bluuebunny/crossref_metadata_2025 huggingface dataset:
Polyphyllin I Inhibits Proliferation and Induces Apoptosis by Downregulating AML1‐ETO and Suppressing C‐KIT/Akt Signaling in t(8;21) Acute Myeloid Leukemia
Authors: Chai Yanting , Si Ying , Xu Jiaxin , Xiang Yuchen , Zhao Hongyan , Si Yuan , Zhang Te , Liu Ying
Published: September 2018

Polyphyllin I (PPI), a bioactive constituent extracted from traditional medicinal herbs, is cytotoxic to several cancer types. However, whether PPI can be used to treat t(8;21) acute myeloid leukemia (AML) cells requires further investigation. Here, we determined the inhibitory effects of PPI on t(8;21) AML cells by Cell Counting Kit‐8 (CCK‐8) and the trypan blue dye exclusion assay. DAPI staining and Wright–Giemsa staining were performed to check for apoptosis. Detection of apoptotic protein and AML1‐ETO signaling protein expression were conducted by Western blot analysis. Our results suggested that PPI decreased growth and induced apoptosis in a dosage‐dependent manner in the t(8;21) AML cell line Kasumi‐1. PPI significantly downregulated AML1‐ETO expression in a dosage‐ and time‐dependent manner. PPI also upregulated P21 and downregulated survivin expression by reducing AML1‐ETO. Mechanistically, PPI significantly reduced the expression of C‐KIT, another therapeutic target for AML with t(8;21), followed by inhibition of Akt signaling. These results suggest that PPI can suppress growth and induce apoptosis of t(8;21) AML by suppressing the AML1‐ETO and C‐KIT/Akt signaling pathways. Therefore, PPI may be an anticancer therapeutic to treat t(8;21) AML.
An RNase P‐Based Assay for Accurate Determination of the 5′‐Deoxy‐5′‐azidoguanosine‐Modified Fraction of in Vitro‐Transcribed RNAs
Authors: Lyon Seth E. , Chen Tien‐Hao , Wallace Andrew J. , Adib Katie , Gopalan Venkat
Published: September 2018

Chemoenzymatic approaches are important for generating site‐specific, chemically modified RNAs, a cornerstone for RNA structure–function correlation studies. T7 RNA polymerase (T7RNAP)‐mediated in vitro transcription (IVT) of a DNA template containing the G‐initiating class III Φ6.5 promoter is typically used to generate 5′‐chemically modified RNAs by including a guanosine analogue (G analogue) initiator in the IVT. However, the yield of 5′‐G analogue‐initiated RNA is often poor and variable due to the high ratios of G analogue:GTP used in IVT. We recently reported that a T7RNAP P266L mutant afforded an approximately three‐fold increase in fluorescent 5′‐thienoguanosine‐initiated pre‐tRNACys compared to the wild type T7RNAP. We have further explored the use of T7RNAP P266L to generate 5′‐deoxy‐5′‐azidoguanosine (azG)‐initiated RNA and found that the mutant yielded approximately four times more azG‐initiated pre‐tRNACys than the wild type in an IVT containing a 10:1 ratio of azG:GTP. For accurate quantitation of the 5′‐azG‐initiated RNA fraction, we employed RNase P, an endonuclease that catalyzes the removal of the 5′‐leader in pre‐tRNAs. Importantly, we show herein how RNase P can be leveraged for assessing 5′‐G analogue incorporation in any RNA by rendering the target RNA, upon its binding to a customized external guide sequence RNA, into an unnatural substrate of RNase P. Such an approach in conjunction with T7RNAP P266L‐based IVT should aid chemoenzymatic methods that are designed to generate 5′‐chemically modified RNAs.
Feasibility and characterization of the cycloamylose production from high amylose corn starch
Authors: Park Jiwoon , Rho Shin‐Joung , Kim Yong‐Ro
Published: September 2018

Background and objectives

Cycloamylose (CA), a promising encapsulating agent, was efficiently produced from high amylose corn starch (HACS, HYLON® VII) by sequentially combined enzyme treatment of isoamylase and Thermus aquaticus 4‐α‐glucanotransferase (TAαGT). The CA production performance of HACS was compared with that of rice starch (RS), especially from the viewpoint of differences in their molecular characteristics.

Findings

The maximum conversion yield of CA from HACS reached 76.35%, which was 2.4 times higher than that of RS (31.36%). The degree of polymerization (DP) of CA produced from HACS ranged from 7 to 41, where a major portion lied in DP 23–41, with DP 26 showing the highest yield. In contrast, CA produced from RS showed a relatively larger amount of smaller cyclic glucans (DP 6–16).

Conclusions

The significantly high production yield and DP profile of CA were attributed to high apparent amylose content and long average amylopectin branch chain length of HACS compared to those RS.

