bluuebunny/crossref_metadata_2025 huggingface dataset:
FHOD1 regulates cytoplasmic actin‐based spindle migration for mouse oocyte asymmetric cell division
Authors: Pan Meng‐Hao , Wang Fei , Lu Yujie , Tang Feng , Duan Xing , Zhang Yu , Xiong Bo , Sun Shao‐Chen
Published: July 2017

FHOD1 is a member of Diaphanous‐related formins (DRFs) which belongs to the Formin family. Previous studies have shown that the DFRs might affect several cellular functions such as morphogenesis, cytokinesis, cell polarity, and embryonic differentiation. However, there is no evidence showing the functions of FHOD1 during oocyte meiosis. This study is aimed at exploring the roles of FHOD1 during the mammalian oocyte maturation. Immunofluorescent staining showed that FHOD1 was restricted to the nucleus in germinal vesicle (GV) stage of the oocytes, after the GV breakdown FHOD1 was primarily located at two poles of the spindle at both metaphases I and II stages. Knockdown of FHOD1 by siRNA injection did not affect polar body extrusion but generated the large polar bodies. In addition, we observed the spindle migration failure in metaphase I oocytes, with a large number of meiotic spindles anchoring in the center of cytoplasm. The expression level of cytoplasmic actin but not cortex actin was significantly reduced, indicating that FHOD1 regulates cytoplasmic actin distribution for the spindle movement. Furthermore, we found that the disruption of ROCK (the Rho‐dependent protein kinase) with inhibitor Y‐27632 caused the decreased FHOD1 protein expression. Therefore, our data indicate that FHOD1 is regulated by ROCK for cytoplasm actin assembly and spindle migration during mouse oocyte meiosis.
Neuroglobin and friends
Authors: Fiocchetti Marco , Cipolletti Manuela , Brandi Valentina , Polticelli Fabio , Ascenzi Paolo
Published: July 2017

In the year 2000, the third member of the globin family was discovered in human and mouse brain and named neuroglobin (Ngb). Neuroglobin overexpression significantly protects both heart and brain from hypoxic/ischemic and oxidative stress‐related insults, whereas decreased Ngb levels lead to an exacerbation of tissue injuries. Moreover, Ngb overexpression protects neurons from mitochondrial dysfunctions and neurodegenerative disorders such as Alzheimer disease; however, it facilitates the survival of cancer cells. Neuroglobin, representing a switch point for cell death and survival, has been reported to recognize a number of proteins involved in several metabolic pathways including ionic homeostasis maintenance, energy metabolism, mitochondrial function, and cell signaling. Here, the recognition properties of Ngb are reviewed to highlight its roles in health and disease.
Double‐mode adjustment of Tibetan Plateau heating to the summer circumglobal teleconnection in the Northern Hemisphere
Authors: Zhang Jie , Jiang Yuanchun , Chen Haishan , Wu Zhiwei
Published: July 2017

A quasi‐stationary circumglobal teleconnection (CGT) in the Northern Hemisphere in summer is associated with summer droughts and floods and exhibits some vorticity anomalies. The CGT anomaly and its forcing sources were explored based on reanalysis data and the EI Nino 3.4 index. The term ∂v′/∂x was used to describe the multi‐scale variability of vorticity and the CGT anomaly, which had a 7‐wavenumber and a small interannual amplitude of ∂v′/∂x from 1987 to 2000 but a large amplitude from 2000 to 2010. The interannual CGT intensity was enhanced by an EI Nino sea surface temperature pattern in spring via key forcing sources that led to an enduring effect on the summer circulation; it was also a response to anomalies in Tibetan Plateau (TP) heating in spring–summer in two ways. First, increasing TP heating in the mid‐eastern TP caused an eastward shift and northerly extension of the South Asian High (SAH), which exhibited a Tibetan‐mode SAH as well as a 7‐wavenumber CGT anomaly. This enhanced the CGT over Eurasia and extended the wave pattern of the EI Nino contribution over the North Pacific and Eurasia. Second, increased snow cover in the west of the TP could have offset the TP heating effect and adjusted the position and intensity of the Tibetan‐mode SAH. This phenomenon weakened vorticity and wave amplitude and finally led to a weak CGT anomaly. This finding indicates a coupled effect of double‐mode TP heating (i.e. both heating and TP snow cover) on the CGT anomaly, which reveals the linkage of TP heating with weather over Eurasia and North America that could be predicted by TP heating and other factors.
Design of a ruthenium(III) immobilized affinity material based on a β‐cyclodextrin‐functionalized poly(glycidyl methacrylate‐ethylene dimethacrylate) monolith for the enrichment of hippuric acid
Authors: Li Xuemei , Li Xiqian , Zheng Haijiao , Ma Jiutong , Xu Guoxing , Jia Qiong
Published: July 2017

