bluuebunny/crossref_metadata_2025 huggingface dataset:
Negative optokinetic afternystagmus in larval zebrafish demonstrates set-point adaptation
Authors: Lin Ting-Feng , Mohammadi Mohammad , Fathalla Ahmed M. , Pul Duygu , Lüthi Dennis , Romano Fausto , Straumann Dominik , Cullen Kathleen E. , Chacron Maurice J. , Huang Melody Ying-Yu
Published: December 2019

Motor learning is essential to maintain accurate behavioral responses. We used a larval zebrafish model to study ocular motor learning behaviors. During a sustained period of optokinetic stimulation in 5-day-old wild-type zebrafish larvae the slow-phase eye velocity decreased over time. Then interestingly, a long-lasting and robust negative optokinetic afternystagmus (OKAN) was evoked upon light extinction. The slow-phase velocity, the quick-phase frequency, and the decay time constant of the negative OKAN were dependent on the stimulus duration and the adaptation to the preceding optokinetic stimulation. Based on these results, we propose a sensory adaptation process during continued optokinetic stimulation, which, when the stimulus is removed, leads to a negative OKAN as the result of a changed retinal slip velocity set point, and thus, a sensorimotor memory. The pronounced negative OKAN in larval zebrafish not only provides a practical solution to the hitherto unsolved problems of observing negative OKAN, but also, and most importantly, can be readily applied as a powerful model for studying sensorimotor learning and memory in vertebrates.
Frailty is Associated with an Increased Risk of Major Adverse Outcomes in Elderly Patients Following Surgical Treatment of Hip Fracture
Authors: Chen Chiu-Liang , Chen Chun-Min , Wang Chun-Yi , Ko Po-Wei , Chen Chung-Hwan , Hsieh Chen-Pu , Chiu Herng-Chia
Published: December 2019

We intended to explore the effect of level of frailty on, and relationship with, 1-, 3-, and 6-month postoperative emergency department visits, readmissions, and mortality. This is a prospective multicenter observational cohort study design. Patients aged 50 years or older treated for hip fracture (n = 245) were taken from Orthopedic wards in one medical center (n = 131) and one district hospital (n = 114) in Changhua County, Taiwan. Frailty was defined as measured by the validated Clinical Frailty Scale and categorized as robust, pre-frail, and frail. We used Kaplan-Meier analysis to estimate survival rates and Cox regression to estimate the risk of frailty associated with adverse outcomes. To examine the longitudinal associations between frailty and adverse outcome, the cross-lagged models were explored. Of the 245 patients, 55 (22.4%) were classified as frail, 113 (46.1%) as pre-frail, and 77 (31.4%) as robust. More cumulative events occurred for frail than for robust patients for each adverse outcome. Frailty has long-term effect on each adverse outcome after discharge, rather than the effect simultaneously. Targeting pre-frailty and frailty is essential for prevent adverse outcomes and improving the overall health of older adults after discharge for hip fracture.
A qPCR method for genome editing efficiency determination and single-cell clone screening in human cells
Authors: Li Bo , Ren Naixia , Yang Lele , Liu Junhao , Huang Qilai
Published: December 2019

CRISPR/Cas9 technology has been widely used for targeted genome modification both in vivo and in vitro. However, an effective method for evaluating genome editing efficiency and screening single-cell clones for desired modification is still lacking. Here, we developed this real time PCR method based on the sensitivity of Taq DNA polymerase to nucleotide mismatch at primer 3′ end during initiating DNA replication. Applications to CRISPR gRNAs targeting EMX1, DYRK1A and HOXB13 genes in Lenti-X 293 T cells exhibited comprehensive advantages. Just in one-round qPCR analysis using genomic DNA from cells underwent CRISPR/Cas9 or BE4 treatments, the genome editing efficiency could be determined accurately and quickly, for indel, HDR as well as base editing. When applied to single-cell clone screening, the genotype of each cell colony could also be determined accurately. This method defined a rigorous and practical way in quantify genome editing events.
Quantum Mechanisms of Electron and Positron Acceleration through Nonlinear Compton Scatterings and Nonlinear Breit-Wheeler Processes in Coherent Photon Dominated Regime
Authors: Zhang Bo , Zhang Zhimeng , Deng Zhi-gang , Teng Jian , He Shu-kai , Hong Wei , Zhou Weimin , Gu Yuqiu
Published: December 2019

Electric force is presently the only means in laboratory to accelerate charged particles to high energies, corresponding acceleration processes are classical and continuous. Here we report on how to accelerate electrons and positrons to high energies using ultra intense lasers (UIL) through two quantum processes, nonlinear Compton scattering and nonlinear Breit-Wheeler process. In the coherent photon dominated regime of these two processes, the former can effectively boost electrons/positrons and the latter can produce high energy electrons and positrons with low energy γ photons. The energy needed for such quantum acceleration (QA) is transferred from large numbers of coherent laser photons through the two quantum processes. QA also collimate the generated high energy electrons and positrons along the laser axis and the effective acceleration distance is of microscopic dimensions. Proof of principle QA experiment can be performed on 100 petawatt (PW) scale lasers which are in building or planning.
Modeling recovery of natural gas from hydrate reservoirs with carbon dioxide sequestration: Validation with Iġnik Sikumi field data
Authors: Palodkar Avinash V. , Jana Amiya K.
Published: December 2019

