The high copper tolerance of Candida albicans is mediated by a P-type ATPase.

The pathogenic yeast Candida albicans has higher resistance than the baker's yeast Saccharomyces cerevisiae to elevated concentrations of copper. To understand the basis of this differential resistance, we performed a functional screen for C. albicans genes involved in copper detoxification. Here, we report the isolation of two such genes: a metallothionein, CaCUP1, and a copper-transporting P-type ATPase, CaCRP1. Both genes are induced by extracellular copper. Gene disruptions indicated that the copper extrusion pump is responsible for the unusual resistance of C. albicans to copper, whereas the metallothionein is responsible for the residual copper resistance of the Cacrp1Delta mutant. We show further that under acidic and anaerobic conditions, such as prevail in the natural niche of C. albicans, the digestive tract of animals, CaCRP1 function becomes essential for survival in the presence of even very low copper concentrations. These observations suggest that copper in the gastrointestinal tract may present a toxic challenge to which enteric organisms had to adapt.

Degradation of the transcription factor Gcn4 requires the kinase Pho85 and the SCF(CDC4) ubiquitin-ligase complex.

Gcn4, a yeast transcriptional activator that promotes the expression of amino acid and purine biosynthesis genes, is rapidly degraded in rich medium. Here we report that SCF(CDC4), a recently characterized protein complex that acts in conjunction with the ubiquitin-conjugating enzyme Cdc34 to degrade cell cycle regulators, is also necessary for the degradation of the transcription factor Gcn4. Degradation of Gcn4 occurs throughout the cell cycle, whereas degradation of the known cell cycle substrates of Cdc34/SCF(CDC4) is cell cycle regulated. Gcn4 ubiquitination and degradation are regulated by starvation for amino acids, whereas the degradation of the cell cycle substrates of Cdc34/SCF(CDC4) is unaffected by starvation. We further show that unlike the cell cycle substrates of Cdc34/SCF(CDC4), which require phosphorylation by the kinase Cdc28, Gcn4 degradation requires the kinase Pho85. We identify the critical target site of Pho85 on Gcn4; a mutation of this site stabilizes the protein. A specific Pho85-Pcl complex that is able to phosphorylate Gcn4 on that site is inactive under conditions under which Gcn4 is stable. Thus, Cdc34/SCF(CDC4) activity is constitutive, and regulation of the stability of its various substrates occurs at the level of their phosphorylation.

Evanescent field sensors with periodically segmented waveguides.

An evanescent field-sensing configuration, based on a periodically segmented waveguide, is proposed and analyzed. It has advantages over existing configurations that relate to its simple realization (in single-step lithography). The sensitivity and operating point can be controlled easily with geometric parameters alone, which facilitates realization of more complex sensing arrays.

Dysembryoplastic neuroepithelial tumor: a curable cause of seizures.

Dysembryoplastic neuroepithelial tumor (DNT) was first characterized in 1988 by Daumas-Duport and Scheithauer [1], who described 39 cases in children with morphologically distinct brain tumors. Partial complex seizures (PCSs), well-defined neuroimages, and typical pathologic findings were characteristic. Surgical resection of the tumor was usually curative. We present a new case of a child with PCSs who was diagnosed and treated for DNT. The clinical presentation and the difficulties of the differential diagnosis are discussed.

Molecular identification of Candida albicans.

The benomyl resistant gene (BenR) found in Candida albicans, but not in other species of Candida, was used as a probe for the identification of C. albicans in clinical specimens. The utility of this probe to detect this species was demonstrated by Southern and dot-blot analysis, and by PCR. The possible use of this gene in C. albicans typing by the RFLP method is also demonstrated.

Second-harmonic generation in Bragg-resonant quasi-phase-matched periodically segmented waveguides.

