bluuebunny/crossref_metadata_2025 huggingface dataset:
Tailoring nanoscopic confines to maximize catalytic activity of hydronium ions
Authors: Shi Hui , Eckstein Sebastian , Vjunov Aleksei , Camaioni Donald M. , Lercher Johannes A.
Published: May 2017

Acid catalysis by hydronium ions is ubiquitous in aqueous-phase organic reactions. Here we show that hydronium ion catalysis, exemplified by intramolecular dehydration of cyclohexanol, is markedly influenced by steric constraints, yielding turnover rates that increase by up to two orders of magnitude in tight confines relative to an aqueous solution of a Brønsted acid. The higher activities in zeolites BEA and FAU than in water are caused by more positive activation entropies that more than offset higher activation enthalpies. The higher activity in zeolite MFI with pores smaller than BEA and FAU is caused by a lower activation enthalpy in the tighter confines that more than offsets a less positive activation entropy. Molecularly sized pores significantly enhance the association between hydronium ions and alcohols in a steric environment resembling the constraints in pockets of enzymes stabilizing active sites.
Digital logic circuits in yeast with CRISPR-dCas9 NOR gates
Authors: Gander Miles W. , Vrana Justin D. , Voje William E. , Carothers James M. , Klavins Eric
Published: May 2017

Natural genetic circuits enable cells to make sophisticated digital decisions. Building equally complex synthetic circuits in eukaryotes remains difficult, however, because commonly used components leak transcriptionally, do not arbitrarily interconnect or do not have digital responses. Here, we designed dCas9-Mxi1-based NOR gates in Saccharomyces cerevisiae that allow arbitrary connectivity and large genetic circuits. Because we used the chromatin remodeller Mxi1, our gates showed minimal leak and digital responses. We built a combinatorial library of NOR gates that directly convert guide RNA (gRNA) inputs into gRNA outputs, enabling the gates to be ‘wired’ together. We constructed logic circuits with up to seven gRNAs, including repression cascades with up to seven layers. Modelling predicted the NOR gates have effectively zero transcriptional leak explaining the limited signal degradation in the circuits. Our approach enabled the largest, eukaryotic gene circuits to date and will form the basis for large, synthetic, cellular decision-making systems.
Solid-state ensemble of highly entangled photon sources at rubidium atomic transitions
Authors: Keil Robert , Zopf Michael , Chen Yan , Höfer Bianca , Zhang Jiaxiang , Ding Fei , Schmidt Oliver G.
Published: May 2017

Semiconductor InAs/GaAs quantum dots grown by the Stranski–Krastanov method are among the leading candidates for the deterministic generation of polarization-entangled photon pairs. Despite remarkable progress in the past 20 years, many challenges still remain for this material, such as the extremely low yield, the low degree of entanglement and the large wavelength distribution. Here, we show that with an emerging family of GaAs/AlGaAs quantum dots grown by droplet etching and nanohole infilling, it is possible to obtain a large ensemble of polarization-entangled photon emitters on a wafer without any post-growth tuning. Under pulsed resonant two-photon excitation, all measured quantum dots emit single pairs of entangled photons with ultra-high purity, high degree of entanglement and ultra-narrow wavelength distribution at rubidium transitions. Therefore, this material system is an attractive candidate for the realization of a solid-state quantum repeater—among many other key enabling quantum photonic elements.
The controlled disassembly of mesostructured perovskites as an avenue to fabricating high performance nanohybrid catalysts
Authors: Wang Yuan , Arandiyan Hamidreza , Tahini Hassan A. , Scott Jason , Tan Xin , Dai Hongxing , Gale Julian D. , Rohl Andrew L. , Smith Sean C. , Amal Rose
Published: May 2017

Versatile superstructures composed of nanoparticles have recently been prepared using various disassembly methods. However, little information is known on how the structural disassembly influences the catalytic performance of the materials. Here we show how the disassembly of an ordered porous La0.6Sr0.4MnO3 perovskite array, to give hexapod mesostructured nanoparticles, exposes a new crystal facet which is more active for catalytic methane combustion. On fragmenting three-dimensionally ordered macroporous (3DOM) structures in a controlled manner, via a process that has been likened to retrosynthesis, hexapod-shaped building blocks can be harvested which possess a mesostructured architecture. The hexapod-shaped perovskite catalyst exhibits excellent low temperature methane oxidation activity (T90%=438 °C; reaction rate=4.84 × 10−7 mol m−2 s−1). First principle calculations suggest the fractures, which occur at weak joints within the 3DOM architecture, afford a large area of (001) surface that displays a reduced energy barrier for hydrogen abstraction, thereby facilitating methane oxidation.
Long-range allosteric regulation of the human 26S proteasome by 20S proteasome-targeting cancer drugs
Authors: Haselbach David , Schrader Jil , Lambrecht Felix , Henneberg Fabian , Chari Ashwin , Stark Holger
Published: May 2017

The proteasome holoenzyme is the major non-lysosomal protease; its proteolytic activity is essential for cellular homeostasis. Thus, it is an attractive target for the development of chemotherapeutics. While the structural basis of core particle (CP) inhibitors is largely understood, their structural impact on the proteasome holoenzyme remains entirely elusive. Here, we determined the structure of the 26S proteasome with and without the inhibitor Oprozomib. Drug binding modifies the energy landscape of conformational motion in the proteasome regulatory particle (RP). Structurally, the energy barrier created by Oprozomib triggers a long-range allosteric regulation, resulting in the stabilization of a non-productive state. Thereby, the chemical drug-binding signal is converted, propagated and amplified into structural changes over a distance of more than 150 Å from the proteolytic site to the ubiquitin receptor Rpn10. The direct visualization of changes in conformational dynamics upon drug binding allows new ways to screen and develop future allosteric proteasome inhibitors.
A reaction mode of carbene-catalysed aryl aldehyde activation and induced phenol OH functionalization
Authors: Chen Xingkuan , Wang Hongling , Doitomi Kazuki , Ooi Chong Yih , Zheng Pengcheng , Liu Wangsheng , Guo Hao , Yang Song , Song Bao-An , Hirao Hajime , Chi Yonggui Robin
Published: May 2017

