bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural history of the narrow endemics Ipomoea cavalcantei and I. marabaensis from Amazon Canga savannahs
Authors: Babiychuk Elena , Kushnir Sergei , Vasconcelos Santelmo , Dias Mariana Costa , Carvalho-Filho Nelson , Nunes Gisele Lopes , dos Santos Jorge Filipe , Tyski Lourival , da Silva Delmo Fonseca , Castilho Alexandre , Fonseca Vera Lucia Imperatriz , Oliveira Guilherme
Published: August 2017

Amazon comprises a vast variety of ecosystems, including savannah-like Canga barrens that evolved on iron-lateritic rock plateaus of the Carajás Mountain range. Individual Cangas are enclosed by the rain forest, indicating insular isolation that enables speciation and plant community differentiation. To establish a framework for the research on natural history and conservation management of endemic Canga species, seven chloroplast DNA loci and an ITS2 nuclear DNA locus were used to study natural molecular variation of the red flowered Ipomoea cavalcantei and the lilac flowered I. marabaensis. Partitioning of the nuclear and chloroplast gene alleles strongly suggested that the species share the most recent common ancestor, pointing a new independent event of the red flower origin in the genus. Chloroplast gene allele analysis showed strong genetic differentiation between Canga populations, implying a limited role of seed dispersal in exchange of individuals between Cangas. Closed haplotype network topology indicated a requirement for the paternal inheritance in generation of cytoplasmic genetic variation. Tenfold higher nucleotide diversity in the nuclear ITS2 sequences distinguished I. cavalcantei from I. marabaensis, implying a different pace of evolutionary changes. Thus, Canga ecosystems offer powerful venues for the study of speciation, multitrait adaptation and the origins of genetic variation.
Association between Frailty and Hypertension Prevalence, Treatment, and Control in the Elderly Korean Population
Authors: Kang Min-gu , Kim Sun-wook , Yoon Sol-Ji , Choi Jung-Yeon , Kim Kwang-il , Kim Cheol-Ho
Published: August 2017

Frailty is a common geriatric syndrome characterized by increased risk of disability, hospitalization, and mortality. Hypertension (HTN) is one of the most common chronic medical conditions in the elderly. However, there have been few studies regarding the association between frailty and HTN prevalence, treatment, and control rates. We analyzed data of 4,352 older adults (age ≥ 65 years) from the fifth Korea National Health and Nutrition Examination Survey. We constructed a frailty index based on 42 items and classified participants as robust, pre-frail, or frail. Of the subjects, 2,697 (62.0%) had HTN and 926 (21.3%) had pre-HTN. Regarding frailty status, 721 (16.6%), 1,707 (39.2%), and 1,924 (44.2%) individuals were classified as robust, pre-frail and frail, respectively. HTN prevalence was higher in frail elderly (67.8%) than pre-frail (60.8%) or robust elderly (49.2%) (P < 0.001). Among hypertensive patients, frail elderly were more likely to be treated than pre-frail or robust elderly (P < 0.001), but the proportion of patients whose blood pressure was under control ( < 150/90 mmHg) was lower in frail elderly (P = 0.005). Considering the adverse cardiovascular outcomes associated with frailty, more attention should be paid to the blood pressure control of the frail elderly.
On the dynamic toroidal multipoles from localized electric current distributions
Authors: Fernandez-Corbaton Ivan , Nanz Stefan , Rockstuhl Carsten
Published: August 2017

We analyze the dynamic toroidal multipoles and prove that they do not have an independent physical meaning with respect to their interaction with electromagnetic waves. We analytically show how the split into electric and toroidal parts causes the appearance of non-radiative components in each of the two parts. These non-radiative components, which cancel each other when both parts are summed, preclude the separate determination of each part by means of measurements of the radiation from the source or of its coupling to external electromagnetic waves. In other words, there is no toroidal radiation or independent toroidal electromagnetic coupling. The formal meaning of the toroidal multipoles is clear in our derivations. They are the higher order terms of an expansion of the multipolar coefficients of electric parity with respect to the electromagnetic size of the source.
Morbidity pattern of traditional Chinese medicine primary care in the Hong Kong population
Authors: Wong Wendy , Lam Cindy Lo Kuen , Bian Xiang Zhao , Zhang Zhang Jin , Ng Sze Tuen , Tung Shong
Published: August 2017

Primary care manages >90% of illnesses requiring medical services in Hong Kong, in which 9,513 registered Chinese medicine practitioners (CMPs) provide 8.2% of the consultations. This is the first study aimed to determine the morbidity pattern in different Traditional Chinese Medicine (TCM) primary care settings in Chinese population. 55,312 patients’ encounters were classified by the International Classification of Primary Care-2 (ICPC-2) from 260 of CMPs. Mean patient age was 50.5 years, with more females than males (67.0% vs 33.0%). Most patients consulted CMPs for chronic (64% vs 33.7%) rather than acute conditions. Among the 30% of patients, hypertension (49.5%) or diabetes (18.5%) were the most common co-morbidity. The most common problems presenting to CMP were respiratory (24.9%), musculoskeletal complaints (22.7%), cough (11.7%), and lower back pain (6.6%). To our knowledge, this was the first study permitting direct comparison with that presenting to Western medicine (WM) primary care by ICPC-2 systems. The results confirmed the role of CMP in primary care for musculoskeletal or chronic illnesses that they may have also received conventional WM treatment. We recommend greater effort and more resources should be invested to promote interdisciplinary communication to ensure safety and synergy of TCM and WM in primary care.
Liquid-based cytopathology test as a novel method to identify Aspergillus in patients with pulmonary aspergillosis
Authors: Shen Yongchun , Zhang Xiaorong , Lin Wenyi , Wan Chun , Li Qiyuan , Jiang Yong
Published: August 2017

