bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystallization and preliminary X-ray crystallographic analysis of a bacterial Asn-transamidosome
Authors: Suzuki Tateki , Yamashita Keitaro , Tanaka Yoshikazu , Tanaka Isao , Yao Min
Published: May 2014

Most canonical aminoacyl-tRNAs are synthesized directly by their cognate aminoacyl-tRNA synthetases (aaRSs), but glutaminyl-tRNAGlnand asparaginyl-tRNAAsnare synthesized indirectly by two-step processes. These processes are catalyzed by the transamidosome, a large ribonucleoprotein particle composed of GatA, GatB, GatC, aaRS and tRNA. In this study, the Asn-transamidosome fromPseudomonas aeruginosawas reconstructed and crystallized by mixing purified GatCAB complex, AspRS and tRNAAsn. The crystal of the Asn-transamidosome belonged to space groupP21, with unit-cell parametersa= 93.3,b= 186.0,c= 287.8 Å, β = 93.3°, and diffracted to 3.73 Å resolution. Preliminary X-ray crystallographic analysis showed that the asymmetric unit contained two Asn-transamidosomes, each composed of two GatCABs, one AspRS dimer and two tRNAAsns, indicating that the construction of the current Asn-transamidosome differs from that ofThermus thermophilus.
Expression, purification, crystallization and preliminary X-ray analysis of the HER3–9E12 Fab complex
Authors: He Kecheng , Huang Ang , Huang Yong , Takeda Hiroaki
Published: May 2014

9E12 is a fully human immunoglobulin G1/κ monoclonal antibody that is specific for the epidermal growth factor receptor 3 (HER3), the overexpression of which has been detected in many tumour types and is associated with poor survival outcomes. To date, knowledge of the molecular mechanism for targeted antibodies that directly inhibit HER3 signalling is limited. Because knowledge of such therapeutic antibodies would help basic immunological therapeutics, structural insights into the HER3–9E12 Fab complex are important. Recombinant human HER3 and Fab fragments of the 9E12 antibody were cloned, expressed and crystallized, and crystallographic data sets were collected. The crystals belonged to space groupP1, with unit-cell parametersa= 74.4,b= 98.6,c= 99.6 Å, α = 106.0, β = 95.0, γ = 102.5° and diffracted to a resolution of 2.1 Å.
Expression, purification, crystallization and preliminary X-ray crystallographic analysis of Enpp6
Authors: Morita Junko , Kato Kazuki , Mihara Emiko , Ishitani Ryuichiro , Takagi Junichi , Nishimasu Hiroshi , Aoki Junken , Nureki Osamu
Published: May 2014

Enpp (ectonucleotide phosphodiesterase/pyrophosphatase) 6 is a membrane-bound glycoprotein that hydrolyzes choline-containing compounds such as lysophosphatidylcholine and glycerophosphorylcholine, and presumably participates in choline metabolism. The catalytic domain of mouse Enpp6 was expressed in HEK293T cells, purified using the TARGET tag/P20.1-Sepharose system and crystallized. An X-ray diffraction data set was collected to 1.8 Å resolution. The crystal belonged to space groupP1, with unit-cell parametersa= 63.7,b= 68.8,c= 69.7 Å, α = 60.6, β = 87.0, γ = 68.1°. Assuming the presence of two protein molecules per asymmetric unit, the solvent content was estimated to be 49.5%.
Crystallization and preliminary X-ray diffraction analysis of (R)-carbonyl reductase fromCandida parapsilosis
Authors: Wang Shanshan , Nie Yao , Yan Xu , Ko Tzu-Ping , Huang Chun-Hsiang , Chan Hsiu-Chien , Guo Rey-Ting , Xiao Rong
Published: May 2014

The NADH-dependent (R)-carbonyl reductase fromCandida parapsilosis(RCR) catalyzes the asymmetric reduction of 2-hydroxyacetophenone (HAP) to produce (R)-1-phenyl-1,2-ethanediol [(R)-PED], which is used as a versatile building block for the synthesis of pharmaceuticals and fine chemicals. To gain insight into the catalytic mechanism, the structures of complexes of RCR with ligands, including the coenzyme, are important. Here, the recombinant RCR protein was expressed and purified inEscherichia coliand was crystallized in the presence of NAD+. The crystals, which belonged to the orthorhombic space groupP212121, with unit-cell parametersa= 85.64,b= 106.11,c= 145.55 Å, were obtained by the sitting-drop vapour-diffusion method and diffracted to 2.15 Å resolution. Initial model building indicates that RCR forms a homotetramer, consistent with previous reports of medium-chain-type alcohol dehydrogenases.
Preliminary crystallographic studies of aSchistosoma mansoniantigen (Sm21.7) dynein light-chain (DLC) domain
Authors: Costa M. A. F. , Rodrigues F. T. G. , Chagas B. C. A. , Rezende C. M. F. , Goes A. M. , Nagem R. A. P.
Published: May 2014

