bluuebunny/crossref_metadata_2025 huggingface dataset:
Flight behaviour and dispersal ofRhynchophorus ferrugineus(Coleoptera: Dryophthoridae) adults using mark-release-recapture method
Authors: Ávalos J.A. , Balasch S. , Soto A.
Published: May 2016

The flight ability and patterns of an insect influence its spread, and the study of its behaviour can be used to improve the strategies to control the pest. RegardingRhynchophorus ferrugineus(Olivier) (Coleoptera: Dryophthoridae), one of the worst threats to palm trees worldwide, laboratory experiments have been conducted to analyze their flight potential. However, these data must be complemented with tests that allow us to know its flight behaviour and dispersal patterns under field conditions. Two mark-release-recapture experiments were conducted in areas withR. ferrugineusinfestations. In the first, the effects of weevil sex, temperature, solar radiation, and relative humidity, on the take-off and flight mobility of adults were analyzed. The second experiment aimed to determine the maximum flight distance covered by adults in field. The take-off rate forR. ferrugineusmales was significantly greater than for females, and was positively influenced by temperature (optimum take-off around 25°C) and solar radiation, both factors being highly correlated. Female weevil recaptures were significantly higher, especially as temperatures increased (optimum recapture around 21°C). Dispersal distances of weevil adults increased when temperatures rose, and while this insect tended to fly short distances (<500 m), it was able to cover up to 7 km. The dispersal ofR. ferrugineusadults mainly occurred during the first 7 days after their release, and when relative humidity increased, their dispersal time was reduced. The results obtained will permit a more effective implementation of certain measures used to controlR. ferrugineus, such as olfactory trapping or intensive surveillance around pest outbreaks.
Associated disease risk from the introduced generalist pathogenSphaerothecum destruens: management and policy implications
Authors: ANDREOU DEMETRA , GOZLAN RODOLPHE ELIE
Published: May 2016

The rosette agentSphaerothecum destruensis a novel pathogen, which is currently believed to have been introduced into Europe along with the introduction of the invasive fish topmouth gudgeonPseudorasbora parva(Temminck & Schlegel, 1846). Its close association withP. parvaand its wide host species range and associated host mortalities, highlight this parasite as a potential source of disease emergence in European fish species. Here, using a meta-analysis of the reportedS. destruensprevalence across all reported susceptible hosts species; we calculated host-specificity providing support thatS. destruensis a true generalist. We have applied all the available information onS. destruensand host-range to an established framework for risk-assessing non-native parasites to evaluate the risks posed byS. destruensand discuss the next steps to manage and prevent disease emergence of this generalist parasite.
C-reactive protein levels in the perioperative period as a predictive marker of endoscopic recurrence after ileo-colonic resection for Crohn’s disease
Authors: Iaculli E , Agostini M , Biancone L , Fiorani C , Di Vizia A , Montagnese F , Sibio S , Manzelli A , Tesauro M , Rufini A , Sica GS
Published: May 2016

The aim of this study was to determine the perioperative behavior of C-reactive protein (CRP) in Crohn’s disease (CD) patients undergoing elective ileo-cecal (IC) resection and to identify association between perioperative CRP levels and endoscopic recurrence at 1 year. Study hypothesis was that perioperative CRP changes are disease specific and could detect subset of patients with more aggressive pathopysiology. Seventy-five patients undergoing IC resection for CD were prospectively enrolled. Serial CRP levels were assessed: preoperative, postoperative day 1 (POD1) and day 5 (POD5). CD patients’ values were compared against same interval assessments of control groups undergoing right colectomy and appendicectomy. At POD1, the serum concentration increase was significantly higher in CD patients than in controls. Comparing with control groups, CRP levels remained remarkably high and showed a lower reduction in CD at POD5. Difference between groups was statistically significant. Optimal cutoff levels have been identified: serum CRP concentrations of >39.8 mg/l at POD1 and of >23.2 mg/l at POD5 have shown a significant association to endoscopic recurrence when using bivariate correlation. In this preliminary series, binary logistic regression could not demonstrate statistical relationship between endoscopic recurrence and any of the variables evaluated as prognostic factor. This is the only study so far that investigates and confirms a disease-specific upregulation of CRP response in the perioperative period for CD patients undergoing surgery. The postoperative CRP levels and kinetics seem to be related to the grade of mucosal inflammation and recurrence rate according to our 12 months endoscopic evaluation.
Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis
Authors:   on behalf of the COMFORT-II Investigators, Harrison C N , Vannucchi A M , Kiladjian J-J , Al-Ali H K , Gisslinger H , Knoops L , Cervantes F , Jones M M , Sun K , McQuitty M , Stalbovskaya V , Gopalakrishna P , Barbui T
Published: May 2016

Ruxolitinib is a Janus kinase (JAK) (JAK1/JAK2) inhibitor that has demonstrated superiority over placebo and best available therapy (BAT) in the Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment (COMFORT) studies. COMFORT-II was a randomized (2:1), open-label phase 3 study in patients with myelofibrosis; patients randomized to BAT could crossover to ruxolitinib upon protocol-defined disease progression or after the primary end point, confounding long-term comparisons. At week 48, 28% (41/146) of patients randomized to ruxolitinib achieved ⩾35% decrease in spleen volume (primary end point) compared with no patients on BAT (P<0.001). Among the 78 patients (53.4%) in the ruxolitinib arm who achieved ⩾35% reductions in spleen volume at any time, the probability of maintaining response was 0.48 (95% confidence interval (CI), 0.35–0.60) at 5 years (median, 3.2 years). Median overall survival was not reached in the ruxolitinib arm and was 4.1 years in the BAT arm. There was a 33% reduction in risk of death with ruxolitinib compared with BAT by intent-to-treat analysis (hazard ratio (HR)=0.67; 95% CI, 0.44–1.02; P=0.06); the crossover-corrected HR was 0.44 (95% CI, 0.18–1.04; P=0.06). There was no unexpected increased incidence of adverse events with longer exposure. This final analysis showed that spleen volume reductions with ruxolitinib were maintained with continued therapy and may be associated with survival benefits.
KCNQ channel openers reverse depressive symptoms via an active resilience mechanism
Authors: Friedman Allyson K. , Juarez Barbara , Ku Stacy M. , Zhang Hongxing , Calizo Rhodora C. , Walsh Jessica J. , Chaudhury Dipesh , Zhang Song , Hawkins Angel , Dietz David M. , Murrough James W. , Ribadeneira Maria , Wong Erik H. , Neve Rachael L. , Han Ming-Hu
Published: May 2016

