Rapid-time-course miniature and evoked excitatory currents at cerebellar synapses in situ.

Neurotransmission from mossy fibre terminals onto cerebellar granule cells is almost certainly mediated by L-glutamate. By taking advantage of the small soma size, limited number of processes and short dendrite length of granule cells, we have obtained high-resolution recordings of spontaneous miniature excitatory postsynaptic currents (m.e.p.s.cs) and evoked currents in thin cerebellar slices. Miniature currents have a similar time-course and pharmacology to evoked currents and consist of an exceptionally fast non-NMDA (N-methyl-D-aspartate) component (measured rise-time, 200 microseconds; estimated pre-filtered rise-time less than 100 microseconds; decay time constant, tau = 1.0 ms), followed by 50 pS NMDA channel openings that are directly resolvable. We could find no evidence for the recent proposal that miniature currents in granule cells are mediated solely by NMDA channels with a novel time course. The non-NMDA receptor component of m.e.p.s.cs has a skewed amplitude distribution, which suggests potential complications for quantal analysis. The difference in time course between the m.e.p.s.cs reported here and other synaptic currents in the brain could reflect differences in synaptic function or electrotonic filtering; the relative contribution of these possibilities has yet to be established.     

Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome.

The inherited osteolyses or 'vanishing bone' syndromes are a group of rare disorders of unknown etiology characterized by destruction and resorption of affected bones. The multicentric osteolyses are notable for interphalangeal joint erosions that mimic severe juvenile rheumatoid arthritis (OMIMs 166300, 259600, 259610 and 277950). We recently described an autosomal recessive form of multicentric osteolysis with carpal and tarsal resorption, crippling arthritic changes, marked osteoporosis, palmar and plantar subcutaneous nodules and distinctive facies in a number of consanguineous Saudi Arabian families. We localized the disease gene to 16q12-21 by using members of these families for a genome-wide search for homozygous-by-descent microsatellite markers. Haplotype analysis narrowed the critical region to a 1.2-cM region that spans the gene encoding MMP-2 (gelatinase A, collagenase type IV; (ref. 3). We detected no MMP2 enzymatic activity in the serum or fibroblasts of affected family members. We identified two family-specific homoallelic MMP2 mutations: R101H and Y244X. The nonsense mutation effects a deletion of the substrate-binding and catalytic sites and the fibronectin type II-like and hemopexin/TIMP2 binding domains. Based on molecular modeling, the missense mutation disrupts hydrogen bond formation within the highly conserved prodomain adjacent to the catalytic zinc ion.     

应用量子力学

量子力学是当前物理学及其相关科学的重要科学分支，也是当前许多新科学技术中的重要应用的基础。本书包含了现代新科学技术工程师所需要的量子力学方面的新材料，如研究和了解原子核、原子、分子和固体材料，以及激光器和其他量子光学器件所需要的科学资料等。     

Changes in glycosaminoglycan sulfation and protein kinase C subcellular distribution during differentiation of the human colon tumor cell line Caco-2

Summary During the spontaneous differentiation (day 5 to day 15 of the culture) of Caco-2 cells, the sulfation of cell layer glycosaminoglycans increased, whereas protein kinase C activity was concomitantly redistributed from the membrane to the cytosol. The protein kinase C activators, 4-phorbol 12-myristate, 13-acetate and 1,2-dioctanoyl-glycerol inhibited glycosaminoglycan sulfation. By contrast, 4-phorbol 12, 13 didecanoate was ineffective.These results suggest that membrane-bound PKC may exert a modulatory effect on glycosaminoglycan sulfation, and this effect is gradually attenuated as Caco-2 cell differentiation progresses.     