Schistosomiasis is an inflammatory chronic disease that represents a major health problem in tropical and subtropical countries. The drug of choice for treatment, praziquantel, is effective in killing adult worms but fails to kill immature forms and prevent reinfection. One prominent antigen candidate for an anti-schistosomiasis vaccine is the protein Sm21.7 (184 amino-acid residues) fromSchistosoma mansoni, a tegumental protein capable of reducing the worm burden in a murine immunization model. In the present work, the Sm21.7 gene was cloned and expressed inEscherichia coliand the full-length protein was purified to homogeneity. Crystals of recombinant Sm21.7 suitable for X-ray diffraction were obtained using PEG monomethyl ether 2000 as a precipitant. X-ray diffraction images of a native crystal (at 2.05 Å resolution) and a quick-cryosoaked NaI derivative (at 1.95 Å resolution) were collected on the W01B-MX2 beamline at the Laboratório Nacional de Luz Síncrotron (LNLS, Brazilian Synchrotron Light Laboratory/MCT). Both crystals belonged to the hexagonal space groupP6122, with similar unit-cell parametersa=b= 108.5,c= 55.8 Å. SIRAS-derived phases were used to generate the first electron-density map, from which a partial three-dimensional model of Sm21.7 (from Gln89 to Asn184) was automatically constructed. Anaysis of dissolved crystals by SDS–PAGE confirmed that the protein was cleaved in the crystallization drop and only the Sm21.7 C-terminal domain was crystallized. The structure of the Sm21.7 C-terminal domain will help in the localization of the epitopes responsible for its protective immune responses, constituting important progress in the development of an anti-schistosomiasis vaccine.
Crystallization and preliminary X-ray diffraction analysis of the peripheral light-harvesting complex LH2 fromMarichromatium purpuratum
Authors: Cranston Laura J. , Roszak Aleksander W. , Cogdell Richard J.
Published: May 2014

LH2 from the purple photosynthetic bacteriumMarichromatium(formerly known asChromatium)purpuratumis an integral membrane pigment–protein complex that is involved in harvesting light energy and transferring it to the LH1–RC `core' complex. The purified LH2 complex was crystallized using the sitting-drop vapour-diffusion method at 294 K. The crystals diffracted to a resolution of 6 Å using synchrotron radiation and belonged to the tetragonal space groupI4, with unit-cell parametersa=b= 109.36,c= 80.45 Å. The data appeared to be twinned, producing apparent diffraction symmetryI422. The tetragonal symmetry of the unit cell and diffraction for the crystals of the LH2 complex from this species reveal that this complex is an octamer.
High-resolution crystal structures of two crystal forms of human cyclophilin D in complex with PEG 400 molecules
Authors: Valasani Koteswara Rao , Carlson Emily A. , Battaile Kevin P. , Bisson Andrea , Wang Chunyu , Lovell Scott , Yan Shirley ShiDu
Published: May 2014

Cyclophilin D (CypD) is a key mitochondrial target for amyloid-β-induced mitochondrial and synaptic dysfunction and is considered a potential drug target for Alzheimer's disease. The high-resolution crystal structures of primitive orthorhombic (CypD-o) and primitive tetragonal (CypD-t) forms have been determined to 1.45 and 0.85 Å resolution, respectively, and are nearly identical structurally. Although an isomorphous structure of CypD-t has previously been reported, the structure reported here was determined at atomic resolution, while CypD-o represents a new crystal form for this protein. In addition, each crystal form contains a PEG 400 molecule bound to the same region along with a second PEG 400 site in CypD-t which occupies the cyclosporine A inhibitor binding site of CypD. Highly precise structural information for CypD should be extremely useful for discerning the detailed interaction of small molecules, particularly drugs and/or inhibitors, bound to CypD. The 0.85 Å resolution structure of CypD-t is the highest to date for any CypD structure.
The effect of extending dinoprostone pessary placement from 12 to 24 h on the need for further mechanical cervical ripening
Authors: Lusink Vanessa , Usher Leila , Day Tania
Published: May 2014

Dinoprostone pessaries (DP) are widely used for cervical ripening, and while licensed for 12‐h administration in Australia, 24‐h use is also reported. We examined 396 consecutive women before and after a protocol change from 12‐h to 24‐h DP use to determine whether extended DP use decreases the need for additional mechanical cervical ripening. No significant difference in cervical ripening balloon (CRB) requirement or vaginal birth rates was detected, showing that prolonged DP use does not reduce subsequent use of CRB.
Critiquing the politics of participatory video and the dangerous romance of liberalism
Authors: Walsh Shannon
Published: May 2014

In this article I argue that participatory video must acknowledge its often technocratic, liberal presumptions, and take a more critical look at the political underpinnings of ‘empowerment’ and ‘voice’. I am interested in how we can use participatory video while resisting the romance of community, seeing beyond short‐term individualist approaches towards a longer‐term collective project of social justice. A reflexive approach to how power and agency work within participatory video is essential if the method is going to effect change and not merely manage social conflict. While the participatory video process can be discussed from many perspectives, I focus here on a critique of the often‐hidden politics of participatory video, its relation to academic research and in turn, to project participants within a progressive social change agenda.
Pluripotency in the light of the developmental hourglass
Authors: Kuijk Ewart , Geijsen Niels , Cuppen Edwin
Published: May 2014

The hourglass model of development postulates divergence in early and late embryo development bridged by a period of developmental constraint at mid‐embryogenesis. Recently, molecular support for the hourglass model of development has accumulated, with the emphasis on studies using zebrafish and Drosophila species. Across mammals, the hourglass model and specifically divergence in early development has thus far received little attention. Divergence in mammalian pre‐implantation development is particularly interesting because of its potential impact on derivation of pluripotent embryonic stem cells. Here, we review recent findings that support the hourglass model of development. We provide striking examples of variation in key events in mammalian peri‐implantation development and their potential consequences for pluripotency of embryonic stem cell lines, including mechanisms of cell signalling and differentiation, gene regulatory networks, X‐chromosome inactivation, and epigenetic regulation. The variation in these processes indicates divergence in early mammalian development as was postulated by the hourglass model of development. We discuss the naive and primed states of pluripotency in light of this developmental divergence and their implications for human pluripotent stem cell states.
Control of the number of cell division rounds in distinct tissues during ascidian embryogenesis
Authors: Yamada Atsuko , Nishida Hiroki
Published: May 2014

