Cryo-EM structure of the E. coli translating ribosome in complex with SRP and its receptor

We report the 'early' conformation of the Escherichia coli signal recognition particle (SRP) and its receptor FtsY bound to the translating ribosome, as determined by cryo-EM. FtsY binds to the tetraloop of the SRP RNA, whereas the NG domains of the SRP protein and FtsY interact weakly in this conformation. Our results suggest that optimal positioning of the SRP RNA tetraloop and the Ffh NG domain leads to FtsY recruitment

Structure and function of eukaryotic fatty acid synthases

In all organisms, fatty acid synthesis is achieved in variations of a common cyclic reaction pathway by stepwise, iterative elongation of precursors with two-carbon extender units. In bacteria, all individual reaction steps are carried out by monofunctional dissociated enzymes, whereas in eukaryotes the fatty acid synthases (FASs) have evolved into large multifunctional enzymes that integrate the whole process of fatty acid synthesis. During the last few years, important advances in understanding the structural and functional organization of eukaryotic FASs have been made through a combination of biochemical, electron microscopic and X-ray crystallographic approaches. They have revealed the strikingly different architectures of the two distinct types of eukaryotic FASs, the fungal and the animal enzyme system. Fungal FAS is a 2·6 MDa α6β6 heterododecamer with a barrel shape enclosing two large chambers, each containing three sets of active sites separated by a central wheel-like structure. It represents a highly specialized micro-compartment strictly optimized for the production of saturated fatty acids. In contrast, the animal FAS is a 540 kDa X-shaped homodimer with two lateral reaction clefts characterized by a modular domain architecture and large extent of conformational flexibility that appears to contribute to catalytic efficienc

Prospective, randomized, double-blind trial to investigate the efficacy and safety of corneal cross-linking to halt the progression of keratoconus

Background: Corneal cross-linking is widely used to treat keratoconus. However, to date, only limited data from randomized trials support its efficacy. Methods: The efficacy and safety of corneal cross-linking for halting progression of keratoconus were investigated in a prospective, randomized, blinded, placebo controlled, multicentre trial. Twenty-nine keratoconus patients were randomized in three trial centres. The mean age at inclusion was 28 years. Longitudinal changes in corneal refraction were assessed by linear regression. The best corrected visual acuity, surface defects and corneal inflammation were also assessed. These data were analysed with a multifactorial linear regression model. Results: A total of 15 eyes were randomized to the treatment and 14 to the control group. Follow-up averaged 1098 days. Corneal refractive power decreased on average (+/-standard deviation) by 0.35 +/- 0.58 dioptres/year in the treatment group. The controls showed an increase of 0.11 +/- 0.61 dioptres/year. This difference was statistically significant (p = 0.02). Conclusions: Our data suggest that corneal cross-linking is an effective treatment for some patients to halt the progression of keratoconus. However, some of the treated patients still progressed, whereas some untreated controls improved. Therefore, further investigations are necessary to decide which patients require treatment and which do not

The 31 Deg2^2 Release of the Stripe 82 X-ray Survey: The Point Source Catalog

We release the next installment of the Stripe 82 X-ray survey point-source catalog, which currently covers 31.3 deg$^2$ of the Sloan Digital Sky Survey (SDSS) Stripe 82 Legacy field. In total, 6181 unique X-ray sources are significantly detected with {\it XMM-Newton} ($>5\sigma$) and {\it Chandra} ($>4.5\sigma$). This catalog release includes data from {\it XMM-Newton} cycle AO 13, which approximately doubled the Stripe 82X survey area. The flux limits of the Stripe 82X survey are $8.7\times10^{-16}$ erg s$^{-1}$ cm$^{-2}$, $4.7\times10^{-15}$ erg s$^{-1}$ cm$^{-2}$, and $2.1\times10^{-15}$ erg s$^{-1}$ cm$^{-2}$ in the soft (0.5-2 keV), hard (2-10 keV), and full bands (0.5-10 keV), respectively, with approximate half-area survey flux limits of $5.4\times10^{-15}$ erg s$^{-1}$ cm$^{-2}$, $2.9\times10^{-14}$ erg s$^{-1}$ cm$^{-2}$, and $1.7\times10^{-14}$ erg s$^{-1}$ cm$^{-2}$. We matched the X-ray source lists to available multi-wavelength catalogs, including updated matches to the previous release of the Stripe 82X survey; 88\% of the sample is matched to a multi-wavelength counterpart. Due to the wide area of Stripe 82X and rich ancillary multi-wavelength data, including coadded SDSS photometry, mid-infrared {\it WISE} coverage, near-infrared coverage from UKIDSS and VHS, ultraviolet coverage from {\it GALEX}, radio coverage from FIRST, and far-infrared coverage from {\it Herschel}, as well as existing $\sim$30\% optical spectroscopic completeness, we are beginning to uncover rare objects, such as obscured high-luminosity AGN at high-redshift. The Stripe 82X point source catalog is a valuable dataset for constraining how this population grows and evolves, as well as for studying how they interact with the galaxies in which they live.Comment: accepted for publication in ApJ; 23 pages (emulateapj

