bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of AlN buffer layer on the growth of self-assembled GaN nanocolumns on graphene
Authors: Liudi Mulyo Andreas , Rajpalke Mohana K. , Vullum Per Erik , Weman Helge , Kishino Katsumi , Fimland Bjørn-Ove
Published: January 2020

GaN nanocolumns were synthesized on single-layer graphene via radio-frequency plasma-assisted molecular beam epitaxy, using a thin migration-enhanced epitaxy (MEE) AlN buffer layer as nucleation sites. Due to the weak nucleation on graphene, instead of an AlN thin-film we observe two distinguished AlN formations which affect the subsequent GaN nanocolumn growth: (i) AlN islands and (ii) AlN nanostructures grown along line defects (grain boundaries or wrinkles) of graphene. Structure (i) leads to the formation of vertical GaN nanocolumns regardless of the number of AlN MEE cycles, whereas (ii) can result in random orientation of the nanocolumns depending on the AlN morphology. Additionally, there is a limited amount of direct GaN nucleation on graphene, which induces non-vertical GaN nanocolumn growth. The GaN nanocolumn samples were characterized by means of scanning electron microscopy, transmission electron microscopy, high-resolution X-ray diffraction, room temperature micro-photoluminescence, and micro-Raman measurements. Surprisingly, the graphene with AlN buffer layer formed using less MEE cycles, thus resulting in lower AlN coverage, has a lower level of nitrogen plasma damage. The AlN buffer layer with lowest AlN coverage also provides the best result with respect to high-quality and vertically-aligned GaN nanocolumns.
County-level analysis reveals a rapidly shifting landscape of insecticide hazard to honey bees (Apis mellifera) on US farmland
Authors: Douglas Margaret R. , Sponsler Douglas B. , Lonsdorf Eric V. , Grozinger Christina M.
Published: January 2020

Each year, millions of kilograms of insecticides are applied to crops in the US. While insecticide use supports food, fuel, and fiber production, it can also threaten non-target organisms, a concern underscored by mounting evidence of widespread decline of pollinator populations. Here, we integrate several public datasets to generate county-level annual estimates of total ‘bee toxic load’ (honey bee lethal doses) for insecticides applied in the US between 1997–2012, calculated separately for oral and contact toxicity. To explore the underlying components of the observed changes, we divide bee toxic load into extent (area treated) and intensity (application rate x potency). We show that while contact-based bee toxic load remained relatively steady, oral-based bee toxic load increased roughly 9-fold, with reductions in application rate outweighed by disproportionate increases in potency (toxicity/kg) and extent. This pattern varied markedly by region, with the greatest increase seen in Heartland (121-fold increase), likely driven by use of neonicotinoid seed treatments in corn and soybean. In this “potency paradox”, farmland in the central US has become more hazardous to bees despite lower volumes of insecticides applied, raising concerns about insect conservation and highlighting the importance of integrative approaches to pesticide use monitoring.
Relationship between nerve fiber layer defect and the presence of epiretinal membrane in a Japanese population: The JPHC-NEXT Eye Study
Authors: Uchida Atsuro , Sasaki Mariko , Motomura Kaoru , Yuki Kenya , Kurihara Toshihide , Tomita Yohei , Ozawa Yoko , Yamagishi Kazumasa , Kawasaki Ryo , Hanyuda Akiko , Sawada Norie , Tsubota Kazuo , Tsugane Shoichiro , Iso Hiroyasu
Published: January 2020

The study subjects were residents of Chikusei city, Japan, aged 40 years or older who attended annual health check-up programs and participated in the JPHC-NEXT Eye Study which performed non-mydriatic fundus photography of both eyes. The relationship of glaucomatous fundus changes such as optic disc cupping (cup to disc ratio ≥ 0.7) and retinal nerve fiber layer defect (NFLD) with the presence of epiretinal membrane (ERM) were examined cross-sectionally. A total of 1990 persons gave consent to participate in this study in 2013. The overall prevalence of ERM was 12.9%. Of these, 1755 had fundus photographs of sufficient quality and no history of intraocular surgery (mean age: 62.3 ± 10.0 years). After adjusting for age, sex and refractive error, NFLD was positively associated with the presence of ERM (odds ratio [OR]: 2.48; 95% confidence interval [CI]: 1.24, 4.96; P = 0.010), but optic disc cupping was not (OR: 1.33; CI: 0.71, 2.48; P = 0.37). The results did not necessarily suggest an association between glaucoma and ERM, but indicated an association between NFLD and ERM.
Differential Abundance Analysis with Bayes Shrinkage Estimation of Variance (DASEV) for Zero-Inflated Proteomic and Metabolomic Data
Authors: Huang Zhengyan , Lane Andrew N. , Fan Teresa W-M. , Higashi Richard M. , Weiss Heidi L. , Yin Xiangrong , Wang Chi
Published: January 2020

Mass spectrometry (MS) is frequently used for proteomic and metabolomic profiling of biological samples. Data obtained by MS are often zero-inflated. Those zero values are called point mass values (PMVs). Zero values can be further grouped into biological PMVs and technical PMVs. The former type is caused by true absence of a compound and the later type is caused by a technical detection limit. Methods based on a mixture model have been developed to separate the two types of zeros and to perform differential abundance analysis comparing proteomic/metabolomic profiles between different groups of subjects. However, we notice that those methods may give unstable estimate of the model variance, and thus lead to false positive and false negative results when the number of non-zero values is small. In this paper, we propose a new differential abundance analysis method, DASEV, which uses an empirical Bayes shrinkage method to more robustly estimate the variance and enhance the accuracy of differential abundance analysis. Simulation studies and real data analysis show that DASEV substantially improves parameter estimation of the mixture model and outperforms current methods in identifying differentially abundant features.
Room Temperature Electrically Detected Nuclear Spin Coherence of NV Centres in Diamond
Authors: Morishita H. , Kobayashi S. , Fujiwara M. , Kato H. , Makino T. , Yamasaki S. , Mizuochi N.
Published: January 2020

