bluuebunny/crossref_metadata_2025 huggingface dataset:
Phytochemical Screening and Free Radical Scavenging Activity of Hydroethanolic Leaf Extract of Senna sieberiana DC (Caesalpiniaceae) and its Fractions
Authors: Fall Alioune Dior , Sy Awa Ndiaye , Dieng Serigne Ibra Mbacké , Sarr Abdou , Dieng Mbaye
Published: October 2019

Objectives: The aim of this study was to identify the phytochemical groups of hydroethanolic leaf extract of Senna sieberiana DC and its fractions and to investigate their free radical scavenging activity.

Methods: S. sieberiana leaves were extracted with hydroethanolic solvent. From the hydroethanolic extract 3 fractions were obtained after a liquid/liquid fractionation (dichloromethane, ethyl acetate and water). Phytochemical screening of the leaf extract and its fractions was done using standard reactions. Free radical scavenging activity was assessed using DPPH and ABTS assays. 

Results: Tannins, flavonoids, anthracenic derivatives, sterols and triterpenoids were the main phytochemical constituents of the leaf extract and fractions. The hydro-ethanolic leaf extract of Senna sieberiana, its dichloromethane, ethyl acetate and aqueous fractions and ascorbic acid had respective IC50 values of 191.6±3.82 - 495.73±8.96 - 165.8±4.85 - 50.40±2.65 - 19.53±0.13 µg/ml in ABTS assay.  In DPPH assay,  the IC50 values were  44.8 ± 1.22 - 218.93±9.01 - 32.13 ± 1.8 - 26.4±0.11- 4.66±0.07 µg/ml respectively for the leaf extract, dichloromethane, ethyl acetate and aqueous fractions and ascorbic acid.

Conclusion: The hydroethanolic leaf extract of S. sieberiana had shown free radical scavenging activity. The aqueous fraction was more active among plant tested samples.
Biometry and Pre-germinating Manilkara zapota L. Seed Treatments
Authors: Melo Luan Danilo Ferreira de Andrade , Junior João Luciano de Andrade Melo , Ramos Marcus Gabriel de Cavalho , De Assis Wesley Oliveira , Paes Reinaldo de Alencar , Andrade Alberício Pereira de , Ferreira Soares Larice Bruna , Oliveira Costa Jaqueline Figueredo de , Souto Priscila Cordeiro , Das Neve Maria Inajal Rodrigues da Silva , Da Rocha Dougllas Ferreira
Published: October 2019

Manilkara zapota L., popularly known as sapoti, has commercial relevance both for fruits, with high prices in the regional markets, and for its wood. Thus, the propagation of this species can be done by seed, however, the germination is slow and uneven. The objective of this work was to study the biometry of the seeds and to evaluate pre-germinative treatments to facilitate the propagation of sapoti. The fruits were from the municipality of Brejão-PE and length, width and thickness were determined in millimeters of each seed and submitted to different pre-germination treatments. The seeds were exposed to the following evaluations: biometry, dormancy overrun, germination tests, germination speed index, root length and aerial part of the seedlings and dry mass of the root and shoot of the seedlings. They have variability regarding their biometry and do not require the adoption of treatments for the breakdown of dormancy, which enables and accelerates the production of seedlings. The treatments aimed at overcoming dormancy of sapoti were not efficient to accelerate the germination of the seeds.
Anti-bacterial Activity of Crude Flavonoid Fraction from Bidens pilosa Leaves against Selected Chronic Wound Bacterial Pathogens
Authors: Nakibuule Maria Kayondo , Ntulume Ibrahim , Mwandah Daniel Chans , Tibyangye Julius , Bashir Alkali , Odoki Martin , Okoche Deogratius , Maniga Josephat N. , Emmanue Eliu , Kwizera Eliah , Richard Bwanika , Aliero Adamu Almustapha
Published: October 2019

Aims: Bidens pilosa is an extraordinary source of phytochemicals particularly flavonoids especially in leaves which have been attributed in various studies due to its antibacterial properties. The present study aimed at addressing bio-burden of chronic wound through proving a possible source of new antimicrobial product for wound healing.

Methodology: Solvent-solvent extraction method was used to isolate crude flavonoid fraction from leaves of B.  pilosa using ether, chloroform, ethylacetate and methanol (1:1:1). Thin-layer chromatography was used to identify crude flavonoid fraction using methanol/n-hexane (1:2: v/v) as mobile phase solvents. Agar well diffusion method was used to determine anti-bacterial activity of crude flavonoid against bacterial pathogens: Susceptible Pseudomonas aeruginosa ATCC®27853™, resistant Pseudomonas aeruginosa susceptible Staphylococcus aureus ATCC®25923™, methicillin resistant Staphylococcus aureus, Streptococcus pneumoniae and methicillin resistant Staphylococcus epidermidis. Minimum inhibitory concentration (MIC) and Minimum bactericidal contrition (MBC) were also determined using broth dilution and culture methods.

Results: Thin-layer chromatographic profiling revealed an identity of three different spots with flavonoids from B. pilosa leaves showing three bands with Rf values 0.51, 0.60 and 0.63. The mean and standard deviation zone of inhibition of crude flavonoids ranged from 11.50±0.50 mm to 17.50±1.50 mm. The mean and standard deviation of positive controls (Ciproflaxacin, Co-Amoxiclay and Voncomycin) ranged from 0.00±0.00 to 22.50±0.50 mm. MIC and MBC of crude flavonoids ranged from 12.5-25.0 mg/mL and 50 to 200 mg/mL respectively. The flavonoid fraction was more effective against gram positive bacteria than on gram negative bacteria and it exhibited bactericidal effect on Methicillin resistant Staphylococcus aureus, resistant P. aureginosa, sensitive P.aureginosa and S. pneumonia.