Structure of the quaternary complex between SRP, SR, and translocon bound to the translating ribosome

During co-translational protein targeting, the signal recognition particle (SRP) binds to the translating ribosome displaying the signal sequence to deliver it to the SRP receptor (SR) on the membrane, where the signal peptide is transferred to the translocon. Using electron cryo-microscopy, we have determined the structure of a quaternary complex of the translating Escherichia coli ribosome, the SRP–SR in the ‘activated’ state and the translocon. Our structure, supported by biochemical experiments, reveals that the SRP RNA adopts a kinked and untwisted conformation to allow repositioning of the ‘activated’ SRP–SR complex on the ribosome. In addition, we observe the translocon positioned through interactions with the SR in the vicinity of the ribosome exit tunnel where the signal sequence is extending beyond its hydrophobic binding groove of the SRP M domain towards the translocon. Our study provides new insights into the mechanism of signal sequence transfer from the SRP to the translocon

As disputas em torno do orçamento público federal: capital financeiro, dívida pública e o novo regime fiscal.

TCC (Graduação) - Universidade Federal de Santa Catarina. Centro Socioeconômico. Serviço Social.O estudo buscou desvelar as formas como o fundo público é apropriado pelo capital rentista, por meio de mecanismos estruturados pelo próprio Estado em detrimento de sua utilização para as políticas sociais, onde o mesmo opera como coadjuvante no sistema de acumulação em prejuízo da classe trabalhadora. Para alcançar este objetivo, o estudo está assentado na pesquisa bibliográfica e na análise crítico-dialética, no sentido de compreender o Estado capitalista, suas leis, suas medidas e sua institucionalização no atual contexto histórico- institucional financeiro rentista, no qual a prioridade tem sido o ajuste fiscal para garantir o pagamento pontual das obrigações do Estado para com os credores relativos à dívida pública. A metodologia do estudo procurou cobrir os interesses que capturam o Estado contemporâneo sob o domínio do capital rentista. Parte-se da constatação da importância da compreensão do processo de arrecadação e composição dos gastos do Orçamento Federal da União, para a correta análise do financiamento das políticas sociais na atual conjuntura da ordem social brasileira. No percurso que embasa teoricamente a pesquisa empírica ressalta-se a concepção histórica e dialética do Estado, fundamentalmente determinado pela estrutura classista da sociedade sob a ordem do capital. A fim de desvelar os mecanismos utilizados pelo governo, e pelo Capital, consideramos analisar alguns dos elementos que incidem no processo de arrecadação a partir de impostos e tributos, que constituem o fundo público, as decisões e interesses que compõem os gastos, e como esses refletem a correlação de forças existentes na disputa pela riqueza socialmente produzida, discutindo a relação entre Dívida Pública, rentismo, crise do capital, e o discurso falacioso do governo atual, com a implementação da Emenda Constitucional N. 95, acompanhado por reformas(contrarreformas) que vem a reforçar a apropriação do fundo público pelo capital em prejuízo aos direitos sociais, agudizando a exploração da classe dominada, caracterizando -se como bárbaro desmonte e retrocesso social, incidindo diretamente nos direitos sociais duramente conquistados pela classe trabalhadora

40S hnRNP particles are a novel class of nuclear biomolecular condensates.

