bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the Clinical Utility of the Eating Beliefs Questionnaire
Authors: Burton Amy L. , Smith Evelyn , Abbott Maree J.
Published: September 2018

Abstract. The Eating Beliefs Questionnaire (EBQ) is a valid and reliable self-report tool measuring positive and negative beliefs about binge eating. This study sought to further investigate the clinical utility of the EBQ using a clinical binge eating sample and a healthy control comparison group. Clinical participants were 74 individuals seeking treatment for eating disorders: 38 with bulimia nervosa and 36 with binge eating disorder. Healthy controls were 114 individuals recruited from the general community. Participants all completed a test battery that included the EBQ. Diagnoses of clinical participants were confirmed using the semi-structured interview, the Eating Disorders Examination, administered by a trained clinician. The EBQ and its subscales showed good internal consistency, and significant differences between the clinical and nonclinical groups were observed for EBQ total and subscales scores, but not between the two clinical groups. Receiver operating characteristic (ROC) curve analyses revealed optimal cutoff scores for the EBQ, which demonstrated excellent sensitivity, specificity, and positive and negative predictive values. Results from this study provide further evidence in support of the EBQ’s psychometric properties. Clinical cutoff scores can be used to assess severity of binge eating-related cognitions in both research and clinical settings.
Models of Saturn's Equatorial Ionosphere Based on In Situ Data From Cassini's Grand Finale
Authors: Moore L. , Cravens T. E. , Müller‐Wodarg I. , Perry M. E. , Waite J. H. , Perryman R. , Nagy A. , Mitchell D. , Persoon A. , Wahlund J.‐E. , Morooka M. W.
Published: September 2018

We present new models of Saturn's equatorial ionosphere based on the first in situ measurements of its upper atmosphere. The neutral spectrum measured by Cassini's Ion and Neutral Mass Spectrometer, which includes substantial methane, ammonia, and organics in addition to the anticipated molecular hydrogen, helium, and water, serves as input for unexpectedly complex ionospheric chemistry. Heavy molecular ions are found to dominate Saturn's equatorial low‐altitude ionosphere, with a mean ion mass of 11 Da. Key molecular ions include H3O+ and HCO+; other abundant heavy ions depend upon the makeup of the mass 28 neutral species, which cannot be uniquely determined. Ion and Neutral Mass Spectrometer neutral species lead to generally good agreement between modeled and observed plasma densities, though poor reproduction of measured H+ and H3+ variability and an overabundance of modeled H3+ potentially hint at missing physical processes in the model, including a loss process that affects H3+ but not H+.
Neuroprotection of retinal ganglion cells by a novel gene therapy construct that achieves sustained enhancement of brain-derived neurotrophic factor/tropomyosin-related kinase receptor-B signaling
Authors: Osborne Andrew , Khatib Tasneem Z. , Songra Lalana , Barber Amanda C. , Hall Katie , Kong George Y. X. , Widdowson Peter S. , Martin Keith R.
Published: September 2018

Previous studies have demonstrated that intravitreal delivery of brain-derived neurotrophic factor (BDNF) by injection of recombinant protein or by gene therapy can alleviate retinal ganglion cell (RGC) loss after optic nerve injury. BDNF gene therapy can improve RGC survival in experimental models of glaucoma, the leading cause of irreversible blindness worldwide. However, the therapeutic efficacy of BDNF supplementation alone is time limited at least in part due to BDNF receptor downregulation. Tropomyosin-related receptor kinase-B (TrkB) downregulation has been reported in many neurological diseases including glaucoma, potentially limiting the effect of sustained or repeated BDNF delivery.

Here, we characterize a novel adeno-associated virus (AAV) gene therapy (AAV2 TrkB-2A-mBDNF) that not only increases BDNF production but also improves long-term neuroprotective signaling by increasing expression of the BDNF receptor (TrkB) within the inner retina. This approach leads to significant and sustained elevation of survival signaling pathways ERK and AKT within RGCs over 6 months and avoids the receptor downregulation which we observe with treatment with AAV2 BDNF alone. We validate the neuroprotective efficacy of AAV2 TrkB-2A-mBDNF in a mouse model of optic nerve injury, where it outperforms conventional AAV2 BDNF or AAV2 TrkB therapy, before showing powerful proof of concept neuroprotection of RGCs and axons in a rat model of chronic intraocular pressure (IOP) elevation. We also show that there are no adverse effects of the vector on retinal structure or function as assessed by histology and electroretinography in young or aged animals. Further studies are underway to explore the potential of this vector as a candidate for progression into clinical studies to protect RGCs in patients with glaucoma and progressive visual loss despite conventional IOP-lowering treatment.
Dereplication of microbial metabolites through database search of mass spectra
Authors: Mohimani Hosein , Gurevich Alexey , Shlemov Alexander , Mikheenko Alla , Korobeynikov Anton , Cao Liu , Shcherbin Egor , Nothias Louis-Felix , Dorrestein Pieter C. , Pevzner Pavel A.
Published: September 2018