Conclusion: B. pilosa leaves could be a potential source for future drug development from flavonoid to address the issue of need for new antibiotics due to alarming burden of antimicrobial resistance in last resort antibiotics.
S
alinibacteraceae
Authors: Viver Tomeu , Rosselló‐Móra Ramon , Antón Josefa
Published: October 2019

Sa.li.ni.bac.te.ra.ce'ae. N.L. masc. n.
Salinibacter
type genus of the family; suff. ‐
aceae
ending to denote a family; N.L. fem. pl. n.
Salinibacteraceae
the family of the genus
Salinibacter
.

Rhodothermaeota / Rhodothermia / Rhodothermales / Salinibacteraceae

Cells are long rods colored red/orange due to their content of carotenoid pigments. Cells stain Gram‐negative. Endospores are not observed. Aerobic. Positive for catalase and oxidase. Members of the family are chemoheterotrophic although they harbor the retinal‐based light‐driven proton pump and thus are putatively able to obtain energy from light. Halophilic or extremely halophilic, able to grow from 5 to 35% NaCl. Mesophilic or slightly thermophilic, growing from 27 to 47°C. This phylum has been circumscribed on the basis of 16S rRNA gene phylogeny, MLSA (multi locus sequence analysis), and whole‐genome phylogenetic analyses.

DNA G + C content (mol%)
: 63–67 (calculated from the genome sequence).

Type genus
:
Salinibacter
Antón, Oren, Benlloch, Rodríguez‐Valera, Amann and Rosselló‐Mora 2002, 490
VP
.

The family currently accommodates the genera
Salinibacter
,
Salisaeta
, and
Salinivenus
.
Organ sparing of linac‐based targeted marrow irradiation over total body irradiation
Authors: Warrell Gregory R. , Colussi Valdir C. , Swanson Wayne L. , Caimi Paolo F. , Mansur David B. , de Lima Marcos J. G. , Pereira Gisele C.
Published: October 2019

Purpose

Targeted marrow irradiation (TMI) is an alternative conditioning regimen to total body irradiation (TBI) before bone marrow transplantation in hematologic malignancies. Intensity‐modulation methods of external beam radiation therapy are intended to permit significant organ sparing while maintaining adequate target coverage, improving the therapeutic ratio. This study directly compares the dose distributions to targets and organs at risk from TMI and TBI, both modalities conducted by general‐use medical linacs at our institution.

Methods

TMI treatments were planned for 10 patients using multi‐isocentric feathered volumetric arc therapy (VMAT) plans, delivered by 6 MV photon beams of Elekta Synergy linacs. The computed tomography (CT) datasets used to obtain these plans were also used to generate dose distributions of TBI treatments given in the AP/PA extended‐field method. We compared dose distributions normalized to the same prescription for both plan types. The generalized equivalent uniform dose (gEUD) of Niemierko for organs and target volumes was used to quantify effective whole structure dose and dose savings.

Results

For the clinical target volume (CTV), no significant differences were found in mean dose or gEUD, although the radical dose homogeneity index (minimum dose divided by maximum dose) was 31.7% lower (P = 0.002) and the standard deviation of dose was 28.0% greater (P = 0.027) in the TMI plans than in the TBI plans. For the TMI plans, gEUD to the lungs, brain, kidneys, and liver was significantly lower (P < 0.001) by 47.8%, 33.3%, 55.4%, and 51.0%, respectively.

Conclusion

TMI is capable of maintaining CTV coverage as compared to that achieved in TBI, while significantly sparing organs at risk. Improvement on sparing organs at risk permits a higher prescribed dose to the target or the maximum number of times marrow conditioning may be delivered to a patient while maintaining similar typical tissue complication rates.
Mechanical and thermal performances of epoxy resin/graphitic carbon nitride composites
Authors: Qi Yuhao , Zhu Guangda , Zheng Junping
Published: October 2019

In this paper, a series of graphitic carbon nitride (g‐C3N4) was synthesized under different thermal oxidation etching temperatures and epoxy/g‐C3N4 composites were prepared via solution blending. The morphology and structure of g‐C3N4 were investigated by transmission electron microscope, X‐ray diffraction (XRD), Fourier transform infrared spectroscopy, and X‐ray photoelectron spectroscopy. The tensile fracture morphology and structure of epoxy resin (EP) composites were demonstrated by scanning electron microscopy and XRD, respectively. Mechanical properties of EP composites were characterized by tensile testing, and the thermal performances were investigated by dynamic mechanical thermal analysis and thermal gravimetric analysis. The results revealed that the active groups on g‐C3N4 sheets increased under thermal oxidation etching and the C to N ratio of g‐C3N4 decreased from 0.94 to 0.76 with the increasing etching temperature. Noticeably, the tensile strength of EP composites was enhanced by 58% with the addition of C3N4‐NS‐500 and the thermal properties were also improved significantly, including T0.5 (the decomposition temperature at the mass loss of 50%) increased by 21.5 °C and glass transition temperature improved by 8 °C. © 2020 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48598.
Power‐law behaviour of hourly precipitation intensity and dry spell duration over the United States
Authors: Yang Lichao , Franzke Christian L. E. , Fu Zuntao
Published: October 2019

