bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in clinical trials for stroke by cell therapy: data mining ClinicalTrials.gov and the ICTRP portal site
Authors: Negoro Takaharu , Okura Hanayuki , Maehata Midori , Hayashi Shigekazu , Yoshida Satoru , Takada Nozomi , Matsuyama Akifumi
Published: November 2019

Definitive treatment of stroke constitutes an important thesis of regenerative medicine in the cerebrovascular field. However, to date, no cell therapy products for stroke are yet on the market. In this study, we examined the clinical research trends related to cell therapy products in the stroke field based on data obtained from the ClinicalTrials.gov website and International Clinical Trials Research Platform (ICTRP) portal site. These data do not offer results of clinical trials comprehensively but provide information regarding various attributes of planned clinical trials including work in progress. We selected 78 cell therapy studies related to the field of stroke treatment from ClinicalTrial.gov and ICTRP. These were analyzed according to, e.g., the reporting countries, origin (autologous or allogeneic), of cell used, cell types and source organs, the progress of translational phases, target phase of the disease (acute or chronic stroke), and route of administration. This analysis revealed a trend whereby in the acute phase, mesenchymal stem cells were administered intravenously at a relatively higher dose, whereas in the chronic phase a small number of cells were administered intracranially. Only two randomized controlled Phase III studies with over 100 patients are registered, but none of them has been completed. Thus, cell therapy against stroke appears to constitute a premature area compared with cartilage repair as assessed in our previous report. In addition, tracking by means of the ID number of each trial via PubMed revealed that 44% of clinical studies in this field have corresponding published results, which was also discussed.
Divergence in Transcriptional and Regulatory Responses to Mating in Male and Female Fruitflies
Authors: Fowler Emily K. , Bradley Thomas , Moxon Simon , Chapman Tracey
Published: November 2019

Mating induces extensive physiological, biochemical and behavioural changes in female animals of many taxa. In contrast, the overall phenotypic and transcriptomic consequences of mating for males, hence how they might differ from those of females, are poorly described. Post mating responses in each sex are rapidly initiated, predicting the existence of regulatory mechanisms in addition to transcriptional responses involvingde novogene expression. That post mating responses appear different for each sex also predicts that the genome-wide signatures of mating should show evidence of sex-specific specialisation. In this study, we used high resolution RNA sequencing to provide the first direct comparisons of the transcriptomic responses of male and femaleDrosophilato mating, and the first comparison of mating-responsive miRNAs in both sexes in any species. As predicted, the results revealed the existence of sex- and body part-specific mRNA and miRNA expression profiles. More genes were differentially expressed in the female head-thorax than the abdomen following mating, whereas the opposite was true in males. Indeed, the transcriptional profile of male head-thorax tissue was largely unaffected by mating, and no differentially expressed genes were detected at the most stringent significance threshold. A subset of ribosomal genes in females were differentially expressed in both body parts, but in opposite directions, consistent with the existence of body part-specific resource allocation switching. Novel, mating-responsive miRNAs in each sex were also identified, and a miRNA-mRNA interactions analysis revealed putative targets among mating-responsive genes. We show that the structure of genome-wide responses by each sex to mating is strongly divergent, and provide new insights into how shared genomes can achieve characteristic distinctiveness.
Dairy cows fed a low energy diet before dry-off show signs of hunger despite ad libitum access
Authors: Franchi Guilherme Amorim , Herskin Mette S. , Jensen Margit Bak
Published: November 2019

Drying-off is one important management step in commercial dairy farms and consists of ceasing milk production artificially at a specific point in time, generally 2 months before the next calving. Drying-off typically comprises dietary changes as well as gradual or abrupt changes in daily milking frequency, which may challenge the welfare of high-yielding cows. This study investigated the isolated and combined effects of different feed energy densities (normal lactation diet versus energy-reduced diet, both offered ad libitum) and daily milking frequencies (twice versus once) on the feeding motivation of dairy cows on two separate days prior to dry-off (i.e. the day of last milking) using a push-gate feeder. During both days, cows on the energy-reduced diet pushed more than five times more weight to earn the final feed reward and were nearly ten times faster to feed on the first reward than cows on the normal lactation diet. Illustrating the importance of developing more animal welfare-friendly dry-off management, these results illustrate that cows show signs of hunger prior to dry-off when provided a diet with reduced energy density, although offered for ad libitum intake.
Smart Lenses with Electrically Tuneable Astigmatism
Authors: Ghilardi Michele , Boys Hugh , Török Peter , Busfield James J. C. , Carpi Federico
Published: November 2019

The holy grail of reconfigurable optics for microscopy, machine vision and other imaging technologies is a compact, in-line, low cost, refractive device that could dynamically tune optical aberrations within a range of about 2–5 wavelengths. This paper presents the first electrically reconfigurable, fully elastomeric, tuneable optical lenses with motor-less electrical controllability of astigmatism in the visible range. By applying different voltage combinations to thin dielectric elastomer actuator segments surrounding a soft silicone lens, we show that the latter can be electrically deformed either radially or along selectable directions, so as to tune defocus or astigmatism, up to about 3 wavelengths. By mounting the new lenses on a commercial camera, we demonstrate their functionality, showing how electrically reconfiguring their shape can be used to dynamically control directional blurring while taking images of different targets, so as to emphasize directional features having orthogonal spatial orientations. Results suggest that the possibility of electrically controlling aberrations inherent to these smart lenses holds promise to develop highly versatile new components for adaptive optics.
Global transcriptome analysis of rat hypothalamic arcuate nucleus demonstrates reversal of hypothalamic gliosis following surgically and diet induced weight loss
Authors: Barkholt Pernille , Rigbolt Kristoffer T. G. , Falkenhahn Mechthilde , Hübschle Thomas , Schwahn Uwe , Fernandez-Cachon Maria Luisa , Schmidt Thorsten , Theis Stefan , Hansen Henrik H. , Hay-Schmidt Anders , Pedersen Philip J. , Vrang Niels , Jelsing Jacob
Published: November 2019

