bluuebunny/crossref_metadata_2025 huggingface dataset:
Three proteins mediate import of transit sequence-less precursors into the inner envelope of chloroplasts in
Arabidopsis thaliana
Authors: Rossig Claudia , Reinbothe Christiane , Gray John , Valdes Oscar , von Wettstein Diter , Reinbothe Steffen
Published: November 2013

Significance

Chloroplasts contain approximately 3,000 proteins, of which most are nuclear gene products synthesized in the cytosol with NH
2
-terminal, cleavable extensions referred to as chloroplast transit peptides for import. Chloroplasts additionally contain a set of plastid proteins lacking cleavable transit peptides. In this article we show how transit sequence-less proteins are transported from the cytosol to the inner envelope of the chloroplast. This import pathway is comparable to the mitochondrial pathway used for the import of carrier proteins and other, hydrophobic proteins without a transit sequence into the inner mitochondrial membrane.
Inositol polyphosphate multikinase is a coactivator for serum response factor-dependent induction of immediate early genes
Authors: Kim Eunha , Tyagi Richa , Lee Joo-Young , Park Jina , Kim Young-ran , Beon Jiyoon , Chen Po Yu , Cha Jiyoung Y. , Snyder Solomon H. , Kim Seyun
Published: November 2013

Significance

The inositol polyphosphate system is a major intracellular signaling modality. Inositol polyphosphate multikinase (IPMK) is essential for this system, converting inositol 1,4,5-trisphosphate (IP3) to IP4 and IP4 to IP5. IPMK also is a physiologic PI3-kinase. In a noncatalytic manner, IPMK stabilizes the mammalian target of rapamycin (mTOR) complex as well as tumor suppressor protein p53 and CREB-binding protein (CBP)/E1A binding protein p300. We now demonstrate that IPMK is a transcriptional coactivator for serum response factor (SRF) signaling, which is markedly reduced in IPMK-deleted mice and augmented by IPMK overexpression. IPMK binds directly to SRF, facilitating its interaction with serum response elements of multiple immediate early genes. Agents influencing IPMK interactions with SRF may be useful in regulating the SRF signaling system.
Lamellipodin branches out
Authors: Short Ben
Published: November 2013

Lamellipodin functions as an essential, general regulator of cell migration via the Scar/WAVE complex.
Langerhans cells are generated by two distinct PU.1-dependent transcriptional networks
Authors: Chopin Michaël , Seillet Cyril , Chevrier Stéphane , Wu Li , Wang Hongsheng , Morse Herbert C. , Belz Gabrielle T. , Nutt Stephen L.
Published: November 2013

Langerhans cells (LCs) are the unique dendritic cells found in the epidermis. While a great deal of attention has focused on defining the developmental origins of LCs, reports addressing the transcriptional network ruling their differentiation remain sparse. We addressed the function of a group of key DC transcription factors—PU.1, ID2, IRF4, and IRF8—in the establishment of the LC network. We show that although steady-state LC homeostasis depends on PU.1 and ID2, the latter is dispensable for bone marrow–derived LCs. PU.1 controls LC differentiation by regulating the expression of the critical TGF-β responsive transcription factor RUNX3. PU.1 directly binds to the Runx3 regulatory elements in a TGF-β–dependent manner, whereas ectopic expression of RUNX3 rescued LC differentiation in the absence of PU.1 and promoted LC differentiation from PU.1-sufficient progenitors. These findings highlight the dual molecular network underlying LC differentiation, and show the central role of PU.1 in these processes.
An Omega-result for Saito-Kurokawa lifts
Authors: Das Soumya , Sengupta Jyoti
Published: November 2013

We prove an Omega-result for the Hecke eigenvalues of Hecke operators acting on the space of Siegel modular forms of degree

2
2

which are Saito–Kurokawa lifts.
Large-scale patterns in puerulus settlement and links to fishery recruitment in the southern rock lobster (Jasus edwardsii), across south-eastern Australia
Authors: Linnane Adrian , McGarvey Richard , Gardner Caleb , Walker Terence I. , Matthews Janet , Green Bridget , Punt André E.
Published: November 2013

Monthly monitoring of puerulus settlement across South Australia, Victoria and Tasmania has been undertaken since the early 1990s. Firstly, annual trends in settlement were spatially analysed across the three States. In South Australian and Victorian settlement patterns were closely related. In Tasmania, settlement sites along the northeast coast were positively correlated, but showed no relationship with areas further south or in any other State. Secondly, annual settlement indices were correlated with lagged estimates of fishery recruitment. In South Australia, the strongest correlations between settlement and recruitment to legal size were observed using a 4–5- year time-lag. Within Victoria and Tasmania, the period from settlement to recruitment at 60 mm carapace length (CL) was 2 and 3 years, respectively. The period from 60 mm to legal size was another 2–3 years, suggesting that the total time from settlement to the fishery ranges from 4–6 years in these regions. The correlation between settlement and recruitment was used to forecast future estimates of exploitable biomass in one region of South Australia. The results indicate that puerulus monitoring is a relatively robust indicator of future fishery performance and should be regarded as an important data source for rock lobster resources within south-eastern Australia.
Testing the Copernican principle by constraining spatial homogeneity
Authors: Valkenburg Wessel , Marra Valerio , Clarkson Chris
Published: November 2013