The research in the field of asymmetric carbene organic catalysis has primarily focused on the activation of carbon atoms in non-aromatic scaffolds. Here we report a reaction mode of carbene catalysis that allows for aromatic aldehyde activation and remote oxygen atom functionalization. The addition of a carbene catalyst to the aldehyde moiety of 2-hydroxyl aryl aldehyde eventually enables dearomatization and remote OH activation. The catalytic process generates a type of carbene-derived intermediate with an oxygen atom as the reactive centre. Inexpensive achiral urea co-catalyst works cooperatively with the carbene catalyst, leading to consistent enhancement of the reaction enantioselectivity. Given the wide presence of aromatic moieties and heteroatoms in natural products and synthetic functional molecules, we expect our reaction mode to significantly expand the power of carbene catalysis in asymmetric chemical synthesis.
Probing the action of a novel anti-leukaemic drug therapy at the single cell level using modern vibrational spectroscopy techniques
Authors: Denbigh Joanna L. , Perez-Guaita David , Vernooij Robbin R. , Tobin Mark J. , Bambery Keith R. , Xu Yun , Southam Andrew D. , Khanim Farhat L. , Drayson Mark T. , Lockyer Nicholas P. , Goodacre Royston , Wood Bayden R.
Published: May 2017

Acute myeloid leukaemia (AML) is a life threatening cancer for which there is an urgent clinical need for novel therapeutic approaches. A redeployed drug combination of bezafibrate and medroxyprogesterone acetate (BaP) has shown anti-leukaemic activity in vitro and in vivo. Elucidation of the BaP mechanism of action is required in order to understand how to maximise the clinical benefit. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, Synchrotron radiation FTIR (S-FTIR) and Raman microspectroscopy are powerful complementary techniques which were employed to probe the biochemical composition of two AML cell lines in the presence and absence of BaP. Analysis was performed on single living cells along with dehydrated and fixed cells to provide a large and detailed data set. A consideration of the main spectral differences in conjunction with multivariate statistical analysis reveals a significant change to the cellular lipid composition with drug treatment; furthermore, this response is not caused by cell apoptosis. No change to the DNA of either cell line was observed suggesting this combination therapy primarily targets lipid biosynthesis or effects bioactive lipids that activate specific signalling pathways.
Plasmacytoid dendritic cells appear inactive during sub-microscopic Plasmodium falciparum blood-stage infection, yet retain their ability to respond to TLR stimulation
Authors: Loughland Jessica R. , Minigo Gabriela , Sarovich Derek S. , Field Matt , Tipping Peta E. , Montes de Oca Marcela , Piera Kim A. , Amante Fiona H. , Barber Bridget E. , Grigg Matthew J. , William Timothy , Good Michael F. , Doolan Denise L. , Engwerda Christian R. , Anstey Nicholas M. , McCarthy James S. , Woodberry Tonia
Published: May 2017

Plasmacytoid dendritic cells (pDC) are activators of innate and adaptive immune responses that express HLA-DR, toll-like receptor (TLR) 7, TLR9 and produce type I interferons. The role of human pDC in malaria remains poorly characterised. pDC activation and cytokine production were assessed in 59 malaria-naive volunteers during experimental infection with 150 or 1,800 P. falciparum-parasitized red blood cells. Using RNA sequencing, longitudinal changes in pDC gene expression were examined in five adults before and at peak-infection. pDC responsiveness to TLR7 and TLR9 stimulation was assessed in-vitro. Circulating pDC remained transcriptionally stable with gene expression altered for 8 genes (FDR < 0.07). There was no upregulation of co-stimulatory molecules CD86, CD80, CD40, and reduced surface expression of HLA-DR and CD123 (IL-3R-α). pDC loss from the circulation was associated with active caspase-3, suggesting pDC apoptosis during primary infection. pDC remained responsive to TLR stimulation, producing IFN-α and upregulating HLA-DR, CD86, CD123 at peak-infection. In clinical malaria, pDC retained HLA-DR but reduced CD123 expression compared to convalescence. These data demonstrate pDC retain function during a first blood-stage P. falciparum exposure despite sub-microscopic parasitaemia downregulating HLA-DR. The lack of evident pDC activation in both early infection and malaria suggests little response of circulating pDC to infection.
Assessment of the diagnostic value of different biomarkers in relation to various stages of diabetic nephropathy in type 2 diabetic patients
Authors: Al-Rubeaan Khalid , Siddiqui Khalid , Al-Ghonaim Mohammed A. , Youssef Amira M. , Al-Sharqawi Ahmed H. , AlNaqeb Dhekra
Published: May 2017

