Molecular basis of osteoarthritis: biomechanical aspects

The unique biomechanical properties of healthy cartilage ensure that articular cartilage is able to transmit force between the joints while maintaining almost friction-free limb movement. In osteoarthritis, the biomechanical properties are compromised, but we still do not understood whether this precedes the onset of the disease or is a result of it. This review focuses on the physical changes to cartilage with age, disease, and mechanical loading, with specific reference to the increased collagen cross-linking that occurs with age (nonenzymatic glycation), and the response of chondrocytes to physiological and pathological loads. In addition, the biomechanical properties and matrix biosynthesis of cartilage from various joint surfaces of the knee and ankle are compared to elucidate reasons why the ankle is less affected by progressive osteoarthritis than the knee.     

Massive gene decay in the leprosy bacillus

Leprosy, a chronic human neurological disease, results from infection with the obligate intracellular pathogen Mycobacterium leprae, a close relative of the tubercle bacillus. Mycobacterium leprae has the longest doubling time of all known bacteria and has thwarted every effort at culture in the laboratory. Comparing the 3.27-megabase (Mb) genome sequence of an armadillo-derived Indian isolate of the leprosy bacillus with that of Mycobacterium tuberculosis (4.41 Mb) provides clear explanations for these properties and reveals an extreme case of reductive evolution. Less than half of the genome contains functional genes but pseudogenes, with intact counterparts in M. tuberculosis, abound. Genome downsizing and the current mosaic arrangement appear to have resulted from extensive recombination events between dispersed repetitive sequences. Gene deletion and decay have eliminated many important metabolic activities including siderophore production, part of the oxidative and most of the microaerophilic and anaerobic respiratory chains, and numerous catabolic systems and their regulatory circuits.     

A measurement of the cosmological mass density from clustering in the 2dF Galaxy Redshift Survey

The large-scale structure in the distribution of galaxies is thought to arise from the gravitational instability of small fluctuations in the initial density field of the Universe. A key test of this hypothesis is that forming superclusters of galaxies should generate a systematic infall of other galaxies. This would be evident in the pattern of recessional velocities, causing an anisotropy in the inferred spatial clustering of galaxies. Here we report a precise measurement of this clustering, using the redshifts of more than 141,000 galaxies from the two-degree-field (2dF) galaxy redshift survey. We determine the parameter beta = Omega0.6/b = 0.43 +/- 0.07, where Omega is the total mass-density parameter of the Universe and b is a measure of the 'bias' of the luminous galaxies in the survey. (Bias is the difference between the clustering of visible galaxies and of the total mass, most of which is dark.) Combined with the anisotropy of the cosmic microwave background, our results favour a low-density Universe with Omega approximately 0.3.     

Coherent manipulation of semiconductor quantum bits with terahertz radiation

Quantum bits (qubits) are the fundamental building blocks of quantum information processors, such as quantum computers. A qubit comprises a pair of well characterized quantum states that can in principle be manipulated quickly compared to the time it takes them to decohere by coupling to their environment. Much remains to be understood about the manipulation and decoherence of semiconductor qubits. Here we show that hydrogen-atom-like motional states of electrons bound to donor impurities in currently available semiconductors can serve as model qubits. We use intense pulses of terahertz radiation to induce coherent, damped Rabi oscillations in the population of two low-lying states of donor impurities in GaAs. Our observations demonstrate that a quantum-confined extrinsic electron in a semiconductor can be coherently manipulated like an atomic electron, even while sharing space with approximately 10(5) atoms in its semiconductor host. We anticipate that this model system will be useful for measuring intrinsic decoherence processes, and for testing both simple and complex manipulations of semiconductor qubits.     

The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) are neurodegenerative conditions that affect large motor neurons of the central nervous system. We have identified a familial juvenile PLS (JPLS) locus overlapping the previously identified ALS2 locus on chromosome 2q33. We report two deletion mutations in a new gene that are found both in individuals with ALS2 and those with JPLS, indicating that these conditions have a common genetic origin. The predicted sequence of the protein (alsin) may indicate a mechanism for motor-neuron degeneration, as it may include several cell-signaling motifs with known functions, including three associated with guanine-nucleotide exchange factors for GTPases (GEFs).     

Complex formation between bee venom melittin and extract of mouse skin detected by sephadex gel filtration

Zusammenfassung Das aus Bienengift vonApis mellifera gewonnene, oberflächenaktive, kationische Polypeptid Melittin bildet mit Hautzellenextrakt, nicht aber mit Serumalbumin, einen stöchiometrischen Komplex, der vermutlich die Transportform des Giftes im Körper darstellt.

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This work was sponsored by the Glenn B. and Gertrude Warren Foundation, Inc., 1361 Myron Street, Schenectedy (New York 12309, USA).     

Mutations of the catalytic subunit of RAB3GAP cause Warburg Micro syndrome

Warburg Micro syndrome (WARBM1) is a severe autosomal recessive disorder characterized by developmental abnormalities of the eye and central nervous system and by microgenitalia. We identified homozygous inactivating mutations in RAB3GAP, encoding RAB3 GTPase activating protein, a key regulator of the Rab3 pathway implicated in exocytic release of neurotransmitters and hormones, in 12 families with Micro syndrome. We hypothesize that the underlying pathogenesis of Micro syndrome is a failure of exocytic release of ocular and neurodevelopmental trophic factors.     

Influence of mean climate change on climate variability from a 155-year tropical Pacific coral record

Today, the El Ni?o/Southern Oscillation (ENSO) system is the primary driver of interannual variability in global climate, but its long-term behaviour is poorly understood. Instrumental observations reveal a shift in 1976 towards warmer and wetter conditions in the tropical Pacific, with widespread climatic and ecological consequences. This shift, unique over the past century, has prompted debate over the influence of increasing atmospheric concentrations of greenhouse gases on ENSO variability. Here we present a 155-year ENSO reconstruction from a central tropical Pacific coral that provides new evidence for long-term changes in the regional mean climate and its variability. A gradual transition in the early twentieth century and the abrupt change in 1976, both towards warmer and wetter conditions, co-occur with changes in variability. In the mid-late nineteenth century, cooler and drier background conditions coincided with prominent decadal variability; in the early twentieth century, shorter-period (approximately 2.9 years) variability intensified. After 1920, variability weakens and becomes focused at interannual timescales; with the shift in 1976, variability with a period of about 4 years becomes prominent. Our results suggest that variability in the tropical Pacific is linked to the region's mean climate, and that changes in both have occurred during periods of natural as well as anthropogenic climate forcing.