Conventional cytopathology examination of respiratory samples can aid in identifying Aspergillus but with poor sensitivity, so this study aimed to assess the potential of the liquid-based cytopathology test (LCT) for improving the identification of Aspergillus in respiratory samples following Papanicolaou’s or Special staining with Grocott’s methenamine silver or periodic acid-Schiff staining. Paired bronchial brushing samples (n = 54) and sputum samples (n = 117) from 171 patients with pulmonary aspergillosis were prepared as slides using either conventional cytopathology or SurePath LCT. LCT slides were generally superior to conventional slides, showing smaller cell monolayer surface area, clearer background and more distinct stereoscopic cytological features. For Papanicolaou’s staining, LCT-prepared slides allowed a higher positive rate of Aspergillus identification than conventional slides for bronchial brushing samples (59.25% vs. 20.37%, P < 0.05) and sputum samples (29.05% vs. 8.55%, P < 0.05). Similarly, Special staining of LCT-prepared slides showed a higher positive rate of Aspergillus identification for bronchial brushing samples (83.33% vs. 57.41%, P < 0.05) and sputum samples (43.59% vs. 19.66%, P < 0.05). This preliminary study suggests that LCT may be better than conventional slide preparation for identifying Aspergillus in respiratory samples from patients with pulmonary aspergillosis.
Perceived stress and smoking across 41 countries: A global perspective across Europe, Africa, Asia and the Americas
Authors: Stubbs Brendon , Veronese Nicola , Vancampfort Davy , Prina A. Mathew , Lin Pao-Yen , Tseng Ping-Tao , Evangelou Evangelos , Solmi Marco , Kohler Cristiano , Carvalho André F. , Koyanagi Ai
Published: August 2017

Within recent years, there has been a seismic shift in smoking rates from high-income to low- and middle-income countries (LMICs). Evidence indicates that perceived stress may comprise a barrier for smoking cessation, but little is known about the association of perceived stress and smoking in LMICs. We conducted a cross-sectional, community-based study comprising 217,561 people [mean age 38.5 (SD = 16.1) years, 49.4% males]. A perceived stress score [range 2 (lowest-stress) 10 (highest-stress)] was computed from the Perceived Stress Scale. Multivariable logistic regression analyses were conducted. In the overall sample, a one-unit increase in perceived-stress resulted in a 5% increased odds of smoking (OR = 1.05; 95%CI = 1.03–1.06). Increased stress was associated with smoking in Africa (OR = 1.06; 95%CI = 1.04–1.09), Americas (OR = 1.03; 95%CI = 1.01–1.05), and Asia (OR = 1.06; 95%CI = 1.04–1.08), but not Europe (OR = 0.99; 95%CI = 0.95–1.02). Increasing levels of perceived stress were significantly associated with heavy smoking (≥30 cigarettes per day) among daily smokers (OR = 1.08; 95%CI = 1.02–1.15). A country-wide meta-analysis showed that perceived stress is associated with daily smoking in most countries. Prospective studies are warranted to confirm/refute this relationship, which may have meaningful public health implications.
Shedding Light on Alzheimer’s β-Amyloidosis: Photosensitized Methylene Blue Inhibits Self-Assembly of β-Amyloid Peptides and Disintegrates Their Aggregates
Authors: Lee Byung Il , Suh Yoon Seok , Chung You Jung , Yu Kweon , Park Chan Beum
Published: August 2017

Abnormal aggregation of β-amyloid (Aβ) peptides is a major hallmark of Alzheimer’s disease (AD). In spite of numerous attempts to prevent the β-amyloidosis, no effective drugs for treating AD have been developed to date. Among many candidate chemicals, methylene blue (MB) has proved its therapeutic potential for AD in a number of in vitro and in vivo studies; but the result of recent clinical trials performed with MB and its derivative was negative. Here, with the aid of multiple photochemical analyses, we first report that photoexcited MB molecules can block Aβ42 aggregation in vitro. Furthermore, our in vivo study using Drosophila AD model demonstrates that photoexcited MB is highly effective in suppressing synaptic toxicity, resulting in a reduced damage to the neuromuscular junction (NMJ), an enhanced locomotion, and decreased vacuole in the brain. The hindrance effect is attributed to Aβ42 oxidation by singlet oxygen (1O2) generated from photoexcited MB. Finally, we show that photoexcited MB possess a capability to disaggregate the pre-existing Aβ42 aggregates and reduce Aβ-induced cytotoxicity. Our work suggests that light illumination can provide an opportunity to boost the efficacies of MB toward photodynamic therapy of AD in future.
The Matrikine Acetylated Proline-Glycine-Proline Couples Vascular Inflammation and Acute Cardiac Rejection
Authors: Payne Gregory A. , Li Jindong , Xu Xin , Jackson Patricia , Qin Hongwei , Pollock David M. , Wells J. Michael , Oparil Suzanne , Leesar Massoud , Patel Rakesh P. , Blalock J. Edwin , Gaggar Amit
Published: August 2017