We present a new programme for placing constraints on radial inhomogeneity in a dark-energy-dominated universe. We introduce a new measure to quantify violations of the Copernican principle. Any violation of this principle would interfere with our interpretation of any dark-energy evolution. In particular, we find that current observations place reasonably tight constraints on possible late-time violations of the Copernican principle: the allowed area in the parameter space of amplitude and scale of a spherical inhomogeneity around the observer has to be reduced by a factor of 3 so as to confirm the Copernican principle. Then, by marginalizing over possible radial inhomogeneity we provide the first constraints on the cosmological constant which are free of the homogeneity prior prevalent in cosmology.
A Metabolomic Approach to the Pathogenesis of Ventilator-induced Lung Injury
Authors: Izquierdo-García José L. , Naz Shama , Nin Nicolás , Rojas Yeny , Erazo Marcela , Martínez-Caro Leticia , García Antonia , de Paula Marta , Fernández-Segoviano Pilar , Casals Cristina , Esteban Andrés , Ruíz-Cabello Jesús , Barbas Coral , Lorente José A.
Published: November 2013

Background:

Global metabolic profiling using quantitative nuclear magnetic resonance spectroscopy (MRS) and mass spectrometry (MS) is useful for biomarker discovery. The objective of this study was to discover biomarkers of acute lung injury induced by mechanical ventilation (ventilator-induced lung injury [VILI]), by using MRS and MS.

Methods:

Male Sprague–Dawley rats were subjected to two ventilatory strategies for 2.5 h: tidal volume 9 ml/kg, positive end-expiratory pressure 5 cm H2O (control, n = 14); and tidal volume 25 ml/kg and positive end-expiratory pressure 0 cm H2O (VILI, n = 10). Lung tissue, bronchoalveolar lavage fluid, and serum spectra were obtained by high-resolution magic angle spinning and 1H-MRS. Serum spectra were acquired by high-performance liquid chromatography coupled to quadupole-time of flight MS. Principal component and partial least squares analyses were performed.

Results:

Metabolic profiling discriminated characteristics between control and VILI animals. As compared with the controls, animals with VILI showed by MRS higher concentrations of lactate and lower concentration of glucose and glycine in lung tissue, accompanied by increased levels of glucose, lactate, acetate, 3-hydroxybutyrate, and creatine in bronchoalveolar lavage fluid. In serum, increased levels of phosphatidylcholine, oleamide, sphinganine, hexadecenal and lysine, and decreased levels of lyso-phosphatidylcholine and sphingosine were identified by MS.

Conclusions:

This pilot study suggests that VILI is characterized by a particular metabolic profile that can be identified by MRS and MS. The metabolic profile, though preliminary and pending confirmation in larger data sets, suggests alterations in energy and membrane lipids.

SUPPLEMENTAL DIGITAL CONTENT IS AVAILABLE IN THE TEXT
Association of Cardiometabolic Risk Factors and Hepatic Enzymes in a National Sample of Iranian Children and Adolescents
Authors: Mohammadi Fatemeh , Qorbani Mostafa , Kelishadi Roya , Baygi Fereshteh , Ardalan Gelayol , Taslimi Mahnaz , Mahmoudarabi Minoosadat , Motlagh Mohammad‐Esmaeil , Asayesh Hamid , Larijani Bagher , Heshmat Ramin
Published: November 2013

Objectives:

Elevated liver enzymes including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) may be associated with metabolic syndrome (MetS) and cardiovascular disease. We investigated the association of cardiometabolic risk factors and liver enzymes in a nationally representative sample of Iranian children and adolescents.

Methods:

The national study was conducted in the framework of the third survey of Childhood and Adolescence Surveillance and PreventIon of Adult Non‐communicable Disease study. Subjects were 3948 students (1942 girls, 67.55% urban, mean age 14.7 ± 2.4 years) who were recruited by multistage random cluster sampling from 27 provincial counties in Iran. Physical examination and laboratory tests were conducted under standard protocols.

Results:

Participants with elevated serum ALT had higher levels of almost all cardiometabolic risk factors than other participants; this difference was not significant for fasting blood glucose, total cholesterol, and diastolic blood pressure in both sexes, as well as low‐density lipoprotein cholesterol in girls. Participants with generalized and abdominal obesity, MetS, elevated blood pressure, triglycerides, and total cholesterol had increased risk for elevated ALT; this risk remained significant after adjusting for sex and age. Low high‐density lipoprotein cholesterol was found as a predictor for both elevated ALT (odds ratio 2.182, 95% confidence interval 1.533–3.105) and AST (odds ratio 2.022, 95% confidence interval 1.438–2.844) even after adjusting for all potential confounders. General (B 0.158, SE 0.030) and abdominal obesity (B 0.058, SE 0.029), MetS (B 0.231, SE 0.048), and triglycerides (B 0.094, SE 0.030) were associated with ALT:AST ratio after adjusting for all potential confounders (P < 0.001).

Conclusions:

We documented strong relations of elevated ALT, AST levels, and ALT:AST ratio with most cardiometabolic risk factors. This relation was independent of anthropometric indexes. Liver enzymes can be considered as a cardiometabolic risk factor from childhood, and as an additional component of the MetS.
Association Between Child Maltreatment and Constipation
Authors: Rajindrajith Shaman , Devanarayana Niranga M. , Lakmini Chamila , Subasinghe Vindya , de Silva D.G. Harendra , Benninga Marc A.
Published: November 2013

Objective:

Child abuse leads to multiple physical and psychosomatic sequelae. The aim of the present study was to evaluate the association between child abuse and constipation among schoolchildren.

Methods:

Children 13 to 18 years of age were selected from 4 semiurban schools in Gampaha District, Sri Lanka. A self‐administered questionnaire was used for data collection. Information regarding sociodemographic factors and gastrointestinal symptoms, child abuse, and somatisation were collected. Constipation was diagnosed using Rome III criteria.