Heterogenous nuclear ribonucleoproteins (hnRNPs) are abundant proteins implicated in various steps of RNA processing that assemble on nuclear RNA into larger complexes termed 40S hnRNP particles. Despite their initial discovery 55 years ago, our understanding of these intriguing macromolecular assemblies remains limited. Here, we report the biochemical purification of native 40S hnRNP particles and the determination of their complete protein composition by label-free quantitative mass spectrometry, identifying A-group and C-group hnRNPs as the major protein constituents. Isolated 40S hnRNP particles dissociate upon RNA digestion and can be reconstituted in vitro on defined RNAs in the presence of the individual protein components, demonstrating a scaffolding role for RNA in nucleating particle formation. Finally, we revealed their nanometer scale, condensate-like nature, promoted by intrinsically disordered regions of A-group hnRNPs. Collectively, we identify nuclear 40S hnRNP particles as novel dynamic biomolecular condensates

The C4 Clustering Algorithm: Clusters of Galaxies in the Sloan Digital Sky Survey

We present the "C4 Cluster Catalog", a new sample of 748 clusters of galaxies identified in the spectroscopic sample of the Second Data Release (DR2) of the Sloan Digital Sky Survey (SDSS). The C4 cluster--finding algorithm identifies clusters as overdensities in a seven-dimensional position and color space, thus minimizing projection effects which plagued previous optical clusters selection. The present C4 catalog covers ~2600 square degrees of sky with groups containing 10 members to massive clusters having over 200 cluster members with redshifts. We provide cluster properties like sky location, mean redshift, galaxy membership, summed r--band optical luminosity (L_r), velocity dispersion, and measures of substructure. We use new mock galaxy catalogs to investigate the sensitivity to the various algorithm parameters, as well as to quantify purity and completeness. These mock catalogs indicate that the C4 catalog is ~90% complete and 95% pure above M_200 = 1x10^14 solar masses and within 0.03 <=z <= 0.12. The C4 algorithm finds 98% of X-ray identified clusters and 90% of Abell clusters within 0.03 <= z <= 0.12. We show that the L_r of a cluster is a more robust estimator of the halo mass (M_200) than the line-of-sight velocity dispersion or the richness of the cluster. L_r. The final SDSS data will provide ~2500 C4 clusters and will represent one of the largest and most homogeneous samples of local clusters.Comment: 32 pages of figures and text accepted in AJ. Electronic version with additional tables, links, and figures is available at http://www.ctio.noao.edu/~chrism/c

Receptor compaction and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER

The conserved signal recognition particle (SRP) cotranslationally delivers ~30% of the proteome to the eukaryotic endoplasmic reticulum (ER). The molecular mechanism by which eukaryotic SRP transitions from cargo recognition in the cytosol to protein translocation at the ER is not understood. Here, structural, biochemical, and single-molecule studies show that this transition requires multiple sequential conformational rearrangements in the targeting complex initiated by guanosine triphosphatase (GTPase)–driven compaction of the SRP receptor (SR). Disruption of these rearrangements, particularly in mutant SRP54G226E linked to severe congenital neutropenia, uncouples the SRP/SR GTPase cycle from protein translocation. Structures of targeting intermediates reveal the molecular basis of early SRP-SR recognition and emphasize the role of eukaryote-specific elements in regulating targeting. Our results provide a molecular model for the structural and functional transitions of SRP throughout the targeting cycle and show that these transitions provide important points for biological regulation that can be perturbed in genetic diseases

Molecular Architecture of the 40S⋅eIF1⋅eIF3 Translation Initiation Complex

Eukaryotic translation initiation requires the recruitment of the large, multiprotein eIF3 complex to the 40S ribosomal subunit. Using X-ray structures of all major components of the minimal, six-subunit Saccharomyces cerevisiae eIF3 core, together with cross-linking coupled to mass spectrometry, we were able to use IMP to position and orient all eIF3 components on the 40S•eIF1 complex, revealing an extended, modular arrangement of eIF3 subunits. For more information about how to reproduce this modeling, see https://salilab.org/40S-eIF1-eIF3 or the README file