The central mechanisms underlying the marked beneficial metabolic effects of bariatric surgery are unclear. Here, we characterized global gene expression in the hypothalamic arcuate nucleus (Arc) in diet-induced obese (DIO) rats following Roux-en-Y gastric bypass (RYGB). 60 days post-RYGB, the Arc was isolated by laser-capture microdissection and global gene expression was assessed by RNA sequencing. RYGB lowered body weight and adiposity as compared to sham-operated DIO rats. Discrete transcriptome changes were observed in the Arc following RYGB, including differential expression of genes associated with inflammation and neuropeptide signaling. RYGB reduced gene expression of glial cell markers, including Gfap, Aif1 and Timp1, confirmed by a lower number of GFAP immunopositive astrocyte profiles in the Arc. Sham-operated weight-matched rats demonstrated a similar glial gene expression signature, suggesting that RYGB and dietary restriction have common effects on hypothalamic gliosis. Considering that RYGB surgery also led to increased orexigenic and decreased anorexigenic gene expression, this may signify increased hunger-associated signaling at the level of the Arc. Hence, induction of counterregulatory molecular mechanisms downstream from the Arc may play an important role in RYGB-induced weight loss.
The Importance of Extensional Rheology in Bolus Control during Swallowing
Authors: Hadde Enrico Karsten , Cichero Julie Ann Yvette , Zhao Shaofeng , Chen Wei , Chen Jianshe
Published: November 2019

Thickened fluids are commonly used in the medical management of individuals who suffer swallowing difficulty (known as dysphagia). Previous studies have shown that the rheological properties of a liquid affect the flow behavior of the bolus in swallowing, such as pharyngeal transit time. While there is no doubt that shear rheology is a highly important factor for bolus flow, it is suspected that extensional properties of a liquid bolus also plays an important role in swallowing, due to elongation of the bolus as it flows through the oropharynx. Our aim in this work was to observe the effect of extensional viscosity on pharyngeal transit time and elongation of the bolus during swallowing. Eight samples of thickened liquid barium that were shear-controlled, but varied in extensional viscosity and two samples that were extensional-controlled, but varied in shear viscosity were swallowed by eight healthy individuals. Data were collected under lateral view of videofluoroscopy swallow study (VFSS); measures of pharyngeal transit time and the ratio of the length to the width of the bolus on the frame of Upper Esophageal Sphincter (UES) opening were taken from the VFSS recordings. It was observed that the pharyngeal transit time generally increases when the fluids are thickened to higher IDDSI consistency. Additionally, higher extensional viscosity fluids reduced the elongation of the bolus during swallowing, thus potentially reducing the risk of post-swallow residue due to bolus breakage. This study confirmed the relevance of the extensional viscosity of the bolus in swallowing.
Design of highly stabilized nanocomposite inks based on biodegradable polymer-matrix and gold nanoparticles for Inkjet Printing
Authors: Begines Belen , Alcudia Ana , Aguilera-Velazquez Raul , Martinez Guillermo , He Yinfeng , Trindade Gustavo F. , Wildman Ricky , Sayagues Maria-Jesus , Jimenez-Ruiz Aila , Prado-Gotor Rafael
Published: November 2019

Nowadays there is a worldwide growing interest in the Inkjet Printing technology owing to its potentially high levels of geometrical complexity, personalization and resolution. There is also social concern about usage, disposal and accumulation of plastic materials. In this work, it is shown that sugar-based biodegradable polyurethane polymers exhibit outstanding properties as polymer-matrix for gold nanoparticles composites. These materials could reach exceptional stabilization levels, and demonstrated potential as novel robust inks for Inkjet based Printing. Furthermore, a physical comparison among different polymers is discussed based on stability and printability experiments to search for the best ink candidate. The University of Seville logo was printed by employing those inks, and the presence of gold was confirmed by ToF-SIMS. This approach has the potential to open new routes and applications for fabrication of enhanced biomedical nanometallic-sensors using stabilized AuNP.
Structural Features of a Conformation-dependent Antigen Epitope on ORFV-B2L Recognized by the 2E4 mAb
Authors: Yu Yongzhong , Zhao Wenbo , Tan Qiang , Zhang Xue , Wang Mengyao , Duan Xuyang , Liu Yuanyuan , Wu Zhijun , Ma Jinzhu , Song Baifen , Zhao Rui , Zhao Kui , Lian Zhengxing , Cui Yudong
Published: November 2019

