bluuebunny/crossref_metadata_2025 huggingface dataset:
Circular RNAs are temporospatially regulated throughout development and ageing in the rat
Authors: Mahmoudi E. , Cairns M. J.
Published: February 2019

Circular RNAs (circRNAs) are covalently closed structural isoforms of linear mRNA which have been observed across a broad range of species and tissues. Here, we provide a comprehensive circRNAs expression catalogue for the rat including 8 organs of both sexes during 4 developmental stages using a public RNAseq dataset. These analyses revealed thousands of circular RNA species, many expressed in an organ-specific manner along with their host genes which were enriched with tissue-specific biological functions. A large number of circRNAs also displayed a developmental-dependent expression pattern and are accumulated during ageing. CircRNAs also displayed some sexually dimorphic expression, with gender associated differences observed in various tissues and developmental stages. These observations suggest that circRNAs are dynamically expressed in a spatial-, temporal- and gender-specific manner in mammals, and may have important biological function in differentiation, development and aging.
The clinical parameters for the diagnosis of hepatitis B virus related acute-on-chronic liver failure with sepsis
Authors: Xue Ran , Zhu Yueke , Liu Hui , Meng Qinghua
Published: February 2019

It is still unknown that whether sepsis with hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) fit into the conventional diagnostic criteria of sepsis. Our aim was to investigate the potential clinical parameters for the diagnosis of HBV-ACLF with sepsis. A retrospective study was conducted in 43 patients with HBV-ACLF and sepsis who underwent orthotopic liver transplantation. All patients were divided into three groups according to the pathological results and laboratory test results. Immunohistochemistry (IHC) staining, hematoxylin-eosin (HE) staining and Gordon Sweet’s reticulin staining were performed in this study. Alanine aminotransferase (ALT), aspartale aminotransferase (AST), total bilirubin (TBiL), cholinesterase (CHE), albumin (ALB), prothrombin activity (PTA), blood routine examination were detected. The results being chosen at admission and before transplantation were analyzed. TBiL had a significant increase (563.5 ± 191.8 umol/L vs. 383.9 ± 157.6 umol/L, 438.3 ± 154.7 umol/L, P = 0.031) and ALT significantly decreased (81.6 ± 66.4 U/L, 754.5 ± 1084.7 U/L, 120.6 ± 102.5 U/L, P = 0.005) in sepsis group before liver transplantation. When sepsis appeared in patients with HBV-ACLF, the ratio of PLT to WBC count before liver transplantation was much lower than it at admission (4.6 ± 2.0 vs. 16.1 ± 7.2, P = 0.000). In conclusion, the clinical parameters of sepsis in patients with HBV-ACLF should be reset. The ratio of PLT/WBC and (WBCBLT/WBCAA)/ (PLTBLT/PLTAA) could remind us the occurring of sepsis in patients with HBV-ACLF.
Affective certainty and congruency of touch modulate the experience of the rubber hand illusion
Authors: Filippetti Maria Laura , Kirsch Louise P. , Crucianelli Laura , Fotopoulou Aikaterini
Published: February 2019

Our sense of body ownership relies on integrating different sensations according to their temporal and spatial congruency. Nevertheless, there is ongoing controversy about the role of affective congruency during multisensory integration, i.e. whether the stimuli to be perceived by the different sensory channels are congruent or incongruent in terms of their affective quality. In the present study, we applied a widely used multisensory integration paradigm, the Rubber Hand Illusion, to investigate the role of affective, top-down aspects of sensory congruency between visual and tactile modalities in the sense of body ownership. In Experiment 1 (N = 36), we touched participants with either soft or rough fabrics in their unseen hand, while they watched a rubber hand been touched synchronously with the same fabric or with a ‘hidden’ fabric of ‘uncertain roughness’. In Experiment 2 (N = 50), we used the same paradigm as in Experiment 1, but replaced the ‘uncertainty’ condition with an ‘incongruent’ one, in which participants saw the rubber hand being touched with a fabric of incongruent roughness and hence opposite valence. We found that certainty (Experiment 1) and congruency (Experiment 2) between the felt and vicariously perceived tactile affectivity led to higher subjective embodiment compared to uncertainty and incongruency, respectively, irrespective of any valence effect. Our results suggest that congruency in the affective top-down aspects of sensory stimulation is important to the multisensory integration process leading to embodiment, over and above temporal and spatial properties.
Fine scale spatial variability in the influence of environmental cycles on the occurrence of dolphins at coastal sites
Authors: Fernandez-Betelu Oihane , Graham Isla M. , Cornulier Thomas , Thompson Paul M.
Published: February 2019

Environmental cycles often influence the presence of animals, creating patterns at different temporal scales, which may mean that their effects overlap and/or interact. Interactions between diel and seasonal cycles have been reported to influence fish behaviour but little is known about such interactions in marine top predators. Here, we studied the combined effect of seasonal, tidal and diel cycles on the occurrence of bottlenose dolphins (Tursiops truncatus) within a Marine Protected Area in Scotland. Our analyses were based on echolocation detections from passive acoustic devices (CPODs) deployed at three coastal sites between 2010 and 2016. We described patterns of dolphins’ occurrence using circular statistics and then used generalised additive mixed models to explore the relative importance of each cycle and any interactions between them. We found site-specific cyclical patterns of presence that remained constant across years. There was a highly significant interaction between seasonal and diel cycles at two sites around deep channels, where occurrence was diurnal in summer but became nocturnal in autumn. The study demonstrates the highly plastic behaviour of bottlenose dolphins and shows a previously unreported behaviour that has management implications for this and other marine protected areas.
Application of metabolomics and molecular networking in investigating the chemical profile and antitrypanosomal activity of British bluebells (Hyacinthoides non-scripta)
Authors: Raheem Dotsha J. , Tawfike Ahmed F. , Abdelmohsen Usama R. , Edrada-Ebel RuAngelie , Fitzsimmons-Thoss Vera
Published: February 2019

