bluuebunny/crossref_metadata_2025 huggingface dataset:
Transparent Bendable Secondary Zinc-Air Batteries by Controlled Void Ionic Separators
Authors: Kwon Ohchan , Hwang Ho Jung , Ji Yunseong , Jeon Ok Sung , Kim Jeong Pil , Lee Chanmin , Shul Yong Gun
Published: February 2019

First ever transparent bendable secondary zinc-air batteries were fabricated. Transparent stainless-steel mesh was utilized as the current collector for the electrodes due to its reliable mechanical stability and electrical conductivity. After which separate methods were used to apply the active redox species. For the preparation of the anode, zinc was loaded by an electroplating process to the mesh. For the cathode, catalyst ink solution was spray coated with an airbrush for desired dimensions. An alkaline gel electrolyte layer was used for the electrolyte. Microscale domain control of the materials becomes a crucial factor for fabricating transparent batteries. As for the presented cell, anionic exchange polymer layer has been uniquely incorporated on to the cathode mesh as the separator which becomes a key procedure in the fabrication process for obtaining the desired optical properties of the battery. The ionic resin is applied in a fashion where controlled voids exist between the openings of the grid which facilitates light passage while guaranteeing electrical insulation between the electrodes. Further analysis correlates the electrode dimensions to the transparency of the system. Recorded average light transmittance is 48.8% in the visible light region and exhibited a maximum power density of 9.77 mW/cm2. The produced battery shows both transparent and flexible properties while maintaining a stable discharge/charge operation.
ATP synthesis at physiological nucleotide concentrations
Authors: Meyrat Axel , von Ballmoos Christoph
Published: February 2019

Synthesis of ATP by the F1F0 ATP synthase in mitochondria and most bacteria is energized by the proton motive force (pmf) established and maintained by respiratory chain enzymes. Conversely, in the presence of ATP and in the absence of a pmf, the enzyme works as an ATP-driven proton pump. Here, we investigate how high concentrations of ATP affect the enzymatic activity of the F1F0 ATP synthase under high pmf conditions, which is the typical situation in mitochondria or growing bacteria. Using the ATP analogue adenosine 5′-O-(1-thiotriphosphate) (ATPαS), we have developed a modified luminescence-based assay to measure ATP synthesis in the presence of millimolar ATP concentrations, replacing an assay using radioactive nucleotides. In inverted membrane vesicles of E. coli, we found that under saturating pmf conditions, ATP synthesis was reduced to ~10% at 5 mM ATPαS. This reduction was reversed by ADP, but not Pi, indicating that the ATP/ADP ratio controls the ATP synthesis rate. Our data suggests that the ATP/ADP ratio ~30 in growing E. coli limits the ATP synthesis rate to ~20% of the maximal rate possible at the applied pmf and that the rate reduction occurs via product inhibition rather than an increased ATP hydrolysis rate.
Regulation of Cathepsin E gene expression by the transcription factor Kaiso in MRL/lpr mice derived CD4+ T cells
Authors: Hiramatsu Sumie , Watanabe Katsue S , Zeggar Sonia , Asano Yosuke , Miyawaki Yoshia , Yamamura Yuriko , Katsuyama Eri , Katsuyama Takayuki , Watanabe Haruki , Takano-Narazaki Mariko , Matsumoto Yoshinori , Kawabata Tomoko , Sada Ken-Ei , Wada Jun
Published: February 2019