We demonstrate electrical detection of the14N nuclear spin coherence of NV centres at room temperature. Nuclear spins are candidates for quantum memories in quantum-information devices and quantum sensors, and hence the electrical detection of nuclear spin coherence is essential to develop and integrate such quantum devices. In the present study, we used a pulsed electrically detected electron-nuclear double resonance technique to measure the Rabi oscillations and coherence time (T2) of14N nuclear spins in NV centres at room temperature. We observedT2≈ 0.9 ms at room temperature, however, this result should be taken as a lower limit due to limitations in the longitudinal relaxation time of the NV electron spins. Our results will pave the way for the development of novel electron- and nuclear-spin-based diamond quantum devices.
Lactobacillus plantarum LMT1-48 exerts anti-obesity effect in high-fat diet-induced obese mice by regulating expression of lipogenic genes
Authors: Choi Woo Jin , Dong Hye Jin , Jeong Hyun Uk , Ryu Dong Wook , Song Soo Min , Kim Yu Ri , Jung Hyun Ho , Kim Tai Hoon , Kim Yeung-Hyen
Published: January 2020

Obesity is a major health problem and is known to be closely associated with metabolic diseases. Abnormal hepatic accumulation of fat causes fatty liver or hepatic steatosis, and long-term consumption of a high-fat diet is known to be a key obesity-causing factor. Recent studies have demonstrated that probiotics such as Lactobacillus strains, exert an anti-obesity effect by regulating adipogenesis. However, it is still unknown how the consumption of probiotics can reduce abdominal fat volume by regulating the hepatic expression of lipogenic genes. Therefore, we evaluated the effect of long-term ingestion of L. plantarum LMT1-48 on the expression of lipogenic genes in high-fat diet (HFD)-fed mice. We observed that treatment of 3T3-L1 adipocytes with L. plantarum LMT1-48 extract inhibited their differentiation and lipid accumulation by downregulating lipogenic genes, namely, PPARγ, C/EBPα, FAS, and FABP4. Interestingly, administration of L. plantarum LMT1-48 reduced liver weight and liver triglycerides concurrently with the downregulation of the lipogenic genes PPARγ, HSL, SCD-1, and FAT/CD36 in the liver, resulting in the reduction of body weight and fat volume in HFD-fed obese mice. Notably, we also observed that the administration of at least 106 CFU of L. plantarum LMT1-48 significantly lowered body weight and abdominal fat volume in modified diet-fed mouse models. Collectively, these data suggest that L. plantarum LMT1-48 is a potential healthy food for obese people.
Preoperative %p2PSA and Prostate Health Index Predict Pathological Outcomes in Patients with Prostate Cancer Undergoing Radical Prostatectomy
Authors: Cheng Yung-Ting , Huang Chao-Yuan , Chen Chung-Hsin , Chiu Shih-Ting , Hong Jian-Hua , Pu Yeong-Shiau , Liu Shih-Ping , Lu Yu-Chuan , Chang Yi-Kai , Chang Hong-Chiang , Huang Kuo-How , Lee Yuan-Ju , Chow Po-Ming , Chiang I-Ni , Hung Shih-Chun , Chiang Chih-Hung
Published: January 2020

To evaluate the predictive accuracy of the %p2PSA and prostate health index (PHI) in predicting aggressive pathological outcomes in patients with prostate cancer (PCa) undergoing radical prostatectomy (RP), we enrolled 91 patients with organ-confined PCa who were treated with robot-assisted RP. p2PSA levels and the PHI were investigated for their ability to predict pathological results. The %p2PSA and PHI were both significantly higher in patients with ≥pT3 disease, high-risk disease, positive surgical margin, or seminal vesical invasion (SVI). In univariable analysis, p2PSA derivatives were significant predictors of the presence of ≥pT3 disease, high-risk disease, positive surgical margin, and SVI. To predict adverse pathological outcomes at a sensitivity of 90%, p2PSA derivatives had higher specificity than standard PSA derivatives. In multivariable analysis, additional increases in the area under the receiver operating characteristic curve (AUC) were observed with the %p2PSA and PHI for ≥pT3 disease, high-risk disease, and positive surgical margin (8.2% and 2.7%, 6.2% and 4.1%, and 8.6% and 5.4%, respectively). A PHI ≥61.26 enhanced the predictive accuracy of the model for SVI by increasing the AUC from 0.624 to 0.819 (p = 0.009). The preoperative %p2PSA and PHI accurately predict adverse pathological results and are useful for decision-making.
Reference gene validation for quantification of gene expression during ovarian development of turbot (Scophthalmus maximus)
Authors: Gao Yunhong , Gao Yuntao , Huang Bin , Meng Zhen , Jia Yudong
Published: January 2020

Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) is a powerful and sensitive method used in gene expression analysis. Suitable reference genes, which are stable under all experimental circumstances and tissues significantly improve the accuracy of qRT-PCR data. In this study, the stability of six genes, namely, 18S ribosomal RNA (18s), beta-actin (actb), elongation factor 1-alpha (ef1α), glyceraldehyde-3-phosphate-dehydrogenase (gapdh), cathepsin D (ctsd), and beta-2-microglobulin (b2m) were evaluated as potential references for qRT-PCR analysis. The genes were examined in the hypothalamus-pituitary-ovary-liver (HPOL) axis throughout turbot ovarian development via using the geNorm, NormFinder and BestKeeper algorithms. Results showed that the most stable reference genes were ef1α, actb, and ctsd in the hypothalamus, pituitary, ovary and liver, respectively. The best-suited gene combinations for normalization were 18s, ef1α, and ctsd in the hypothalamus; actb, ctsd, and 18s in the pituitary; actb, and ctsd in the ovary; gapdh and ctsd in the liver. Moreover, the expression profile of estrogen receptor α (erα) manifested no significant difference normalization to the aforementioned best-suited gene during turbot ovarian development. However, no single gene or pair of genes is suitable as an internal control and account for the amplification differences among the four tissues during ovarian development. In summary, these results provide a basic data for the optimal reference gene selection and obtain highly accurate normalization of qRT-PCR data in HPOL axis-related gene expression analysis during turbot ovarian development.
Multiscale Process Modelling in Translational Systems Biology of Leishmania major: A Holistic view
Authors: Chauhan Nutan , Singh Shailza
Published: January 2020

Present work aims to utilize systems biology and molecular modelling approach to understand the inhibition kinetics ofLeishmania majorGLO I and identifying potential hit followed by their validation throughin vitroand animal studies. Simulation of GLO I inhibition has shown to affect reaction fluxes of almost all reactions in the model that led to increased production of various AGEs and free radicals. Further,in vitrotesting of C1 and C2, selected through molecular modelling revealed remarkable morphological alterations like size reduction, membrane blebbing and loss in motility of the parasite, however, only C1 showed better antileishmanial activity. Additionally, C1 showed apoptosis mediated leishmanicidal activity (apoptosis-like cell death) along with cell-cycle arrest at sub-G0/G1 phase and exhibited potent anti-leishmanial effect against intracellular amastigotes. Furthermore, decrease in parasite load was also observed in C1 treated BALB/c female mice. Our results indicate that C1 has healing effect in infected mice and effectively reduced the parasitic burden. Hence, we suggest C1 as a lead molecule which on further modification, may be used to develop novel therapeutics againstLeishmaniasis.
Comparison of methods for miRNA isolation and quantification from ovine plasma
Authors: Wright Kathryn , de Silva Kumudika , Purdie Auriol C. , Plain Karren M.
Published: January 2020

microRNA (miRNA) are promising candidates for disease biomarkers as they are abundant in circulation, highly stable in biological fluids and may yield diagnostic biomarker signatures. The reported issues with miRNA isolation using traditional RNA reagents necessitates the optimisation of miRNA isolation from challenging samples. In this study we compared six commercial RNA extraction kits to evaluate their ability to isolate miRNA from ovine plasma. We also compared three methods for quantification of small RNA extracted from plasma to determine the most reliable. Using minimal sample inputs of fresh and frozen plasma from five sheep, we compared the six kits (Kit A-F) using quantitative PCR. Operational factors were also assessed for each kit. Kits A and B provided the best detection of the miRNA qPCR reference genes across fresh and frozen samples (p < 0.001) followed by Kit C. The Qubit and microRNA assay provided the least variation (% CV 5.47, SEM ± 0.07), followed by the NanoDrop (% CV 7.01, SEM ± 0.92) and Agilent Bioanalyzer (% CV 59.21, SEM ± 1.31). We identify Kit A to be optimal for isolating miRNA from small volumes of fresh and frozen ovine plasma, and Kit B the top performing kit taking into consideration miRNA detection and operational factors. The Qubit fluorometer using a microRNA assay was the most reliable miRNA quantification method.
Astrocyte Support for Oligodendrocyte Differentiation can be Conveyed via Extracellular Vesicles but Diminishes with Age
Authors: Willis Cory M. , Nicaise Alexandra M. , Bongarzone Ernesto R. , Givogri Maria , Reiter Cory R. , Heintz Olivia , Jellison Evan R. , Sutter Pearl A. , TeHennepe Gregg , Ananda Guruprasad , Vella Anthony T. , Crocker Stephen J.
Published: January 2020

The aging brain is associated with significant changes in physiology that alter the tissue microenvironment of the central nervous system (CNS). In the aged CNS, increased demyelination has been associated with astrocyte hypertrophy and aging has been implicated as a basis for these pathological changes. Aging tissues accumulate chronic cellular stress, which can lead to the development of a pro-inflammatory phenotype that can be associated with cellular senescence. Herein, we provide evidence that astrocytes aged in culture develop a spontaneous pro-inflammatory and senescence-like phenotype. We found that extracellular vesicles (EVs) from young astrocyte were sufficient to convey support for oligodendrocyte differentiation while this support was lost by EVs from aged astrocytes. Importantly, the negative influence of culture age on astrocytes, and their cognate EVs, could be countered by treatment with rapamycin. Comparative proteomic analysis of EVs from young and aged astrocytes revealed peptide repertoires unique to each age. Taken together, these findings provide new information on the contribution of EVs as potent mediators by which astrocytes can extert changing influence in either the disease or aged brain.
Cycling hypoxia promotes a pro-inflammatory phenotype in macrophages via JNK/p65 signaling pathway
Authors: Delprat Victor , Tellier Céline , Demazy Catherine , Raes Martine , Feron Olivier , Michiels Carine
Published: January 2020