Fundamental understanding of guest gas replacement in hydrate reservoirs is crucial for the enhanced recovery of natural gas and carbon dioxide (CO2) sequestration. To gain physical insight into this exchange process, this work aims at developing and validating a clathrate hydrate model for gas replacement. Most of the practical concerns associated with naturally occurring gas hydrates, including hydrate formation and dissociation in interstitial pore space between distributed sand particles in the presence of salt ions and in irregular nanometer-sized pores of those particles, irregularity in size of particles and shape of their pores, interphase dynamics during hydrate formation and decay, and effect of surface tension, are addressed. An online parameter identification technique is devised for automatic tuning of model parameters in the field. This model is employed to predict the laboratory-scale data for methane hydrate formation and decomposition. Subsequently, the model is validated with the field data of the Prudhoe Bay Unit on the Alaska North Slope during 2011 and 2012. In this Iġnik Sikumi field experiment, mixed CO2 (i.e., CO2 + N2) is used as a replacement agent for natural gas recovery. It is observed that the proposed formulation secures a promising performance with a maximum absolute average relative deviation (AARD) of about 2.83% for CH4, which is even lower, 0.84% for CO2 and 1.67% for N2.
Finnish Parkinson’s disease study integrating protein-protein interaction network data with exome sequencing analysis
Authors: Siitonen Ari , Kytövuori Laura , Nalls Mike A. , Gibbs Raphael , Hernandez Dena G. , Ylikotila Pauli , Peltonen Markku , Singleton Andrew B. , Majamaa Kari
Published: December 2019

Variants associated with Parkinson’s disease (PD) have generally a small effect size and, therefore, large sample sizes or targeted analyses are required to detect significant associations in a whole exome sequencing (WES) study. Here, we used protein-protein interaction (PPI) information on 36 genes with established or suggested associations with PD to target the analysis of the WES data. We performed an association analysis on WES data from 439 Finnish PD subjects and 855 controls, and included a Finnish population cohort as the replication dataset with 60 PD subjects and 8214 controls. Single variant association (SVA) test in the discovery dataset yielded 11 candidate variants in seven genes, but the associations were not significant in the replication cohort after correction for multiple testing. Polygenic risk score using variants rs2230288 and rs2291312, however, was associated to PD with odds ratio of 2.7 (95% confidence interval 1.4–5.2; p < 2.56e-03). Furthermore, an analysis of the PPI network revealed enriched clusters of biological processes among established and candidate genes, and these functional networks were visualized in the study. We identified novel candidate variants for PD using a gene prioritization based on PPI information, and described why these variants may be involved in the pathogenesis of PD.
Combined Ultrasound/Microwave Chemocatalytic Method for Selective Conversion of Cellulose into Lactic Acid
Authors: Tallarico Sofia , Costanzo Paola , Bonacci Sonia , Macario Anastasia , Di Gioia Maria Luisa , Nardi Monica , Procopio Antonio , Oliverio Manuela
Published: December 2019

Cellulose is the main component of lignocellulosic biomass. Its direct chemocatalytic conversion into lactic acid (LA), a powerful biobased chemical platform, represents an important, and more easily scalable alternative to the fermentative way. In this paper, we present the selective hydrothermal conversion of cellulose and simple sugars into LA, under mild reaction conditions in presence of ErCl3 grafted on the mesoporous silica (MCM-41) surface. High yields and selectivity were obtained for the conversion of sugars under microwave (MW) irradiation at a relatively low temperature (200 °C) and short reaction times (10 min) under microwave (MW) irradiation. Ultrasounds (US) pre-treatment was investigated to reduce the cellulose crystallinity, before the MW-assisted conversion, providing LA with a yield of 64% within 90 min at 220 °C below the subcritical water conditions with increased operational safety. We finally discuss the scalability of the process and the recyclability of the catalyst.
Mechanical feedback cooling assisted by optical cavity cooling of the thermal vibration of a microcantilever
Authors: Kawamura Y.
Published: December 2019

This study describes a new two-step process to cool the thermal vibration of microcantilevers. The process combines active mechanical feedback cooling and optical cavity cooling. A micro-Fabry–Perot interferometer, built in-house, is set atop a microcantilever to measure the vibration amplitude, the high optical power density of which induces cavity cooling in the optical cavity. Using a two-step cooling procedure, the equivalent temperature of the thermal vibration of a microcantilever is lowered from room temperature to the theoretical cooling limit of 0.063 K, a much lower temperature than that achieved via simple cavity cooling (18 K), and then by mechanical feedback cooling (0.135 K) obtained for the same type of microcantilevers in previous studies. This experimental demonstration showcases a new type of cooling process of the amplitude of thermal vibration for micro-mechanical resonators to a lower temperature and does not need additional cooling using a conventional cryogenic refrigerator.
Immunity to Influenza is dependent on MHC II polymorphism: study with 2 HLA transgenic strains
Authors: Luckey David , Weaver Eric A. , Osborne Douglas G. , Billadeau Daniel D. , Taneja Veena
Published: December 2019

