Ccdc11 is a novel centriolar satellite protein essential for ciliogenesis and establishment of left-right asymmetry

The establishment of left–right (L-R) asymmetry in vertebrates is dependent on the sensory and motile functions of cilia during embryogenesis. Mutations in CCDC11 disrupt L-R asymmetry and cause congenital heart disease in humans, yet the molecular and cellular functions of the protein remain unknown. Here we demonstrate that Ccdc11 is a novel component of centriolar satellites—cytoplasmic granules that serve as recruitment sites for proteins destined for the centrosome and cilium. Ccdc11 interacts with core components of satellites, and its loss disrupts the subcellular organization of satellite proteins and perturbs primary cilium assembly. Ccdc11 colocalizes with satellite proteins in human multiciliated tracheal epithelia, and its loss inhibits motile ciliogenesis. Similarly, depletion of CCDC11 in Xenopus embryos causes defective assembly and motility of cilia in multiciliated epidermal cells. To determine the role of CCDC11 during vertebrate development, we generated mutant alleles in zebrafish. Loss of CCDC11 leads to defective ciliogenesis in the pronephros and within the Kupffer’s vesicle and results in aberrant L-R axis determination. Our results highlight a critical role for Ccdc11 in the assembly and function of motile cilia and implicate centriolar satellite–associated proteins as a new class of proteins in the pathology of L-R patterning and congenital heart disease

Improved drought tolerance in wheat is required to unlock the production potential of the Brazilian Cerrado.

ABSTRACT Improving rainfed wheat cultivation in central Brazil, where the Cerrado biome (Brazilian savanna) is predominant, remains a bottleneck for future increases in domestic wheat production. In the Cerrado, the limited water availability during the wheat-growing season is an obstacle to increase wheat yield. To address this issue, the physiological and molecular drought response of wheat and the environmental conditions of this region must be better understood. In this review, we characterized the impact of drought on rainfed wheat production in the Cerrado. Based on the peculiarities of this environment, we suggest that certain traits should be prioritized in selection. These traits and their molecular basis are important to raise wheat yields in the Cerrado and also to improve food security in Brazil, one of the top wheat-importing countries in the world

Optimal strategies : theoretical approaches to the parametrization of the dark energy equation of state

The absence of compelling theoretical model requires the parameterizing the dark energy to probe its properties. The parametrization of the equation of state of the dark energy is a common method. We explore the theoretical optimization of the parametrization based on the Fisher information matrix. As a suitable parametrization, it should be stable at high redshift and should produce the determinant of the Fisher matrix as large as possible. For the illustration, we propose one parametrization which can satisfy both criteria. By using the proper parametrization, we can improve the constraints on the dark energy even for the same data. We also show the weakness of the so-called principal component analysis method.Comment: 7pages, 11 figures, 2 tables, To match the version accepted by AS

Ciliary Extracellular Vesicles are Distinct from the Cytosolic Extracellular Vesicles

Extracellular vesicles (EVs) are cell‐derived membrane vesicles that are released into the extracellular space. EVs encapsulate key proteins and mediate intercellular signalling pathways. Recently, primary cilia have been shown to release EVs under fluid‐shear flow, but many proteins encapsulated in these vesicles have never been identified. Primary cilia are ubiquitous mechanosensory organelles that protrude from the apical surface of almost all human cells. Primary cilia also serve as compartments for signalling pathways, and their defects have been associated with a wide range of human genetic diseases called ciliopathies. To better understand the mechanism of ciliopathies, it is imperative to know the distinctive protein profiles of the differently sourced EVs (cilia vs cytosol). Here, we isolated EVs from ciliated wild‐type (WT) and non‐ciliated IFT88 knockout (KO) mouse endothelial cells using fluid‐shear flow followed by a conventional method of EV isolation. EVs isolated from WT and KO exhibited distinctive sizes. Differences in EV protein contents were studied using liquid chromatography with tandem mass spectrometry (LC‐MS‐MS) and proteomic comparative analysis, which allowed us to classify proteins between ciliary EVs and cytosolic EVs derived from WT and KO, respectively. A total of 79 proteins were exclusively expressed in WT EVs, 145 solely in KO EVs, and 524 in both EVs. Our bioinformatics analyses revealed 29% distinct protein classes and 75% distinct signalling pathways between WT and KO EVs. Based on our statistical analyses and in vitro studies, we identified NADPH‐cytochrome P450 reductase (POR), and CD166 antigen (CD166) as potential biomarkers for ciliary and cytosolic EVs, respectively. Our protein‐protein interaction network analysis revealed that POR, but not CD166, interacted with either established or strong ciliopathy gene candidates. This report shows the unique differences between EVs secreted from cilia and the cytosol. These results will be important in advancing our understanding of human genetic diseases