Cycling hypoxia (cyH), also called intermittent hypoxia, occurs in solid tumors and affects different cell types in the tumor microenvironment and in particular the tumor-associated macrophages (TAMs). As cyH and TAMs both favor tumor progression, we investigated whether cyH could drive the pro-tumoral phenotype of macrophages. Here, the effects of cyH on human THP-1 macrophages and murine bone marrow-derived macrophages (BMDM), either unpolarized M0, or polarized in M1 or M2 phenotype were studied. In M0 macrophages, cyH induced a pro-inflammatory phenotype characterized by an increase in TNFα and IL-8/MIP-2 secretion. CyH amplified the pro-inflammatory phenotype of M1 macrophages evidenced by an increased pro-inflammatory cytokine secretion and pro-inflammatory gene expression. Furthermore, cyH increased c-jun activation in human M0 macrophages and highly increased c-jun and NF-κB activation in M1 macrophages. C-jun and p65 are implicated in the effects of cyH on M0 and M1 macrophages since inhibition of their activation prevented the cyH pro-inflammatory effects. In conclusion, we demonstrated that cyH induces or amplifies a pro-inflammatory phenotype in M0 and M1 macrophages by activating JNK/p65 signaling pathway. These results highlight a specific role of cyH in the amplification of tumor-related inflammation by modulating the inflammatory phenotype of macrophages.
Predictive factors of postoperative infection-related complications in adult patients with cerebral cavernous malformations
Authors: Ding Chen-Yu , Lian Bao-Qiang , Ge Hong-Liang , He Qiu , Li Ang , Chen Xiao-Yong , Xu Jia-Heng , Lin Fu-Xin , Lin Yuan-Xiang , Kang De-Zhi
Published: January 2020

Postoperative infection is an important factor contributing to poor prognosis after surgical treatment of cerebral cavernous malformations (CCM). However, the predictive factors of postoperative infection-related complications in adult patients with CCM have still not been well established. To identify possible predictive factors of postoperative infection after CCM surgery, we retrospectively evaluated the data of CCM patients who were enrolled into our prospective registry database. The relationship between preoperative characteristics of patients and postoperative infection-related complications was analyzed. A total of 167 CCM patients were included in this study. The average age was 39.69 ± 15.27 years old, and 21 of them had postoperative infection. For patients with postoperative infection, the Glasgow Coma Scale (GCS), Modified Rankin Scale (mRS), white blood cell (WBC) count, and neutrophil (NEU) count were all significantly higher than those of the group without infection. Our preliminary results showed that NEU count might have significant predictive value of intracranial infection, and GCS, mRS and CCM presenting with hemorrhage were all factors significantly related to postoperative pneumonia. Preoperative GCS, mRS and CCM presenting with hemorrhage might be used as predictive factors for postoperative pneumonia after CCM surgery, while preoperative NEU count can be used as an important predictive factor for postoperative intracranial infection after CCM surgery. Further large-scale studies are still needed to confirm this finding.
Induction of left ventricular hypoplasia by occluding the foramen ovale in the fetal lamb
Authors: Wong Flora Y. , Veldman Alex , Sasi Arun , Teoh Mark , Edwards Andrew , Chan Yuen , Graupner Oliver , Enzensberger Christian , Axt-Fliedner Roland , Black Mary Jane , Schranz Dietmar
Published: January 2020

Disturbed fetal haemodynamics often affects cardiac development and leads to congenital cardiac defects. Reduced left ventricular (LV) preload in the fetus may result in hypoplastic LV, mitral and aortic valve, mimicking a moderate form of hypoplastic left heart complex. We aimed to induce LV hypoplasia by occluding the foramen ovale (FO) to reduce LV preload in the fetal sheep heart, using percutaneous trans-hepatic catheterisation. Under maternal anaesthesia and ultrasound guidance, hepatic venous puncture was performed in six fetal lambs (0.7–0.75 gestation). A coronary guidewire was advanced into the fetal inferior vena cava, right and left atrium. A self-expandable stent was positioned across the FO. An Amplatzer Duct Occluder was anchored within the stent for FO occlusion. Euthanasia and post-mortem examination was performed after 3 weeks. Nine fetuses were used as age-matched controls. Morphometric measurements and cardiac histopathology were performed. Compared with controls, fetal hearts with occluded FO had smaller LV chamber, smaller mitral and aortic valves, lower LV-to-RV ratio in ventricular weight and wall volume, and lower number of LV cardiomyocyte nuclei. We conclude that fetal FO occlusion leads to a phenotype simulating LV hypoplasia. This large animal model may be useful for understanding and devising therapies for LV hypoplasia.
Silencing of SENP2 in Multiple Myeloma Induces Bortezomib Resistance by Activating NF-κB Through the Modulation of IκBα Sumoylation
Authors: Xie Hongyi , Gu Yuanliang , Wang Wenjuan , Wang Xuyao , Ye Xiaojuan , Xin Chao , Lu Mengjiao , Reddy B. Ashok , Shu Peng
Published: January 2020