Results:

A total of 1792 children were included in the analysis (boys 975 [54.4%], mean age 14.4 years, standard deviation [SD] 1.3 years). One hundred thirty‐eight (7.7%) fulfilled Rome III criteria for constipation. The number of children exposed to physical, emotional, and sexual abuse were, respectively, 438 (24.4%), 396 (22.1%), and 51 (2.8%). The prevalence of constipation was significantly higher in those exposed to sexual (5.8% vs 2.6% P = 0.03), emotional (40.9% vs 20.8%, P < 0.0001), and physical abuse (41.6% vs 23.2%, P < 0.0001). Mean somatisation score was higher in the total group of abused children with constipation (mean 18.6, SD 12.5) compared with those without (mean 13.9, SD 12.3; P = 0.027). Children with a history of abuse did not seek health care more often than children without this history. Patient‐perceived severity of bowel symptoms was higher in children with physical abuse (23.7 vs 19.7 P = 0.001) and emotional abuse (25.4 vs 19.3 P < 0.0001).

Conclusions:

Childhood constipation shows a significant association with physical, sexual, and emotional abuse. Children with constipation complain of more somatic symptoms and bowel symptoms when they are exposed to abuse.
Entropy and convexity for nonlinear partial differential equations
Authors: Ball John M. , Chen Gui-Qiang G.
Published: November 2013

Partial differential equations are ubiquitous in almost all applications of mathematics, where they provide a natural mathematical description of many phenomena involving change in physical, chemical, biological and social processes. The concept of entropy originated in thermodynamics and statistical physics during the nineteenth century to describe the heat exchanges that occur in the thermal processes in a thermodynamic system, while the original notion of convexity is for sets and functions in mathematics. Since then, entropy and convexity have become two of the most important concepts in mathematics. In particular, nonlinear methods via entropy and convexity have been playing an increasingly important role in the analysis of nonlinear partial differential equations in recent decades. This opening article of the Theme Issue is intended to provide an introduction to entropy, convexity and related nonlinear methods for the analysis of nonlinear partial differential equations. We also provide a brief discussion about the content and contributions of the papers that make up this Theme Issue.
Cahn–Hilliard equations incorporating elasticity: analysis and comparison to experiments
Authors: Blesgen Thomas , Chenchiah Isaac Vikram
Published: November 2013

We consider a generalization of the Cahn–Hilliard equation that incorporates an elastic energy density which, being quasi-convex, incorporates micro-structure formation on smaller length scales. We explore the global existence of weak solutions in two and three dimensions. We compare theoretical predictions with experimental observations of coarsening in superalloys.
Entropy inequality and hydrodynamic limits for the Boltzmann equation
Authors: Saint-Raymond Laure
Published: November 2013

Boltzmann brought a fundamental contribution to the understanding of the notion of entropy, by giving a microscopic formulation of the second principle of thermodynamics. His ingenious idea, motivated by the works of his contemporaries on the atomic nature of matter, consists of describing gases as huge systems of identical and indistinguishable elementary particles. The state of a gas can therefore be described in a statistical way. The evolution, which introduces couplings, loses part of the information, which is expressed by the decay of the so-called mathematical entropy (the opposite of physical entropy!).
A Major Role for the Plastid-Encoded RNA Polymerase Complex in the Expression of Plastid Transfer RNAs
Authors: Williams-Carrier Rosalind , Zoschke Reimo , Belcher Susan , Pfalz Jeannette , Barkan Alice
Published: November 2013

Chloroplast transcription in land plants relies on collaboration between a plastid-encoded RNA polymerase (PEP) of cyanobacterial ancestry and a nucleus-encoded RNA polymerase of phage ancestry. PEP associates with additional proteins that are unrelated to bacterial transcription factors, many of which have been shown to be important for PEP activity in Arabidopsis (Arabidopsis thaliana). However, the biochemical roles of these PEP-associated proteins are not known. We describe phenotypes conditioned by transposon insertions in genes encoding the maize (Zea mays) orthologs of five such proteins: ZmPTAC2, ZmMurE, ZmPTAC10, ZmPTAC12, and ZmPRIN2. These mutants have similar ivory/virescent pigmentation and similar reductions in plastid ribosomes and photosynthetic complexes. RNA gel-blot and microarray hybridizations revealed numerous changes in plastid transcript populations, many of which resemble those reported for the orthologous mutants in Arabidopsis. However, unanticipated reductions in the abundance of numerous transfer RNAs (tRNAs) dominated the microarray data and were validated on RNA gel blots. The magnitude of the deficiencies for several tRNAs was similar to that of the most severely affected messenger RNAs, with the loss of trnL-UAA being particularly severe. These findings suggest that PEP and its associated proteins are critical for the robust transcription of numerous plastid tRNAs and that this function is essential for the prodigious translation of plastid-encoded proteins that is required during the installation of the photosynthetic apparatus.
Spatio-Temporal Transcript Profiling of Rice Roots and Shoots in Response to Phosphate Starvation and Recovery
Authors: Secco David , Jabnoune Mehdi , Walker Hayden , Shou Huixia , Wu Ping , Poirier Yves , Whelan James
Published: November 2013

