Some bacterial species are able to utilize extracellular mineral forms of iron and manganese as respiratory electron acceptors. In Shewanella oneidensis this involves decaheme cytochromes that are ...located on the bacterial cell surface at the termini of trans-outer-membrane electron transfer conduits. The cell surface cytochromes can potentially play multiple roles in mediating electron transfer directly to insoluble electron sinks, catalyzing electron exchange with flavin electron shuttles or participating in extracellular intercytochrome electron exchange along "nanowire" appendages. We present a 3.2-à crystal structure of one of these decaheme cytochromes, MtrF, that allows the spatial organization of the 10 hemes to be visualized for the first time. The hemes are organized across four domains in a unique crossed conformation, in which a staggered 65-à octaheme chain transects the length of the protein and is bisected by a planar 45-à tetraheme chain that connects two extended Greek key split β-barrel domains. The structure provides molecular insight into how reduction of insoluble substrate (e.g., minerals), soluble substrates (e.g., flavins), and cytochrome redox partners might be possible in tandem at different termini of a trifurcated electron transport chain on the cell surface.
The mineral-respiring bacterium Shewanella oneidensis uses a protein complex, MtrCAB, composed of two decaheme cytochromes, MtrC and MtrA, brought together inside a transmembrane porin, MtrB, to ...transport electrons across the outer membrane to a variety of mineral-based electron acceptors. A proteoliposome system containing a pool of internalized electron carriers was used to investigate how the topology of the MtrCAB complex relates to its ability to transport electrons across a lipid bilayer to externally located Fe(III) oxides. With MtrA facing the interior and MtrC exposed on the outer surface of the phospholipid bilayer, the established in vivo orientation, electron transfer from the interior electron carrier pool through MtrCAB to solid-phase Fe(III) oxides was demonstrated. The rates were 10³ times higher than those reported for reduction of goethite, hematite, and lepidocro cite by S. oneidensis, and the order of the reaction rates was consistent with those observed in S. oneidensis cultures. In contrast, established rates for single turnover reactions between purified MtrC and Fe(III) oxides were 10³ times lower. By providing a continuous flow of electrons, the proteoliposome experiments demonstrate that conduction through MtrCAB directly to Fe(III) oxides is sufficient to support in vivo, anaerobic, solid-phase iron respiration.
A multicentennial and absolutely-dated shell-based chronology for the marine environment of the North Icelandic Shelf has been constructed using annual growth increments in the shell of the ...long-lived bivalve clam Arctica islandica. The region from which the shells were collected is close to the North Atlantic Polar Front and is highly sensitive to the varying influences of Atlantic and Arctic water masses. A strong common environmental signal is apparent in the increment widths, and although the correlations between the growth increment indices and regional sea surface temperatures are significant at the 95% confidence level, they are low (r~0.2), indicating that a more complex combination of environmental forcings is driving growth. Remarkable longevities of individual animals are apparent in the increment-width series used in the chronology, with several animals having lifetimes in excess of 300years and one, at 507years, being the longest-lived non-colonial animal so far reported whose age at death can be accurately determined. The sample depth is at least three shells after AD 1175, and the time series has been extended back to AD 649 with a sample depth of one or two by the addition of two further series, thus providing a 1357-year archive of dated shell material. The statistical and spectral characteristics of the chronology are investigated by using two different methods of removing the age-related trend in shell growth. Comparison with other proxy archives from the same region reveals several similarities in variability on multidecadal timescales, particularly during the period surrounding the transition from the Medieval Climate Anomaly to the Little Ice Age.
► A shell-based proxy archive for the marine environment north of Iceland. ► The longest (at 1357 years) crossdated shell-based archive so far constructed. ► Includes the longest-lived (at 507 years) non-colonial animal known to science. ► A strong common environmental signal is apparent in the shells. ► There is a possible signal of the timing of the transition from the MCA to the LIA.