An important question in developmental biology is how the number of cells constituting the body is regulated during development. After termination of cell divisions, cells enter the postmitotic phase, but the mechanisms determining the timing of final cell division remain unclear. In ascidians, the egg develops into a tadpole larva consisting of a relatively small number of cells (approximately 2800), indicating that embryonic cells divide 11.5 times on average after fertilization, although the number of cell division rounds differs among tissues. This article discusses the possible mechanisms that control the timing of the final cell division: these include (i) the analog and digital clock models, in which the elapsed time and number of cell division cycles are measured after fertilization, respectively, and (ii) the analog and digital timer models, in which the elapsed time and number of cell divisions are measured after cell fate specification, respectively. In notochord and muscle cells of ascidian embryos, cell division termination involves cell fate specification by inductive FGF signaling, followed by activation of the tissue‐specific key transcription factors, Brachyury and Tbx6, which then induce gene expression of an effector, Cdk inhibitor. The present evidence suggests that these timing mechanisms comprise two functional phases: (i) an analog timer, which is mediated by accumulation of Cdk inhibitor protein after cell fate specification, and (ii) a timekeeper, which confines the timing, when the above timer is triggered by Brachyury and Tbx6, to the appropriate stage.
Impact of tillage intensity on carbon and nitrogen pools in surface and sub‐surface soils of three long‐term field experiments
Authors: Kaiser M. , Piegholdt C. , Andruschkewitsch R. , Linsler D. , Koch H.‐J. , Ludwig B.
Published: May 2014

Summary

Management options such as the intensity of tillage are known to influence the turnover dynamics of soil organic matter. However, less information is available about the influence of the tillage intensity on individual soil organic matter pools with different turnover dynamics in surface as compared with sub‐surface soils. This study aimed to analyse the impact of no tillage (NT), reduced tillage (RT) and conventional tillage (CT) on labile, intermediate and stable carbon (C) and nitrogen (N) pools in surface and sub‐surface soils. We took surface and sub‐surface soil samples from the three tillage systems in three long‐term field experiments in Germany. The labile, intermediate and stable C and N pool sizes were determined by using the combined application of a decomposition experiment and a physical‐chemical separation procedure. For the surface soils, we found larger stocks of the labile C and N pool under NT and RT (C, 1.7 and 1.3 t ha−1; N, 180 and 160 kg ha−1) than with CT (C, 0.5 t ha−1; N, 60 kg ha−1). In contrast, we found significantly larger stocks of the labile C pool under CT (2.7 t ha−1) than with NT and RT (2 t ha−1) for the sub‐surface soils. The intermediate pool accounted for 75–84% of the soil organic C and total N stocks. However, the stocks of the intermediate N and C pools were only distinctly larger for NT than for CT in the surface soils. The stocks of the stable C and N pools were not affected by the tillage intensity but were positively correlated with the stocks of the clay‐size fraction and oxalate soluble aluminum, indicating a strong influence of site‐specific mineral characteristics on the size of these pools. Our results indicate soil depth‐specific variations in the response of organic matter pools to tillage of different intensity. This means that the potential benefits of decreasing tillage intensity with respect to soil functions that are closely related to organic matter dynamics have to be evaluated separately for surface and sub‐surface soils.
Abnormal response to photic stimulation in Juvenile Myoclonic Epilepsy: An EEG‐fMRI study
Authors: Bartolini Emanuele , Pesaresi Ilaria , Fabbri Serena , Cecchi Paolo , Giorgi Filippo Sean , Sartucci Ferdinando , Bonuccelli Ubaldo , Cosottini Mirco
Published: May 2014

Objective

Juvenile myoclonic epilepsy (JME) is a young‐onset electroclinical syndrome, characterized by myoclonic, generalized tonic–clonic, and possibly typical absence seizures. Interictal electroencephalography (EEG) displays 3–6 Hz spike/polyspike and wave pattern. Photosensitivity is common. Our aim was to explore the blood oxygen level–dependent (BOLD) response evoked by a highly provocative photic stimulus in a cohort of people with JME compared to a group of nonphotosensitive healthy controls, and to investigate the hemodynamic phenomena seen in patients with photosensitive JME.

Methods

We studied 13 JME patients and 18 healthy controls using EEG–functional magnetic resonance imaging (fMRI) performed during low luminance intermittent photic stimulation (IPS). The BOLD response to IPS was investigated both in JME and control groups. In photosensitive JME subjects, we also performed a dynamic evaluation of BOLD signal changes evoked by the photoparoxysmal response (PPR) in a time frame ranging from 10 s before the onset of the EEG paroxysm up until 10 s afterward.

Results

The IPS evoked a positive BOLD response in striate and extrastriate visual areas, which was less in JME patients than in controls. Moreover, people with JME had a reduced positive BOLD response in the frontoparietal areas and putamen but a stronger negative BOLD response in the primary sensorimotor cortex (SM1) and in cortical regions belonging to the default mode network (DMN). In JME, the dynamic evaluation of BOLD signal changes related to PPR revealed an early positive response in the putamen and SM1, followed by BOLD signal decrements in the putamen, caudate nuclei, thalami, and SM1.