Significance and novelty

This study can provide a better understanding of CA production depending on starch molecular characteristics and attract industrial consideration in utilizing HACS for CA production.
Improving the Performance of Micro‐Silicon Anodes in Lithium‐Ion Batteries with a Functional Carbon Nanotube Interlayer
Authors: Wei Denghu , Gao Xiang , Zeng Suyuan , Li Haibo , Li Huaiyong , Li Wenzhi , Tao Xuquan , Xu Leilei , Chen Peng
Published: September 2018

There is currently intense research interest in silicon based anodes in lithium‐ion batteries. Modification approaches for nano‐sized silicon materials are popular, while much less attention has been paid on irregular bulk silicon particles. Here, we report that soft multiwall carbon nanotube membranes could be functioned as a shield on low‐cost micro‐sized silicon anodes to improve the cycling stability. The micro‐sized silicon could deliver a high reversible capacity of over 1000 mAh g−1 after 50 cycles at 0.36 A g−1 with the protection of a soft multiwall carbon nanotube membrane. Furthermore, the capacity could also be retained at ∼610 mAh g−1 at 0.5 A g−1 after 1200 cycles. The much improved performance upon cycling is mainly attributed to the alleviation of the large volume change. This strategy has also been proved effective in traditional nano‐silicon anodes, as a quite high capacity of about 5 mAh cm−2 could be obtained after 200 cycles. Overall, simply using a soft multiwall carbon nanotube membrane is a so far overlooked strategy, which is effective for improving performance of silicon anodes.
Photocatalytic Properties Dependent on the Interfacial Defects of Intergrains within TiO2 Mesocrystals
Authors: Wang Hui , Chen Qifeng , Luan Qingrui , Duan Ran , Guan Ruifang , Cao Xingzhong , Hu Xun
Published: September 2018

The regulation of interfacial defects of nanocrystals aligned orderly in a superstructured photocatalyst is an effective approach to improve the photocatalytic performance. However, the synthesis of ordered self‐assemblies with abundant interfacial defects and reactive sites is hard to achieve, and applications are limited due to the unclear physicochemical properties, which result from the unique mesocrystalline microstructures. It is reported herein that the photocatalytic properties depend on the interfacial defects of intergrains in anatase TiO2 mesocrystals (TMCs). Research reveals that the photocatalytic activity largely depends on defects, such as lattice distortion and oxygen vacancies, which are located at highly aligned interfaces of intergrains within TMCs. Moreover, the mesocrystalline TiO2 photocatalysts exhibit higher photocatalytic performance in organic degradation and hydrogen evolution, compared with single crystals and polycrystals; this can be ascribed to an appropriate amount of interfacial defects at the intergrains and improved carrier separation efficiency through the highly oriented interfaces. In addition, the photocatalytic performance of the TMCs could be further improved through regulation of defects by undergoing an annealing process under a redox atmosphere. This work can provide an avenue to defect engineering for improved photocatalytic performance.
Diprotonation of Guanidine in Superacidic Solutions
Authors: Morgenstern Yvonne , Zischka Florian , Kornath Andreas
Published: September 2018

Guanidinium chloride reacts with the superacidic solutions HF/MF5 (M=As, Sb) at a molar ratio of 1:2 under formation of the diprotonated guanidinium salts [C(NH2)2(NH3)][AsF6]2 and [C(NH2)2(NH3)][SbF6]2. The compounds were characterized by using infrared and Raman spectroscopy. Furthermore, single‐crystal X‐ray structure analysis of the guanidinium(2+) salts [C(NH2)2(NH3)][SbF6]2⋅HF, [C(NH2)2(NH3)]2[Ge3F16]⋅HF, and [C(NH2)2(NH3)]2[Ge3F16]⋅2 HF and the guanidinium(1+) salt [C(NH2)3][SbF6] is reported. The discussion of the experimental data is supported by quantum‐chemical calculations of the [C(NH2)2(NH3)]2+ and [C(NH2)3]+ ions to investigate the modification of the resonance stabilization during the protonation process at the PBE1PBE/6–311G++(3df,3pd) level of theory. The planar CN3 skeleton of the guanidinium(2+) ion has two carbon–nitrogen bonds in the range 1.286(4)–1.293(4) Å and one carbon–nitrogen bond of 1.453(4) Å, which can be explained with a decreased resonance stabilization relative to the guanidinium(1+) ion.
Catalytic Isohypsic‐Redox Sequences for the Rapid Generation of Csp3‐Containing Heterocycles
Authors: Smith Craig D. , Phillips David , Tirla Alina , France David J.
Published: September 2018

Cross‐coupling reactions catalyzed by transition metals are among the most influential in modern synthetic chemistry. The vast majority of transition‐metal‐catalyzed cross‐couplings rely on a catalytic cycle involving alternating oxidation and reduction of the metal center and are generally limited to forging just one type of new bond per reaction (e.g., the biaryl linkage formed during a Suzuki cross‐coupling). This work presents an Isohypsic‐Redox Sequence (IRS) that uses one metal to effect two catalytic cycles, thereby generating multiple new types of bonds from a single catalyst source. We show that the IRS strategy is amenable to several widely used transformations including the Suzuki–Miyaura coupling, Buchwald–Hartwig amination, and Wacker oxidation. Furthermore, each of these reactions generates value‐added heterocycles with significant sp3‐C (3‐dimensional) content. Our results provide a general framework for generating complex products by using a single metal to fulfill multiple roles. By uniting different combinations of reactions in the isohypsic and redox phases of the process, this type of catalytic multiple bond‐forming platform has the potential for wide applicability in the efficient synthesis of functional organic molecules.
Total Synthesis of (−)‐Cylindrocyclophane F: A Yardstick for Probing New Catalytic C−C Bond‐Forming Methodologies
Authors: Berthold Dino , Breit Bernhard
Published: September 2018

