bluuebunny/crossref_metadata_2025 huggingface dataset:
Cellular glycosylation senses metabolic changes and modulates cell plasticity during epithelial to mesenchymal transition
Authors: Carvalho‐cruz Patricia , Alisson‐Silva Frederico , Todeschini Adriane R. , Dias Wagner B.
Published: July 2017

Epithelial to mesenchymal transition (EMT) is a developmental program reactivated by tumor cells that leads to the switch from epithelial to mesenchymal phenotype. During EMT, cells are transcriptionally regulated to decrease E‐cadherin expression while expressing mesenchymal markers such as vimentin, fibronectin, and N‐cadherin. Growing body of evidences suggest that cells engaged in EMT undergo a metabolic reprograming process, redirecting glucose flux toward hexosamine biosynthesis pathway (HBP), which fuels aberrant glycosylation patterns that are extensively observed in cancer cells. HBP depends on nutrient availability to produce its end product UDP‐GlcNAc, and for this reason is considered a metabolic sensor pathway. UDP‐GlcNAc is the substrate used for the synthesis of major types of glycosylation, including O‐GlcNAc and cell surface glycans. In general, the rate limiting enzyme of HBP, GFAT, is overexpressed in many cancer types that present EMT features as well as aberrant glycosylation. Moreover, altered levels of O‐GlcNAcylation can modulate cell morphology and favor EMT. In this review, we summarize some of the current knowledge that correlates glucose metabolism, aberrant glycosylation and hyper O‐GlcNAcylation supported by HBP that leads to EMT activation. Developmental Dynamics 247:481–491, 2018. © 2017 Wiley Periodicals, Inc.
The double edge to parasite escape: invasive host is less infected but more infectable
Authors: Keogh Carolyn L. , Miura Osamu , Nishimura Tomohiro , Byers James E.
Published: July 2017

Nonnative species that escape their native‐range parasites may benefit not only from reduced infection pathology, but also from relaxed selection on costly immune defenses, promoting reallocation of resources toward growth or reproduction. However, benefits accruing from a reduction in defense could come at the cost of increased infection susceptibility. We conducted common garden studies of the shore crab Hemigrapsus sanguineus from highly parasitized native (Japan) populations and largely parasite‐free invasive (USA) populations to test for differences in susceptibility to infection by native‐range rhizocephalan parasites, and to explore differences in host resource allocation. Nonnative individuals showed at least 1.8 times greater susceptibility to infection than their native counterparts, and had reduced standing metabolic rates, suggesting that less of their energy was spent on physiological self‐maintenance. Our results support an indirect advantage to parasite escape via the relaxation of costly physiological defenses. However, this advantage comes at the cost of heightened susceptibility, a trade‐off of parasite escape that is seldom considered.
Investigation of Degradation and Voltage Response of Lithium‐Ion Battery Based on Impedance and Electromotive Force Measurement
Authors: INUI YOSHITAKA , SAKAMOTO SHINICHI , TANAKA TADASHI
Published: July 2017

Detailed information on degradation process of lithium‐ion batteries is essential to manage the batteries throughout their lifetime because degradation of the batteries associated with long‐term usage is inevitable. To evaluate degradation degree of the batteries in detail, it is necessary to separately make clear the decrease in output power due to the increase in AC impedance and the decrease in battery capacity caused by the decrease in electromotive force. In this study, therefore, the authors at first propose a new evaluation method of detailed degradation process of lithium‐ion batteries through measurements of AC impedance and electromotive force of degraded batteries. It is made clear that this proposed evaluation method can provide simple but detailed diagnosis of battery degradation degree, indicating usefulness of the proposed method. Next, as a first step for performance simulation of degraded lithium‐ion batteries, the authors make clear that the already developed simulation method of battery transient voltage response, validity of which has been confirmed only for new batteries, is also applicable to degraded batteries.
Diagnosis Criterion of Abnormality of Transformer Winding by Frequency Response Analysis (FRA) ‐ Urgent Diagnosis of Turn Short and Heavy Deformation ‐
Authors: MIYAZAKI SATORU , MIZUTANI YOSHINOBU , TAGUCHI AKIRA , MURAKAMI JUNICHI , TSUJI NAOKAZU , TAKASHIMA MASAHIRO , KATO OSAMU
Published: July 2017

Soundness confirmation of internal windings of power transformers is important for reliable operation. In urgent situations such as invasions of lightning surge and external short‐circuit faults, it is important to diagnose turn shorts and/or deformation of winding. In this paper, criteria in diagnosing turn shorts or heavy deformations of transformer windings using frequency response analysis (FRA) are proposed. In FRA, measured transfer functions are compared with past measured data in principle. However, past measured data are not necessary in proposed diagnosis criteria. Therefore, proposed criteria are useful in soundness confirmation of transformer winding in the urgent situation.
1,3,2‐Diazaborolyl Anions – From Laboratory Curiosities to Versatile Reagents in Synthesis
Authors: Weber Lothar
Published: July 2017

Diazaborolyl anions with coordinatively unsaturated boron centers are exceedingly powerful in their nature as nucleophiles, Brønsted bases, or reducing agents. Lithium‐, magnesium‐, and zinc‐diazaborolyls find use as excellent transfer reagents of the borolyl group to s‐and p‐block elements, transition metals, and lanthanides. Cross couplings with bromoarenes or acyl chlorides affording 2‐aryl‐diazaboroles and the related acyl boranes were elegantly carried out by use of the more selective zinc diazaborolyls. Particular highlights in this chemistry are the syntheses of stable bis(diazaborolyl) metal(II)‐radicals of gallium, indium, and thallium as well as 1,2‐bis(diazaborolidinyl)diphosphenyl radical anions. Moreover, stability is imparted to the first isolable digermavinylidene by two geminal diazaborolyl substituents.
Organocatalytic Asymmetric Synthesis of Tetrahydrothiophenes and Tetrahydrothiopyrans
Authors: Mondal Buddhadeb , Nandi Shiny , Pan Subhas Chandra
Published: July 2017

