Editors' Choice

Science  29 Apr 2005:
Vol. 308, Issue 5722, pp. 603

    Sidelining Quality Control

    1. Stella M. Hurtley

    Quality control within the endoplasmic reticulum has long been regarded as a mechanism that prevents the secretion of misfolded proteins: Endoplasmic reticulum-associated degradation (ERAD) and the inability of incorrectly folded proteins to access the export machinery are its key factors. However, in some cases, quality-control mechanisms fail, and misfolded or misassembled proteins are secreted and cause disease. One class of such diseases is known as the familial amyloidoses, in which aberrant forms of the protein transthyretin are secreted, become misfolded, and form pathological aggregates.

    Sekijima et al. have examined the thermodynamics and kinetics of the folding and assembly of disease-associated forms of transthyretin. The endoplasmic reticulum is the entry site of the protein secretory pathway, and export from this compartment allows aberrant or misfolded proteins to transit to the Golgi and beyond. For many mutant forms of transthyretin, the balance between endoplasmic reticulum-assisted folding (ERAF) and ERAD determines the overall performance of this gatekeeping stage, and some cell types can actually secrete aberrant transthyretin efficiently. The competition between these intracompartmental pathways defines the ability of a particular type of cell or tissue to restrict or permit the secretion of aberrant proteins, and thereby determines the tissue selectivity and severity of protein-folding disorders. — SMH

    Cell121, 73 (2005).

    J. Am. Chem. Soc. 10.1021/ja0315154 (2004).


    Dendritic Cells, Part 1

    1. Stephen J. Simpson

    The recognition of the molecular patterns of pathogens by innate immune receptors is a well-established function of the Toll-like receptor (TLR) family; similar activities are now being ascribed to other families of host cell proteins. For example, the C-type lectin Dectin-1 enables phagocytosis of yeast by scavenger cells by binding the yeast cell wall carbohydrates (β glucans), and it has been shown to act as a coreceptor for TLR2, leading to inflammatory cytokine expression.

    Rogers et al. show that Dectin-1 can signal directly to initiate cytokine transcription. The production of interleukin-2 (IL-2) and IL-10 could be induced upon exposure of dendritic cells to a yeast cell wall extract and was partially blocked by a soluble β glucan. An equivalent phenotype could be conferred on a B cell hybridoma line (LK cells) by transduction of Dectin-1. Transcription of both cytokines was dependent on the intracellular tyrosine kinase, Syk, which was recruited by the immunoreceptor tyrosine-based activation motif in the cytoplasmic tail of Dectin-1. The distinct cytokine profiles induced by Dectin-1 in the context of Syk signals, versus co-signaling with TLR2, suggest flexibility in innate pattern recognition that could be tailored for a pathogen- specific adaptive immune response. — SJS

    Immunity 22, 509 (2005).


    Preserved in Salt

    1. Brooks Hanson

    The most ancient living organism is claimed to be a bacterium that has been extracted and cultured from a small bubble of fluid trapped in a Permian-aged (∼250 million years ago) salt crystal, similar to the way that, for example, insects are trapped in amber. The idea is that this bacterium became entombed in a fluid inclusion in the salt crystal and remained dormant until it was resuscitated. One criticism has been that the inclusion in the salt crystal, and hence the bacterium, might be a contaminant of an uncertain and possibly younger age; the retention of younger fluids flowing through or adjacent to older rock is not uncommon.

    Satterfield et al. have now determined the chemistry of the fluid inclusions in these salt crystals. Earth's ocean chemistry has changed over time, and the Late Permian oceans were depleted in Mg and sulfate as compared with today's oceans, which provides a signature that is diagnostic for this time period. The chemistry of the inclusions fits with that of Permian seawater, suggesting that the bacterium is indeed old. — BH

    Geology 33, 265 (2005).