A short and efficient total synthesis of the C2‐symmetric (−)‐cylindrocyclophane F is presented, using a cross olefin metathesis dimerization strategy for construction of the [7,7]‐paracyclophane macrocycle. The synthesis of the dimerization building block includes a Pd‐catalyzed sp3‐sp2 Negishi cross coupling of a sterically hindered Zn‐reagent with an aromatic triflate, an enantiospecific Zn‐catalyzed sp3‐sp3 cross coupling of an α‐hydroxy ester triflate with a Grignard reagent and the application of an enantioselective Rh‐catalyzed C‐allylation of an electron rich arene.
Performance of multitarget stool DNA testing in African American patients
Authors: Cooper Gregory S. , Markowitz Sanford D. , Chen Zhengyi , Tuck Missy , Willis Joseph E. , Berger Barry M. , Brenner Dean E. , Li Li
Published: September 2018

BACKGROUND

Multitarget stool DNA (mt‐sDNA) is an approved method for colon cancer screening that is especially relevant for patients who cannot undergo colonoscopy. Although the test performance has been evaluated in a large clinical trial, it was limited to a predominantly white population. Given differences in the epidemiology and biology of colon cancer in African American individuals, the authors sought to compare the performance of mt‐sDNA between racial groups.

METHODS

The authors prospectively identified patients aged ≥40 years who were referred for colonoscopy at an academic medical center and 2 satellite facilities. Prior to the colonoscopy, the authors collected stool for mt‐sDNA and fecal immunochemical testing (FIT). They compared the sensitivity, specificity, and receiver operating characteristic curve between African American and white patients for the detection of advanced lesions or any adenoma.

RESULTS

A total of 760 patients were included, 34.9% of whom were African American. The prevalence of any adenoma (38.9% for African American patients and 33.9% for white patients) and that for advanced lesions (6.8% and 6.7%, respectively) were similar between groups. The overall sensitivities of mt‐sDNA for the detection of advanced lesions and any adenoma were 43% and 19%, respectively, and the specificities were 91% and 93%, respectively. In general, mt‐sDNA was more sensitive and less specific than FIT. When stratified by race, the sensitivity, specificity, and receiver operating characteristic curve area were similar between African American and white patients for both mt‐sDNA and FIT.

CONCLUSIONS

Test performance characteristics of mt‐sDNA were comparable in African American and white patients. Given the lower uptake of colonoscopy in African American individuals, mt‐sDNA may offer a promising screening alternative in this patient population.
The aid of colour on visuospatial navigation of elderly people in a virtual polyclinic environment
Authors: Süzer Özge Kumoğlu , Olguntürk Nilgün
Published: September 2018

It is well documented that elderly people often have difficulties in finding their way in unfamiliar environments. In this study, we aimed to explore the usage of colour as visuospatial navigation tool for elderly people by testing in a virtually simulated polyclinic environment. We compared neutral, warm and cool coloured experiment settings to find out the effect of different colours on elderly people's visuospatial navigation performances. We conducted our experiment with 90 participants in two phases, each with a specific task (Route Replication and Picture Classification). The findings showed that neutral coloured setting affected participants' visuospatial navigation performances negatively compared to warm and cool coloured settings. However, there was no significant performance difference between warm and cool coloured environments. In addition to that, when they were asked to reach to the destination point, male participants spent shorter time, did fewer wrong turns, experienced fewer hesitations and traveled shorter distances compared to female participants. Currently, due to the increase in the elderly population, designing well‐functioning interior spaces for the elderly has become a more pressing matter. We believe that the findings of this study will provide important clues for both interior designers and environmental psychologists.
Committee II: Guidelines for cytologic sampling techniques of lung and mediastinal lymph nodes
Authors: Michael C. W. , Faquin W. , Jing X. , Kaszuba F. , Kazakov J. , Moon E. , Toloza E. , Wu R. I. , Moreira A. L.
Published: September 2018

The Papanicolaou Society of Cytopathology has developed a set of guidelines for pulmonary cytology including indications for bronchial brushings, washings, and endobronchial ultrasound guided transbronchial fine‐needle aspiration (EBUS‐TBNA), technical recommendations for cytological sampling, recommended terminology and classification schemes, recommendations for ancillary testing and recommendations for post‐cytological management and follow‐up. All recommendations are based on the expertise of the authors, an extensive literature review and feedback from presentations at national and international conferences. This document selectively presents the results of these discussions. The present document summarizes recommendations regarding techniques used to obtain cytological and small histologic specimens from the lung and mediastinal lymph nodes including rapid on‐site evaluation (ROSE), and the triage of specimens for immunocytochemical and molecular studies.
Can a threshold for 11‐nor‐9‐carboxy‐Δ9 ‐tetrahydrocannabinol in hair be derived when its respective concentration in blood serum indicates regular use?
Authors: Zinka Bettina , Epple Sabine , Schick Sylvia , Skopp Gisela , Graw Matthias , Musshoff Frank
Published: September 2018

A 100 μg/L or higher concentration of 11‐nor‐9‐carboxy‐Δ9‐tetrahydrocannabinol (THC‐COOH) in blood serum is generally assumed to be associated with regular and/or heavy use of cannabis. At present, determination of the extent of cannabis use by means of the concentration of THC‐COOH in hair has not been assessed. Therefore, we aimed at establishing a threshold for THC‐COOH concentrations in hair to prove frequent consumption by comparing THC‐COOH concentrations in 129 corresponding serum and hair samples, respectively.