Bulb, leaf, scape and flower samples of British bluebells (Hyacinthoides non-scripta) were collected regularly for one growth period. Methanolic extracts of freeze-dried and ground samples showed antitrypanosomal activity, giving more than 50% inhibition, for 20 out of 41 samples. High-resolution mass spectrometry was used in the dereplication of the methanolic extracts of the different plant parts. The results revealed differences in the chemical profile with bulb samples being distinctly different from all aerial parts. High molecular weight metabolites were more abundant in the flowers, shoots and leaves compared to smaller molecular weight ones in the bulbs. The anti-trypanosomal activity of the extracts was linked to the accumulation of high molecular weight compounds, which were matched with saponin glycosides, while triterpenoids and steroids occurred in the inactive extracts. Dereplication studies were employed to identify the significant metabolites via chemotaxonomic filtration and considering their previously reported bioactivities. Molecular networking was implemented to look for similarities in fragmentation patterns between the isolated saponin glycoside at m/z 1445.64 [M + formic-H]− equivalent to C64H104O33 and the putatively found active metabolite at m/z 1283.58 [M + formic-H]− corresponding to scillanoside L-1. A combination of metabolomics and bioactivity-guided approaches resulted in the isolation of a norlanostane-type saponin glycoside with antitrypanosomal activity of 98.9% inhibition at 20 µM.
Broadband circular polarizer for randomly polarized light in few-layer metasurface
Authors: Mun Sang-Eun , Hong Jongwoo , Yun Jeong-Geun , Lee Byoungho
Published: February 2019

Controlling the polarization state of light has been a significant issue for various integrated optical devices such as optical imaging, sensors, and communications. Recent advances in metamaterials enable the optical elements for controlling light to be miniaturized and to have various multi-functions in subwavelength scale. However, a conventional approach of a circular polarizer has an inherent limitation to eliminate the unwanted circular polarization, which means that the efficiency varies significantly depending on the polarization state of incident light. Here, we propose a novel concept of a circular polarizer by combining two functions of transmission and conversion for orthogonal circular polarizations with a total thickness of 440 nm. The proposed three-layer metasurface composed of rotating silver nanorods transmits the left-handed circularly polarized (LCP) light with maintaining its own polarization state, whereas the right-handed circularly polarized (RCP) light is converted into LCP light. Regardless of the polarization state of incoming light, the polarization of light in the last medium is LCP state in the broadband operating wavelength range from 800 nm to 1100 nm. The converted RCP and the transmitted LCP have efficiencies of up to 48.5% and 42.3%, respectively. Thus the proposed metasurface serves as a stable circular polarizer for a randomly polarized light. In addition, high-efficiency asymmetric transmission of about 0.47 is achieved at the same time due to the conversion characteristic of RCP component. The proposed metasurface has the significance as an ultra-thin optical element applicable to optical switching, sensors, and communications in unidirectional channel as well as a broadband circular polarizer for randomly polarized light.
An automated microliter-scale high-throughput screening system (MSHTS) for real-time monitoring of protein aggregation using quantum-dot nanoprobes
Authors: Sasaki Rina , Tainaka Reina , Ando Yuichi , Hashi Yurika , Deepak Hadya V. , Suga Yoshiko , Murai Yuta , Anetai Masaki , Monde Kenji , Ohta Kiminori , Ito Ikuko , Kikuchi Haruhisa , Oshima Yoshiteru , Endo Yasuyuki , Nakao Hitomi , Sakono Masafumi , Uwai Koji , Tokuraku Kiyotaka
Published: February 2019

Protein aggregation is the principal component of numerous protein misfolding pathologies termed proteinopathies, such as Alzheimer’s disease, Parkinson’s disease, prion disease, and AA amyloidosis with unmet treatment needs. Protein aggregation inhibitors have great potential for the prevention and treatment of proteinopathies. Here we report the development of an automated real-time microliter-scale high throughput screening (MSHTS) system for amyloid aggregation inhibitors using quantum-dot nanoprobes. Screening 504 crude extracts and 134 low molecular weight aromatic compounds revealed the relationship of amyloid-β (Aβ) aggregation inhibitory activities of plant extracts using a plant-based classification. Within the eudicots, rosids, Geraniales and Myrtales showed higher activity. Screening low molecular weight aromatic compounds demonstrated that the structure of tropolone endows it with potential Aβ aggregation inhibitory activity. The activity of the most active tropolone derivative was higher than that of rosmarinic acid. MSHTS also identified three chaperone molecules as tau aggregation inhibitors. These results demonstrate that our automated MSHTS system is a novel and robust tool that can be adapted to a wide range of compounds and aggregation-prone polypeptides.
Changes in microbiome diversity following beta-lactam antibiotic treatment are associated with therapeutic versus subtherapeutic antibiotic exposure in cystic fibrosis
Authors: Hahn Andrea , Fanous Hani , Jensen Caroline , Chaney Hollis , Sami Iman , Perez Geovanny F. , Koumbourlis Anastassios C. , Louie Stan , Bost James E. , van den Anker John N. , Freishtat Robert J. , Zemanick Edith T. , Crandall Keith A.
Published: February 2019