Precipitation is an important meteorological variable which is critical for weather risk assessment. For instance, intense but short precipitation events can lead to flash floods and landslides. Most statistical modelling studies assume that the occurrence of precipitation events is based on a Poisson process with exponentially distributed waiting times while precipitation intensities are typically described by a gamma distribution or a mixture of two exponential distributions. Here, we show by using hourly precipitation data over the United Sates that the waiting time between precipitation events is non‐exponentially distributed and best described by a fractional Poisson process. A systematic model selection procedure reveals that the hourly precipitation intensities are best represented by a two‐distribution model for about 90% of all stations. The two‐distribution model consists of (a) a generalized Pareto distribution (GPD) model for bulk precipitation event sizes and (b) a power‐law distribution for large and extreme events. Finally, we analyse regional climate model output to evaluate how the climate models represent the high‐frequency temporal structure of U.S. precipitation. Our results reveal that these regional climate models fail to accurately reproduce the power‐law behaviour of intensities and severely underestimate the long durations between events.
An improved moisture and wind maximization method for probable maximum precipitation estimation and its application to a small catchment in China
Authors: Zhou Yan , Liang Zhongmin , Hu Yiming , Li Dayang , Liu Tian , Lei Xiaohui
Published: October 2019

The probable maximum flood (PMF) is the highest design criterion for major hydraulic projects whose failure might cause severe loss of life and property. The probable maximum precipitation (PMP) is the corresponding extreme design rainfall, which is defined as the theoretically greatest depth of precipitation for a given duration over a particular area under modern meteorological conditions. The moisture and wind maximization (MWM) method is widely used in deriving 24‐hr PMP. However, variables in MWM factor (e.g., maximum precipitable water and wind speed) are collected from full study durations regardless of their respective main moisture inflow directions in each year. This issue could lead to higher PMP estimates which could lead to costs in the construction of hydraulic structures. To alleviate this possible problem, an improved moisture and wind maximization (IMWM) approach is proposed based on the concept of a “wind rose diagram”, data (e.g., rainfall, wind speed, dew point) are grouped according to the main moisture inflow directions of a study catchment. Analysis shows the IMWM approach has the potential to provide lower PMPs, which would have economic implications for hydraulic designs. The storm transposition approach is applied for safety, extraordinary storms occurring in the homogeneous rainfall region are transposed to a study catchment after being maximized by the IMWM method. In addition, statistical methods, including storm formulation, trend analysis and hydrological frequency analysis, are used for deriving short‐duration PMPs. The Nash instantaneous unit hydrograph coupled with regional empirical formulas is then applied to estimate PMFs. As an example, PMP/PMF estimation approaches are applied to an important flood control project located in a small ungauged catchment of China. The study can provide a scientific basis for the construction of the study project as well as a reference for similar high‐hazard projects.
Interleaved, undersampled radial multiple‐acquisition steady‐state free precession for improved left atrial cine imaging
Authors: Robb Jaime S. , Hu Chenxi , Peters Dana C.
Published: October 2019

Purpose

Balanced steady‐state free precession (bSSFP) left atrial (LA) cine suffers from off‐resonance artifacts, particularly in the pulmonary veins (PVs). Linear combination or multiple‐acquisition SSFP (MA‐SSFP) effectively removes banding but greatly increases scan time. We hypothesized that MA‐SSFP with interleaved radial undersampling, where each phase‐cycling is acquired with an interleaved set of radial projections, would improve image quality of LA cine with a small increase of scan time and streak artefacts.

Methods

Undersampled radial MA‐SSFP with and without interleaving was compared with fully sampled radial bSSFP by means of simulations, phantoms, and in vivo imaging. Ten healthy subjects were imaged on a 3T scanner, with bSSFP and MA‐SSFP cine of the left atrium, and B0‐mapping. Images were assessed (1 = worst, 5 = best) by 2 independent readers, with respect to 5 qualitative criteria and apparent signal‐to‐noise ratio.

Results

In healthy subjects, off‐resonance differed from the right inferior PVs to the LA cavity by 163 Hz ± 73 Hz at 3T. Compared with fully sampled radial bSSFP, interleaved radial MA‐SSFP significantly improved image quality with respect to off‐resonance artifacts (3.8 ± 0.6 versus 2.3 ± 1.0; P = 0.005), PV conspicuity (2.8 ± 1.0 versus 4.3 ± 0.5; P = 0.005), and the number of visualized PVs (1.7 ± 0.4 versus 0.9 ± 0.7; P = 0.008), although with greater streak artifacts (3.4 ± 0.4 versus 4.9 ± 0.2; P = 0.004) and lower measured apparent signal‐to‐noise ratio (24 ± 9 versus 69 ± 36; P = 0.002). Flow artifacts were similar. Interleaved radial MA‐SSFP reduced streaking artifacts and increased apparent signal‐to‐noise ratio versus noninterleaved radial.

Conclusions

Interleaved radial MA‐SSFP cine reduces banding artifacts with an acceptable increase of scan time and streak artifacts. The proposed technique improves the LA and PV visualization in bSSFP cine imaging.
Displaying enhancing factors on the surface of occlusion bodies improves the insecticidal efficacy of a baculovirus
Authors: Lei Chengfeng , Yang Shili , Lei Wenxiao , Nyamwasa Innocent , Hu Jia , Sun Xiulian
Published: October 2019

BACKGROUND

Baculoviruses provide long‐lasting control of crop pests and are harmless to humans and non‐target animals, making them attractive bioinsecticides. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) has a wide‐host range and is one such commercial bioinsecticide, but its low infectivity to older larvae and less‐sensitive species precludes its large‐scale application. We sought to improve the infectivity of AcMNPV.