Albuminuria is widely used to indicate early phases of diabetic nephropathy although it is limited by the fact that structural damage might precede albumin excretion. This necessitates identifying better biomarkers that diagnose or predict diabetic nephropathy. This is a cross-sectional hospital based study recruiting type 2 diabetic patients cohort aged 35–75 years with diabetes duration of ≥10 years. Out of total eligible 467 patients, 200 patients were with normal albumin excretion, 184 patients with microalbuminuria and 83 patients with macroalbuminuria. All the patients were tested for the 22 selected biomarkers including serum, plasma and urinary markers. Sensitivity, specificity, and area under the curve (AUC) were calculated as measures of diagnostic accuracy. Out of the tested biomarkers, urinary transferrin, urinary Retinol binding protein (RBP) and serum osteopontin had the best diagnostic value for diabetic nephropathy presence based on the AUC value. The rest of the biomarkers had comparatively less or even no discriminative power. The urinary transferrin and RBP and serum osteopontin, had the best diagnostic value in type 2 diabetic patients at different stages of diabetic nephropathy. Further longitudinal prospective studies are needed to evaluate the predictive power of those markers for detecting diabetic nephropathy before any structural damage occurs.
The Argi system: one-step purification of proteins tagged with arginine-rich cell-penetrating peptides
Authors: Bartnicki Filip , Bonarek Piotr , Kowalska Ewa , Strzalka Wojciech
Published: May 2017

The discovery of cell penetrating peptides (CPPs) opened new perspectives for the delivery of proteins into human cells. It is considered that in the future CPP-mediated transport of therapeutic proteins may find applications in the treatment of human diseases. Despite this fact a fast and simple method for the purification of CPP-tagged proteins, free of additional tags, was not available to date. To fill this gap we developed the Argi system for one-step purification of proteins tagged with arginine rich CPPs.
Bi-specific molecule against EGFR and death receptors simultaneously targets proliferation and death pathways in tumors
Authors: Zhu Yanni , Bassoff Nicole , Reinshagen Clemens , Bhere Deepak , Nowicki Michal O. , Lawler Sean E. , Roux Jérémie , Shah Khalid
Published: May 2017

Developing therapeutics that target multiple receptor signaling pathways in tumors is critical as therapies targeting single specific biomarker/pathway have shown limited efficacy in patients with cancer. In this study, we extensively characterized a bi-functional molecule comprising of epidermal growth factor receptor (EGFR) targeted nanobody (ENb) and death receptor (DR) targeted ligand TRAIL (ENb-TRAIL). We show that ENb-TRAIL has therapeutic efficacy in tumor cells from different cancer types which do not respond to either EGFR antagonist or DR agonist monotherapies. Utilizing pharmacological inhibition, genetic loss of function and FRET studies, we show that ENb-TRAIL blocks EGFR signalling via the binding of ENb to EGFR which in turn induces DR5 clustering at the plasma membrane and thereby primes tumor cells to caspase-mediated apoptosis. In vivo, using a clinically relevant orthotopic resection model of primary glioblastoma and engineered stem cells (SC) expressing ENb-TRAIL, we show that the treatment with synthetic extracellular matrix (sECM) encapsulated SC-ENb-TRAIL alleviates tumor burden and significantly increases survival. This study is the first to report novel mechanistic insights into simultaneous targeting of receptor-mediated proliferation and cell death signaling pathways in different tumor types and presents a promising approach for translation into the clinical setting.
Dysregulation of angiogenesis-specific signalling in adult testis results in xenograft degeneration
Authors: Devi Lalitha , Pothana Lavanya , Goel Sandeep
Published: May 2017

Ectopic xenografting of testis is a feasible option for preservation of male fertility and angiogenesis plays a pivotal role in xenograft survival and functionality. When compared to immature testis, the adult testis is unable to establish functional xenografts due to potentially lower efficiency to induce angiogenesis. The precise molecular mechanism, however, remains elusive. In the present study, we compared adult and immature testis xenografts for survival, maturation and germ cell differentiation. Further, we evaluated differential expression of angiogenesis signalling-specific proteins in adult and immature testis and their xenografts. Results showed that adult testis xenografts degenerated whereas immature testis xenografts survived and established spermatogenesis with the production of haploid germ cells. Protein expression analysis demonstrated that immature testis xenografts were able to establish angiogenesis either through eNOS activation via VEGF and PI3K/AKT or through EGFR-mediated STAT3 pathway. The role of ERK/MAPK pathway in xenograft angiogenesis was ruled out. The absence or reduced expression of angiogenesis-specific proteins in adult testis and its xenografts possibly resulted in poor angiogenesis and in their subsequent degeneration. This study provides insight into angiogenesis mechanism that can be utilized to augment testis xenografting efficiency.
Use of Patterned Collagen Coated Slides to Study Normal and Scleroderma Lung Fibroblast Migration
Authors: Ahmed Abdi Bahja , Lopez Henry , Karrar Sarah , Renzoni Elisabetta , Wells Athol , Tam Angela , Etomi Oseme , Hsuan J. Justin , Martin George R. , Shiwen Xu , Denton Christopher P. , Abraham David , Stratton Richard
Published: May 2017

Systemic sclerosis (SSc) is a spreading fibrotic disease affecting the skin and internal organs. We aimed to model pathogenic fibroblast migration in SSc in order to identify enhancing factors, measure the effect of migrating cells on underlying extracellular matrix (ECM) and test possible therapeutic inhibitors. Novel patterned collagen substrates were used to investigate alignment and migration of skin and lung fibroblasts from SSc patients and healthy controls. Normal lung but not skin fibroblasts consistently elongated and aligned with underlying collagen and migrated dependent on PDGF or serum. SSc lung fibroblasts remained growth factor dependent, did not migrate more rapidly and were less restricted to alignment of the collagen. Multiple collagen proline and lysine-modifying enzymes were identified in SSc but not control fibroblast extracellular matrix preparations, indicating differential levels of ECM modification by the diseased cells. Profiling of migrating cells revealed a possible SCF/c-Kit paracrine mechanism contributing to migration via a subpopulation of cells. Heparin, which binds ligands including PDGF and SCF, and imatininib which blocks downstream tyrosine kinase receptors, both inhibited lung fibroblast migration individually but showed synergy in SSc cells. Pathologic lung fibroblasts from SSc patients modify ECM during migration but remain growth factor dependent and sensitive to inhibitors.
Early Detection and Serial Monitoring of Anthracycline-Induced Cardiotoxicity Using T1-mapping Cardiac Magnetic Resonance Imaging: An Animal Study
Authors: Hong Yoo Jin , Park Heae Surng , Park Jeffrey Kihyun , Han Kyunghwa , Park Chul Hwan , Kim Tai Kyung , Yoo Sae Jong , Lee Ji Yeon , Kim Pan Ki , Hur Jin , Lee Hye-Jeong , Kim Young Jin , Suh Young Joo , Paek Mun Young , Choi Byoung Wook
Published: May 2017