The proteasome inhibitor bortezomib is the most successfully applied chemotherapeutic drug for treating multiple myeloma. However, its clinical efficacy reduced due to resistance development. The underlying molecular mechanisms of bortezomib resistance are poorly understood. In this study, by combining in silico analysis and sgRNA library based drug resistance screening assay, we identified SENP2 (Sentrin/SUMO-specific proteases-2) as a bortezomib sensitive gene and found its expression highly downregulated in bortezomib resistant multiple myeloma patient’s samples. Furthermore, down regulation of SENP2 in multiple myeloma cell line RPMI8226 alleviated bortezomib induced cell proliferation inhibition and apoptosis, whereas, overexpression of SENP2 sensitized these cells to bortezomib treatment. We further demonstrate that knockdown of SENP2 in RPMI8226 cells increased SUMO2 conjugated IκBα that resulted in the activation of NF-κB. Taken together, we report that silencing of SENP2 and consequent activation of NF-κB through the modulation of IκBα sumoylation as a novel mechanism inducing bortezomib resistance in multiple myeloma.
Regulation of histamine and diamine oxidase in patients undergoing orthotopic liver transplantation
Authors: Schiefer Judith , Baron-Stefaniak Joanna , Boehm Thomas , Wadowski Patricia , Berlakovich Gabriela , Kuessel Lorenz , Mühlbacher Jakob , Jilma-Stohlawetz Petra , Schwameis Michael , Jilma Bernd , Faybik Peter
Published: January 2020

Increased concentrations of the vasodilator histamine have been observed in patients undergoing abdominal surgery. The role of histamine during orthotopic liver transplantation (OLT) has only been studied in animals. The aim of this study was to measure plasma concentrations of histamine and its degrading enzyme diamine oxidase (DAO) in patients undergoing orthotopic liver transplantation, and assess whether histamine or DAO correlate with intraoperative noradrenaline requirements. Histamine and DAO concentrations were measured in 22 adults undergoing liver transplantation and 22 healthy adults. Furthermore, norepinephrine requirements during liver transplantation were recorded. Baseline concentrations of histamine and DAO were greater in patients, who underwent liver transplantation, than in healthy individuals (Histamine: 6.4 nM, IQR[2.9–11.7] versus 4.3 nM, IQR[3.7–7.1], p = 0.029; DAO: 2.0 ng/mL, IQR[1.5–4.1] versus <0,5 ng/mL, IQR[<0.5–1.1], p < 0.001). During liver transplantation, histamine concentrations decreased to 1.8 nM, IQR[0.5–4.9] in the anhepatic phase (p < 0.0001 versus baseline), and to 1.5 nM, IQR[0.5–2.9] after reperfusion (p < 0.0001 versus baseline). In contrast, DAO concentrations increased to 35.5 ng/ml, IQR[20–50] in the anhepatic phase (p = 0.001 versus baseline) and to 39.5 ng/ml, IQR[23–64] after reperfusion (p = 0.001 versus baseline), correlating inversely with histamine. Norepinephrine requirements during human liver transplantation correlated significantly with DAO concentrations in the anhepatic phase (r = 0.58, p = 0.011) and after reperfusion (r = 0.56; p = 0.022). In patients undergoing orthotopic liver transplantation, histamine concentrations decrease whereas DAO concentrations increase manifold. Diamine oxidase correlates with intraoperative norepinephrine requirements in patients undergoing OLT.
Effects of metazachlor and its major metabolite metazachlor OA on early life stages of marbled crayfish
Authors: Velisek Josef , Stara Alzbeta , Kubec Jan , Zuskova Eliska , Buric Milos , Kouba Antonin
Published: January 2020

The effects of the herbicide metazachlor and its major metabolite metazachlor OA at two concentrations, including environmentally relevant concentrations of metazachlor (0.0115 µmol/l and 0.0790 µmol/l) and metazachlor OA (0.0117 µmol/l and 0.0805 µmol/l), respectively, were evaluated on early ontogeny, growth, behaviour, oxidative stress, antioxidant enzyme levels, histology, and mortality of marbled crayfish Procambarus virginalis. Both tested concentrations of metazachlor and metazachlor OA were associated with significantly lower growth and delayed ontogenetic development compared to controls. Exposure of metazachlor at 0.0115 µmol/l and metazachlor OA at 0.0117 µmol/l and 0.0805 µmol/l resulted in significantly lower activity of total superoxide dismutase (SOD), catalase (CAT), glutathione s-transferase (GST), glutathione reductase (GR), and reduced glutathione (GSH) compared with control and resulted in gill anomalies ranging from wall thinning to focal disintegration of branchial structure. Metazachlor at the environmentally relevant concentration of 0.0790 µmol/l was associated with significant alterations of crayfish distance moved and walking speed. The potential risk associated with metazachlor use in agriculture related to effects on non-target aquatic organisms.
Lack of maintenance of motorway fences works against their intended purpose with potential negative impacts on protected species
Authors: Farfán Miguel A. , Fa Julia E. , Martín-Taboada Adrián , García-Carrasco José María , Duarte Jesús
Published: January 2020

Linear infrastructure intrusions into natural ecosystems, such as motorways and high-speed railways, causes direct loss of habitat but also impacts fauna through collisions. Wildlife road mortality is well documented and extensive conservation legislation exists in many countries to minimise the negative impact of these infrastructures. However, although these measures are implemented because of legislation, these structures are often not adequately maintained. Here we present data on the functionality of perimeter fences along two motorways in Malaga province (southern Spain) erected to prevent collisions with the common chameleon (Chamaeleo chamaeleon). We sampled the fences along the 14 km of the two motorways included in the 17 1 × 1 km squares of the study area. Our results show that the reptile fence is permeable throughout at those points where the metal sheeting was absent and where the vegetation had overgrown around the fence, hence allowing chameleons to cross. Given our results, we conclude that this situation is likely to be similar in other regions of Spain and in other countries. This is because construction/concessionary companies do not consider the environmental impact of construction projects in the medium and long term, and environmental authorities do not ensure that companies comply with the legislation.
Pharmacological enrichment of polygenic risk for precision medicine in complex disorders
Authors: Reay William R. , Atkins Joshua R. , Carr Vaughan J. , Green Melissa J. , Cairns Murray J.
Published: January 2020

