| 941. |
- Russell, Alistair B., et al.
(författare)
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Diverse type VI secretion phospholipases are functionally plastic antibacterial effectors
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 496:7446, s. 508-512
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Tidskriftsartikel (refereegranskat)abstract
- Membranes allow the compartmentalization of biochemical processes and are therefore fundamental to life. The conservation of the cellular membrane, combined with its accessibility to secreted proteins, has made it a common target of factors mediating antagonistic interactions between diverse organisms. Here we report the discovery of a diverse superfamily of bacterial phospholipase enzymes. Within this superfamily, we defined enzymes with phospholipase A(1) and A(2) activity, which are common in host-cell-targeting bacterial toxins and the venoms of certain insects and reptiles(1,2). However, we find that the fundamental role of the superfamily is to mediate antagonistic bacterial interactions as effectors of the type VI secretion system (T6SS) translocation apparatus; accordingly, we name these proteins type VI lipase effectors. Our analyses indicate that PldA of Pseudomonas aeruginosa, a eukaryotic-like phospholipase D-3, is a member of the type VI lipase effector superfamily and the founding substrate of the haemolysin co-regulated protein secretion island II T6SS (H2-T6SS). Although previous studies have specifically implicated PldA and the H2-T6SS in pathogenesis(3-5), we uncovered a specific role for the effector and its secretory machinery in intra-and interspecies bacterial interactions. Furthermore, we find that this effector achieves its antibacterial activity by degrading phosphatidylethanolamine, the major component of bacterial membranes. The surprising finding that virulence-associated phospholipases can serve as specific antibacterial effectors suggests that interbacterial interactions are a relevant factor driving the continuing evolution of pathogenesis.
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| 942. |
- Russo, C, et al.
(författare)
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Presenilin-1 mutations in Alzheimer's disease
- 2000
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 405:6786, s. 531-532
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Tidskriftsartikel (refereegranskat)
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| 943. |
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| 944. |
- Ryan, K. K., et al.
(författare)
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FXR is a molecular target for the effects of vertical sleeve gastrectomy
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 509:7499, s. 183-188
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Tidskriftsartikel (refereegranskat)abstract
- Bariatric surgical procedures, such as vertical sleeve gastrectomy (VSG), are at present the most effective therapy for the treatment of obesity, and are associated with considerable improvements in co-morbidities, including type-2 diabetes mellitus. The underlying molecular mechanisms contributing to these benefits remain largely undetermined, despite offering the potential to reveal new targets for therapeutic intervention. Substantial changes in circulating total bile acids are known to occur after VSG. Moreover, bile acids are known to regulate metabolism by binding to the nuclear receptor FXR (farsenoid-X receptor, also known as NR1H4). We therefore examined the results of VSG surgery applied to mice with diet-induced obesity and targeted genetic disruption of FXR. Here we demonstrate that the therapeutic value of VSG does not result from mechanical restriction imposed by a smaller stomach. Rather, VSG is associated with increased circulating bile acids, and associated changes to gut microbial communities. Moreover, in the absence of FXR, the ability of VSG to reduce body weight and improve glucose tolerance is substantially reduced. These results point to bile acids and FXR signalling as an important molecular underpinning for the beneficial effects of this weight-loss surgery.
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| 945. |
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| 946. |
- Sagués Carracedo, Ana, et al.