The concentration of THC‐COOH in the serum was analyzed by gas chromatography–mass spectrometry and in the hair by liquid chromatography–tandem mass spectrometry. Data were statistically evaluated using receiver operating characteristic curves and contingency tables. Our results suggest that a THC‐COOH concentration of ≥4.2 pg/mg in hair was always accompanied by a THC‐COOH concentration of at least 100 μg/L in blood serum. Should this be confirmed by further studies of a larger study population, a hair concentration of 4.2 pg/mg THC‐COOH can be set as a threshold to predict regular and/or heavy consumption of cannabis even if no corresponding blood sample is available for analysis.
Multiple incidence of the prescription diuretic hydrochlorothiazide in compounded nutritional supplements
Authors: Favretto Donata , Visentin Sindi , Scrivano Salvatore , Roselli Emanuele , Mattiazzi Fabio , Pertile Roberto , Vogliardi Susanna , Tucci Marianna , Montisci Massimo
Published: September 2018

Diuretic agents are prohibited in sports in‐ and out‐of‐competition according to the regulations of the World Anti‐Doping Agency (WADA) because of their possible masking effects on other doping agents in urine samples, and their ability to produce fast acute weight losses. Despite previous studies reported adverse analytical findings (AAFs) resulting from contaminations at ppm level (μg/g) of medicinal products, and recommended to introduce reporting limits for diuretics in doping controls, these are not adopted in analyses performed by WADA‐accredited laboratories. We report the case of an athlete with two AAFs for hydrochlorothiazide (HCTZ) at low urinary concentrations (<10 ng/mL), who declared the use of nutritional supplements prepared in a compounding pharmacy. His nutritional supplements were analyzed revealing HCTZ presence in different concentrations, at the ppm level (μg/g and ng/mL).

With the aim of testing the plausibility of the observed urinary HCTZ concentrations with the nutritional supplement ingestion, a urinary excretion study with three healthy volunteers was performed. HCTZ‐contaminated powder (6.4 μg/g of HCTZ) was administered to each subject in different dosages, reproducing the possible ingestion pattern occurred. Urine specimens were collected before and after ingestion of the powder, up to 24 hours, and underwent liquid–liquid extraction and liquid chromatography–tandem mass spectrometry determination.

Post‐administration specimens were found to contain HCTZ at concentrations of 5–230 ng/mL, which supported the accidental inadvertent intake of the prohibited substance by the athlete. This study makes the argument that the introduction of reporting limits for diuretics are warranted in doping control samples, in order to protect against inadvertent AAFs due to contaminated products.
Cre/lox‐controlled spatiotemporal perturbation of FGF signaling in zebrafish
Authors: Kirchgeorg Lucia , Felker Anastasia , van Oostrom Marek , Chiavacci Elena , Mosimann Christian
Published: September 2018

Background: Spatiotemporal perturbation of signaling pathways in vivo remains challenging and requires precise transgenic control of signaling effectors. Fibroblast growth factor (FGF) signaling guides multiple developmental processes, including body axis formation and cell fate patterning. In zebrafish, mutants and chemical perturbations affecting FGF signaling have uncovered key developmental processes; however, these approaches cause embryo‐wide perturbations, rendering assessment of cell‐autonomous vs. non‐autonomous requirements for FGF signaling in individual processes difficult.

Results: Here, we created the novel transgenic line fgfr1‐dn‐cargo, encoding dominant‐negative Fgfr1a with fluorescent tag under combined Cre/lox and heatshock control to perturb FGF signaling spatiotemporally. Validating efficient perturbation of FGF signaling by fgfr1‐dn‐cargo primed with ubiquitous CreERT2, we established that primed, heatshock‐induced fgfr1‐dn‐cargo behaves similarly to pulsed treatment with the FGFR inhibitor SU5402. Priming fgfr1‐dn‐cargo with CreERT2 in the lateral plate mesoderm triggered selective cardiac and pectoral fin phenotypes without drastic impact on overall embryo patterning. Harnessing lateral plate mesoderm‐specific FGF inhibition, we recapitulated the cell‐autonomous and temporal requirement for FGF signaling in pectoral fin outgrowth, as previously inferred from pan‐embryonic FGF inhibition.

Conclusions: As a paradigm for rapid Cre/lox‐mediated signaling perturbations, our results establish fgfr1‐dn‐cargo as a genetic tool to define the spatiotemporal requirements for FGF signaling in zebrafish. Developmental Dynamics 247:1146‐1159, 2018. © 2018 Wiley Periodicals, Inc.
Factors influencing experimental estimation of scavenger removal and observer detection in bird–window collision surveys
Authors: Riding Corey S. , Loss Scott R.
Published: September 2018

Wildlife collisions with human‐built structures are a major source of direct anthropogenic mortality. Understanding and mitigating the impact of anthropogenic collisions on wildlife populations require unbiased mortality estimates. However, counts of collision fatalities are underestimated due to several bias sources, including scavenger removal of carcasses between fatality surveys and imperfect detection of carcasses present during surveys. These biases remain particularly understudied for bird–window collisions, the largest source of avian collision mortality. In Stillwater, Oklahoma, USA, we used bird carcasses collected during window collision monitoring to experimentally assess factors influencing scavenging and observer detection, and we employed trail cameras to characterize the scavenger community and timing of scavenging. We recorded nine scavenger species, but the domestic cat and Virginia opossum were responsible for 73% of known‐species scavenging events. The most frequent scavenger species were primarily nocturnal, and 68% of scavenging events occurred at night. Scavenger species best predicted time to first scavenging event, season best predicted carcass persistence time, and both season and carcass size predicted whether any carcass remains persisted after scavenging. Our results also suggest that observer detection was influenced by substrate, with greater detection of carcasses on artificial substrates. Our findings related to scavenging timing have important implications for the unbiased estimation of collision mortality because the timing of peak scavenging relative to timing of peak mortality can substantially influence accuracy of adjusted mortality estimates. Further, the differences in correlates for time to first scavenging and time to carcass removal (i.e., persistence time) illustrate the importance of explicitly measuring these often‐independent events that are frequently conflated in the anthropogenic mortality literature.
Pace of life syndrome under warming and pollution: integrating life history, behavior, and physiology across latitudes
Authors: Debecker Sara , Stoks Robby
Published: September 2018