Natural products have traditionally been rich sources for drug discovery. In order to clear the road toward the discovery of unknown natural products, biologists need dereplication strategies that identify known ones. Here we report DEREPLICATOR+, an algorithm that improves on the previous approaches for identifying peptidic natural products, and extends them for identification of polyketides, terpenes, benzenoids, alkaloids, flavonoids, and other classes of natural products. We show that DEREPLICATOR+ can search all spectra in the recently launched Global Natural Products Social molecular network and identify an order of magnitude more natural products than previous dereplication efforts. We further demonstrate that DEREPLICATOR+ enables cross-validation of genome-mining and peptidogenomics/glycogenomics results.
Molecular characterization and prospective isolation of human fetal cochlear hair cell progenitors
Authors: Roccio Marta , Perny Michael , Ealy Megan , Widmer Hans Ruedi , Heller Stefan , Senn Pascal
Published: September 2018

Sensory hair cells located in the organ of Corti are essential for cochlear mechanosensation. Their loss is irreversible in humans resulting in permanent hearing loss. The development of therapeutic interventions for hearing loss requires fundamental knowledge about similarities and potential differences between animal models and human development as well as the establishment of human cell based-assays. Here we analyze gene and protein expression of the developing human inner ear in a temporal window spanning from week 8 to 12 post conception, when cochlear hair cells become specified. Utilizing surface markers for the cochlear prosensory domain, namely EPCAM and CD271, we purify postmitotic hair cell progenitors that, when placed in culture in three-dimensional organoids, regain proliferative potential and eventually differentiate to hair cell-like cells in vitro. These results provide a foundation for comparative studies with otic cells generated from human pluripotent stem cells and for establishing novel platforms for drug validation.
Author Correction: Dynamically induced cascading failures in power grids
Authors: Schäfer Benjamin , Witthaut Dirk , Timme Marc , Latora Vito
Published: September 2018

The original version of this Article omitted the following from the Acknowledgements: ‘Finally, we gratefully acknowledge support from the German Science Foundation (DFG) by a grant toward the Cluster of Excellence “Center for Advancing Electronics Dresden” (cfaed)’. This has been corrected in both the PDF and HTML versions of the Article.
Molecular architecture and regulation of BCL10-MALT1 filaments
Authors: Schlauderer Florian , Seeholzer Thomas , Desfosses Ambroise , Gehring Torben , Strauss Mike , Hopfner Karl-Peter , Gutsche Irina , Krappmann Daniel , Lammens Katja
Published: September 2018

The CARD11-BCL10-MALT1 (CBM) complex triggers the adaptive immune response in lymphocytes and lymphoma cells. CARD11/CARMA1 acts as a molecular seed inducing BCL10 filaments, but the integration of MALT1 and the assembly of a functional CBM complex has remained elusive. Using cryo-EM we solved the helical structure of the BCL10-MALT1 filament. The structural model of the filament core solved at 4.9 Å resolution identified the interface between the N-terminal MALT1 DD and the BCL10 caspase recruitment domain. The C-terminal MALT1 Ig and paracaspase domains protrude from this core to orchestrate binding of mediators and substrates at the filament periphery. Mutagenesis studies support the importance of the identified BCL10-MALT1 interface for CBM complex assembly, MALT1 protease activation and NF-κB signaling in Jurkat and primary CD4 T-cells. Collectively, we present a model for the assembly and architecture of the CBM signaling complex and how it functions as a signaling hub in T-lymphocytes.
A High-Speed SSVEP-Based BCI Using Dry EEG Electrodes
Authors: Xing Xiao , Wang Yijun , Pei Weihua , Guo Xuhong , Liu Zhiduo , Wang Fei , Ming Gege , Zhao Hongze , Gui Qiang , Chen Hongda
Published: September 2018

A high-speed steady-state visual evoked potentials (SSVEP)-based brain-computer interface (BCI) system using dry EEG electrodes was demonstrated in this study. The dry electrode was fabricated in our laboratory. It was designed as claw-like structure with a diameter of 14 mm, featuring 8 small fingers of 6 mm length and 2 mm diameter. The structure and elasticity can help the fingers pass through the hair and contact the scalp when the electrode is placed on head. The electrode was capable of recording spontaneous EEG and evoked brain activities such as SSVEP with high signal-to-noise ratio. This study implemented a twelve-class SSVEP-based BCI system with eight electrodes embedded in a headband. Subjects also completed a comfort level questionnaire with the dry electrodes. Using a preprocessing algorithm of filter bank analysis (FBA) and a classification algorithm based on task-related component analysis (TRCA), the average classification accuracy of eleven participants was 93.2% using 1-second-long SSVEPs, leading to an average information transfer rate (ITR) of 92.35 bits/min. All subjects did not report obvious discomfort with the dry electrodes. This result represented the highest communication speed in the dry-electrode based BCI systems. The proposed system could provide a comfortable user experience and a stable control method for developing practical BCIs.
Assembly of Schizosaccharomyces cryophilus chromosomes and their comparative genomic analyses revealed principles of genome evolution of the haploid fission yeasts
Authors: Ács-Szabó Lajos , Papp László Attila , Antunovics Zsuzsa , Sipiczki Matthias , Miklós Ida
Published: September 2018

The fission yeast clade, which has a distinct life history from other yeasts, can provide important clues about evolutionary changes. To reveal these changes the large S. cryophilus supercontigs were assembled into chromosomes using synteny relationships and the conserved pericentromeric, subtelomeric genes. Togetherness of the supercontigs was confirmed by PCR. Investigation of the gene order revealed localisation of the rDNA arrays, more than 300 new conserved orthologues and proved that S. cryophilus supercontigs were mosaics of collinear blocks. PFGE analysis showed that size of the S. cryophilus chromosomes differ from the S. pombe chromosomes. Comparative genomic analyses of the newly assembled chromosomes confirmed that the closest relative of S. cryophilus was S. octosporus not just in sequence similarity but also in a structural way, and revealed that preservation of the conserved regions did not arise from the lower number of chromosomal rearrangements. Translocations were more typical in the closely related species, while the number of inversions increased with the phylogenetic distances. Our data suggested that sites of the chromosomal rearrangements were not random and often associated with repetitive sequences, structural- and nucleotide evolution might correlate. Chromosomal rearrangements of the fission yeasts compared to other lineages were also discussed.
A genetic perspective on the relationship between eudaimonic –and hedonic well-being
Authors: Baselmans B. M. L. , Bartels M.
Published: September 2018