The extracellular matrix (ECM) is a dynamic, bioactive structure critical to organ development, structure and function. Excessive remodeling of the ECM is a hallmark of a variety of inflammatory conditions including vascular disease. Endothelin-1 (ET1) synthesis is understood to promote cardiovascular diseases including acute cardiac transplant rejection; however, the contribution of ECM-derived chemokines (matrikines) to vascular inflammation remains poorly understood. Herein we report that the matrikine acetylated Pro-Gly-Pro (PGP) stimulates vascular inflammation through activation of endothelial CXC Chemokine Receptor 2 (CXCR2) and production of endothelin-1 both in vitro and in vivo. As a proof of hypothesis, we demonstrate that coronary PGP levels associate with both circulating endothelin-1 and acute rejection in cardiac transplant patients (sensitivity of 100% and specificity of 86%). These findings establish PGP as a novel mediator in cardiovascular disease, and implicate bioactive matrix fragments as underappreciated agents potentially active in numerous conditions propagated by progressive vascular inflammation.
H-Ferritin-nanocaged olaparib: a promising choice for both BRCA-mutated and sporadic triple negative breast cancer
Authors: Mazzucchelli S. , Truffi M. , Baccarini F. , Beretta M. , Sorrentino L. , Bellini M. , Rizzuto M. A. , Ottria R. , Ravelli A. , Ciuffreda P. , Prosperi D. , Corsi F.
Published: August 2017

Poly(ADP-ribose) polymerase (PARP) inhibitors represent a promising strategy toward the treatment of triple-negative breast cancer (TNBC), which is often associated to genomic instability and/or BRCA mutations. However, clinical outcome is controversial and no benefits have been demonstrated in wild type BRCA cancers, possibly due to poor drug bioavailability and low nuclear delivery. In the attempt to overcome these limitations, we have developed H-Ferritin nanoformulated olaparib (HOla) and assessed its anticancer efficacy on both BRCA-mutated and non-mutated TNBC cells. We exploited the natural tumor targeting of H-Ferritin, which is mediated by the transferrin receptor-1 (TfR1), and its physiological tropism toward cell nucleus. TNBC cell lines over-expressing TfR-1 were successfully recognized by H-Ferritin, displaying a fast internalization into the cells. HOla induced remarkable cytotoxic effect in cancer cells, exhibiting 1000-fold higher anticancer activity compared to free olaparib (Ola). Accordingly, HOla treatment enhanced PARP-1 cleavage, DNA double strand breaks and Ola delivery into the nuclear compartment. Our findings suggest that H-Ferritin nanoformulation strongly enhances cytotoxic efficacy of Ola as a stand-alone therapy in both BRCA-mutated and wild type TNBC cells, by promoting targeted nuclear delivery.
Preventing inflammation inhibits biopsy-mediated changes in tumor cell behavior
Authors: Alieva Maria , Margarido Andreia S. , Wieles Tamara , Abels Erik R. , Colak Burcin , Boquetale Carla , Jan Noordmans Herke , Snijders Tom J. , Broekman Marike L. , van Rheenen Jacco
Published: August 2017

Although biopsies and tumor resection are prognostically beneficial for glioblastomas (GBM), potential negative effects have also been suggested. Here, using retrospective study of patients and intravital imaging of mice, we identify some of these negative aspects, including stimulation of proliferation and migration of non-resected tumor cells, and provide a strategy to prevent these adverse effects. By repeated high-resolution intravital microscopy, we show that biopsy-like injury in GBM induces migration and proliferation of tumor cells through chemokine (C-C motif) ligand 2 (CCL-2)-dependent recruitment of macrophages. Blocking macrophage recruitment or administrating dexamethasone, a commonly used glucocorticoid to prevent brain edema in GBM patients, suppressed the observed inflammatory response and subsequent tumor growth upon biopsy both in mice and in multifocal GBM patients. Taken together, our study suggests that inhibiting CCL-2-dependent recruitment of macrophages may further increase the clinical benefits from surgical and biopsy procedures.
The FAD synthetase from the human pathogen Streptococcus pneumoniae: a bifunctional enzyme exhibiting activity-dependent redox requirements
Authors: Sebastián María , Lira-Navarrete Erandi , Serrano Ana , Marcuello Carlos , Velázquez-Campoy Adrián , Lostao Anabel , Hurtado-Guerrero Ramón , Medina Milagros , Martínez-Júlvez Marta
Published: August 2017

Prokaryotic bifunctional FAD synthetases (FADSs) catalyze the biosynthesis of FMN and FAD, whereas in eukaryotes two enzymes are required for the same purpose. FMN and FAD are key cofactors to maintain the flavoproteome homeostasis in all type of organisms. Here we shed light to the properties of the hitherto unstudied bacterial FADS from the human pathogen Streptococcus pneumoniae (SpnFADS). As other members of the family, SpnFADS catalyzes the three typical activities of prokaryotic FADSs: riboflavin kinase (RFK), ATP:FMN:adenylyltransferase (FMNAT), and FAD pyrophosphorylase (FADpp). However, several SpnFADS biophysical properties differ from those of other family members. In particular; i) the RFK activity is not inhibited by the riboflavin (RF) substrate, ii) the FMNAT and FADSpp activities require flavin substrates in the reduced state, iii) binding of adenine nucleotide ligands is required for the binding of flavinic substrates/products and iv) the monomer is the preferred state. Collectively, our results add interesting mechanistic differences among the few prokaryotic bifunctional FADSs already characterized, which might reflect the adaptation of the enzyme to relatively different environments. In a health point of view, differences among FADS family members provide us with a framework to design selective compounds targeting these enzymes for the treatment of diverse infectious diseases.
Whole transcriptome profiling of taste bud cells
Authors: Sukumaran Sunil K. , Lewandowski Brian C. , Qin Yumei , Kotha Ramana , Bachmanov Alexander A. , Margolskee Robert F.
Published: August 2017

