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Kennedy Space Center : gateway to space
Provides detailed information on the earliest developments of rockets, the Apollo program, the Space Station, and the future of space exploration, offering a look at the departure gate for every space mission and the launching point of other advanced scientific spacecraft.
Book
Structure, function and regulation of the hsp90 machinery
Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone which is essential in eukaryotes. It is required for the activation and stabilization of a wide variety of client proteins and many of them are involved in important cellular pathways. Since Hsp90 affects numerous physiological processes such as signal transduction, intracellular transport, and protein degradation, it became an interesting target for cancer therapy. Structurally, Hsp90 is a flexible dimeric protein composed of three different domains which adopt structurally distinct conformations. ATP binding triggers directionality in these conformational changes and leads to a more compact state. To achieve its function, Hsp90 works together with a large group of cofactors, termed co-chaperones. Co-chaperones form defined binary or ternary complexes with Hsp90, which facilitate the maturation of client proteins. In addition, posttranslational modifications of Hsp90, such as phosphorylation and acetylation, provide another level of regulation. They influence the conformational cycle, co-chaperone interaction, and inter-domain communications. In this review, we discuss the recent progress made in understanding the Hsp90 machinery.
Journal Article
Gromov’s Theory of Multicomplexes with Applications to Bounded Cohomology and Simplicial Volume
The simplicial volume is a homotopy invariant of manifolds introduced by Gromov in his pioneering paper
The first aim of this paper is to lay the foundation of the theory of
multicomplexes. After setting the main definitions, we construct the singular multicomplex
In the second part of this work we apply the theory of multicomplexes to the study of the bounded
cohomology of topological spaces. Our constructions and arguments culminate in the complete proofs of Gromov’s Mapping Theorem (which
implies in particular that the bounded cohomology of a space only depends on its fundamental group) and of Gromov’s Vanishing Theorem,
which ensures the vanishing of the simplicial volume of closed manifolds admitting an amenable cover of small multiplicity.
The
third and last part of the paper is devoted to the study of locally finite chains on non-compact spaces, hence to the simplicial volume
of open manifolds. We expand some ideas of Gromov to provide detailed proofs of a criterion for the vanishing and a criterion for the
finiteness of the simplicial volume of open manifolds. As a by-product of these results, we prove a criterion for the
eBook
Association of blood pressure control with atrial and ventricular ectopy in SPRINT
BackgroundPrevious epidemiological studies demonstrated that premature atrial contractions (PACs) and premature ventricular contractions (PVCs) detected by single 12-lead ECGs can predict incident cardiovascular disease and death. The determinants of cardiac ectopy remain unknown, with some evidence that hypertension may contribute.ObjectiveTo determine if intensive blood pressure (BP) control reduces the incidence of cardiac ectopy.MethodsWe performed a post-hoc analysis of the Systolic Blood Pressure Intervention trial, which randomised hypertensive participants to standard treatment (BP target <140 mm Hg) or intensive treatment (<120 mm Hg) with ECGs obtained at baseline, 2 years, 4 years and 5 years. The primary outcomes were incidence of ectopy (PACs or PVCs) as coded by Minnesota ECG classification, censoring for pacing, atrioventricular block, pre-excitation or atrial fibrillation/flutter. We performed Cox proportional hazards regression to determine the association of treatment group with outcomes.ResultsThe analysis cohort comprised 3910 participants randomised to standard treatment and 3911 to intensive treatment, of whom 452 had ectopy on baseline ECG. After excluding those with baseline ectopy, there was no significant difference in the incidence of ectopy (incidence rate ratio 0.93 (95% CI 0.81 to 1.05)). There was no significant association between treatment group and ectopy incidence, with an unadjusted Cox HR of 0.93 (95% CI 0.82 to 1.07), and HR of 1 (95% CI 0.81 to 1.25) after adjusting for covariates.ConclusionIntensive BP control did not reduce the incidence of cardiac ectopy in patients with hypertension. Given the variable nature of PAC and PVC burden, further studies with continuous monitoring or more frequent sampling in larger populations are warranted.