Immobilized metal affinity chromatography has drawn great attention as a widespread separation and purification approach. In this work, ruthenium was firstly introduced into the preparation of immobilized metal affinity chromatography considering its affinity to N,O‐donor ligands. A β‐cyclodextrin‐functionalized poly(glycidyl methacrylate‐ethylene dimethacrylate) monolith was designed and employed as the supporting material in immobilized metal affinity chromatography. Thiosemicarbazide was introduced into the synthesis process, which not only acted as a bridge between β‐cyclodextrin and glycidyl methacrylate, but also chelated with ruthenium because of its mixed hard‐soft donor characteristics. The developed monolithic ruthenium(III)‐immobilized metal affinity chromatography column was utilized for the adsorption and separation of hippuric acid, a biological indicator of toluene exposure. To achieve high extraction capacity, the parameters affecting the extraction efficiency were investigated with an orthogonal experiment design, L9 (34). Under the optimized conditions, the enrichment factor of hippuric acid was 16.7‐fold. The method reproducibility was investigated in terms of intra‐ and interday precisions with relative standard deviations lower than 8.7 and 9.5%, respectively. In addition, ruthenium(III)‐immobilized metal affinity chromatography material could be used for up to 80 extractions without an apparent change in extraction recovery.
Shear Wave Elastography for Surgically Verified Breast Papillary Lesions: Is It Effective for Differentiation Between Benign and Malignant Lesions?
Authors: Choi Hye Jeong , Ko Kyung Hee , Jung Hae Kyoung
Published: July 2017

Objectives

To evaluate the effectiveness of shear wave elastography (SWE) for differentiating benign from malignant breast papillary lesions

Methods

B‐mode ultrasound (US) and SWE were available in 56 surgically confirmed papillary lesions (48 [85.7%] benign and 8 [14.3%] malignant). The diagnostic performances of US, SWE parameters, and combined US with SWE parameters were calculated by receiver operating characteristic curve analysis and compared.

Results

The highest area under the receiver operating characteristic curve (Az) value for US was 0.500 (95% confidence interval [CI], 0.363, 0.637). The sensitivity was 100% (8 of 8), and the specificity was 0% (0 of 48). False‐positive biopsy results were obtained in 48 (85.7%) of 56 lesions. The Az value for mean elasticity (0.721; 95% CI, 0.585, 0.833) was higher than that for B‐mode US (P < .01) and the highest with the optimal cutoff value of 44.3 kPa (sensitivity, 75%; specificity, 75%). By adding the mean elasticity cutoff value of 44.3 kPa to B‐mode US, the performance was increased (Az, 0.781; 95% CI, 0.585, 0.833) with sensitivity of 87.5% and specificity of 68.8%, and false‐positive biopsy results were reduced to 26.8%.

Conclusions

The additional use of SWE to B‐mode US may be effective for differentiating benign and malignant breast papillary lesions, with a significant decrease in the false‐positive biopsy rate.
Apple's disaster: Linking two‐sided markets and strategic delegation
Authors: Ribeiro Vitor Miguel
Published: July 2017

Asymmetric pricing structure and different intergroup network externalities are characteristics of two‐sided markets not captured in the analysis of one‐sided markets. Focusing on Cournot duopoly where membership decision may be delegated to a manager, several equilibrium regimes are sustained depending on the fixed cost of managerial hiring and strength of the network externality exerted by the side whose demand is more price sensitive. The change from null to full delegation sharpens the asymmetric pricing structure and reduces the price level in two‐sided markets. Contrary to one‐sided markets with direct network effects, the prisoner's dilemma holds for sufficiently strong indirect network externalities. Imperfect interside discrimination of managerial incentives ensures profit maximization and efficient consumers' allocation. Private hiring should occur when the two‐sided market exhibits symmetric pricing structure. An explanation for Apple's unprecedented event is provided. The reduction of revenue and managerial bonus in 2016 may be justified by the dissemination of full delegation in the Chinese information technology industry. Apple's upcoming strategy may consist on reducing both access prices, although the side whose demand is more price sensitive should have a greater price reduction. Alternatively, improving the content quality may constitute Apple's corporate strategy, thereby inducing a skimming pricing strategy on Chinese rivals.
Hyperpolarized 13C magnetic resonance evaluation of renal ischemia reperfusion injury in a murine model
Authors: Baligand Celine , Qin Hecong , True‐Yasaki Aisha , Gordon Jeremy W. , von Morze Cornelius , Santos Justin Delos , Wilson David M. , Raffai Robert , Cowley Patrick M. , Baker Anthony J. , Kurhanewicz John , Lovett David H. , Wang Zhen Jane
Published: July 2017

Acute kidney injury (AKI) is a major risk factor for the development of chronic kidney disease (CKD). Persistent oxidative stress and mitochondrial dysfunction are implicated across diverse forms of AKI and in the transition to CKD. In this study, we applied hyperpolarized (HP) 13C dehydroascorbate (DHA) and 13C pyruvate magnetic resonance spectroscopy (MRS) to investigate the renal redox capacity and mitochondrial pyruvate dehydrogenase (PDH) activity, respectively, in a murine model of AKI at baseline and 7 days after unilateral ischemia reperfusion injury (IRI). Compared with the contralateral sham‐operated kidneys, the kidneys subjected to IRI showed a significant decrease in the HP 13C vitamin C/(vitamin C + DHA) ratio, consistent with a decrease in redox capacity. The kidneys subjected to IRI also showed a significant decrease in the HP 13C bicarbonate/pyruvate ratio, consistent with impaired PDH activity. The IRI kidneys showed a significantly higher HP 13C lactate/pyruvate ratio at day 7 compared with baseline, although the 13C lactate/pyruvate ratio was not significantly different between the IRI and contralateral sham‐operated kidneys at day 7. Arterial spin labeling magnetic resonance imaging (MRI) demonstrated significantly reduced perfusion in the IRI kidneys. Renal tissue analysis showed corresponding increased reactive oxygen species (ROS) and reduced PDH activity in the IRI kidneys. Our results show the feasibility of HP 13C MRS for the non‐invasive assessment of oxidative stress and mitochondrial PDH activity following renal IRI.
High‐order compact schemes for fractional differential equations with mixed derivatives
Authors: Vong Seakweng , Shi Chenyang , Lyu Pin
Published: July 2017