A reliable, non-invasive diagnostic method is needed for early detection and serial monitoring of cardiotoxicity, a well-known side effect of chemotherapy. This study aimed to assess the feasibility of T1-mapping cardiac magnetic resonance imaging (CMR) for evaluating subclinical myocardial changes in a doxorubicin-induced cardiotoxicity rabbit model. Adult male New Zealand White rabbits were injected twice-weekly with doxorubicin and subjected to CMR on a clinical 3T MR system before and every 2–4 weeks post-drug administration. Native T1 and extracellular volume (ECV) values were measured at six mid-left ventricle (LV) and specific LV lesions. Histological assessments evaluated myocardial injury and fibrosis. Three pre-model and 11 post-model animals were included. Myocardial injury was observed from 3 weeks. Mean LV myocardium ECV values increased significantly from week 3 before LV ejection fraction decreases (week 6), and ECVs of the RV upper/lower insertion sites and papillary muscle exceeded those of the LV. The mean native T1 value in the mid-LV increased significantly increased from week 6, and LV myocardium ECV correlated strongly with the degree of fibrosis (r = 0.979, p < 0.001). Myocardial T1 mapping, particularly ECV values, reliably and non-invasively detected early cardiotoxicity, allowing serial monitoring of chemotherapy-induced cardiotoxicity.
Mesenchymal stem cells correct haemodynamic dysfunction associated with liver injury after extended resection in a pig model
Authors: Tautenhahn Hans-Michael , Brückner Sandra , Uder Christiane , Erler Silvio , Hempel Madlen , von Bergen Martin , Brach Janine , Winkler Sandra , Pankow Franziska , Gittel Claudia , Baunack Manja , Lange Undine , Broschewitz Johannes , Dollinger Matthias , Bartels Michael , Pietsch Uta , Amann Kerstin , Christ Bruno
Published: May 2017

In patients, acute kidney injury (AKI) is often due to haemodynamic impairment associated with hepatic decompensation following extended liver surgery. Mesenchymal stem cells (MSCs) supported tissue protection in a variety of acute and chronic diseases, and might hence ameliorate AKI induced by extended liver resection. Here, 70% liver resection was performed in male pigs. MSCs were infused through a central venous catheter and haemodynamic parameters as well as markers of acute kidney damage were monitored under intensive care conditions for 24 h post-surgery. Cytokine profiles were established to anticipate the MSCs’ potential mode of action. After extended liver resection, hyperdynamic circulation, associated with hyponatraemia, hyperkalaemia, an increase in serum aldosterone and low urine production developed. These signs of hepatorenal dysfunction and haemodynamic impairment were corrected by MSC treatment. MSCs elevated PDGF levels in the serum, possibly contributing to circulatory homeostasis. Another 14 cytokines were increased in the kidney, most of which are known to support tissue regeneration. In conclusion, MSCs supported kidney and liver function after extended liver resection. They probably acted through paracrine mechanisms improving haemodynamics and tissue homeostasis. They might thus provide a promising strategy to prevent acute kidney injury in the context of post-surgery acute liver failure.
MicroRNA-150 modulates intracellular Ca
2+
levels in naïve CD8+ T cells by targeting TMEM20
Authors: Kim Tae-Don , Jung Hong-Ryul , Seo Sang-Hwan , Oh Se-Chan , Ban Youngho , Tan Xiaoxia , Min Kim Jung , Hyun Lee Sang , Koh Duk-Su , Jung Haiyoung , Park Young-Jun , Ran Yoon Suk , Doh Junsang , Ha Sang-Jun , Choi Inpyo , Greenberg Philip D.
Published: May 2017

Regulation of intracellular Ca2+ signaling is a major determinant of CD8+ T cell responsiveness, but the mechanisms underlying this regulation of Ca2+ levels, especially in naïve CD8+ T cells, are not fully defined. Here, we showed that microRNA-150 (miR-150) controls intracellular Ca2+ levels in naïve CD8+ T cells required for activation by suppressing TMEM20, a negative regulator of Ca2+ extrusion. miR-150 deficiency increased TMEM20 expression, which resulted in increased intracellular Ca2+ levels in naïve CD8+ T cells. The subsequent increase in Ca2+ levels induced expression of anergy-inducing genes, such as Cbl-b, Egr2, and p27, through activation of NFAT1, as well as reduced cell proliferation, cytokine production, and the antitumor activity of CD8+ T cells upon antigenic stimulation. The anergy-promoting molecular milieu and function induced by miR-150 deficiency were rescued by reinstatement of miR-150. Additionally, knockdown of TMEM20 in miR-150-deficient naïve CD8+ T cells reduced intracellular Ca2+ levels. Our findings revealed that miR-150 play essential roles in controlling intracellular Ca2+ level and activation in naïve CD8+ T cells, which suggest a mechanism to overcome anergy induction by the regulation of intracellular Ca2+ levels.
Thickness-dependent Crack Propagation in Uniaxially Strained Conducting Graphene Oxide Films on Flexible Substrates
Authors: Sakorikar Tushar , Kavitha Maheswari Kavirajan , Vayalamkuzhi Pramitha , Jaiswal Manu
Published: May 2017