Significance

Our results confirm the hypothesis that people with JME might have an altered interaction between the motor circuit and other neuronal networks, with prominent involvement of basal ganglia circuitry. The PPR could be a final expression of pathogenic phenomena occurring in the striato‐thalamocortical system, possibly a core feature of system epilepsy JME.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Biochemical characterization of the tandem HAMP domain from Natronomonas pharaonis as an intraprotein signal transducer
Authors: Natarajan Janani , Schultz Anita , Kurz Ursula , Schultz Joachim E.
Published: May 2014

Available structures of HAMP domains suggest rotation as one potential mechanism in intraprotein signal transduction. It has been proposed that in poly‐HAMP modules the signal sign is inverted with each additional HAMP. We examined signal transduction through the HAMP tandem domain from the phototaxis transducer of the halophilic archaeon Natronomonas pharaonis in membrane‐bound chimeras consisting of the Escherichia coli chemotaxis receptor for serine, Tsr, as an input and the mycobacterial adenylyl cyclase Rv3645 as an output domain, i.e. the basic chimera was ‘Tsr–NpHAMP tandem–Rv3645 cyclase’. Neither of the NpHAMP units alone nor the NpHAMP tandem transduced a serine signal. After five targeted point mutations in the first α‐helix of NpHAMP1, the non‐functional NpHAMP modules combined into a functional HAMP tandem. 1 mm serine significantly inhibited cyclase activity (−35%; IC50 = 30 μm) in disagreement with the structure‐based predictions. Surprisingly, replacement of NpAS11 in the tandem by the respective AS1 from HAMPTsr resulted in signal inversion, i.e. serine activated cyclase (+129%; EC50 = 10 μm). Examination of 48 mutants of AS11 in the HAMP tandem including two residues of a putative N‐terminal control cable identified five residues in NpAS11 which probably define different ground states of the output domain and thus affect the sign of signal output. The data question the predicted HAMP rotation as the predominant mechanism of intraprotein signal transduction and point to as yet unrecognized conformational motions of HAMP domains in intraprotein signaling.
Apical extrusion of debris using ProTaper Universal and ProTaper Next rotary systems
Authors: Koçak M. M. , Çiçek E. , Koçak S. , Sağlam B. C. , Yılmaz N.
Published: May 2014

Aim

To assess and compare the amount of extruded debris after canal preparation using ProTaper Universal and ProTaper Next files.

Methodology

Forty extracted mandibular premolars with single canals and of similar lengths were instrumented using the ProTaper Universal F3 or the ProTaper Next X3. The extruded debris during instrumentation was collected into pre‐weighed Eppendorf tubes. The tubes were stored in an incubator for 5 days. The tubes were weighed to obtain the final dry weight of the extruded debris. The amount of apically extruded debris was calculated by subtracting the initial weight of the tube from the final weight. The distribution of the data was examined using the Shapiro–Wilks test. Continuous variables were compared with an independent‐samples t‐test for two groups.

Results

All specimens were associated with apical debris extrusion. The ProTaper Universal group produced a significantly greater amount of debris extrusion (P < 0.001). The lowest and highest amounts of debris for PTU and PTN groups were recorded as 0.00117–0.00165 g and 0.00017–0.00067 g, respectively.

Conclusion

ProTaper Next files was associated with significantly less extruded apical debris when compared to ProTaper Universal files.
Effect of surgical incision management on wound infections in a poststernotomy patient population
Authors: Grauhan Onnen , Navasardyan Artashes , Tutkun Baris , Hennig Felix , Müller Peter , Hummel Manfred , Hetzer Roland
Published: May 2014

Skin breakdown and infiltration of skin flora are key causative elements in poststernotomy wound infections. We hypothesised that surgical incision management (SIM) using negative pressure wound therapy over closed surgical incisions for 6–7 days would reduce wound infections in a comprehensive poststernotomy patient population. ‘All comers’ undergoing median sternotomy at our institution were analysed prospectively from 1 September to 15 October 2013 (study group, n = 237) and retrospectively from January 2008 to December 2009 (historical control group, n = 3508). The study group had SIM (Prevena™ Therapy) placed immediately after skin suturing and applied at −125 mmHg for 6–7 days, whereas control group received conventional sterile wound tape dressings. Primary endpoint was wound infection within 30 days. Study group had a significantly lower infection rate than control group: 1·3% (3 patients) versus 3·4% (119 patients), respectively (P < 0·05; odds ratio 2·74). In the study group, when the foam dressing was removed after 6–7 days, the incision was primarily closed in 234 of 237 patients (98·7%). SIM over clean, closed incisions for the first 6‐7 postoperative days significantly reduced the incidence of wound infection after median sternotomy. Based on these data SIM may be cost‐effective in patients undergoing cardiac surgery.
A simple novel technique for enteroatmospheric fistulae: silicone fistula plug
Authors: Ozer M Tahir , Sinan Hüseyin , Zeybek Nazif , Peker Yusuf
Published: May 2014

Enteroatmospheric fistulae (EAFs), a rare condition that develops in patients treated with an open abdomen, present serious problems for the surgeon. There are no fixed algorithms for treatment of EAF, and treatment options are determined based on the experience of the surgeon and status of the patient. We developed a ‘suspended silicone fistula plug’ for treating a patient who developed an EAF after undergoing multiple operations in a short period of time. Used in conjunction with negative pressure wound therapy, application of this novel therapy resulted in EAF closure and patient discharge.
Long‐term outcome of Guillain‐Barré syndrome in children
Authors: Roodbol Joyce , de Wit Marie‐Claire Y. , Aarsen Femke K. , Catsman‐Berrevoets Coriene E. , Jacobs Bart C.
Published: May 2014