    A Shipping Forecast

    1. Julia Fahrenkamp-Uppenbrink

    Phytoplankton are responsible for 45% of plant primary production and absorb large amounts of carbon dioxide from the atmosphere. From 1997 to 2002, the satellite-based Sea-viewing Wide Field-of-view Sensor (SeaWiFS) collected global data on the distribution of chlorophyll a, a measure of phytoplankton concentration; however, this data set is too short to provide insights into decadal changes in phytoplankton.

    Raitsos et al. have turned therefore to measurements of the phytoplankton color index, which have been collected since 1931 along shipping routes in the North Sea and the North Atlantic and which have used a consistent sampling and measurement methodology since 1948. The authors demonstrate a significant correlation between the two data sets from 1997 to 2002 and then use this correlation to retrospectively calculate monthly changes in chlorophyll a concentrations since 1948. The results show a marked increase in chlorophyll a in the mid-1980s, a time when the composition and productivity of the regional ecosystem are known to have changed. This data set will be useful for biogeochemical and climate modeling studies that aim to understand the links between marine biology and climate. — JFU

    Geophys. Res. Lett. 32, 10.1029/2005GL022484 (2005).


    Not-So-Thermal Desorption

    1. Phillip D. Szuromi

    The desorption of atoms or molecules from surfaces is thought to proceed through one of two mechanisms. Heating of the surface usually results in thermal desorption, in which the bonds holding the adsorbed species are put into such high vibrational states that they break. In electron- or photon-stimulated desorption, excitation of the adsorbate into an antibonding electronic state leads to desorption.

    Trenhaile et al. followed the desorption of Br from the Si(100)-(2×1) surface at 620 to 775 K via scanning tunneling microscopy. Their analysis shows that this process does not proceed through vibrational excitation but by electron capture into long-lived states that then populate an antibonding σ* state that then ejects the Br atom. The excitation energy for desorption changes with the Fermi level for different silicon doping levels. Entropy can actually help drive this process, in which 10 to 20 optical phonons come together to push the electron over its barrier. — PDS

    Surf. Sci. 10.1016/j.susc.2005.3.053 (2005).


    Dendritic Cells, Part 2

    1. Caroline Ash

    The first step to infection is capture by a cell-surface receptor. A broad range of viruses, bacteria, and other human pathogens initiate infection by attaching to dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN), a C-type lectin encoded by the gene CD209. The usual role of DC-SIGN is to mediate contact between dendritic cells and T cells and to promote the migration of dendritic cells through tissues.

    Sakuntabhai et al. have explored the effects of genetic variation in CD209 on the specific disease syndromes caused by dengue virus. They recruited school-aged children with classical incapacitating dengue fever from three hospitals in Thailand. Screening CD209 for genetic polymorphisms revealed that a dominant protective effect against dengue fever (without leakage of plasma), but not dengue hemorrhagic fever, lay in a G allele in the promoter region of CD209. This polymorphism influences the binding of the transcription factor Sp1 and may ultimately affect disease progression as well as the distinct pathophysiologies of dengue fever and dengue hemorrhagic fever. — CA

    Nat. Genet. 10.1038/ng1550 (2005).


    Traits in Common

    1. Gilbert J. Chin

    The five-factor model of personality posits five basic dimensions of personality: neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness. Previous cross-cultural work has relied primarily on self-report measures collected mostly from Westernized college students. Using a third-person form of the NEO personality inventory, McCrae et al. present an intercontinental analysis of observer ratings. College students were asked to rate individuals from one of four groups—college-aged men and women and adult men and women—on six facets in each of the five dimensions. They find that their model does appear to apply across all 50 cultures (including Arabic and black African); the fit isn't perfect, but some of the variation may be due to mismatches between the questionnaire items and cultural contexts. Women were generally rated more highly than men, confirming data from self-report inventories, and scored higher on all six facets of agreeableness, which is consistent with earlier observations that women are more lenient when rating others. One interesting trend is that adult men scored higher than women on the conscientious facet “achievement striving,” whereas the opposite ranking applied for college-age individuals, possibly reflecting a role reversal across generations. — GJC

    J. Pers. Soc. Psychol. 88, 547 (2005).

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