic material (or genotypes). Here we address this cosmopolitan distribution through the analysis of phage communities in modern microbialites, the living representatives of one of the most ancient life forms on Earth. On the basis of a comparative metagenomic analysis of viral communities associated with marine (Highborne Cay, Bahamas) and freshwater (Pozas Azules II and Rio Mesquites, Mexico) microbialites, we show that some phage genotypes are geographically restricted. The high percentage of unknown sequences recovered from the three metagenomes (>97%), the low percentage similarities with sequences from other environmental viral (n = 42) and microbial (n = 36) metagenomes, and the absence of viral genotypes shared among microbialites indicate that viruses are genetically unique in these environments. Identifiable sequences in the Highborne Cay metagenome were dominated by single-stranded DNA microphages that were not detected in any other samples examined, including sea water, fresh water, sediment, terrestrial, extreme, metazoan-associated and marine microbial mats. Finally, a marine signature was present in the phage community of the Pozas Azules II microbialites, even though this environment has not been in contact with the ocean for tens of millions of years. Taken together, these results prove that viruses in modern microbialites display biogeographical variability and suggest that they may be derived from an ancient community.     

Reciprocal connections between substantia nigra and medullary reticular formation in the rat

Summary Electrophysiological analysis shows reciprocal connections between substantia nigra and medullary reticular formation (nucleus reticularis giganto celullaris). The nigro-reticular connection appears to be monosynaptic, as shown by antidromic activation, and comprises an ipsi and a contralateral component. Its effect is mainly inhibitory. The reticulonigral component produces mainly excitatory effects and includes fibres from nucleus giganto celullaris and nucleus parvocelullaris in the medullary reticular formation.This work was aided by a grant from CONICIT (projecto 31.26.S1-0412).     

Inhibition of monoamine oxidase by 3-amino-2-oxazolidinone and 2-hydroxy-ethylhydrazine

Zusammenfassung Die MAO-hemmende Aktivität von 3-Amino-2-Oxazolidinon und von 2-Hydroxy-Äthylhydrazin wird beschrieben.     

DEVELOPMENT MODEL OF TEXTILE COMPLEX -A CASE OF HONG KONG

Experience of industrialized countries revealed that there exists a generalized pattern in the development of textile complex in the world. A model proposed by Toyne et al. was found to be generally acceptable. However, the development of this model was primarily based on observation rather than supported by empirical evidence. It is the aim of this research, by using the generalized model, to determine the development pattern of the Hong Kong textile complex. It was revealed that the local development process had both conformance and inconsistencies when compared with the model. The inconsistencies, in particular, provide implications to the application of the model in describing the global situation.