Tetrahydrothiophenes and tetrahydrothiopyrans are an important class of compounds both from synthetic and biological points of view and have attracted the attention of many synthetic chemists and biologists over the years. Their high synthetic utility and diverse distribution in nature have made tetrahydrothiophenes and tetrahydrothiopyrans privileged motifs in organic chemistry. The last decade has witnessed great exploration of organocatalytic domino methods for the synthesis of enantiopure tetrahydrothiophenes and tetrahydrothiopyrans containing multiple stereocentres. The application of new bidentate reagents containing sulfur moieties in the development of double Michael reactions has revolutionized their synthesis. This microreview highlights recent organocatalytic asymmetric approaches to the synthesis of tetrahydrothiophenes and tetrahydrothiopyrans and describes the advances that have been made over the years.
Activated Glycerol Carbonates, Versatile Reagents with Aliphatic Amines: Formation and Reactivity of Glycidyl Carbamates and Trialkylamines
Authors: Legros Vanessa , Taing Guillaume , Buisson Pierre , Schuler Marie , Bostyn Stéphane , Rousseau Jolanta , Sinturel Christophe , Tatibouët Arnaud
Published: July 2017

The reactivity of mesylated and tosylated glycerol carbonate towards secondary and tertiary amines has been studied, and allowed regioselective access to carbamates which could then be transformed into glycidyl carbamates. By tuning the reaction conditions, we were able to direct the reaction towards the synthesis of new 5‐aminomethyldioxolan‐2‐one derivatives. The opening of glycidyl carbamates with various amines was also explored, and showed the opportunity to use glycerol as a linker between two different amine moieties.
Association between chronic musculoskeletal pain and executive function in community‐dwelling older adults
Authors: Murata S. , Sawa R. , Nakatsu N. , Saito T. , Sugimoto T. , Nakamura R. , Misu S. , Ueda Y. , Ono R.
Published: July 2017

Background

We examined the association of chronic musculoskeletal pain with executive function in community‐dwelling older adults.

Method

This cross‐sectional study recruited 234 community‐dwelling older adults in Japan (mean age: 72.7, women: 62.8%). Chronic musculoskeletal pain was defined as having moderate or more severe pain lasting ≥ 3 months. Executive function was assessed using the Digit Symbol Substitution Test (DSST), Trail Making Test (TMT) parts A and B, Letter Verbal Fluency Test (LVFT) and Category Verbal Fluency Test (CVFT).

Results

Prevalence of chronic musculoskeletal pain was 19% (n = 44). In the univariate analysis, the DSST and CVFT scores were significantly lower in the chronic musculoskeletal pain group than in the control group (DSST: chronic musculoskeletal pain group vs. control group, 40.2 vs. 45.4, respectively, p < 0.05; CVFT: 13.7 vs. 15.6, respectively, p < 0.05), whereas the TMT parts A and B and LVFT scores were not. The multivariate linear regression models adjusted for covariates showed that the chronic musculoskeletal pain group had significantly lower DSST (adjusted β = –0.13, p < 0.05) and CVFT scores (adjusted β = –0.17, p < 0.05) than the control group.

Conclusion

Chronic musculoskeletal pain may interfere with the elements of executive function, processing speed and semantic fluency, in community‐dwelling older adults. The association of chronic musculoskeletal pain with executive function requires further investigation.

Significance

Our results suggest an association between moderate‐severe chronic musculoskeletal pain and impairments of semantic fluency and processing speed in community‐dwelling older adults.
Delta‐9‐tetrahydrocannabinol decreases masticatory muscle sensitization in female rats through peripheral cannabinoid receptor activation
Authors: Wong H. , Hossain S. , Cairns B.E.
Published: July 2017

Background

This study investigated whether intramuscular injection of delta‐9‐tetrahydrocannabinol (THC), by acting on peripheral cannabinoid (CB) receptors, could decrease nerve growth factor (NGF)‐induced sensitization in female rat masseter muscle; a model which mimics the symptoms of myofascial temporomandibular disorders.

Methods

Immunohistochemistry was used to explore the peripheral expression of cannabinoid receptors in the masseter muscle while behavioural and electrophysiology experiments were employed to assess the functional effects of intramuscular injection of THC.

Results

It was found that CB1 and CB2 receptors are expressed by trigeminal ganglion neurons that innervate the masseter muscle and also on their peripheral endings. Their expression was greater in TRPV1‐positive ganglion neurons. Three days after intramuscular injection of NGF, ganglion neuron expression of CB1 and CB2, but not TPRV1, was decreased. In behavioural experiments, intramuscular injection (10 μL) of THC (1 mg/mL) attenuated NGF‐induced mechanical sensitization. No change in mechanical threshold was observed in the contralateral masseter muscles and no impairment of motor function was found after intramuscular injections of THC. In anaesthetized rats, the same concentration of THC increased the mechanical thresholds of masseter muscle mechanoreceptors. Co‐administration of the CB1 antagonist AM251 blocked the effect of THC on masseter muscle mechanoreceptors while the CB2 antagonist AM630 had no effect.

Conclusions

These results suggest that reduced inhibitory input from the peripheral cannabinoid system may contribute to NGF‐induced local myofascial sensitization of mechanoreceptors. Peripheral application of THC may counter this effect by activating the CB1 receptors on masseter muscle mechanoreceptors to provide analgesic relief without central side effects.