Less than half of patients suffering from major depressive disorder, a leading cause of disability worldwide, achieve remission with current antidepressants, making it imperative to develop more effective treatment. A new therapeutic direction is emerging from the increased understanding of natural resilience as an active stress-coping process. It is known that potassium (K+) channels in the ventral tegmental area (VTA) are an active mediator of resilience. However, no druggable targets have been identified to potentiate active resilience mechanisms. In the chronic social defeat stress model of depression, we report that KCNQ-type K+ channel openers, including FDA-approved drug retigabine (ezogabine), show antidepressant efficacy. We demonstrate that overexpression of KCNQ channels in the VTA dopaminergic neurons and either local infusion or systemic administration of retigabine normalized neuronal hyperactivity and depressive behaviours. These findings identify KCNQ as a target for conceptually novel antidepressants that function through the potentiation of active resilience mechanisms.
Spin–valley locking in the normal state of a transition-metal dichalcogenide superconductor
Authors: Bawden L. , Cooil S. P. , Mazzola F. , Riley J. M. , Collins-McIntyre L. J. , Sunko V. , Hunvik K. W. B. , Leandersson M. , Polley C. M. , Balasubramanian T. , Kim T. K. , Hoesch M. , Wells J. W. , Balakrishnan G. , Bahramy M. S. , King P. D. C.
Published: May 2016

Metallic transition-metal dichalcogenides (TMDCs) are benchmark systems for studying and controlling intertwined electronic orders in solids, with superconductivity developing from a charge-density wave state. The interplay between such phases is thought to play a critical role in the unconventional superconductivity of cuprates, Fe-based and heavy-fermion systems, yet even for the more moderately-correlated TMDCs, their nature and origins have proved controversial. Here, we study a prototypical example, 2H-NbSe2, by spin- and angle-resolved photoemission and first-principles theory. We find that the normal state, from which its hallmark collective phases emerge, is characterized by quasiparticles whose spin is locked to their valley pseudospin. This results from a combination of strong spin–orbit interactions and local inversion symmetry breaking, while interlayer coupling further drives a rich three-dimensional momentum dependence of the underlying Fermi-surface spin texture. These findings necessitate a re-investigation of the nature of charge order and superconducting pairing in NbSe2 and related TMDCs.
Calorie-induced ER stress suppresses uroguanylin satiety signaling in diet-induced obesity
Authors: Kim G W , Lin J E , Snook A E , Aing A S , Merlino D J , Li P , Waldman S A
Published: May 2016

Background/Objectives:

The uroguanylin-GUCY2C gut–brain axis has emerged as one component regulating feeding, energy homeostasis, body mass and metabolism. Here, we explore a role for this axis in mechanisms underlying diet-induced obesity (DIO).

Subjects/Methods:

Intestinal uroguanylin expression and secretion, and hypothalamic GUCY2C expression and anorexigenic signaling, were quantified in mice on high-calorie diets for 14 weeks. The role of endoplasmic reticulum (ER) stress in suppressing uroguanylin in DIO was explored using tunicamycin, an inducer of ER stress, and tauroursodeoxycholic acid (TUDCA), a chemical chaperone that inhibits ER stress. The impact of consumed calories on uroguanylin expression was explored by dietary manipulation. The role of uroguanylin in mechanisms underlying obesity was examined using Camk2a-Cre-ERT2-Rosa-STOPloxP/loxP-Guca2b mice in which tamoxifen induces transgenic hormone expression in brain.

Results:

DIO suppressed intestinal uroguanylin expression and eliminated its postprandial secretion into the circulation. DIO suppressed uroguanylin through ER stress, an effect mimicked by tunicamycin and blocked by TUDCA. Hormone suppression by DIO reflected consumed calories, rather than the pathophysiological milieu of obesity, as a diet high in calories from carbohydrates suppressed uroguanylin in lean mice, whereas calorie restriction restored uroguanylin in obese mice. However, hypothalamic GUCY2C, enriched in the arcuate nucleus, produced anorexigenic signals mediating satiety upon exogenous agonist administration, and DIO did not impair these responses. Uroguanylin replacement by transgenic expression in brain repaired the hormone insufficiency and reconstituted satiety responses opposing DIO and its associated comorbidities, including visceral adiposity, glucose intolerance and hepatic steatosis.