Major histocompatibility complex II (MHC II) molecules are involved in antigen presentation and the development of a functional adaptive immune response. Evolutionary selection for MHC molecules that effectively clear infectious agents provides an advantage to humans. However, certain class II molecules are associated with autoimmune diseases. In this study we infected autoimmune-susceptible DRB1*0401.AEo and non-susceptible *0402.AEo mice with H1N1 influenza and determined clearance and protective immunity to H3N2 virus. *0401 mice generated a robust TLR-triggered immune response and cleared H1N1 influenza virus infection. After vaccination and challenge with H1N1, *0401 mice, when challenged with H3N2, generated cross-protective immunity to heterosubtypic H3N2 influenza strain whereas *0402 mice cleared the H1N1 infection but did not generate cross-protective immunity against the H3N2 influenza strain. The intracellular trafficking route of MHCII revealed that *0401 molecules traffic through the late endosome/lysosomes while *0402 molecules traffic into early endosomes. This suggested that trafficking of MHCII could affect the functional output of the innate immune response and clearance of viral infections. Also, DRB1*0401 mice live longer than HLA-DRB1*0402 mice. The study provides a potential hypothesis for evolutionary selection of *0401 molecule, even though it is associated with autoreactivity, which may be dependent on the availability of peptide repertoire of self-antigens.
Au-PDA@SiO2 core-shell nanospheres decorated rGO modified electrode for electrochemical sensing of cefotaxime
Authors: Khan M. Z. H. , Daizy M. , Tarafder C. , Liu X.
Published: December 2019

In this work, we have successfully synthesized core-shell structured Au-PDA@SiO2 nanospheres and decorated on reduced graphene oxide (rGO) modified glassy carbon electrode for the electrochemical detection of cefotaxime. The one-pot hydrothermal method was used to synthesis core-shell nanostructures by loading Au nanoparticles on polydopamine (PDA) coated SiO2 nanospheres. The as-prepared Au-PDA@SiO2 nanospheres were used to fabricate electrochemically reduced graphene oxide (rGO) modified glassy carbon electrode (Au-PDA@SiO2/rGO/GCE) for electrochemical determination of cefotaxime. Scanning electron microscopy, powder x-ray diffraction, transmission electron microscopy, and Fourier-transform infrared spectroscopy were used to confirm the structure and morphology of the as-prepared nanospheres. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were performed for electrochemical characterizations different modified electrodes. It was revealed that the nanocomposite modified electrodes exhibited excellent electrochemical performances for electrooxidation of target analytes and could achieve ultra-sensitive detections. A linear relationship was observed between peak currents and concentrations in the ranges of 1.0 × 10−9 to 5.0 × 10−8 M (R2 = 0.9877), and 1.0 × 10−7 to 5.0 × 10−6 M (R2 = 0.9821) for cefotaxime with a detection limit (S/N = 3) of 1.0 × 10−10 M. It can be deduced that the proposed sensor is suitable for the sensitive detection of cefotaxime in pharmaceutical samples.
Tryptone-stabilized gold nanoparticles induce unipolar clustering of supernumerary centrosomes and G1 arrest in triple-negative breast cancer cells
Authors: Nirmala J. Grace , Lopus Manu
Published: December 2019

Gold nanoparticles of different sizes, shapes, and decorations exert a variety of effects on biological systems. We report a novel mechanism of action of chemically modified, tryptone-stabilized gold nanoparticles (T-GNPs) in the triple-negative breast cancer (TNBC) cell line, MDA-MB-231. The T-GNPs, synthesized using HAuCl4.3H2O and tryptone and characterized by an assortment of spectroscopy techniques combined with high-resolution electron microscopy, demonstrated strong antiproliferative and anti-clonogenic potential against MDA-MB-231 cells, arresting them at the G1 phase of the cell cycle and promoting apoptosis. The molecular mechanism of action of these particles involved induction of unipolar clustering and hyper amplification of the supernumerary centrosomes (a distinctive feature of many tumour cells, including TNBC cells). The clustering was facilitated by microtubules with suppressed dynamicity. Mass spectrometry-assisted proteomic analysis revealed that the T-GNP-induced G1 arrest was facilitated, at least in part, by downregulation of ribosome biogenesis pathways. Due to the presence of supernumerary centrosomes in many types of tumour cells, we propose chemical induction of their unipolar clustering as a potential therapeutic strategy.
Electric readout of magnetic stripes in insulators
Authors: Chen Yao , Shiomi Yuki , Qiu Zhiyong , Niizeki Tomohiko , Umeda Maki , Saitoh Eiji
Published: December 2019

In superconductors, a topological configuration of the superconducting order parameter called a superconducting vortex carries magnetization. Such a magnetic topological object behaves like a minute particle generating a magnetic flux. Since the flux is localized with a nanometer scale, the vortex provides a nano-scale probe for local magnetic fields. Here we show that information of magnetic stripes in insulators can be read out by using vortices in an adjacent superconductor film as a probe. The orientation and width of magnetic micro stripes are both transcribed into resistance change of the superconductor through the modulation of vortex mobility affected by local magnetization. By changing the direction of external magnetic fields, zero-field resistance changes continuously according to the stripe orientation, and its modulation magnitude reaches up to 100%. The width of the stripes can also be estimated from the oscillatory magnetoresistance. Our results demonstrate a new possibility for non-volatile analog memory devices based on topological objects.
Incidence of Terson Syndrome in Treated Subarachnoid Hemorrhage in South Korea: a National Health Insurance Database Study
Authors: Hong Eun Hee , Seong Mincheol , Yeom Hosuck , Choi Sungyong , Choi Kyu-Sun , Kang Min Ho , Cho Heeyoon , Shin Yong Un
Published: December 2019