Using rice (Oryza sativa) as a model crop species, we performed an in-depth temporal transcriptome analysis, covering the early and late stages of Pi deprivation as well as Pi recovery in roots and shoots, using next-generation sequencing. Analyses of 126 paired-end RNA sequencing libraries, spanning nine time points, provided a comprehensive overview of the dynamic responses of rice to Pi stress. Differentially expressed genes were grouped into eight sets based on their responses to Pi starvation and recovery, enabling the complex signaling pathways involved in Pi homeostasis to be untangled. A reference annotation-based transcript assembly was also generated, identifying 438 unannotated loci that were differentially expressed under Pi starvation. Several genes also showed induction of unannotated splice isoforms under Pi starvation. Among these, PHOSPHATE2 (PHO2), a key regulator of Pi homeostasis, displayed a Pi starvation–induced isoform, which was associated with increased translation activity. In addition, microRNA (miRNA) expression profiles after long-term Pi starvation in roots and shoots were assessed, identifying 20 miRNA families that were not previously associated with Pi starvation, such as miR6250. In this article, we present a comprehensive spatio-temporal transcriptome analysis of plant responses to Pi stress, revealing a large number of potential key regulators of Pi homeostasis in plants.
Improving the soluble expression of recombinant proteins by randomly shuffling 5′ and 3′ coding-sequence ends
Authors: Bignon Christophe , Li Changqing , Lichière Julie , Canard Bruno , Coutard Bruno
Published: November 2013

Many structural genomics (SG) programmes rely on the design of soluble protein domains. The production and screening of large libraries to experimentally select these soluble protein-encoding constructs are limited by the technologies and efforts that can be devoted to a single target. Using basic technologies available in any laboratory, a method named `boundary shuffling' was devised to generate orientated libraries for soluble domain selection without impeding the target flow.
Insights into the mechanism of X-ray-induced disulfide-bond cleavage in lysozyme crystals based on EPR, optical absorption and X-ray diffraction studies
Authors: Sutton Kristin A. , Black Paul J. , Mercer Kermit R. , Garman Elspeth F. , Owen Robin L. , Snell Edward H. , Bernhard William A.
Published: November 2013

Electron paramagnetic resonance (EPR) and online UV–visible absorption microspectrophotometry with X-ray crystallography have been used in a complementary manner to follow X-ray-induced disulfide-bond cleavage. Online UV–visible spectroscopy showed that upon X-irradiation, disulfide radicalization appeared to saturate at an absorbed dose of approximately 0.5–0.8 MGy, in contrast to the saturating dose of ∼0.2 MGy observed using EPR at much lower dose rates. The observations suggest that a multi-track model involving product formation owing to the interaction of two separate tracks is a valid model for radiation damage in protein crystals. The saturation levels are remarkably consistent given the widely different experimental parameters and the range of total absorbed doses studied. The results indicate that even at the lowest doses used for structural investigations disulfide bonds are already radicalized. Multi-track considerations offer the first step in a comprehensive model of radiation damage that could potentially lead to a combined computational and experimental approach to identifying when damage is likely to be present, to quantitate it and to provide the ability to recover the native unperturbed structure.
Duplex–quadruplex motifs in a peculiar structural organization cooperatively contribute to thrombin binding of a DNA aptamer
Authors: Russo Krauss Irene , Pica Andrea , Merlino Antonello , Mazzarella Lelio , Sica Filomena
Published: November 2013

Potent second-generation thrombin aptamers adopt a duplex–quadruplex bimodular folding and recognize thrombin exosite II with very high affinity and specificity. A sound model of these oligonucleotides, either free or in complex with thrombin, is not yet available. Here, a structural study of one of these aptamers, HD22-27mer, is presented. The crystal structure of this aptamer in complex with thrombin displays a novel architecture in which the helical stem is enchained to a pseudo-G-quadruplex. The results also underline the role of the residues that join the duplex and quadruplex motifs and control their recruitment in thrombin binding.
LigSearch: a knowledge-based web server to identify likely ligands for a protein target
Authors: de Beer Tjaart A. P. , Laskowski Roman A. , Duban Mark-Eugene , Chan A. W. Edith , Anderson Wayne F. , Thornton Janet M.
Published: November 2013

Identifying which ligands might bind to a protein before crystallization trials could provide a significant saving in time and resources.LigSearch, a web server aimed at predicting ligands that might bind to and stabilize a given protein, has been developed. Using a protein sequence and/or structure, the system searches against a variety of databases, combining available knowledge, and provides a clustered and ranked output of possible ligands.LigSearchcan be accessed at http://www.ebi.ac.uk/thornton-srv/databases/LigSearch.
The TLR signalling adaptor TRIF/TICAM-1 has an N-terminal helical domain with structural similarity to IFIT proteins
Authors: Ullah M. Obayed , Ve Thomas , Mangan Matthew , Alaidarous Mohammed , Sweet Matthew J. , Mansell Ashley , Kobe Bostjan
Published: November 2013

TRIF/TICAM-1 (TIR domain-containing adaptor inducing interferon-β/TIR domain-containing adaptor molecule 1) is the adaptor protein in the Toll-like receptor (TLR) 3 and 4 signalling pathway that leads to the production of type 1 interferons and cytokines. The signalling involves TIR (Toll/interleukin-1 receptor) domain-dependent TRIF oligomerization. A protease-resistant N-terminal region is believed to be involved in self-regulation of TRIF by interacting with its TIR domain. Here, the structural and functional characterization of the N-terminal domain of TRIF (TRIF-NTD) comprising residues 1–153 is reported. The 2.22 Å resolution crystal structure was solved by single-wavelength anomalous diffraction (SAD) using selenomethionine-labelled crystals of TRIF-NTD containing two additional introduced Met residues (TRIF-NTDA66M/L113M). The structure consists of eight antiparallel helices that can be divided into two subdomains, and the overall fold shares similarity to the interferon-induced protein with tetratricopeptide repeats (IFIT) family of proteins, which are involved in both the recognition of viral RNA and modulation of innate immune signalling. Analysis of TRIF-NTD surface features and the mapping of sequence conservation onto the structure suggest several possible binding sites involved in either TRIF auto-regulation or interaction with other signalling molecules or ligands. TRIF-NTD suppresses TRIF-mediated activation of the interferon-β promoter, as well as NF-κB-dependent reporter-gene activity. These findings thus identify opportunities for the selective targeting of TLR3- and TLR4-mediated inflammation.
Structural characterization of the ribonuclease H-like type ASKHA superfamily kinase MK0840 fromMethanopyrus kandleri
Authors: Schacherl Magdalena , Waltersperger Sandro , Baumann Ulrich
Published: November 2013