Conclusions:

These studies reveal a novel pathophysiological mechanism contributing to obesity in which calorie-induced suppression of intestinal uroguanylin impairs hypothalamic mechanisms regulating food consumption through loss of anorexigenic endocrine signaling. The correlative therapeutic paradigm suggests that, in the context of hormone insufficiency with preservation of receptor sensitivity, obesity may be prevented or treated by GUCY2C hormone replacement.
RAC-tagging: Recombineering And Cas9-assisted targeting for protein tagging and conditional analyses
Authors: Baker Oliver , Gupta Ashish , Obst Mandy , Zhang Youming , Anastassiadis Konstantinos , Fu Jun , Stewart A. Francis
Published: May 2016

A fluent method for gene targeting to establish protein tagged and ligand inducible conditional loss-of-function alleles is described. We couple new recombineering applications for one-step cloning of gRNA oligonucleotides and rapid generation of short-arm (~1 kb) targeting constructs with the power of Cas9-assisted targeting to establish protein tagged alleles in embryonic stem cells at high efficiency. RAC (Recombineering And Cas9)-tagging with Venus, BirM, APEX2 and the auxin degron is facilitated by a recombineering-ready plasmid series that permits the reuse of gene-specific reagents to insert different tags. Here we focus on protein tagging with the auxin degron because it is a ligand-regulated loss-of-function strategy that is rapid and reversible. Furthermore it includes the additional challenge of biallelic targeting. Despite high frequencies of monoallelic RAC-targeting, we found that simultaneous biallelic targeting benefits from long-arm (>4 kb) targeting constructs. Consequently an updated recombineering pipeline for fluent generation of long arm targeting constructs is also presented.
Quantitative evidence for the effects of multiple drivers on continental-scale amphibian declines
Authors: Grant Evan H. Campbell , Miller David A. W. , Schmidt Benedikt R. , Adams Michael J. , Amburgey Staci M. , Chambert Thierry , Cruickshank Sam S. , Fisher Robert N. , Green David M. , Hossack Blake R. , Johnson Pieter T. J. , Joseph Maxwell B. , Rittenhouse Tracy A. G. , Ryan Maureen E. , Waddle J. Hardin , Walls Susan C. , Bailey Larissa L. , Fellers Gary M. , Gorman Thomas A. , Ray Andrew M. , Pilliod David S. , Price Steven J. , Saenz Daniel , Sadinski Walt , Muths Erin
Published: May 2016

Since amphibian declines were first proposed as a global phenomenon over a quarter century ago, the conservation community has made little progress in halting or reversing these trends. The early search for a “smoking gun” was replaced with the expectation that declines are caused by multiple drivers. While field observations and experiments have identified factors leading to increased local extinction risk, evidence for effects of these drivers is lacking at large spatial scales. Here, we use observations of 389 time-series of 83 species and complexes from 61 study areas across North America to test the effects of 4 of the major hypothesized drivers of declines. While we find that local amphibian populations are being lost from metapopulations at an average rate of 3.79% per year, these declines are not related to any particular threat at the continental scale; likewise the effect of each stressor is variable at regional scales. This result - that exposure to threats varies spatially, and populations vary in their response - provides little generality in the development of conservation strategies. Greater emphasis on local solutions to this globally shared phenomenon is needed.
Leaf epidermis images for robust identification of plants
Authors: da Silva Núbia Rosa , Oliveira Marcos William da Silva , Filho Humberto Antunes de Almeida , Pinheiro Luiz Felipe Souza , Rossatto Davi Rodrigo , Kolb Rosana Marta , Bruno Odemir Martinez
Published: May 2016

This paper proposes a methodology for plant analysis and identification based on extracting texture features from microscopic images of leaf epidermis. All the experiments were carried out using 32 plant species with 309 epidermal samples captured by an optical microscope coupled to a digital camera. The results of the computational methods using texture features were compared to the conventional approach, where quantitative measurements of stomatal traits (density, length and width) were manually obtained. Epidermis image classification using texture has achieved a success rate of over 96%, while success rate was around 60% for quantitative measurements taken manually. Furthermore, we verified the robustness of our method accounting for natural phenotypic plasticity of stomata, analysing samples from the same species grown in different environments. Texture methods were robust even when considering phenotypic plasticity of stomatal traits with a decrease of 20% in the success rate, as quantitative measurements proved to be fully sensitive with a decrease of 77%. Results from the comparison between the computational approach and the conventional quantitative measurements lead us to discover how computational systems are advantageous and promising in terms of solving problems related to Botany, such as species identification.
A new class of large band gap quantum spin hall insulators: 2D fluorinated group-IV binary compounds
Authors: Padilha J. E. , Pontes R. B. , Schmidt T. M. , Miwa R. H. , Fazzio A.
Published: May 2016

We predict a new class of large band gap quantum spin Hall insulators, the fluorinated PbX (X = C, Si, Ge and Sn) compounds, that are mechanically stable two-dimensional materials. Based on first principles calculations we find that, while the PbX systems are not topological insulators, all fluorinated PbX (PbXF2) compounds are 2D topological insulators. The quantum spin Hall insulating phase was confirmed by the explicitly calculation of the Z2 invariant. In addition we performed a thorough investigation of the role played by the (i) fluorine saturation, (ii) crystal field and (iii) spin-orbital coupling in PbXF2. By considering nanoribbon structures, we verify the appearance of a pair of topologically protected Dirac-like edge states connecting the conduction and valence bands. The insulating phase which is a result of the spin orbit interaction, reveals that this new class of two dimensional materials present exceptional nontrivial band gaps, reaching values up to 0.99 eV at the Γ point and an indirect band gap of 0.77 eV. The topological phase is arisen without any external field, making this system promising for nanoscale applications, using topological properties.
High light intensity plays a major role in emergence of population level variation in Arabidopsis thaliana along an altitudinal gradient
Authors: Tyagi Antariksh , Yadav Amrita , Tripathi Abhinandan Mani , Roy Sribash
Published: May 2016