The objective of this study is to determine the long‐term outcome and consequences of Guillain‐Barré syndrome (GBS) in children. This is an observational cross‐sectional cohort study of children diagnosed with GBS (0–18 years old) at the Sophia Children's Hospital in Rotterdam from 1987 to 2009. All patients were invited for a structured interview, questionnaires, and full neurologic exam to record their current clinical condition focused on complaints and symptoms, neurological deficits, disabilities, behavior, and quality of life. Thirty‐seven patients participated, 23 were now adults, with a median age of 20 years (range 4–39 years) and a median follow‐up time of 11 years (range 1–22 years). Residual complaints were reported by 24 (65%) patients, including paresthesias (38%), unsteadiness of gait in the dark (37%), painful hands or feet (24%), and severe fatigue (22%). Four patients had severe neurological deficits, including facial diplegia and limb weakness. Two patients had had a recurrence of GBS. In 10 patients (26%), GBS had a negative impact on their school career. Questionnaires identified a wide range of behavioral problems. Quality of life was below normal on the subscale vitality, and above normal on the subscales social functioning and positive emotions in the adult group. Most children show good recovery of neurological deficits after GBS, but many have persisting long‐term residual complaints and symptoms that may lead to psychosocial problems interfering with participation in daily life.
Design rules for efficient transgene expression in plants
Authors: Jackson Mark A. , Sternes Peter R. , Mudge Stephen R. , Graham Michael W. , Birch Robert G.
Published: May 2014

Sustained expression of transgenes in specified developmental patterns is commonly needed in plant biotechnology, but obstructed by transgene silencing. Here, we present a set of gene design rules, tested on the silencing‐susceptible beetle luc and bacterial ims genes, expressed in sugarcane. Designs tested independently or in combination included removal of rare codons, removal of RNA instability sequences, blocking of likely endogenous sRNA binding sites and randomization of non‐rare codons. Stable transgene expression analyses, on multiple independent lines per construct, showed greatest improvement from the removal of RNA instability sequences, accompanied by greatly reduced transcript degradation evident in northern blot analysis. We provide a set of motifs that readily can be eliminated concurrently with rare codons and undesired structural features such as repeat sequences, using Gene Designer 2.0 software. These design rules yielded 935‐ and 5‐fold increased expression in transgenic callus, relative to the native luc and ims sequences; and gave sustained expression under the control of sugarcane and heterologous promoters over several years in greenhouse and field trials. The rules can be applied easily with codon usage tables from any plant species, providing a simple and effective means to achieve sustained expression of otherwise silencing‐prone transgenes in plants.
The CRISPR/Cas9 system produces specific and homozygous targeted gene editing in rice in one generation
Authors: Zhang Hui , Zhang Jinshan , Wei Pengliang , Zhang Botao , Gou Feng , Feng Zhengyan , Mao Yanfei , Yang Lan , Zhang Heng , Xu Nanfei , Zhu Jian‐Kang
Published: May 2014

The CRISPR/Cas9 system has been demonstrated to efficiently induce targeted gene editing in a variety of organisms including plants. Recent work showed that CRISPR/Cas9‐induced gene mutations in Arabidopsis were mostly somatic mutations in the early generation, although some mutations could be stably inherited in later generations. However, it remains unclear whether this system will work similarly in crops such as rice. In this study, we tested in two rice subspecies 11 target genes for their amenability to CRISPR/Cas9‐induced editing and determined the patterns, specificity and heritability of the gene modifications. Analysis of the genotypes and frequency of edited genes in the first generation of transformed plants (T0) showed that the CRISPR/Cas9 system was highly efficient in rice, with target genes edited in nearly half of the transformed embryogenic cells before their first cell division. Homozygotes of edited target genes were readily found in T0 plants. The gene mutations were passed to the next generation (T1) following classic Mendelian law, without any detectable new mutation or reversion. Even with extensive searches including whole genome resequencing, we could not find any evidence of large‐scale off‐targeting in rice for any of the many targets tested in this study. By specifically sequencing the putative off‐target sites of a large number of T0 plants, low‐frequency mutations were found in only one off‐target site where the sequence had 1‐bp difference from the intended target. Overall, the data in this study point to the CRISPR/Cas9 system being a powerful tool in crop genome engineering.
Three‐year stability of cardiovascular and autonomic nervous system responses to psychological stress
Authors: Dragomir Anda I. , Gentile Christina , Nolan Robert P. , D'Antono Bianca
Published: May 2014

Chronically heightened physiological reactivity to or delayed recovery from stress may contribute to cardiovascular (CV) risk and mortality. Long‐term stability of physiological stress responses has received little attention. Our objectives were to evaluate the 3‐year stability of reactivity and recovery change scores across CV and autonomic parameters and assess whether sex and age moderate stability. A total of 134 healthy participants underwent two laboratory stress protocols, including four 5‐min interpersonal stressors, each followed by a 5‐min recovery period. Heart rate (HR), blood pressure (BP), and HR variability (high frequency, low frequency, very low frequency [VLF]) were obtained. Spearman rank correlations and linear regressions were performed. Significant correlations emerged for all physiological measures except diastolic BP and VLF recovery. No significant sex or age differences were found. Stress responses represent stable individual traits little affected by sex or age.
Melting of subducted basalt at the core-mantle boundary
Authors: Andrault Denis , Pesce Giacomo , Bouhifd Mohamed Ali , Bolfan-Casanova Nathalie , Hénot Jean-Marc , Mezouar Mohamed
Published: May 2014