In this article, we consider two‐dimensional fractional subdiffusion equations with mixed derivatives. A high‐order compact scheme is proposed to solve the problem. We establish a sufficient condition and show that the scheme converges with fourth order in space and second order in time under this condition.© 2017 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 33: 2141–2158, 2017
Defining the metal specificity of a multifunctional biofilm adhesion protein
Authors: Chaton Catherine T. , Herr Andrew B.
Published: July 2017

The accumulation associated protein (Aap) of Staphylococcus epidermidis mediates intercellular adhesion events necessary for biofilm growth. This process depends upon Zn2+‐induced self‐assembly of G5 domains within the B‐repeat region of the protein, forming anti‐parallel, intertwined protein “ropes” between cells. Pleomorphism in the Zn2+‐coordinating residues was observed in previously solved crystal structures, suggesting that the metal binding site might accommodate other transition metals and thereby support dimerization. By use of carefully selected buffer systems and a specialized approach to analyze sedimentation velocity analytical ultracentrifugation data, we were able to analyze low‐affinity metal binding events in solution. Our data show that both Zn2+ and Cu2+ support B‐repeat assembly, whereas Mn2+, Co2+, and Ni2+ bind to Aap but do not support self‐association. As the number of G5 domains are increased in longer B‐repeat constructs, the total concentration of metal required for dimerization decreases and the transition between monomer and dimer becomes more abrupt. These characteristics allow Aap to function as an environmental sensor that regulates biofilm formation in response to local concentrations of Zn2+ and Cu2+, both of which are implicated in immune cell activity.
Identification of in vivo induced maternal haploids in maize using seedling traits
Authors: Chaikam Vijay , Lopez Luis Antonio , Martinez Leocadio , Burgueño Juan , Boddupalli Prasanna M.
Published: July 2017

In vivo haploid induction in high frequency followed by efficient identification of haploids are important components of deriving completely homozygous doubled haploid (DH) lines in maize. Several genetic marker systems were proposed and/or used for identification of in vivo maternal haploids in maize, such as R1-nj (Navajo), high oil, red root and transgenic markers. In this study, we propose a new method of haploid/diploid identification based on natural differences in seedling traits of haploids and diploids, which can be used in any induction cross independently of the genetic marker systems. Using confirmed haploids and diploids from five different populations, the study established that haploid and diploid seedlings exhibit significant differences for seedling traits, particularly radicle length (RL), coleoptile length (CL), and number of lateral seminal roots (NLSR). In six populations that exhibited complete inhibition of the commonly used R1-nj (Navajo) marker, we could effectively differentiate haploids from diploids by visual inspection of the seedling traits. In the haploid seed fraction identified based on R1-nj marker in ten populations, false positives were reduced several-fold by early identification of haploids at seedling stage using the seedling traits. We propose that seedling traits may be integrated at the haploid identification stage, especially in populations that are not amenable to use of genetic markers, and for improving the efficiency of DH line production by reducing the false positives.
Biosafety Evaluation of Three Sodium Lauryl N‐Amino Acids Synthesized from Silk Industrial Waste in Mice
Authors: Ding Biao , Wan Liang‐Ze , Zhang Yu‐Qing
Published: July 2017

In this study, three amino acid mixtures recovered from silk industry waste were reacted with lauryl chloride to synthesize three sodium laurel N‐amino acid surfactants. The three types of anionic surfactants are referred to as silk fibroin surfactant, silk sericin surfactant, and silkworm pupae surfactant. All three surfactants showed good surface properties. To evaluate biological safety, we added these three surfactants to the normal diet of mice for 8 weeks. Blood indices, blood lipid, antioxidant capacity (GSH‐PX, MDA, T‐AOC, and T‐SOD), and lipid metabolism key enzyme mRNA (PPAR‐γ, SREBP, FASN, and C/EBP‐α) levels in the liver were measured. No evident histopathological changes were found in the liver and kidney. The results showed no significant difference in their indexes between the surfactant‐fed and normal diet‐fed mice. Thus, the three amino acid surfactants are biologically safe and can be used in daily chemical cleaning products. These surfactants will not only help to reduce wastage of resources and damage to the environment, but also yield economic benefits to the silk industry in the future.
The bridge between design and analysis
Authors: Leppink Jimmie , O’Sullivan Patricia , Winston Kal
Published: July 2017

The overall purpose of the ‘Statistical Points and Pitfalls’ series is to help readers and researchers alike increase awareness of how to use statistics and why/how we fall into inappropriate choices or interpretations. We hope to help readers understand common misconceptions and give clear guidance on how to avoid common pitfalls by offering simple tips to improve your reporting of quantitative research findings. Each entry discusses a commonly encountered inappropriate practice and alternatives from a pragmatic perspective with minimal mathematics involved. We encourage readers to share comments on or suggestions for this section on Twitter, using the hashtag: #mededstats
The association between metformin use and colorectal cancer survival among patients with diabetes mellitus: An updated meta‐analysis
Authors: Tian Shan , Lei Hong‐Bo , Liu Yu‐Lan , Chen Yan , Dong Wei‐Guo
Published: July 2017

Objective

Recent studies have reported conflicting results on the correlation between metformin use and outcomes in patients with colorectal cancer (CRC). A meta‐analysis was performed to evaluate the efficacy of metformin therapy on the prognosis of CRC patients with type 2 diabetes mellitus (T2DM).