Previously, we successfully prepared a monoclonal antibody (mAb) named 2E4, that directly recognizes the major envelope protein B2L of the orf virus (ORFV), but there is little information about its epitope. Here, we meticulously mapped the 2E4 epitope through combinatorial programs and identified the functional binding domain and a key amino acid residue. Briefly, the simulated epitope peptide closely resembles84VDVQSKDKDADELR97located at the N-terminus of B2L, strongly suggesting that the epitope is conformationally or spatially structure-dependent. Subsequently, we combined these findings with the results from the antigenicity prediction of B2L to design three truncated fragments of B2L (F1, F2 and F3) selected using 2E4, and only the F1 fragment was found to be eligible for the advanced stage. Alanine-scanning mutagenesis suggested that the D94residue is structurally crucial for the 2E4 epitope. The other participating residues, including K61, E62, and D92, together with D94were responsible for enabling 2E4 binding and served as factors that synergistically enabled binding to the whole 2E4 epitope. In this paper, we describe, for the first time, the architecture of an ORFV conformational epitope, and it is also expected that mAb 2E4 and its epitope can be used for applications relating to orf control.
Work disability patterns before and after incident acute myocardial infarction and subsequent risk of common mental disorders: A Swedish cohort study
Authors: Bokenberger K. , Rahman S. , Wang M. , Vaez M. , Dorner T. E. , Helgesson M. , Ivert T. , Mittendorfer-Rutz E.
Published: November 2019

This study investigated the extent to which work disability patterns including sickness absence and disability pension (SA/DP) before and after acute myocardial infarction (AMI) were associated with subsequent common mental disorders (CMDs) such as depression and anxiety in AMI patients without previous CMD. Total 11,493 patients 26–64 years with incident AMI during 2008–10 were followed up for CMD (measured as antidepressant prescription) through 2013. Four SA/DP trajectory groups during the 3-years pre-AMI and 1-year post-AMI were identified. Hazard ratios (HRs) with 95% confidence intervals for subsequent CMD were estimated in Cox models. Higher pre-AMI SA/DP annual levels (>1–12 months/year) were associated with 40–60% increased CMD rate than the majority (78%) with low increasing levels (increasing up to 1 month/year). Regarding post-AMI findings, constant high (~25–30 days/month) SA/DP levels within the first 3 months was associated with a 76% higher CMD rate, compared to constant low (0 days/month). A gradually decreasing post-AMI SA/DP pattern over a 12-month period suggested protective influences for CMD (HR = 0.80). This is the first study to demonstrate that pre- and post-AMI work disability patterns are associated with subsequent CMD risk in AMI patients. Work disability patterns should be considered as an indicator of AMI prognosis in terms of CMD risk.
A highly specific and sensitive nanoimmunosensor for the diagnosis of neuromyelitis optica spectrum disorders
Authors: de Souza Moraes Ariana , Brum Doralina Guimarães , Ierich Jéssica Cristiane Magalhães , Higa Akemi Martins , Assis Amanda Stefanie Jabur , Miyazaki Celina Massumi , Shimizu Flávio Makoto , Peroni Luís Antonio , Machini M. Teresa , Barreira Amilton Antunes , Ferreira Marystela , Oliveira Osvaldo N. , Leite Fabio Lima
Published: November 2019

A precise diagnosis for neuromyelitis optica spectrum disorders (NMOSD) is crucial to improve patients’ prognostic, which requires highly specific and sensitive tests. The cell-based assay with a sensitivity of 76% and specificity of 100% is the most recommended test to detect anti-aquaporin-4 antibodies (AQP4-Ab). Here, we tested four AQP4 external loop peptides (AQP461–70, AQP4131–140, AQP4141–150, and AQP4201–210) with an atomic force microscopy nanoimmunosensor to develop a diagnostic assay. We obtained the highest reactivity with AQP461–70-nanoimunosensor. This assay was effective in detecting AQP4-Ab in sera of NMOSD patients with 100% specificity (95% CI 63.06–100), determined by the cut-off adhesion force value of 241.3 pN. NMOSD patients were successfully discriminated from a set of healthy volunteers, patients with multiple sclerosis, and AQP4-Ab-negative patients. AQP461–70 sensitivity was 81.25% (95% CI 56.50–99.43), slightly higher than with the CBA method. The results with the AQP461–70-nanoimmunosensor indicate that the differences between NMOSD seropositive and seronegative phenotypes are related to disease-specific epitopes. The absence of AQP4-Ab in sera of NMOSD AQP4-Ab-negative patients may be interpreted by assuming the existence of another potential AQP4 peptide sequence or non-AQP4 antigens as the antibody target.
Discovery of a new Theileria sp. closely related to Theileria annulata in cattle from Sri Lanka
Authors: Sivakumar Thillaiampalam , Fujita Shiori , Tuvshintulga Bumduuren , Kothalawala Hemal , Silva Seekkuge Susil Priyantha , Yokoyama Naoaki
Published: November 2019

Theileria annulatais a haemoprotozoan parasite that causes a cancer-like illness known as tropical theileriosis in cattle. In the course of analyzing the genetic diversity ofT.annulatain Sri Lanka, we observed that merozoite-piroplasm surface antigen (tams1) and surface protein (tasp)-like gene sequences obtained from bovine blood DNA samples, which were PCR-positive forT.annulata, were conserved but shared low identity withT.annulataGenBank sequences. Moreover, the 18S rRNA sequences from the Sri Lankan samples contained ten unique single-nucleotide polymorphisms compared with all knownT.annulatasequences. The cytochrome b (cob) gene sequences isolated from the Sri Lankan samples were highly conserved and shared low identity scores with similarly conservedT.annulatasequences from GenBank. Phylogenetic analysis showed that the Sri Lankantams1-like,tasp-like, 18S rRNA, andcobsequences clustered together and formed sister clades to the common ancestors of all knownT.annulataandTheileria lestoquardisequences. These findings demonstrated that the Sri Lankan cattle were not infected withT.annulatabut with a newTheileriasp. (designated asTheileriasp. Yokoyama) closely related toT.annulata.
Extracellular vesicles from endothelial progenitor cells prevent steroid-induced osteoporosis by suppressing the ferroptotic pathway in mouse osteoblasts based on bioinformatics evidence
Authors: Lu Jinsen , Yang Jiazhao , Zheng Yongshun , Chen Xiaoyu , Fang Shiyuan
Published: November 2019