In persons with cystic fibrosis (CF), decreased airway microbial diversity is associated with lower lung function. Conflicting data exist on the impact of short-term antibiotics for treatment of acute pulmonary exacerbations. However, whether differences in antibiotic exposure impacts airway microbiome changes has not been studied. We hypothesized that subtherapeutic beta-lactam antibiotic exposure, determined by the pharmacokinetics and pharmacodynamics (PK/PD) after intravenous (IV) antibiotic administration, would be associated with different patterns of changes in CF airway microbial diversity. Eligible children were enrolled when well; study assessments were performed around the time of pulmonary exacerbation. Plasma drug concentrations and bacterial minimum inhibitory concentrations (MICs) were used to determine therapeutic versus subtherapeutic beta-lactam antibiotic exposure. Respiratory samples were collected from children, and extracted bacterial DNA was amplified for the V4 region of the 16S rRNA gene. Twenty children experienced 31 APEs during the study; 45% (n = 14) of antibiotic courses were deemed therapeutic. Those in the therapeutic group had more significant decreases in alpha diversity at end of treatment and post-recovery compared to baseline than those in the subtherapeutic group. Therapeutic and subtherapeutic beta-lactam use is associated with different patterns of changes in CF airway microbial diversity following antibiotic administration.
An intact model for quantifying functional selectivity
Authors: Zhu Xiao , Finlay David B. , Glass Michelle , Duffull Stephen B.
Published: February 2019

A ligand that acts on a target receptor to activate particular multiple signalling pathways with activity that is distinct from other ligands is termed ligand bias. Quantification of ligand bias is based on applying the operational model to each pathway separately and subsequent calculation of the ligand bias metric (ΔΔlogR). This approach implies independence among different pathways and causes propagation of error in the calculation. Here, we propose a semi-mechanism-based model which allows for receptor selectivity across all the pathways simultaneously (termed the ‘intact operational model’). The power of the intact model for detecting ligand bias was evaluated via stochastic simulation estimation studies. It was also applied to two examples: (1) opposing effects of Gi/Gs signalling of α2-adrenergic receptors and (2) simultaneous measurement of arachidonic acid release and inositol phosphate accumulation following 5-HT2C receptor activation. The intact operational model demonstrated greater power to detect ligand bias in the simulation. In the applications, it provided better precision of estimation and identified biased ligands that were missed by analysis of traditional methods. Issues identified in both examples might lead to different interpretations of the data. The intact operational model may elucidate greater understanding of the underlying mechanisms of functional selectivity.
Chlorin e6-Coated Superparamagnetic Iron Oxide Nanoparticle (SPION) Nanoclusters as a Theranostic Agent for Dual-Mode Imaging and Photodynamic Therapy
Authors: Amirshaghaghi Ahmad , Yan Lesan , Miller Joann , Daniel Yonathan , Stein Joel M. , Busch Theresa M. , Cheng Zhiliang , Tsourkas Andrew
Published: February 2019

Photodynamic therapy (PDT) is an approved modality for the treatment of various types of maligancies and diseased states. However, most of the available photosensitizers (PS) are highly hydrophobic, which limits their solubility and dispersion in biological fluids and can lead to self-quenching and sub-optimal therapeutic efficacy. In this study, chlorin e6 (Ce6)-coated superparamagnetic iron oxide nanoparticle (SPION) nanoclusters (Ce6-SCs) were prepared via an oil-in-water emulsion. The physical-chemical properties of the Ce6-SCs were systematically evaluated. Dual-mode imaging and PDT was subsequently performed in tumor-bearing mice. Chlorin e6 is capable of solubilizing hydrophobic SPION into stable, water-soluble nanoclusters without the use of any additional amphiphiles or carriers. The method is reproducible and the Ce6-SCs are highly stable under physiological conditions. The Ce6-SCs have an average diameter of 92 nm and low polydispersity (average PDI < 0.2). Encapsulation efficiency of both Ce6 and SPION is ≈100%, and the total Ce6 payload can be as high as 56% of the total weight (Ce6 + Fe). The Ce6-SCs localize within tumors via enhanced permeability and retention and are detectable by magnetic resonance (MR) and optical imaging. With PDT, Ce6-SCs demonstrate high singlet oxygen generation and produce a significant delay in tumor growth in mice.
Home-based Aerobic Exercise and Resistance Training in Peritoneal Dialysis Patients: A Randomized Controlled Trial
Authors: Uchiyama Kiyotaka , Washida Naoki , Morimoto Kohkichi , Muraoka Kaori , Kasai Takahiro , Yamaki Kentaro , Miyashita Kazutoshi , Wakino Shu , Itoh Hiroshi
Published: February 2019