Whether hedonism or eudaimonia are two distinguishable forms of well-being is a topic of ongoing debate. To shed light on the relation between the two, large-scale available molecular genetic data were leveraged to gain more insight into the genetic architecture of the overlap between hedonic and eudaimonic well-being. Hence, we conducted the first genome-wide association studies (GWAS) of eudaimonic well-being (N = ~108 K) and linked it to a GWAS of hedonic well-being (N = ~222 K). We identified the first two genome-wide significant independent loci for eudaimonic well-being and six independent loci for hedonic well-being. Joint analyses revealed a moderate phenotypic correlation (r = 0.53) and a high genetic correlation (rg = 0.78) between eudaimonic and hedonic well-being. This indicates that the genetic etiology of hedonic and eudaimonic well-being is substantially shared, with divergent (environmental) factors contributing to their phenotypic divergence. Loci regulating expression showed significant enrichment in the brain cortex, brain cerebellum, frontal cortex, as well as the cerebellar hemisphere for eudaimonic well-being. No significant enrichment for hedonic well-being is observed, although brain tissues were top ranked. Genetic correlations patterns with a range of positive and negative related phenotypes were largely similar for hedonic –and eudaimonic well-being. Our results reveal a large overlap between the genes that influence hedonism and the genes that influence eudaimonia.
Clinical value of bioelectrical properties of cancerous tissue in advanced epithelial ovarian cancer patients
Authors: Cunnea Paula , Gorgy Tommy , Petkos Konstantinos , Gowers Sally A.N. , Lu Haonan , Morera Cristina , Wu Wen , Lawton Phillip , Nixon Katherine , Leong Chi Leng , Sorbi Flavia , Domenici Lavinia , Paterson Andrew , Curry Ed , Gabra Hani , Boutelle Martyn G. , Drakakis Emmanuel M. , Fotopoulou Christina
Published: September 2018

Currently, there are no valid pre-operatively established biomarkers or algorithms that can accurately predict surgical and clinical outcome for patients with advanced epithelial ovarian cancer (EOC). In this study, we suggest that profiling of tumour parameters such as bioelectrical-potential and metabolites, detectable by electronic sensors, could facilitate the future development of devices to better monitor disease and predict surgical and treatment outcomes. Biopotential was recorded, using a potentiometric measurement system, in ex vivo paired non-cancerous and cancerous omental tissues from advanced stage EOC (n = 36), and lysates collected for metabolite measurement by microdialysis. Consistently different biopotential values were detected in cancerous tissue versus non-cancerous tissue across all cases (p < 0.001). High tumour biopotential levels correlated with advanced tumour stage (p = 0.048) and tumour load, and negatively correlated with stroma. Within our EOC cohort and specifically the high-grade serous subtype, low biopotential levels associated with poorer progression-free survival (p = 0.0179, p = 0.0143 respectively). Changes in biopotential levels significantly correlated with common apoptosis related pathways. Lactate and glucose levels measured in paired tissues showed significantly higher lactate/glucose ratio in tissues with low biopotential (p < 0.01, n = 12). Our study proposes the feasibility of biopotential and metabolite monitoring as a biomarker modality profiling EOC to predict surgical and clinical outcomes.
Lower extremity joint-level responses to pelvis perturbation during human walking
Authors: Vlutters Mark , van Asseldonk Edwin H. F. , van der Kooij Herman
Published: September 2018

The human leg joints play a major role in balance control during walking. They facilitate leg swing, and modulate the ground (re)action forces to prevent a fall. The aim of this study is to provide and explore data on perturbed human walking to gain a better understanding of balance recovery during walking through joint-level control. Healthy walking subjects randomly received anteroposterior and mediolateral pelvis perturbations at the instance of toe-off. The open-source modeling tool OpenSim was used to perform inverse kinematics and inverse dynamics analysis. We found hip joint involvement in accelerating and then halting leg swing, suggesting active preparation for foot placement. Additionally, responses in the stance leg’s ankle and hip joints contribute to balance recovery by decreasing the body’s velocity in the perturbation direction. Modulation also occurs in the plane perpendicular to the perturbation direction, to safeguard balance in both planes. Finally, the recorded muscle activity suggests both spinal and supra-spinal mediated contributions to balance recovery, scaling with perturbation magnitude and direction. The presented data provide a unique and multi-joint insight in the complexity of both frontal and sagittal plane balance control during human walking in terms of joint angles, moments, and power, as well as muscle EMG responses.
The terpenes of leaves, pollen, and nectar of thyme (Thymus vulgaris) inhibit growth of bee disease-associated microbes
Authors: Wiese Natalie , Fischer Juliane , Heidler Jenifer , Lewkowski Oleg , Degenhardt Jörg , Erler Silvio
Published: September 2018