The geological materials in Earth's lowermost mantle control the characteristics and interpretation of seismic ultra–low velocity zones at the base of the core-mantle boundary. Partial melting of the bulk lower mantle is often advocated as the cause, but this does not explain the nonubiquitous character of these regional seismic features. We explored the melting properties of mid-oceanic ridge basalt (MORB), which can reach the lowermost mantle after subduction of oceanic crust. At a pressure representative of the core-mantle boundary (135 gigapascals), the onset of melting occurs at ~3800 kelvin, which is ~350 kelvin below the mantle solidus. The SiO
2
-rich liquid generated either remains trapped in the MORB material or solidifies after reacting with the surrounding MgO-rich mantle, remixing subducted MORB with the lowermost mantle.
Income inequality in the developing world
Authors: Ravallion Martin
Published: May 2014

Should income inequality be of concern in developing countries? New data reveal less income inequality in the developing world than 30 years ago. However, this is due to falling inequality between countries. Average inequality within developing countries has been slowly rising, though staying fairly flat since 2000. As a rule, higher rates of growth in average incomes have not put upward pressure on inequality within countries. Growth has generally helped reduce the incidence of absolute poverty, but less so in more unequal countries. High inequality also threatens to stall future progress against poverty by attenuating growth prospects. Perceptions of rising absolute gaps in living standards between the rich and the poor in growing economies are also consistent with the evidence.
“Undemocracy”: inequalities in science
Authors: Xie Yu
Published: May 2014

Inequality, an intrinsic feature of science, has trended upward in recent years
Real-space imaging of molecular structure and chemical bonding by single-molecule inelastic tunneling probe
Authors: Chiang Chi-lun , Xu Chen , Han Zhumin , Ho W.
Published: May 2014

The arrangement of atoms and bonds in a molecule influences its physical and chemical properties. The scanning tunneling microscope can provide electronic and vibrational signatures of single molecules. However, these signatures do not relate simply to the molecular structure and bonding. We constructed an inelastic tunneling probe based on the scanning tunneling microscope to sense the local potential energy landscape of an adsorbed molecule with a carbon monoxide (CO)–terminated tip. The skeletal structure and bonding of the molecule are revealed from imaging the spatial variations of a CO vibration as the CO-terminated tip probes the core of the interactions between adjacent atoms. An application of the inelastic tunneling probe reveals the sharing of hydrogen atoms among multiple centers in intramolecular and extramolecular bonding.
A unified cause for adrenal Cushing's syndrome
Authors: Kirschner Lawrence S.
Published: May 2014

Mutations in a signaling protein underlie a class of functional adrenal tumors

[Also see Reports by

Cao
et al.

and

Sato
et al.

]
Identifying the infiltrators
Authors: Perdiguero Elisa Gomez , Geissmann Frederic
Published: May 2014

Molecular characterization of macrophages reveals distinct types during tumorigenesis

[Also see Report by

Franklin
et al.

]
Record-breaking winters and global climate change
Authors: Palmer Tim
Published: May 2014

Rising greenhouse gas emissions may have played a role in the severe 2013–2014 winter in the U.S. Midwest
Our egalitarian Eden
Authors: Pennisi Elizabeth
Published: May 2014

Hunter-gatherers—and presumably all our ancestors—lived as equals
Genome Sequence of the Pathogenic FungusSporothrix schenckii(ATCC 58251)
Authors: Cuomo Christina A. , Rodriguez-Del Valle Nuri , Perez-Sanchez Lizaida , Abouelleil Amr , Goldberg Jonathan , Young Sarah , Zeng Qiandong , Birren Bruce W.
Published: May 2014

Sporothrix schenckiiis a pathogenic dimorphic fungus that grows as a yeast and as mycelia. This species is the causative agent of sporotrichosis, typically a skin infection. We report the genome sequence ofS. schenckii, which will facilitate the study of this fungus and of theSporothrix schenckiigroup.
Draft Genome Sequence of Streptococcus parauberis Strain SK-417, Isolated from Diseased
Sebastes ventricosus
in Kagoshima, Japan
Authors: Oguro Kazuki , Yamane Jin , Yamamoto Takeshi , Ohnishi Kouhei , Oshima Syun-ichirou , Imajoh Masayuki
Published: May 2014

Streptococcus parauberis
strain SK-417 was isolated from the brain of a diseased
Sebastes ventricosus
, collected from an aquaculture farm in April 2013 in Kagoshima Prefecture, Japan. The draft genome sequence, obtained with a 454 GS Junior sequencing system, consists of 33 large contigs of >500 bp, totaling 1,958,836 bp, and has a G+C content of 35.4%.
Severe mitral regurgitation due to anterior mitral leaflet perforation after surgical treatment of discrete subaortic stenosis
Authors: Ozyuksel Arda , Yildirim Ozgur , Onsel Ibrahim , Bilal Mehmet Salih
Published: May 2014

Congenital subvalvular aortic stenosis may be associated with anomalies of the mitral valve. In this case, we present a patient with severe mitral valve regurgitation due to a perforation in the anterior mitral leaflet detected 4 months after an operation for relief of subaortic stenosis. A 10-year-old male patient who was operated for subvalvular aortic stenosis in another clinic was admitted to our hospital, and transthoracic echocardiography revealed severe mitral valve regurgitation due to a defect that was demonstrated at the anterior valve leaflet. The perforated area at the mitral valve zone A1 was repaired with a PTFE patch. The patient was successfully operated for the mitral valve perforation and the postoperative course was uneventful. In our case, the perforation in the anterior mitral leaflet implies a possible implementation of inappropriate surgical technique which necessitated a second surgical intervention after the initial operation.
2014 Consensus Statement from the first Economics of Physical Inactivity Consensus (EPIC) Conference (Vancouver)
Authors: Davis Jennifer C , Verhagen Evert , Bryan Stirling , Liu-Ambrose Teresa , Borland Jeff , Buchner David , Hendriks Marike RC , Weiler Richard , Morrow James R , van Mechelen Willem , Blair Steven N , Pratt Mike , Windt Johann , al-Tunaiji Hashel , Macri Erin , Khan Karim M ,   The EPIC Group
Published: May 2014