Significance

Our results suggest THC could reduce masticatory muscle pain through activating peripheral CB1 receptors. Peripheral application of cannabinoids could be a novel approach to provide analgesic relief without central side effects.
Surface isoelectric focusing (sIEF) with carrier ampholyte pH gradient
Authors: Wang Zhichao , Ivory Cornelius , Minerick Adrienne R.
Published: July 2017

Isoelectric focusing (IEF) is a powerful tool for amphoteric protein separations because of high sensitivity, bio‐compatibility, and reduced complexity compared to chromatography or mechanical separation techniques. IEF miniaturization is attractive because it enables rapid analysis, easier adaptation to point of care applications, and smaller sample demands. However, existing small‐scale IEF tools have not yet been able to analyze single protein spots from array libraries, which are ubiquitous in many pharmaceutical discovery and screening protocols. Thus, we introduce an in situ, novel, miniaturized protein analysis approach that we have termed surface isoelectric focusing (sIEF). Low volume printed sIEF gels can be run at length scales of ∼300 μm, utilize ∼0.9 ng of protein with voltages below 10 V. Further, the sIEF device platform is so simple that it can be integrated with protein library arrays to reduce cost; devices demonstrate reusability above 50 uses. An acrylamide monomer solution containing broad‐range carrier ampholytes was microprinted with a Nano eNablerTM between micropatterned gold electrodes spaced 300 μm apart on a glass slide. The acrylamide gel was polymerized in situ followed by protein loading via printed diffusional exchange. A pH gradient formed via carrier ampholyte stacking when electrodes were energized; the gradient was verified using ratiometric pH‐sensitive FITC/TRITC dyes. Green fluorescent protein (GFP) and R‐phycoerythrin (R‐PE) were utilized both as pI markers and to test sIEF performance as a function of electric field strength and ampholyte concentration. Factors hampering sIEF included cathodic drift and pH gradient compression, but were reduced by co‐printing non‐ionic Synperonic® F‐108 surfactant to reduce protein–gel interactions. sIEF gels achieved protein separations in <10 min yielding bands < 50 μm wide with peak capacities of ∼8 and minimum pI differences from 0.12 to 0.14. This new sIEF technique demonstrated comparable focusing at ∼100 times smaller dimensions than any previous IEF. Further, sample volumes required were reduced four orders of magnitude from 20 μL for slab gel IEF to 0.002 μL for sIEF. In summary, sIEF advantages include smaller volumes, reduced power consumption, and microchip surface accessibility to focused bands along with equivalent separation resolutions to prior IEF tools. These attributes position this new technology for rapid, in situ protein library analysis in clinical and pharmaceutical settings.
The preparation of microfluidic architecture with monolithic materials using a dual porous silica structure
Authors: Birch Christopher , Esfahani Mohammad Mehdi Nasr , Shaw Kirsty J , Kemp Cordula , Haswell Stephen James , Dyer Charlotte
Published: July 2017

A microfluidic device (MD) has been developed which features a porous silica (PS) monolithic disk synthesized from tetramethyl orthosilicate, incorporated into the device post‐fabrication and sealed in place with a second PS monolithic layer, synthesized from potassium silicate. This dual porous silica (DPS) structure provides a pathway for sample introduction to the MD and offers an ideal platform for solid phase extraction (SPE) methodologies which can be rapidly and efficiently integrated into a chip‐based format. All silica disk manufacture and functionalization was carried out in batch to provide a readily scalable method of production. Application of this design for processing samples was demonstrated using two alternative nucleic acid purification chemistries, yielding polymerase chain reaction amplifiable DNA extracted from 150 μL of human urine in less than 35 min. It is proposed that this DPS system could be further developed for a diverse range of chip‐based SPE applications, providing an interface facilitating sample delivery and enabling SPE on‐chip. Furthermore, to the author's knowledge it is the first reporting of two different types of PS amalgamated in a single MD.
Molybdenum Ditelluride Rendered into an Efficient and Stable Electrocatalyst for the Hydrogen Evolution Reaction by Polymorphic Control
Authors: McGlynn Jessica C. , Cascallana‐Matías Irene , Fraser James P. , Roger Isolda , McAllister James , Miras Haralampos N. , Symes Mark D. , Ganin Alexey Y.
Published: July 2017

The electrocatalytic hydrogen evolution reaction (HER) is of central importance for the production of H2 from sustainable sources. Currently, Pt is the best electrocatalyst for this transformation, but other materials based on less‐precious elements are now attracting increased attention. Of these alternatives, the molybdenum chalcogenides show particular promise. MoS2 has been explored extensively in this regard, which has highlighted the important role of polymorphism for catalytic activity. However, the conversion into an active polymorph is complex, and the stability of the catalyst under electrochemical conditions is poor. In contrast, MoTe2 has been barely studied as an electrocatalyst for the HER. Herein, we isolate the semiconducting and metallic polymorphs of MoTe2 using an easy solid‐state route and show that interconversion between the two polymorphs of MoTe2 can be achieved without a change in morphology by a simple temperature‐annealing protocol. Although the semiconducting form is a rather poor electrocatalyst for the HER, the metallic 1T′‐MoTe2 polymorph is an efficient and stable electrocatalyst for the HER in 1 m H2SO4. Even in the bulk form, it achieved a low overpotential with a Tafel slope of (78±4) mV dec−1 and full Faradaic efficiency. These findings highlight the importance of polymorphic control in the development of HER catalysts and suggest an efficient route for the discovery of new and improved electrocatalysts.
Bioaccumulation-based silver nanoparticle toxicity in Daphnia magna and maternal impacts
Authors: Pakrashi Sunandan , Tan Cheng , Wang Wen-Xiong
Published: July 2017

