Gene identification for the cblD defect of vitamin B12 metabolism

Background Vitamin B12 (cobalamin) is an essential cofactor in several metabolic pathways. Intracellular conversion of cobalamin to its two coenzymes, adenosylcobalamin in mitochondria and methylcobalamin in the cytoplasm, is necessary for the homeostasis of methylmalonic acid and homocysteine. Nine defects of intracellular cobalamin metabolism have been defined by means of somatic complementation analysis. One of these defects, the cblD defect, can cause isolated methylmalonic aciduria, isolated homocystinuria, or both. Affected persons present with multisystem clinical abnormalities, including developmental, hematologic, neurologic, and metabolic findings. The gene responsible for the cblD defect has not been identified. Methods We studied seven patients with the cblD defect, and skin fibroblasts from each were investigated in cell culture. Microcell-mediated chromosome transfer and refined genetic mapping were used to localize the responsible gene. This gene was transfected into cblD fibroblasts to test for the rescue of adenosylcobalamin and methylcobalamin synthesis. Results The cblD gene was localized to human chromosome 2q23.2, and a candidate gene, designated MMADHC (methylmalonic aciduria, cblD type, and homocystinuria), was identified in this region. Transfection of wild-type MMADHC rescued the cellular phenotype, and the functional importance of mutant alleles was shown by means of transfection with mutant constructs. The predicted MMADHC protein has sequence homology with a bacterial ATP-binding cassette transporter and contains a putative cobalamin binding motif and a putative mitochondrial targeting sequence. Conclusions Mutations in a gene we designated MMADHC are responsible for the cblD defect in vitamin B12 metabolism. Various mutations are associated with each of the three biochemical phenotypes of the disorder

Habitat requirements and ecological niche of two cryptic amphipod species at landscape and local scales

Cryptic species are phylogenetically diverged taxa that are morphologically indistinguishable and may differ in their ecological and behavioral requirements. This may have important implications for ecosystem services and conservation of biodiversity. We investigated whether two ecologically important cryptic species of the freshwater amphipod Gammarus fossarum (types A and B) are associated with different habitats. We collected data on their occurrence at both the landscape scale (large watersheds) and at the local scale (river reach) to compare macro- and microscale environmental parameters associated with their presence. Analysis of the landscape scale data showed that occurrence of types A and B differ with respect to watershed and river size and, interestingly, human impact on river ecomorphology. Whereas type B was mainly found in less forested areas with higher human impact, type A showed the opposite occurrence pattern. Analyses of the local scale data suggested that habitats occupied by type A were characterized by larger gravel, larger stones and less macrophytes than habitats occupied by type B. The landscape and local data set showed contradicting patterns with regard to stream size. Overall, the observed differences between the two types of G. fossarum most likely reflect ecological differences between them, but alternative explanations (e.g., historical colonization processes) cannot be completely ruled out. Our study underlines that common cryptic species can differ in their ecology and response to anthropogenic influence. Such differences in habitat requirements among difficult-to-identify taxa present a challenge for biodiversity and ecosystem management. Our results emphasize the importance of conservative and precautionary approaches in maintenance of habitat diversity and environmental heterogeneity

Robust polarization-based quantum key distribution over collective-noise channel

We present two polarization-based protocols for quantum key distribution. The protocols encode key bits in noiseless subspaces or subsystems, and so can function over a quantum channel subjected to an arbitrary degree of collective noise, as occurs, for instance, due to rotation of polarizations in an optical fiber. These protocols can be implemented using only entangled photon-pair sources, single-photon rotations, and single-photon detectors. Thus, our proposals offer practical and realistic alternatives to existing schemes for quantum key distribution over optical fibers without resorting to interferometry or two-way quantum communication, thereby circumventing, respectively, the need for high precision timing and the threat of Trojan horse attacks.Comment: Minor changes, added reference

Ceftriaxone acts synergistically with levofloxacin in experimental meningitis and reduces levofloxacin-induced resistance in penicillin-resistant pneumococci