Methods

We conducted a systematic search of PubMed, EMBASE, the Cochrane Library, and the Web of Science for related articles up to August 2016. Two investigators independently identified and extracted information. Pooled risk estimates [hazard ratios (HRs)] and 95% confidence intervals (CIs) were calculated using fixed‐effects models. The risk of publication bias was assessed by examining funnel plot asymmetry as well as Egger's test and Begg's test.

Results

Of 81 articles identified, 8 retrospective cohort studies, representing 6098 cases of CRC patients with T2DM who used metformin and 4954 cases of CRC patients with T2DM who did not use metformin, were included in this meta‐analysis. There was no significant heterogeneity and quality difference between studies. Metformin users had significantly improved overall survival (OS) (HR = 0.82, 95% CI: 0.77–0.87, P = 0.000). However, Metformin use cannot affect CRC‐specific survival (HR = 0.84, 95% CI: 0.69–1.02, P = 0.079) compared to non‐users.

Conclusion

This meta‐analysis suggests that metformin use may improve survival among CRC patients with T2DM. However, prospective controlled studies are still needed to rigorously evaluate the efficacy of metformin as an anti‐tumor agent.
Cost and quality issues in establishing hematopoietic cell transplant program in developing countries
Authors: Hashmi Shahrukh K. , Srivastava Alok , Rasheed Walid , Adil Salman , Wu Tong , Jagasia Madan , Nassar Amr , Hwang William Y.K. , Hamidieh Amir Ali , Greinix Hildegard T. , Pasquini Marcelo C. , Apperley Jane F. , Aljurf Mahmoud
Published: July 2017

The hematopoietic cell transplant (HCT) activity has grown significantly over the past two decades in both developing and developed countries. Many challenges arise in establishing new HCT programs in developing countries, due to scarcity of resources and manpower in expertise in HCT. While cost issues can potentially hinder establishment of new HCT programs in certain regions, the focus on quality and value should be included in the general vision of leadership before establishing an HCT program. The main challenge in most developing countries is the lack of trained/qualified personnel, enormous start-up costs for a tertiary care center, and quality maintenance. Herein, we discuss the main challenges from a cost and quality perspective which occur at initiation of a new HCT program. We give real world examples of two developing countries that have recently started new HCT programs despite significant financial constraints. We also portray recommendations from the Worldwide Network of Blood and Marrow Transplantation for levels of requirements for a new HCT program. We hope that this review will serve as a general guide for new transplant program leadership with respect to the concerns of balancing high quality with concurrently lowering costs.
BMP‐2 combined with salvianolic acid B promotes cardiomyocyte differentiation of rat bone marrow mesenchymal stem cells
Authors: Lv Yang , Gao Chen‐Wei , Liu Bo , Wang Hao‐Yu , Wang Hai‐Ping
Published: July 2017

The present study tested the hypotheses that bone morphogenetic protein 2(BMP‐2) combined with salvianolic acid B(Sal‐B) enhance the differentiation of rat bone marrow mesenchymal stem cells (BMSCs) towards cardiomyocytes in vitro. BMSCs were treated with BMP‐2 and Sal‐B, alone or in combination, for 72 h, then added new media (excluding inductive substance) and cultured for 4 weeks. The morphologic characteristics, surface antigens and mRNA expression of several transcription factors were also assessed. We found that they could all be identified by the positive staining for cardiomyocyte‐specific proteins, desmin and cardiac troponin T, in these cells. Furthermore, the mRNA expression of GATA‐4 and Nkx2.5 genes was slightly increased on day 7, enhanced on day 14 and decreased on day 28 while α‐MHC gene was not expressed on day 7, but expressed slightly on day 14 and enhanced on day 28. The expression of these cardiac‐specific markers in treatment groups were all significantly higher than those in the control group, respectively (P < 0.05). Transmission electron microscopy showed that BMSCs in treatment groups all had myofilaments, z line‐like substances and mitochondria. Taken together, these results indicate that BMP‐2 combined with Sal‐B promotes myocardial differentiation of BMSCs, which may represent a potential therapeutic strategy for the treatment of ischemic heart disease.
Advancing Empire
Authors: Roper L. H.
Published: July 2017

In Advancing Empire, L. H. Roper explores the origins and early development of English overseas expansion. Roper focuses on the networks of aristocrats, merchants, and colonial-imperialists who worked to control the transport and production of exotic commodities, such as tobacco and sugar, as well as the labor required to produce them. He is primarily interested in the relationship between the English state and the people it governed, the role of that state in imperial development, the socio-political character of English colonies and English relations with Asians, Africans, American Indians, and other Europeans overseas. The activities stimulated the expansion and integration of global territorial and commercial interests that became the British Empire in the eighteenth century. In exploring these activities from a wider perspective, Roper offers a novel conclusion that revises popular analyses of the English Empire and of Anglo-America.
Corporate Islam
Authors: Sloane-White Patricia
Published: July 2017

Compelling and original, this book offers a unique insight into the modern Islamic corporation, revealing how power, relationships, individual identities, gender roles, and practices - and often massive financial resources - are mobilized on behalf of Islam. Focusing on Muslims in Malaysia, Patricia Sloane-White argues that sharia principles in the region's Islamic economy produce a version of Islam that is increasingly conservative, financially and fiscally powerful, and committed to social control over Muslim and non-Muslim public and private lives. Packed with fascinating details, the book is essential reading for anyone with an interest in Islamic politics and culture in modern life.
Eating Nature in Modern Germany
Authors: Treitel Corinna
Published: July 2017