Potential effects of aerobic and resistance training in peritoneal dialysis (PD) patients have been partially elucidated. We investigated effects of a home-based exercise program on physical functioning and health-related quality of life (HRQOL) in PD patients. Patients were randomly assigned to exercise (n = 24) and usual care (n = 23) groups. The exercise patients performed aerobic exercise thrice weekly and resistance training twice weekly at home for 12 weeks. The usual care patients received no specific intervention. The distance in incremental shuttle walking test significantly improved in the exercise group compared with the usual care group (P = 0.02). Among the HRQOL subscales assessed using the Kidney Disease Quality of Life-Short Form questionnaire, kidney disease component summary (P = 0.03), physical role functioning (P = 0.01), emotional role functioning (P < 0.01), and role/social component summary (P < 0.01) significantly improved in the exercise group. Moreover, serum albumin was significantly maintained in the exercise group (P = 0.03). There were no reported adverse events associated with the intervention. To our knowledge, this is the first randomized controlled trial to indicate the beneficial effects of a 12-week home-based exercise program exclusively in PD patients.
Sodium-activated potassium channels shape peripheral auditory function and activity of the primary auditory neurons in mice
Authors: Reijntjes Daniël O. J. , Lee Jeong Han , Park Seojin , Schubert Nick M. A. , van Tuinen Marcel , Vijayakumar Sarath , Jones Timothy A. , Jones Sherri M. , Gratton Michael Anne , Xia Xiao-Ming , Yamoah Ebenezer N. , Pyott Sonja J.
Published: February 2019

Potassium (K+) channels shape the response properties of neurons. Although enormous progress has been made to characterize K+ channels in the primary auditory neurons, the molecular identities of many of these channels and their contributions to hearing in vivo remain unknown. Using a combination of RNA sequencing and single molecule fluorescent in situ hybridization, we localized expression of transcripts encoding the sodium-activated potassium channels KNa1.1 (SLO2.2/Slack) and KNa1.2 (SLO2.1/Slick) to the primary auditory neurons (spiral ganglion neurons, SGNs). To examine the contribution of these channels to function of the SGNs in vivo, we measured auditory brainstem responses in KNa1.1/1.2 double knockout (DKO) mice. Although auditory brainstem response (wave I) thresholds were not altered, the amplitudes of suprathreshold responses were reduced in DKO mice. This reduction in amplitude occurred despite normal numbers and molecular architecture of the SGNs and their synapses with the inner hair cells. Patch clamp electrophysiology of SGNs isolated from DKO mice displayed altered membrane properties, including reduced action potential thresholds and amplitudes. These findings show that KNa1 channel activity is essential for normal cochlear function and suggest that early forms of hearing loss may result from physiological changes in the activity of the primary auditory neurons.
Imatinib treatments have long-term impact on placentation and embryo survival
Authors: Salem Wael , Li Kailiang , Krapp Christopher , Ingles Sue Ann , Bartolomei Marisa S. , Chung Karine , Paulson Richard J. , Nowak Romana A. , McGinnis Lynda K.
Published: February 2019

Imatinib is an oral chemotherapeutic used primarily to treat chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST). The potential effects of cancer treatments on a patient’s future fertility  are a major concern affecting the quality of life for cancer survivors. The effects of imatinib on future fertility are unknown. It is teratogenic. Therefore, patients are advised to stop treatment before pregnancy. Unfortunately, CML and GIST have high rates of recurrence in the absence of the drug, therefore halting imatinib during pregnancy endangers the mother. Possible long-term (post-treatment) effects of imatinib on reproduction have not been studied. We have used a mouse model to examine the effects of imatinib on the placenta and implantation after long-term imatinib exposure. We found significant changes in epigenetic markers of key imprinted genes in the placenta. There was a significant decrease in the labyrinth zone and vasculature of the placenta, which could impact fetal growth later in pregnancy. These effects on placental growth occurred even when imatinib was stopped prior to pregnancy. These results indicate potential long-term effects of imatinib on pregnancy and implantation. A prolonged wash-out period prior to pregnancy or extra monitoring for possible placental insufficiency may be advisable.
Choosing a laser for laser speckle contrast imaging
Authors: Postnov Dmitry D. , Cheng Xiaojun , Erdener Sefik Evren , Boas David A.
Published: February 2019

The use of laser speckle contrast imaging (LSCI) has expanded rapidly for characterizing the motion of scattering particles. Speckle contrast is related to the dynamics of the scattering particles via a temporal autocorrelation function, but the quality of various elements of the imaging system can adversely affect the quality of the signal recorded by LSCI. While it is known that the laser coherence affects the speckle contrast, it is generally neglected in in vivo LSCI studies and was not thoroughly addressed in a practical matter. In this work, we address the question of how the spectral width of the light source affects the speckle contrast both experimentally and through numerical simulations. We show that commonly used semiconductor laser diodes have a larger than desired spectral width that results in a significantly reduced speckle contrast compared with ideal narrow band lasers. This results in a reduced signal-to-noise ratio for estimating changes in the motion of scattering particles. We suggest using a volume holographic grating stabilized laser diode or other diodes that have a spectrum of emitted light narrower than ≈1 nm to improve the speckle contrast.
Transcriptomic profiles of retinal ganglion cells are defined by the magnitude of intraocular pressure elevation in adult mice
Authors: Park Yong H. , Snook Joshua D. , Ostrin Edwin J. , Kim Sangbae , Chen Rui , Frankfort Benjamin J.
Published: February 2019