In the present study, we tested whether bioaccumulation in specific tissues of Daphnia magna could explain silver nanoparticle (AgNP) toxicity. Daphnids were exposed to different concentrations of well-suspended AgNPs and AgNO3. The accumulations of Ag in the whole body, gut, and nongut tissues, as well as the mortality of daphnids, were recorded over a period of 7 d. Regression analysis showed a higher degree of positive correlation between the concentration of Ag in the nongut tissues than gut tissues and the mortality of daphnids. The results strongly suggested that the toxicity of AgNPs could be better explained in terms of bioaccumulation of AgNPs in the nongut tissues. We further tested the maternal transfer of AgNPs in daphnids into the next generation using radioactive tracers, which were able to detect as low as 1.0 to 3.2% of total accumulated Ag transferred to the neonates. The AgNPs significantly affected the reproduction process during the first 2 broods after exposure, whereas AgNO3 only had significant effects on the first brood. It is possible that AgNPs have longer adverse effects than AgNO3 on the reproduction of Daphnia. The present study identified the sensitive site of AgNP toxic action in daphnids and documented the extent of maternal transfer and the significant influence of AgNPs on the reproduction of daphnids. Environ Toxicol Chem 2017;36:3359–3366. © 2017 SETAC
Petrological study of the early Mesoproterozoic Glauconitic Sandstone and Olive Shale members from the Semri Group, Vindhyan Supergroup in Central India: Implications to input from intrabasinal felsic volcanic source and glauconitization
Authors: Mishra Meenal , Sen Shinjana
Published: July 2017

The Semri Group of the Vindhyan Supergroup contains widespread intrabasinal felsic volcanic rocks in the Porcellanite Formation formed during the early Mesoproterozoic. This widespread felsic volcanism was followed by the deposition of siliciclastic sedimentary rocks of the Kheinjua Formation containing the Olive Shale, Fawn Limestone, Glauconitic Sandstone members, the last one dominantly arkose and litharenite. The volcanic products resulting from volcanic activity during deposition of Porcellanite Formation were predominantly fine volcanic ash or dust that settled very slowly in the water column of the basin. The ranges of 28 elemental ratios for the Olive Shale and Glauconitic Sandstone members overlapped with those of the Porcellanite Shale Formation. The contemporaneous intermingling of the detrital input from volcanic products with the terrigenous detritus received by the basin from the Bundelkhand Craton in the north is reflected in the geochemical signatures. Various plots of elemental ratios and ternary plots for the siliciclastic rocks overlap those of the Porcellanite Shale Formation and Bundelkhand Tonalite‐trondhjemite‐granodiorite (TTG) suggesting that they might be the source rocks. The mixing of detritus from volcanic products was perhaps responsible for the widespread appearance of glauconite‐bearing sediments in the subsequent deposits. Glauconitization of detrital K‐feldspars, clay peloids, and volcanic lithic fragments is evident from the petrography. The shallow marine environment, slow sedimentation rates, elevated surface temperatures and mildly reducing conditions (CO2 got released from explosive volcanism) are considered as the favourable conditions for glauconitization, which prevailed within the Vindhyan Basin. Under these conditions the detrital input received as the result of previous volcanism during deposition of the porcellanite shale (glass, pumice lithic fragments, and feldspars) were transformed into clays such as illite and glauconite during the deposition of siliciclastic rocks of the Kheinjua Formation within the basin.
Astrocytes follow ganglion cell axons to establish an angiogenic template during retinal development
Authors: O'Sullivan Matthew L. , Puñal Vanessa M. , Kerstein Patrick C. , Brzezinski Joseph A. , Glaser Tom , Wright Kevin M. , Kay Jeremy N.
Published: July 2017

Immature astrocytes and blood vessels enter the developing mammalian retina at the optic nerve head and migrate peripherally to colonize the entire retinal nerve fiber layer (RNFL). Retinal vascularization is arrested in retinopathy of prematurity (ROP), a major cause of bilateral blindness in children. Despite their importance in normal development and ROP, the factors that control vascularization of the retina remain poorly understood. Because astrocytes form a reticular network that appears to provide a substrate for migrating endothelial cells, they have long been proposed to guide angiogenesis. However, whether astrocytes do in fact impose a spatial pattern on developing vessels remains unclear, and how astrocytes themselves are guided is unknown. Here we explore the cellular mechanisms that ensure complete retinal coverage by astrocytes and blood vessels in mouse. We find that migrating astrocytes associate closely with the axons of retinal ganglion cells (RGCs), their neighbors in the RNFL. Analysis of Robo1; Robo2 mutants, in which RGC axon guidance is disrupted, and Math5 (Atoh7) mutants, which lack RGCs, reveals that RGCs provide directional information to migrating astrocytes that sets them on a centrifugal trajectory. Without this guidance, astrocytes exhibit polarization defects, fail to colonize the peripheral retina, and display abnormal fine‐scale spatial patterning. Furthermore, using cell type‐specific chemical–genetic tools to selectively ablate astrocytes, we show that the astrocyte template is required for angiogenesis and vessel patterning. Our results are consistent with a model whereby RGC axons guide formation of an astrocytic network that subsequently directs vessel development.
Minocycline reduces microgliosis and improves subcortical white matter function in a model of cerebral vascular disease
Authors: Manso Yasmina , Holland Philip R. , Kitamura Akihiro , Szymkowiak Stefan , Duncombe Jessica , Hennessy Edel , Searcy James L. , Marangoni Martina , Randall Andrew D. , Brown Jon T. , McColl Barry W. , Horsburgh Karen
Published: July 2017