Adolf Hitler was a vegetarian and the Dachau concentration camp had an organic herb garden. Vegetarianism, organic farming, and other such practices have enticed a wide variety of Germans, from socialists, liberals, and radical anti-Semites in the nineteenth century to fascists, communists, and Greens in the twentieth century. Corinna Treitel offers a fascinating new account of how Germans became world leaders in developing more 'natural' ways to eat and farm. Used to conserve nutritional resources with extreme efficiency at times of hunger and to optimize the nation's health at times of nutritional abundance, natural foods and farming belong to the biopolitics of German modernity. Eating Nature in Modern Germany brings together histories of science, medicine, agriculture, the environment, and popular culture to offer the most thorough and historically comprehensive treatment yet of this remarkable story.
Water entry of deformable spheres
Authors: Hurd Randy C. , Belden Jesse , Jandron Michael A. , Tate Fanning D. , Bower Allan F. , Truscott Tadd T.
Published: July 2017

When a rigid body collides with a liquid surface with sufficient velocity, it creates a splash curtain above the surface and entrains air behind the sphere, creating a cavity below the surface. While cavity dynamics has been studied for over a century, this work focuses on the water entry characteristics of deformable elastomeric spheres, which has not been studied. Upon free surface impact, an elastomeric sphere deforms significantly, giving rise to large-scale material oscillations within the sphere resulting in unique nested cavities. We study these phenomena experimentally with high-speed imaging and image processing techniques. The water entry behaviour of deformable spheres differs from rigid spheres because of the pronounced deformation caused at impact as well as the subsequent material vibration. Our results show that this deformation and vibration can be predicted from material properties and impact conditions. Additionally, by accounting for the sphere deformation in an effective diameter term, we recover previously reported characteristics for time to cavity pinch off and hydrodynamic force coefficients for rigid spheres. Our results also show that velocity change over the first oscillation period scales with the dimensionless ratio of material shear modulus to impact hydrodynamic pressure. Therefore, we are able to describe the water entry characteristics of deformable spheres in terms of material properties and impact conditions.
Through the Looking Glass: Young People, Work and the Transition between Education and Employment in a post-Brexit UK
Authors: ELLISON MARION
Published: July 2017

The prospect of a profound transformation in the relationship between the UK and the European Union has raised a range of economic, social and political concerns (Dhingraet al., 2016; Boothet al., 2015; Irwin, 2015; Ebell and Warren, 2016). Whilst the ultimate shape of a negotiated post-Brexit settlement is uncertain, the potential loss or reduction in access to EU funding streams, educational mobility, EU labour market access, and changes to employment rights and regulations will impact significantly upon young people across the UK. Underlining this, the transition between education and employment has been evidenced as a period when young people experience increased risk of poverty and social exclusion (MacDonald, 2011; Furlong and Cartmel, 2004; Ellison, 2014; ILO, 2016). This article provides an analysis of the role of EU funding streams and operational programmes directed at young people's transitions between education and employment across the UK. The co-ordinated use of EU funding instruments aimed at rebalancing economic and social inequalities between wealthier and poorer regions and groups within the EU is evidenced as improving labour market outcomes for young people living in the most disadvantaged regions of the UK. In light of this, the article contends that future post-Brexit UK governments will need to develop redistributive investment strategies within coherent policy architectures and inclusive forms of governance to ensure the continued delivery of operational programmes for young people which are relevant, effective and sustainable at a local level.
Re-Doubling the Crises of the Welfare State: The impact of Brexit on UK welfare politics
Authors: TAYLOR-GOOBY PETER
Published: July 2017

The double crisis approach distinguishes two kinds of challenge confronting modern welfare states: long-term structural problems and short-term difficulties resulting from policy choices which affect the success with which the long-term issues can be addressed. Structural challenges include two main areas:

•

globalisation and technological changes demanding that governments direct attention to national competitiveness, and

•

population ageing, requiring more spending on pensions, and health and social care.

Recent policy-related problems include the austerity programme since 2010 which has been particularly directed towards benefits and services for working-age people. Responses to both kinds of challenge have set the stage for Brexit.
Atrial septal defect and an unusual anatomical variant of double-chambered right ventricle presenting with cyanosis
Authors: Rothman Abraham , Singh Gagandeep , Evans William N.
Published: July 2017

We treated two patients with unexplained cyanosis, an atrial septal defect and an unusual form of non-obstructive double-chambered right ventricle, with device closure of the atrial septal defect.
Ligand-induced type II interleukin-4 receptor dimers are sustained by rapid re-association within plasma membrane microcompartments
Authors: Richter David , Moraga Ignacio , Winkelmann Hauke , Birkholz Oliver , Wilmes Stephan , Schulte Markos , Kraich Michael , Kenneweg Hella , Beutel Oliver , Selenschik Philipp , Paterok Dirk , Gavutis Martynas , Schmidt Thomas , Garcia K. Christopher , Müller Thomas D. , Piehler Jacob
Published: July 2017

