Biomechanics: robotic whiskers used to sense features

Whiskers mimicking those of seals or rats might be useful for underwater tracking or tactile exploration. Several species of terrestrial and marine mammals with whiskers (vibrissae) use them to sense and navigate in their environment--for example, rats use their whiskers to discern the features of objects, and seals rely on theirs to track the hydrodynamic trails of their prey. Here we show that the bending moment--sometimes referred to as torque--at the whisker base can be used to generate three-dimensional spatial representations of the environment, and we use this principle to construct robotic whisker arrays that extract precise information about object shape and fluid flow. Our results will contribute to the development of versatile tactile-sensing systems for robotic applications, and demonstrate the value of hardware models in understanding how sensing mechanisms and movement control strategies are interlocked.     

Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin

Parkinson's disease is the second most common neurodegenerative disorder and is characterized by the degeneration of dopaminergic neurons in the substantia nigra. Mitochondrial dysfunction has been implicated as an important trigger for Parkinson's disease-like pathogenesis because exposure to environmental mitochondrial toxins leads to Parkinson's disease-like pathology. Recently, multiple genes mediating familial forms of Parkinson's disease have been identified, including PTEN-induced kinase 1 (PINK1; PARK6) and parkin (PARK2), which are also associated with sporadic forms of Parkinson's disease. PINK1 encodes a putative serine/threonine kinase with a mitochondrial targeting sequence. So far, no in vivo studies have been reported for pink1 in any model system. Here we show that removal of Drosophila PINK1 homologue (CG4523; hereafter called pink1) function results in male sterility, apoptotic muscle degeneration, defects in mitochondrial morphology and increased sensitivity to multiple stresses including oxidative stress. Pink1 localizes to mitochondria, and mitochondrial cristae are fragmented in pink1 mutants. Expression of human PINK1 in the Drosophila testes restores male fertility and normal mitochondrial morphology in a portion of pink1 mutants, demonstrating functional conservation between human and Drosophila Pink1. Loss of Drosophila parkin shows phenotypes similar to loss of pink1 function. Notably, overexpression of parkin rescues the male sterility and mitochondrial morphology defects of pink1 mutants, whereas double mutants removing both pink1 and parkin function show muscle phenotypes identical to those observed in either mutant alone. These observations suggest that pink1 and parkin function, at least in part, in the same pathway, with pink1 functioning upstream of parkin. The role of the pink1-parkin pathway in regulating mitochondrial function underscores the importance of mitochondrial dysfunction as a central mechanism of Parkinson's disease pathogenesis.     

Production of the antimalarial drug precursor artemisinic acid in engineered yeast

Malaria is a global health problem that threatens 300-500 million people and kills more than one million people annually. Disease control is hampered by the occurrence of multi-drug-resistant strains of the malaria parasite Plasmodium falciparum. Synthetic antimalarial drugs and malarial vaccines are currently being developed, but their efficacy against malaria awaits rigorous clinical testing. Artemisinin, a sesquiterpene lactone endoperoxide extracted from Artemisia annua L (family Asteraceae; commonly known as sweet wormwood), is highly effective against multi-drug-resistant Plasmodium spp., but is in short supply and unaffordable to most malaria sufferers. Although total synthesis of artemisinin is difficult and costly, the semi-synthesis of artemisinin or any derivative from microbially sourced artemisinic acid, its immediate precursor, could be a cost-effective, environmentally friendly, high-quality and reliable source of artemisinin. Here we report the engineering of Saccharomyces cerevisiae to produce high titres (up to 100 mg l(-1)) of artemisinic acid using an engineered mevalonate pathway, amorphadiene synthase, and a novel cytochrome P450 monooxygenase (CYP71AV1) from A. annua that performs a three-step oxidation of amorpha-4,11-diene to artemisinic acid. The synthesized artemisinic acid is transported out and retained on the outside of the engineered yeast, meaning that a simple and inexpensive purification process can be used to obtain the desired product. Although the engineered yeast is already capable of producing artemisinic acid at a significantly higher specific productivity than A. annua, yield optimization and industrial scale-up will be required to raise artemisinic acid production to a level high enough to reduce artemisinin combination therapies to significantly below their current prices.     

