The origin of spontaneous activity in the developing auditory system

Spontaneous activity in the developing auditory system is required for neuronal survival as well as the refinement and maintenance of tonotopic maps in the brain. However, the mechanisms responsible for initiating auditory nerve firing in the absence of sound have not been determined. Here we show that supporting cells in the developing rat cochlea spontaneously release ATP, which causes nearby inner hair cells to depolarize and release glutamate, triggering discrete bursts of action potentials in primary auditory neurons. This endogenous, ATP-mediated signalling synchronizes the output of neighbouring inner hair cells, which may help refine tonotopic maps in the brain. Spontaneous ATP-dependent signalling rapidly subsides after the onset of hearing, thereby preventing this experience-independent activity from interfering with accurate encoding of sound. These data indicate that supporting cells in the organ of Corti initiate electrical activity in auditory nerves before hearing, pointing to an essential role for peripheral, non-sensory cells in the development of central auditory pathways.     

Nitrogen cycle: what governs nitrogen loss from forest soils?

Nitrogen is lost as dissolved organic compounds in stream waters from unpolluted South American forests, but it is lost mainly as inorganic nitrate in streams flowing from North American forests that suffer nitrogen deposition from the atmosphere. From this it has been inferred that the standard thinking about how nature deals with nitrogen in soils and waters needs to be re-evaluated and that the conventional wisdom of how nitrogen is absorbed and released by plants must be wrong. We disagree, however, on the grounds that there are other, more likely interpretations of the new results.     

Antagonism by deoxyribosides of the inhibitory action of certain hydroxamic acids on deoxyribonucleic acid synthesis

Résumé L'action inhibitrice de l'hydroxyurée (HU) sur une synthèse de DNA peut être antagonisée par des déoxyribosides (dR). De même, un mélange de déoxyadénosine, de déoxyguanosine, et de déoxycytidine annule complètement l'action de l'acide oxanyl hydroxamique (OHA) et inverse, en partie, les effets de l'acide salicylhydroxamique (SHA) et de l'acide (dihydroxybenzoyl-2.3)-hydroxamique (DHB). Lorsqu'on ajoute de la thymidine à une solution de dR, le schéma général d'antagonisme est similaire. De plus, en présence des quatre dR, l'action de l'acétoxyoxamide (AOA) est en partie antagonisée. Il a été conclu que ces acides hydroxamiques, comme l'HU, interviennent, à un degré plus ou moins grand, avec réduction des ribosides.

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Aided by grant No. GM-13958 from the National Institutes of Health, United States Public Health Service.     

Subtractive proteomic mapping of the endothelial surface in lung and solid tumours for tissue-specific therapy

The molecular complexity of tissues and the inaccessibility of most cells within a tissue limit the discovery of key targets for tissue-specific delivery of therapeutic and imaging agents in vivo. Here, we describe a hypothesis-driven, systems biology approach to identifying a small subset of proteins induced at the tissue-blood interface that are inherently accessible to antibodies injected intravenously. We use subcellular fractionation, subtractive proteomics and bioinformatics to identify endothelial cell surface proteins exhibiting restricted tissue distribution and apparent tissue modulation. Expression profiling and gamma-scintigraphic imaging with antibodies establishes two of these proteins, aminopeptidase-P and annexin A1, as selective in vivo targets for antibodies in lungs and solid tumours, respectively. Radio-immunotherapy to annexin A1 destroys tumours and increases animal survival. This analytical strategy can map tissue- and disease-specific expression of endothelial cell surface proteins to uncover novel accessible targets useful for imaging and therapy.     

Vascular-specific growth factors and blood vessel formation

A recent explosion in newly discovered vascular growth factors has coincided with exploitation of powerful new genetic approaches for studying vascular development. An emerging rule is that all of these factors must be used in perfect harmony to form functional vessels. These new findings also demand re-evaluation of therapeutic efforts aimed at regulating blood vessel growth in ischaemia, cancer and other pathological settings.     

Forecasting Hourly Peak Call Volume for a Rural Electric Cooperative Call Center

This research forecasts peak call volume of a centralized after‐hours call center for rural electric cooperatives to help the call center determine staffing levels. A Gaussian copula is used to capture the dependence among non‐normal distributions. Using a centralized call center reduces costs by approximately 75% compared to having individual call centers at each cooperative. Adding cooperatives to the centralized call center is projected to further decrease costs per member. An out‐of‐sample forecasting exercise after the call center expanded validated the model's forecast that additional cooperatives could be added without a proportional increase in the peak number of calls. Copyright © 2011 John Wiley & Sons, Ltd.     

奇异的农作物

大家还记得芹菜事件的教训么？80年代中期，美国的芹菜培植者曾推崇过一种他们认为非常好的新品种，不仅抗虫性强，而且可以使产量显著提高。但是有一个小问题，触弄过此芹菜梗的人不久就开始为发生严重皮疹而抱怨。皮肤病学家发现，这种芹菜会不断分泌出扫若仑（psoralen），一种在阳光下会变成刺激物和诱变物的天然化学物质。实际上，人们全都搞错了，许多生物技术业内人士和政府食品管理机构官员（尤其是美国）如是说。到“基因食品”上了人们餐桌的时候，它并非只是同传统食物一样没有危险，而且在某些方面其实还更安全，因为有管理部门…