The spatiotemporal organization of cytokine receptors in the plasma membrane is still debated with models ranging from ligand-independent receptor pre-dimerization to ligand-induced receptor dimerization occurring only after receptor uptake into endosomes. Here, we explore the molecular and cellular determinants governing the assembly of the type II interleukin-4 receptor, taking advantage of various agonists binding the receptor subunits with different affinities and rate constants. Quantitative kinetic studies using artificial membranes confirm that receptor dimerization is governed by the two-dimensional ligand–receptor interactions and identify a critical role of the transmembrane domain in receptor dimerization. Single molecule localization microscopy at physiological cell surface expression levels, however, reveals efficient ligand-induced receptor dimerization by all ligands, largely independent of receptor binding affinities, in line with the similar STAT6 activation potencies observed for all IL-4 variants. Detailed spatiotemporal analyses suggest that kinetic trapping of receptor dimers in actin-dependent microcompartments sustains robust receptor dimerization and signalling.
DNA binding drives the association of BRG1/hBRM bromodomains with nucleosomes
Authors: Morrison Emma A. , Sanchez Julio C. , Ronan Jehnna L. , Farrell Daniel P. , Varzavand Katayoun , Johnson Jenna K. , Gu Brian X. , Crabtree Gerald R. , Musselman Catherine A.
Published: July 2017

BRG1 and BRM, central components of the BAF (mSWI/SNF) chromatin remodelling complex, are critical in chromatin structure regulation. Here, we show that the human BRM (hBRM) bromodomain (BRD) has moderate specificity for H3K14ac. Surprisingly, we also find that both BRG1 and hBRM BRDs have DNA-binding activity. We demonstrate that the BRDs associate with DNA through a surface basic patch and that the BRD and an adjacent AT-hook make multivalent contacts with DNA, leading to robust affinity and moderate specificity for AT-rich elements. Although we show that the BRDs can bind to both DNA and H3K14ac simultaneously, the histone-binding activity does not contribute substantially to nucleosome targeting in vitro. In addition, we find that neither BRD histone nor DNA binding contribute to the global chromatin affinity of BRG1 in mouse embryonic stem cells. Together, our results suggest that association of the BRG1/hBRM BRD with nucleosomes plays a regulatory rather than targeting role in BAF activity.
Reactogenicity to major tuberculosis antigens absent in BCG is linked to improved protection against Mycobacterium tuberculosis
Authors: Aguilo Nacho , Gonzalo-Asensio Jesus , Alvarez-Arguedas Samuel , Marinova Dessislava , Gomez Ana Belen , Uranga Santiago , Spallek Ralf , Singh Mahavir , Audran Regine , Spertini François , Martin Carlos
Published: July 2017

MTBVAC is a live-attenuated Mycobacterium tuberculosis vaccine, currently under clinical development, that contains the major antigens ESAT6 and CFP10. These antigens are absent from the current tuberculosis vaccine, BCG. Here we compare the protection induced by BCG and MTBVAC in several mouse strains that naturally express different MHC haplotypes differentially recognizing ESAT6 and CFP10. MTBVAC induces improved protection in C3H mice, the only of the three tested strains reactive to both ESAT6 and CFP10. Deletion of both antigens in MTBVAC reduces its efficacy to BCG levels, supporting a link between greater efficacy and CFP10- and ESAT6-specific reactogenicity. In addition, MTBVAC (but not BCG) triggers a specific response in human vaccinees against ESAT6 and CFP10. Our results warrant further exploration of this response as potential biomarker of protection in MTBVAC clinical trials.
4-alkyl-L-(Dehydro)proline biosynthesis in actinobacteria involves N-terminal nucleophile-hydrolase activity of γ-glutamyltranspeptidase homolog for C-C bond cleavage
Authors: Zhong Guannan , Zhao Qunfei , Zhang Qinglin , Liu Wen
Published: July 2017

γ-Glutamyltranspeptidases (γ-GTs), ubiquitous in glutathione metabolism for γ-glutamyl transfer/hydrolysis, are N-terminal nucleophile (Ntn)-hydrolase fold proteins that share an autoproteolytic process for self-activation. γ-GT homologues are widely present in Gram-positive actinobacteria where their Ntn-hydrolase activities, however, are not involved in glutathione metabolism. Herein, we demonstrate that the formation of 4-Alkyl-L-(dehydro)proline (ALDP) residues, the non-proteinogenic α-amino acids that serve as vital components of many bioactive metabolites found in actinobacteria, involves unprecedented Ntn-hydrolase activity of γ-GT homologue for C–C bond cleavage. The related enzymes share a key Thr residue, which acts as an internal nucleophile for protein hydrolysis and then as a newly released N-terminal nucleophile for carboxylate side-chain processing likely through the generation of an oxalyl-Thr enzyme intermediate. These findings provide mechanistic insights into the biosynthesis of various ALDP residues/associated natural products, highlight the versatile functions of Ntn-hydrolase fold proteins, and particularly generate interest in thus far less-appreciated γ-GT homologues in actinobacteria.
Structural and functional characterization of a DARPin which inhibits Ras nucleotide exchange
Authors: Guillard Sandrine , Kolasinska-Zwierz Paulina , Debreczeni Judit , Breed Jason , Zhang Jing , Bery Nicolas , Marwood Rose , Tart Jon , Overman Ross , Stocki Pawel , Mistry Bina , Phillips Christopher , Rabbitts Terence , Jackson Ronald , Minter Ralph
Published: July 2017