To fully comprehend and predict the impact of drivers of global change such as climate warming and pollution, integrated multi‐trait approaches are needed. As organismal traits are often correlated, responses to stressors are expected to induce coordinated changes in many traits. A promising framework to study this is the pace of life syndrome (POLS), which predicts the integration of life history, behavioral, and physiological traits along a fast‐slow continuum. Using an integrative multi‐trait approach, we evaluated the presence of a POLS both within and across latitudes and how POLS patterns are affected by warming and metal pollution. We studied this in Ischnura elegans damselfly larvae of replicated low‐ and high‐latitude populations that strongly differ in voltinism (three to four generations per year vs. one generation every two years) reared in a common‐garden experiment at two temperatures. Across latitudes, life history, behavior, and physiology covaried in accordance with the POLS, with the fast‐paced low‐latitude damselflies characterized by a fast growth rate, high activity, and more explorative and risk‐taking behavior, fast metabolic rate, and low investment in immune function (activity of phenoloxidase). This fast POLS strategy was associated with a higher sensitivity to metal exposure and a higher vulnerability to predation. Warming caused opposite responses between the latitudes consistent with differential thermal adaptation in growth rate, behavior, and oxidative stress parameters. Despite this, damselflies of both latitudes showed a consistent pattern in phenotypic correlations among traits that, moreover, was not affected by warming and metal exposure. Within latitudes, there was no full support for the POLS. More active larvae were more explorative and risk taking, which aligned with the fast‐slow life history axis, but less strong than at the across‐latitude level. Physiological traits were also integrated within latitudes, yet there was no unambiguous coupling with the fast‐slow life history continuum. The consistent syndrome structure, if underpinned by genetic correlations, may restrict the independent evolution of individual traits, yet may not necessarily constrain adaptive evolution of integrated trait sets. This is because the covariance pattern was to a large extent similar across latitudes and within latitudes, suggesting adaptive trait integration guiding adaptive evolution of trait sets along the fast‐slow continuum.
Biofluid pumping and mixing by an AC electrothermal micropump embedded with a spiral microelectrode pair in a cylindrical microchannel
Authors: Gao Xiaobo , Li Yuxiao
Published: September 2018

In this paper, we numerically investigated a multifunctional AC electrothermal (ACET) micropump embedded with an asymmetric spiral microelectrode pair in a cylindrical microchannel for simultaneous pumping and mixing in high‐conductivity fluids, which makes the pump useful for biofluid applications. When an AC signal was applied to the asymmetric spiral electrode pair, the vortices induced on the electrode surfaces with centerlines along the corresponding spiral electrode length exhibit a spiral distribution, and the net flow in the cylindrical microchannel is generated by the ACET effect. The vorticity field distribution can explain the mechanism of simultaneous pumping and mixing. Because the vorticity field is inclined against the microchannel direction, vortices on top of the spiral electrodes can affect the ACET flow in the following two aspects at the same time: one is pumping the flow in the microchannel direction, and the other is mixing the samples by stirring the flow. We also determined that the geometric ratios of the electrode width to the gap or slant angle of the spiral electrodes can feasibly be used to control the relative strength of the pumping and mixing capabilities, and we achieved an optimal design that gives both desirable pumping and mixing efficiencies. This study shows that the spiral ACET micropump design can rapidly drive the high‐conductivity fluids and efficiently mix samples simultaneously. The numerical simulation of the spiral ACET micropump is of significant importance for practical, chemical and biological applications, and feasible fabrication techiniques should be experimentally investigated in future studies.
Covalent organic framework TpPa‐1 as stationary phase for capillary electrochromatographic separation of drugs and food additives
Authors: Kong Deying , Chen Zilin
Published: September 2018

Because of unique properties like permanent porosity, low density and large surface area, covalent organic frameworks are attractive microporous materials as stationary phase for CEC. Among them, COF‐TpPa‐1 possesses extraordinary chemical stability and common features of covalent organic frameworks. So, COF‐TpPa‐1 could be a promising material as stationary phase to enhance separation selectivity and tolerate the acid or alkaline electrochromatographic separation conditions. Here, we report the preparation of COF‐TpPa‐1 modified capillary column by in situ growth for electrochromatographic separation. The immobilization of COF‐TpPa‐1 on the inner wall of capillary column was confirmed by Fourier transform infrared spectroscopy, scanning electron microscopy and X‐ray diffraction. The fabricated COF‐TpPa‐1 modified capillary column indicated good resolution for the separation of neutral analytes, nonsteroidal anti‐inflammatory drugs and food additives in open‐tubular CEC mode. Compared with bare capillary column, the COF‐TpPa‐1 modified capillary column improved separation selectivity remarkably for tested analytes, including hydrophobic, π–π and hydrogen bond interactions. Besides, the prepared capillary column showed excellent repeatability and stability. The intraday, interday and column‐to‐column relative standard deviations of migration time for neutral analytes were less than 3.54%. This work shows enamine‐linked covalent organic frameworks have great potential as stationary phases in CEC.
Alkanethiol‐functionalized organosilicon monoliths for nano‐reversed‐phase liquid chromatography
Authors: Demir Cihan , Kip Çiğdem , Tuncel Ali
Published: September 2018