Second-harmonic generation in Bragg-resonant quasi-phase-matched periodically segmented waveguides is studied experimentally and theoretically. At resonance, a deep spectral valley appears in the quasi-phase-matching curve. Nevertheless, in practice, the conversion efficiency is significant, in spite of this effect, because of reduced reflections, especially at 2omega. The mechanism behind this reduction seems to be small random variation in the location and shape of the domain boundaries.

Periodically segmented waveguides in Ti:LiNbO(3).

Periodically segmented waveguides with periods of few tens of micrometers and nonconnected segments are studied experimentally in Ti:LiNbO(3). The near-field patterns were found to expand with decreasing duty cycle but to be independent of the segmentation period. The measured segmentation losses vary between 0.5 and 2.5 dB/cm, depending on the period and the duty cycle. These results agree with a simple numerical model, based on two loss mechanisms: waveguide segmentation and surface relief related to Ti indiffusion.

Very low-loss Y-junction power divider.

The design of an efficient wide-angle dielectric optical waveguide Y-junction power divider is outlined. The method has several degrees of freedom that can be used to optimize the device's performance to achieve minimization of the radiation loss for a specified mode at the input and equalization of the modal losses in a dual-mode device.

Thrombopoietic activity in preterm newborns and infants.

Platelet count and thrombopoietic activity were investigated in preterm infants at birth and during their first four months of life. Thrombopoiesis stimulating factor activity in cord serum was significantly lower than that of adults and of the respective mothers. No difference was noted between thrombopoietic activity in cord serum in the various gestational ages studied--that is, 24 through 39 weeks. Preterm infants followed during their first four months of life showed a mean platelet count significantly higher than that observed in term infants at the respective age. Furthermore, thrombocytosis was found in premature thriving infants at the age of 1 and 2 months. It is suggested that this thrombocytosis is responsible for the low thrombopoietic activity observed in these infants during their first four months of life.

Thrombopoietic activity in newborn infants.

Platelet count and thrombopoietic activity were investigated in newborns and in infants during their first 4 months of life. Four-day-old newborns, although not thrombocytopenic, showed a significantly reduced platelet count as compared to that of control adults. Furthermore, a significantly lower thrombopoietic activity was found in the sera of newborns compared to that in the sera of adults. In addition, the thrombopoiesis-stimulating factor (TSF) activity in cord serum was significantly lower than that in the mothers' sera. Since 7 of 37 newborns examined in the present study showed a very low TSF activity, lower than that found in the saline controls, the possibility that an inhibitor for thrombopoiesis exists in the newborns is suggested and discussed. The follow-up study revealed a low TSF activity in the sera of 1-month-old infants followed by a gradually increased activity, reaching in the 4th month levels similar to those of adults. Concomitantly with the rise in TSF activity in the serum, an increased platelet count was observed.

Middle ear mucosa and secretory otitis media.

Recent investigations have identified the viscous middle ear effusion in secretory otitis media (S.O.M.) as being of the same nature as true mucus--the "backbone" of which is glycoprotein. The source of the mucus is mucus-producing cells in greater number than found in the normal middle ear lining. The pathological state which leads to excessive mucus production and maturation of numerous mucus cells is an inflammation associated with deficient ventilation of the middle ear. In the presence of inflammation, especially when CO2 tension is high, mucosal stem cells differentiate metaplastically into numerous mucus-producing cells, as demonstrated by us in tissue cultures. The higher CO2 tension in S.O.M. is due to eustacian tube insufficiency (not blockage) which is a smaller than normal amount of air introduced into the middle ear per unit of time. Ventilating tubes restore CO2 tension to normal and equalize the slight barometric negative pressure (average 3.35 H2O)--the latter being related to mucociliary clearance. Evidence for an allergic factor as a pathogen is also not available. The mucus in the middle ear is probably not noxious by itself and ears should be ventilated surgically only when hearing is below social level perception. Most S.O.M. ears will clear sooner or later spontaneously. A minority of these ears will progress with time into atelectatic ears and some might perforate later on.