CONVERGENT AND DIVERGENT ANGLES OF A SOLID-FUEL ROCKET NOZZLE AND ITS INFLUENCES ON THE MOTOR’S THRUST CURVE

The main goal of this work is to investigate how the angles of a convergent-divergent rocket nozzle influence the thrust curve of a solid-propulsion rocket. The work has been conducted within an academic rocketry team. As there is not clear reasoning on how to define these angles, the present research provides insights on how these geometrical parameters influence the performance of a rocket motor. A 2D-axisymmetric CFD domain is considered, comprising the fluid domain inside and outside the nozzle, to give room for the shock waves to happen and also accommodate the flow. The study comprises a baseline geometry and twelve modified designs, varying the convergent and the divergent angles of the nozzle. Since the convergent diameter must match the chamber diameter, it is fixed. For the divergent diameter, there is no such restriction; therefore, there are two possibilities: a divergent section with the same divergent diameter or with the same length as the baseline. The benchmark thrust curve is generated with a MATLAB code based on solid-fuel modeling and the De Laval theory. The curve is divided into six steady-state simulations, using boundary conditions of mass flow, pressure and temperature at the inlet and pressure and temperature at the outlet. The baseline geometry is simulated in Ansys Fluent and normalized by the MATLAB benchmark. A mesh study selects which mesh and turbulence model to use based on this normalization. The modified geometries are then compared to the baseline. The main quantity of interest is the thrust but quantities such as static pressure and average velocity at the nozzle exit aid the understanding of the changes in thrust

Passive galaxies as tracers of cluster environments at z~2

Even 10 billion years ago, the cores of the first galaxy clusters are often found to host a characteristic population of massive galaxies with already suppressed star formation. Here we search for distant cluster candidates at z~2 using massive passive galaxies as tracers. With a sample of ~40 spectroscopically confirmed passive galaxies at 1.3<z<2.1, we tune photometric redshifts of several thousands passive sources in the full 2 sq.deg. COSMOS field. This allows us to map their density in redshift slices, probing the large scale structure in the COSMOS field as traced by passive sources. We report here on the three strongest passive galaxy overdensities that we identify in the redshift range 1.5<z<2.5. While the actual nature of these concentrations is still to be confirmed, we discuss their identification procedure, and the arguments supporting them as candidate galaxy clusters (likely mid-10^13 M_sun range). Although this search approach is likely biased towards more evolved structures, it has the potential to select still rare, cluster-like environments close to their epoch of first appearance, enabling new investigations of the evolution of galaxies in the context of structure growth.Comment: 5 pages, 5 figures; A&A Letters, in pres

Pervasive and dynamic protein binding sites of the mRNA transcriptome in Saccharomyces cerevisiae

Abstract Background Protein-RNA interactions are integral components of nearly every aspect of biology, including regulation of gene expression, assembly of cellular architectures, and pathogenesis of human diseases. However, studies in the past few decades have only uncovered a small fraction of the vast landscape of the protein-RNA interactome in any organism, and even less is known about the dynamics of protein-RNA interactions under changing developmental and environmental conditions. Results Here, we describe the gPAR-CLIP (global photoactivatable-ribonucleoside-enhanced crosslinking and immunopurification) approach for capturing regions of the untranslated, polyadenylated transcriptome bound by RNA-binding proteins (RBPs) in budding yeast. We report over 13,000 RBP crosslinking sites in untranslated regions (UTRs) covering 72% of protein-coding transcripts encoded in the genome, confirming 3' UTRs as major sites for RBP interaction. Comparative genomic analyses reveal that RBP crosslinking sites are highly conserved, and RNA folding predictions indicate that secondary structural elements are constrained by protein binding and may serve as generalizable modes of RNA recognition. Finally, 38% of 3' UTR crosslinking sites show changes in RBP occupancy upon glucose or nitrogen deprivation, with major impacts on metabolic pathways as well as mitochondrial and ribosomal gene expression. Conclusions Our study offers an unprecedented view of the pervasiveness and dynamics of protein-RNA interactions in vivo.http://deepblue.lib.umich.edu/bitstream/2027.42/112318/1/13059_2012_Article_3050.pd

Amine-Gold Linked Single-Molecule Junctions: Experiment and Theory

The measured conductance distribution for single molecule benzenediamine-gold junctions, based on 59,000 individual conductance traces recorded while breaking a gold point contact in solution, has a clear peak at 0.0064 G$_{0}$ with a width of $\pm$ 40%. Conductance calculations based on density functional theory (DFT) for 15 distinct junction geometries show a similar spread. Differences in local structure have a limited influence on conductance because the amine-Au bonding motif is well-defined and flexible. The average calculated conductance (0.046 G$_{0}$) is seven times larger than experiment, suggesting the importance of many-electron corrections beyond DFT