Elevated intraocular pressure (IOP) is the major risk factor for glaucoma, a sight threatening disease of retinal ganglion cells (RGCs) and their axons. Despite the central importance of IOP, details of the impact of IOP elevation on RGC gene expression remain elusive. We developed a 4-step immunopanning protocol to extract adult mouse RGCs with high fidelity and used it to isolate RGCs from wild type mice exposed to 2 weeks of IOP elevation generated by the microbead model. IOP was elevated to 2 distinct levels which were defined as Mild (IOP increase >1 mmHg and <4 mmHg) and Moderate (IOP increase ≥4 mmHg). RNA sequencing was used to compare the transcriptional environment at each IOP level. Differentially expressed genes were markedly different between the 2 groups, and pathway analysis revealed frequently opposed responses between the IOP levels. These results suggest that the magnitude of IOP elevation has a critical impact on RGC transcriptional changes. Furthermore, it is possible that IOP-based set points exist within RGCs to impact the direction of transcriptional change. It is possible that this improved understanding of changes in RGC gene expression can ultimately lead to novel diagnostics and therapeutics for glaucoma.
Archean crust and metallogenic zones in the Amazonian Craton sensed by satellite gravity data
Authors: Motta J. G. , SOUZA FILHO C. R. de , Carranza E. J. M. , Braitenberg C.
Published: February 2019

The formation of ore deposits has been extensively studied from a shallow crust perspective. In contrast, the association of mineral systems with deep crustal structure of their host terranes remains relatively undisclosed, and there is evidence that processes throughout the lithosphere are coupled for their evolution. The current debate centers on the control of the regional deep crustal architecture in focusing and transferring fluids between geochemical reservoirs. Defining such architecture is not unequivocal, and involves combining indirect information in order to constrain its physical properties and evolution. Herein, based on evidence from satellite gravity, constrained by airborne potential field data (gravity and magnetics), we provide an example on how the lithosphere geometry controlled the location of copper and gold systems in the world-class Archean Carajás Mineral Province (Amazonian Craton, South America). Validation with information from passive seismic (wave speeds, crustal and lithospheric thickness) and geochronologic data (model, crystallization ages, and Neodymium isotope ratio determinations) portrays a significantly enlarged, poly-phase, Archean crust that exerted geometric control on the location of the mineral systems within and adjacent to the province during tectonic quiescence and switches. This new geologic scenario impacts the understanding of the Amazonian Craton. Synergy between multi-source data, as experimented here, can provide robust models efficiently and, conceivably, help to unveil similar terrains elsewhere.
Effects of a Saccharomyces cerevisiae fermentation product on liver abscesses, fecal microbiome, and resistome in feedlot cattle raised without antibiotics
Authors: Huebner Katherine L. , Martin Jennifer N. , Weissend Carla J. , Holzer Katlyn L. , Parker Jennifer K. , Lakin Steven M. , Doster Enrique , Weinroth Margaret D. , Abdo Zaid , Woerner Dale R. , Metcalf Jessica L. , Geornaras Ifigenia , Bryant Tony C. , Morley Paul S. , Belk Keith E.
Published: February 2019

Liver abscesses in feedlot cattle form secondary to high concentrate feeds and rumen acidosis. Antimicrobial drugs are commonly included in cattle feed for prevention of liver abscesses, but concerns regarding antimicrobial resistance have increased the need for alternative treatments. A block randomized clinical trial was conducted to evaluate the effects of aSaccharomyces cerevisiaefermentation product (SCFP) on liver abscesses, fecal microbiomes, and resistomes in cattle raised without antibiotics in a Colorado feedlot. At enrollment, steers (n = 4,689) were sorted, by weight and source, into 2 pens comprising a block (n = 14 blocks, 28 pens); pens were randomly allocated to either the control group or the treatment group, where the diet was supplemented with SCFP. Prior to harvest, composited feces were collected for characterization of the microbiome and resistome using 16S rRNA gene and shotgun sequencing. At harvest, liver abscess severity was quantified for individual cattle. There were no statistical differences detected by treatment group in animal health, liver abscess prevalence or severity. Organisms classified to phylum, Elusimicrobia were more abundant in the feces of treated cattle, however, there were no differences in the resistome by treatment group. Both microbiome and resistome varied significantly among enrollment blocks.
Basal forebrain somatostatin cells differentially regulate local gamma oscillations and functionally segregate motor and cognitive circuits
Authors: Espinosa Nelson , Alonso Alejandra , Lara-Vasquez Ariel , Fuentealba Pablo
Published: February 2019

The basal forebrain delivers extensive axonal projections to the cortical mantle regulating brain states and cognitive processing. Recent evidence has established the basal forebrain as a subcortical node of the default mode network that directionally influences cortical dynamics trough gamma oscillations, yet their synaptic origin has not been established. Here, we used optogenetic stimulation and in vivo recordings of transgenic mice to show that somatostatin neurons exert an anatomically specialized role in the coordination of subcortical gamma oscillations of the rostral basal forebrain. Indeed, the spike timing of somatostatin cells was tightly correlated with gamma oscillations in the ventral pallidum, but not in the medial septum. Consequently, optogenetic inactivation of somatostatin neurons selectively disrupted the amplitude and coupling of gamma oscillations only in the ventral pallidum. Moreover, photosupression of somatostatin cells produced specific behavioral interferences, with the ventral pallidum regulating locomotor speed and the medial septum modulating spatial working memory. Altogether, these data suggest that basal forebrain somatostatin cells can selectively synchronize local neuronal networks in the gamma band directly impinging on cortical dynamics and behavioral performance. This further supports the role of the basal forebrain as a subcortical switch commanding transitions between internally and externally oriented brain states.
A Systematic Review and Meta-Analysis Comparing Programmed Intermittent Bolus and Continuous Infusion as the Background Infusion for Parturient-Controlled Epidural Analgesia
Authors: Xu Jiqian , Zhou Jie , Xiao Hairong , Pan Shangwen , Liu Jie , Shang You , Yao Shanglong
Published: February 2019