Abnormal antioxidative capabilities were observed in the pathogenesis of steroid-induced osteoporosis (SIOP). Ferroptosis is a recently discovered type of cell death that is characterized by the overproduction of ROS in response to GPX4 and system Xc− downregulation, which is mediated by an Fe2+ fenton reaction. However, investigations focusing on the relationship between ferroptosis and steroid-induced bone disease remain limited. In the present study, high-dose dexamethasone was used to establish a mouse SIOP model, and extracellular vesicles extracted from bone marrow-derived endothelial progenitor cells (EPC-EVs) alleviated the pathological changes in SIOP via microtomography (micro-CT), with elevations in bone volume (BV), bone surface (BS), trabecular thickness (Tb.Th), and trabecular connectivity density (Conn-D) and decreases in trabecular separation (Tb.sp) and the structure model index (SMI). Histopathological analysis, such as haematoxylin and eosin (HE) and Masson staining, showed that EPC-EVs treatment increased the volume and density of the trabecular bone and bone marrow. RNA sequencing (RNA-seq) and bioinformatics analysis revealed subcellular biological alterations upon steroid and EPC-EVs treatment. Compared with the control, high-dose dexamethasone downregulated GPX4 and system XC−, and the Kyoto Encyclopedia of Genes and Genomes (KEGG)-based gene set enrichment analysis suggested that the ferroptotic pathway was activated. In contrast, combination treatment with EPC-EVs partly reversed the KEGG-mapped changes in the ferroptotic pathway at both the gene and mRNA expression levels. In addition, alterations in ferroptotic marker expression, such as SLC3A2, SLC7A11, and GPX4, were further confirmed by RNA-seq. EPC-EVs were able to reverse dexamethasone treatment-induced alterations in cysteine and several oxidative injury markers, such as malondialdehyde (MDA), glutathione (GSH), and glutathione disulphide (GSSG) (as detected by ELISA). In conclusion, EPC-EVs prevented mouse glucocorticoid-induced osteoporosis by suppressing the ferroptotic pathway in osteoblasts, which may provide a basis for novel therapies for SIOP in humans.
Detection of bovine serum albumin using hybrid TiO2 + graphene oxide based Bio – resistive random access memory device
Authors: Sahu Dwipak Prasad , Jammalamadaka S. Narayana
Published: November 2019

Bio – molecules detection and their quantification with a high precision is essential in modern era of medical diagnostics. In this context, the memristor device which can change its resistance state is a promising technique to sense the bio - molecules. In this work, detection of the Bovine Serum Albumin (BSA) protein using resistive switching memristors based on TiO2 and TiO2 + graphene oxide (GO) is explored. The sensitivity of BSA detection is found to be 4 mg/mL. Both the devices show an excellent bipolar resistive switching with an on/off ratio of 73 and 100 respectively, which essentially demonstrates that the device with GO, distinguishes the resistance states with a high precision. The enhanced performance in the GO inserted device (~ 650 cycles) is attributed to the prevention of multi-dimensional and random growth of conductive paths.
Fitness response variation within and among consumer species can be co-mediated by food quantity and biochemical quality
Authors: Schälicke Svenja , Teubner Johannes , Martin-Creuzburg Dominik , Wacker Alexander
Published: November 2019

In natural heterogeneous environments, the fitness of animals is strongly influenced by the availability and composition of food. Food quantity and biochemical quality constraints may affect individual traits of consumers differently, mediating fitness response variation within and among species. Using a multifactorial experimental approach, we assessed population growth rate, fecundity, and survival of six strains of the two closely related freshwater rotifer speciesBrachionus calyciflorussensu stricto andBrachionus fernandoi. Therefore, rotifers fed low and high concentrations of three algal species differing in their biochemical food quality. Additionally, we explored the potential of a single limiting biochemical nutrient to mediate variations in population growth response. Therefore, rotifers fed a sterol-free alga, which we supplemented with cholesterol-containing liposomes. Co-limitation by food quantity and biochemical food quality resulted in differences in population growth rates among strains, but not between species, although effects on fecundity and survival differed between species. The effect of cholesterol supplementation on population growth was strain-specific but not species-specific. We show that fitness response variations within and among species can be mediated by biochemical food quality. Dietary constraints thus may act as evolutionary drivers on physiological traits of consumers, which may have strong implications for various ecological interactions.
Effects of suspended micro- and nanoscale particles on zooplankton functional diversity of drainage system reservoirs at an open-pit mine
Authors: Goździejewska Anna Maria , Gwoździk Monika , Kulesza Sławomir , Bramowicz Mirosław , Koszałka Jacek
Published: November 2019

