Mutation of TBCE causes hypoparathyroidism-retardation-dysmorphism and autosomal recessive Kenny-Caffey syndrome

The syndrome of congenital hypoparathyroidism, mental retardation, facial dysmorphism and extreme growth failure (HRD or Sanjad-Sakati syndrome; OMIM 241410) is an autosomal recessive disorder reported almost exclusively in Middle Eastern populations. A similar syndrome with the additional features of osteosclerosis and recurrent bacterial infections has been classified as autosomal recessive Kenny-Caffey syndrome (AR-KCS; OMIM 244460). Both traits have previously been mapped to chromosome 1q43-44 (refs 5,6) and, despite the observed clinical variability, share an ancestral haplotype, suggesting a common founder mutation. We describe refinement of the critical region to an interval of roughly 230 kb and identification of deletion and truncation mutations of TBCE in affected individuals. The gene TBCE encodes one of several chaperone proteins required for the proper folding of alpha-tubulin subunits and the formation of alpha-beta-tubulin heterodimers. Analysis of diseased fibroblasts and lymphoblastoid cells showed lower microtubule density at the microtubule-organizing center (MTOC) and perturbed microtubule polarity in diseased cells. Immunofluorescence and ultrastructural studies showed disturbances in subcellular organelles that require microtubules for membrane trafficking, such as the Golgi and late endosomal compartments. These findings demonstrate that HRD and AR-KCS are chaperone diseases caused by a genetic defect in the tubulin assembly pathway, and establish a potential connection between tubulin physiology and the development of the parathyroid.     

RNA aptamers as reversible antagonists of coagulation factor IXa

Many therapeutic agents are associated with adverse effects in patients. Anticoagulants can engender acute complications such as significant bleeding that increases patient morbidity and mortality. Antidote control provides the safest means to regulate drug action. For this reason, despite its known limitations and toxicities, heparin use remains high because it is the only anticoagulant that can be controlled by an antidote, the polypeptide protamine. To date, no generalizable strategy for developing drug-antidote pairs has been described. We investigated whether drug-antidote pairs could be rationally designed by taking advantage of properties inherent to nucleic acids to make antidote-controlled anticoagulant agents. Here we show that protein-binding oligonucleotides (aptamers) against coagulation factor IXa are potent anticoagulants. We also show that oligonucleotides complementary to these aptamers can act as antidotes capable of efficiently reversing the activity of these new anticoagulants in plasma from healthy volunteers and from patients who cannot tolerate heparin. This generalizable strategy for rationally designing a drug-antidote pair thus opens up the way for developing safer regulatable therapeutics.     

A nebula of gases from Io surrounding Jupiter

Several planetary missions have reported the presence of substantial numbers of energetic ions and electrons surrounding Jupiter; relativistic electrons are observable up to several astronomical units (au) from the planet. A population of energetic (>30[?]keV) neutral particles also has been reported, but the instrumentation was not able to determine the mass or charge state of the particles, which were subsequently labelled energetic neutral atoms. Although images showing the presence of the trace element sodium were obtained, the source and identity of the neutral atoms---and their overall significance relative to the loss of charged particles from Jupiter's magnetosphere---were unknown. Here we report the discovery by the Cassini spacecraft of a fast (>103[?]km[?]s-1) and hot magnetospheric neutral wind extending more than 0.5[?]au from Jupiter, and the presence of energetic neutral atoms (both hot and cold) that have been accelerated by the electric field in the solar wind. We suggest that these atoms originate in volcanic gases from Io, undergo significant evolution through various electromagnetic interactions, escape Jupiter's magnetosphere and then populate the environment around the planet. Thus a 'nebula' is created that extends outwards over hundreds of jovian radii.     

High-power terahertz radiation from relativistic electrons

Terahertz (THz) radiation, which lies in the far-infrared region, is at the interface of electronics and photonics. Narrow-band THz radiation can be produced by free-electron lasers and fast diodes. Broadband THz radiation can be produced by thermal sources and, more recently, by table-top laser-driven sources and by short electron bunches in accelerators, but so far only with low power. Here we report calculations and measurements that confirm the production of high-power broadband THz radiation from subpicosecond electron bunches in an accelerator. The average power is nearly 20 watts, several orders of magnitude higher than any existing source, which could enable various new applications. In particular, many materials have distinct absorptive and dispersive properties in this spectral range, so that THz imaging could reveal interesting features. For example, it would be possible to image the distribution of specific proteins or water in tissue, or buried metal layers in semiconductors; the present source would allow full-field, real-time capture of such images. High peak and average power THz sources are also critical in driving new nonlinear phenomena and for pump-probe studies of dynamical properties of materials.     

The motion of Mars in Egyptian planetary tables

B. L. van der Waerden's thesis, that the motion of Mars in the Stobart Tables has been computed by linear methods based on the assumption of a piece-wise constant velocity, is discussed in this paper, and some further evidence presented.     

Forecasting marginal costs of a multiple-output production technology

This paper presents the results of fitting a scaled translog restricted profit function to ‘pseudo’-data formed by repeated runs of a large linear programming model of domestic and international refining. The translog approximation is designed to estimate the marginal cost of producing eight petroleum products given the amounts of each product demanded and the price of crude oil. We test the model against out-of-sample data from the refinery model and historical data. The model is used in the US Department of Energy's Annual Energy Outlook forecasting system.     

Lipase activity in insect flight muscle

Zusammenfassung Die Lipaseaktivität von wässerigen Extrakten der Libelle (Pentala flavescens), der Heuschrecke (Schistocerca gregaria) und der Hummel (Xylocopa sp.) wurde manometrisch festgestellt, unter Verwendung von Tributyrin als Substrat. Die höchste Lipaseaktivität wurde in der Libelle gefunden, die niedrigste in der Hummel. Der hohe Gehalt der Flugmuskulatur der Insekten an Lipase wird in Zusammenhang gebracht mit der Benutzung von Fett als Brennstoff bei dauernder Muskeltätigkeit. Die Lipaseaktivität in der Flugmuskulatur der Libelle und der Heuschrecke wird histochemisch nachgewiesen mit dem Verfahren nachGomori, unter Verwendung von «Tween 80» als Substrat.