Organosilicon monoliths carrying chromatographic ligands with different alkyl chain lengths were obtained by thiol‐methacrylate photopolymerization. The use of thiol‐ene chemistry in the presence of a main monomer with a series of methacrylate functionality (i.e., methacrylate substituted polyhedral oligomeric silsesquioxane) allowed the synthesis of organosilicon monoliths with high cross‐linking density and carrying hydrophobic alkyl‐chain ligands by a one‐pot process. In the synthesis runs, 1‐butanethiol, 1‐octanethiol, and 1‐octadecanethiol were used as the hydrophobic thiol ligands with the number of methylene units between 4 and 18. The selectivity analysis performed using cytosine/uracil retention ratio showed that alkanethiol‐attached organosilicon monoliths exhibited hydrophobicity close to octadecyl‐attached silica‐based RP columns. In the RP, chromatographic runs performed in nano‐liquid chromatography, phenols, alkylbenzenes, and PAHs were used as the analytes. Among the synthesized monoliths, retention‐independent plate height behavior and the smallest plate heights were obtained with 1‐octadecanethiol‐attached organosilicon monolith for the analytes in a wide polarity range. With this monolith, the mobile phases prepared with ACN contents ranging between 35 and 85% v/v could be used for satisfactory separation of analytes in a wide polarity range.
Effects of electrode size and surface morphology on electrode polarization in physiological buffers
Authors: Koklu Anil , Mansoorifar Amin , Beskok Ali
Published: September 2018

Electrode polarization (EP) is inevitable in high conductivity buffers at low AC frequencies due to the accumulation of free charges at the electrode/electrolyte interface. Electrode miniaturization increases EP effect on impedance measurements. In this paper, six gold planar (GP) electrodes having different diameters () were used to investigate the size effect on EP with parallel plate electrode geometry. GP electrode surface was electrochemically deposited with gold nanostructures (GNs) to minimize the EP effect. Equivalent circuit model was used to attain electrode/electrolyte interfacial impedance. Constant phase element model was used to analyze the relation between the size and morphology of electrodes on EP. The surface morphology of gold nanostructured electrodes was examined using SEM, and the influence of different applied potential on the growth of GNs was elucidated with Nernst equilibrium condition. Surface roughness and wettability characteristics were examined performing surface roughness and contact angle measurements, respectively. The improvement of GNs deposited electrode performance was investigated by analytically generated Jurkat cell suspension spectra. The results show that the error in estimating the subcellular properties can be drastically reduced by using GNs deposited electrodes.
Have Fish Will Travel—A Scientist's View of the World
Authors: Swales Stephen
Published: September 2018

In this article, I provide a brief description of my experience working in the field of fisheries in various countries around the world from Europe to Australasia. The fish and fisheries of New Zealand, Australia, and Papua New Guinea are discussed and the various factors affecting them are summarized and compared. Although environmental conditions and fish faunas vary considerably among these countries, all are affected to various degrees by human disturbances to land and water. Many fish species are particularly threatened by river modifications, such as impoundment and abstraction, resource development (e.g., mining), and changes in land use through forest clearance and agricultural development, as well as by the effects of introduced species, such as carp and trout. However, continued improvements in environmental management and implementation of species conservation programs provide hope that the declines may be halted or reversed. My experience suggests that working in a range of countries can provide a unique perspective on the problems facing the world's fish and fisheries.
Signal transduction in astrocytes: Localization and release of inorganic polyphosphate
Authors: Angelova Plamena R. , Iversen Kathrine Z. , Teschemacher Anja G. , Kasparov Sergey , Gourine Alexander V. , Abramov Andrey Y.
Published: September 2018

Inorganic polyphosphate (polyP) is present in every cell and is highly conserved from primeval times. In the mammalian cells, polyP plays multiple roles including control of cell bioenergetics and signal transduction. In the brain, polyP mediates signaling between astrocytes via activation of purinergic receptors, however, the mechanisms of polyP release remain unknown. Here we report identification of polyP‐containing vesicles in cortical astrocytes and the main triggers that evoke vesicular polyP release. In cultured astrocytes, polyP was localized predominantly within the intracellular vesicular compartments which express vesicular nucleotide transporter VNUT (putative ATP‐containing vesicles), but not within the compartments expressing vesicular glutamate transporter 2 (VGLUT2). The number of lysosomes which contain polyP was dependent on the conditions of astrocytes. Release of polyP from a proportion of lysosomes could be induced by calcium ionophores. In contrast, polyP release from the VNUT‐containing vesicles could be triggered by various physiological stimuli, such as pH changes, polyP induced polyP release and other stimuli which increase [Ca2+]
i. These data suggest that astrocytes release polyP predominantly via exocytosis from the VNUT‐containing vesicles. © 2018 Wiley Periodicals, Inc.
Nav1.5 in astrocytes plays a sex‐specific role in clinical outcomes in a mouse model of multiple sclerosis
Authors: Pappalardo Laura W. , Samad Omar A. , Liu Shujun , Zwinger Pamela J. , Black Joel A. , Waxman Stephen G.
Published: September 2018