Individuals with complex disorders typically have a heritable burden of common variation that can be expressed as a polygenic risk score (PRS). While PRS has some predictive utility, it lacks the molecular specificity to be directly informative for clinical interventions. We therefore sought to develop a framework to quantify an individual’s common variant enrichment in clinically actionable systems responsive to existing drugs. This was achieved with a metric designated the pharmagenic enrichment score (PES), which we demonstrate for individual SNP profiles in a cohort of cases with schizophrenia. A large proportion of these had elevated PES in one or more of eight clinically actionable gene-sets enriched with schizophrenia associated common variation. Notable candidates targeting these pathways included vitamins, antioxidants, insulin modulating agents, and cholinergic drugs. Interestingly, elevated PES was also observed in individuals with otherwise low common variant burden. The biological saliency of PES profiles were observed directly through their impact on gene expression in a subset of the cohort with matched transcriptomic data, supporting our assertion that this gene-set orientated approach could integrate an individual’s common variant risk to inform personalised interventions, including drug repositioning, for complex disorders such as schizophrenia.
Solving the transcription start site identification problem with ADAPT-CAGE: a Machine Learning algorithm for the analysis of CAGE data
Authors: Georgakilas Georgios K. , Perdikopanis Nikos , Hatzigeorgiou Artemis
Published: January 2020

Cap Analysis of Gene Expression (CAGE) has emerged as a powerful experimental technique for assisting in the identification of transcription start sites (TSSs). There is strong evidence that CAGE also identifies capping sites along various other locations of transcribed loci such as splicing byproducts, alternative isoforms and capped molecules overlapping introns and exons. We present ADAPT-CAGE, a Machine Learning framework which is trained to distinguish between CAGE signal derived from TSSs and transcriptional noise. ADAPT-CAGE provides highly accurate experimentally derived TSSs on a genome-wide scale. It has been specifically designed for flexibility and ease-of-use by only requiring aligned CAGE data and the underlying genomic sequence. When compared to existing algorithms, ADAPT-CAGE exhibits improved performance on every benchmark that we designed based on both annotation- and experimentally-driven strategies. This performance boost brings ADAPT-CAGE in the spotlight as a computational framework that is able to assist in the refinement of gene regulatory networks, the incorporation of accurate information of gene expression regulators and alternative promoter usage in both physiological and pathological conditions.
MTAP-deficiency could predict better treatment response in advanced lung adenocarcinoma patients initially treated with pemetrexed-platinum chemotherapy and bevacizumab
Authors: Jing Wang , Zhu Hui , Liu Wenjuan , Zhai Xiaoyang , Tian Hairong , Yu Jinming
Published: January 2020

To investigate the predictive value of methylthioadenosine phosphorylase (MTAP) on treatment response and survival in advanced lung adenocarcinoma. MTAP expression was detected by immunohistochemistry. Treatment response and survival were compared according to MTAP expression level. The results indicated MTAP-low expression was observed in 61.2% (101/165) of all patients. The objective response rate and disease control rate improved in the MTAP-low group (64.4% vs 46.9%, p = 0.035; 92.1% vs. 79.7%, p = 0.03; respectively). The median progression-free survival and survival time in the MTAP-low group were significantly lower than that in the MTAP-high group (8.1 vs. 13.1 months, p = 0.002; 22 vs. 32 months, p = 0.044). Multivariate analysis demonstrated that brain metastasis (HR 1.55, p = 0.046), thoracic radiation (HR 0.52, p = 0.026), and MTAP-low expression (HR 1.36, p = 0.038) were independent factors on survival. It is concluded that MTAP-low expression could predict improved treatment response but worsened survival in advanced lung adenocarcinoma.
Expression and functional analysis of the hydrogen peroxide biosensors HyPer and HyPer2 in C2C12 myoblasts/myotubes and single skeletal muscle fibres
Authors: Fernández-Puente Escarlata , Sánchez-Martín Manuel A. , de Andrés Jorge , Rodríguez-Izquierdo Lorena , Méndez Lucía , Palomero Jesús
Published: January 2020

Hydrogen peroxide (H2O2) is generated in cells and plays an important role as a signalling molecule. It has been reported that H2O2 is involved in physiological and pathological processes in skeletal muscle. However, H2O2 detection in cells with traditional techniques produces frequent artefacts. Currently, the HyPer biosensor detects intracellular H2O2 specifically in real time using fluorescence microscopy. The aim of this study was to develop and optimize approaches used to express the HyPer biosensor in different models of skeletal muscle cells, such as the C2C12 myoblast/myotube cell line and mature skeletal muscle fibres isolated from C57BL/6J mice, and to measure intracellular H2O2 in real time in these cells. The results show that the expression of the HyPer biosensor in skeletal muscle cells is possible. In addition, we demonstrate that HyPer is functional and that this biosensor detects changes and fluctuations in intracellular H2O2 in a reversible manner. The HyPer2 biosensor, which is a more advanced version of HyPer, presents improved properties in terms of sensitivity in detecting lower concentrations of H2O2 in skeletal muscle fibres. In conclusion, the expression of the HyPer biosensor in the different experimental models combined with fluorescence microscopy techniques is a powerful methodology to monitor and register intracellular H2O2 specifically in skeletal muscle. The innovation of the methodological approaches presented in this study may present new avenues for studying the role of H2O2 in skeletal muscle pathophysiology. Furthermore, the methodology may potentially be adapted to yield other specific biosensors for different reactive oxygen and nitrogen species or metabolites involved in cellular functions.
Structural Analysis and Optimization of Convolutional Neural Networks with a Small Sample Size
Authors: D’souza Rhett N. , Huang Po-Yao , Yeh Fang-Cheng
Published: January 2020