100-metre-diameter moonlets in Saturn's A ring from observations of 'propeller' structures

Saturn's main rings are composed predominantly of water-ice particles ranging between about 1 centimetre and 10 metres in radius. Above this size range, the number of particles drops sharply, according to the interpretation of spacecraft and stellar occultations. Other than the gap moons Pan and Daphnis (the provisional name of S/2005 S1), which have sizes of several kilometres, no individual bodies in the rings have been directly observed, and the population of ring particles larger than ten metres has been essentially unknown. Here we report the observation of four longitudinal double-streaks in an otherwise bland part of the mid-A ring. We infer that these 'propeller'-shaped perturbations arise from the effects of embedded moonlets approximately 40 to 120 m in diameter. Direct observation of this phenomenon validates models of proto-planetary disks in which similar processes are posited. A population of moonlets, as implied by the size distribution that we find, could help explain gaps in the more tenuous regions of the Cassini division and the C ring. The existence of such large embedded moonlets is most naturally compatible with a ring originating in the break-up of a larger body, but accretion from a circumplanetary disk is also plausible if subsequent growth onto large particles occurs after the primary accretion phase has concluded.     

Resveratrol improves health and survival of mice on a high-calorie diet

Resveratrol (3,5,4'-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing.     

Platensimycin is a selective FabF inhibitor with potent antibiotic properties

Bacterial infection remains a serious threat to human lives because of emerging resistance to existing antibiotics. Although the scientific community has avidly pursued the discovery of new antibiotics that interact with new targets, these efforts have met with limited success since the early 1960s. Here we report the discovery of platensimycin, a previously unknown class of antibiotics produced by Streptomyces platensis. Platensimycin demonstrates strong, broad-spectrum Gram-positive antibacterial activity by selectively inhibiting cellular lipid biosynthesis. We show that this anti-bacterial effect is exerted through the selective targeting of beta-ketoacyl-(acyl-carrier-protein (ACP)) synthase I/II (FabF/B) in the synthetic pathway of fatty acids. Direct binding assays show that platensimycin interacts specifically with the acyl-enzyme intermediate of the target protein, and X-ray crystallographic studies reveal that a specific conformational change that occurs on acylation must take place before the inhibitor can bind. Treatment with platensimycin eradicates Staphylococcus aureus infection in mice. Because of its unique mode of action, platensimycin shows no cross-resistance to other key antibiotic-resistant strains tested, including methicillin-resistant S. aureus, vancomycin-intermediate S. aureus and vancomycin-resistant enterococci. Platensimycin is the most potent inhibitor reported for the FabF/B condensing enzymes, and is the only inhibitor of these targets that shows broad-spectrum activity, in vivo efficacy and no observed toxicity.     

Isolation of a novel acidiphilic methanogen from an acidic peat bog

Acidic peatlands are among the largest natural sources of atmospheric methane and harbour a large diversity of methanogenic Archaea. Despite the ubiquity of methanogens in these peatlands, indigenous methanogens capable of growth at acidic pH values have resisted culture and isolation; these recalcitrant methanogens include members of an uncultured family-level clade in the Methanomicrobiales prevalent in many acidic peat bogs in the Northern Hemisphere. However, we recently succeeded in obtaining a mixed enrichment culture of a member of this clade. Here we describe its isolation and initial characterization. We demonstrate that the optimum pH for methanogenesis by this organism is lower than that of any previously described methanogen.     

Structure of the catalytic domain of the hepatitis C virus NS2-3 protease

Hepatitis C virus is a major global health problem affecting an estimated 170 million people worldwide. Chronic infection is common and can lead to cirrhosis and liver cancer. There is no vaccine available and current therapies have met with limited success. The viral RNA genome encodes a polyprotein that includes two proteases essential for virus replication. The NS2-3 protease mediates a single cleavage at the NS2/NS3 junction, whereas the NS3-4A protease cleaves at four downstream sites in the polyprotein. NS3-4A is characterized as a serine protease with a chymotrypsin-like fold, but the enzymatic mechanism of the NS2-3 protease remains unresolved. Here we report the crystal structure of the catalytic domain of the NS2-3 protease at 2.3 A resolution. The structure reveals a dimeric cysteine protease with two composite active sites. For each active site, the catalytic histidine and glutamate residues are contributed by one monomer, and the nucleophilic cysteine by the other. The carboxy-terminal residues remain coordinated in the two active sites, predicting an inactive post-cleavage form. Proteolysis through formation of a composite active site occurs in the context of the viral polyprotein expressed in mammalian cells. These features offer unexpected insights into polyprotein processing by hepatitis C virus and new opportunities for antiviral drug design.     

癌生长是寄主中的过寄生现象

报道了人乳腺癌细胞MCF7和正常细胞MCF10,MRC5混合培养实验,分析了实验结果．结果表明：在营养物充足条件下癌细胞和正常细胞系寄生共存关系,而在饥饿条件下癌细胞和正常细胞是过寄生-捕食者和食饵的关系．讨论了此结果的生物医学含义．