RESULTS

Two enhancing factors, the truncated enhancin from Agrotis segetum granulovirus and GP37 from Cydia pomonella granulovirus, were expressed in fusion with the N‐terminal and middle domain of the polyhedrin envelope protein of AcMNPV. Western blotting and immunoelectron microscopy analysis indicated that the enhancing factors were expressed on the occlusion bodies of the resulting AcMNPV variants. Bioassays showed that the median lethal doses of the recombinant viruses were 3.9‐fold to 7.4‐fold lower than those of the wild‐type virus against the second and fourth instar of Spodoptera exigua larvae. The yields of occlusion bodies from the two recombinants in S. exigua larvae were comparable with those of the wild‐type virus both in vitro and in vivo. Further bioassays showed that the AcMNPV variants fusing the enhancing factors were incapable of infecting the second instar larvae of S. litura, Helicoverpa armigera, and Pyrausta nubilalis, which were not sensitive to the wild‐type AcMNPV.

CONCLUSION

These genetically modified AcMNPV variants exhibited an enhanced infectivity and may offer better baculovirus control of crop pests. © 2019 Society of Chemical Industry
Higgs and Goldstone Modes in Crystalline Solids
Authors: Vallone Marco
Published: October 2019

In crystalline solids, the acoustic phonon can be described either as a Goldstone or as a non‐Abelian gauge boson. However, the non‐Abelianity of the related gauge group apparently makes the acoustic phonon a frequency‐gapped mode, in contradiction with the other description. In a different perspective, overcoming this contradiction, both acoustic and optical phonon—the latter never appearing following the other two approaches—emerge, respectively, as the gapless Goldstone (phase) and the gapped Higgs (amplitude) fluctuation mode of an order parameter arising from the spontaneous breaking of a global symmetry, without invoking the gauge principle. In addition, the Higgs mechanism describes all the phonon–phonon interactions, including a possible perturbation of the acoustic phonon's frequency dispersion relation induced by the eventual optical phonon, a peculiar behavior that is able to produce mini‐gaps inside the phonon Brillouin zone.
Solution‐Processed High‐Quality Cu2O Thin Films as Hole Transport Layers for Pushing the Conversion Efficiency Limit of Cu2O/Si Heterojunction Solar Cells
Authors: Liu Yujin , Zhu Jundong , Cai Lun , Yao Zhirong , Duan Chunyan , Zhao Zhijuan , Zhao Chuanxi , Mai Wenjie
Published: October 2019

Cuprous oxide (Cu2O) is a nontoxic and earth‐abundant semiconductor material, which is a promising candidate for low‐cost photovoltaic applications. Although Cu2O‐based solar cells have been studied for a few decades, they still suffer from disappointing photovoltaic performance due to its high trap‐state density and inferior carrier collection efficiency. Herein, a facile solution method is demonstrated to synthesize high‐quality Cu2O films with low defects as hole transport layers (HTLs) and the Cu2O/Si heterojunction solar cells are fabricated. Moreover, a variety of interfacial engineering and light management strategies are adopted to push the efficiency limit of Cu2O/Si solar cells, including a Ag transparent conductive layer, HNO3 passivation, Mg electrode back contact, and MoOx antireflection layer, which enable the boosting of carrier separation and reduce the loss of incident solar light, yielding a record high power conversion efficiency of 9.54%. This work may pave the way for economical and environment‐friendly use of Cu2O/Si heterojunction solar cells in daily life.
A Model for Optimizing Railway Alignment Considering Bridge Costs, Tunnel Costs, and Transition Curves
Authors: Ghoreishi Benyamin , Shafahi Yousef , Hashemian Seyed Elyas
Published: October 2019

Owing to wide-ranging searches (there are various alignments between two points) as well as complex and nonlinear cost functions and a variety of geometric constraints, the problem of optimal railway alignment is classified as a complex problem. Thus, choosing an alignment between two points is usually done based on a limited number of alignments designed by experts. In recent years, the study of railway alignment optimization has shown the importance of optimization and the introduction of various algorithms and their usefulness in solving different problems. It is expected that applying meta-heuristic optimization algorithms such as methods based on swarm intelligence can lead to better alignments. In this study, we tried to modify models based on previous studies in order to design and develop a model based on a single framework to provide three-dimensional optimization of alignments applicable in the real world. To obtain this, the particle swarm algorithm is used and a geographic information system is incorporated as a means of search in three-dimensional space. In particular, the cost function used in previous studies considering the costs related to structures (bridges and tunnels) are improved regarding hydraulic structure alignments. Furthermore, the transition curve of horizontal alignment and slope restrictions of curves are considered in this project by using the penalty function in order to obtain the most practical results possible. Finally, this study examines three problems for which the results are acceptable in cases of railway alignment geometry and its application in the real world.
Lithium Metal Anode Materials Design: Interphase and Host
Authors: Wang Hansen , Liu Yayuan , Li Yuzhang , Cui Yi
Published: October 2019

Li metal is the ultimate anode choice due to its highest theoretical capacity and lowest electrode potential, but it is far from practical applications with its poor cycle lifetime. Recent research progresses show that materials designs of interphase and host structures for Li metal are two effective ways addressing the key issues of Li metal anodes. Despite the exciting improvement on Li metal cycling capability, problems still exist with these methodologies, such as the deficient long-time cycling stability of interphase materials and the accelerated Li corrosion for high surface area three-dimensional composite Li anodes. As a result, Coulombic efficiency of Li metal is still not sufficient for full-cell cycling. In the near future, an interphase protected three-dimensional composite Li metal anode, combined with high performance novel electrolytes might be the ultimate solution. Besides, nanoscale characterization technologies are also vital for guiding future Li metal anode designs.