Environmental conditions play an important role in the emergence of genetic variations in natural populations. We identified genome-wide patterns of nucleotide variations in the coding regions of natural Arabidopsis thaliana populations. These populations originated from 700 m to 3400 m a.m.s.l. in the Western Himalaya. Using a pooled RNA-Seq approach, we identified the local and global level population-specific SNPs. The biological functions of the SNP-containing genes were primarily related to the high light intensity prevalent at high-altitude regions. The novel SNPs identified in these genes might have arisen de novo in these populations. In another approach, the FSTs of SNP-containing genes were correlated with the corresponding climatic factors. ‘Radiation in the growing season’ was the only environmental factor found to be strongly correlated with the gene-level FSTs. In both the approaches, the high light intensity was identified as the primary abiotic stress associated with the variations in these populations. The differential gene expression analysis between field and controlled condition grown plants also showed high light intensity as the primary abiotic stress, particularly for the high altitude populations. Our results provide a genome-wide perspective of nucleotide variations in populations along altitudinal gradient and their putative role in emergence of these variations.
Conditional Disease Development extracted from Longitudinal Health Care Cohort Data using Layered Network Construction
Authors: Kannan Venkateshan , Swartz Fredrik , Kiani Narsis A. , Silberberg Gilad , Tsipras Giorgos , Gomez-Cabrero David , Alexanderson Kristina , Tegnèr Jesper
Published: May 2016

Health care data holds great promise to be used in clinical decision support systems. However, frequent near-synonymous diagnoses recorded separately, as well as the sheer magnitude and complexity of the disease data makes it challenging to extract non-trivial conclusions beyond confirmatory associations from such a web of interactions. Here we present a systematic methodology to derive statistically valid conditional development of diseases. To this end we utilize a cohort of 5,512,469 individuals followed over 13 years at inpatient care, including data on disability pension and cause of death. By introducing a causal information fraction measure and taking advantage of the composite structure in the ICD codes, we extract an effective directed lower dimensional network representation (100 nodes and 130 edges) of our cohort. Unpacking composite nodes into bipartite graphs retrieves, for example, that individuals with behavioral disorders are more likely to be followed by prescription drug poisoning episodes, whereas women with leiomyoma were more likely to subsequently experience endometriosis. The conditional disease development represent putative causal relations, indicating possible novel clinical relationships and pathophysiological associations that have not been explored yet.
Soluble CD59 is a Novel Biomarker for the Prediction of Obstructive Chronic Lung Allograft Dysfunction After Lung Transplantation
Authors: Budding Kevin , van de Graaf Eduard. A. , Kardol-Hoefnagel Tineke , Kwakkel-van Erp Johanna M. , Luijk Bart D. , Oudijk Erik-Jan D. , van Kessel Diana A. , Grutters Jan C. , Hack C. Erik , Otten Henderikus G.
Published: May 2016

CD59 is a complement regulatory protein that inhibits membrane attack complex formation. A soluble form of CD59 (sCD59) is present in various body fluids and is associated with cellular damage after acute myocardial infarction. Lung transplantation (LTx) is the final treatment for end-stage lung diseases, however overall survival is hampered by chronic lung allograft dysfunction development, which presents itself obstructively as the bronchiolitis obliterans syndrome (BOS). We hypothesized that, due to cellular damage and activation during chronic inflammation, sCD59 serum levels can be used as biomarker preceding BOS development. We analyzed sCD59 serum concentrations in 90 LTx patients, of whom 20 developed BOS. We observed that BOS patients exhibited higher sCD59 serum concentrations at the time of diagnosis compared to clinically matched non-BOS patients (p = 0.018). Furthermore, sCD59 titers were elevated at 6 months post-LTx (p = 0.0020), when patients had no BOS-related symptoms. Survival-analysis showed that LTx patients with sCD59 titers ≥400 pg/ml 6 months post-LTx have a significant (p < 0.0001) lower chance of BOS-free survival than patients with titers ≤400 pg/ml, 32% vs. 80% respectively, which was confirmed by multivariate analysis (hazard ratio 6.2, p < 0.0001). We propose that circulating sCD59 levels constitute a novel biomarker to identify patients at risk for BOS following LTx.
Regenerative repair of Pifithrin-α in cerebral ischemia via VEGF dependent manner
Authors: Zhang Ping , Lei Xuhui , Sun Ying , Zhang Haitao , Chang Liang , Li Chenlong , Liu Daming , Bhatta Nishant , Zhang Zhiren , Jiang Chuanlu
Published: May 2016

Promoting regenerative repair, including neurogenesis and angiogenesis, may provide a new therapeutic strategy for treatment of stroke. P53, a well-documented transcription factor, has been reported to be involved in cerebral ischemia and also serves as an important regulator of vascular endothelial growth factor (VEGF). However, the role of p53 in endogenous regenerative repair after brain ischemia is poorly understood. In this study, we investigated the effects of PFT-α, a specific p53 inhibitor on neurogenesis and angiogenesis improvement and associated signal pathways in rats impaired by cerebral artery occlusion (MCAo). PFT-α induced neuroprotection, reduced infarct volume and neurological functional impairment after ischemic stroke. More importantly, neurogenesis and angiogenesis were greatly enhanced by PFT-α and accompanied by increased expression of VEGF. Moreover, we got consistent results in neural stem cells (NSCs) isolated from fetal rats. In contrast, application of the anti-VEGF neutralizing antibody (RB-222) partially reversed PFT-α-induced neuroprotection and rescued p53 expression. Noteworthily, inhibition of p53 after ischemic stroke in these rats improved their outcomes via promotion of regenerative repair. In conclusion, PFT-α could serve as a promising therapeutic strategy for ischemic stroke by promoting regenerative repair.
Strength of weak layers in cascading failures on multiplex networks: case of the international trade network
Authors: Lee Kyu-Min , Goh K.-I.
Published: May 2016