The aim of this study is to investigate the incidence and mortality of Terson syndrome in patients with treated subarachnoid hemorrhage (SAH) in South Korea. In this nationwide, population-based study, we used the National Health Insurance(NHI) database (2011–2015) to identify patients aged ≥18 years. Newly diagnosed non-traumatic SAH, treated using clipping or coil embolization, were identified, and Terson syndrome was defined as newly diagnosed retinal or vitreous hemorrhage within 3 months of SAH diagnosis. We identified 22,864 patients with treated SAH (tSAH), 196 of whom had Terson syndrome, with the cumulative incidence during 5 years of 0.86% (95% CI: 0.74–0.98): 1.10% (95% CI: 0.88–1.33) in men and 0.71% (95% CI, 0.58–0.85) in women. The cumulative incidence of Terson syndrome in patients aged under 40 was higher than in those aged 40 or over (1.41% vs. 0.81%; p = 0.007). The mortality rate of Terson syndrome in patients with tSAH was not different from that in those without Terson syndrome (4.08% vs. 7.30%; p = 0.089). This was the first nationwide epidemiological study of Terson syndrome using a population-based database. The incidence of Terson syndrome in patients with tSAH was higher in those age under 40 than in those aged 40 or over.
The discrimination of facial sex in developmental prosopagnosia
Authors: Marsh Jade E. , Biotti Federica , Cook Richard , Gray Katie L. H.
Published: December 2019

Developmental prosopagnosia (DP) is a neurodevelopmental condition characterised by difficulties recognising and discriminating faces. It is currently unclear whether the perceptual impairments seen in DP are restricted to identity information, or also affect the perception of other facial characteristics. To address this question, we compared the performance of 17 DPs and matched controls on two sensitive sex categorisation tasks. First, in a morph categorisation task, participants made binary decisions about faces drawn from a morph continuum that blended incrementally an average male face and an average female face. We found that judgement precision was significantly lower in the DPs than in the typical controls. Second, we used a sex discrimination task, where female or male facial identities were blended with an androgynous average face. We manipulated the relative weighting of each facial identity and the androgynous average to create four levels of signal strength. We found that DPs were significantly less sensitive than controls at each level of difficulty. Together, these results suggest that the visual processing difficulties in DP extend beyond the extraction of facial identity and affects the extraction of other facial characteristics. Deficits of facial sex categorisation accord with an apperceptive characterisation of DP.
Microphysical Features of Rain and Rain events during different Seasons over a Tropical Mountain location using an Optical Disdrometer
Authors: Sreekanth T. S. , Varikoden Hamza , Mohan Kumar G. , Resmi E. A.
Published: December 2019

In the present study, seven-year-long observations of rain microphysical properties are presented using a ground-based disdrometer located at Braemore; a site on the windward slope of the Western Ghats (WG) over the Indian Peninsula. The annual cycle of rainfall shows a bimodal distribution with a primary peak during summer monsoon and secondary peak during pre-monsoon. Pre-monsoon rain events are less in number but are with high intensity and characterize large raindrops and low number concentration. During summer monsoon, short and less intense rain events with small drops are noticed. Post-monsoon rain is having a long duration less intense events with lower concentration of large raindrops compared to the summer monsoon. In the seasonal variation of mean diameter (Dm) and raindrop concentration (NT) with Rain Intensity (RI), winter and pre-monsoon rains exhibit higher values of Dm and lower values of NT compared to the summer and post-monsoon seasons for all the RI ranges. The mean features of the rain microphysical parameters are also supported by the case studies of rain events. RI, Dm and NT are categorized into different range bins for all the seasons to identify their variation and relative rainfall contribution to the total seasonal rainfall. Heavy drizzle/Light rain has maximum rain duration, and the relative contribution to the rainfall is high from heavy rain type. Winter and pre-monsoon rains are mostly contributed from the larger raindrops (>Dm3), and during summer and post-monsoons it is from Dm2 onwards. The distribution of occurrence frequency of NT and rainfall are similar during all four seasons. NT2 recorded rainfall percentage nearly the same as NT1 in summer monsoon and this also supports large number of raindrops in this season. In RI-Duration analysis, all seasons showed similar distribution, and 90% of total duration is contributed from RI with less than 20 mm h−1.
Construction of 3D-rendering imaging of an ischemic rat brain model using the planar FMMD technique
Authors: Kim Chang-Beom , Park Sang-Jin , Jeong Jae-Chan , Choi Seung-Min , Krause Hans-Joachim , Song Dae-Yong , Hong Hyobong
Published: December 2019