Astrogliosis is a hallmark of neuroinflammatory disorders such as multiple sclerosis (MS). A detailed understanding of the underlying molecular mechanisms governing astrogliosis might facilitate the development of therapeutic targets. We investigated whether Nav1.5 expression in astrocytes plays a role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a murine model of MS. We created a conditional knockout of Nav1.5 in astrocytes and determined whether this affects the clinical course of EAE, focal macrophage and T cell infiltration, and diffuse activation of astrocytes. We show that deletion of Nav1.5 from astrocytes leads to significantly worsened clinical outcomes in EAE, with increased inflammatory infiltrate in both early and late stages of disease, unexpectedly, in a sex‐specific manner. Removal of Nav1.5 in astrocytes leads to increased inflammation in female mice with EAE, including increased astroglial response and infiltration of T cells and phagocytic monocytes. These cellular changes are consistent with more severe EAE clinical scores. Additionally, we found evidence suggesting possible dysregulation of the immune response—particularly with regard to infiltrating macrophages and activated microglia—in female Nav1.5 KO mice compared with WT littermate controls. Together, our results show that deletion of Nav1.5 from astrocytes leads to significantly worsened clinical outcomes in EAE, with increased inflammatory infiltrate in both early and late stages of disease, in a sex‐specific manner.
How to reprogram microglia toward beneficial functions
Authors: Fumagalli Marta , Lombardi Marta , Gressens Pierre , Verderio Claudia
Published: September 2018

Microglia, brain cells of nonneural origin, orchestrate the inflammatory response to diverse insults, including hypoxia/ischemia or maternal/fetal infection in the perinatal brain. Experimental studies have demonstrated the capacity of microglia to recognize pathogens or damaged cells activating a cytotoxic response that can exacerbate brain damage. However, microglia display an enormous plasticity in their responses to injury and may also promote resolution stages of inflammation and tissue regeneration. Despite the critical role of microglia in brain pathologies, the cellular mechanisms that govern the diverse phenotypes of microglia are just beginning to be defined. Here we review emerging strategies to drive microglia toward beneficial functions, selectively reporting the studies which provide insights into molecular mechanisms underlying the phenotypic switch. A variety of approaches have been proposed which rely on microglia treatment with pharmacological agents, cytokines, lipid messengers, or microRNAs, as well on nutritional approaches or therapies with immunomodulatory cells. Analysis of the molecular mechanisms relevant for microglia reprogramming toward pro‐regenerative functions points to a central role of energy metabolism in shaping microglial functions. Manipulation of metabolic pathways may thus provide new therapeutic opportunities to prevent the deleterious effects of inflammatory microglia and to control excessive inflammation in brain disorders.
A Model to Predict 1‐Month Risk of Transplant or Death in Hepatitis A–Related Acute Liver Failure
Authors: Kim Jin Dong , Cho Eun Ju , Ahn Choonghyun , Park Sue K. , Choi Jong Young , Lee Han Chu , Kim Do Young , Choi Moon Seok , Wang Hee Jung , Kim In Hee , Yeon Jong Eun , Seo Yeon Seok , Tak Won Young , Kim Moon Young , Lee Heon Ju , Kim Yun Soo , Jun Dae Won , Sohn Joo Hyun , Kwon So Young , Park Sang Hoon , Heo Jeong , Jeong Sook‐Hyang , Lee Jeong‐Hoon , Nakayama Nobuaki , Mochida Satoshi , Ido Akio , Tsubouchi Hirohito , Takikawa Hazime , Shalimar  , Acharya Subrat Kumar , Bernal William , O’Grady John , Kim Yoon Jun
Published: September 2018

Acute liver failure (ALF) caused by hepatitis A is a rare but fatal disease. Here, we developed a model to predict outcome in patients with ALF caused by hepatitis A. The derivation set consisted of 294 patients diagnosed with hepatitis A–related ALF (ALFA) from Korea, and a validation set of 56 patients from Japan, India, and United Kingdom. Using a multivariate proportional hazard model, a risk‐prediction model (ALFA score) consisting of age, international normalized ratio, bilirubin, ammonia, creatinine, and hemoglobin levels acquired on the day of ALF diagnosis was developed. The ALFA score showed the highest discrimination in the prediction of liver transplant or death at 1 month (c‐statistic, 0.87; 95% confidence interval [CI], 0.84‐0.92) versus King’s College criteria (KCC; c‐statistic, 0.56; 95% CI, 0.53‐0.59), U.S. Acute Liver Failure Study Group index specific for hepatitis A virus (HAV‐ALFSG; c‐statistic, 0.70; 95% CI, 0.65‐0.76), the new ALFSG index (c‐statistic, 0.79; 95% CI, 0.74‐0.84), Model for End‐Stage Liver Disease (MELD; c‐statistic, 0.79; 95% CI, 0.74‐0.84), and MELD including sodium (MELD‐Na; c‐statistic, 0.78; 95% CI, 0.73‐0.84) in the derivation set (all P < 0.01). In the validation set, the performance of the ALFA score (c‐statistic, 0.84; 95% CI, 0.74‐0.94) was significantly better than that of KCC (c‐statistic, 0.65; 95% CI, 0.52‐0.79), MELD (c‐statistic, 0.74; 95% CI, 0.61‐0.87), and MELD‐Na (c‐statistic, 0.72; 95% CI, 0.58‐0.85) (all P < 0.05), and better, but not statistically significant, than that of the HAV‐ALFSG (c‐statistic, 0.76; 95% CI, 0.61‐0.90; P = 0.28) and new ALFSG indices (c‐statistic, 0.79; 95% CI, 0.65‐0.93; P = 0.41). The model was well‐calibrated in both sets. Conclusion: Our disease‐specific score provides refined prediction of outcome in patients with ALF caused by hepatitis A.
Synthesis of a Monomer for Two‐Dimensional Polymerization under Technically Feasible Conditions
Authors: Tanner Philipp , Maier Gerhard , Schlüter A. Dieter
Published: September 2018