This article describes major topics discussed from the ‘Economics of Physical Inactivity Consensus Workshop’ (EPIC), held in Vancouver, Canada, in April 2011. Specifically, we (1) detail existing evidence on effective physical inactivity prevention strategies; (2) introduce economic evaluation and its role in health policy decisions; (3) discuss key challenges in establishing and building health economic evaluation evidence (including accurate and reliable costs and clinical outcome measurement) and (4) provide insight into interpretation of economic evaluations in this critically important field. We found that most methodological challenges are related to (1) accurately and objectively valuing outcomes; (2) determining meaningful clinically important differences in objective measures of physical inactivity; (3) estimating investment and disinvestment costs and (4) addressing barriers to implementation. We propose that guidelines specific for economic evaluations of physical inactivity intervention studies are developed to ensure that related costs and effects are robustly, consistently and accurately measured. This will also facilitate comparisons among future economic evidence.
PROSPECTIV—a pilot trial of a nurse-led psychoeducational intervention delivered in primary care to prostate cancer survivors: study protocol for a randomised controlled trial
Authors: Watson Eila , Rose Peter , Frith Emma , Hamdy Freddie , Neal David , Kastner Christof , Russell Simon , Walter Fiona M , Faithfull Sara , Wolstenholme Jane , Perera Rafael , Weller David , Campbell Christine , Wilkinson Clare , Neal Richard , Sooriakumaran Prasanna , Butcher Hugh , Matthews Mike
Published: May 2014

Background

Prostate cancer survivors can experience physical, sexual, psychological and emotional problems, and there is evidence that current follow-up practices fail to meet these men's needs. Studies show that secondary and primary care physicians see a greater role for primary care in delivering follow-up, and that primary care-led follow-up is acceptable to men with prostate cancer.

Methods and analysis

A two-phase study with target population being men who are 9–24 months from diagnosis. Phase 1 questionnaire aims to recruit 300 men and measure prostate-related quality of life and unmet needs. Men experiencing problems with urinary, bowel, sexual or hormonal function will be eligible for phase 2, a pilot trial of a primary care nurse-led psychoeducational intervention. Consenting eligible participants will be randomised either to intervention plus usual care, or usual care alone (40 men in each arm). The intervention, based on a self-management approach, underpinned by Bandura's Social Cognitive Theory, will provide advice and support tailored to these men's needs and address any problems they are experiencing. Telephone follow-up will take place at 6 months. Study outcomes will be measured by a questionnaire at 7 months. Phase 1 will allow us to estimate the prevalence of urinary, sexual, bowel and hormone-related problems in prostate cancer survivors and the level of unmet needs. ‘Usual care’ will also be documented. Phase 2 will provide information on recruitment and retention, acceptability of the intervention/outcome measures, effect sizes of the intervention and cost-effectiveness data, which is required to inform development of a larger, phase 3 randomised controlled trial. The main outcome of interest is change in prostate-cancer-related quality of life. Methodological issues will also be addressed.

Ethics and dissemination

Ethics approval has been gained (Oxford REC A 12/SC/0500). Findings will be disseminated in peer-reviewed journals, at conferences, through user networks and relevant clinical groups.

Trial registration number

ISRCTN 97242511.
Factors predictive of subsequent injury in a longitudinal cohort study
Authors: Harcombe Helen , Derrett Sarah , Samaranayaka Ari , Davie Gabrielle , Wyeth Emma , Wilson Suzanne
Published: May 2014

Objectives

The aims are to: (1) Determine the cumulative incidence of self-reported subsequent injury (of any anatomical site or injury type) occurring between 3 months and 12 months after a sentinel injury among participants in the Prospective Outcomes of Injury Study in New Zealand and (2) Examine the preinjury and injury-related predictors of subsequent injury.

Methods

Prospective Outcomes of Injury Study participants (n=2282) were interviewed 3 months, 5 months and 12 months after a sentinel injury event. Data were collected about a range of preinjury and injury-related factors at the 3-month interview and about subsequent injury at the 5-month and 12-month interviews. Poisson regression modelling was used to determine the preinjury and injury-related predictors of subsequent injury.

Results

Between the 3-month and 12 month interviews 28% of the participants reported at least one subsequent injury. Subsequent injury was 34% more likely among participants with a prior injury affecting them at the time of the sentinel injury compared with participants without a prior injury affecting them, and more likely among non-workers (31% more likely) and trade/manual workers (32% more likely) compared with professionals. Participants whose sentinel injury was due to assault were 43% more likely to report a subsequent injury compared with those whose sentinel injury was accidental. A subsequent injury was 23% less likely if the sentinel injury was a lower extremity fracture compared with other injuries, and 21% less likely if the sentinel injury event involved hospitalisation.