Honey bees are highly prone to infectious diseases, causing colony losses in the worst case. However, they combat diseases through a combination of their innate immune system and social defence behaviours like foraging for health-enhancing plant products (e.g. nectar, pollen and resin). Plant secondary metabolites are not only highly active against bacteria and fungi, they might even enhance selective foraging and feeding decisions in the colony. Here, we tested six major plant terpenes and their corresponding acetates, characterizing six natural Thymus vulgaris chemotypes, for their antimicrobial activity on bacteria associated with European foulbrood. Comparison of the inhibitory activity revealed the highest activity for carvacrol and thymol whereas the acetates mostly did not inhibit bacterial growth. All terpenes and acetates are present in the nectar and pollen of thyme, with pollen containing concentrations higher by several orders of magnitude. The physiological response was tested on forager and freshly emerged bees by means of antennal electroantennography. Both responded much stronger to geraniol and trans-sabinene hydrate compared to carvacrol and thymol. In conclusion, bee-forageable thyme product terpenes (mainly from pollen) yield effective antibiotic activity by reducing the growth of bee disease-associated bacteria and can be detected with different response levels by the honey bees’ antennae. This is a further step forward in understanding the complex pathogen-pollinator-plant network.
OligoPVP: Phenotype-driven analysis of individual genomic information to prioritize oligogenic disease variants
Authors: Boudellioua Imane , Kulmanov Maxat , Schofield Paul N. , Gkoutos Georgios V. , Hoehndorf Robert
Published: September 2018

An increasing number of disorders have been identified for which two or more distinct alleles in two or more genes are required to either cause the disease or to significantly modify its onset, severity or phenotype. It is difficult to discover such interactions using existing approaches. The purpose of our work is to develop and evaluate a system that can identify combinations of alleles underlying digenic and oligogenic diseases in individual whole exome or whole genome sequences. Information that links patient phenotypes to databases of gene–phenotype associations observed in clinical or non-human model organism research can provide useful information and improve variant prioritization for genetic diseases. Additional background knowledge about interactions between genes can be utilized to identify sets of variants in different genes in the same individual which may then contribute to the overall disease phenotype. We have developed OligoPVP, an algorithm that can be used to prioritize causative combinations of variants in digenic and oligogenic diseases, using whole exome or whole genome sequences together with patient phenotypes as input. We demonstrate that OligoPVP has significantly improved performance when compared to state of the art pathogenicity detection methods in the case of digenic diseases. Our results show that OligoPVP can efficiently prioritize sets of variants in digenic diseases using a phenotype-driven approach and identify etiologically important variants in whole genomes. OligoPVP naturally extends to oligogenic disease involving interactions between variants in two or more genes. It can be applied to the identification of multiple interacting candidate variants contributing to phenotype, where the action of modifier genes is suspected from pedigree analysis or failure of traditional causative variant identification.
Genomic assemblies of newly sequenced Trypanosoma cruzi strains reveal new genomic expansion and greater complexity
Authors: Callejas-Hernández Francisco , Rastrojo Alberto , Poveda Cristina , Gironès Núria , Fresno Manuel
Published: September 2018

Chagas disease is a complex illness caused by the protozoan Trypanosoma cruzi displaying highly diverse clinical outcomes. In this sense, the genome sequence elucidation and comparison between strains may lead to disease understanding. Here, two new T. cruzi strains, have been sequenced, Y using Illumina and Bug2148 using PacBio, assembled, analyzed and compared with the T. cruzi annotated genomes available to date. The assembly stats from the new sequences show effective improvement of T. cruzi genome over the actual ones. Such as, the largest contig assembled (1.3 Mb in Bug2148) in de novo attempts and the highest mean assembly coverage (71X for Y). Our analysis reveals a new genomic expansion and greater complexity for those multi-copy gene families related to infection process and disease development, such as Trans-sialidases, Mucins and Mucin Associated Surface Proteins, among others. On one side, we demonstrate that multi-copy gene families are located near telomeric regions of the “chromosome-like” 1.3 Mb contig assembled of Bug2148, where they likely suffer high evolutive pressure. On the other hand, we identified several strain-specific single copy genes that might help to understand the differences in infectivity and physiology among strains. In summary, our results indicate that T. cruzi has a complex genomic architecture that may have promoted its evolution.
Multivariate analysis of short time series in terms of ensembles of correlation matrices
Authors: Vyas Manan , Guhr T. , Seligman T. H.
Published: September 2018

When dealing with non-stationary systems, for which many time series are available, it is common to divide time in epochs, i.e. smaller time intervals and deal with short time series in the hope to have some form of approximate stationarity on that time scale. We can then study time evolution by looking at properties as a function of the epochs. This leads to singular correlation matrices and thus poor statistics. In the present paper, we propose an ensemble technique to deal with a large set of short time series without any consideration of non-stationarity. Given a singular data matrix, we randomly select subsets of time series and thus create an ensemble of non-singular correlation matrices. As the selection possibilities are binomially large, we will obtain good statistics for eigenvalues of correlation matrices, which are typically not independent. Once we defined the ensemble, we analyze its behavior for constant and block-diagonal correlations and compare numerics with analytic results for the corresponding correlated Wishart ensembles. We discuss differences resulting from spurious correlations due to repetitive use of time-series. The usefulness of this technique should extend beyond the stationary case if, on the time scale of the epochs, we have quasi-stationarity at least for most epochs.
Urinary Exosomal and cell-free DNA Detects Somatic Mutation and Copy Number Alteration in Urothelial Carcinoma of Bladder
Authors: Lee Dong Hyeon , Yoon Hana , Park Sanghui , Kim Jeong Seon , Ahn Young-Ho , Kwon Kihwan , Lee Donghwan , Kim Kwang Hyun
Published: September 2018

