Degeneration of noradrenergic nerve terminals in submucous ganglia of the rat duodenum following treatment with 6-hydroxydopamine

Zusammenfassung Nachweis adrenerger Synapsen an Zellkörpern der duodenalen submukösen Ganglien von Ratten nach 6-Hydroxydopamin-Behandlung.

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Part of this work was done while I was on sabbatical leave in the Department of Anatomy, Monash University, in 1972, and I thank ProfessorG. C. Schofield for his kindness and encouragement during my stay there. Mr.H. L. Chan rendered invaluable technical assistance.     

Quantum simulation of ferrocytochrome c

The dramatic progress in the understanding of the dynamics of biomolecules has been largely fuelled by computer simulations based on the law of classical mechanics. However in some respects biomolecules are at the borders of the domain of applicability of classical mechanics. The role of quantum mechanical effects in biomolecular structure and function is therefore worth investigating. Here we present preliminary results from a quantum simulation of a protein and contrast them with results from full classical simulations. The most significant differences are found in motions of high frequency, such as bond stretching or the torsional oscillation of groups that bear hydrogen atoms. The amplitudes of such motions are significantly increased by the penetration of atoms into classically forbidden regions. These differences will directly influence the rates of such processes as proton and electron transfer.     

Potential aldose reductase inhibitors: 1,2,4-triazolidine-3,5-diones and 2-(3,4,5-trimethoxybenzoyl)-4,4-diethyl-3,5-isoxazolidinedione

1,2,4-Triazolidine-3,5-diones and the 3,5-isoxazolidinedione were, observed to be, potent inhibitors of rat lens aldose reductase activity. In vivo in streptozotocin-diabetic rats, selected agents at 20 mg/kg/day, orally for 21 days reduced significantly the sorbitol levels of rbc, lens and sciatic nerves, suggesting that these derivatives may have some usefulness to treat clinical complications of diabetes mellitus.     

Asymptotic properties of univariate sample k-means clusters

A random sample of sizeN is divided intok clusters that minimize the within clusters sum of squares locally. Some large sample properties of this k-means clustering method (ask approaches withN) are obtained. In one dimension, it is established that the sample k-means clusters are such that the within-cluster sums of squares are asymptotically equal, and that the sizes of the cluster intervals are inversely proportional to the one-third power of the underlying density at the midpoints of the intervals. The difficulty involved in generalizing the results to the multivariate case is mentioned.This research was supported in part by the National Science Foundation under Grant MCS75-08374. The author would like to thank John Hartigan and David Pollard for helpful discussions and comments.     

The effect of nicotine on ethanol-induced gastric ulcers in rats

Summary Nicotine, in concentrations of 5 and 25 g/ml drinking water, given ad libitum for 10 days, dose-dependently increased lesion formation and worsened ethanol-induced ulceration in rat stomachs. Daily fluid intake and b.wt gain were not adversely affected by nicotine pretreatment.The authors are grateful to Mr C.T. Luk for his skilled technical assistance.     

Depth of a strong jovian jet from a planetary-scale disturbance driven by storms

The atmospheres of the gas giant planets (Jupiter and Saturn) contain jets that dominate the circulation at visible levels. The power source for these jets (solar radiation, internal heat, or both) and their vertical structure below the upper cloud are major open questions in the atmospheric circulation and meteorology of giant planets. Several observations and in situ measurements found intense winds at a depth of 24 bar, and have been interpreted as supporting an internal heat source. This issue remains controversial, in part because of effects from the local meteorology. Here we report observations and modelling of two plumes in Jupiter's atmosphere that erupted at the same latitude as the strongest jet (23 degrees N). The plumes reached a height of 30 km above the surrounding clouds, moved faster than any other feature (169 m s(-1)), and left in their wake a turbulent planetary-scale disturbance containing red aerosols. On the basis of dynamical modelling, we conclude that the data are consistent only with a wind that extends well below the level where solar radiation is deposited.     

Innate immunity and intestinal microbiota in the development of Type 1 diabetes

Type 1 diabetes (T1D) is a debilitating autoimmune disease that results from T-cell-mediated destruction of insulin-producing beta-cells. Its incidence has increased during the past several decades in developed countries, suggesting that changes in the environment (including the human microbial environment) may influence disease pathogenesis. The incidence of spontaneous T1D in non-obese diabetic (NOD) mice can be affected by the microbial environment in the animal housing facility or by exposure to microbial stimuli, such as injection with mycobacteria or various microbial products. Here we show that specific pathogen-free NOD mice lacking MyD88 protein (an adaptor for multiple innate immune receptors that recognize microbial stimuli) do not develop T1D. The effect is dependent on commensal microbes because germ-free MyD88-negative NOD mice develop robust diabetes, whereas colonization of these germ-free MyD88-negative NOD mice with a defined microbial consortium (representing bacterial phyla normally present in human gut) attenuates T1D. We also find that MyD88 deficiency changes the composition of the distal gut microbiota, and that exposure to the microbiota of specific pathogen-free MyD88-negative NOD donors attenuates T1D in germ-free NOD recipients. Together, these findings indicate that interaction of the intestinal microbes with the innate immune system is a critical epigenetic factor modifying T1D predisposition.     

Towards a proteome-scale map of the human protein-protein interaction network

Systematic mapping of protein-protein interactions, or 'interactome' mapping, was initiated in model organisms, starting with defined biological processes and then expanding to the scale of the proteome. Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties, suggesting that a human interactome map will provide insight into development and disease mechanisms at a systems level. Here we describe an initial version of a proteome-scale map of human binary protein-protein interactions. Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of approximately 8,100 currently available Gateway-cloned open reading frames and detected approximately 2,800 interactions. This data set, called CCSB-HI1, has a verification rate of approximately 78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by approximately 70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins. This work represents an important step towards a systematic and comprehensive human interactome project.