Chronic cerebral hypoperfusion is a key mechanism associated with white matter disruption in cerebral vascular disease and dementia. In a mouse model relevant to studying cerebral vascular disease, we have previously shown that cerebral hypoperfusion disrupts axon‐glial integrity and the distribution of key paranodal and internodal proteins in subcortical myelinated axons. This disruption of myelinated axons is accompanied by increased microglia and cognitive decline. The aim of the present study was to investigate whether hypoperfusion impairs the functional integrity of white matter, its relation with axon‐glial integrity and microglial number, and whether by targeting microglia these effects can be improved. We show that in response to increasing durations of hypoperfusion, the conduction velocity of myelinated fibres in the corpus callosum is progressively reduced and that paranodal and internodal axon‐glial integrity is disrupted. The number of microglial cells increases in response to hypoperfusion and correlates with disrupted paranodal and internodal integrity and reduced conduction velocities. Further minocycline, a proposed anti‐inflammatory and microglia inhibitor, restores white matter function related to a reduction in the number of microglia. The study suggests that microglial activation contributes to the structural and functional alterations of myelinated axons induced by cerebral hypoperfusion and that dampening microglia numbers/proliferation should be further investigated as potential therapeutic benefit in cerebral vascular disease.
Validation of brain‐derived signals in near‐infrared spectroscopy through multivoxel analysis of concurrent functional magnetic resonance imaging
Authors: Moriguchi Yoshiya , Noda Takamasa , Nakayashiki Kosei , Takata Yohei , Setoyama Shiori , Kawasaki Shingo , Kunisato Yoshihiko , Mishima Kazuo , Nakagome Kazuyuki , Hanakawa Takashi
Published: July 2017

Near‐infrared spectroscopy (NIRS) is a convenient and safe brain‐mapping tool. However, its inevitable confounding with hemodynamic responses outside the brain, especially in the frontotemporal head, has questioned its validity. Some researchers attempted to validate NIRS signals through concurrent measurements with functional magnetic resonance imaging (fMRI), but, counterintuitively, NIRS signals rarely correlate with local fMRI signals in NIRS channels, although both mapping techniques should measure the same hemoglobin concentration. Here, we tested a novel hypothesis that different voxels within the scalp and the brain tissues might have substantially different hemoglobin absorption rates of near‐infrared light, which might differentially contribute to NIRS signals across channels. Therefore, we newly applied a multivariate approach, a partial least squares regression, to explain NIRS signals with multivoxel information from fMRI within the brain and soft tissues in the head. We concurrently obtained fMRI and NIRS signals in 9 healthy human subjects engaging in an n‐back task. The multivariate fMRI model was quite successfully able to predict the NIRS signals by cross‐validation (interclass correlation coefficient = ∼0.85). This result confirmed that fMRI and NIRS surely measure the same hemoglobin concentration. Additional application of Monte‐Carlo permutation tests confirmed that the model surely reflects temporal and spatial hemodynamic information, not random noise. After this thorough validation, we calculated the ratios of the contributions of the brain and soft‐tissue hemodynamics to the NIRS signals, and found that the contribution ratios were quite different across different NIRS channels in reality, presumably because of the structural complexity of the frontotemporal regions. Hum Brain Mapp 38:5274–5291, 2017. © 2017 Wiley Periodicals, Inc.
Impairment due to combined sleep restriction and alcohol is not mitigated by decaying breath alcohol concentration or rest breaks
Authors: Manousakis Jessica E. , Anderson Clare
Published: July 2017

Objective

Epidemiological and laboratory‐based driving simulator studies have shown the detrimental impact of moderate, legal levels of alcohol consumption on driving performance in sleepy drivers. As less is known about the time course of decaying alcohol alongside performance impairment, our study examined impairment and recovery of performance alongside decaying levels of alcohol, with and without sleep restriction.

Methods

Sixteen healthy young males (18–27 years) underwent 4 counterbalanced conditions: Baseline, Alcohol (breath alcohol concentration [BrAC] < 0.05%), Sleep Restriction (5 hr time in bed), and Combined. Participants consumed alcohol (or control drink) ~4.5 hr post wake (12:30 p.m.). To test on the descending limb of alcohol, attention and vigilance test batteries commenced 1 hr after consumption and were completed every 30 min for 2 hr (1:30 p.m.–3:30 p.m.).

Results

The Combined condition impaired subjective and objective sleepiness. Here, performance deficits peaked 90 min after alcohol consumption or 30 min after the BrAC peak. Performance did not return to baseline levels until 2.5 hr following consumption, despite receiving rest breaks in between testing.

Conclusions

These findings suggest that (a) falling BrACs are an inadequate guide for performance/safety and (b) rest breaks without sleep are not a safety measure for mitigating performance impairment when consuming alcohol following restricted sleep.
The Mincle ligand trehalose dibehenate differentially modulates M1‐like and M2‐like macrophage phenotype and function via Syk signaling
Authors: Kodar Kristel , Harper Jacquie L. , McConnell Melanie J. , Timmer Mattie S. M. , Stocker Bridget L.
Published: July 2017

Introduction

Macrophages play a significant role in the progression of diseases, such as cancer, making them a target for immune‐modulating agents. Trehalose dibehenate (TDB) is known to activate M1‐like macrophages via Mincle, however, the effect of TDB on M2‐like macrophages, which are found in the tumor microenvironment, has not been studied.

Methods

qRT‐PCR, flow cytometry, cytokine ELISA, and Western Blotting were used to study the effect of TDB on GM‐CSF and M‐CSF/IL‐4 derived bone marrow macrophages (BMMs) from C57BL/6 and Mincle−/− mice.