Urothelial bladder carcinoma (UBC) is characterized by a large number of genetic alterations. DNA from urine is a promising source for liquid biopsy in urological malignancies. We aimed to assess the availability of cell-free DNA (cfDNA) and exosomal DNA (exoDNA) in urine as a source for liquid biopsy in UBC. We included 9 patients who underwent surgery for UBC and performed genomic profiling of tumor samples and matched urinary cfDNA and exoDNA. For mutation analysis, deep sequencing was performed for 9 gene targets and shallow whole genome sequencing (sWGS) was used for the detection of copy number variation (CNV). We analyzed whether genetic alteration in tumor samples was reflected in urinary cfDNA or exoDNA. To measure the similarity between copy number profiles of tumor tissue and urinary DNA, the Pearson’s correlation coefficient was calculated. We found 17 somatic mutations in 6 patients. Of the 17 somatic mutations, 14 and 12 were identified by analysis of cfDNA and exoDNA with AFs of 56.2% and 65.6%, respectively. In CNV analysis using sWGS, although the mean depth was 0.6X, we found amplification of MDM2, ERBB2, CCND1 and CCNE1, and deletion of CDKN2A, PTEN and RB1, all known to be frequently altered in UBC. CNV plots of cfDNA and exoDNA showed a similar pattern with those from the tumor samples. Pearson’s correlation coefficients of tumor vs. cfDNA (0.481) and tumor vs. exoDNA (0.412) were higher than that of tumor vs. normal (0.086). We successfully identified somatic mutations and CNV in UBC using urinary cfDNA and exoDNA. Urinary exoDNA could be another source for liquid biopsy. Also, CNV analysis using sWGS is an alternative strategy for liquid biopsy, providing data from the whole genome at a low cost.
A magnetically recyclable photocatalyst with commendable dye degradation activity at ambient conditions
Authors: Pant Abhilasha , Tanwar Ruchika , Kaur Bikramjit , Mandal Uttam Kumar
Published: September 2018

An efficient, economical, environment-friendly and easy separable catalyst to treat environmental contaminants is an enduring attention in recent years due to their great potential for environmental protection and remediation. Here we have reported the excellent performance of polyaniline activated heterojunctured Ni0.5Zn0.5Fe2O4 catalyst to degrade azo dye in an aqueous solution at ambient condition. The catalyst was prepared via a simple facile polymerization procedure. The physicochemical properties and structure of the synthesized catalyst was confirmed by TGA, PXRD, FTIR, SEM, HRTEM, XPS, EDX, and DRS techniques. The developed catalyst has shown an accelerated degradation ability of an organic pollutant Orange ll Sodium salt azo dye about 100% for the dye concentration of 50 ppm within five minutes at ambient conditions with 1 g/l loading of catalyst. Simple facile synthesis, easy separation by an external magnet, good reusability and high degradation capability of the catalyst may promote the practical applications of the heterostructured catalyst at ambient condition for water remediation. The present study also explored possible credible charge transfer directions and mechanism of photocatalysis supported by trapping experiments and electrochemical impedance spectroscopy (EIS) measurement for the effective improvement of photocatalytic activity and enhancement of the visible light adsorption.
Comparative study of substrate free and amniotic membrane scaffolds for cultivation of limbal epithelial sheet
Authors: Lee Hyun Jung , Nam Sang Min , Choi Sae Kyung , Seo Kyoung Yul , Kim Hyun Ok , Chung So-Hyang
Published: September 2018

Transplantation of cultivated limbal epithelial transplantation has been proven to restore the corneal surface in limbal stem cell deficiency (LSCD). Here we comparatively investigated the optimized conditions and the efficiency of limbal epithelial sheet growth in three media conditions as well as with substrate free (transwell), human amniotic membrane (HAM) sutured onto transwell inserts (HAMTW), and HAM slide scaffold (HAMS). Outcomes evaluated were outgrowth sheet size from limbal explants, expression of stem/progenitor cell markers p63α, ABCG2 and CK15, and colony formation efficiency (CFE). Additionally, limbal epithelial sheets on HAMS were transplanted into corneas of LSCD rabbit models. Limbal epithelial sheets with 5% human AB serum showed the greatest increase in ABCG2 efflux activity (JC1low), p63α expression, and CFE compared in both conditions without HAM and with HAM, respectively. The outgrowth sheet size, cell yield, and Ki67 expression were increased in limbal epithelial sheets on HAMS compared to transwell and HAMTW. ABCG2 efflux activity, p63α and CK15 expressions, and CFE were also increased in limbal epithelial sheets on HAMS as well. In corneas of transplanted rabbit LSCD models, p63α expressions were noted in the basal layers and CK12 expressions were observed in superficial layers. Cultivation of limbal epithelial sheet on HAMS with xeno-free medium enhances the growth and stemness of limbal epithelial sheets.
Heterogeneity of a landscape influences size of home range in a North American cervid
Authors: Walter W. David , Evans Tyler S. , Stainbrook David , Wallingford Bret D. , Rosenberry Christopher S. , Diefenbach Duane R.
Published: September 2018