The programmed intermittent epidural bolus (PIEB) technique offers multiple benefits over continuous epidural infusion (CEI), but controversy still exists when it is used in conjunction with a parturient-controlled epidural analgesia (PCEA) regimen. A systematic review and meta-analysis was thus conducted using the Medline, EMBASE, CENTRAL and Web of Science databases with the aim of identifying those randomized controlled trials (RCTs) that performed a comparison between PIEB and CEI in healthy parturients using a PCEA regimen with regard to the duration of labor, labor pain, anesthesia interventions, maternal satisfaction and main side effects. The data were analyzed using a random-effects model. Eleven eligible trials were included, in which 717 participants were allocated to the PIEB + PCEA group and 650 patients were allocated to the CEI + PCEA group. The rate of instrumental delivery, incidence of breakthrough pain, PCEA usage rates and local anesthetic usage were significantly reduced, the labor duration was statistically shorter, and the maternal satisfaction score was significantly improved in the PIEB + PCEA group compared with that in the CEI + PCEA group. There were no differences in the side effects between the two groups. The results of the present study suggest that the PIEB technique in conjunction with the PCEA regimen was more advantageous than CEI + PCEA, but additional studies should be conducted to consistently demonstrate an improvement in the maternal and fetal obstetric outcomes.
Socioeconomic disparity in prefrontal development during early childhood
Authors: Moriguchi Yusuke , Shinohara Ikuko
Published: February 2019

Socioeconomic status (SES) has a powerful influence on cognitive, social and brain development. Children from low-SES backgrounds show poor executive function (EF). However, it is unclear if there is a SES-dependent disparity in functional brain development. The present study examined whether the SES of preschool children (N = 93) is associated with prefrontal activation during cognitive shifting tasks as measured by near-infrared spectroscopy. Low-SES children did not show activation in lateral prefrontal regions during the tasks, whereas middle- and high-SES children showed prefrontal activations, although no differences were found in terms of behavioural performance. These results suggest that SES can affect the functional development of the prefrontal regions. In this study, we discuss the practical implications of the results.
A RNA sequencing-based six-gene signature for survival prediction in patients with glioblastoma
Authors: Zuo Shuguang , Zhang Xinhong , Wang Liping
Published: February 2019

Glioblastoma (GBM) is an aggressive tumor of the central nervous system that has poor prognosis despite extensive therapy. Therefore, it is essential to identify a gene expression-based signature for predicting GBM prognosis. The RNA sequencing data of GBM patients from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases were employed in our study. The univariate and multivariate regression models were utilized to assess the relative contribution of each gene to survival prediction in both cohorts, and the common genes in two cohorts were identified as a final prognostic model. A prognostic risk score was calculated based on the prognostic gene signature. This prognostic signature stratified the patients into the low- and high-risk groups. Multivariate regression and stratification analyses were implemented to determine whether the gene signature was an independent prognostic factor. We identified a 6-gene signature through univariate and multivariate regression models. This prognostic signature stratified the patients into the low- and high-risk groups, implying improved and poor outcomes respectively. Multivariate regression and stratification analyses demonstrated that the predictive value of the 6-gene signature was independent of other clinical factors. This study highlights the significant implications of having a gene signature as a prognostic predictor in GBM, and its potential application in personalized therapy.
New alleles for chlorophyll content and stay-green traits revealed by a genome wide association study in rice (Oryza sativa)
Authors: Zhao Yan , Qiang Chenggen , Wang Xueqiang , Chen Yanfa , Deng Jinqiang , Jiang Conghui , Sun Xingming , Chen Haiyang , Li Jin , Piao Weilan , Zhu Xiaoyang , Zhang Zhanying , Zhang Hongliang , Li Zichao , Li Jinjie
Published: February 2019

Higher chlorophyll content (CC) and strong stay-green (SG) traits are conducive for improvement of photosynthetic efficiency in plants. Exploration of natural elite alleles for CC and SG, and highly resolved gene haplotypes are beneficial to rational design of breeding for high-photosynthetic efficiency. Phenotypic analysis of 368 rice accessions showed no significant correlation between CC and SG, and higher CC and stronger SG in japonica than in indica. Genome-wide association studies of six indices for CC and SG identified a large number of association signals, among which 14 were identified as pleiotropic regions for CC and SG. Twenty-five known genes and pleiotropic candidate gene OsSG1 accounted for natural variation in CC and SG. Further analysis indicated that 20 large-effect, non-synonymous SNPs within six known genes around GWAS signals and three SNPs in the promoter of OsSG1 could be functional causing significant phenotypic differences between alleles. Superior haplotypes were identified based on these potentially functional SNPs. Population analyses of 368 cultivated accessions and 446 wild accessions based on SNPs within genes for CC and SG suggested that these genes had been subjected to strong positive selection in japonica in the process of spreading from its subtropical origin to the North China temperate zone. Our studies point to important genes that account for natural variation and provide superior haplotypes of possible functional SNPs that will be beneficial in breeding for high-photosynthetic efficiency in rice.
Oxygen conduction mechanism in Ca3Fe2Ge3O12 garnet-type oxide
Authors: Lee Joohwi , Ohba Nobuko , Asahi Ryoji
Published: February 2019