Results

TDB treatment up‐regulated M1 markers over M2 markers by GM‐CSF BMMs, whereas M‐CSF/IL‐4 BMMs down‐regulated marker gene expression overall. TDB treatment resulted in Mincle‐independent down‐regulation of CD11b, CD115, and CD206 expression by GM‐CSF macrophages and CD115 in M‐CSF/IL‐4 macrophages. GM‐CSF BMMs produced of significant levels of proinflammatory cytokines (IL‐1β, IL‐6, TNF‐α), which was Mincle‐dependent and further enhanced by LPS priming. M‐CSF BMMs produced little or no cytokines in response to TDB regardless of LPS priming. Western blot analysis confirmed that the absence of cytokine production was associated with a lack of activation of the Syk kinase pathway.

Conclusion

This study illustrates that TDB has the potential to differentially regulate M1‐ and M2‐like macrophages in the tumor environment.
Activation of the B‐cell receptor successively activates NF‐κB and STAT3 in chronic lymphocytic leukemia cells
Authors: Rozovski Uri , Harris David M. , Li Ping , Liu Zhiming , Jain Preetesh , Veletic Ivo , Ferrajoli Alessandra , Burger Jan , Thompson Philip , Jain Nitin , Wierda William , Keating Michael J. , Estrov Zeev
Published: July 2017

In chronic lymphocytic leukemia (CLL) cells, both interleukin‐6 (IL‐6) and the B‐cell receptor (BCR) activate Janus kinase 2 (JAK2) and induce the phosphorylation of signal transduction and activator of transcription 3 (STAT3) on tyrosine 705 residues. However, whereas IL‐6 phosphorylates STAT3 within 15 min, stimulation of the BCR with anti‐immunoglobulin M (IgM) antibodies phosphorylates STAT3 in 2–4 hr. Here, we show that this process takes longer because it requires transcriptional activity of NF‐κB. Using an electromobility shift assay, we found that incubation with IgM antibodies for 4 or 18 hr, but not 15 min, increased NF‐κB DNA‐binding of CLL cells and increased binding was translated to increased transcriptional activity. Hence, 42% of the 83 NF‐κB target genes were constitutively expressed in all CLL cells prior to any inducible stimuli. However, activation of the BCR increased the number of NF‐κB target genes with detectable expression by 23%. Remarkably, prolonged incubation with anti‐IgM antibodies induced a time‐dependent transcription, production and secretion of IL‐6 protein. The IgM‐induced production of IL‐6 prompted the phosphorylation of STAT3 on tyrosine residues. This effect was inhibited by the JAK1/2 inhibitor of the JAK/STAT3 pathway ruxolitinib. Taken together, these results suggest that in CLL cells, constitutive tonic activation of NF‐κB can be further enhanced by the BCR and that the BCR‐induced activation of the JAK/STAT3 pathway depends on the NF‐κB induced production of IL‐6.
Developing new targeting strategy for androgen receptor variants in castration resistant prostate cancer
Authors: Wang Bin , Lo U‐Ging , Wu Kaijie , Kapur Payal , Liu Xiangyang , Huang Jun , Chen Wei , Hernandez Elizabeth , Santoyo John , Ma Shi‐Hong , Pong Rey‐Chen , He Dalin , Cheng Yi‐Qiang , Hsieh Jer‐Tsong
Published: July 2017

The presence of androgen receptor variant 7 (AR‐V7) variants becomes a significant hallmark of castration‐resistant prostate cancer (CRPC) relapsed from hormonal therapy and is associated with poor survival of CRPC patients because of lacking a ligand‐binding domain. Currently, it still lacks an effective agent to target AR‐V7 or AR‐Vs in general. Here, we showed that a novel class of agents (thailanstatins, TSTs and spliceostatin A analogs) can significantly suppress the expression of AR‐V7 mRNA and protein but in a less extent on the full‐length AR expression. Mechanistically, TST‐D is able to inhibit AR‐V7 gene splicing by interfering the interaction between U2AF65 and SAP155 and preventing them from binding to polypyrimidine tract located between the branch point and the 3′ splice site. In vivo, TST‐D exhibits a potent tumor inhibitory effect on human CRPC xenografts leading to cell apoptosis. The machinery associated with AR gene splicing in CRPC is a potential target for drugs. Based on their potency in the suppression of AR‐V7 responsible for the growth/survival of CRPC, TSTs representing a new class of anti‐AR‐V agents warrant further development into clinical application.
Asbestos‐associated genome‐wide DNA methylation changes in lung cancer
Authors: Kettunen Eeva , Hernandez‐Vargas Hector , Cros Marie‐Pierre , Durand Geoffroy , Le Calvez‐Kelm Florence , Stuopelyte Kristina , Jarmalaite Sonata , Salmenkivi Kaisa , Anttila Sisko , Wolff Henrik , Herceg Zdenko , Husgafvel‐Pursiainen Kirsti
Published: July 2017

Previous studies have revealed a robust association between exposure to asbestos and human lung cancer. Accumulating evidence has highlighted the role of epigenome deregulation in the mechanism of carcinogen‐induced malignancies. We examined the impact of asbestos on DNA methylation. Our genome‐wide studies (using Illumina HumanMethylation450K BeadChip) of lung cancer tissue and paired normal lung from 28 asbestos‐exposed or non‐exposed patients, mostly smokers, revealed distinctive DNA methylation changes. We identified a number of differentially methylated regions (DMR) and differentially variable, differentially methylated CpGs (DVMC), with individual CpGs further validated by pyrosequencing in an independent series of 91 non‐small cell lung cancer and paired normal lung. We discovered and validated BEND4, ZSCAN31 and GPR135 as significantly hypermethylated in lung cancer. DMRs in genes such as RARB (FDR 1.1 × 10−19, mean change in beta [Δ] −0.09), GPR135 (FDR 1.87 × 10−8, mean Δ −0.09) and TPO (FDR 8.58 × 10−5, mean Δ −0.11), and DVMCs in NPTN, NRG2, GLT25D2 and TRPC3 (all with p <0.05, t‐test) were significantly associated with asbestos exposure status in exposed versus non‐exposed lung tumors. Hypomethylation was characteristic to DVMCs in lung cancer tissue from asbestos‐exposed subjects. When DVMCs related to asbestos or smoking were analyzed, 96% of the elements were unique to either of the exposures, consistent with the concept that the methylation changes in tumors may be specific for risk factors. In conclusion, we identified novel DNA methylation changes associated with lung tumors and asbestos exposure, suggesting that changes may be present in causal pathway from asbestos exposure to lung cancer.
Data Entrepreneurship: A Necessary Mindset for Institutional Research Effectiveness
Authors: Prewitt‐Freilino Polly A. , Rush Nathan A.
Published: July 2017