Recently, coherent control of the optical response of thin films in standing waves has attracted considerable attention, ranging from applications in excitation-selective spectroscopy and nonlinear ...optics to all-optical image processing. Here, we show that integration of metamaterial and optical fibre technologies allows the use of coherently controlled absorption in a fully fiberized and packaged switching metadevice. With this metadevice, which controls light with light in a nanoscale plasmonic metamaterial film on an optical fibre tip, we provide proof-of-principle demonstrations of logical functions XOR, NOT and AND that are performed within a coherent fibre network at wavelengths between 1530 and 1565 nm. The metadevice has been tested at up to 40 gigabits per second and sub-milliwatt power levels. Since coherent absorption can operate at the single-photon level and with 100 THz bandwidth, we argue that the demonstrated all-optical switch concept has potential applications in coherent and quantum information networks.
The Life History of 21 Breast Cancers Nik-Zainal, Serena; Van Loo, Peter; Wedge, David C. ...
Cell,
05/2012, Letnik:
149, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Cancer evolves dynamically as clonal expansions supersede one another driven by shifting selective pressures, mutational processes, and disrupted cancer genes. These processes mark the genome, such ...that a cancer's life history is encrypted in the somatic mutations present. We developed algorithms to decipher this narrative and applied them to 21 breast cancers. Mutational processes evolve across a cancer's lifespan, with many emerging late but contributing extensive genetic variation. Subclonal diversification is prominent, and most mutations are found in just a fraction of tumor cells. Every tumor has a dominant subclonal lineage, representing more than 50% of tumor cells. Minimal expansion of these subclones occurs until many hundreds to thousands of mutations have accumulated, implying the existence of long-lived, quiescent cell lineages capable of substantial proliferation upon acquisition of enabling genomic changes. Expansion of the dominant subclone to an appreciable mass may therefore represent the final rate-limiting step in a breast cancer's development, triggering diagnosis.
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► Genome-wide analyses of mutations emerging through time in 21 breast cancers ► Minimal expansion of subclones occurs until thousands of mutations have accumulated ► Cancer-specific signatures of point mutations and genomic instability emerge late ► ERBB2 amplification begins early but continues to evolve over long molecular time
Newly developed algorithms allow the reconstruction of the genomic history of different breast cancers, tracing the temporal evolution of each tumor and the emergence of the dominant subclones that will eventually trigger diagnosis.
It is unclear how the prevalence of people who believe the gluten-free diet (GFD) to be generally healthy ("Lifestylers") is impacting the overall rates of self-reported gluten sensitivity (GS). We ...repeated a population survey from 2012 in order to examine how attitudes towards GS have changed over time. Our survey (
= 1004) was administered in Sheffield (UK) in 2015, replicating the 2012 experiment. The questionnaire included a food frequency survey and assessed self-reported GS as well as associated variables (prevalence, current diet, pre-existing conditions, etc.). The overall rates of key variables and chi-squared analysis in comparison to the previous survey were as follows: self-reported GS was 32.8% (previously 12.9%,
< 0.001), pre-existing coeliac disease (CD) was 1.2% (previously 0.8%,
= 0.370), following a GFD was 3.7% (previously 3.7%,
= 0.997). Self-reported GS was positively associated with some pre-existing conditions, including anxiety, depression, chronic fatigue, headaches, and other food allergies/intolerances (including irritable bowel syndrome (IBS); chi-squared analyses, all
< 0.001). Over a 3-year period, the fraction of people who self-reported GS increased by over 250%. Despite this, arguably more meaningful indications of underlying physiological GS remained comparable. This research suggests that the public perception of gluten is causing a marked increase in the number of people who erroneously believe they are sensitive to it.
Summary
Many species of bacteria can couple anaerobic growth to the respiratory reduction of insoluble minerals containing Fe(III) or Mn(III/IV). It has been suggested that in Shewanella species ...electrons cross the outer membrane to extracellular substrates via ‘porin–cytochrome’ electron transport modules. The molecular structure of an outer‐membrane extracellular‐facing deca‐haem terminus for such a module has recently been resolved. It is debated how, once outside the cells, electrons are transferred from outer‐membrane cytochromes to insoluble electron sinks. This may occur directly or by assemblies of cytochromes, perhaps functioning as ‘nanowires’, or via electron shuttles. Here we review recent work in this field and explore whether it allows for unification of the electron transport mechanisms supporting extracellular mineral respiration in Shewanella that may extend into other genera of Gram‐negative bacteria.
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