Many real-world complex systems across natural, social, and economical domains consist of manifold layers to form multiplex networks. The multiple network layers give rise to nonlinear effect for the emergent dynamics of systems. Especially, weak layers that can potentially play significant role in amplifying the vulnerability of multiplex networks might be shadowed in the aggregated single-layer network framework which indiscriminately accumulates all layers. Here we present a simple model of cascading failure on multiplex networks of weight-heterogeneous layers. By simulating the model on the multiplex network of international trades, we found that the multiplex model produces more catastrophic cascading failures which are the result of emergent collective effect of coupling layers, rather than the simple sum thereof. Therefore risks can be systematically underestimated in single-layer network analyses because the impact of weak layers can be overlooked. We anticipate that our simple theoretical study can contribute to further investigation and design of optimal risk-averse real-world complex systems.
Increased arachidonic acid-containing phosphatidylcholine is associated with reactive microglia and astrocytes in the spinal cord after peripheral nerve injury
Authors: Xu Dongmin , Omura Takao , Masaki Noritaka , Arima Hideyuki , Banno Tomohiro , Okamoto Ayako , Hanada Mitsuru , Takei Shiro , Matsushita Shoko , Sugiyama Eiji , Setou Mitsutoshi , Matsuyama Yukihiro
Published: May 2016

Peripheral nerve injury (PNI) triggers cellular and molecular changes in the spinal cord. However, little is known about how the polyunsaturated fatty acid-containing phosphatidylcholines (PUFA-PCs) are regulated in the spinal cord after PNI and the association of PUFA-PCs with the non-neuronal cells within in the central nervous system (CNS). In this study, we found that arachidonic acid-containing phosphatidylcholine (AA-PC), [PC(16:0/20:4)+K]+, was significantly increased in the ipsilateral ventral and dorsal horns of the spinal cord after sciatic nerve transection and the increased expression of [PC(16:0/20:4)+K]+ spatiotemporally resembled the increase of reactive microglia and the astrocytes. From the lipidomics point of view, we conclude that [PC(16:0/20:4)+K]+ could be the main phospholipid in the spinal cord influenced by PNI and the regulation of specific phospholipid molecule in the CNS after PNI is associated with the reactive microglia and astrocytes.
Arbuscular mycorrhizal symbiosis affects the grain proteome of Zea mays: a field study
Authors: Bona Elisa , Scarafoni Alessio , Marsano Francesco , Boatti Lara , Copetta Andrea , Massa Nadia , Gamalero Elisa , D’Agostino Giovanni , Cesaro Patrizia , Cavaletto Maria , Berta Graziella
Published: May 2016

Maize is one of the most important crops worldwide and is strongly dependent on arbuscular mycorrhiza (AM) fungi, organisms that form a mutualistic association with land plants. In maize, AM symbiosis enhances spike dry weight, spike length, spike circumference and the dry weight and dimensions of the grain. Notwithstanding its ubiquitous nature, the detailed relationship between AM fungal colonization and plant development is not completely understood. To facilitate a better understanding of the effects of AM fungi on plants, the work reported here assessed the effects of a consortium of AM fungi on the kernel proteome of maize, cultivated in open-field conditions. To our knowledge, this is the first report of the modulation of a plant seed proteome following AM fungal inoculation in the field. Here, it was found that AM fungi modify the maize seed proteome by up-regulating enzymes involved in energetic metabolism, embryo development, nucleotide metabolism, seed storage and stress responses.
Whole exome sequencing links dental tumor to an autosomal-dominant mutation in ANO5 gene associated with gnathodiaphyseal dysplasia and muscle dystrophies
Authors: Andreeva T. V. , Tyazhelova T. V. , Rykalina V. N. , Gusev F. E. , Goltsov A. Yu. , Zolotareva O. I. , Aliseichik M. P. , Borodina T. A. , Grigorenko A. P. , Reshetov D. A. , Ginter E. K. , Amelina S. S. , Zinchenko R. A. , Rogaev E. I.
Published: May 2016

Tumors of the jaws may represent different human disorders and frequently associate with pathologic bone fractures. In this report, we analyzed two affected siblings from a family of Russian origin, with a history of dental tumors of the jaws, in correspondence to original clinical diagnosis of cementoma consistent with gigantiform cementoma (GC, OMIM: 137575). Whole exome sequencing revealed the heterozygous missense mutation c.1067G > A (p.Cys356Tyr) in ANO5 gene in these patients. To date, autosomal-dominant mutations have been described in the ANO5 gene for gnathodiaphyseal dysplasia (GDD, OMIM: 166260) and multiple recessive mutations have been described in the gene for muscle dystrophies (OMIM: 613319, 611307); the same amino acid (Cys) at the position 356 is mutated in GDD. These genetic data and similar clinical phenotypes demonstrate that the GC and GDD likely represent the same type of bone pathology. Our data illustrate the significance of mutations in single amino-acid position for particular bone tissue pathology. Modifying role of genetic variations in another gene on the severity of the monogenic trait pathology is also suggested. Finally, we propose the model explaining the tissue-specific manifestation of clinically distant bone and muscle diseases linked to mutations in one gene.
Novel application of hydrophobin in medical science: a drug carrier for improving serum stability
Authors: Zhao Liqiang , Xu Haijin , Li Ying , Song Dongmin , Wang Xiangxiang , Qiao Mingqiang , Gong Min
Published: May 2016