We demonstrate that crack propagation in uniaxially strained reduced graphene oxide (rGO) films is substantially dependent on the film thickness, for films in the sub-micron regime. rGO film on flexible polydimethylsiloxane (PDMS) substrate develop quasi-periodic cracks upon application of strain. The crack density and crack width follow contrasting trends as film thickness is increased and the results are described in terms of a sequential cracking model. Further, these cracks also have a tendency to relax when the strain is released. These features are also reflected in the strain-dependent electrical dc and ac conductivity studies. For an optimal thickness (3-coat), the films behave as strain-resistant, while for all other values it becomes strain-responsive, attributed to a favorable combination of crack density and width. This study of the film thickness dependent response and the crack propagation mechanism under strain is a significant step for rationalizing the application of layered graphene-like systems for flexible optoelectronic and strain sensing applications. When the thickness is tuned for enhanced extent of crack propagation, strain-sensors with gauge factor up to ∼470 are realized with the same material. When thickness is chosen to suppress the crack propagation, strain-resistive flexible TiO2- rGO UV photoconductor is realized.
Analysis of Parasitic Protozoa at the Single-cell Level using Microfluidic Impedance Cytometry
Authors: McGrath J. S. , Honrado C. , Spencer D. , Horton B. , Bridle H. L. , Morgan H.
Published: May 2017

At present, there are few technologies which enable the detection, identification and viability analysis of protozoan pathogens including Cryptosporidium and/or Giardia at the single (oo)cyst level. We report the use of Microfluidic Impedance Cytometry (MIC) to characterise the AC electrical (impedance) properties of single parasites and demonstrate rapid discrimination based on viability and species. Specifically, MIC was used to identify live and inactive C. parvum oocysts with over 90% certainty, whilst also detecting damaged and/or excysted oocysts. Furthermore, discrimination of Cryptosporidium parvum, Cryptosporidium muris and Giardia lamblia, with over 92% certainty was achieved. Enumeration and identification of (oo)cysts can be achieved in a few minutes, which offers a reduction in identification time and labour demands when compared to existing detection methods.
EMBuilder: A Template Matching-based Automatic Model-building Program for High-resolution Cryo-Electron Microscopy Maps
Authors: Zhou Niyun , Wang Hongwei , Wang Jiawei
Published: May 2017

The resolution of electron-potential maps in single-particle cryo-electron microscopy (cryoEM) is approaching atomic or near- atomic resolution. However, no program currently exists for de novo cryoEM model building at resolutions exceeding beyond 3.5 Å. Here, we present a program, EMBuilder, based on template matching, to generate cryoEM models at high resolution. The program identifies features in both secondary-structure and Cα stages. In the secondary structure stage, helices and strands are identified with pre-computed templates, and the voxel size of the entire map is then refined to account for microscopic magnification errors. The identified secondary structures are then extended from both ends in the Cα stage via a log-likelihood (LLK) target function, and if possible, the side chains are also assigned. This program can build models of large proteins (~1 MDa) in a reasonable amount of time (~1 day) and thus has the potential to greatly decrease the manual workload required for model building of high-resolution cryoEM maps.
Strategies for reducing the fertilizer application rate in the ridge and furrow rainfall harvesting system in semiarid regions
Authors: Lian Yanhao , Meng Xiangping , Yang Zhen , Wang Tianlu , Ali Shahzad , Yang Baoping , Zhang Peng , Han Qingfang , Jia Zhikuan , Ren Xiaolong
Published: May 2017

The ridge and furrow rainwater harvesting (RFRH) system is a promising water-saving planting technique for dryland farming, but we lack a full understanding of the effects of different fertilizer rates (N:P) on plant nutrient uptake and nutrient use efficiency (NuUE) in foxtail millet using this planting method, as well as the available nutrient residues in the soil. We conducted field studies (Loess Plateau, China) comparing RFRH planting (R) and traditional flat planting (T) at four different fertilizer rates to determine suitable fertilizer application rates for R during 2013–2015. Compared with T, R improved the soil moisture and the utilization of rainwater and fertilizer, thereby enhancing the grain yield, water use efficiency (WUE), grain nutrient uptake, and NUE in a dry year, but with no improvements in a rainy year. The grain yield and WUE exhibited parabolic increasing trends as the fertilizer application rate increased over three years, but no significant increase was found when the fertilizer rate exceeded 189:96 kg N:P ha−1 under R, which significantly reduced the NuUE and might waste nutrients. Therefore, we recommend R combined with 189:96 kg N:P ha−1 as a promising planting strategy for foxtail millet in semiarid areas.
Novel approach for accurate tissue-based protein colocalization and proximity microscopy
Authors: Lutz Mirjam I. , Schwaiger Carmen , Hochreiter Bernhard , Kovacs Gabor G. , Schmid Johannes A.
Published: May 2017

Fluorescence colocalization microscopy is frequently used to assess potential links between distinct molecules; however, this method can lead to striking false-positive results and erroneous conclusions. Here we developed a novel approach with more sophisticated mathematical colocalization analyses together with visualization of physical proximity using fluorescence resonance energy transfer (FRET). To verify our results we used the proximity ligation assay (PLA). With these methods we could demonstrate that distinct neurodegeneration-related proteins either not or only rarely interact in human brain tissue.
Node Attribute-enhanced Community Detection in Complex Networks
Authors: Jia Caiyan , Li Yafang , Carson Matthew B. , Wang Xiaoyang , Yu Jian
Published: May 2017