Analysis of single-cell RNA-Seq data can provide insights into the specific functions of individual cell types that compose complex tissues. Here, we examined gene expression in two distinct subpopulations of mouse taste cells: Tas1r3-expressing type II cells and physiologically identified type III cells. Our RNA-Seq libraries met high quality control standards and accurately captured differential expression of marker genes for type II (e.g. the Tas1r genes, Plcb2, Trpm5) and type III (e.g. Pkd2l1, Ncam, Snap25) taste cells. Bioinformatics analysis showed that genes regulating responses to stimuli were up-regulated in type II cells, while pathways related to neuronal function were up-regulated in type III cells. We also identified highly expressed genes and pathways associated with chemotaxis and axon guidance, providing new insights into the mechanisms underlying integration of new taste cells into the taste bud. We validated our results by immunohistochemically confirming expression of selected genes encoding synaptic (Cplx2 and Pclo) and semaphorin signalling pathway (Crmp2, PlexinB1, Fes and Sema4a) components. The approach described here could provide a comprehensive map of gene expression for all taste cell subpopulations and will be particularly relevant for cell types in taste buds and other tissues that can be identified only by physiological methods.
Structural characterization of human Vaccinia-Related Kinases (VRK) bound to small-molecule inhibitors identifies different P-loop conformations
Authors: Couñago Rafael M. , Allerston Charles K. , Savitsky Pavel , Azevedo Hatylas , Godoi Paulo H. , Wells Carrow I. , Mascarello Alessandra , de Souza Gama Fernando H. , Massirer Katlin B. , Zuercher William J. , Guimarães Cristiano R. W. , Gileadi Opher
Published: August 2017

The human genome encodes two active Vaccinia-related protein kinases (VRK), VRK1 and VRK2. These proteins have been implicated in a number of cellular processes and linked to a variety of tumors. However, understanding the cellular role of VRKs and establishing their potential use as targets for therapeutic intervention has been limited by the lack of tool compounds that can specifically modulate the activity of these kinases in cells. Here we identified BI-D1870, a dihydropteridine inhibitor of RSK kinases, as a promising starting point for the development of chemical probes targeting the active VRKs. We solved co-crystal structures of both VRK1 and VRK2 bound to BI-D1870 and of VRK1 bound to two broad-spectrum inhibitors. These structures revealed that both VRKs can adopt a P-loop folded conformation, which is stabilized by different mechanisms on each protein. Based on these structures, we suggest modifications to the dihydropteridine scaffold that can be explored to produce potent and specific inhibitors towards VRK1 and VRK2.
Graphene nanoplatelets based matrix solid-phase dispersion microextraction for phenolic acids by ultrahigh performance liquid chromatography with electrochemical detection
Authors: Peng Li-Qing , Yi Ling , Yang Qiu-Cheng , Cao Jun , Du Li-Jing , Zhang Qi-Dong
Published: August 2017

A simple, rapid and eco-friendly approach based on matrix solid-phase dispersion microextraction (MSPDM) followed by ultrahigh performance liquid chromatography coupled with electrochemical detection (UHPLC-ECD) was presented for the microextraction and determination of six phenolic acids in a plant preparation (Danshen tablets). The parameters that influenced the extraction performance of phenolic acids were investigated and optimized. The optimal MSPDM conditions were determined as follows: sorbent, using graphene nanoplatelets with sample/sorbent ratio of 1:1, grinding time set at 60 s, and 0.2 mL of water as elution solvent. Under the optimum conditions, the validation experiments indicated that the proposed method exhibited good linearity (r2 ≥ 0.9991), excellent precision (RSD ≤ 4.57%), and satisfactory recoveries (82.34–98.34%). The limits of detection were from 1.19 to 4.62 ng/mL for six phenolic acids. Compared with other reported methods, this proposal required less sample, solvent and extraction time. Consequently, the proposed method was successfully used to the extraction and determination of phenolic acids in Danshen tablets.
High sensitivity guided-mode-resonance optical sensor employing phase detection
Authors: Sahoo Pankaj K. , Sarkar Swagato , Joseph Joby
Published: August 2017

We report an ultra-sensitive refractive index (RI) sensor employing phase detection in a guided mode resonance (GMR) structure. By incorporating the GMR structure in to a Mach-Zehnder Interferometer, we measured the phase of GMR signal by calculating the amount of fringe shift. Since the phase of GMR signal varies rapidly around the resonance wavelength, the interference fringe pattern it forms with the reference signal becomes very sensitive to the surrounding RI change. The sensitivity comes out to be 0.608π phase shift per 10−4 RI change in water medium which is more than 100 times higher than the other reported GMR based phase detection method. In our setup, we can achieve a minimum phase shift of (1.94 × 10−3) π that corresponds to a RI change of 3.43 × 10−7, outperforming any of reported optical sensors and making it useful to detect RI changes in gaseous medium as well. We have developed a theoretical model to numerically estimate the phase shift of the GMR signal that predicts the experimental results very well. Our phase detection method comes out to be much more sensitive than the conventional GMR sensors based on wavelength or angle resolved scanning methods.
From Mechanistic Study to Chiral Catalyst Optimization: Theoretical Insight into Binaphthophosphepine-catalyzed Asymmetric Intramolecular [3 + 2] Cycloaddition
Authors: Duan Meng , Zhu Lei , Qi Xiaotian , Yu Zhaoyuan , Li Yingzi , Bai Ruopeng , Lan Yu
Published: August 2017

Density functional M11 was used to study the mechanism and enantioselectivity of a binaphthophosphepine-catalyzed intramolecular [3 + 2] cycloaddition reaction. The computational results revealed that this reaction proceeds through nucleophilic addition of the phosphine catalyst to the allene, which yields a zwitterionic phosphonium intermediate. The subsequent stepwise [3 + 2] annulation process, which starts with the intramolecular nucleophilic addition of the allenoate moiety to the electron-deficient olefin group, determines the enantioselectivity of the reaction. This step is followed by a ring-closing reaction and water-assisted proton-transfer process to afford the final product with concomitant regeneration of the phosphine catalyst. Theoretical predictions of the enantioselectivity for various phosphine catalysts were consistent with experimental observations, and 2D contour maps played an important role in explaining the origin of the enantioselectivity. Moreover, on the basis of our theoretical study, new binaphthophosphepine catalysts were designed and that are expecting to afford higher enantioselectivity in this cycloaddition reaction.
Long-range spontaneous droplet self-propulsion on wettability gradient surfaces
Authors: Liu Chaoran , Sun Jing , Li Jing , Xiang Chenghao , Che Lufeng , Wang Zuankai , Zhou Xiaofeng
Published: August 2017