Chemical ecology of oviposition in phytophagous insects

Summary Selection of a suitable site for oviposition by phytophagous insects is critical for successful development of the offspring. The behavioral events leading to oviposition are mediated to a large extent by chemical cues associated with potential host plants. Orientation and landing are primarily guided by volatile constituents of a plant, whereas assessment of a leaf surface depends on contact stimuli. Chemical mechanisms that ensure adequate spacing of progeny on limited resources include the production of oviposition-deterring pheromones as well as recognition of plant constituents released as a result of previous damage. Perception of chemical cues that affects oviposition involves receptors on antennae, tarsi, mouthparts or the ovipositor. Complex behavior such as tarsal drumming or stem runs may serve to provide increased receptor contact with chemical stimuli. Abiotic and biotic environmental factors often influence the production or release of behavior-modifying chemicals by a plant, and therefore affect oviposition preferences. Plant chemistry may be involved in associative learning, but may also lead to mistakes. Thus a clear correlation between oviposition preference and offspring success does not always exist.     

Goniothalamicin and annonacin: Bioactive acetogenins fromGoniothalamus giganteus (Annonaceae)

Summary Using brine shrimp lethality for activity-directed fractionation, goniothalamicin (I), a new tetrahydroxy-mono-tetrahydrofuran fatty acid -lactone (acetogenin), has been isolated from ethanolic extracts of the stem bark ofGoniothalamus giganteus Hook. f., Thomas (Annonaceae). This novel compound was found to be cytotoxic and insecticidal and inhibited the formation of crown gall tumors on potato discs. Annonacin (II), the only other reported mono-tetrahydrofuran acetogenin, was also isolated; the previously reported 9ASK (astrocytoma reversal) activity ofII was confirmed, andII is now also found to be weakly active against 3PS murine leukemia.     

Pharmacodynamic profile of CQP 201-403, a novel 8α-amino-ergoline

Summary The profile of action in animals of CQP 201-403, a novel 8-amino-ergoline, is in most aspects that of a very potent dopaminomimetic, both as a prolactin secretion inhibitor, and at the levels of the CNS and the cardiovascular system. Qualitatively CQP 201-403 differs slightly from bromocriptine and apomorphine in its effects on the CNS (no influence on serotonin metabolism in the rat cortex; induction of masculine mounting behavior in rats) and the cardiovascular system of the dog (reflex tachycardia in response to a blood-pressure fall). In man the new compound proved to be highly active in lowering prolactin serum levels and to be more potent than bromocriptine (Parlodel^®).In memory of Dr Annemarie Closse, who died 14 June 1987.     

Free R value: a novel statistical quantity for assessing the accuracy of crystal structures

The determination of macromolecular structure by crystallography involves fitting atomic models to the observed diffraction data. The traditional measure of the quality of this fit, and presumably the accuracy of the model, is the R value. Despite stereochemical restraints, it is possible to overfit or 'misfit' the diffraction data: an incorrect model can be refined to fairly good R values as several recent examples have shown. Here I propose a reliable and unbiased indicator of the accuracy of such models. By analogy with the cross-validation method of testing statistical models I define a statistical quantity (R(free) (T) that measures the agreement between observed and computed structure factor amplitudes for a 'test' set of reflections that is omitted in the modelling and refinement process. As examples show, there is a high correlation between R(free) (T) and the accuracy of the atomic model phases. This is useful because experimental phase information is usually inaccurate, incomplete or unavailable. I expect that R(free) (T) will provide a measure of the information content of recently proposed models of thermal motion and disorder, time-averaging and bulk solvent.     

The dead-end elimination theorem and its use in protein side-chain positioning

The prediction of a protein's tertiary structure is still a considerable problem because the huge amount of possible conformational space1 makes it computationally difficult. With regard to side-chain modelling, a solution has been attempted by the grouping of side-chain conformations into representative sets of rotamers2??. Nonetheless, an exhaustive combinatorial search is still limited to carefully indentified packing units?? containing a limited number of residues. For larger systems other strategies had to be developed, such as the Monte Carlo Procedure?? and the genetic algorithm and clustering approach?. Here we present a theorem, referred to as the 'dead-end elimination' theorem, which imposes a suitable condition to identify rotamers that cannot be members of the global minimum energy conformation. Application of this theorem effectively controls the computational explosion of the rotamer combinatorial problem, thereby allowing the determination of the global minimum energy conformation of a large collection of side chains.