Deep neural networks have gained immense popularity in the Big Data problem; however, the availability of training samples can be relatively limited in specific application domains, particularly medical imaging, and consequently leading to overfitting problems. This “Small Data” challenge may need a mindset that is entirely different from the existing Big Data paradigm. Here, under the small data scenarios, we examined whether the network structure has a substantial influence on the performance and whether the optimal structure is predominantly determined by sample size or data nature. To this end, we listed all possible combinations of layers given an upper bound of the VC-dimension to study how structural hyperparameters affected the performance. Our results showed that structural optimization improved accuracy by 27.99%, 16.44%, and 13.11% over random selection for a sample size of 100, 500, and 1,000 in the MNIST dataset, respectively, suggesting that the importance of the network structure increases as the sample size becomes smaller. Furthermore, the optimal network structure was mostly determined by the data nature (photographic, calligraphic, or medical images), and less affected by the sample size, suggesting that the optimal network structure is data-driven, not sample size driven. After network structure optimization, the convolutional neural network could achieve 91.13% accuracy with only 500 samples, 93.66% accuracy with only 1000 samples for the MNIST dataset and 94.10% accuracy with only 3300 samples for the Mitosis (microscopic) dataset. These results indicate the primary importance of the network structure and the nature of the data in facing the Small Data challenge.
Different performances of Ni3(PO4)2 in TiO2 photocatalysis under aerobic and anaerobic conditions
Authors: Wang Yaru , Zhao Jianjun , Chen Chen , Xu Yiming
Published: January 2020

A nickel phosphate deposited TiO2 was more photoactive than TiO2, not only for phenol oxidation under air, but also for proton reduction under N2. These are due to formation and involvement of highly reactive Ni4+ and catalytic Ni0, respectively.
Trinuclear vanadium(iv) and vanadium(v) complexes derived from 2,4,6-triacetylphloroglucinol and study of their peroxidase mimicking activity
Authors: Maurya Mannar R. , Tomar Reshu , Avecilla Fernando , Ribeiro Nádia , Carvalho M. Fernanda N. N. , Kuznetsov Maxim L. , Correia Isabel , Pessoa João Costa
Published: January 2020

Solid state and solution studies of trinuclear VIVO- and VVO2-complexes and their peroxidase mimicking activity, through oxidation of dopamine to aminochrome, are reported.
Nanoelectrode-mediated single neuron activation
Authors: Kwon Juyoung , Ko Sukjin , Lee Jaejun , Na Jukwan , Sung Jaesuk , Lee Hyo-Jung , Lee Seonghyeon , Chung Seungsoo , Choi Heon-Jin
Published: January 2020

A spatially and temporally confined single neuron activation method exploiting the strong interfaces between a neuron and a nanowire electrode.
Enantioselective nickel-catalyzed arylative and alkenylative intramolecular 1,2-allylations of tethered allene–ketones
Authors: Di Sanza Riccardo , Nguyen Thi Le Nhon , Iqbal Naeem , Argent Stephen P. , Lewis William , Lam Hon Wai
Published: January 2020

Chiral tertiary-alcohol-containing aza- and carbocycles are produced in high diastereo- and enantioselectivities by the nickel-catalyzed reaction of tethered allene–ketones with (hetero)arylboronic acids or potassium vinyltrifluoroborate.
Identification of 13 novel USH2A mutations in Chinese retinitis pigmentosa and Usher syndrome patients by targeted next-generation sequencing
Authors: Qu Ling-hui , Jin Xin , Long Yan-ling , Ren Jia-yun , Weng Chuang-huang , Xu Hai-wei , Liu Yong , Meng Xiao-hong , Li Shi-ying , Yin Zheng-qin
Published: January 2020

Background: The USH2A gene encodes usherin, a basement membrane protein that is involved in the development and homeostasis of the inner ear and retina. Mutations in USH2A are linked to Usher syndrome type II (USH II) and non-syndromic retinitis pigmentosa (RP). Molecular diagnosis can provide insight into the pathogenesis of these diseases, facilitate clinical diagnosis, and identify individuals who can most benefit from gene or cell replacement therapy. Here, we report 21 pathogenic mutations in the USH2A gene identified in 11 Chinese families by using the targeted next-generation sequencing (NGS) technology.

Methods: In all, 11 unrelated Chinese families were enrolled, and NGS was performed to identify mutations in the USH2A gene. Variant analysis, Sanger validation, and segregation tests were utilized to validate the disease-causing mutations in these families.

Results: We identified 21 pathogenic mutations, of which 13, including 5 associated with non-syndromic RP and 8 with USH II, have not been previously reported. The novel variants segregated with disease phenotype in the affected families and were absent from the control subjects. In general, visual impairment and retinopathy were consistent between the USH II and non-syndromic RP patients with USH2A mutations.