The directional and long-range droplet transportation is of great importance in microfluidic systems. However, it usually requires external energy input. Here we designed a wettability gradient surface that can drive droplet motion by structural topography. The surface has a wettability gradient range of over 150° from superhydrophobic to hydrophilic, which was achieved by etching silicon nanopillars and adjusting the area of hydrophilic silicon dioxide plane. We conducted force analysis to further reveal the mechanism for droplet self-propulsion, and found that the nanostructures are critical to providing a large driving force and small resistance force. Theoretical calculation has been used to analyze the maximal self-propulsion displacement on different gradient surfaces with different volumes of droplets. On this basis, we designed several surfaces with arbitrary paths, which achieved directional and long-range transportation of droplet. These results clarify a driving mechanism for droplet self-propulsion on wettability gradient surfaces, and open up new opportunities for long-range and directional droplet transportation in microfluidic system.
CRISPR/Cas9-mediated genome editing efficiently creates specific mutations at multiple loci using one sgRNA in Brassica napus
Authors: Yang Hong , Wu Jia-Jing , Tang Ting , Liu Ke-De , Dai Cheng
Published: August 2017

CRISPR/Cas9 is a valuable tool for both basic and applied research that has been widely applied to different plant species. Nonetheless, a systematical assessment of the efficiency of this method is not available for the allotetraploid Brassica napus—an important oilseed crop. In this study, we examined the mutation efficiency of the CRISPR/Cas9 method for 12 genes and also determined the pattern, specificity and heritability of these gene modifications in B. napus. The average mutation frequency for a single-gene targeted sgRNA in the T0 generation is 65.3%. For paralogous genes located in conserved regions that were targeted by sgRNAs, we observed mutation frequencies that ranged from 27.6% to 96.6%. Homozygotes were readily found in T0 plants. A total of 48.2% of the gene mutations, including homozygotes, bi-alleles, and heterozygotes were stably inherited as classic Mendelian alleles in the next generation (T1) without any new mutations or reversions. Moreover, no mutation was found in the putative off-target sites among the examined T0 plants. Collectively, our results demonstrate that CRISPR/Cas9 is an efficient tool for creating targeted genome modifications at multiple loci that are stable and inheritable in B. napus. These findings open many doors for biotechnological applications in oilseed crops.
Enhancing structural robustness of scale-free networks by information disturbance
Authors: Wu Jun , Tan Suo-Yi , Liu Zhong , Tan Yue-Jin , Lu Xin
Published: August 2017

Many real-world systems can be described by scale-free networks with power-law degree distributions. Scale-free networks show a “robust yet fragile” feature due to their heterogeneous degree distributions. We propose to enhance the structural robustness of scale-free networks against intentional attacks by changing the displayed network structure information rather than modifying the network structure itself. We first introduce a simple mathematical model for attack information and investigate the impact of attack information on the structural robustness of scale-free networks. Both analytical and numerical results show that decreasing slightly the attack information perfection by information disturbance can dramatically enhance the structural robustness of scale-free networks. Then we propose an optimization model of disturbance strategies in which the cost constraint is considered. We analyze the optimal disturbance strategies and show an interesting but counterintuitive finding that disturbing “poor nodes” with low degrees preferentially is more effective than disturbing “rich nodes” with high degrees preferentially. We demonstrate the efficiency of our method by comparison with edge addition method and validate the feasibility of our method in two real-world critical infrastructure networks.
Nijmegen Breakage Syndrome fibroblasts and iPSCs: cellular models for uncovering disease-associated signaling pathways and establishing a screening platform for anti-oxidants
Authors: Mlody Barbara , Wruck Wasco , Martins Soraia , Sperling Karl , Adjaye James
Published: August 2017

Nijmegen Breakage Syndrome (NBS) is associated with cancer predisposition, premature aging, immune deficiency, microcephaly and is caused by mutations in the gene coding for NIBRIN (NBN) which is involved in DNA damage repair. Dermal-derived fibroblasts from NBS patients were reprogrammed into induced pluripotent stem cells (iPSCs) in order to bypass premature senescence. The influence of antioxidants on intracellular levels of ROS and DNA damage were screened and it was found that EDHB-an activator of the hypoxia pathway, decreased DNA damage in the presence of high oxidative stress. Furthermore, NBS fibroblasts but not NBS-iPSCs were found to be more susceptible to the induction of DNA damage than their healthy counterparts. Global transcriptome analysis comparing NBS to healthy fibroblasts and NBS-iPSCs to embryonic stem cells revealed regulation of P53 in NBS fibroblasts and NBS-iPSCs. Cell cycle related genes were down-regulated in NBS fibroblasts. Furthermore, oxidative phosphorylation was down-regulated and glycolysis up-regulated specifically in NBS-iPSCs compared to embryonic stem cells. Our study demonstrates the utility of NBS-iPSCs as a screening platform for anti-oxidants capable of suppressing DNA damage and a cellular model for studying NBN de-regulation in cancer and microcephaly.
Deterministic control of magnetic vortex wall chirality by electric field
Authors: Beardsley R. P. , Bowe S. , Parkes D. E. , Reardon C. , Edmonds K. W. , Gallagher B. L. , Cavill S. A. , Rushforth A. W.
Published: August 2017