(författare)
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A very luminous jet from the disruption of a star by a massive black hole
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 612:7940, s. 430-434
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Tidskriftsartikel (refereegranskat)abstract
- Tidal disruption events (TDEs) are bursts of electromagnetic energy that are released when supermassive black holes at the centres of galaxies violently disrupt a star that passes too close1. TDEs provide a window through which to study accretion onto supermassive black holes; in some rare cases, this accretion leads to launching of a relativistic jet2,3,4,5,6,7,8,9, but the necessary conditions are not fully understood. The best-studied jetted TDE so far is Swift J1644+57, which was discovered in γ-rays, but was too obscured by dust to be seen at optical wavelengths. Here we report the optical detection of AT2022cmc, a rapidly fading source at cosmological distance (redshift z = 1.19325) the unique light curve of which transitioned into a luminous plateau within days. Observations of a bright counterpart at other wavelengths, including X-ray, submillimetre and radio, supports the interpretation of AT2022cmc as a jetted TDE containing a synchrotron ‘afterglow’, probably launched by a supermassive black hole with spin greater than approximately 0.3. Using four years of Zwicky Transient Facility10 survey data, we calculate a rate of 0.02+0.04−0.01 Gpc−3 yr−1 for on-axis jetted TDEs on the basis of the luminous, fast-fading red component, thus providing a measurement complementary to the rates derived from X-ray and radio observations11. Correcting for the beaming angle effects, this rate confirms that approximately 1 per cent of TDEs have relativistic jets. Optical surveys can use AT2022cmc as a prototype to unveil a population of jetted TDEs.
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| 947. |
- Sahu, Kailash C., et al.
(författare)
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Transiting extrasolar planetary candidates in the Galactic bulge
- 2006
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 443:7111, s. 534-540
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Tidskriftsartikel (refereegranskat)abstract
- More than 200 extrasolar planets have been discovered around relatively nearby stars, primarily through the Doppler line shifts owing to reflex motions of their host stars, and more recently through transits of some planets across the faces of the host stars. The detection of planets with the shortest known periods, 1.2 - 2.5 days, has mainly resulted from transit surveys which have generally targeted stars more massive than 0.75 M-., where M-. is the mass of the Sun. Here we report the results from a planetary transit search performed in a rich stellar field towards the Galactic bulge. We discovered 16 candidates with orbital periods between 0.4 and 4.2 days, five of which orbit stars of masses in the range 0.44 - 0.75 M-.. In two cases, radial-velocity measurements support the planetary nature of the companions. Five candidates have orbital periods below 1.0 day, constituting a new class of ultra-short-period planets, which occur only around stars of less than 0.88 M-.. This indicates that those orbiting very close to more-luminous stars might be evaporatively destroyed or that jovian planets around stars of lower mass might migrate to smaller radii.
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| 948. |
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| 949. |
- Sakmar, TP, et al.
(författare)
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Pharmacology: Inside-out receptor inhibition
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 540:7633, s. 344-345
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Tidskriftsartikel (refereegranskat)
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| 950. |
- Sanchez, Sophie, et al.
(författare)
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Life history of the stem tetrapod Acanthostega revealed by synchrotron microtomography
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 537:7620, s. 408-
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Tidskriftsartikel (refereegranskat)abstract
- The transition from fish to tetrapod was arguably the most radical series of adaptive shifts in vertebrate evolutionary history. Data are accumulating rapidly for most aspects of these events(1-5), but the life histories of the earliest tetrapods remain completely unknown, leaving a major gap in our understanding of these organisms as living animals. Symptomatic of this problem is the unspoken assumption that the largest known Devonian tetrapod fossils represent adult individuals. Here we present the first, to our knowledge, life history data for a Devonian tetrapod, from the Acanthostega mass-death deposit of Stensio Bjerg, East Greenland(6,7). Using propagation phase-contrast synchrotron microtomography (PPC-SR mu CT)(8) to visualize the histology of humeri (upper arm bones) and infer their growth histories, we show that even the largest individuals from this deposit are juveniles. A long early juvenile stage with unossified limb bones, during which individuals grew to almost final size, was followed by a slow-growing late juvenile stage with ossified limbs that lasted for at least six years in some individuals. The late onset of limb ossification suggests that the juveniles were exclusively aquatic, and the predominance of juveniles in the sample suggests segregated distributions of juveniles and adults at least at certain times. The absolute size at which limb ossification began differs greatly between individuals, suggesting the possibility of sexual dimorphism, adaptive strategies or competition-related size variation.
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