Occlusion of the major cerebral artery usually results in brain hypoxic-ischemic injury, which evokes neuroinflammation and microglial activation. Activated microglia are considered a source of multiple neurotoxic factors, such as reactive oxygen species (ROS), in the central nervous system (CNS). We herein present a 3D-rendering brain imaging technique in an experimental rodent model of cerebral ischemia based on 2D magnetic images of superparamagnetic iron oxide nanoparticles (SPIONs) using the planar frequency mixing magnetic detection (p-FMMD) technique. A rat model of cerebral ischemia was established by unilateral middle cerebral artery occlusion with reperfusion (MCAO/R) injury. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was performed to demonstrate the irreversibly damaged ischemic brain tissues, and double immunofluorescent labeling of OX6 (activated microglial marker) and ethidium (ROS marker) was conducted to confirm ROS generation in the activated microglia in the infarcted brain region. The ischemic brain sections treated with OX6-conjugated SPIONs were scanned using our p-FMMD system, yielding 2D images on the basis of the nonlinear magnetic characteristics inherent in SPIONs. The p-FMMD signal images representing microglia activation show an infarct ratio of 44.6 ± 7.1% compared to the contralateral counterpart, which is smaller than observed by TTC (60.9 ± 4.9%) or magnetic resonance imaging (MRI, 65.7 ± 2.7%). Furthermore, we developed a 3D-rendering brain imaging process based on the 2D p-FMMD signal images. The 3D reconstructed model showed a decreased ratio of coincidence of the ischemic regions compared with MRI models. In this study, we successfully conducted a feasibility test on whether our p-FMMD technology, a technique for signaling and imaging based on the nonlinearity of SPIONs, can be used to visualize the ischemic brain region in real time by detecting activated microglia in an MCAO/R animal model. Therefore, our method might allow for a different approach to analyze the pathophysiology of ischemic stroke through molecular imaging. Furthermore, we propose that this magnetic particle imaging (MPI) technique that detects the nonlinear magnetization properties of SPIONs could be applied not only to a stroke model but also to various types of pathophysiological studies as a new bioimaging tool.
Novel halo- and thermo-tolerant Cohnella sp. A01 L-glutaminase: heterologous expression and biochemical characterization
Authors: Mosallatpour Samaneh , Aminzadeh Saeed , Shamsara Mehdi , Hajihosseini Reza
Published: December 2019

L-glutaminase importance to use in the food industry and medicine has attracted much attention. Enzymes stability has always been a challenge while working with them. We heterologously expressed and characterized a novel stable L-glutaminase from an extremophile bacterium (Cohnella sp. A01, PTCC No: 1921). Km, Vmax, catalytic efficiency and specific activity of rSAM were respectively 1.8 mM, 49 µmol/min, 1851 1/(S.mM) and 9.2 IU/mg. Activation energy for substrate to product conversion and irreversible thermo-inactivation were respectively 4 kJ/mol and 105 kJ/mol from the linear Arrhenius plot. rSAM had the highest activity at temperature 50 °C, pH 8 and was resistant to a wide range of temperature and pH. In compare to the other characterized glutaminases, rSAM was the most resistant to NaCl. Mg2+, glycerol, DTT, and BME enhanced the enzyme activity and iodoacetate and iodoacetamide inhibited it. rSAM had only been partially digested by some proteases. According to the Fluorimetry and Circular dichroism analysis, rSAM in pH range from 4 to 11 and temperatures up to 60 °C had structural stability. A cysteine residue in the enzyme active site and a thiol bond were predicted upon the modeled tertiary structure of rSAM. Present structural studies also confirmed the presence of a thiol bond in its structure.
Comprehensive and semi-quantitative analysis of carboxyl-containing metabolites related to gut microbiota on chronic kidney disease using 2-picolylamine isotopic labeling LC-MS/MS
Authors: Kanemitsu Yoshitomi , Mishima Eikan , Maekawa Masamitsu , Matsumoto Yotaro , Saigusa Daisuke , Yamaguchi Hiroaki , Ogura Jiro , Tsukamoto Hiroki , Tomioka Yoshihisa , Abe Takaaki , Mano Nariyasu
Published: December 2019

Carboxyl-containing metabolites, such as bile acids and fatty acids, have many important functions and microbiota is involved in the production of them. In the previous study, we found that the chronic kidney disease (CKD) model mice raised under germ-free conditions provided more severe renal damage than the mice with commensal microbiota. However, the precise influence by the microbiome and carboxyl-containing metabolites to the renal functions is unknown. In this study, we aimed to develop a novel chemical isotope labeling-LC-MS/MS method using the 2-picolylamine and its isotopologue and applied the analysis of effects of microbiome and CKD pathophysiology. The developed semi-quantitative method provided the high accuracy not inferior to the absolute quantification. By comparing of four groups of mice, we found that both microbiota and renal function can alter the composition and level of these metabolites in both plasma and intestine. In particular, the intestinal level of indole-3-acetic acid, short-chain fatty acids and n-3 type of polyunsaturated fatty acid, which play important roles in the endothelial barrier function, were significantly lower in germ-free conditions mice with renal failure. Accordingly, it is suggested these metabolites might have a renoprotective effect on CKD by suppressing epithelial barrier disruption.
Novel insights into molecular mechanisms of Pseudourostyla cristata encystment using comparative transcriptomics
Authors: Pan Nan , Niu Tao , Bhatti Muhammad Zeeshan , Zhang Haiyang , Fan Xinpeng , Ni Bing , Chen Jiwu
Published: December 2019

The encystment of many ciliates is an advanced survival strategy against adversity and the most important reason for ciliates existence worldwide. However, the molecular mechanism for the encystment of free-living ciliates is poorly understood. Here, we performed comparative transcriptomic analysis of dormant cysts and trophonts from Pseudourostyla cristata using transcriptomics, qRT-PCR and bioinformatic techniques. We identified 2565 differentially expressed unigenes between the dormant cysts and the trophonts. The total number of differentially expressed genes in GO database was 1752. The differential unigenes noted to the GO terms were 1993. These differential categories were mainly related to polyamine transport, pectin decomposition, cytoplasmic translation, ribosome, respiratory chain, ribosome structure, ion channel activity, and RNA ligation. A total of 224 different pathways were mapped. Among them, 184 pathways were upregulated, while 162 were downregulated. Further investigation showed that the calcium and AMPK signaling pathway had important induction effects on the encystment. In addition, FOXO and ubiquitin-mediated proteolysis signaling pathway jointly regulated the encystment. Based on these findings, we propose a hypothetical signaling network that regulates Pseudourostyla cristata encystment. Overall, these results provide deeper insights into the molecular mechanisms of ciliates encystment and adaptation to adverse environments.
Association of pre- and post-stroke glycemic status with clinical outcome in spontaneous intracerebral hemorrhage
Authors: Kang Kaijiang , Lu Jingjing , Ju Yi , Wang Wenjuan , Shen Yuan , Wang Anxin , Cao Zhentang , Zhao Xingquan
Published: December 2019