Graphic Abstract
Impacts of Currents and Waves on Bottom Drag Coefficient in the East China Shelf Seas
Authors: Fan Renfu , Zhao Liang , Lu Youyu , Nie Hongtao , Wei Hao
Published: October 2019

High‐frequency measurements of waves, currents, and turbulence were made using the bottom‐mounted tripod equipped with the Nortek 6‐MHz acoustic Doppler velocimetry at eight mooring stations in the East China Shelf Seas. The observational data are analyzed to estimate the bottom drag coefficient and also the contributions from currents and waves. Variations of bottom drag coefficient caused by currents show no obvious relationship with water depth. Generally, the current‐induced drag coefficient decreases with the strengthening currents, and the wave‐induced drag coefficient increases with the enhancing waves. Synthesis analyses of the observational data reveal a scale relationship between the current‐induced drag coefficient and the turbulent Reynolds number and that between the wave‐induced drag coefficient and the bottom wave orbital velocity. The analyses show no significant impacts of waves on turbulent Reynolds stress, and the total bottom drag coefficient is the sum of that due to currents and waves. The empirical formula for bottom drag coefficient derived from this study may help to improve the simulation of tides, storm surges, and sediment transport in coastal seas.
Simulation of Chemical Transport by Typhoon Mireille (1991)
Authors: Preston Ari D. , Fuelberg Henry E. , Barth Mary C.
Published: October 2019

This study examines the transport of chemical species to the upper troposphere/lower stratosphere (UTLS) by Typhoon Mireille (1991). We follow an integrated research approach, using in situ flight data when available and results from a high‐resolution chemical transport model. The Weather Research and Forecasting model coupled with chemistry (WRF‐Chem) was used with an innermost grid spacing of 3 km to explicitly resolve the convection being studied. Mireille was well simulated based on comparisons between the simulated fields and in situ chemical measurements from NASA's Pacific Exploratory Mission‐West A field project. Results from the simulated fields show that pollution from distant sources is ingested by Mireille and subsequently lofted by eyewall convection to the upper troposphere, enhancing concentrations in this region. Flux calculations suggest that a strong tropical cyclone (TC), such as Mireille, can impact UTLS chemistry as much as a continental middle‐latitude cyclone. Furthermore, overshooting convective cells in Mireille produced values of chemical flux density at tropopause level that are as much as 15–30 times greater than that of theTC as a whole. Although overshooting tops comprise only a small area of the simulated total TC, they transport large quantities of gaseous species to the upper troposphere because of their strong updrafts.
Silk sericin intake leads to increases in l-serine and l-tyrosine levels in the mouse brain and the simultaneous facilitation of brain noradrenergic turnover
Authors: Kawano Yui , Yating Hu , Sasaki Masahiro , Furuya Shigeki
Published: October 2019

Sericin is a protein component of the silkworm cocoon, and contains a high proportion of L-serine, but it has been mostly disposed of as an industrial waste. However, recent studies have revealed its unique biological functionalities beneficial to human health. This study aimed to evaluate the effect of acute oral intake of sericin on amino acid and neurotransmitter metabolism in the mouse brain. Acute administration of chemically modified sericin (0.26 g/30 g body weight) increased L-serine and L-tyrosine levels in the serum and brain, although the L-tyrosine content in the sericin was less than 3% (w/w). In addition, sericin administration led to a significant facilitation of noradrenergic turnover via enhancement of 3-methoxy-4-hydroxyphenylethyleneglycol, a principal metabolite of noradrenaline, in several of the brain regions examined. These present findings suggest that oral intake of sericin efficiently delivers L-serine and L-tyrosine to the brain, thus stimulating noradrenergic activity in the brain.

Abbreviations: DA: dopamine; 5-HIAA: 5-hydroxyindoleicetic acid; 5-HT: 5-hydroxytryptamine; HVA: homovanillic acid; MHPG: 3-methoxy-4-hydroxyphenylethyleneglycol; 3-MT: 3-methoxytyramine; NA: noradrenaline; NM: normetanephrine; Veh: vehicle
Role of Cycle Threshold in Clostridioides difficile Polymerase Chain Reaction Testing as a Predictor of Clinical Outcomes in Patients With Inflammatory Bowel Disease
Authors: Jonica Emily R , Sulis Carol A , Soni Kanupriya , Hughes Michelle , Jones Eric , Weinberg Janice , Miller Nancy S , Farraye Francis A
Published: October 2019

Background

Distinguishing Clostridioides difficile infection from colonization is challenging in patients with Inflammatory Bowel Disease (IBD). Cycle threshold (Ct), the cutoff for PCR positivity, has been investigated in non-IBD patients.

Methods

Patients with positive C. difficile PCR (25 IBD, 51 non-IBD) were identified retrospectively. Fifteen-day outcomes were assessed.

Results

Ct correlated with diarrheal days in non-IBD (P = 0.048), but not IBD patients (P = 0.769). IBD patients had shorter LOS and less severe infection, but more diarrheal days (P < 0.05).