We investigate the oxygen conduction mechanism in a garnet-type oxide, Ca3Fe2Ge3O12, for the first time in detail by first-principle calculations. The nudged elastic band results confirm that this oxide has a lower migration barrier energy (0.45 eV) for an oxygen interstitial (Oi) with the kick-out mechanism than that (0.76 eV) for an oxygen vacancy. The migration paths for Oi are delocalized and connected to the neighboring cells in three-dimensional space. This oxide does not have a very low formation energy of Oi when the Fermi level is near the lowest unoccupied molecular orbital at a high temperature, which implies the possibility of electron doping by high-valence cations. These theoretical results suggest that the doping of Ca3Fe2Ge3O12 for generation of excess Oi provides a good oxygen-ion conductivity, along with the electronic conductivity.
Moraxella catarrhalis NucM is an entry nuclease involved in extracellular DNA and RNA degradation, cell competence and biofilm scaffolding
Authors: Tan Aimee , Li Wing-Sze , Verderosa Anthony D. , Blakeway Luke V. , D. Mubaiwa Tsitsi , Totsika Makrina , Seib Kate L.
Published: February 2019

Moraxella catarrhalisis a host-adapted bacterial pathogen that causes otitis media and exacerbations of chronic obstructive pulmonary disease. This study characterises the conservedM.catarrhalisextracellular nuclease, a member of the ββα metal finger family of nucleases, that we have named NucM. NucM shares conserved sequence motifs from the ββα nuclease family, including the DRGH catalytic core and Mg2+co-ordination site, but otherwise shares little primary sequence identity with other family members, such as theSerratiaNuc and pneumococcal EndA nucleases. NucM is secreted from the cell and digests linear and circular nucleic acid. However, it appears that a proportion of NucM is also associated with the cell membrane and acts as an entry nuclease, facilitating transformation ofM.catarrhaliscells. This is the first example of a ββα nuclease in a Gram negative bacteria that acts as an entry nuclease. In addition to its role in competence, NucM affects cell aggregation and biofilm formation byM.catarrhalis, with ΔnucMmutants having increased biofilm biomass. NucM is likely to increase the ability of cells to survive and persistin vivo, increasing the virulence ofM.catarrhalisand potentially affecting the behaviour of other pathogens that co-colonise the otorhinolaryngological niche.
SUNRED, a natural extract-based biostimulant, application stimulates anthocyanin production in the skins of grapes
Authors: Deng Qunxian , Xia Hui , Lin Lijin , Wang Jin , Yuan Lu , Li Kangning , Zhang Jinrong , Lv Xiulan , Liang Dong
Published: February 2019

Anthocyanins are important components in skins of red table grapes and contribute to the berries appearance, a key quality characteristic for customers. In recent years, exogenous foliage fertilizers has been applied to grapevines to improve the pigmentation of the fruit. The present study examines the effect on a biostimulant (SUNRED) pre-véraison application in the accumulation of anthocyanins in ‘Red Globe’ grapes, and investigates the related changes in expression of key genes and their enzyme activities in the flavonoid pathways. Additionally, abscisic acid (S-ABA) was also applied to grapevines to evaluate the comparative effect of SUNRED. Our analyses showed that total anthocyanin contents increased in both SUNRED and S-ABA treated grapes; for S-ABA, a 1% dilution (A100) of the commercially available stock solution treatments represented the greatest effect on pigmentation; for SUNRED, a 0.1% dilution (S1000) was most effective. The anthocyanin contents increased by 1.16-fold and 1.4-fold after A100 and S1000 treatments, respectively. The gene expression analyses showed that almost all genes involved in the anthocyanin biosynthesis pathway up-regulated after A100 and S1000 treatments, suggesting that the increment in total anthocyanin content was attributed to the increased expression level of related genes. Moreover, the activities of phenylalanine ammonia-lyase (PAL), chalcone isomerase (CHI), UDP glucose: flavonoid 3-o-glucosyl transferase (UFGT) and dihydroflavonol 4-reductase (DFR), key enzymes for biosynthesis of anthocyanin, were increased by the exogenous treatments. Overall, our findings clearly demonstrate that application of exogenous biostimulant have a positive effect on the pigment characteristics of grape crop.
Photoprotection of Cerium Oxide Nanoparticles against UVA radiation-induced Senescence of Human Skin Fibroblasts due to their Antioxidant Properties
Authors: Li Yaxi , Hou Xiaoyang , Yang Chunsheng , Pang Yanyu , Li Xinxin , Jiang Guan , Liu Yanqun
Published: February 2019