In this study, we aimed to disclose the association of pre- and post-stroke glycemic status with clinical outcome in patients with spontaneous intracerebral hemorrhage (sICH). It was a multicenter, prospective, observational cohort study, conducted in 13 hospitals in Beijing from January 2014 to September 2016. The association of admission random blood glucose (RBG), fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) with clinical outcome at 90 days after sICH onset were analyzed comprehensively. Poor outcome was defined as death or modified Rankin Scale (mRS) score >2. The results showed that elevated RBG and FBG were associated with larger hematoma volume, lower GCS, higher NIHSS (P < 0.001), and poor outcome, but HbA1c was not (P > 0.05). In stratified analysis, the association of poor outcome with elevated FBG or RBG retained statistical significance just in patients without diabetes. Kaplan-Meier curve and Cox regression showed that patients with elevated FBG or RBG had significantly higher risk of death within 90 days (P < 0.05). So we conclude that poststroke hyperglycemia was associated with larger hematoma volume, severe neurological damage and poor clinical outcome, but HbA1c was not relevant to hematoma volume or clinical outcome in patients with sICH.
HIPP1 stabilizes the interaction between CP190 and Su(Hw) in the Drosophila insulator complex
Authors: Melnikova Larisa , Molodina Varvara , Erokhin Maksim , Georgiev Pavel , Golovnin Anton
Published: December 2019

Suppressor of Hairy-wing [Su(Hw)] is one of the best characterized architectural proteins in Drosophila and recruits the CP190 and Mod(mdg4)-67.2 proteins to chromatin, where they form a well-known insulator complex. Recently, HP1 and insulator partner protein 1 (HIPP1), a homolog of the human co-repressor Chromodomain Y-Like (CDYL), was identified as a new partner for Su(Hw). Here, we performed a detailed analysis of the domains involved in the HIPP1 interactions with Su(Hw)-dependent complexes. HIPP1 was found to directly interact with the Su(Hw) C-terminal region (aa 720–892) and with CP190, but not with Mod(mdg4)-67.2. We have generated Hipp1 null mutants (HippΔ1) and found that the loss of Hipp1 does not affect the enhancer-blocking or repression activities of the Su(Hw)-dependent complex. However, the simultaneous inactivation of both HIPP1 and Mod(mdg4)-67.2 proteins resulted in reduced CP190 binding with Su(Hw) sites and significantly altered gypsy insulator activity. Taken together, these results suggested that the HIPP1 protein stabilized the interaction between CP190 and the Su(Hw)-dependent complex.
Deep whole-genome sequencing of 3 cancer cell lines on 2 sequencing platforms
Authors: Arora Kanika , Shah Minita , Johnson Molly , Sanghvi Rashesh , Shelton Jennifer , Nagulapalli Kshithija , Oschwald Dayna M. , Zody Michael C. , Germer Soren , Jobanputra Vaidehi , Carter Jade , Robine Nicolas
Published: December 2019

To test the performance of a new sequencing platform, develop an updated somatic calling pipeline and establish a reference for future benchmarking experiments, we performed whole-genome sequencing of 3 common cancer cell lines (COLO-829, HCC-1143 and HCC-1187) along with their matched normal cell lines to great sequencing depths (up to 278x coverage) on both Illumina HiSeqX and NovaSeq sequencing instruments. Somatic calling was generally consistent between the two platforms despite minor differences at the read level. We designed and implemented a novel pipeline for the analysis of tumor-normal samples, using multiple variant callers. We show that coupled with a high-confidence filtering strategy, the use of combination of tools improves the accuracy of somatic variant calling. We also demonstrate the utility of the dataset by creating an artificial purity ladder to evaluate the somatic pipeline and benchmark methods for estimating purity and ploidy from tumor-normal pairs. The data and results of the pipeline are made accessible to the cancer genomics community.
Interaction of melatonin and Bmal1 in the regulation of PI3K/AKT pathway components and cellular survival
Authors: Beker Mustafa C. , Caglayan Berrak , Caglayan Ahmet B. , Kelestemur Taha , Yalcin Esra , Caglayan Aysun , Kilic Ulkan , Baykal Ahmet T. , Reiter Russel J. , Kilic Ertugrul
Published: December 2019