Conclusions

IBD patients had a milder course but Ct results were not significant. Larger studies are needed to clarify utility of Ct in IBD.
Time series forecasting with model selection applied to anomaly detection in network traffic
Authors: Saganowski Łukasz , Andrysiak Tomasz
Published: October 2019

In herein article an attempt of problem solution connected with anomaly detection in network traffic with the use of statistic models with long or short memory dependence was presented. In order to select the proper type of a model, the parameter describing memory on the basis of the Geweke and Porter-Hudak test was estimated. Bearing in mind that the value of statistic model depends directly on quality of data used for its creation, at the initial stage of the suggested method, outliers were identified and then removed. For the implementation of this task, the criterion using the value of interquartile range was used. The data prepared in this manner were useful for automatic creation of statistic models classes, such as ARFIMA and Holt-Winters. The procedure of calculation of model parameters’ optimal values was carried out as a compromise between the models coherence and the size of error estimation. Then, relations between the estimated network model and its actual parameters were used in order to detect anomalies in the network traffic. Considering the possibility of appearance of significant real traffic network fluctuations, procedure of updating statistic models was suggested. The results obtained in the course of performed experiments proved efficacy and efficiency of the presented solution.
Association of Circulating Vitamin D With Colorectal Cancer Depends on Vitamin D–Binding Protein Isoforms: A Pooled, Nested, Case-Control Study
Authors: Gibbs David Corley , Song Mingyang , McCullough Marjorie L , Um Caroline Y , Bostick Roberd M , Wu Kana , Flanders W Dana , Giovannucci Edward , Jenab Mazda , Brustad Magritt , Tjønneland Anne , Perez-Cornago Aurora , Trichopoulou Antonia , Tsilidis Konstantinos K , Hultdin Johan , Barricarte Gurrea Aurelio , Bueno-de-Mesquita Bas , Mahamat-Saleh Yahya , Kühn Tilman , Gunter Marc J , Weiderpass Elisabete , Fedirko Veronika
Published: October 2019

Background

Higher circulating 25-hydroxyvitamin-D [25(OH)D] concentrations are consistently inversely associated with colorectal cancer (CRC) risk in observational studies. However, it is unknown whether this association depends on the functional GC-rs4588*A (Thr436Lys) variant encoding the vitamin D–binding protein-2 (DBP2) isoform, which may affect vitamin D status and bioavailability.

Methods

We analyzed data from 1710 incident CRC cases and 1649 incidence-density–matched controls nested within three prospective cohorts of mostly Caucasians. Study-specific incidence rate ratios (RRs) for associations of prediagnostic, season-standardized 25(OH)D concentrations according to DBP2 isoform with CRC were estimated using multivariable unconditional logistic regression and were pooled using fixed-effects models. All statistical significance tests were two-sided.

Results

The odds of having 25(OH)D concentrations less than 50 nmol/L (considered insufficient by the Institute of Medicine) were 43% higher for each DBP2-encoding variant (rs4588*A) inherited (per DBP2 odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.27 to 1.62, Ptrend = 1.2 × 10−8). The association of 25(OH)D concentrations with CRC risk differed by DBP2: 25(OH)D concentrations considered sufficient (≥ 50 nmol/L), relative to deficient (< 30 nmol/L), were associated with a 53% lower CRC risk among individuals with the DBP2 isoform (RR = 0.47, 95% CI = 0.33 to 0.67), but with a non–statistically significant 12% lower risk among individuals without it (RR = 0.88, 95% CI = 0.61 to 1.27) (Pheterogeneity = .01).

Conclusions

Our results suggest that the 25(OH)D-CRC association may differ by DBP isoform, and those with a DBP2-encoding genotype linked to vitamin D insufficiency may particularly benefit from adequate 25(OH)D for CRC prevention.
Flow Cytometry in the Differential Diagnosis of CD10-Positive Nodal Lymphomas
Authors: Sorigue Marc , Santos-Gomez Mireia , Comes Martina , Raya Minerva , Vergara Sara , Tapia Gustavo , Navarro José-Tomas , Morales-Indiano Cristian , Junca Jordi
Published: October 2019

Background

Differences between follicular lymphoma (FL) and diffuse large B-cell lymphoma/high-grade B-cell lymphoma (DLBCL/HGBL) by flow cytometry are underexplored.

Methods

We retrospectively assessed flow cytometry results from 191 consecutive lymph node biopsies diagnosed with FL or DLBCL/HGBL.

Results

The only parameters that differed between the 2 groups in the derivation cohort were forward scatter and side scatter (P < 10–6; area under the curve [AUC], 0.75–0.8) and %CD23 (P = .004; area under the receiver characteristic operating curve, 0.64). However, since light scatter characteristics did not distinguish between grade 3 FL and DLBCL/HGBL, we set out to develop a model with high sensitivity for the exclusion of the latter. Several models, including FS and %CD23, were tested, and 2 models showed a sensitivity of >0.90, with negative predictive values of ≥0.95, albeit with low specificity (0.45 to 0.57).

Conclusion

Two simple models enable the exclusion of DLBCL/HGBL with a high degree of confidence.
DisProt: intrinsic protein disorder annotation in 2020
Authors: Hatos András , Hajdu-Soltész Borbála , Monzon Alexander M , Palopoli Nicolas , Álvarez Lucía , Aykac-Fas Burcu , Bassot Claudio , Benítez Guillermo I , Bevilacqua Martina , Chasapi Anastasia , Chemes Lucia , Davey Norman E , Davidović Radoslav , Dunker A Keith , Elofsson Arne , Gobeill Julien , Foutel Nicolás S González , Sudha Govindarajan , Guharoy Mainak , Horvath Tamas , Iglesias Valentin , Kajava Andrey V , Kovacs Orsolya P , Lamb John , Lambrughi Matteo , Lazar Tamas , Leclercq Jeremy Y , Leonardi Emanuela , Macedo-Ribeiro Sandra , Macossay-Castillo Mauricio , Maiani Emiliano , Manso José A , Marino-Buslje Cristina , Martínez-Pérez Elizabeth , Mészáros Bálint , Mičetić Ivan , Minervini Giovanni , Murvai Nikoletta , Necci Marco , Ouzounis Christos A , Pajkos Mátyás , Paladin Lisanna , Pancsa Rita , Papaleo Elena , Parisi Gustavo , Pasche Emilie , Barbosa Pereira Pedro J , Promponas Vasilis J , Pujols Jordi , Quaglia Federica , Ruch Patrick , Salvatore Marco , Schad Eva , Szabo Beata , Szaniszló Tamás , Tamana Stella , Tantos Agnes , Veljkovic Nevena , Ventura Salvador , Vranken Wim , Dosztányi Zsuzsanna , Tompa Peter , Tosatto Silvio C E , Piovesan Damiano
Published: October 2019