Concepts for information storage and logical processing based on magnetic domain walls have great potential for implementation in future information and communications technologies. To date, the need to apply power hungry magnetic fields or heat dissipating spin polarized currents to manipulate magnetic domain walls has limited the development of such technologies. The possibility of controlling magnetic domain walls using voltages offers an energy efficient route to overcome these limitations. Here we show that a voltage-induced uniaxial strain induces reversible deterministic switching of the chirality of a magnetic vortex wall. We discuss how this functionality will be applicable to schemes for information storage and logical processing, making a significant step towards the practical implementation of magnetic domain walls in energy efficient computing.
Seasonal changes in energy expenditure, body temperature and activity patterns in llamas (Lama glama)
Authors: Riek Alexander , Brinkmann Lea , Gauly Matthias , Perica Jurcevic , Ruf Thomas , Arnold Walter , Hambly Catherine , Speakman John R. , Gerken Martina
Published: August 2017

Mammals typically keep their body temperature (Tb) within a narrow limit with changing environmental conditions. There are indications that some wild ungulates can exhibit certain forms of energy saving mechanisms when ambient temperatures are low and/or food is scarce. Therefore, the aim of the study was to determine if the llama, one of the most extensively kept domestic livestock species, exhibits seasonal adjustment mechanisms in terms of energy expenditure, Tband locomotion. For that purpose llamas (N = 7) were kept in a temperate habitat on pasture. Locomotor activity, Tb(measured in the rumen) and the location of each animal were recorded continuously for one year using a telemetry system. Daily energy expenditure was measured as field metabolic rate (FMR). FMR fluctuated considerably between seasons with the lowest values found in winter (17.48 ± 3.98 MJ d−1, 402 kJ kg−0.75 d−1) and the highest in summer (25.87 ± 3.88 MJ d−1, 586 kJ kg−0.75 d−1). Llamas adjusted their energy expenditure, Tband locomotor activity according to season and also time of day. Thus, llamas seem to have maintained the ability to reduce their energy expenditure and adjust their Tbunder adverse environmental conditions as has been reported for some wild ungulates.
Anti-colon cancer effect of caffeic acid p-nitro-phenethyl ester in vitro and in vivo and detection of its metabolites
Authors: Tang Hao , Yao Xiaofang , Yao Cong , Zhao Xiaoyan , Zuo Hua , Li Zhubo
Published: August 2017

Caffeic acid phenethyl ester (CAPE), extracted from propolis, was proven to inhibit colon cancer. Caffeic acid p-nitro-phenethyl ester (CAPE-pNO2), a derivative of CAPE, was determined to be an anti-platelet agent and a protector of myocardial ischaemia with more potent effects. In the present study, CAPE-pNO2 showed stronger cytotoxic activity than CAPE. We revealed interactions between CAPE-pNO2 and experimental cells. CAPE-pNO2 induced apoptosis in HT-29 cells by up-regulating P53, cleaved-caspase-3, Bax, P38 and CytoC; CAPE-pNO2 also up-regulated P21Cip1 and P27Kip1 and down-regulated CDK2 and c-Myc to promote cell cycle arrest in G0/G1. In xenograft studies, CAPE-pNO2 remarkably suppressed tumour growth dose dependently and decreased the expression of VEGF (vascular endothelial growth factor) in tumour tissue. Moreover, HE staining showed that no observable toxicity was found in the heart, liver, kidney and spleen. In addition, metabolites of CAPE-pNO2 in HT-29 cells and organs were detected. In conclusion, para-nitro may enhance the anticancer effect of CAPE by inhibiting colon cancer cell viability, inducing apoptosis and cell cycle arrest via the P53 pathway and inhibiting tumour growth and reducing tumour invasion by decreasing the expression of VEGF; additionally, metabolites of CAPE-pNO2 showed differences in cells and organs.
Early skeletal muscle loss during target therapy is a prognostic biomarker in metastatic renal cell carcinoma patients
Authors: Gu Weijie , Wu Junlong , Liu Xiaohang , Zhang Hailiang , Shi Guohai , Zhu Yao , Ye Dingwei
Published: August 2017

Skeletal muscle depletion is common in patients with advanced cancer and may be associated with a poor outcome. To investigate whether the changes in skeletal muscle in metastatic renal cell carcinoma (mRCC) patients receiving targeted therapy are associated with clinical outcome, we undertook an observational cohort study using data from a number of randomized clinical trials previously conducted at the Fudan University Shanghai Cancer Center. The muscle mass was evaluated by comparing computed tomography images obtained at baseline with those obtained after 3–4 months of treatment. A total 101 patients were included in the study. The mean skeletal muscle area reduced from 41.6 cm2/m2 to 39.9 cm2/m2 after 3–4 months of targeted therapy. In multivariable analyses adjusted for the number of baseline covariates, muscle loss ≥5% was shown to be a significant prognostic factor for both progression-free (hazard ratio [HR]: 1.744, 95% confidence interval [CI]: 1.077–2.826, P = 0.024) and overall survival (HR: 2.367, 95%CI: 1.253–4.469, P = 0.008). The addition of muscle loss to the Heng model significantly improved its discriminative ability. In summary, early skeletal muscle loss is frequently observed in mRCC patients and can add prognostic information to current clinical risk scores.
Synthesis and structural studies of N-heterocyclic carbene Ag(I) and Hg(II) complexes and recognition of dihydrogen phosphate anion
Authors: Liu Qingxiang , Zhao Xiaoqiang , Hu Zeliang , Zhao Zhixiang , Wang Hong
Published: August 2017