Murein recycling is a process in which microorganisms recover peptidoglycan-degradation products in order to utilize them in cell wall biosynthesis or basic metabolic pathways. Methanogens such asMethanopyrus kandlericontain pseudomurein, which differs from bacterial murein in its composition and branching. Here, four crystal structures of the putative sugar kinase MK0840 fromM. kandleriin apo and nucleotide-bound states are reported. MK0840 shows high similarity to bacterial anhydro-N-acetylmuramic acid kinase, which is involved in murein recycling. The structure shares a common fold with panthothenate kinase and the 2-hydroxyglutaryl-CoA dehydratase component A, both of which are members of the ASKHA (acetate and sugar kinases/Hsc70/actin) superfamily of phosphotransferases. Local conformational changes in the nucleotide-binding site between the apo and holo forms are observed upon nucleotide binding. Further insight is given into domain movements and putative active-site residues are identified.
High-resolution crystal structure of copper amine oxidase fromArthrobacter globiformis: assignment of bound diatomic molecules as O2
Authors: Murakawa Takeshi , Hayashi Hideyuki , Sunami Tomoko , Kurihara Kazuo , Tamada Taro , Kuroki Ryota , Suzuki Mamoru , Tanizawa Katsuyuki , Okajima Toshihide
Published: November 2013

The crystal structure of a copper amine oxidase fromArthrobacter globiformiswas determined at 1.08 Å resolution with the use of low-molecular-weight polyethylene glycol (LMW PEG; average molecular weight ∼200) as a cryoprotectant. The final crystallographicRfactor andRfreewere 13.0 and 15.0%, respectively. Several molecules of LMW PEG were found to occupy cavities in the protein interior, including the active site, which resulted in a marked reduction in the overallBfactor and consequently led to a subatomic resolution structure for a relatively large protein with a monomer molecular weight of ∼70 000. About 40% of the presumed H atoms were observed as clear electron densities in theFo−Fcdifference map. Multiple minor conformers were also identified for many residues. Anisotropic displacement fluctuations were evaluated in the active site, which contains a post-translationally derived quinone cofactor and a Cu atom. Furthermore, diatomic molecules, most likely to be molecular oxygen, are bound to the protein, one of which is located in a region that had previously been proposed as an entry route for the dioxygen substrate from the central cavity of the dimer interface to the active site.
Improvements in the order, isotropy and electron density of glypican-1 crystals by controlled dehydration
Authors: Awad Wael , Svensson Birkedal Gabriel , Thunnissen Marjolein M. G. M. , Mani Katrin , Logan Derek T.
Published: November 2013

The use of controlled dehydration for improvement of protein crystal diffraction quality is increasing in popularity, although there are still relatively few documented examples of success. A study has been carried out to establish whether controlled dehydration could be used to improve the anisotropy of crystals of the core protein of the human proteoglycan glypican-1. Crystals were subjected to controlled dehydration using the HC1 device. The optimal protocol for dehydration was developed by careful investigation of the following parameters: dehydration rate, final relative humidity and total incubation timeTinc. Of these, the most important was shown to beTinc. After dehydration using the optimal protocol the crystals showed significantly reduced anisotropy and improved electron density, allowing the building of previously disordered parts of the structure.
Protein energy landscapes determined by five-dimensional crystallography
Authors: Schmidt Marius , Srajer Vukica , Henning Robert , Ihee Hyotcherl , Purwar Namrta , Tenboer Jason , Tripathi Shailesh
Published: November 2013

Free-energy landscapes decisively determine the progress of enzymatically catalyzed reactions [Cornish-Bowden (2012),Fundamentals of Enzyme Kinetics, 4th ed.]. Time-resolved macromolecular crystallography unifies transient-state kinetics with structure determination [Moffat (2001),Chem. Rev.101, 1569–1581; Schmidtet al.(2005),Methods Mol. Biol.305, 115–154; Schmidt (2008),Ultrashort Laser Pulses in Medicine and Biology] because both can be determined from the same set of X-ray data. Here, it is demonstrated how barriers of activation can be determined solely from five-dimensional crystallography, where in addition to space and time, temperature is a variable as well [Schmidtet al.(2010),Acta Cryst.A66, 198–206]. Directly linking molecular structures with barriers of activation between them allows insight into the structural nature of the barrier to be gained. Comprehensive time series of crystallographic data at 14 different temperature settings were analyzed and the entropy and enthalpy contributions to the barriers of activation were determined. One hundred years after the discovery of X-ray scattering, these results advance X-ray structure determination to a new frontier: the determination of energy landscapes.
Structural basis of SUFU–GLI interaction in human Hedgehog signalling regulation
Authors: Cherry Amy L. , Finta Csaba , Karlström Mikael , Jin Qianren , Schwend Thomas , Astorga-Wells Juan , Zubarev Roman A. , Del Campo Mark , Criswell Angela R. , de Sanctis Daniele , Jovine Luca , Toftgård Rune
Published: November 2013