Conclusions: These findings provide a basis for investigating genotype–phenotype relationships in Chinese USH II and RP patients and for clarifying the pathophysiology and molecular mechanisms of the diseases associated with USH2A mutations.
Short-chain fatty acids accompanying changes in the gut microbiome contribute to the development of hypertension in patients with preeclampsia
Authors: Chang Yanling , Chen Yunyan , Zhou Qiong , Wang Chuan , Chen Lei , Di Wen , Zhang Yu
Published: January 2020

Preeclampsia (PE) is regarded as a pregnancy-associated hypertension disorder that is related to excessive inflammatory responses. Although the gut microbiota (GM) and short-chain fatty acids (SCFAs) have been related to hypertension, their effects on PE remain unknown. We determined the GM abundance and faecal SCFA levels by 16S ribosomal RNA (rRNA) sequencing and gas chromatography, respectively, using faecal samples from 27 patients with severe PE and 36 healthy, pregnant control subjects. We found that patients with PE had significantly decreased GM diversity and altered GM abundance. At the phylum level, patients with PE exhibited decreased abundance of Firmicutes albeit increased abundance of Proteobacteria; at the genus level, patients with PE had lower abundance of Blautia, Eubacterium_rectale, Eubacterium_hallii, Streptococcus, Bifidobacterium, Collinsella, Alistipes, and Subdoligranulum, albeit higher abundance of Enterobacter and Escherichia_Shigella. The faecal levels of butyric and valeric acids were significantly decreased in patients with PE and significantly correlated with the above-mentioned differential GM abundance. We predicted significantly increased abundance of the lipopolysaccharide (LPS)-synthesis pathway and significantly decreased abundance of the G protein-coupled receptor (GPCR) pathway in patients with PE, based on phylogenetic reconstruction of unobserved states (PICRUSt). Finally, we evaluated the effects of oral butyrate on LPS-induced hypertension in pregnant rats. We found that butyrate significantly reduced the blood pressure (BP) in these rats. In summary, we provide the first evidence linking GM dysbiosis and reduced faecal SCFA to PE and demonstrate that butyrate can directly regulate BP in vivo, suggesting its potential as a therapeutic agent for PE.
Widened nested array: configuration design, optimal array and DOA estimation algorithm
Authors: Lin Xinping , Gong Pan , He Lang , Li Jianfeng
Published: January 2020

A generalised nested array (GNA) configuration with large minimum inter‐element spacing is attractive to alleviate mutual coupling. In this study, by decomposing and rearranging the sub‐arrays of GNA, the authors propose a new nested array configuration named as widened nested array (WNA). The WNA enables to provide the reduced mutual coupling, enhanced degrees of freedom (DOFs), extended array aperture and improved direction of arrival (DOA) estimation performance compared to GNA. The closed‐form expressions for sensor positions of WNA are given and the optimal array configuration for largest DOFs is derived. Meanwhile, the authors propose a partial angular compressed sensing(CS) based DOA estimation algorithm for WNA. Specifically, discrete Fourier transform method is first derived for consecutive DOFs of WNA to obtain initial DOA estimates. Subsequently, the initial estimates are utilised to compress the angular range of overcomplete dictionary of the CS algorithm, which is exploited to obtain the fine DOA estimates. Extensive simulation results testify that the proposed algorithm has the same estimation accuracy as CS algorithm with lower complexity.
Modelling and robust control of digitally controlled large‐scale PV plants
Authors: Xie Bao , Mao Mingxuan , Guo Ke , Zhou Lin , Liu Tiantian , Zhang Qianjin , Wan Yihao
Published: January 2020

Large‐scale photovoltaic (PV) plants may be destabilised by the large grid impedance introduced by transformers and long transmission lines. When considering the digital control delay of grid‐connected inverters, the problem will become more serious. In this study, the equivalent impedance model of digitally controlled large‐scale PV plants is established, considering that the values of the parameters of the LCL filter follow Gaussian distributions. Then, the system stability can be analysed conveniently, and the stability analysis shows that the digital control delay will make the system robust to large grid impedance worse. To enhance the stability‐robustness of the system, an H∞ robust controller is proposed in this study. By properly selecting the weighting functions, the desired tracking error performance and robustness are achieved on the basis of the mixed‐sensitivity optimisation control design. Compared with the traditional dual current loop control strategy, the H∞ robust controller improves significantly the system stability‐robustness against large grid impedance. Finally, simulation and experimental tests are carried out in this study, and the results demonstrate the effectiveness of the proposed H∞ robust controller.
Three‐stage SiC‐based bi‐directional on‐board battery charger with titanium level efficiency
Authors: Radimov Nikolay , Li Guibin , Tang Mengting , Wang Xiaoyu
Published: January 2020

This Letter proposes a novel control and optimisation strategy for a bi‐directional, three‐stage, on‐board battery charger (OBC) achieving 80 PLUS Titanium efficiency. The proposed strategy utilises the benefits of silicon carbide (SiC) devices and is based on direct current hysteretic control (DCHC) with optimisation of switching patterns and dead time. The OBC first stage is a solid‐state transformer that provides the isolation barrier and is operated under zero‐current switching/zero‐voltage switching (ZVS) conditions. The second stage is a bi‐directional buck–boost converter that operates in critical conduction mode (CRM) with automatic dead time optimisation to achieve ZVS operation. The third stage is an H‐bridge inverter with a DCHC controlled current loop to optimise dynamic and steady‐state performance and provide a smooth transition between CRM and continuous conduction mode. The DCHC is implemented using a hybrid software/hardware approach. The experimental results show that the OBC can not only change the power flow direction within a few milliseconds but can also provide reactive power support for the grid. Additionally, the OBC achieves a peak efficiency of 96.65% and a minimum total harmonic distortion equal to 1%.