Bis-benzimidazolium salt (S)-2,2′-bis[2″-(N-Et-benzimidazoliumyl)ethoxy]-1,1′-binaphthyl hexafluorophosphate [(S)-L1H2]·(PF6)2 and bis-imidazolium salts (S)-2,2′-bis[2″-(N-R-imidazoliumyl)ethoxy]-1,1′-binaphthyl hexafluorophosphate [(S)-L2H2]·(PF6)2 and [(S)-L3H2]·(PF6)2 (R = ethyl or benzyl), as well as their five N-heterocyclic carbene Hg(II) and Ag(I) complexes such as [(S)-L1Hg(HgBr4)] (1), [(S)-L2Hg(HgBr4)] (2), [(S)-L2Hg(HgI4)] (3), {[(S)-L2Ag](PF6)}n (4) and [(S)-L3Ag](PF6) (5) have been prepared and characterized. Each of complexes 1–3 consists of two rings (one 6-membered ring and one 11-membered ring), in which the oxygen atom in the ligand participates in coordination with Hg(II) ion. In complex 4, 1D helical polymeric chain is formed via biscarbene ligand (S)-L2 and Ag(I) ion. A 15-membered macrometallocycle is constructed through a ligand (S)-L3 and a Ag(I) ion in complex 5. Additionally, the selective recognition of H2PO4− using complex 5 as a receptor was investigated on the basis of fluorescence and UV/vis spectroscopic titrations. The results indicate that complex 5 can distinguish effectively H2PO4− from other anions.
Knockdown of HIF-1α by siRNA-expressing plasmid delivered by attenuated Salmonella enhances the antitumor effects of cisplatin on prostate cancer
Authors: Gu Junlian , Li Yang , Zeng Jun , Wang Bo , Ji Kun , Tang Yufeng , Sun Qing
Published: August 2017

Resistance to cisplatin (DDP) and dose-related toxicity remain two important obstacles in the treatment of prostate cancer (PCa) patients with DDP-based chemotherapy. We have investigated whether the knockdown of hypoxia-inducible factor-1 alpha (HIF-1α) by siRNA could enhance the antitumor activity of DDP, and aimed to determine the underlying mechanisms. Intravenous injection of attenuated Salmonella carrying a HIF-1α siRNA-expressing plasmid was used to knockdown HIF-1α in a PC-3 xenograft model. The in vitro and in vivo effects of HIF-1α siRNA treatment and/or DPP on PCa cell proliferation, apoptosis, glycolysis, and production of reactive oxygen species (ROS) were assessed by examining molecular markers specific to each process. The results demonstrated that the treatment of tumor-bearing mice with attenuated Salmonella carrying the HIF-1α siRNA plasmid greatly enhanced the antitumor effects of low-dose DDP. Further mechanistic studies demonstrated that knockdown of HIF-1α improved the response of PCa cells to DDP by redirecting aerobic glycolysis toward mitochondrial oxidative phosphorylation, leading to cell death through overproduction of ROS. Our findings indicate that DDP-based chemotherapy combined with targeting the HIF-1α-regulated cancer metabolism pathway might be an ideal strategy to treat PCa.
Three TF Co-expression Modules Regulate Pressure-Overload Cardiac Hypertrophy in Male Mice
Authors: Chang Yao-Ming , Ling Li , Chang Ya-Ting , Chang Yu-Wang , Li Wen-Hsiung , Shih Arthur Chun-Chieh , Chen Chien-Chang
Published: August 2017

Pathological cardiac hypertrophy, a dynamic remodeling process, is a major risk factor for heart failure. Although a number of key regulators and related genes have been identified, how the transcription factors (TFs) dynamically regulate the associated genes and control the morphological and electrophysiological changes during the hypertrophic process are still largely unknown. In this study, we obtained the time-course transcriptomes at five time points in four weeks from male murine hearts subjected to transverse aorta banding surgery. From a series of computational analyses, we identified three major co-expression modules of TF genes that may regulate the gene expression changes during the development of cardiac hypertrophy in mice. After pressure overload, the TF genes in Module 1 were up-regulated before the occurrence of significant morphological changes and one week later were down-regulated gradually, while those in Modules 2 and 3 took over the regulation as the heart size increased. Our analyses revealed that the TF genes up-regulated at the early stages likely initiated the cascading regulation and most of the well-known cardiac miRNAs were up-regulated at later stages for suppression. In addition, the constructed time-dependent regulatory network reveals some TFs including Egr2 as new candidate key regulators of cardiovascular-associated (CV) genes.
A family of archaea-like carboxylesterases preferentially expressed in the symbiotic phase of the mycorrhizal fungus Tuber melanosporum
Authors: Cavazzini Davide , Grossi Guido , Levati Elisabetta , Vallese Francesca , Montanini Barbara , Bolchi Angelo , Zanotti Giuseppe , Ottonello Simone
Published: August 2017

An increasing number of esterases is being revealed by (meta) genomic sequencing projects, but few of them are functionally/structurally characterized, especially enzymes of fungal origin. Starting from a three-member gene family of secreted putative “lipases/esterases” preferentially expressed in the symbiotic phase of the mycorrhizal fungusTuber melanosporum(“black truffle”), we show here that these enzymes (TmelEST1-3) are dimeric, heat-resistant carboxylesterases capable of hydrolyzing various short/medium chain p-nitrophenyl esters. TmelEST2 was the most active (kcat = 2302 s−1for p-nitrophenyl-butyrate) and thermally stable (T50 = 68.3 °C), while TmelEST3 was the only one displaying some activity on tertiary alcohol esters. X-ray diffraction analysis of TmelEST2 revealed a classical α/β hydrolase-fold structure, with a network of dimer-stabilizing intermolecular interactions typical of archaea esterases. The predicted structures of TmelEST1 and 3 are overall quite similar to that of TmelEST2 but with some important differences. Most notably, the much smaller volume of the substrate-binding pocket and the more acidic electrostatic surface profile of TmelEST1. This was also the only TmelEST capable of hydrolyzing feruloyl-esters, suggestinng a possible role in root cell-wall deconstruction during symbiosis establishment. In addition to their potential biotechnological interest, TmelESTs raise important questions regarding the evolutionary recruitment of archaea-like enzymes into mesophilic subterranean fungi such as truffles.
Prediction of infarction volume and infarction growth rate in acute ischemic stroke
Authors: Kamran Saadat , Akhtar Naveed , Alboudi Ayman , Kamran Kainat , Ahmad Arsalan , Inshasi Jihad , Salam Abdul , Shuaib Ashfaq , Qidwai Uvais
Published: August 2017