The Database of Protein Disorder (DisProt, URL: https://disprot.org) provides manually curated annotations of intrinsically disordered proteins from the literature. Here we report recent developments with DisProt (version 8), including the doubling of protein entries, a new disorder ontology, improvements of the annotation format and a completely new website. The website includes a redesigned graphical interface, a better search engine, a clearer API for programmatic access and a new annotation interface that integrates text mining technologies. The new entry format provides a greater flexibility, simplifies maintenance and allows the capture of more information from the literature. The new disorder ontology has been formalized and made interoperable by adopting the OWL format, as well as its structure and term definitions have been improved. The new annotation interface has made the curation process faster and more effective. We recently showed that new DisProt annotations can be effectively used to train and validate disorder predictors. We believe the growth of DisProt will accelerate, contributing to the improvement of function and disorder predictors and therefore to illuminate the ‘dark’ proteome.
Targeted DNA methylation of neurodegenerative disease genes via homology directed repair
Authors: Cali Christopher P , Park Daniel S , Lee Edward B
Published: October 2019

DNA methyltransferases (DNMTs) are thought to be involved in the cellular response to DNA damage, thus linking DNA repair mechanisms with DNA methylation. In this study we present Homology Assisted Repair Dependent Epigenetic eNgineering (HARDEN), a novel method of targeted DNA methylation that utilizes endogenous DNA double strand break repair pathways. This method allows for stable targeted DNA methylation through the process of homology directed repair (HDR) via an in vitro methylated exogenous repair template. We demonstrate that HARDEN can be applied to the neurodegenerative disease genes C9orf72 and APP, and methylation can be induced via HDR with both single and double stranded methylated repair templates. HARDEN allows for higher targeted DNA methylation levels than a dCas9-DNMT3a fusion protein construct at C9orf72, and genome-wide methylation analysis reveals no significant off-target methylation changes when inducing methylation via HARDEN, whereas the dCas9-DNMT3a fusion construct causes global off-target methylation. HARDEN is applied to generate a patient derived iPSC model of amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD) that recapitulates DNA methylation patterns seen in patients, demonstrating that DNA methylation of the 5′ regulatory region directly reduces C9orf72 expression and increases histone H3K9 tri-methylation levels.
Bidirectional neuron-glioma interactions: effects of glioma cells on synaptic activity and its impact on tumor growth
Authors: Tantillo Elena , Vannini Eleonora , Cerri Chiara , Maria Mazzanti Chiara , Costa Mario , Caleo Matteo
Published: October 2019

Gliomas grow in a neuronal environment, but little is known on the functional changes in peritumoral neurons during tumor development. Moreover, investigations on the role of neural activity in glioma progression have yielded contradictory results. Here, we monitored longitudinal changes in network activity by recording visual evoked potentials (VEP) and local field potentials (LFP) after transplant of GL261 glioma cells in mouse visual cortex. We detected a progressive deterioration of VEP amplitudes in glioma-bearing mice, accompanied by an increase in slow network oscillations. At the cellular level, the analysis of microdissected peritumoral neurons showed alterations in both pre- and post-synaptic markers. To investigate whether glioma-driven alterations in synaptic function may impact on tumor growth, we manipulated levels of afferent cortical activity in glioma-bearing mice. Specifically, we tested blockade of synaptic activity via botulinum neurotoxin A (BoNT/A), visual deprivation (dark rearing, DR) and visual stimulation (VS). Replicating cells were quantified via immunostaining for BrdU and Ki67. We found that manipulation of cortical activity bidirectionally regulated glioma proliferation. Silencing of cortical synapses with BoNT/A and DR increased tumor proliferation while daily VS had the opposite effect.

These findings demonstrate reduced responsiveness of peritumoral neurons which may in turn stimulate tumor cell proliferation, thus triggering a vicious loop that exacerbates glioma progression. Physiological stimulation of neural activity appears to restrain glioma proliferation so it could be implemented in the clinical setting as an adjuvant therapy.
Multi-colour lineage tracing to asses intra-tumour heterogeneity in glioblastoma multiforme
Authors: Innes James , Brandner Sebastian , Marino Silvia
Published: October 2019

Background

Glioblastoma multiforme (GBM) represents nearly 50% of all malignant brain tumours. Molecular and genomic diagnostics are beginning to unravel the variation between individual tumours. However, there is growing evidence that cellular heterogeneity exists within a single malignancy. Singe cell analysis has demonstrated the presence of subpopulations corresponding to distinct expression profiles.

Objective and experimental approach

characterisation of the intratumor heterogeneity is essential to understand biological behaviour and therapy response. Through combining a genetically labelled mouse model (rosa26-confetti lineage tracing locus) with genetically engineered GBM model we can label distinct cellular lineages.

Results

For three-dimensional imaging of these fluorescently labelled tumours we have optimised tissue clearing protocols. Fluorescence activated sorting of genetically labelled tumour cells identifies distinct populations within single tumours. With these techniques can now interrogate the spatial organisation of clones across large areas and we can compare distinct tumour lineages.