Community detection involves grouping the nodes of a network such that nodes in the same community are more densely connected to each other than to the rest of the network. Previous studies have focused mainly on identifying communities in networks using node connectivity. However, each node in a network may be associated with many attributes. Identifying communities in networks combining node attributes has become increasingly popular in recent years. Most existing methods operate on networks with attributes of binary, categorical, or numerical type only. In this study, we introduce kNN-enhance, a simple and flexible community detection approach that uses node attribute enhancement. This approach adds the k Nearest Neighbor (kNN) graph of node attributes to alleviate the sparsity and the noise effect of an original network, thereby strengthening the community structure in the network. We use two testing algorithms, kNN-nearest and kNN-Kmeans, to partition the newly generated, attribute-enhanced graph. Our analyses of synthetic and real world networks have shown that the proposed algorithms achieve better performance compared to existing state-of-the-art algorithms. Further, the algorithms are able to deal with networks containing different combinations of binary, categorical, or numerical attributes and could be easily extended to the analysis of massive networks.
Construction of novel repeat proteins with rigid and predictable structures using a shared helix method
Authors: Youn Suk-Jun , Kwon Na-Young , Lee Ji Hyun , Kim Jin Hong , Choi Jinwoo , Lee Hayyoung , Lee Jie-Oh
Published: May 2017

Generating artificial protein assemblies with complex shapes requires a method for connecting protein components with stable and predictable structures. Currently available methods for creating rigid protein assemblies rely on either complicated calculations or extensive trial and error. We describe a simple and efficient method for connecting two proteins via a fused alpha helix that is formed by joining two preexisting helices into a single extended helix. Because the end-to-end ligation of helices does not guarantee the formation of a continuous helix, we superimposed 1–2 turns of pairs of connecting helices by using a molecular graphics program. Then, we chose amino acids from the two natural sequences that would stabilize the connecting helix. This “shared helix method” is highly efficient. All the designed proteins that could be produced in Escherichia coli were readily crystallized and had the expected fusion structures. To prove the usefulness of this method, we produced two novel repeat proteins by assembling several copies of natural or artificial proteins with alpha helices at both termini. Their crystal structures demonstrated the successful assembly of the repeating units with the intended curved shapes. We propose that this method could dramatically expand the available repertoire of natural repeat proteins.
Control of light absorbance using plasmonic grating based perfect absorber at visible and near-infrared wavelengths
Authors: Nguyen Duc Minh , Lee Dasol , Rho Junsuk
Published: May 2017

Conventional metamaterial absorbers have multilayer designs, where the dielectric interlayer is sandwiched between a top patterned metallic structure and bottom metallic film. Here, we demonstrate that a highly polarization-sensitive perfect absorber canbe realized by replacing the bottom metallic film with a plasmonic grating. Designs for broadband and narrowband of wavelength are proposed and numerically investigated. The designed absorbers perform high light absorption, which is above 90% over the wavelength range of 0.4–1.4 µm for the broadband absorber and 98% for the absorption peak in case of the narrowband design, with a specific polarization of incident light. We find that the absorption is tunable by changing the polarization. Such absorbers offer new approach for active control of light absorbance with strong impacts for solar energy harvesting, light emitting and sensing.
Environmentally driven sexual segregation in a marine top predator
Authors: Paiva Vitor H. , Pereira Justin , Ceia Filipe R. , Ramos Jaime A.
Published: May 2017

Sexual segregation in foraging occurs in many animal species, resulting in the partitioning of resources and reduction of competition between males and females, yet the patterns and drivers of such segregation are still poorly understood. We studied the foraging movements (GPS-tracking), habitat use (habitat modelling) and trophic ecology (stable isotope analysis) of female and male Cory’s shearwatersCalonectris borealisduring the mid chick-rearing period of six consecutive breeding seasons (2010–2015). We found a clear sexual segregation in foraging in years of greater environmental stochasticity, likely years of lower food availability. When food became scarce, females undertook much longer foraging trips, exploited more homogeneous water masses, had a larger isotopic niche, fed on lower trophic level prey and exhibited a lower body condition, when compared to males. Sexual competition for trophic resources may be stronger when environmental conditions are poor. A greater foraging success of one sex may result in differential body condition of pair mates when enduring parental effort, and ultimately, in an increased probability of breeding failure.
Oncopig Soft-Tissue Sarcomas Recapitulate Key Transcriptional Features of Human Sarcomas
Authors: Schachtschneider Kyle M. , Liu Yingkai , Mäkeläinen Suvi , Madsen Ole , Rund Laurie A. , Groenen Martien A. M. , Schook Lawrence B.
Published: May 2017

Human soft-tissue sarcomas (STS) are rare mesenchymal tumors with a 5-year survival rate of 50%, highlighting the need for further STS research. Research has been hampered by limited human sarcoma cell line availability and the large number of STS subtypes, making development of STS cell lines and animal models representative of the diverse human STS subtypes critical. Pigs represent ideal human disease models due to their similar size, anatomy, metabolism, and genetics compared to humans. The Oncopig encodes inducible KRAS
G12D
and TP53
R167H
transgenes, allowing for STS modeling in a spatial and temporal manner. This study utilized Oncopig STS cell line (fibroblast) and tumor (leiomyosarcoma) RNA-seq data to compare Oncopig and human STS expression profiles. Altered expression of 3,360 and 7,652 genes was identified in Oncopig STS cell lines and leiomyosarcomas, respectively. Transcriptional hallmarks of human STS were observed in Oncopig STS, including altered TP53 signaling, Wnt signaling activation, and evidence of epigenetic reprogramming. Furthermore, master regulators of Oncopig STS expression were identified, including FOSL1, which was previously identified as a potential human STS therapeutic target. These results demonstrate the Oncopig STS model’s ability to mimic human STS transcriptional profiles, providing a valuable resource for sarcoma research and cell line development.
β-lapachone suppresses tumour progression by inhibiting epithelial-to-mesenchymal transition in NQO1-positive breast cancers
Authors: Yang Yang , Zhou Xianchun , Xu Ming , Piao Junjie , Zhang Yuan , Lin Zhenhua , Chen Liyan
Published: May 2017