Multiple physiological properties of glucagon-like peptide-1 (GLP-1) ensure that it is a promising drug candidate for the treatment of type 2 diabetes. However, the in vivo half-life of GLP-1 is short because of rapid degradation by dipeptidyl peptidase-IV (DPP-IV) and renal clearance. The poor serum stability of GLP-1 has significantly limited its clinical utility, although many studies are focused on extending the serum stability of this molecule. Hydrophobin, a self-assembling protein, was first applied as drug carrier to stabilize GLP-1 against protease degradation by forming a cavity. The glucose tolerance test clarified that the complex retained blood glucose clearance activity for 72 hours suggesting that this complex might be utilized as a drug candidate administered every 2–3 days. Additionally, it was found that the mutagenesis of hydrophobin preferred a unique pH condition for self-assembly. These findings suggested that hydrophobin might be a powerful tool as a drug carrier or a pH sensitive drug-release compound. The novel pharmaceutical applications of hydrophobin might result in future widespread interest in hydrophobin.
A Rapid Method for Refolding Cell Surface Receptors and Ligands
Authors: Zhai Lu , Wu Ling , Li Feng , Burnham Robert S. , Pizarro Juan C. , Xu Bin
Published: May 2016

Production of membrane-associated cell surface receptors and their ligands is often a cumbersome, expensive, and time-consuming process that limits detailed structural and functional characterization of this important class of proteins. Here we report a rapid method for refolding inclusion-body-based, recombinant cell surface receptors and ligands in one day, a speed equivalent to that of soluble protein production. This method efficiently couples modular on-column immobilized metal ion affinity purification and solid-phase protein refolding. We demonstrated the general utility of this method for producing multiple functionally active immunoreceptors, ligands, and viral decoys, including challenging cell surface proteins that cannot be produced using typical dialysis- or dilution-based refolding approaches.
A Relation for Nanodroplet Diffusion on Smooth Surfaces
Authors: Li Chu , Huang Jizu , Li Zhigang
Published: May 2016

In this work, we study the diffusion of nanodroplets on smooth surfaces through molecular dynamics (MD) simulations and theoretical analyses. Molecular dynamics simulations show that nanodroplet surface diffusion is different from that of single molecules and solid particles. The dependence of nanodroplet diffusion coefficient on temperature undergoes a transition from linear to nonlinear as the surface wettability is weakened due to the coupling of temperature and surface energy. We also develop a simple relation for the diffusion coefficient by using the contact angle and contact radius of the droplet. It works well for a wide range of surface wettabilities and different sized nanodroplets, as confirmed by MD simulations.
The independent contribution of miRNAs to the missing heritability in CYP3A4/5 functionality and the metabolism of atorvastatin
Authors: Liu Ju-E , Ren Bin , Tang Lan , Tang Qian-Jie , Liu Xiao-Ying , Li Xin , Bai Xue , Zhong Wan-Ping , Meng Jin-Xiu , Lin Hao-Ming , Wu Hong , Chen Ji-Yan , Zhong Shi-Long
Published: May 2016

To evaluate the independent contribution of miRNAs to the missing heritability in CYP3A4/5 functionality and atorvastatin metabolism, the relationships among three levels of factors, namely (1) clinical characteristics, CYP3A4/5 genotypes and miRNAs, (2) CYP3A4 and CYP3A5 mRNAs and (3) CYP3A activity, as well as their individual impacts on atorvastatin metabolism, were assessed in 55 human liver tissues. MiR-27b, miR-206 and CYP3A4 mRNA respectively accounted for 20.0%, 5.8% and 9.5% of the interindividual variations in CYP3A activity. MiR-142 was an independent contributor to the expressions of CYP3A4 mRNA (partial R2 = 0.12, P = 0.002) and CYP3A5 mRNA (partial R2 = 0.09, P = 0.005) but not CYP3A activity or atorvastatin metabolism. CYP3A activity was a unique independent predictor of variability of atorvastatin metabolism, explaining the majority of the variance in reduction of atorvastatin (60.0%) and formation of ortho-hydroxy atorvastatin (78.8%) and para-hydroxy atorvastatin (83.9%). MiR-27b and miR-206 were found to repress CYP3A4 gene expression and CYP3A activity by directly binding to CYP3A4 3′-UTR, while miR-142 was found to indirectly repress CYP3A activity. Our study indicates that miRNAs play significant roles in bridging the gap between epigenetic effects and missing heritability in CYP3A functionality.
Cell type-dependent Erk-Akt pathway crosstalk regulates the proliferation of fetal neural progenitor cells
Authors: Rhim Ji heon , Luo Xiangjian , Gao Dongbing , Xu Xiaoyun , Zhou Tieling , Li Fuhai , Wang Ping , Wong Stephen T. C. , Xia Xiaofeng
Published: May 2016

Neural progenitor (NP) cells are the multipotent cells that produce neurons and glia in the central nervous system. Compounds regulating their proliferation are key to both understanding brain development and unlocking their potential in regenerative repair. We discuss a chemical screen that unexpectedly identified inhibitors of Erk signaling potently promoting the self-renewing divisions of fetal NP cells. This occurred through crosstalk between Erk and Akt signaling cascades. The crosstalk mechanism is cell type-specific and is not detected in adult NP cells as well as brain tumor cells. The mechanism was also shown to be independent from the GSK-3 signaling pathway, which has been reported to be a major regulator of NP cell homeostasis and inhibitors to which were also identified in the screen. In vitro Erk inhibition led to the prolonged rapid expansion of fetal NP cells while retaining their multipotency. In vivo inhibitor administration significantly inhibited the neuronal differentiation and resulted in increased proliferative progenitor cells in the ventricular/subventricular zone (VZ/SVZ) of the embryonic cortex. Our results uncovered a novel regulating pathway for NP cell proliferation in the developing brain. The discovery provides a pharmacological basis for in vitro expansion and in vivo manipulation of NP cells.
Dlg5 maintains apical polarity by promoting membrane localization of Crumbs during Drosophila oogenesis
Authors: Luo Jun , Wang Heng , Kang Di , Guo Xuan , Wan Ping , Wang Dou , Chen Jiong
Published: May 2016