Journal Article
This is the way to the moon
\"In This is the Way to the Moon, first published in 1963, Sasek rockets readers to Cape Canaveral--the space capital of the world, a science-fiction-turned-fact spot on the Florida coast--with a nostalgic look at the electronic brains that put our man up into space and brought him down again. Also included are the updated statistics about the lunar landing and a mini history of NASAs space program.\"--Amazon.com.
BOOK
Atomic structure of the APC/C and its mechanism of protein ubiquitination
The anaphase-promoting complex (APC/C) is a multimeric RING E3 ubiquitin ligase that controls chromosome segregation and mitotic exit. Its regulation by coactivator subunits, phosphorylation, the mitotic checkpoint complex and interphase early mitotic inhibitor 1 (Emi1) ensures the correct order and timing of distinct cell-cycle transitions. Here we use cryo-electron microscopy to determine atomic structures of APC/C–coactivator complexes with either Emi1 or a UbcH10–ubiquitin conjugate. These structures define the architecture of all APC/C subunits, the position of the catalytic module and explain how Emi1 mediates inhibition of the two E2s UbcH10 and Ube2S. Definition of Cdh1 interactions with the APC/C indicates how they are antagonized by Cdh1 phosphorylation. The structure of the APC/C with UbcH10–ubiquitin reveals insights into the initiating ubiquitination reaction. Our results provide a quantitative framework for the design of future experiments to investigate APC/C functions
in vivo
.
A cryo-electron microscopy determination of the atomic structures of anaphase-promoting complex (APC/C)–coactivator complexes with either Emi1 or a UbcH10–ubiquitin conjugate.
APC/C ubiquitination mechanism
This paper describes the atomic structures of the anaphase-promoting complex (APC/C) bound to the coactivator Cdh1 and the early mitotic inhibitor Emi1, or the E2 enzyme UbcH10 conjugated to ubiquitin. The (APC/C) is a multisubunit E3 ubiquitin ligase enzyme that controls chromosome segregation and the subsequent exit from mitotic cell division. The resolutions the authors achieved (3.6 Å and 4.1 Å) allow them to define the architecture of all APC/C subunits and inter-subunit interactions within the assembly and the position of the catalytic module. The structures explain how Emi1 mediates inhibition of not just UbcH10 but also another E2 enzyme, Ube2S. Among other insights gained is how the association of APC/C with the coactivator Cdh1 is antagonized by Cdh1 phosphorylation.
Journal Article
Structure of photosystem I-LHCI-LHCII from the green alga Chlamydomonas reinhardtii in State 2
Photosystem I (PSI) and II (PSII) balance their light energy distribution absorbed by their light-harvesting complexes (LHCs) through state transition to maintain the maximum photosynthetic performance and to avoid photodamage. In state 2, a part of LHCII moves to PSI, forming a PSI-LHCI-LHCII supercomplex. The green alga
Chlamydomonas reinhardtii
exhibits state transition to a far larger extent than higher plants. Here we report the cryo-electron microscopy structure of a PSI-LHCI-LHCII supercomplex in state 2 from
C. reinhardtii
at 3.42 Å resolution. The result reveals that the PSI-LHCI-LHCII of
C. reinhardtii
binds two LHCII trimers in addition to ten LHCI subunits. The PSI core subunits PsaO and PsaH, which were missed or not well-resolved in previous Cr-PSI-LHCI structures, are observed. The present results reveal the organization and assembly of PSI core subunits, LHCI and LHCII, pigment arrangement, and possible pathways of energy transfer from peripheral antennae to the PSI core.
Photosystems (PS) I and II undergo state transitions to optimize photosynthesis and photoprotection. Here the authors report a cryo-electron microscopy structure of the state 2 PSI-LHCI-LHCII supercomplex from
C. reinhardtii
revealing subunit organization and possible pathways of energy transfer.
Journal Article
Acute Effects of Coffee Consumption on Health among Ambulatory Adults
In a randomized trial, coffee consumption was not associated with more premature atrial contractions than caffeine avoidance but was associated with more premature ventricular contractions and daily steps and less sleep.
Journal Article