Hedgehog signalling plays a fundamental role in the control of metazoan development, cell proliferation and differentiation, as highlighted by the fact that its deregulation is associated with the development of many human tumours. SUFU is an essential intracellular negative regulator of mammalian Hedgehog signalling and acts by binding and modulating the activity of GLI transcription factors. Despite its central importance, little is known about SUFU regulation and the nature of SUFU–GLI interaction. Here, the crystal and small-angle X-ray scattering structures of full-length human SUFU and its complex with the key SYGHL motif conserved in all GLIs are reported. It is demonstrated that GLI binding is associated with major conformational changes in SUFU, including an intrinsically disordered loop that is also crucial for pathway activation. These findings reveal the structure of the SUFU–GLI interface and suggest a mechanism for an essential regulatory step in Hedgehog signalling, offering possibilities for the development of novel pathway modulators and therapeutics.
3-[1-(4-Bromophenyl)ethoxy]-2,2,5-trimethyl-4-phenyl-3-azahexane
Authors: Pitliya Praveen , Butcher Ray J. , Karim A. , Hudrlik Paul F. , Hudrlik Anne M. , Raghavan D.
Published: November 2013

The title compound, C22H30BrNO, is an alkoxyamine compound, an effective initiator in nitroxide-mediated free radical polymerization. It was prepared as a mixture of two diasteromers; the crystal for the X-ray analysis showed one of these as a pair ofR,SandS,Renantiomers. Thetert-butyl and isopropyl groups are in an almostanticonformation in the crystal [C—N—C—C torsion angle = −168.8 (1)°], and the methyl group of the ethoxy group is in an approximateantirelationship to thetert-butyl group. The dihedral angle between the phenyl and benzene rings is 33.12 (7)°. The Br atom is disordered over two positions, with occupancies of 0.9139 (16) and 0.0861 (16). In the crystal, weak C—H...Br contacts link the molecules into chains along [-110].
Poly[di-μ9-citrato-tetrasodiumzinc]
Authors: Ma Yu-Hong , Yang Hong-Wei , Hao Jing-Tuan , Ma Pi-Zhuang , Yao Ting
Published: November 2013

In the title compound, [Na4Zn(C6H5O7)2]n, the ZnIIion lies on an inversion center and is coordinated by six O atoms from two citrate ligands, forming a distorted octahedral geometry. There are two crystallographically independent Na+cations in the asymmetric unit. One Na+cation exhibits a distorted square-pyramidal geometry defined by five O atoms from four citrate ligands. The other Na+cation is surrounded by six O atoms from five citrate ligands in a distorted octahedral geometry. The Na+cations are bridged by citrate carboxylate groups, forming a layer parallel to (100). The layers are further assembled into a three-dimensional network with the [Zn(citrate)2]4−building units as `pillars'; O—H...O hydrogen bonds also stabilize the structure.
[6,6′-Bis(1,1-dimethylethyl)-4,4′-dimethyl-2,2′-methylenediphenolato-κ2O,O′]dichlorido(9H-fluoren-9-ol-κO)titanium(IV)–fluorene–diethyl ether (1/0.5/1)
Authors: Nielson Alastair J. , Shen Chaohong , Waters Joyce M.
Published: November 2013

The title adduct, [TiCl2(C23H30O2)(C13H10O]·0.5C13H10·C4H10O, is a monomer with a trigonal–bypyramidal coordination sphere of the TiIVatom in which the ligand O atoms of the bidentate diphenolate anion are located in both apical and equatorial positions. Chloride ligands occupy the remaining two equatorial sites of the trigonal bypyramid with the fluoren-9-ol O atom occupying the other apical site. The hydroxy group H atom of this latter group is hydrogen bonded to an O atom of a non-coordinating diethyl ether molecule. The title compound also contains a further fluorene solvent molecule, which lies across a centre of symmetry and which is equally disordered over an inversion centre.
13-(N,N-Dimethylamino)micheliolide 0.08-hydrate
Authors: Bommagani Shobanbabu , Penthala Narsimha Reddy , Janganati Venumadhav , Parkin Sean , Crooks Peter A.
Published: November 2013

The title compound, C17H27NO3·0.08H2O {sytematic name: (3R,3aS,9R,9aS,9bS)-3-[(dimethylamino)methyl]-9-hydroxy-6,9-dimethyl-3,3a,4,5,7,8,9,9a-octahydroazuleno[4,5-b]furan-2(9bH)-one 0.08-hydrate}, exhibits intramolecular O—H...O hydrogen bonding to form a ring of graph-set motifS(6). As well as this intramolecular hydrogen bond with the lactone-ring O atom, the hydroxy H atom forms an O—H...O hydrogen bond to the low-occupancy partial water molecule [occupancy = 0.078 (2)]. The water molecule is correlated with disorder of the N(CH3)2group [major–minor occupancy factors are 0.922 (2):0.078 (2)]. The dihedral angle between the mean planes of thetrans-fused seven-membered ring and the lactone ring is 4.42 (9)°.
A triclinic polymorph of (−)-(S)-N-benzyl-2-[(R)-6-fluorochroman-2-yl]-2-hydroxyethanaminium bromide
Authors: Rousselin Yoann , Laureano Hugo , Clavel Alexandre
Published: November 2013

The title salt, C18H21FNO2+·Br−, determined at 115 K, crystallizes in the triclinic space groupP1. The previously reported polymorph occurs in the monoclinic space groupP21and has two independent molecules in the asymmetric unit [Peeterset al.(1993).Acta Cryst.C49, 2157–2160]. In the title molecule, the pyran rings adopt half-chair conformations. The absolute configuration isSfor the hydroxy-bearing C atom andRfor the asymmetric C atom in the dihydropyran unit. In the crystal, the components are linked by N—H...Br and O—H...Br hydrogen bonds, forming chains along thec-axis direction. The crystal studied was refined as an inversion twin.
2,4,6-Trinitrophenyl 4-bromobenzoate
Authors: Moreno-Fuquen Rodolfo
Published: November 2013