In the northeastern United States, chronic wasting disease has recently been detected in white-tailed deer (Odocoileus virginianus) populations, and understanding the relationship between landscape configuration and home range may improve disease surveillance and containment efforts. The objectives of our study were to compare size of home range for deer occupying a continuum of forested landscapes and to investigate relationships between size of home range and measures of landscape configuration. We used a movement-based kernel density estimator to estimate home range at five spatial scales among deer across study areas. We developed 7 linear regression models that used measures of the configuration of the forested landscape to explain size of home range. We observed differences in size of home range between sexes among areas that differed based on landscape configuration. We documented size of home range changed with various metrics that identifying connectivity of forested patches. Generally, size of home range increased with an increasing proportion of homogenous forest. Our results suggest that deer in our region occupy a landscape at hierarchically-nested scales that is controlled by the connectivity of the forested landscape across local or broad geographical regions.
Arrowtail RNA for Ligand Display on Ginger Exosome-like Nanovesicles to Systemic Deliver siRNA for Cancer Suppression
Authors: Li Zhefeng , Wang Hongzhi , Yin Hongran , Bennett Chad , Zhang Huang-ge , Guo Peixuan
Published: September 2018

Exosomes have shown increasing potential as delivery vesicles for therapy, but challenges like cost/yield, drug payload, and targeting specificity still exist. Plant derived exosome-like nanoparticles have been reported as a promising substitution and exhibit biocompatibility through oral, intranasal administration; however, systemic delivery of siRNA by exosome-like nanoparticles directly isolated from plants has not been reported. Recently, we reported the control of RNA orientation to decorate human derived exosome with cell targeting ligands for specific delivery of siRNA to tumors. Here, we expand to the application of arrowtail RNA nanoparticles for displaying ligands on ginger derived exosome-like nanovesicles (GDENs) for siRNA delivery and tumor inhibition through IV administration. Cushion ultracentrifugation coupled with equilibrium density gradient ultracentrifugation were used for purifying GDENs that displayed size, density, and morphology similar to human derived exosomes. Folic acid (FA), as a ligand, was displayed on the surface of GDENs for targeted delivery of survivin siRNA to KB cancer models. In vitro gene knockdown efficacy by FA-3WJ/GDENs/siRNA complex was comparable to transfection. We observed inhibition of tumor growth on a xenograft model by intravenous administration, which reveals the potential of GDENs as an economic delivery system for siRNA.
Diagnostic value of plasma tryptophan and symmetric dimethylarginine levels for acute kidney injury among tacrolimus-treated kidney transplant patients by targeted metabolomics analysis
Authors: Zhang Feng , Wang Qinghua , Xia Tianyi , Fu Shangxi , Tao Xia , Wen Yan , Chan Shen’an , Gao Shouhong , Xiong Xiaojuan , Chen Wansheng
Published: September 2018

Few literatures have evaluated the exact role of metabolomics in the identification process of potential biomarkers for acute kidney injury among the patients receiving renal transplantation. On top of this, the success of metabolomics in biomarker translation seems to lie in the robust quantitative method. As such, a single-center retrospective observational study was conducted enrolling 42 patients underwent renal transplantation with/without acute kidney injury, as well as 24 healthy volunteers, in Shanghai Changzheng Hospital. Plasma amino acid metabolic patterns for the participants were investigated by targeted UHPLC-MS/MS metabolic profiling. The most significant changes of the explored metabolites were related to the disturbance of tryptophan metabolism and arginine metabolism. Abnormal circulating tryptophan and symmetric dimethylarginine were identified to be potential biomarkers of acute kidney injury, combination of which showed a higher area under receiver-operator curve value (AUC = 0.901), improved sensitivity (0.889) and specificity (0.831) compared with creatinine only. Overall, these results revealed that targeted metabolomics analysis would be a potent and promising strategy for identification and pre-validation of biomarkers of acute kidney injury in renal transplantation patients.
A novel antimicrobial peptide acting via formyl peptide receptor 2 shows therapeutic effects against rheumatoid arthritis
Authors: Park Yoo Jung , Park Byunghyun , Lee Mingyu , Jeong Yu Sun , Lee Ha Young , Sohn Dong Hyun , Song Jason Jungsik , Lee Joon Ha , Hwang Jae Sam , Bae Yoe-Sik
Published: September 2018

In oriental medicine, centipede Scolopendra subspinipes mutilans has long been used as a remedy for rheumatoid arthritis (RA), a well-known chronic autoimmune disorder. However, the molecular identities of its bioactive components have not yet been extensively investigated. We sought to identify bioactive molecules that control RA with a centipede. A novel antimicrobial peptide (AMP) (scolopendrasin IX) was identified from Scolopendra subspinipes mutilans. Scolopendrasin IX markedly activated mouse neutrophils, by enhancing cytosolic calcium increase, chemotactic cellular migration, and generation of superoxide anion in neutrophils. As a target receptor for scolopendrasin IX, formyl peptide receptor (FPR)2 mediates neutrophil activation induced by the AMP. Furthermore, scolopendrasin IX administration strongly blocked the clinical phenotype of RA in an autoantibody-injected model. Mechanistically, the novel AMP inhibited inflammatory cytokine synthesis from the joints and neutrophil recruitment into the joint area. Collectively, we suggest that scolopendrasin IX is a novel potential therapeutic agent for the control of RA via FPR2.
In Utero Heat Stress Alters the Offspring Epigenome
Authors: Skibiel A. L. , Peñagaricano F. , Amorín R. , Ahmed B. M. , Dahl G. E. , Laporta J.
Published: September 2018