Ultraviolet (UV) irradiation, particularly ultraviolet A (UVA), stimulates reactive oxygen species (ROS) production in the epidermis and dermis, which plays a major part in the photoageing of human skin. Several studies have demonstrated that cerium oxide nanoparticles (CeO2 NP) can exhibit an antioxidant effect and free radical scavenging activity. However, the protective role of CeO2 NP in skin photoageing and the underlying mechanisms are unclear. In this study, we investigated the effects of CeO2 NP on UVA-irradiated human skin fibroblasts (HSFs) and explored the potential signalling pathway. CeO2 NP had no apparent cytotoxicity, and could reduce the production of proinflammatory cytokines, intracellular ROS, senescence-associated β-galactosidase activity, and downregulate phosphorylation of c-Jun N-terminal kinases (JNKs) after exposure to UVA radiation. Based on our findings, CeO2 NPs have great potential against UVA radiation-induced photoageing in HSFs via regulating the JNK signal-transduction pathway to inhibit oxidative stress and DNA damage.
Detection of cannabinoids in hair after cosmetic application of hemp oil
Authors: Paul R. , Williams R. , Hodson V. , Peake C.
Published: February 2019

The detection of cannabis constituents and metabolites in hair is an established procedure to provide evidence of exposure to cannabis. We present the first known evidence to suggest that applying hemp oil to hair, as cosmetic treatment, may result in the incorporation of Δ9-tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol (CBD) and in one instance, the metabolite 11-hydroxy-Δ9-tetrahydrocannabinol (THC-OH). 10 volunteers treated their head hair daily with commercially available hemp oil for a period of 6 weeks. Head hair samples were collected before and after the application period. Hair samples were washed with methanol and subjected to clean up via liquid/liquid and solid phase extraction procedures, and then GC-MS/MS for the analysis of THC, CBN, CBD, THC-OH and THC-COOH. Application of hemp oil to hair resulted in the incorporation of one or more cannabis constituents in 89% of volunteers, and 33% of the group tested positive for the three major constituents, THC, CBN and CBD. One volunteer showed low levels of the metabolite THC-OH. We suggest that cosmetic use of hemp oil should be recorded when sampling head hair for analysis, and that the interpretative value of cannabinoid hair measurements from people reporting application of hemp oil is treated with caution in both criminology and public health.
Multiple molecular defense strategies in Brachypodium distachyon surmount Hessian fly (Mayetiola destructor) larvae-induced susceptibility for plant survival
Authors: Subramanyam Subhashree , Nemacheck Jill A. , Hargarten Andrea M. , Sardesai Nagesh , Schemerhorn Brandon J. , Williams Christie E.
Published: February 2019

The Hessian fly is a destructive pest of wheat causing severe economic damage. Numerous genes and associated biological pathways have been implicated in defense against Hessian fly. However, due to limited genetic resources, compounded with genome complexity, functional analysis of the candidate genes are challenging in wheat. Physically, Brachypodium distachyon (Bd) exhibits nonhost resistance to Hessian fly, and with a small genome size, short life cycle, vast genetic resources and amenability to transformation, it offers an alternate functional genomic model for deciphering plant-Hessian fly interactions. RNA-sequencing was used to reveal thousands of Hessian fly-responsive genes in Bd one, three, and five days after egg hatch. Genes encoding defense proteins, stress-regulating transcription factors, signaling kinases, and secondary metabolites were strongly up-regulated within the first 24 hours of larval feeding indicating an early defense, similar to resistant wheat. Defense was mediated by a hypersensitive response that included necrotic lesions, up-regulated ROS-generating and -scavenging enzymes, and H2O2 production. Suppression of cell wall-associated proteins and increased cell permeability in Bd resembled susceptible wheat. Thus, Bd molecular responses shared similarities to both resistant and susceptible wheat, validating its suitability as a model genome for undertaking functional studies of candidate Hessian fly-responsive genes.
Site-specific chelation therapy with EDTA-loaded albumin nanoparticles reverses arterial calcification in a rat model of chronic kidney disease
Authors: Karamched Saketh R. , Nosoudi Nasim , Moreland Hannah E. , Chowdhury Aniqa , Vyavahare Naren R.
Published: February 2019

Medial arterial calcification (MAC) is a common outcome in diabetes and chronic kidney disease (CKD). It occurs as linear mineral deposits along the degraded elastin lamellae and is responsible for increased aortic stiffness and subsequent cardiovascular events. Current treatments for calcification, particularly in CKD, are predominantly focused on regulating the mineral disturbance and other risk factors. Ethylene diamine tetraacetic acid (EDTA), a chelating agent, can resorb mineral deposits, but the systemic delivery of EDTA may cause side effects such as hypocalcemia and bone resorption. We have developed elastin antibody conjugated albumin nanoparticles that target only degraded elastin in vasculature while sparing healthy tissues. In this study, we tested a targeted nanoparticle-based EDTA chelation therapy to reverse CKD-associated MAC. Renal failure was induced in Sprague-Dawley rats by a high adenine diet supplemented by high P and Ca for 28 days that led to MAC. Intravenous delivery of DiR dye-loaded nanoparticles confirmed targeting to vascular degraded elastin and calcification sites within 24 hours. Next, EDTA-loaded albumin nanoparticles conjugated with an anti-elastin antibody were intravenously injected twice a week for two weeks. The targeted nanoparticles delivered EDTA at the site of vascular calcification and reversed mineral deposits without any untoward effects. Systemic EDTA injections or blank nanoparticles were ineffective in reversing MAC. Reversal of calcification seems to be stable as it did not return after the treatment was stopped for an additional four weeks. Targeted EDTA chelation therapy successfully reversed calcification in this adenine rat model of CKD. We consider that targeted NP therapy will provide an attractive option to reverse calcification and has a high potential for clinical translation.