Apical-basal polarity plays critical roles in the functions of epithelial tissues. However, the mechanisms of epithelial polarity establishment and maintenance remain to be fully elucidated. Here we show that the membrane-associated guanylate kinase (MAGUK) family protein Dlg5 is required for the maintenance of apical polarity of follicle epithelium during Drosophila oogenesis. Dlg5 localizes at the apical membrane and adherens junction (AJ) of follicle epithelium in early stage egg chambers. Specifically, we demonstrate that the major function of Dlg5 is to promote apical membrane localization of Crumbs, since overexpression of Crumbs but not other major apical or AJ components could rescue epithelial polarity defects resulted from loss of Dlg5. Furthermore, we performed a structure-function analysis of Dlg5 and found that the C-terminal PDZ3 and PDZ4 domains are required for all Dlg5’s functions as well as its ability to localize to apical membrane. The N-terminal coiled-coil motif could be individually targeted to the apical membrane, while the central linker region could be targeted to AJ. Lastly, the MAGUK core domains of PDZ4-SH3-GUK could be individually targeted to apical, AJ and basolateral membranes.
An inhibitor of the Keap1-Nrf2 protein-protein interaction protects NCM460 colonic cells and alleviates experimental colitis
Authors: Lu Meng-Chen , Ji Jian-Ai , Jiang Yong-Lin , Chen Zhi-Yun , Yuan Zhen-Wei , You Qi-Dong , Jiang Zheng-Yu
Published: May 2016

Ulcerative colitis (UC) is a chronic relapsing-remitting form of inflammatory bowel disease (IBD) that increases the risk of colorectal cancer, the third most common malignancy in humans. Oxidative stress is a risk factor for the development of UC. The Keap1-Nrf2-ARE pathway is one of the most important defensive mechanisms against oxidative and/or electrophilic stresses. In this study, we identified CPUY192018 as a potent small-molecule inhibitor of the Keap1-Nrf2 PPI, investigated the cyto-protective effects of CPUY192018 on the NCM460 colonic cells and evaluated whether treatment with the inhibitor of the Keap1-Nrf2 PPI exerts protection on an established experimental model of UC induced by dextran sodium sulfate (DSS). Our study clearly demonstrated that CPUY192018 had a cytoprotective effect against DSS in both NCM460 cells and mouse colon via the activation of Nrf2 signaling. These results suggested that activation of Nrf2 by directly inhibiting the Keap1-Nrf2 PPI may be beneficial as a treatment for UC.
Mesenchymal stem cells are sensitive to bleomycin treatment
Authors: Nicolay Nils H. , Rühle Alexander , Perez Ramon Lopez , Trinh Thuy , Sisombath Sonevisay , Weber Klaus-Josef , Ho Anthony D. , Debus Jürgen , Saffrich Rainer , Huber Peter E.
Published: May 2016

Mesenchymal stem cells (MSCs) have been shown to attenuate pulmonary damage induced by bleomycin-based anticancer treatments, but the influence of bleomycin on the stem cells themselves remains largely unknown. Here, we demonstrate that human bone marrow-derived MSCs are relatively sensitive to bleomycin exposure compared to adult fibroblasts. MSCs revealed increased levels of apoptosis after bleomycin treatment, while cellular morphology, stem cell surface marker expression and the ability for adhesion and migration remained unchanged. Bleomycin treatment also resulted in a reduced adipogenic differentiation potential of these stem cells. MSCs were found to efficiently repair DNA double strand breaks induced by bleomycin, mostly through non-homologous end joining repair. Low mRNA and protein expression levels of the inactivating enzyme bleomycin hydrolase were detected in MSCs that may contribute to the observed bleomycin-sensitive phenotype of these cells. The sensitivity of MSCs against bleomycin needs to be taken into consideration for ongoing and future treatment protocols investigating these stem cells as a potential treatment option for bleomycin-induced pulmonary damage in the clinic.
Predominance of sperm motion in corners
Authors: Nosrati Reza , Graham Percival J. , Liu Qiaozhi , Sinton David
Published: May 2016

Sperm migration through the female tract is crucial to fertilization, but the role of the complex and confined structure of the fallopian tube in sperm guidance remains unknown. Here, by confocal imaging microchannels head-on, we distinguish corner- vs. wall- vs. bulk-swimming bull sperm in confined geometries. Corner-swimming dominates with local areal concentrations as high as 200-fold that of the bulk. The relative degree of corner-swimming is strongest in small channels, decreases with increasing channel size and plateaus for channels above 200 μm. Corner-swimming remains predominant across the physiologically-relevant range of viscosity and pH. Together, boundary-following sperm account for over 95% of the sperm distribution in small rectangular channels, which is similar to the percentage of wall swimmers in circular channels of similar size. We also demonstrate that wall-swimming sperm travel closer to walls in smaller channels (~100 μm), where the opposite wall is within the hydrodynamic interaction length-scale. The corner accumulation effect is more than the superposition of the influence of two walls and over 5-fold stronger than that of a single wall. These findings suggest that folds and corners are dominant in sperm migration in the narrow (sub-mm) lumen of the fallopian tube and microchannel-based sperm selection devices.
A genomic screen for long noncoding RNA genes epigenetically silenced by aberrant DNA methylation in colorectal cancer
Authors: Kumegawa Kohei , Maruyama Reo , Yamamoto Eiichiro , Ashida Masami , Kitajima Hiroshi , Tsuyada Akihiro , Niinuma Takeshi , Kai Masahiro , Yamano Hiro-o , Sugai Tamotsu , Tokino Takashi , Shinomura Yasuhisa , Imai Kohzoh , Suzuki Hiromu
Published: May 2016