In the title benzoate derivative, C13H6BrN3O8, the benzene rings form a dihedral angle of 80.90 (9)°. The ester moiety forms dihedral angles of 3.2 (2) and 82.8 4(10)° with the benzene and picryl rings, respectively. The Br atom is disordered over two positions, with the site occupancy for the minor component being 0.48 (4). The crystal structure features C—H...O interactions, which generate a three-dimensional network.
5-(5′-Fluoro-2′-methoxybiphenyl-3-yl)-1,3,4-oxadiazol-2-amine
Authors: Usha M. K. , Ramaprasad G. C. , Kalluraya Balakrishna , Kant Rajni , Gupta Vivek K. , Revannasiddaiah D.
Published: November 2013

In the title compound, C15H12FN3O2, the dihedral angles between the central benzene ring and the pendant benzene and oxadiazole rings are 45.05 (13) and 15.60 (14)°, respectively. The C atom of the methoxy group is roughly coplanar with its attached ring [displacement = 0.178 (4) Å]. In the crystal, N—H...N hydrogen bonds link the molecules into [010] chains. Weak C—H...π interactions are also observed.
2-[(Ferrocen-1-yl)(hydroxy)methyl]prop-2-enenitrile
Authors: Selvanayagam S. , Ravikumar K. , Kathiravan S. , Raghunathan R.
Published: November 2013

In the title ferrocene derivative, [Fe(C5H5)(C9H8NO)], the dihedral angle between the enenitrile group and the substituted cyclopentadienyl ring is 71.2 (1)°. The cyclopentadienyl rings of the ferrocene moiety are arranged in an eclipsed conformation. The hydroxy group, and the corresponding methine H atom, are disordered over two sets of sites with site-occupancy factors of 0.744 (4) and 0.256 (4). An intramolecular C—H...O close contact is observed. In the crystal, O—H...N hydrogen bonds form aC(6) chain along [100].
Poly[bis(μ2-1,3-phenylenediamine-κ2N:N′)di-μ-thiocyanato-κ2N:S;κ2S:N-cadmium]
Authors: Chemli Rakia , Kamoun Slaheddine , Roisnel Thierry
Published: November 2013

The structure of the title polymeric compound, [Cd(SCN)2(C6H8N2)2]n, exhibits a two-dimensional staircase-like structure parallel to (010) in which the CdIIatom lies on a twofold rotation axis and has a distorted octahedral CdS2N4geometry involving four μ-1,3-(SCN) group donors and two N-atom donors from 1,3-phenylenediamine ligands, which also have twofold symmetry. The major contributions to the cohesion and the stability of this two-dimensional polymeric structure are the covalent Cd—S,N bonds and one weak intralayer N—H...S hydrogen bond.
Lack of coherence in the warming responses of marine crustaceans
Authors: Faulkner Katelyn T. , Clusella‐Trullas Susana , Peck Lloyd S. , Chown Steven L.
Published: November 2013

Understanding the extent to which organisms are affected by climate change and are capable of adapting to warming is essential for managing biodiversity. Recent macrophysiological analyses suggest that range‐related responses to warming may be more coherent (less variable) and predictable in marine than in terrestrial systems.

To examine this generalization, we investigate basal upper thermal tolerances (measured asCTmax), the extent of their phenotypic plasticity and the impacts of different rates of temperature change on these tolerances, in five species of intertidal crustaceans from three distinct thermal regimes, incorporating South African (RSA) shores and sub‐Antarctic Marion Island (MI).

For all species, lower rates of change resulted in lowerCTmax,while acclimation resulted in varied responses depending on the rate of temperature change. At fast rates of temperature change, higher temperature acclimation resulted in elevatedCTmax,while at slow rates of change, acclimation had no effect or resulted in a decline inCTmax.

Maximum habitat temperatures recorded at the organisms' microsites were lower than theCTmaxfor theMIpopulations but were aboveCTmaxat slow rates of change forRSApopulations. Thus, populations from more equatorward locations have a lower tolerance of extremes than those from cooler regions. In addition to reduced warming tolerance,RSApopulations had a lower acclimation capacity than their sub‐Antarctic counterparts.

We find substantial differences in long‐term responses among groups in different areas as a consequence of spatial variation in the interactions among basal tolerance, phenotypic plasticity and thermal environments. These outcomes emphasize the significance of examining forecasts using a range of data and approaches so that their certainty can be established to inform key policy decisions in a spatially appropriate context.
Genome‐guided insights into the versatile metabolic capabilities of the mercaptosuccinate‐utilizing β‐proteobacterium Variovorax paradoxus strain B4
Authors: Brandt Ulrike , Hiessl Sebastian , Schuldes Jörg , Thürmer Andrea , Wübbeler Jan Hendrik , Daniel Rolf , Steinbüchel Alexander
Published: November 2013

Variovorax paradoxus B4 is able to utilize 2‐mercaptosuccinate (MS) as sole carbon, sulfur and energy source. The whole genome of V. paradoxus B4 was sequenced, annotated and evaluated with special focus on genomic elements related to MS metabolism. The genome encodes two chromosomes harbouring 5 795 261 and 1 353 255 bp. A total of 6753 putative protein‐coding sequences were identified. Based on the genome and in combination with results from previous studies, a putative pathway for the degradation of MS could be postulated. The putative molybdopterin oxidoreductase identified during transposon mutagenesis probably catalyses the conversion of MS first into sulfinosuccinate and then into sulfosuccinate by successive transfer of oxygen atoms. Subsequently, the cleavage of sulfosuccinate yields oxaloacetate and sulfite, while the latter is oxidized to sulfate. The expression of the putative molybdopterin oxidoreductase was induced by MS, but not by gluconate, as confirmed by reverse transcriptase polymerase chain reaction. Further, in silico studies combined with experiments and comparative genomics revealed high metabolic diversity of strain B4. It bears a high potential as plant growth‐promoting bacterium and as candidate for degradation and detoxification of xenobiotics and other hardly degradable substances. Additionally, the strain is of special interest for production of polythioesters with sulfur‐containing precursors as MS.
Developing a Chinese version of anAuthor Recognition Testfor college students in Taiwan
Authors: Chen Su‐Yen , Fang Sheng‐Ping
Published: November 2013