Ceftriaxone acted synergistically with levofloxacin in time-killing assays in vitro over 8 h against two penicillin-resistant pneumococcal strains (WB4 and KR4; MIC of penicillin: 4 mg/L). Synergy was confirmed with the chequerboard method, showing FIC indices of 0.25. In the experimental rabbit meningitis model, ceftriaxone (1× 125 mg/kg) was slightly less bactericidal (-0.30 Δlog10 cfu/mL.h) compared with levofloxacin (-0.45 Δlog10 cfu/mL.h) against the penicillin-resistant strain WB4. The combination therapy (levofloxacin and ceftriaxone) was significantly superior (-0.64 Δlog10 cfu/mL.h) to either monotherapy. In cycling experiments in vitro, the addition of ceftriaxone at a sub-MIC concentration (1/16 MIC) reduced levofloxacin-induced resistance in the two strains KR4 and WB4. After 12 cycles with levofloxacin monotherapy, the MIC increased 64-fold in both strains versus a 16-fold increase with the combination (levofloxacin + ceftriaxone 1/16 MIC). In both strains, levofloxacin-induced resistance was confirmed by mutations detected in the genes parC and gyrA, encoding for subunits of topoisomerase IV and gyrase, respectively. The addition of ceftriaxone suppressed mutations in parC but led to a new mutation in parE in both strain

Diodes with Breakdown Voltages Enhanced by the Metal-Insulator Transition of LaAlO3_3-SrTiO3_3 Interfaces

Using the metal-insulator transition that takes place as a function of carrier density at the LaAlO$_3$-SrTiO$_3$ interface, oxide diodes have been fabricated with room-temperature breakdown voltages of up to 200 V. With applied voltage, the capacitance of the diodes changes by a factor of 150. The diodes are robust and operate at temperatures up to 270 C

Description of a quantum convolutional code

We describe a quantum error correction scheme aimed at protecting a flow of quantum information over long distance communication. It is largely inspired by the theory of classical convolutional codes which are used in similar circumstances in classical communication. The particular example shown here uses the stabilizer formalism, which provides an explicit encoding circuit. An associated error estimation algorithm is given explicitly and shown to provide the most likely error over any memoryless quantum channel, while its complexity grows only linearly with the number of encoded qubits.Comment: 4 pages, uses revtex4. Minor correction in the encoding and decoding circuit

Meropenem Prevents Levofloxacin-Induced Resistance in Penicillin-Resistant Pneumococci and Acts Synergistically with Levofloxacin in Experimental Meningitis

The aim of the present study was to investigate the potential synergy between meropenem and levofloxacin in vitro and in experimental meningitis and to determine the effect of meropenem on levofloxacin-induced resistance in vitro. Meropenem increased the efficacy of levofloxacin against the penicillin-resistant pneumococcal strain KR4 in time-killing assays in vitro and acted synergistically against a second penicillin-resistant strain WB4. In the checkerboard, only an additive effect (FIC indices: 1.0) was observed for both strains. In cycling experiments in vitro, levofloxacin alone led to a 64-fold increase in the MIC for both strains after 12 cycles. Addition of meropenem in sub-MIC concentrations (0.25×MIC) completely inhibited the selection of levofloxacin-resistant mutants in WB4 after 12 cycles. In KR4, the addition of meropenem led to just a twofold increase in the MIC for levofloxacin after 12 cycles. Mutations detected in the genes encoding for topoisomerase IV (parC) and gyrase (gyrA) confirmed the levofloxacin-induced resistance in both strains. Addition of meropenem was able to completely suppress levofloxacin-induced mutations in WB4 and led to only one mutation in parE in KR4. In experimental meningitis, meropenem, given in two doses (2×125mg/kg), produced a good bactericidal activity (−0.45 Δlog10 cfu/ml·h) comparable to one dose (1×10mg/kg) of levofloxacin (−0.44 Δlog10 cfu/ml·h) against the penicillin-resistant strain WB4. Meropenem combined with levofloxacin acted synergistically (−0.93 Δlog10 cfu/ml·h), sterilizing the CSF of all rabbit

Experimental polarization encoded quantum key distribution over optical fibres with real-time continuous birefringence compensation

In this paper we demonstrate an active polarization drift compensation scheme for optical fibres employed in a quantum key distribution experiment with polarization encoded qubits. The quantum signals are wavelength multiplexed in one fibre along with two classical optical side channels that provide the control information for the polarization compensation scheme. This set-up allows us to continuously track any polarization change without the need to interrupt the key exchange. The results obtained show that fast polarization rotations of the order of 40*pi rad/s are effectively compensated for. We demonstrate that our set-up allows continuous quantum key distribution even in a fibre stressed by random polarization fluctuations. Our results pave the way for Bell-state measurements using only linear optics with parties separated by long-distance optical fibres

Design Studies Suggested by an Abstract Model for Medical Information System

We have developed a formal model of a database system that is unusual in that it has the ability to represent information about its own structure and to insure semantic consistency. The model distinguishes general laws from instances of events and objects, but many of its mechanisms serve both categories of information. The model form a substrate upon which an information structure appropriate to neonatology is being developed. Some example queries are shown and a design study for an associative memory suggested by the model is described briefly