The prediction of infarction volume after stroke onset depends on the shape of the growth dynamics of the infarction. To understand growth patterns that predict lesion volume changes, we studied currently available models described in literature and compared the models with Adaptive Neuro-Fuzzy Inference System [ANFIS], a method previously unused in the prediction of infarction growth and infarction volume (IV). We included 67 patients with malignant middle cerebral artery [MMCA] stroke who underwent decompressive hemicraniectomy. All patients had at least three cranial CT scans prior to the surgery. The rate of growth and volume of infarction measured on the third CT was predicted with ANFIS without statistically significant difference compared to the ground truth [P = 0.489]. This was not possible with linear, logarithmic or exponential methods. ANFIS was able to predict infarction volume [IV3] over a wide range of volume [163.7–600 cm3] and time [22–110 hours]. The cross correlation [CRR] indicated similarity between the ANFIS-predicted IV3 and original data of 82% for ANFIS, followed by logarithmic 70%, exponential 63% and linear 48% respectively. Our study shows that ANFIS is superior to previously defined methods in the prediction of infarction growth rate (IGR) with reasonable accuracy, over wide time and volume range.
Determination of the endothelin-1 recognition sites of endothelin receptor type A by the directed-degeneration method
Authors: Han Seong-Gu , Ko Sanghwan , Lee Won-Kyu , Jung Sang Taek , Yu Yeon Gyu
Published: August 2017

G-protein coupled receptors (GPCRs) play indispensable physiological roles in cell proliferation, differentiation, and migration; therefore, identifying the mechanisms by which ligands bind to GPCRs is crucial for developing GPCR-targeting pharmaceutics and for understanding critical biological functions. Although some structural information is available regarding the interactions between GPCRs and their small molecule ligands, knowledge of how GPCRs interact with their corresponding macromolecule ligands, such as peptides and proteins, remains elusive. In this study, we have developed a novel strategy to investigate the precise ligand recognition mechanisms involved in the interaction of endothelin receptor type A (ETA) with its ligand, endothelin-1 (ET-1); we call this method “directed degeneration” method. Through flow cytometric screening of a randomized ETA library, statistical analysis of the identified sequences, and biochemical studies, the ligand interaction map was successfully obtained.
Self-controlled wave propagation in hyperelastic media
Authors: Xin Fengxian , Lu Tian Jian
Published: August 2017

We demonstrate theoretically that an ultrasonic wave propagating in a hyperelastic medium can self-control its phase velocities. This phenomenon occurs because the propagation of the ultrasonic wave generates acoustic radiation stresses in the medium, which can induce large deformation of the medium with significant stiffening effect. In turn, such deformation reshapes the wave propagation while the deformation stiffening changes significantly the phase velocities of the wave till the acoustic radiation stresses are balanced by elastic stresses in the current configuration of the hyperelastic medium. As a result of deformation stiffening, an initially isotropic medium becomes anisotropic, thus enabling self-control or self-bending of the wave propagation. We further reveal that, due to snap-through instability of acoustomechanical deformation in the hyperelastic medium, the ultrasonic wave can discontinuously switch its phase velocities from one state to another by jumping over a large unstable regime. This self-control and switchable mechanism of ultrasonic wave propagation in homogenous hyperelastic media offers innovative design opportunities for phononic, thermal and acoustic materials and devices.
Anti-SmD1 antibodies are associated with renal disorder, seizures, and pulmonary arterial hypertension in Chinese patients with active SLE
Authors: Hu Chaojun , Li Mengtao , Liu Jian , Qian Junyan , Xu Dong , Zhang Shulan , Li Ping , Zhao Jiulang , Tian Xinping , Zeng Xiaofeng
Published: August 2017

Detection of autoantibodies in systemic lupus erythematosus (SLE) plays an important role in timely diagnosis and earlier treatment of SLE. In this study, we used a SmD1 polypeptide-based ELISA to determine anti-SmD1 antibody in 269 SLE, including100 naïve (had not been treated with steroids or immunosuppressants at study inception) SLE patients and 169 non-naive SLE patients; 233 controls with other rheumatic diseases (RDC) (70 RA, 40 AS, 73SSc, and 50 SS), and 110 healthy controls (HC) group. The positive rate of anti-SmD1 among all SLE patients was 60.97%, higher than that in the RDC group (13.30%,P = 0.000) or the HC group (9.09%,P = 0.000). The positive rate of anti-SmD1 in non-naive SLE patients was higher than that for anti-dsDNA antibodies (44.97%,P = 0.03). Positivity for anti-SmD1 only was found in 14.00% of naive SLE patients and 16.00% of non-naive SLE patients. In naive SLE patients, the serum concentration of anti-SmD1 was lower after treatment than before treatment (P = 0.039). Active SLE patients positive for anti-SmD1 were more likely to have malar rash, rash, nonscarring alopecia, PAH and hypocomplementemia. High positivity for anti-SmD1 only in patients with SLE indicated the importance and necessity of detection of anti-SmD1 in patients with SLE.