The circadian rhythm is driven by a master clock within the suprachiasmatic nucleus which regulates the rhythmic secretion of melatonin. Bmal1 coordinates the rhythmic expression of transcriptome and regulates biological activities, involved in cell metabolism and aging. However, the role of Bmal1 in cellular- survival, signaling, its interaction with intracellular proteins, and how melatonin regulates its expression is largely unclear. Here we observed that melatonin increases the expression of Bmal1 and both melatonin and Bmal1 increase cellular survival after oxygen glucose deprivation (OGD) while the inhibition of Bmal1 resulted in the decreased cellular survival without affecting neuroprotective effects of melatonin. By using a planar surface immunoassay for PI3K/AKT signaling pathway components, we revealed that both melatonin and Bmal1 increased phosphorylation of AKT, ERK-1/2, PDK1, mTOR, PTEN, GSK-3αβ, and p70S6K. In contrast, inhibition of Bmal1 resulted in decreased phosphorylation of these proteins, which the effect of melatonin on these signaling molecules was not affected by the absence of Bmal1. Besides, the inhibition of PI3K/AKT decreased Bmal1 expression and the effect of melatonin on Bmal1 after both OGD in vitro and focal cerebral ischemia in vivo. Our data demonstrate that melatonin controls the expression of Bmal1 via PI3K/AKT signaling, and Bmal1 plays critical roles in cellular survival via activation of survival kinases.
hASH1 nuclear localization persists in neuroendocrine transdifferentiated prostate cancer cells, even upon reintroduction of androgen
Authors: Fraser Jennifer A. , Sutton Joseph E. , Tazayoni Saba , Bruce Isla , Poole Amy V.
Published: December 2019

Neuroendocrine prostate cancer (NEPC) is thought to arise as prostate adenocarcinoma cells transdifferentiate into neuroendocrine (NE) cells to escape potent anti-androgen therapies however, the exact molecular events accompanying NE transdifferentiation and their plasticity remain poorly defined. Cell fate regulator ASCL1/hASH1’s expression was markedly induced in androgen deprived (AD) LNCaP cells and prominent nuclear localisation accompanied acquisition of the NE-like morphology and expression of NE markers (NSE). By contrast, androgen-insensitive PC3 and DU145 cells displayed clear nuclear hASH1 localisation under control conditions that was unchanged by AD, suggesting AR signalling negatively regulated hASH1 expression and localisation. Synthetic androgen (R1881) prevented NE transdifferentiation of AD LNCaP cells and markedly suppressed expression of key regulators of lineage commitment and neurogenesis (REST and ASCL1/hASH1). Post-AD, NE LNCaP cells rapidly lost NE-like morphology following R1881 treatment, yet ASCL1/hASH1 expression was resistant to R1881 treatment and hASH1 nuclear localisation remained evident in apparently dedifferentiated LNCaP cells. Consequently, NE cells may not fully revert to an epithelial state and retain key NE-like features, suggesting a “hybrid” phenotype. This could fuel greater NE transdifferentiation, therapeutic resistance and NEPC evolution upon subsequent androgen deprivation. Such knowledge could facilitate CRPC tumour stratification and identify targets for more effective NEPC management.
A Calculation Model of the General Theory of Interaction Potentials for Stoichiometric Lanthanide Type Crystals: Applications to the Cs2KLnCl6 System
Authors: Soto Andres , Shajahan Shanavas , Acevedo Roberto
Published: December 2019

This article aims to develop a generalized model calculation model to be applicable to the general theory of interaction potentials with reference to the stoichiometric elpasolite type crystals. In this study, we have chosen to report both a theoretical model and a calculation strategy to undertake semi empirical calculations of thermodynamic properties, such as reticular energies and heats of formation for the series of systems such as: Cs2KLnCl6. We have also carried out quite a number of calculations for a variety of systems such as: Cs2NaLnF6, Cs2NaLnCl6, Cs2NaLnBr6, Rb2NaLnF6and Cs2KLnF6 in the Fm3m space group since we aim to check the strengths and weaknesses of our model calculations. We have analyzed a substantial number of approximate theoretical models and have carried a formidable amount of computing simulations to estimate the reticular energies and the corresponding heat of formation for these type of crystal using a semi empirical model. We made use of the thermodynamic cycles of Born-Haber so as to get a broad view with reference to the accuracy of our semi empirical theoretical models. The problem itself is quite challenging since we have focused our attention upon trivalent lanthanide ions $$L{n}^{+3}$$Ln+3 in the first inner transition series of the chemical elements: (Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu). There are a significant amount of outstanding research works published in the literature with reference to structural analysis, one photon spectroscopy, vibrionic intensity model calculations and generalized models to deal with these kind of complex crystals. The calculated energy values associated with these observables seems to be most reasonable, and these follow the expected trends, as may be expected on both theoretical and experimental grounds. Both, the advantages and disadvantages of the current model calculations, have been tested against other previous calculations performed for this type of complex systems. It is of a paramount importance, the results obtained and reported in this article with regards to convergence tests as well as some master equations derived to account for the various contributions to the total energy. The Born-Mayer-Buckingham potential is carefully examined with reference to these lanthanide type crystals Cs2KLnCl6. Finally but not at last, the most likely sources for improvement are carefully discussed in this work. We strongly believe that there is enough room for improvement and have therefore initiated a new research program of activities tackling systems of well-known optical and structural properties.
Influence of reflective foil on persimmon (Diospyros kaki Thunb.) fruit peel colour and selected bioactive compounds
Authors: Smrke Tina , Persic Martina , Veberic Robert , Sircelj Helena , Jakopic Jerneja
Published: December 2019