Exposure to intrauterine heat stress during late gestation affects offspring performance into adulthood. However, underlying mechanistic links between thermal insult in fetal life and postnatal outcomes are not completely understood. We examined morphology, DNA methylation, and gene expression of liver and mammary gland for bull calves and heifers that were gestated under maternal conditions of heat stress or cooling (i.e. in utero heat stressedvs. in utero cooled calves). Mammary tissue was harvested from dairy heifers during their first lactation and liver from bull calves at birth. The liver of in utero heat stressed bull calves contained more cells and the mammary glands of in utero heat stressed heifers were comprised of smaller alveoli. We identified more than 1,500 CpG sites differently methylated between maternal treatment groups. These CpGs were associated with approximately 400 genes, which play a role in processes, such asdevelopment,innate immune defense, cell signaling, andtranscription and translation. We also identified over 100 differentially expressed genes in the mammary gland with similar functions. Interestingly, fifty differentially methylated genes were shared by both bull calf liver and heifer mammary gland. Intrauterine heat stress alters the methylation profile of liver and mammary DNA and programs their morphology in postnatal life, which may contribute to the poorer performance of in utero heat stressed calves.
Mutations at the hydrophobic core affect Hal3 trimer stability, reducing its Ppz1 inhibitory capacity but not its PPCDC moonlighting function
Authors: Santolaria Carlos , Velázquez Diego , Strauss Erick , Ariño Joaquín
Published: September 2018

S.cerevisiaeHal3 (ScHal3) is a moonlighting protein that, is in its monomeric state, regulates the Ser/Thr protein phosphatase Ppz1, but also joins ScCab3 (and in some instances the Hal3 paralog Vhs3) to form an unusual heterotrimeric phosphopantothenoylcysteine decarboxylase (PPCDC) enzyme. PPCDC is required for CoA biosynthesis and in most eukaryotes is a homotrimeric complex with three identical catalytic sites at the trimer interfaces. However, inS.cerevisiaethe heterotrimeric arrangement results in a single functional catalytic center. Importantly, the specific structural determinants that direct Hal3’s oligomeric state and those required for Ppz1 inhibition remain largely unknown. We mutagenized residues in the predicted hydrophobic core of ScHal3 (L403–L405) and the plantArabidopsis thalianaHal3 (AtHal3, G115–L117) oligomers and characterized their properties as PPCDC components and, for ScHal3, also as Ppz1 inhibitor. We found that in AtHal3 these changes do not affect trimerization or PPCDC function. Similarly, mutation of ScHal3 L403 has no effect. In contrast, ScHal3 L405E fails to form homotrimers, but retains the capacity to bind Cab3—explaining its ability to rescue ahal3 vhs3synthetically lethal mutation. Remarkably, the L405E mutation decreases Hal3’s ability to interact with and to inhibit Ppz1, confirming the importance of the oligomer/monomer equilibrium in Hal3’s Ppz1 regulating function.
An engineered arginine-rich α-helical antimicrobial peptide exhibits broad-spectrum bactericidal activity against pathogenic bacteria and reduces bacterial infections in mice
Authors: Yang Chin-Hao , Chen Yi-Cheng , Peng Shih-Yi , Tsai Andy Po-Yi , Lee Tony Jer-Fu , Yen Jui-Hung , Liou Je-Wen
Published: September 2018

The increase in the prevalence of antibiotic-resistant bacteria has become a major public health concern. Antimicrobial peptides (AMPs) are emerging as promising candidates addressing this issue. In this study, we designed several AMPs by increasing α-helical contents and positive charges and optimizing hydrophobicity and amphipathicity in the Sushi 1 peptide from horseshoe crabs. A neural network–based bioinformatic prediction tool was used for the first stage evaluations of peptide properties. Among the peptides designed, Sushi-replacement peptide (SRP)-2, an arginine-rich and highly α-helical peptide, showed broad-spectrum bactericidal activity against both Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus and multidrug-resistant Acinetobacter baumannii; nevertheless, it showed little hemolytic and cytotoxic activity against mammalian cells. Atomic force microscopy results indicated that SRP-2 should interact directly with cell membrane components, resulting in bacterial cell death. SRP-2 also neutralized LPS-induced macrophage activation. Moreover, in an intraperitoneal multidrug-resistant A. baumannii infection mouse model, SRP-2 successfully reduced the bacterial number in ascitic fluid and tumor necrosis factor-α production. Our study findings demonstrate that bioinformatic calculations can be powerful tools to help design potent AMPs and that arginine is superior to lysine for providing positive charges for AMPs to exhibit better bactericidal activity and selectivity against bacterial cells.
Paradoxical positive association of serum adiponectin with all-cause mortality based on body composition in Japanese haemodialysis patients
Authors: Machiba Yuri , Inaba Masaaki , Mori Katsuhito , Kurajoh Masafumi , Nishide Kozo , Norimine Kyoko , Yamakawa Tomoyuki , Shoji Shigeichi , Okuno Senji
Published: September 2018