Water from mining drainage is turbid because of suspensions. We tested the hypothesis that the chemical composition as well as shape and size of particles in suspensions of natural origin affect the density and functional diversity of zooplankton. The suspensions were analyzed with atomic force microscopy (AFM), energy dispersive X-ray spectroscopy (EDS), scanning electron microscopy (SEM), and optical microscopy. Elements found in the beidellite clays were also identified in the mineral structure of the particles. As the size of the microparticles decreased, the weight proportions of phosphorus, sulfur, and chlorine increased in the suspensions. These conditions facilitated the biomass growth of large and small microphages and raptorials. As the size of the nanoparticles decreased, the shares of silicon, aluminum, iron, and magnesium increased. These conditions inhibited raptorials the most. Ecosystem functionality was the highest with intermediate suspension parameters, which were at the lower range of the microphase and the upper range of the nanophase. The functional traits of zooplankton demonstrate their potential for use as sensitive indicators of disruptions in aquatic ecosystems that are linked with the presence of suspensions, and they facilitate gaining an understanding of the causes and scales of the impact of suspensions.
Degradation Mechanism Detection in Photovoltaic Backsheets by Fully Convolutional Neural Network
Authors: Zhang Binbin , Grant Joydan , Bruckman Laura S. , Wodo Olga , Rai Rahul
Published: November 2019

Materials and devices age with time. Material aging and degradation has important implications for lifetime performance of materials and systems. While consensus exists that materials should be studied and designed for degradation, materials inspection during operation is typically performed manually by technicians. The manual inspection makes studies prone to errors and uncertainties due to human subjectivity. In this work, we focus on automating the process of degradation mechanism detection through the use of a fully convolutional deep neural network architecture (F-CNN). We demonstrate that F-CNN architecture allows for automated inspection of cracks in polymer backsheets from photovoltaic (PV) modules. The developed F-CNN architecture enabled an end-to-end semantic inspection of the PV module backsheets by applying a contracting path of convolutional blocks (encoders) followed by an expansive path of decoding blocks (decoders). First, the hierarchy of contextual features is learned from the input images by encoders. Next, these features are reconstructed to the pixel-level prediction of the input by decoders. The structure of the encoder and the decoder networks are thoroughly investigated for the multi-class pixel-level degradation type prediction for PV module backsheets. The developed F-CNN framework is validated by reporting degradation type prediction accuracy for the pixel level prediction at the level of 92.8%.
Evolutionary origin and functioning of pregenital abdominal outgrowths in a viviparous insect, Arixenia esau
Authors: Tworzydlo Waclaw , Jaglarz Mariusz K. , Pardyak Laura , Bilinska Barbara , Bilinski Szczepan M.
Published: November 2019

Although pregenital abdominal outgrowths occur only rarely in pterygote insects, they are interesting from the evolutionary viewpoint because of their potential homology to wings. Our previous studies of early development of an epizoic dermapteran, Arixenia esau revealed that abdominal segments of the advanced embryos and larvae, growing inside a mother’s uterus, are equipped with paired serial outgrowths. Here, we focus on the origin and functioning of these outgrowths. We demonstrate that they bud from the lateral parts of the abdominal nota, persist till the end of intrauterine development, and remain in contact with the uterus wall. We also show that the bundles of muscle fibers associated with the abdominal outgrowths may facilitate flow of the haemolymph from the outgrowths’ lumen to the larval body cavity. Following completion of the intrauterine development, abdominal outgrowths are shed together with the larval cuticle during the first molt after the larva birth. Using immunohistochemical and biochemical approaches, we demonstrate that the Arixenia abdominal outgrowths represent an evolutionary novelty, presumably related to intrauterine development, and suggest that they are not related to serial wing homologs.
Encephalitis and aseptic meningitis: short-term and long-term outcome, quality of life and neuropsychological functioning
Authors: Quist-Paulsen Else , Ormaasen Vidar , Kran Anne-Marte B. , Dunlop Oona , Ueland Per Magne , Ueland Thor , Eikeland Randi , Aukrust Pål , Nordenmark Tonje H.
Published: November 2019

For those surviving encephalitis, the influence on daily life of patients and their relatives may be substantial. In contrast, the prognosis after aseptic meningitis (ASM) is considered good. In this prospective study in patients with encephalitis (n = 20) and ASM (n = 46), we show that both groups experienced reduced Health Related Quality of Life (HRQoL) at two months after discharge, and that workability was reduced in 37% of the patients with ASM. However, 12 months after discharge no neuropsychological deficits were detected in the ASM group, whereas patients with encephalitis had lower scores on tests of fine motor and psychomotor skills as well as on learning and memory. We also found that for patients with encephalitis, neopterin, as a marker of Th1 cell induced macrophage activation, and a putatively neurotoxic ratio of the kynurenine pathway (KP) measured during the acute phase was associated with lower HRQoL. Our data show that not only encephalitis, but also ASM has substantial short-term influence on HRQoL and workability. For patients with encephalitis we suggest a link between immune activation and activation of the KP during the acute phase with impaired HRQoL.
Evaluating the photocatalytic efficiency of the BiVO4/rGO photocatalyst
Authors: Phanichphant Sukon , Nakaruk Auppatham , Chansaenpak Kantapat , Channei Duangdao
Published: November 2019

