Physicochemical principles that regulate the competition between functional and dysfunctional association of proteins

To maintain protein homeostasis, a variety of quality control mechanisms, such as the unfolded protein response and the heat shock response, enable proteins to fold and to assemble into functional complexes while avoiding the formation of aberrant and potentially harmful aggregates. We show here that a complementary contribution to the regulation of the interactions between proteins is provided by the physicochemical properties of their amino acid sequences. The results of a systematic analysis of the protein-protein complexes in the Protein Data Bank (PDB) show that interface regions are more prone to aggregate than other surface regions, indicating that many of the interactions that promote the formation of functional complexes, including hydrophobic and electrostatic forces, can potentially also cause abnormal intermolecular association. We also show, however, that aggregation-prone interfaces are prevented from triggering uncontrolled assembly by being stabilized into their functional conformations by disulfide bonds and salt bridges. These results indicate that functional and dysfunctional association of proteins are promoted by similar forces but also that they are closely regulated by the presence of specific interactions that stabilize native states

Self-healing behavior of a polyelectrolyte-based lubricant additive for aqueous lubrication of oxide materials

We report on the self-healing behavior of a polyelectrolyte-based aqueous lubricant additive, poly(l-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG), during aqueous lubrication of an oxide-based tribosystem. Combined pin-on-disk tribometry and fluorescence microscopy experiments have shown that stable lubricating performance was enabled by means of rapid healing of the worn tribopair surface by polymers dissolved in the adjoining bulk lubricant. This rapid ‘self-healing' of PLL-g-PEG is attributed to electrostatic interactions between the polycationic poly(l-lysine) (PLL) backbone of the polymer and negatively charged oxide surface. In contrast, a similar healing effect was not readily achievable in the case of methoxy-poly(ethylene glycol)-trimethylsilylether (Sil-PEG), a lubricant additive that is covalently bonded to the surface prior to tribological stres

New On Line Resource for Psycholinguistic

Picture naming is a widely used technique in psycholinguistic studies. Here, we describe new on-line resources that our project has compiled and made available to researchers on the world wide web at http://crl.ucsd.edu/~aszekely/ipnp/. The website provides access to a wide range of picture stimuli and related norms in seven languages. Picture naming norms, including indices of name agreement and latency, for 520 black-and-white drawings of common objects and 275 concrete transitive and intransitive actions are presented. Norms for age-of-acquisition, word-frequency, familiarity, goodness-of-depiction, and visual complexity are included. An on-line database query system can be used to select a specific range of stimuli, based on parameters of interest for a wide range of studies on healthy and clinical populations, as well as studies of language development

Gene content evolution in the arthropods

Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods. Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception. These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity

Myosin VI Drives Clathrin-Mediated AMPA Receptor Endocytosis to Facilitate Cerebellar Long-Term Depression

Myosin VI is an actin-based cytoskeletal motor implicated in various steps of membrane trafficking. Here, we investigated whether this myosin is crucial for synaptic function and plasticity in neurons. We find that myosin VI localizes at cerebellar parallel fiber to Purkinje cell synapses and that the myosin is indispensable for long-term depression of AMPA-receptor-mediated synaptic signal transmission at this synapse. Moreover, direct visualization of GluA2-containing AMPA receptors in Purkinje cells reveals that the myosin drives removal of AMPA receptors from the surface of dendritic spines in an activity-dependent manner. Co-immunoprecipitation and super-resolution microscopy indicate that specifically the interaction of myosin VI with the clathrin adaptor component alpha-adaptin is important during long-term depression. Together, these data suggest that myosin VI directly promotes clathrin-mediated endocytosis of AMPA receptors in Purkinje cells to mediate cerebellar long-term depression. Our results provide insights into myosin VI function and the molecular mechanisms underlying synaptic plasticity

Estudo comparativo entre métodos de coloração para a pesquisa do bacilo álcool-ácido resistente em secreções pulmonares

Apresentação do resultado comparativo entre dois métodos de coloração Osol e Ziehl-Neelsen para a pesquisa do bacilo álcool-ácido resistente, em 337 amostras secreção pulmonar. Foi realizada uma avaliação cultural de 287 amostras, mostrando que o método de Osol apresenta-se melhor nas baciloscopias discordantes e que há tendência em apresentar maior riqueza de germe.The comparative results obtained with the study of two staining methods, the Ziehl-Neelsen and the Osol ones, are presented. The study was performed with the alcohol acid resistant bacilli of 337 pulmonary secretion specimens. Evaluation cultures of 287 of these specimens were made. The Osol method proved to be better than the Ziehl-Neelsen one when dealing with discordant baciloscopic evidence. There tended to be a larger ammount of bacilli, too, when the former was used

A New Paradigm for Large Earthquakes in Stable Continental Plate Interiors

Large earthquakes within stable continental regions (SCR) show that significant amounts of elastic strain can be released on geological structures far from plate boundary faults, where the vast majority of the Earth's seismic activity takes place. SCR earthquakes show spatial and temporal patterns that differ from those at plate boundaries and occur in regions where tectonic loading rates are negligible. However, in the absence of a more appropriate model, they are traditionally viewed as analogous to their plate boundary counterparts, occuring when the accrual of tectonic stress localized at long-lived active faults reaches failure threshold. Here we argue that SCR earthquakes are better explained by transient perturbations of local stress or fault strength that release elastic energy from a pre-stressed lithosphere. As a result, SCR earthquakes can occur in regions with no previous seismicity and no surface evidence for strain accumulation. They need not repeat, since the tectonic loading rate is close to zero. Therefore, concepts of recurrence time or fault slip rate do not apply. As a consequence, seismic hazard in SCRs is likely more spatially distributed than indicated by paleoearthquakes, current seismicity, or geodetic strain rates