This study set out to develop a Chinese Author Recognition Test (CART) that might be used as a measure of objective print exposure for college students in Taiwan. We found that there is a linkage between print exposure and general reading achievement for college students. We also found that, among self‐reported reading habits, comparative reading habits and CART, primary print knowledge scores within the CART family have the strongest prediction power for both the ‘General Scholastic Ability Test‐Chinese’ and the ‘Department Required Test‐Chinese’ beyond the joint contributions of vocabulary size and reading comprehension. By sharing the process of developing the instrument, we shed some light for researchers from regions other than English‐speaking countries on how they might move forward in future investigations.
Prediction of time to return to work after gynaecological surgery: a prospective cohort study in the Netherlands
Authors: Vonk Noordegraaf A , Anema JR , Louwerse MD , Heymans MW , van Mechelen W , Brölmann HAM , Huirne JAF
Published: November 2013

Objective

To measure the impact of the level of invasiveness of gynaecological procedures on time to full Return to Work (RTW) and to identify the most important preoperative sociodemographic, medical and work‐related factors that predict the risk of prolonged sick leave.

Design

Prospective cohort study.

Setting

Dutch university hospital.

Population

A total of 148 women aged 18–65 years scheduled for gynaecological surgery for benign indications.

Methods

A questionnaire regarding the surgical procedure as well as perioperative and postoperative complications was completed by the attending resident at baseline and 6 weeks after surgery. All other outcome measures were assessed using self‐reported patient questionnaires at baseline and 12 weeks post‐surgery. The follow‐up period was extended up to 1 year after surgery in women failing to return to work. Surgical procedures were categorised into diagnostic, minor, intermediate and major surgery.

Main outcome measures

Time to RTW and important predictors for prolonged sick leave after surgery.

Results

Median time to RTW was 7 days (interquartile range [IQR] 5–14) for diagnostic surgery, 14 days (IQR 9–28) for minor surgery, 60 days (IQR 28–101) for intermediate surgery and 69 days (IQR 56–135) for major surgery. Multivariable analysis showed a strongest predictive value of RTW 1 year after surgery for level of invasiveness of surgery (minor surgery hazard ratio [HR] 0.51, 95% CI 0.32–0.81; intermediate surgery HR 0.20, 95% CI 0.12–0.34; major surgery HR 0.09, 95% CI 0.06–0.16), RTW expectations before surgery (HR 0.55, 95% CI 0.36–0.84), and preoperative functional status (HR 1.09, 95% CI 1.04–1.13). A prediction model regarding the probability of prolonged sick leave at 6 weeks was developed, with a sensitivity of 89% and a specificity of 86%.

Conclusions

RTW often takes a long time, especially after intermediate and major surgery. This study reveals important predictors for prolonged sick leave and provides a prediction model for the risk of sick leave extending 6 weeks after benign gynaecological surgery in the Netherlands.
Equity in Access to Health Care Services in Italy
Authors: Glorioso Valeria , Subramanian S. V.
Published: November 2013

Objective

To provide new evidence on whether and how patterns of health care utilization deviate from horizontal equity in a country with a universal and egalitarian public health care system: Italy.

Data Sources

Secondary analysis of data from the Health Conditions and Health Care Utilization Survey 2005, conducted by the Italian National Institute of Statistics on a probability sample of the noninstitutionalized Italian population.

Study Design

Using multilevel logistic regression, we investigated how the probability of utilizing five health care services varies among individuals with equal health status but different SES.

Data Collection/Extraction

Respondents aged 18 or older at the interview time (n = 103,651).

Principal Findings

Overall, we found that use of primary care is inequitable in favor of the less well‐off, hospitalization is equitable, and use of outpatient specialist care, basic medical tests, and diagnostic services is inequitable in favor of the well‐off. Stratifying the analysis by health status, however, we found that the degree of inequity varies according to health status.

Conclusions

Despite its universal and egalitarian public health care system, Italy exhibits a significant degree of SES‐related horizontal inequity in health services utilization.
Economic Determinants and Information Environment Effects of Earnouts: New Insights from SFAS 141(R)
Authors: CADMAN BRIAN , CARRIZOSA RICHARD , FAUREL LUCILE
Published: November 2013

Contingent considerations (earnouts) in acquisition agreements provide sellers with future payments conditional on meeting certain conditions. Prior research provides evidence that acquiring firms use earnouts to minimize agency costs associated with acquisitions. Using earnout fair value information, recently mandated by SFAS 141(R), we provide new insights into the economic determinants to include earnout provisions in acquisition agreements, including motivations to resolve moral hazard and adverse selection problems, bridge valuation gaps, and retain target firm managers. We document variations in initial earnout fair value estimates and earnout fair value adjustments that correspond with these underlying motivations. We also provide evidence that target managers stay longer with the firm after the acquisition when earnouts are included primarily to retain target managers. Finally, we demonstrate that earnout fair value adjustments required by SFAS 141(R) provide valuable information to market participants and are negatively associated with the likelihood of contemporaneous and future goodwill impairments.