The present study reported the preparation of BiVO4 by co-precipitation method. The as-prepared BiVO4 photocatalyst were deposited on rGO sheets to form BiVO4/rGO via the hydrothermal method. The crystalline structure, morphological, optical properties, and surface properties of the synthesized pure BiVO4 compared to BiVO4/rGO composite were studied using X-ray diffraction (XRD), scanning electronmicroscopy (SEM), photoluminescence (PL) spectrophotoscopy, UV–vis spectrophotometer with an integrating sphere, and N2 adsorption-desorption isotherm based on BET theory. The photocatalytic activity of the prepared samples were evaluated by the degradation of MB dye in aqueous medium under visible light irradiation. The result showed that the BiVO4/rGO composite exhibited greater photocatalytic efficiency compared to pure BiVO4 with the photocatalytic degradation efficiency remains stable up to fifth cycle. The improved activity of the BiVO4/rGO composite might be attributed to the high surface area available to adsorb more MB molecules, and efficient charge separation of BiVO4 through π electron on the rGO structure. According to experimental results, the possible photocatalytic mechanism of the BiVO4/rGO composite were determined and the active species hydroxyl radical were reported. Based on photocatalytic activity inhibition in the presence of both h+ (VB) and O2•− (CB) scavengers over the BiVO4 photocatalyst, it can be proposed that the hydroxyl radical generated during the photocatalytic degradation mechanism is mainly responsible by the main active species of h+ and O2•− at VB and CB positions, respectively.
Genome-wide transcriptional profiling for elucidating the effects of brassinosteroids on Glycine max during early vegetative development
Authors: Song Li , Chen Wei , Yao Qiuming , Guo Binhui , Valliyodan Babu , Wang Zhiyong , Nguyen Henry T.
Published: November 2019

Soybean is a widely grown grain legume and one of the most important economic crop species. Brassinosteroids play a crucial role in plant vegetative growth and reproductive development. However, it remains unclear how BRs regulate the developmental processes in soybean, and the molecular mechanism underlying soybean early development is largely unexplored. In this study, we first characterized how soybean early vegetative growth was specifically regulated by the BR biosynthesis inhibitor propiconazole; this characterization included shortened root and shoot lengths, reduced leaf area, and decreased chlorophyll content. In addition, the growth inhibition induced by Pcz could be rescued by exogenous brassinolide application. The RNA-seq technique was employed to investigate the BR regulatory networks during soybean early vegetative development. Identification and analysis of differentially expressed genes indicated that BRs orchestrate a wide range of cellular activities and biological processes in soybean under various BR concentrations. The regulatory networks between BRs and multiple hormones or stress-related pathways were investigated. The results provide a comprehensive view of the physiological functions of BRs and new insights into the molecular mechanisms at the transcriptional level of BR regulation of soybean early development.
Variation of Burkholderia cenocepacia cell wall morphology and mechanical properties during cystic fibrosis lung infection, assessed by atomic force microscopy
Authors: Hassan A. Amir , Vitorino Miguel V. , Robalo Tiago , Rodrigues Mário S. , Sá-Correia Isabel
Published: November 2019

The influence that Burkholderia cenocepacia adaptive evolution during long-term infection in cystic fibrosis (CF) patients has on cell wall morphology and mechanical properties is poorly understood despite their crucial role in cell physiology, persistent infection and pathogenesis. Cell wall morphology and physical properties of three B. cenocepacia isolates collected from a CF patient over a period of 3.5 years were compared using atomic force microscopy (AFM). These serial clonal variants include the first isolate retrieved from the patient and two late isolates obtained after three years of infection and before the patient’s death with cepacia syndrome. A consistent and progressive decrease of cell height and a cell shape evolution during infection, from the typical rods to morphology closer to cocci, were observed. The images of cells grown in biofilms showed an identical cell size reduction pattern. Additionally, the apparent elasticity modulus significantly decreases from the early isolate to the last clonal variant retrieved from the patient but the intermediary highly antibiotic resistant clonal isolate showed the highest elasticity values. Concerning the adhesion of bacteria surface to the AFM tip, the first isolate was found to adhere better than the late isolates whose lipopolysaccharide (LPS) structure loss the O-antigen (OAg) during CF infection. The OAg is known to influence Gram-negative bacteria adhesion and be an important factor in B. cenocepacia adaptation to chronic infection. Results reinforce the concept of the occurrence of phenotypic heterogeneity and adaptive evolution, also at the level of cell size, form, envelope topography and physical properties during long-term infection.
Empirical design of a variant quality control pipeline for whole genome sequencing data using replicate discordance
Authors: Adelson Robert P. , Renton Alan E. , Li Wentian , Barzilai Nir , Atzmon Gil , Goate Alison M. , Davies Peter , Freudenberg-Hua Yun
Published: November 2019

The success of next-generation sequencing depends on the accuracy of variant calls. Few objective protocols exist for QC following variant calling from whole genome sequencing (WGS) data. After applying QC filtering based on Genome Analysis Tool Kit (GATK) best practices, we used genotype discordance of eight samples that were sequenced twice each to evaluate the proportion of potentially inaccurate variant calls. We designed a QC pipeline involving hard filters to improve replicate genotype concordance, which indicates improved accuracy of genotype calls. Our pipeline analyzes the efficacy of each filtering step. We initially applied this strategy to well-characterized variants from the ClinVar database, and subsequently to the full WGS dataset. The genome-wide biallelic pipeline removed 82.11% of discordant and 14.89% of concordant genotypes, and improved the concordance rate from 98.53% to 99.69%. The variant-level read depth filter most improved the genome-wide biallelic concordance rate. We also adapted this pipeline for triallelic sites, given the increasing proportion of multiallelic sites as sample sizes increase. For triallelic sites containing only SNVs, the concordance rate improved from 97.68% to 99.80%. Our QC pipeline removes many potentially false positive calls that pass in GATK, and may inform future WGS studies prior to variant effect analysis.
Evaluating differential nanoparticle accumulation and retention kinetics in a mouse model of traumatic brain injury via Ktrans mapping with MRI
Authors: Miller Hunter A. , Magsam Alexander W. , Tarudji Aria W. , Romanova Svetlana , Weber Laura , Gee Connor C. , Madsen Gary L. , Bronich Tatiana K. , Kievit Forrest M.
Published: November 2019