NQO1 is a FAD-binding protein that can form homodimers and reduce quinones to hydroquinones, and a growing body of evidence currently suggests that NQO1 is dramatically elevated in solid cancers. Here, we demonstrated that NQO1 was elevated in breast cancer and that its expression level was positively correlated with invasion and reduced disease free survival (DFS) and overall survival (OS) rates. Next, we found that β-lapachone exerted significant anti-proliferation and anti-metastasis effects in breast cancer cell lines due to its effects on NQO1 expression. Moreover, we revealed that the anti-cancer effects of β-lapachone were mediated by the inactivation of the Akt/mTOR pathway. In conclusion, these results demonstrated that NQO1 could be a useful prognostic biomarker for patients with breast cancer, and its bioactivatable drug, β-lapachone represented a promising new development and an effective strategy for indicating the progression of NQO1-positive breast cancers.
Fiber-utilizing capacity varies in Prevotella- versus Bacteroides-dominated gut microbiota
Authors: Chen Tingting , Long Wenmin , Zhang Chenhong , Liu Shuang , Zhao Liping , Hamaker Bruce R.
Published: May 2017

The gut microbiota of individuals are dominated by different fiber-utilizing bacteria, which ferment dietary fiber into short chain fatty acids (SCFAs) known to be important for human health. Here, we show that the dominance of Prevotella versus Bacteroides in fecal innocula, identified into two different enterotypes, differentially impacts in vitro fermentation profiles of SCFAs from fibers with different chemical structures. In a microbiome of the Prevotella enterotype, fructooligosaccharides, and sorghum and corn arabinoxylans significantly promoted one single Prevotella OTU with equally high production of total SCFAs with propionate as the major product. Conversely, in the Bacteroides-dominated microbiota, the three fibers enriched different OTUs leading to different levels and ratios of SCFAs. This is the first report showing how individual differences in two enterotypes cause distinctly different responses to dietary fiber. Microbiota dominated by different fiber-utilizing bacteria may impact host health by way of producing different amounts and profiles of SCFAs from the same carbohydrate substrates.
Generation of a planar direct-current glow discharge in atmospheric pressure air using rod array electrode
Authors: Li Xuechen , Zhang Panpan , Jia Pengying , Chu Jingdi , Chen Junying
Published: May 2017

Scaling up atmospheric pressure glow discharge to large volume is desirable for low-temperature plasma applications. In this paper, an approach to generate a glow discharge in a planar shape with a fairly large volume is proposed in atmospheric pressure air through utilizing a direct-current excited rod array electrode. The planar discharge with a wide gap originates from three discrete discharges with a narrow gap. Based on electrical method and optical emission spectroscopy, it is found that gap voltage increases, while discharge current remains constant with increasing the gap width. Temperature and electron density of the discharge decrease with increasing the gap width.
Determination of bismuth(iii) in environmental and pharmaceutical samples using an organic reagent
Authors: Verma Chitra , Tapadia Kavita , Soni Anupam Bala , Sharma Ashima
Published: May 2017

Nanodrop spectrophotometric determination of bismuth(iii).
Unveiling the correlation between structural order–disorder character and photoluminescence emissions of NaNbO3
Authors: Teixeira Guilhermina Ferreira , Silva Junior Euripedes , Simões Alexandre Zirpoli , Longo Elson , Zaghete Maria Aparecida
Published: May 2017

Orthorhombic NaNbO3 particles obtained via the MAH route show photoluminescence emission related to the structural disorder effect at the medium-range.
Modelling charge transfer processes in C2+–tetrahydrofuran collision for ion-induced radiation damage in DNA building blocks
Authors: Erdmann Ewa , Bacchus-Montabonel Marie-Christine , Łabuda Marta
Published: May 2017

Investigations of the collision-induced processes involving carbon ions and molecules of biological interest, in particular DNA building blocks, are crucial to model the effect of radiation on cells to improve medical treatments for cancer therapy.
Multi-level quantum mechanics theories and molecular mechanics study of the double-inversion mechanism of the F−+ CH3I reaction in aqueous solution
Authors: Liu Peng , Zhang Jingxue , Wang Dunyou
Published: May 2017

A new, double-inversion mechanism was discovered for the nucleophilic substitution reaction F−+ CH3I in aqueous solution.
Emerging investigators series: hydrogen sulfide production in municipal stormwater retention ponds under ice covered conditions: a study of water quality and SRB populations
Authors: D'Aoust Patrick M. , Delatolla Robert , Poulain Alexandre , Guo Galen , Wang Ru , Rennie Colin , Chen Liyu , Pick Frances R.
Published: May 2017

Sulfide production in stormwater ponds is a result of increased ubiquitous SRB activity.
Potential antiproliferative activity of polyphenol metabolites against human breast cancer cells and their urine excretion pattern in healthy subjects following acute intake of a polyphenol-rich juice of grumixama (Eugenia brasiliensis Lam.)
Authors: Teixeira L. L. , Costa G. R. , Dörr F. A. , Ong T. P. , Pinto E. , Lajolo F. M. , Hassimotto N. M. A.
Published: May 2017