We have previously reported a paradoxical association of serum adiponectin with aortic calcification in haemodialysis patients. Because serum adiponectin is a nutritional marker, we examined the association between serum adiponectin and all-cause mortality based on body composition in haemodialysis patients. The trunk and total body fat were determined. The patients were divided into two groups based on serum adiponectin levels. In Kaplan–Meier analysis, the higher adiponectin group showed higher mortality than the lower adiponectin group. Serum adiponectin showed an inverse correlation with the percentage of truncal fat, suggesting serum adiponectin as an inverse marker for adiposity in haemodialysis patients. However, even after adjustment for other factors, multivariate Cox proportional hazards analysis identified higher serum adiponectin as an independent factor positively associated with higher mortality in haemodialysis patients. This association held true even when the total fat mass was replaced with the percentage of truncal fat, and when total fat mass and percentage of truncal fat were simultaneously included. Thus, we found a paradoxical association of higher serum adiponectin with higher all-cause mortality in Japanese haemodialysis patients, independent of adiposity.
Ecological conditions drive pace-of-life syndromes by shaping relationships between life history, physiology and behaviour in two populations of Eastern mosquitofish
Authors: Polverino Giovanni , Santostefano Francesca , Díaz-Gil Carlos , Mehner Thomas
Published: September 2018

The pace-of-life syndrome (POLS) hypothesis predicts variation in behaviour and physiology among individuals to be associated with variation in life history. Thus, individuals on the “fast” end of POLS continuum grow faster, exhibit higher metabolism, are more risk prone, but die earlier than ones on the “slow” end. Empirical support is nevertheless mixed and modelling studies suggested POLS to vary along selection gradients. Therefore, including ecological variation when testing POLS is vastly needed to determine whether POLS is a fixed construct or the result of specific selection processes. Here, we tested POLS predictions between and within two fish populations originating from different ecological conditions. We observed opposing life histories between populations, characterized by differential investments into growth, fecundity, and functional morphology under identical laboratory conditions. A slower life history was, on average, associated with boldness (latency to emergence from a refuge), high activity (short freezing time and long distance travelled), and increased standard metabolism. Correlation structures among POLS traits were not consistent between populations, with the expression of POLS observed in the slow-growing but not in the fast-growing population. Our results suggest that POLS traits can evolve independently from one another and that their coevolution depends upon specific ecological processes.
Hydrogen sulfide limits neutrophil transmigration, inflammation, and oxidative burst in lipopolysaccharide-induced acute lung injury
Authors: Faller Simone , Hausler Florian , Goeft Andreas , von Itter Marc-Nicolas André , Gyllenram Veronica , Hoetzel Alexander , Spassov Sashko G.
Published: September 2018

Transmigration and activation of neutrophils in the lung reflect key steps in the progression of acute lung injury (ALI). It is known that hydrogen sulfide (H2S) can limit neutrophil activation, but the respective mechanisms remain elusive. Here, we aimed to examine the underlying pathways in pulmonary inflammation. In vivo, C57BL/6N mice received the H2S slow releasing compound GYY4137 prior to lipopolysaccharide (LPS) inhalation. LPS challenge led to pulmonary injury, inflammation, and neutrophil transmigration that were inhibited in response to H2S pretreatment. Moreover, H2S reduced mRNA expression of macrophage inflammatory protein-2 (MIP-2) and its receptor in lung tissue, as well as the accumulation of MIP-2 and interleukin-1β in the alveolar space. In vitro, GYY4137 did not exert toxic effects on Hoxb8 neutrophils, but prevented their transmigration through an endothelial barrier in the presence and absence of MIP-2. In addition, the release of MIP-2 and reactive oxygen species from LPS-stimulated Hoxb8 neutrophils were directly inhibited by H2S. Taken together, we provide first evidence that H2S limits lung neutrophil sequestration upon LPS challenge. As proposed underlying mechanisms, H2S prevents neutrophil transmigration through the inflamed endothelium and directly inhibits pro-inflammatory as well as oxidative signalling in neutrophils. Subsequently, H2S pretreatment ameliorates LPS-induced ALI.
Surfactant/organic solvent free single-step engineering of hybrid graphene-Pt/TiO2 nanostructure: Efficient photocatalytic system for the treatment of wastewater coming from textile industries
Authors: Ghouri Zafar Khan , Elsaid Khaled , Abdala Ahmed , Al-Meer Saeed , Barakat Nasser A. M.
Published: September 2018

In this study, hybrid graphene-Pt/TiO2 nanostructure were synthesized by single-step, inexpensive and surfactant/organic solvent free route; hydrothermal technique. The physicochemical properties of hybrid graphene-Pt/TiO2 nanostructure were carefully analyzed by multiple techniques, including X-ray diffractometer (XRD), X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscope (FESEM) and transmission electron microscope (TEM). The synthesized hybrid nanostructures were utilized as photocatalyst for the degradation of methylene blue (MB) dye under natural environment at average ambient temperature and mean daily global solar radiation, of about 22–25 °C and 374.9 mWh/cm2, respectively. The activity performance indicated considerable degradation of methylene blue (MB) dye and was in the following order Gr (13%), TiO2 (60%) and hybrid graphene-Pt/TiO2 nanostructure (90%) over 21 min under the natural light illumination. The physiochemical characterization suggests that, the tightly attached metalized TiO2 nanoparticles (Pt-TiO2) on the high surface area graphene sheets improved utilization of visible light and increased separation and transfer of photo-excited electron (ē) hole (h+) pairs. Notably, the hybrid graphene-Pt/TiO2 nanostructure exhibited an excellent cyclic stability for methylene blue (MB) dye removal. Finally, the kinetic behavior indicated that the photocatalytic degradation reaction of the dye obeyed the pseudo-first order (Langmuir-Hinshelwood) kinetics model.