Long noncoding RNAs (lncRNAs) have emerged as key components in multiple cellular processes, although their physiological and pathological functions are not fully understood. To identify cancer-related lncRNAs, we screened for those that are epigenetically silenced in colorectal cancer (CRC). Through a genome-wide analysis of histone modifications in CRC cells, we found that the transcription start sites (TSSs) of 1,027 lncRNA genes acquired trimethylation of histone H3 lysine 4 (H3K4me3) after DNA demethylation. Integrative analysis of chromatin signatures and the DNA methylome revealed that the promoter CpG islands (CGIs) of 66 lncRNA genes contained cancer-specific methylation. By validating the expression and methylation of lncRNA genes in CRC cells, we ultimately identified 20 lncRNAs, including ZNF582-AS1, as targets of epigenetic silencing in CRC. ZNF582-AS1 is frequently methylated in CRC cell lines (87.5%), primary CRCs (77.2%), colorectal adenomas (44.7%) and advanced adenomas (87.8%), suggesting that this methylation is an early event during colorectal tumorigenesis. Methylation of ZNF582-AS1 is associated with poor survival of CRC patients and ectopic expression of ZNF582-AS1 suppressed colony formation by CRC cells. Our findings offer insight into the association between epigenetic alterations and lncRNA dysregulation in cancer and suggest that ZNF582-AS1 may be a novel tumor-suppressive lncRNA.
CdS/ZnIn2S4/TiO2 3D-heterostructures and their photoelectrochemical properties
Authors: Yin Xuehua , Sheng Pengtao , Zhong Fenfen , Nguyen VanManh , Cai Qingyun , Grimes Craig
Published: May 2016

A CdS/ZnIn2S4/TiO2 3D-heterostructure with high photoconversion efficiency and photocatalytic activity was synthesized and applied.
Vibrational solvatochromism of nitrile infrared probes: beyond the vibrational Stark dipole approach
Authors: Błasiak Bartosz , Ritchie Andrew W. , Webb Lauren J. , Cho Minhaeng
Published: May 2016

Systematic probing of local environments around biopolymers is important for understanding their functions.
Photoluminescence enhancement of ZnO nanowire arrays by atomic layer deposition of ZrO2 layers and thermal annealing
Authors: Zhang Yuan , Lu Hong-Liang , Wang Tao , Ren Qing-Hua , Chen Hong-Yan , Zhang Hao , Ji Xin-Ming , Liu Wen-Jun , Ding Shi-Jin , Zhang David Wei
Published: May 2016

The ultraviolet emission of ZnO nanowires was enhanced significantly after coating with thin ZrO2 layers and thermal annealing.
Highly selective uptake of carbon dioxide on the zeolite |Na10.2KCs0.8|-LTA – a possible sorbent for biogas upgrading
Authors: Cheung Ocean , Wardecki Dariusz , Bacsik Zoltán , Vasiliev Petr , McCusker Lynne B. , Hedin Niklas
Published: May 2016

Zeolite |Na10.2KCs0.8|-LTA was found to be a promising adsorbent for applications such as biogas upgrading. The CO2-over-CH4 selectivity was very high (over 1500).
Is formamide a geochemically plausible prebiotic solvent?
Authors: Bada Jeffrey L. , Chalmers John H. , Cleaves H. James
Published: May 2016

From a geochemical perspective, significant amounts of pure formamide (HCONH2) would have likely been rare on the early Earth.
Graphene-based microfluidics for serial crystallography
Authors: Sui Shuo , Wang Yuxi , Kolewe Kristopher W. , Srajer Vukica , Henning Robert , Schiffman Jessica D. , Dimitrakopoulos Christos , Perry Sarah L.
Published: May 2016

A robust strategy for the incorporation of graphene films as a diffusion barrier in ultra-thin X-ray compatible microfluidic devices.
A systematic study of protein labeling by fluorogenic probes using cysteine targeting vinyl sulfone-cyclooctyne tags
Authors: Söveges B. , Imre T. , Szende T. , Póti Á. L. , Cserép G. B. , Hegedűs T. , Kele P. , Németh K.
Published: May 2016

Protein labeling by cycloocytynylated vinyl sulfone linkers is fast and thiol-selective, and subsequent click reaction with fluorogenic azides generates intensive fluorescence.
Monoclonal antibody capture from cell culture supernatants using epitope imprinted macroporous membranes
Authors: Schwark Sebastian , Sun Wei , Stute Jörg , Lütkemeyer Dirk , Ulbricht Mathias , Sellergren Börje
Published: May 2016

A straightforward epitope imprinting procedure is used to prepare IgG affinity membranes directly applicable to mAb capture under near process realistic conditions.
Propargylation of 1,3-dicarbonyl compounds catalyzed by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and sodium nitrite in the presence of molecular oxygen and formic acid
Authors: Cheng Dongping , Zhou Xiayi , Xu Xiaoliang , Yan Jizhong
Published: May 2016

The coupling reaction of 1,3-diarylpropyne and 1,3-dicarbonyl compounds using molecular oxygen as a terminal oxidation was developed. Catalyzed by DDQ and NaNO2 in the presence of HCOOH, the corresponding products were obtained in 37–87% yields.
Repeat protein scaffolds: ordering photo- and electroactive molecules in solution and solid state
Authors: Mejías Sara H. , López-Andarias Javier , Sakurai Tsuneaki , Yoneda Satoru , Erazo Kevin P. , Seki Shu , Atienza Carmen , Martín Nazario , Cortajarena Aitziber L.
Published: May 2016

An innovative approach is investigated in which a protein building block is designed to organize porphyrin molecules. The strategy is based on a modular protein unit with tunable properties including stability, function and self-assembly.