Strong relationships with senior administrators, effective cross‐campus collaboration, and efficient use of technology are central to impactful IR in small colleges.
The Evolution of Institutional‐Research Professionals in Small‐ and Medium‐Sized Institutions
Authors: Brown Narren J. , Hewitt Gordon J. , Lin Wei‐Fang , Vater Ruth
Published: July 2017

This concluding chapter discusses the main challenges currently facing institutional research at small‐ and medium‐sized colleges and describes how the field may evolve.
Metformin‐induced alterations in nucleotide metabolism cause 5‐fluorouracil resistance but gemcitabine susceptibility in oesophageal squamous cell carcinoma
Authors: Mynhardt Charissa , Damelin Leonard H. , Jivan Rupal , Peres Jade , Prince Sharon , Veale Robin B. , Mavri‐Damelin Demetra
Published: July 2017

5‐Fluorouracil (5‐FU) is a chemotherapeutic agent used to treat a variety of gastric cancers including oesophageal squamous cell carcinoma (OSCC), for which the 5‐year mortality rate exceeds 85%. Our study investigated the effects of metformin, an antidiabetic drug with established anti‐cancer activity, in combination with 5‐FU as a novel chemotherapy strategy, using the OSCC cell lines, WHCO1 and WHCO5. Our results indicate that metformin treatment induces significant resistance to 5‐FU in WHCO1 and WHCO5 cells, by more than five‐ and sixfolds, respectively, as assessed by MTT assay. We show that this is due to global alterations in nucleotide metabolism, including elevated expression of thymidylate synthase and thymidine kinase 1 (established 5‐FU resistance mechanisms), which likely result in an increase in intracellular dTTP pools and a “dilution” of 5‐FU anabolites. Metformin treatment also increases deoxycytidine kinase (dCK) expression and, as the chemotherapeutic agent gemcitabine relies on dCK for its efficient activity, we speculated that metformin would enhance the sensitivity of OSCC cells to gemcitabine. Indeed we show that metformin pre‐treatment greatly increases gemcitabine toxicity and DNA fragmentation in comparison to gemcitabine alone. Taken together, our findings show that metformin alters nucleotide metabolism in OSCC cells and while responsible for inducing resistance to 5‐FU, it conversely increases sensitivity to gemcitabine, thereby highlighting metformin and gemcitabine as a potentially novel combination therapy for OSCC.
The role of β‐adrenergic receptors and p38MAPK signaling pathways in physiological processes of cardiosphere‐derived cells
Authors: Zhang Wen‐bo , Liu Yun‐qi , Zhang Xi , Lin Lin , Yin Sheng‐li
Published: July 2017

The effects of β adrenergic receptors (β‐ARs) and p38 mitogen‐activated protein kinases (MAPK) pathways on cardiosphere‐derived cells (CDCs) are largely unknown. This study aimed to investigate the roles of β‐ARs and p38MAPK pathways on the proliferation, apoptosis, and differentiation capacity of CDCs. The CDCs were treated with β1‐AR blocker (Met group), β2‐AR antagonist (ICI group), and p38MAPK inhibitor (SB group), non‐selective β‐AR blocker (PRO group), and β‐AR agonist (ISO group). The viability, apoptotic rate and differentiation status of CDCs were determined by MST‐1 assay, flow cytometery, and Western blot, respectively. The CDCs viability significantly reduced in ICI group (all P < 0.05), and SB group had a significant high viability after 48 h treatment (P < 0.05). Compared with control group, all treated groups had a low apoptotic rate. After treatment for 72 h, ISO treatment elevated the expression of Nkx2.5, and could partially or fully attenuate the inhibitory effects of β‐AR antagonists and/or p38MAPK inhibitor. A similar overall trend of protein expression levels among all groups could be observed between protein pairs of cTnT and β1‐AR as well as c‐Kit and β2‐AR, respectively. These results suggested that β‐ARs and p38MAPK signaling pathways play crucial roles in the proliferation and differentiation of CDCs. Our findings should be helpful for better understanding the molecular mechanism underlying the physiological processes of CDCs.
Downregulation of microRNA‐15a‐3p is correlated with clinical outcome and negatively regulates cancer proliferation and migration in human osteosarcoma
Authors: Shi Jiyuan , Fu Qiang , Yang Pei , Liu Huitong , Ji Le , Wang Kunzheng
Published: July 2017