Conclusions

Among general injury populations it may be possible to identify people at increased risk for subsequent injury.
Effects of pomegranate extract on blood flow and running time to exhaustion
Authors: Trexler Eric T. , Smith-Ryan Abbie E. , Melvin Malia N. , Roelofs Erica J. , Wingfield Hailee L.
Published: May 2014

Recent research has shown that dietary nitrate has favorable effects on blood flow and exercise performance. The purpose of this randomized, double-blind, placebo-controlled crossover study was to investigate the acute effects of pomegranate extract on blood flow, vessel diameter, and exercise performance in active individuals. Nineteen men and women (mean ± SD: age, 22.2 ± 2.2 years; height, 174.8 ± 10.7 cm; body mass, 71.9 ± 13.5 kg) were randomly assigned to a placebo (PL) or pomegranate extract (PE) group. Participants performed a maximal oxygen consumption treadmill test to determine peak velocity (PV). Participants returned after 24–48 h and ingested either PL or PE. Brachial artery blood flow was assessed using ultrasound at baseline and 30 min post-ingestion (30minPI). Three treadmill runs to exhaustion were performed at 90%, 100%, and 110% PV. Blood flow was assessed immediately after each exercise bout and 30 min postexercise (30minPEx). After a 7–10 day washout, participants repeated the same procedures, ingesting the opposite supplement. Separate repeated measures ANOVAs were performed for blood flow, vessel diameter, and time to exhaustion (TTE). Blood flow was significantly augmented (p = 0.033) 30minPI with PE in comparison with PL. Vessel diameter was significantly larger (p = 0.036) 30minPEx with PE. Ingestion of PE was found to significantly augment TTE at 90% (p = 0.009) and 100% PV (p = 0.027). Acute ingestion of PE 30 min before exercise may enhance vessel diameter and blood flow and delay fatigue during exercise. Results of the current study indicate that PE is ergogenic for intermittent running, eliciting beneficial effects on blood flow.
How many tuples of group elements have a given property? With an appendix by Dmitrii V. Trushin
Authors: Klyachko Anton A. , Mkrtchyan Anna A.
Published: May 2014

Generalizing Solomon's theorem, Gordon and Rodriguez-Villegas have proven recently that, in any group, the number of solutions to a system of coefficient-free equations is divisible by the order of this group whenever the rank of the matrix composed of the exponent sums of ith unknown in jth equation is less than the number of unknowns. We generalize this result in two directions: first, we consider equations with coefficients, and second, we consider not only systems of equations but also any first-order formulae in the group language (with constants). Our theorem implies some amusing facts; for example, the number of group elements whose squares lie in a given subgroup is divisible by the order of this subgroup.
EFFECT OF ULTRASONIC ON COPPER ELECTROPLATING FROM THE NON-CYANIDE ALKALINE BATHS
Authors: LI MINGGANG , HU SHUANGSHUANG , YANG YEJIONG , XU SHUHAN , ZHAO XIXI , WEI GUOYING
Published: May 2014

Effects of the different ultrasonic powers on copper electrodeposition from non-cyanide alkaline baths by using pyrophosphate as complexing agent were investigated by different electrochemical methods. Cyclic voltammetry and current transient measurements were used to characterize the nucleation and growth mechanism. It is very obvious that the reduction potential moves to more positive one as the ultrasonic power increases. The quartz crystal microbalance (QCM) and chronoamperometric method were used to study the relationship between the mass change and the deposition time. It was found that the current efficiency of electrolyte under 0, 60, 80 and 100 W is 91.95%, 92.14%, 89.25% and 96.11%, respectively measured by QCM measurements. The surface morphology of the electrodeposited Cu films is analyzed by scanning electron microscopy (SEM). The morphology of copper films electrodeposited under the power of 60 W and 80 W presents a compact surface and the grains are fine and uniform.
Interacting closed string tachyon with generalized cosmic Chaplygin gas
Authors: Amani Ali R. , Pourhassan B.
Published: May 2014

In this paper, we consider interacting closed string tachyon with generalized cosmic Chaplygin gas as a cosmological model of Universe. We obtained cosmological parameters and discuss about fixed point for stability analysis. We find appropriate conditions where the theory is stable.
A large, anatomically primitive tristichopterid (Sarcopterygii: Tetrapodomorpha) from the Late Devonian (Frasnian) Alves Beds, Upper Old Red Sandstone, Moray, Scotland
Authors: Parfitt Matthew , Johanson Zerina , Giles Sam , Friedman Matt
Published: May 2014

Synopsis

A nearly complete mandible of a large tetrapodomorph sarcopterygian from the Frasnian Alves Beds is studied with the aid of computed tomography. The absence of cosmine, a small parasymphysial dental plate bearing dentition that is discontinuous with that of the coronoids, and the presence of an elongated posterior coronoid that bears two fang pairs restrict placement of the tetrapodomorph from the Alves Beds to Tristichopteridae, and suggest that is a member of the clade that is sister to the anatomically primitive Givetian genus
Tristichopterus
. Taxa from this segment of tristichopterid phylogeny include the Givetian–Frasnian
Eusthenopteron
and Frasnian
Jarvikina
, but the tristichopterid from the Alves Beds is distinguished from both by the presence of an organized row of well-developed teeth on the posterior coronoid. This character has been proposed as a synapomorphy of taxa crownward of Trischopteridae, but is widely distributed among tetrapodomorph fishes. Our reinterpretation of lower jaw material of
Tinirau clackae
suggests this species is a member of the Tristichopteridae rather than the ‘Elpistostegalia’, and likely includes material assigned to a second species and genus of tetrapodomorph from the Red Hill site,
Bruehnopteron murphyi
. Proposal of a formal taxonomic name for the tristichopterid from the Alves Beds is withheld pending the discovery or analysis of further material from these deposits.