Traumatic brain injury (TBI) is a leading cause of injury-related death worldwide, yet there are no approved neuroprotective therapies that improve neurological outcome post-injury. Transient opening of the blood-brain barrier following injury provides an opportunity for passive accumulation of intravenously administered nanoparticles through an enhanced permeation and retention-like effect. However, a thorough understanding of physicochemical properties that promote optimal uptake and retention kinetics in TBI is still needed. In this study, we present a robust method for magnetic resonance imaging of nanoparticle uptake and retention kinetics following intravenous injection in a controlled cortical impact mouse model of TBI. Three contrast-enhancing nanoparticles with different hydrodynamic sizes and relaxivity properties were compared. Accumulation and retention were monitored by modelling the permeability coefficient, Ktrans, for each nanoparticle within the reproducible mouse model. Quantification of Ktrans for different nanoparticles allowed for non-invasive, multi-time point assessment of both accumulation and retention kinetics in the injured tissue. Using this method, we found that 80 nm poly(lactic-co-glycolic acid) nanoparticles had maximal Ktrans in a TBI when injected 3 hours post-injury, showing significantly higher accumulation kinetics than the small molecule, Gd-DTPA. This robust method will enable optimization of administration time and nanoparticle physicochemical properties to achieve maximum delivery.
Geothermal sweetspots identified in a volcanic lake integrating bathymetry and fluid chemistry
Authors: Brehme Maren , Giese Ronny , Suherlina Lily , Kamah Yustin
Published: November 2019

We investigate fluid pathways beneath volcanic lakes using bathymetry and geochemical measurements to locate best-possible drilling sites. Highly permeable structures, such as faults, provide fluid channels that are the most suitable access points to the geothermal resource. Accurate mapping of these structures therefore guides the successful targeting of wells. Lakes, rivers or ocean, can hide surface footprints of these permeable structures, such as in our case beneath Lake Linau. High-resolution bathymetry identifies linear and conical discontinuities, which are linked to offshore tectonic structures as confirmed by surrounding outcrops and hot springs. Geochemical measurements document inflow of hot saline acidic water into the lake verifying bathymetry-located highly permeable structures. Integrating onshore well data, our bathymetry and chemical results locates an ideal drilling site into the geothermal reservoir beneath the western shore line of Lake Linau.
Phytoplankton community and algal toxicity at a recurring bloom in Sullivan Bay, Kabetogama Lake, Minnesota, USA
Authors: Christensen Victoria G. , Maki Ryan P. , Stelzer Erin A. , Norland Jack E. , Khan Eakalak
Published: November 2019

Kabetogama Lake in Voyageurs National Park, Minnesota, USA suffers from recurring late summer algal blooms that often contain toxin-producing cyanobacteria. Previous research identified the toxin microcystin in blooms, but we wanted to better understand how the algal and cyanobacterial community changed throughout an open water season and how changes in community structure were related to toxin production. Therefore, we sampled one recurring bloom location throughout the entire open water season. The uniqueness of this study is the absence of urban and agricultural nutrient sources, the remote location, and the collection of samples before any visible blooms were present. Through quantitative polymerase chain reaction (qPCR), we discovered that toxin-forming cyanobacteria were present before visible blooms and toxins not previously detected in this region (anatoxin-a and saxitoxin) were present, indicating that sampling for additional toxins and sampling earlier in the season may be necessary to assess ecosystems and human health risk.
Novel insights into transketolase activation by cofactor binding identifies two native species subpopulations
Authors: Wilkinson Henry C. , Dalby Paul A.
Published: November 2019

Transketolase (TK) cofactor binding has been studied extensively over many years, yet certain mysteries remain, such as a lack of consensus on the cooperativity of thiamine pyrophosphate (TPP) binding into the two active sites, in the presence and absence of the divalent cation, Mg2+. Using a novel fluorescence-based assay, we determined directly the dissociation constants and cooperativity of TPP binding and provide the first comprehensive study over a broad range of cofactor concentrations. We confirmed the high-affinity dissociation constants and revealed a dependence of both the affinity and cooperativity of binding on [Mg2+], which explained the previous lack of consensus. A second, discrete and previously uncharacterised low-affinity TPP binding-site was also observed, and hence indicated the existence of two forms of TK with high- (TKhigh) and low-affinity (TKlow). The relative proportions of each dimer were independent of the monomer-dimer transition, as probed by analytical ultracentrifugation at various [TK]. Mass spectrometry revealed that chemical oxidation of TKlow led to the formation of TKhigh, which was 22-fold more active than TKlow. Finally, we propose a two-species model of transketolase activation that describes the interconversions between apo-/holo-TKhigh and TKlow, and the potential to significantly improve biocatalytic activity by populating only the most active form.
Protective effects of seaweed supplemented diet on antioxidant and immune responses in European seabass (Dicentrarchus labrax) subjected to bacterial infection
Authors: Peixoto Maria J. , Ferraz Renato , Magnoni Leonardo J. , Pereira Rui , Gonçalves José F. , Calduch-Giner Josep , Pérez-Sánchez Jaume , Ozório Rodrigo O. A.
Published: November 2019