The main metabolites of anthocyanins and ellagitannins in urine after acute intake of grumixama: hippuric acid and urolithins, respectively.
Non-matrix-matched standardisation in LA-ICP-MS analysis: general approach, and application to allanite Th–U–Pb dating
Authors: Burn Marco , Lanari Pierre , Pettke Thomas , Engi Martin
Published: May 2017

We present a step-by-step procedure on how to calibrate a given LA-ICP-MS instrumentation in order to achieve matrix-independent standardisation that yields precise and accurate isotopic ratios and age data.
Mono-, tri- and polynuclear copper(ii) complexes of Schiff-base ligands: synthesis, characterization and catalytic activity towards alcohol oxidation
Authors: Bhattacharjee Aradhita , Halder Shibashis , Ghosh Koushik , Rizzoli Corrado , Roy Partha
Published: May 2017

A mononuclear copper(ii) complex acts as a superior catalyst compared to a tri- or polynuclear complex towards oxidation of alcohols to the corresponding aldehydes.
Modified carbon nanotubes in online speciation of chromium in real water samples using hyphenated FI-FAAS
Authors: Tiwari Shelja , Sharma Niharika , Saxena Reena
Published: May 2017

Fast preconcentrative speciation of chromium in polluted water samples using l-arginine functionalized multi-walled carbon nanotubes.
Surface-enhanced hyper Raman hyperspectral imaging and probing in animal cells
Authors: Heiner Zsuzsanna , Gühlke Marina , Živanović Vesna , Madzharova Fani , Kneipp Janina
Published: May 2017

The location of nanoprobes in endosomes of live cells is mapped by off-resonant, two-photon excited vibrational imaging.
Interaction of human serum albumin with uremic toxins: a thermodynamic study
Authors: Yu Shun , Schuchardt Mirjam , Tölle Markus , van der Giet Markus , Zidek Walter , Dzubiella Joachim , Ballauff Matthias
Published: May 2017

Interaction of uremic toxins with HSA is studied by ITC and understood in terms of thermodynamic driving forces.
Synthesis of α-CaSO4·0.5H2O from flue gas desulfurization gypsum regulated by C4H4O4Na2·6H2O and NaCl in glycerol-water solution
Authors: Guan Qing-Jun , Sun Wei , Hu Yue-Hua , Yin Zhi-Gang , Guan Chang-Ping
Published: May 2017

A brand new method to prepare α-CaSO4·0.5H2O with low aspect ratios from flue gas desulfurization gypsum in glycerol-water solution was presented, in which NaCl was used as the phase transition accelerator and C4H4O4Na2·6H2O as the crystal modifier.
Quantitative investigation of the decomposition of organic lithium ion battery electrolytes with LC-MS/MS
Authors: Schultz Carola , Vedder Sven , Streipert Benjamin , Winter Martin , Nowak Sascha
Published: May 2017

A novel high performance liquid chromatography hyphenated to tandem mass spectrometry method for the separation and quantification of components from common organic carbonate-based electrolyte systems in lithium ion batteries was developed.
Synthesis and characterization of some nanostructured composite oxides for low temperature catalytic combustion of dilute propane
Authors: Doroftei C. , Leontie L.
Published: May 2017

Five nanosized perovskite and four ferrospinel powders were prepared by sol–gel self-combustion technique. The La0.6Pb0.2Mg0.2MnO3 perovskite was found to exhibit the best catalytic performance with respect to propane combustion at low temperatures.
Investigating the interaction mechanism of fluorescent whitening agents to human serum albumin using saturation transfer difference-NMR, multi-spectroscopy, and docking studies
Authors: Zhao Ludan , Liu Jiuyang , Guo Ronghui , Sun Qiaomei , Yang Hongqin , Li Hui
Published: May 2017

Characterization of the interaction between two fluorescent whitening agents and human serum albumin: 1H STD-NMR, multi-spectroscopy, and docking studies.
Synthesis of α-aminophosphonates using solvate ionic liquids
Authors: Eyckens Daniel J. , Henderson Luke C.
Published: May 2017

A range of α-aminophosphonates were accessed in high yields and very rapidly, using solvate ionic liquids as the reaction media.
Hydrophilic–hydrophobic diblock copolymers based on polyphenylenes for cathode ionomers of fuel cells
Authors: Akizuki K. , Ohma A. , Miura S. , Matsuura T. , Yoshizawa-Fujita M. , Takeoka Y. , Rikukawa M.
Published: May 2017

Polyphenylene-based hydrophilic–hydrophobic diblock copolymers were developed and used as ionomers in the catalyst layers (CLs) of polymer electrolyte membrane fuel cells.
A temperature-responsive poly(vinyl alcohol) gel for controlling fluidity of an inorganic phase change material
Authors: Karimineghlani Parvin , Emmons Emily , Green Micah J. , Shamberger Patrick , Sukhishvili Svetlana A.
Published: May 2017

A temperature-responsive PVA gel is achieved that reversibly holds fluid lithium nitrate trihydrate and releases it in response to temperature for easy gelling in-place and later removal from heat-exchange modules.
Ultra long-term cellular tracing by a fluorescent AIE bioconjugate with good water solubility over a wide pH range
Authors: Wang Zhengke , Yang Ling , Liu Yalan , Huang Xiaofei , Qiao Fenghui , Qin Wei , Hu Qiaoling , Tang Ben Zhong
Published: May 2017

TPE-NSCS, which displayed an AIE effect, could be solubilized in water over a wide pH range, and used in cell tracing for 30 passages.
A reversibly electro-controllable polymer brush for electro-switchable friction
Authors: Zeng Hulie , Zhang Yong , Mao Sifeng , Nakajima Hizuru , Uchiyama Katsumi
Published: May 2017

We report electrically switchable friction, which is reversibly manipulated by an external electric field via an electro-controllable polymer branched brush.