The synthesis of a promising 2D polymer uses the double decker rotor‐shaped monomer 1, containing three anthracene moieties. To accelerate the development of the field of 2D polymers, this monomer was selected for scale‐up that would allow its synthesis to be performed on the kg scale under technical conditions. This goal was achieved in collaboration with Polymaterials AG, Kaufbeuren, Germany. Not only was the synthetic route shortened, but each and every aspect of the remaining steps was streamlined so as to render them applicable to technical conditions. This involved the entire sequence to be adapted to metal instead of glass reactors and to a number of safety and toxicity concerns. Additionally, not only the utilization of the reactors had to meet strict efficiency requirements, but also the work‐up procedures had to be facile. The whole sequence was then tested for feasibility under realistic conditions at Polymaterials AG. While this test afforded 130 g of monomer 1, it has the clear potential for the kg scale, supposed the safety equipment for the hydrogen evolution for the conversion of compound 2a – 3 is available.
Avoiding confusion between pressure front pulse displacement and groundwater displacement: Illustration with the pumping test in a confined aquifer
Authors: Chesnaux Romain
Published: September 2018

Two distinct phenomena may be distinguished and defined during a pumping test conducted in a confined aquifer: the pressure front pulse displacement and the groundwater displacement. This Scientific briefing examines and clarifies the difference between the pressure wave displacement and the groundwater displacement, by stating the differences in their respective transit times and velocities. The pressure front pulse displacement is controlled by the diffusivity of the aquifer, whereas groundwater displacement is controlled by the pumping flow rate and the effective porosity of the aquifer. To calculate the transit time and velocity of each type of displacement, several equations are presented and compared. An example is provided to illustrate the differences in velocity between the pressure front pulse displacement and the groundwater displacement.
Genetic susceptibility in the development of colorectal adenomas according to family history of colorectal cancer
Authors: Gargallo Carla J. , Lanas Ángel , Carrera‐Lasfuentes Patricia , Ferrandez Ángel , Quintero Enrique , Carrillo Marta , Alonso‐Abreu Inmaculada , García‐Gonzalez María Asunción
Published: September 2018

Our study aimed to evaluate the relevance of genetic susceptibility in the development of colorectal adenomas (CRA) and its relationship with the presence of family history of colorectal cancer (CRC). Genomic DNA from 750 cases (first degree relatives of patients with CRC) and 750 controls (subjects with no family history of CRC) was genotyped for 99 single nucleotide polymorphisms (SNPs) previously associated with CRC/CRA risk by GWAS and candidate gene studies by using the MassArray™ (Sequenom) platform. Cases and controls were matched by gender, age and histological lesion. Eight hundred and fifty‐eight patients showed no neoplastic lesions, whereas 288 patients showed low‐risk adenomas, and 354 patients presented high‐risk adenomas. Two SNPs (rs10505477, rs6983267) in the CASC8 gene were associated with a reduced risk of CRA in controls (log‐additive models, OR: 0.67, 95%CI:0.54–0.83, and OR:0.66, 95%CI:0.54–0.84, respectively). Stratified analysis by histological lesion revealed the association of rs10505477 and rs6983267 variants with reduced risk of low‐ and high‐risk adenomas in controls, being this effect stronger in low‐risk adenomas (log‐additive models, OR:0.63, 95%CI:0.47–0.84 and OR:0.64, 95%CI:0.47–0.86, respectively). Moreover, 2 SNPs (rs10795668, rs11255841) in the noncoding LINC00709 gene were significantly associated with a reduced risk of low‐risk adenomas in cases (recessive models, OR:0.22, 95%CI:0.06–0.72, and OR:0.08, 95%CI:0.03–0.61) and controls (dominant models, OR:0.50, 95%CI:0.34–0.75, and OR:0.52, 95%CI:0.35–0.78, respectively). In conclusion, some variants associated with CRC risk (rs10505477, rs6983267, rs10795668 and rs11255841) are also involved in the susceptibility to CRA and specific subtypes. These associations are influenced by the presence of family history of CRC.
PDEδ inhibition impedes the proliferation and survival of human colorectal cancer cell lines harboring oncogenic KRas
Authors: Klein Christian H. , Truxius Dina C. , Vogel Holger A. , Harizanova Jana , Murarka Sandip , Martín‐Gago Pablo , Bastiaens Philippe I.H.
Published: September 2018

Ras proteins, most notably KRas, are prevalent oncogenes in human cancer. Plasma membrane localization and thereby signaling of KRas is regulated by the prenyl‐binding protein PDEδ. Recently, we have reported the specific anti‐proliferative effects of PDEδ inhibition in KRas‐dependent human pancreatic ductal adenocarcinoma cell lines. Here, we investigated the proliferative dependence on the solubilizing activity of PDEδ of human colorectal cancer (CRC) cell lines with or without oncogenic KRas mutations. Our results show that genetic and pharmacologic interference with PDEδ specifically inhibits proliferation and survival of CRC cell lines harboring oncogenic KRas mutations whereas isogenic cell lines in which the KRas oncogene has been removed, or cell lines with oncogenic BRaf mutations or EGFR overexpression are not dependent on PDEδ. Pharmacological PDEδ inhibition is therefore a possible new avenue to target oncogenic KRas bearing CRC.