Ras mutations are the oncogenic drivers of many human cancers and yet there are still no approved Ras-targeted cancer therapies. Inhibition of Ras nucleotide exchange is a promising new approach but better understanding of this mechanism of action is needed. Here we describe an antibody mimetic, DARPin K27, which inhibits nucleotide exchange of Ras. K27 binds preferentially to the inactive Ras GDP form with aKdof 4 nM and structural studies support its selectivity for inactive Ras. Intracellular expression of K27 significantly reduces the amount of active Ras, inhibits downstream signalling, in particular the levels of phosphorylated ERK, and slows the growth in soft agar of HCT116 cells. K27 is a potent, non-covalent inhibitor of nucleotide exchange, showing consistent effects across different isoforms of Ras, including wild-type and oncogenic mutant forms.
Correction: Corrigendum: Glacial isostatic uplift of the European Alps
Authors: Mey Jürgen , Scherler Dirk , Wickert Andrew D. , Egholm David L. , Tesauro Magdala , Schildgen Taylor F. , Strecker Manfred R.
Published: July 2017

Nature Communications 7: Article number:13382 (2016); Published 10 November 2016; Updated 14 July 2017 In an earlier publication, Norton and Hampel proposed post-glacial uplift promoted the re-advance of glaciers at the onset of the Younger Dryas by enlarging their accumulation areas, and estimated a maximum present-day uplift rate due to deglaciation of ∼0.
Probing low-energy hyperbolic polaritons in van der Waals crystals with an electron microscope
Authors: Govyadinov Alexander A. , Konečná Andrea , Chuvilin Andrey , Vélez Saül , Dolado Irene , Nikitin Alexey Y. , Lopatin Sergei , Casanova Fèlix , Hueso Luis E. , Aizpurua Javier , Hillenbrand Rainer
Published: July 2017

Van der Waals materials exhibit intriguing structural, electronic, and photonic properties. Electron energy loss spectroscopy within scanning transmission electron microscopy allows for nanoscale mapping of such properties. However, its detection is typically limited to energy losses in the eV range—too large for probing low-energy excitations such as phonons or mid-infrared plasmons. Here, we adapt a conventional instrument to probe energy loss down to 100 meV, and map phononic states in hexagonal boron nitride, a representative van der Waals material. The boron nitride spectra depend on the flake thickness and on the distance of the electron beam to the flake edges. To explain these observations, we developed a classical response theory that describes the interaction of fast electrons with (anisotropic) van der Waals slabs, revealing that the electron energy loss is dominated by excitation of hyperbolic phonon polaritons, and not of bulk phonons as often reported. Thus, our work is of fundamental importance for interpreting future low-energy loss spectra of van der Waals materials.
A haplotype in CFH family genes confers high risk of rare glomerular nephropathies
Authors: Ding Yin , Zhao Weiwei , Zhang Tao , Qiang Hao , Lu Jianping , Su Xin , Wen Shuzhen , Xu Feng , Zhang Mingchao , Zhang Haitao , Zeng Caihong , Liu Zhihong , Chen Huimei
Published: July 2017

Despite distinct renal lesions, a series of rare glomerular nephropathies are reportedly mediated by complement overactivation. Genetic variations in complement genes contribute to disease risk, but the relationship of genotype to phenotype has not been straightforward. Here, we screened 11 complement genes from 91 patients with atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G) and membranoproliferative glomerulonephritis type I (MPGN I), and identified the concomitant presence of three missense variations located within the human complement Factor H (CFH) gene cluster. The three variations, rs55807605, rs61737525 and rs57960694, have strong linkage disequilibrium; subsequent haplotype analysis indicated that ATA increased the susceptibility of these renal diseases. In silico analysis, the CFHR3 rs61737525-T risk allele altered the physical and structural properties and generated a reduction in binding affinity of the CFHR3/C3b complex. Surface plasmon resonance (SPR) binding analysis further demonstrated the substitution induced a decrease of two orders of magnitude in C3b-binding properties, with a declined cofactor activity in fluid phase. These data suggest that the haplotype carrying the causative allele behaves as a partial C3 convertase deficiency, predisposing individuals to diverse pathologic lesions underlying complement overactivation. Such genotype-phenotype discrepancies allow better understanding about these nephropathies mediated by genetic complement disorders.
Direct Growth of MoS2 Nanowalls on Carbon Nanofibers for Use in Supercapacitor
Authors: Sari Fitri Nur Indah , Ting Jyh-Ming
Published: July 2017

Direct growth of MoS2 nanowalls on vapor grown carbon nanofibers (VGCNFs) has been achieved using a microwave-assisted hydrothermal (MAH) method under an acidic condition. The acidic condition was obtained through the addition of an HCl aqueous solution. We demonstrate that the HCl not only modifies the pH value for limiting the growth rate but also leads to the formation of NaCl, which is the key for the direct and unique growth of MoS2 on the VGCNF surface. A growth mechanism is therefore proposed. The growth of MoS2 onto the high electrically conducting VGCNF creates a unique structure that not only reduces the aggregation of MoS2 but also improves the electrical conductivity of the resulting composite electrode. The MoS2 nanowall/VGCNF composite shows Csp as high as 248 F g−1 at 5 mV s−1 and excellent electrochemical stability with a retention of 96% after 1,000 cycles at a high charge rate of 200 mV s−1. The ease of composite fabrication and electrochemical stability suggest that the MoS2 nanowall/VGCNF composite is a promising candidate electrode material for supercapacitor.
Comparative transcriptome analysis of the floral transition in Rosa chinensis ‘Old Blush’ and R. odorata var. gigantea
Authors: Guo Xuelian , Yu Chao , Luo Le , Wan Huihua , Li Yushu , Wang Jia , Cheng Tangren , Pan Huitang , Zhang Qixiang
Published: July 2017