Outlook

Currently, we are engineering human glioblastoma cell lines with genetic fluorescent labels for lineage tracing. Several genetically characterised human cell lines are available for which novel therapeutic targets have been identified. We will apply our lineage tracing approach to investigate the clonal effects of these tailored therapeutics.
Introducing Fluorescence Guided Surgery into Neuro-Oncology Practice and Getting It Right First Time
Authors: Vaqas Babar , Hill Ciaran , Qin Cathy , Glover Sophie , Maniar Ruchi
Published: October 2019

Introduction

Fluorescence Guided Surgery (FGS) using 5-ALA is recommended for patients undergoing resection of suspected high grade glioma and this type of surgery is increasingly being used in more units throughout the UK. We report on our experience of introducing 5-ALA guided surgery for suspected HGG in a regional neurosciences unit.

Methods

Consecutive series of the first 24 patients in our unit to receive 5-ALA guided surgery for suspected HGG from June 2017 to October 2018. Data was prospectively collected.

Results

5-ALA fluorescence guided surgery was used for a range of histologically confirmed WHO grade III-IV gliomas. All but 1 tumour (GBM) fluoresced with 5-ALA, with strong fluorescence in recurrent GBM and anaplastic foci of grade 3 tumours. EOR varied according to the eloquence of the lesion with 70% of cases achieving gross total resection. 40% of cases used awake mapping or intraoperative neurophysiology. 5 patients (20.8%) had temporary neurological deficits which resolved in all cases. Individual surgeon learning curves resulted in 2 styles of practice- complete FGS with fluorescence used throughout the case, and intermittent use of fluorescence as an adjunct often at the end of debulking under white light.

Conclusions

Adopting 5-ALA use comes with specific challenges in terms of service organisation, learning curves and complication avoidance. Our experience is that it is useful both to improve EOR and as an adjunct to identify tumour tissue in eloquent region tumours with monitoring of function. This is possible through a day admission pathway in line with GIRFT.
Functionalised LRP1 targeted carbon nanotubes across the blood-brain barrier in vitro and in vivo after intravenous injection
Authors: Wang Julie , Kafa Houmam , Rubio Noelia , Bansal Sukhvinder , Festy Frederic , Sosabowski Jane , Abbott Joan , Al-Jamal Khuloud
Published: October 2019

Despite extensive research in drug development, brain cancer is still lacking an efficacious cure due to the inability to deliver current therapeutics to the brain across the blood-brain barrier (BBB). Chemically functionalized carbon nanotubes (f-CNT) constitute a novel class of nanomaterials with attractive physical, chemical and electronic properties. The key advantage of f-CNTs is the extremely high surface area to size ratio allowing a high degree of chemical functionalization making them invaluable tools for designing drug delivery systems to the brain. One of the most interesting characteristics of f-CNTs is their ability to translocate across plasma membranes and enter the cells either passively by direct translocation across membranes or actively via endocytosis.

Herein, we confirmed the ability of f-CNTs to cross the BBB and reach the brain in in vitro using a co-culture model of PBEC and primary rat astrocytes and in vivo after intravenous injection. Thanks to their unique optical properties, the uptake of f-CNT in brain was confirmed using state-of-the-art spectroscopic imaging techniques such as multi-photon luminescence imaging, fluorescence lifetime microscopy and Raman spectroscopy. Conjugation with angiopep-2 (ANG), a small peptide targeting the LRP1 receptor overexpressed in the BBB and glioma cells, further enhanced brain parenchyma accumulation in healthy brains. Higher uptake in glioma than brain parenchyma was also observed in glioma-bearing mice after intravenous administration.

The inherent brain accumulation ability of f-CNTs coupled with improved brain-targeting by ANG favours the future clinical applications of f-CNTs-ANG to deliver active therapeutics for brain glioma therapy.
Intra-tumoural perfusion habitats showed prognostic value in glioblastoma patients
Authors: Li Chao , Sun Chang , Wang Shuo , Price Stephen
Published: October 2019

The perfusion within glioblastoma is associated with tumour microenvironment and may create invasive tumor habitats that could potentially be revealed by perfusion imaging. The purpose of this study is to characterize the peritumoural habitats of glioblastoma for treatment target. Dynamic susceptibility contrast-enhancement (DSC) MRI was acquired pre-operatively on 115 newly-diagnosed glioblastoma patients. All images were co-registered to post-contrast T1-weighted images. The relative cerebral blood volume (rCBV), mean transit time (MTT) and relative cerebral blood flow (rCBF) maps were generated from the DSC images. The contrast-enhanced and peritumoural tumor regions were semi-automatically segmented from the post-contrast T1-weighted and FLAIR images. To delineate the habitats of different perfusion levels, a two clusters mixture model with Gaussian distribution was fitted to the rCBV, rCBF, and MTT within both contrast-enhanced and peritumoural regions. Perfusion parameters of the identified habitats were compared, and the prognostic values of habitats were investigated using survival analysis. The results showed that although non-enhanced, the peritumoral high perfusion (PHP) habitat demonstrated similar perfusion level with the contrast high perfusion (CHP) habitat, with similar rCBV (PHP: 1.13 ± 0.18, 95% CI [1.10, 1.15]; CHP: 1.21 ± 0.25, 95% CI [1.16, 1.21]) and rCBF (PHP: 1.08 ± 0.23, 95% CI [1.05, 1.08]; CHP: 1.08 ± 0.19, 95% CI [1.05, 1.08]). Multivariate Cox regression showed that the volumes of both habitats were associated with worse patient overall survival (PHP: P = 0.032; HR= 7.09; CHP: P = 0.008; HR= 12.01). Our results suggest that the intra-tumoural perfusion habitats may potentially offer treatment targets.