In this study, we investigated the expression, correlation to clinical outcomes and biological functions of microRNA‐15a‐3p (miR‐15a‐3p) in human osteosarcoma. MiR‐15a‐3p expressions in osteosarcoma cell lines and clinical tissues of osteosarcoma patients were measured by qPCR. Relevance of endogenous miR‐15a‐3p to osteosarcoma patients' clinicopathological factors or overall survival was statistically analyzed. In addition, the independence of miR‐15a‐3p predicting cancer patients' overall survival was analyzed by Cox regression method. Furthermore, in osteosarcoma cell lines, Saos‐2 and HOS cells, miR‐15a‐3p was overexpressed through stable lentiviral transduction. The functional regulations of miR‐15a‐3p overexpression on cancer ell proliferation and migration were then analyzed. MiR‐15a‐3p was significantly downregulated in osteosarcoma cell lines and human osteosarcoma tumors. Downregulation of endogenous miR‐15a‐3p in osteosarcoma tumors was significantly associated with cancer patient's poor clinical outcomes and low survival rate. Also, endogenous miR‐15a‐3p was confirmed to be an independent biomarker for predicating cancer patients' survival. In Saos‐2 and HOS cells, lentivirus‐induced miR‐15a‐3p overexpression had significantly tumor suppressing functions, by inhibiting both proliferation and migration. Significant downregulation of miR‐15a‐3p in osteosarcoma may be an independent biomarker to predicting cancer patients' poor prognosis. Overexpression miR‐15a‐3p may be an efficient functional meaning to suppress osteosarcoma development.
Primary familial brain calcification with a novel SLC20A2 mutation: Analysis of PiT‐2 expression and localization
Authors: Taglia Ilaria , Formichi Patrizia , Battisti Carla , Peppoloni Giulia , Barghigiani Melissa , Tessa Alessandra , Federico Antonio
Published: July 2017

Primary familial brain calcification (PFBC) is an autosomal dominant rare disorder characterized by bilateral and symmetric brain calcifications, and neuropsychiatric manifestations. Four genes have been linked to PFBC: SLC20A2, PDGFRB, PDGFB, and XPR1. In this study, we report molecular and clinical data of a PFBC patient carrying a novel SLC20A2 mutation and we investigate the impact of the mutation on PiT‐2 expression and function. Sanger sequencing of SLC20A2, PDGFRB, PDGFB, XPR1 led to the identification of a novel duplication of twelve nucleotides (c.1876_1887dup/ p.Trp626_Thr629dup) in SLC20A2 gene. SLC20A2 encodes for a cell membrane transporter (PiT‐2) involved in maintenance of inorganic phosphate homeostasis. We performed an analysis of expression and functionality of PiT‐2 protein in patient primary cultured fibroblasts. In patient fibroblasts, the mutation does not affect PiT‐2 expression but alter sub‐cellular localization. The Pi‐uptake assay revealed a less Pi depletion in patient than in control fibroblasts, suggesting that SLC20A2 duplication may impair Pi internalization. This is the first study reporting sub‐cellular expression analysis of mutant PiT‐2 in primary cultured fibroblasts from a PFBC patient, showing that p.Trp626_Thr629dup in SLC20A2 alters PiT‐2 sub‐cellular localization and reduces Pi‐uptake, leading to onset of PFBC in our patient.
Reflective Decision‐Making in Elementary Students' Engineering Design
Authors: Wendell Kristen Bethke , Wright Christopher G. , Paugh Patricia
Published: July 2017

Background

A key feature of engineering design is collaborative, deliberate decision making that takes into account information about design options. K‐12 students need opportunities for this kind of decision making if they are to meet the learning standards for engineering set out in the Next Generation Science Standards.

Purpose

This qualitative study sought to propose and operationalize a definition of reflective decision‐making among elementary students. We investigated how urban elementary students enact reflective decision‐making in a formal engineering design curriculum.

Method

We used naturalistic inquiry methodology and video recorded seven Engineering is Elementary design challenges in four classrooms. Students worked in small teams, and we focused on their planning and redesign phases. Maximum variation sampling, constant comparative analysis, and microethnographic accounts demonstrated the diversity of resources students utilized in their decision making.

Results

In student discourse, we found evidence for six reflective decision‐making elements: articulating multiple solutions, evaluating pros and cons, intentionally selecting a solution, retelling the performance of a solution, analyzing a solution according to evidence, and purposefully choosing improvements. The discourse patterns used to enact these elements both supported and interfered with students' achievement of design goals.

Conclusions

Our results suggest that during engineering design tasks, young learners working in small teams can respond productively to opportunities to engage in sophisticated discourse. However, further work is needed on tools and strategies that support reflective decision‐making by all students during engineering design in elementary school.
Surface‐enhanced Raman spectroscopy of dye molecules on Ag‐modified silicon nanowire substrates: influence of photoinduced probe degradation on enhancement factors
Authors: Mehrvar L. , Sadeghipari M. , Tavassoli S. H. , Mohajerzadeh S.
Published: July 2017

Photobleaching effect is an immense problem in optical spectroscopy, especially when fluorophores are adsorbed on metal nanoparticles (NPs). Nevertheless, little effort has been assigned to the study of fluorophore photostability under this condition. In this paper, the effect of photobleaching on the Raman signal enhancement factor (RS‐EF) of dye molecules on Ag‐modified silicon nanowire (SiNW) substrates is investigated. For this purpose, SiNWs are fabricated by using the vapor–liquid–solid growth mechanism and decorated with Ag NPs by means of electroless deposition method. This process provides the possibility of forming uniformly and tightly packed Ag NPs on SiNWs. The effect of photostability of the crystal violet as analyte molecules on surface‐enhanced Raman spectroscopy is investigated as a function of time evolution and laser power. The influence of Ag NP deposition time on Raman signal enhancement is explored. Our work shows how we can optimize the excitation power for achievement of higher RS‐EF and, consequently, lower detectable concentration. Time evolution of surface‐enhanced Raman spectroscopy signal shows an exponential decay behavior, which indicates an almost uniform distribution of EFs. Capability of our nanostructure is assessed for different concentration, and subsequently, limit of detection of 10 pm with RS‐EF of 2.4×109 is obtained. Copyright © 2017 John Wiley & Sons, Ltd.