The floral transition is a crucial developmental event, but little is known about the underlying regulatory networks in seasonally and continuously flowering roses. In this study, we compared the genetic basis of flowering in two rose species, Rosa chinensis ‘Old Blush’, which flowers continuously, and R. odorata var. gigantea, which blooms in early spring. Gene ontology (GO) terms related to methylation, light reaction, and starch metabolism were enriched in R. odorata var. gigantea and terms associated with sugar metabolism were enriched in R. chinensis ‘Old Blush’ during the floral transition. A MapMan analysis revealed that genes involved in hormone signaling mediate the floral transition in both taxa. Furthermore, differentially expressed genes (DEGs) involved in vernalization, photoperiod, gibberellin (GA), and starch metabolism pathways converged on integrators, e.g., LFY, AGL24, SOC1, CAL, and COLs, to regulate the floral transition in R. odorata var. gigantea, while DEGs related to photoperiod, sugar metabolism, and GA pathways, including COL16, LFY, AGL11, 6PGDH, GASA4, and BAM, modulated the floral transition in R. chinensis ‘Old Blush.’ Our analysis of the genes underlying the floral transition in roses with different patterns of flowering provides a basis for further functional studies.
Endolysosomal targeting of a clinical chlorin photosensitiser for light-triggered delivery of nano-sized medicines
Authors: Yaghini Elnaz , Dondi Ruggero , Tewari Kunal M. , Loizidou Marilena , Eggleston Ian M. , MacRobert Alexander J.
Published: July 2017

A major problem with many promising nano-sized biotherapeutics including macromolecules is that owing to their size they are subject to cellular uptake via endocytosis, and become entrapped and then degraded within endolysosomes, which can significantly impair their therapeutic efficacy. Photochemical internalisation (PCI) is a technique for inducing cytosolic release of the entrapped agents that harnesses sub-lethal photodynamic therapy (PDT) using a photosensitiser that localises in endolysosomal membranes. Using light to trigger reactive oxygen species-mediated rupture of the photosensitised endolysosomal membranes, the spatio-temporal selectivity of PCI then enables cytosolic release of the agents at the selected time after administration so that they can reach their intracellular targets. However, conventional photosensitisers used clinically for PDT are ineffective for photochemical internalisation owing to their sub-optimal intracellular localisation. In this work we demonstrate that such a photosensitiser, chlorin e6, can be repurposed for PCI by conjugating the chlorin to a cell penetrating peptide, using bioorthogonal ligation chemistry. The peptide conjugation enables targeting of endosomal membranes so that light-triggered cytosolic release of an entrapped nano-sized cytotoxin can be achieved with consequent improvement in cytotoxicity. The photoproperties of the chlorin moiety are also conserved, with comparable singlet oxygen quantum yields found to the free chlorin.
Therapeutic effects of long-circulating miR-135a-containing cationic immunoliposomes against gallbladder carcinoma
Authors: Yang Guanghua , Yin Baobing
Published: July 2017

Gallbladder carcinoma (GBC) is the most common malignant tumour in the biliary tract, but effective therapeutics are lacking. Based on our previous studies, miR-135a is a potential tool to inhibit GBC proliferation. In this study, we constructed miR-135a-loaded DSPE-PEG2000 liposomes modified with Anti-EGFR antibodies (Anti-EGFR-CIL-miR-135a). The results of an analysis of their physicochemical properties indicated the particle size of it was 222.0 ± 2.1 nm in diameter with an uptake efficiency of 86.5%. Next, the post-treatment biological behaviours of GBC, specifically, invasion, metastasis and apoptosis, were evaluated. miR-135a inhibited GBC invasion and metastasis and promoted apoptosis compared to controls. Additionally, miR-135a targeted and regulated the expression of ROCK1, HOXA10 and BCL-2. Due to the targeted effects of Anti-EGFR-CIL-miR-135a, the GBC tumour growth rate was 60% lower in an in vivo xenograft-bearing mouse model compared to controls. Thus, Anti-EGFR-CIL-miR-135a is a promising therapeutic strategy to combat GBC.
A Model-Based Estimate of Regional Wheat Yield Gaps and Water Use Efficiency in Main Winter Wheat Production Regions of China
Authors: Lv Zunfu , Liu Xiaojun , Cao Weixing , Zhu Yan
Published: July 2017

Wheat production is of great importance for national food security and is greatly influenced by the spatial variation of climatic variables, soils, cultivars, etc. This study used WheatGrow and CERES-Wheat models integrated with a GIS to estimate winter wheat productivity, yield gap and water use in the main wheat production regions of China. The results showed that the potential wheat yield gradually increased from south to north and from west to east, with a spatial distribution consistent with the accumulated hours of sunshine. The gap between potential and actual yield varied from 382 to 7515 kg ha−1, with the highest values in Shanxi, Gansu and Shaanxi provinces and the lowest values in Sichuan province. The rainfed yield decreased gradually from south to north, roughly following the pattern of the ratio of accumulated precipitation to accumulated potential evapotranspiration. Under the scenario of autoirrigation, relatively high irrigation water use efficiency was found in western Shandong and southern Sichuan, as well as in northern Henan, Shanxi and Shaanxi. Furthermore, the limiting factors were analysed, and effective measures were suggested for improving regional winter wheat productivity. These results can be helpful for national policy making and water redistribution for agricultural production in China.