European seabass (Dicentrarchus labrax) production is often hampered by bacterial infections such as photobacteriosis caused by Photobacterium damselae subsp. piscicida (Phdp). Since diet can impact fish immunity, this work investigated the effect of dietary supplementation of 5% Gracilaria sp. aqueous extract (GRA) on seabass antioxidant capacity and resistance against Phdp. After infection, mortality was delayed in fish fed GRA, which also revealed increased lysozyme activity levels, as well as decreased lipid peroxidation, suggesting higher antioxidant capacity than in fish fed a control diet. Dietary GRA induced a down-regulation of hepatic stress-responsive heat shock proteins (grp-78, grp-170, grp-94, grp-75), while bacterial infection caused a down-regulation in antioxidant genes (prdx4 and mn-sod). Diet and infection interaction down-regulated the transcription levels of genes associated with oxidative stress response (prdx5 and gpx4) in liver. In head-kidney, GRA led to an up-regulation of genes associated with inflammation (il34, ccr9, cd33) and a down-regulation of genes related to cytokine signalling (mif, il1b, defb, a2m, myd88). Additionally, bacterial infection up-regulated immunoglobulins production (IgMs) and down-regulated the transcription of the antimicrobial peptide leap2 in head kidney. Overall, we found that GRA supplementation modulated seabass resistance to Phdp infection.
Author Correction: Large-scale variation in density of an aquatic ecosystem indicator species
Authors: Sutherland Chris , Fuller Angela K. , Royle J. Andrew , Hare Matthew P. , Madden Sean
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher Correction: Effect of endogenous microbiota on the molecular composition of cloud water: a study by Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS)
Authors: Bianco Angelica , Deguillaume Laurent , Chaumerliac Nadine , Vaïtilingom Mickaël , Wang Miao , Delort Anne-Marie , Bridoux Maxime C.
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Pupil size reflects successful encoding and recall of memory in humans
Authors: Kucewicz Michal T. , Dolezal Jaromir , Kremen Vaclav , Berry Brent M. , Miller Laura R. , Magee Abigail L. , Fabian Vratislav , Worrell Gregory A.
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Redox chemistry of π-extended tellurophenes
Authors: Shida Naoki , Nishiyama Hiroki , Zheng Feng , Ye Shuyang , Seferos Dwight S. , Tomita Ikuyoshi , Inagi Shinsuke
Published: November 2019

In the past decade, the incorporation of tellurophene motifs into organic devices has been a promising strategy for the design of advanced materials. However, fundamental redox behavior of tellurophene-containing materials have never been comprehensively explored. Here, we report unique redox behavior of π-extended tellurophenes. The facile coordination of solvent molecules and/or anions becomes evident, in addition to the attachment of nucleophilic halides. This indicates that the tellurium center in oxidized 2,5-diphenyltellurophene is highly electron-deficient and easily yields coordinated structures. This coordination appears to trap the positive charge on the tellurium center rather than delocalizing it over the π-system. When no coordinating counter ion is present, however, oxidation appears to be delocalized over the entire π-system. Additionally, by using more delocalized structures, we show that coordination and charge-delocalization can co-exist. These results provide important insights to understand the properties of tellurophene-containing molecules and materials with extended π-systems.
Reliable, high-quality suppression of NMR signals arising from water and macromolecules: application to bio-fluid analysis
Authors: Aguilar Juan A. , Cassani Julia , Probert Fay , Palace Jacqueline , Claridge Tim D. W. , Botana Adolfo , Kenwright Alan M.
Published: November 2019

This paper proposes a family of pulse sequences (the WASTED family) that improves the capabilities of the presat-CPMG pulse sequence traditionally used to suppress signals from water and macromolecules.
A surface-enhanced electrochemiluminescence sensor based on Au-SiO2 core–shell nanocomposites doped with Ru(bpy)32+ for the ultrasensitive detection of prostate-specific antigen in human serum
Authors: Wang Daifang , Zhou Jin , Guo Longhua , Qiu Bin , Lin Zhenyu
Published: November 2019

This study reports a surface-enhanced electrochemiluminescence (SEECL) sensor for the ultrasensitive detection of prostate-specific antigen (PSA) in human serum.
Mass spectrometry imaging (MSI) of fresh bones using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI)
Authors: Khodjaniyazova Sitora , Hanne Nicholas J. , Cole Jacqueline H. , Muddiman David C.
Published: November 2019

Direct analysis and IR-MALDESI mass spectrometry imaging of fresh mouse bones that underwent no chemical treatments other than flash-freezing.
A kinetics study on intercalation pseudocapacitance of layered TiS2 in K-ion batteries
Authors: Zhang Rongyu , Yang Xu , Xu Shifeng , Xu Dan , Du Fei
Published: November 2019

The diffusion behavior of K+ in layered TiS2 shows character of both capacitor and battery, which proved to be an intercalation pseudocapacitance by kinetics study.