The purpose of this work was to investigate how to overcome the negative effect of anti-hail netting on the photosynthetic photon flux density (PPFD) in persimmon trees and persimmon fruit colour, flesh firmness, total soluble solids (TSS) and individual carotenoid and phenolic compound contents (determined via HPLC-MS) under a hail net with the use of reflective foil. Reflective foil increased the PPFD on the lower side of the fruits, while there was no significant difference on the upper side compared to those of the control group. The CIE colour parameters a* and h° indicated more intense red colouration of the fruits in the foil treatment than those in the control. Among carotenoids, the content of β-carotene increased, and the content of zeaxanthin decreased in fruits in the reflective foil treatment group, while the content of other carotenoids was not affected by the reflective foil. Among individual phenolic compounds in the persimmon peel, greater light intensity significantly influenced all three phenolic compound subgroups: phenolic acids, flavan-3-ols and flavonols. The content of gallic acid in the persimmon flesh increased the most, while other phenolics did not show any significant differences in concentrations between the foil and control groups. This study is the first to examine the influence of reflective foil on bioactive compounds in persimmon fruit. The use of reflective foil in persimmon orchards improves persimmon fruit colour and selected bioactive compound contents.
The effects of different instruments and suture methods of conization for cervical lesions
Authors: Wang Xiaoyu , Li Lei , Bi Yalan , Wu Huanwen , Wu Ming , Lang Jinghe
Published: December 2019

This study is to compare the surgical outcomes of patients undergoing cold knife conization (CKC) versus electrosurgical conization (ESC). Among 10,086 patients in a single center admitted between January 2000 and January 2019, CKS or ESC was used for grade 3 cervical intraepithelial neoplasia (CIN3) or more severe lesions. Modified Sturmdorf or Figure-of-eight sutures were applied after conization. A regression model was used to determine the risk factors for margin involvement and short-term post-operative complications. In total, 7275 (72.1%) and 2811 (27.9%) patients underwent CKC and ESC, respectively. Women who underwent ESC were older and had a higher risk of margin involvement and endocervical glandular involvement than those who underwent CKC in univariate analysis. However, in the multivariate analysis, age (odds ratio [OR] 1.032, 95% confidence interval [95% CI] 1.025–1.038) and glandular involvement (OR 2.196, 95% CI 1.915–2.517) were the independent risk factors associated with margin involvement, but the incision methods used caused no significant difference. Modified Sturmdorf sutures and Figure-of-eight sutures were applied in 3520 (34.9%) and 6566 (65.1%) patients, respectively. The modified Sturmdorf sutures was the only risk factor associated with wound hemorrhage (OR 1.852, 95% CI 1.111–3.085) after adjusted with other epidemiological and surgical factors. Various incision or suture methods had similar risk of cervical stenosis. Therefore, ESC is an acceptable alternative to CKC for the diagnosis and treatment of cervical lesions regarding the pathologic accuracy and integrity, and short-term safety. Modified Sturmdorf sutures increased the risk of wound hemorrhage compared with Figure-of-eight sutures.
Formation of decimeter-scale, long-lived elevated ionic conductivity regions in thunderclouds
Authors: Iudin D. I. , Rakov V. A. , Syssoev A. A. , Bulatov A. A. , Hayakawa M.
Published: December 2019

We propose a scenario in which elevated ionic conductivity regions (EICRs) with dimensions of the order of 0.1–1 m are formed in the turbulent thundercloud environment. The starting point in this scenario is the occurrence of electron avalanches in the vicinity of colliding hydrometeors, leading to the formation of ion production centers. Their dimensions are of the order of $$1{0}^{-3}-1{0}^{-2}$$10−3−10−2 m, and their lifetime is of the order of $$1{0}^{-4}-1{0}^{-3}$$10−4−10−3 s. When a new ion production center is created inside the decimeter-scale residual ion concentration spot left behind by a previously established center, the local ion concentration steadily increases, which leads to the formation of decimeter-scale EICRs whose lifetime is measured in seconds. The relatively high conductivity of EICRs (up to $$1{0}^{-9}$$10−9 S/m or so) relative to the background conductivity ($$1{0}^{-14}$$10−14 S/m or less) ensures their polarization in external electric field within a few milliseconds or so. The EICR formation mechanism requires only one condition: the rate of occurrence of ion production centers per unit time in a unit volume should exceed the percolation-theory-based critical level of $$1{0}^{-1}$$10−1 m$${}^{-3}$$−3 s$${}^{-1}$$−1. Hydrometeor collision rates three and even four orders of magnitude higher than this value have been reported from observations. Presence of EICRs in the cloud provides local electric field enhancements and pre-ionization levels that will lead to the formation of additional ion production centers and may be sufficient for the initiation and development of streamers and, eventually, lightning.
Phonon-assisted processes in the ultraviolet-transient optical response of graphene
Authors: Novko Dino , Kralj Marko
Published: December 2019

Many recent experiments investigated potential and attractive means of modifying many-body interactions in two-dimensional materials through time-resolved spectroscopy techniques. However, the role of ultrafast phonon-assisted processes in two-dimensional systems is rarely discussed in depth. Here, we investigate the role of electron–phonon interaction in the transient optical absorption of graphene by means of first-principles methods. It is shown at equilibrium that the phonon-assisted transitions renormalize significantly the electronic structure. As a result, absorption peak around the Van-Hove singularity broadens and redshifts by ~100 meV. In addition, temperature increase and chemical doping are shown to notably enhance these phonon-assisted features. In the photoinduced transient response, we obtain spectral changes in close agreement with the experiments, and we associate them to the strong renormalization of occupied and unoccupied $$\pi$$π bands, which predominantly comes from the coupling with the zone-center $${E}_{2g}$$E2g optical phonon. Our estimation of the Coulomb interaction effects shows that the phonon-assisted processes can have a dominant role even in the subpicosecond regime.