Global DNA hypomethylation in CD4+ cells in systemic lupus erythematosus (SLE) was suggested to play a key role in the pathogenesis. To identify new methylation-sensitive genes, we integrated genome-wide DNA methylation and mRNA profiling data in CD4+ cells of MRL/lpr (MRL) and C57BL6/J (B6) mice. We identified Cathepsin E (Ctse), in which 13 methyl-CpGs within 583 bp region of intron 1 were hypomethylated, and Ctse mRNA upregulated in MRL compared with B6 mice. One of methyl-CpGs, mCGCG was 93.3 ± 2.05% methylated in B6 mice, while 80.0 ± 6.2% methylated and mutated to CGGG in MRL mice. Kaiso is known to bind to mCGCG and we hypothesized that it represses expression of Ctse in B6 mice. The binding of Kaiso to mCGCG site in B6 mice was reduced in MRL mice revealed by ChIP-PCR. EL4 cells treated with 5-azaC and/or Trichostatin A showed the suppression of binding of Kaiso to mCGCG motif by ChIP-PCR and the overexpression of Ctse was demonstrated by qPCR. Ctse gene silencing by siRNA in EL4 cells resulted in reduction of IL-10 secretion. The hypomethylation of mCGCG motif, reduced recruitment of Kaiso, and increased expression of Ctse and Il-10 in CD4+ cells may be involved in the pathogenesis of SLE.
Probing the Solute-Solvent Interaction of an Azo-Bonded Prodrug in Neat and Binary Media: Combined Experimental and Computational Study
Authors: Bani-Yaseen Abdulilah Dawoud , Al-Jaber Amina S. , Ali Heba M.
Published: February 2019

Preferential solvation has significant importance in interpreting the molecular physicochemical properties of wide spectrum of materials in solution. In this work, the solute-solvent interaction of pro-drug Sulfasalazine (SSZ) in neat and binary media was investigated experimentally and computationally. The solute-solvent interactions of interest were spectrophotometrically probed and computationally investigated for providing insights concerning the molecular aspects of SSZ:media interaction. Experimentally, the obtained results in 1,4-dioxane:water binary mixture demonstrated a dramatic non-linear changes in the spectral behavior of SSZ indicative of the dependency of its molecular behaviors on the compositions of the molecular microenvironment in the essence of solute-solvent interaction. Computationally, geometry optimization and simulation of the absorption spectra of SSZ in media of interest were performed employing DFT and TD-DFT methods, respectively, where the solvent effects on the absorption were examined implicitly using IEFPCM method. Obtained results revealed a nonpolar nature of the molecular orbitals that are directly involved in the SSZ:medium interaction. As in good correspondence with the experimental results, these simulations demonstrated that these orbitals are of non-polar nature and hence minimally affected by polarity of the media and in turn favoring the non-polar molecular environments. On the other hand, the molecular origin of SSZ:media interaction was demonstrated explicitly through complexation of SSZ with water molecules revealing a cooperative hydrogen bonding stabilization with an average length of 1.90 Å. The findings of this work demonstrate the significance of the preferential solvation and composition of the molecular microenvironment on the physicochemical properties of molecules of pharmaceutical importance.
Assessing the effects of Ang-(1-7) therapy following transient middle cerebral artery occlusion
Authors: Arroja M. M. C. , Reid E. , Roy L. A. , Vallatos A. V. , Holmes W. M. , Nicklin S. A. , Work L. M. , McCabe C.
Published: February 2019

The counter-regulatory axis, Angiotensin Converting Enzyme 2, Angiotensin-(1-7), Mas receptor (ACE2/Ang-1-7/MasR), of the renin angiotensin system (RAS) is a potential therapeutic target in stroke, with Ang-(1-7) reported to have neuroprotective effects in pre-clinical stroke models. Here, an extensive investigation of the functional and mechanistic effects of Ang-(1-7) was performed in a rodent model of stroke. Using longitudinal magnetic resonance imaging (MRI) it was observed that central administration of Ang-(1-7) following transient middle cerebral artery occlusion (MCAO) increased the amount of tissue salvage compared to reperfusion alone. This protective effect was not due to early changes in blood brain barrier (BBB) permeability, microglia activation or inflammatory gene expression. However, increases in NADPH oxidase 1 (Nox1) mRNA expression were observed in the treatment group compared to control. In order to determine whether Ang-(1-7) has direct cerebrovascular effects, laser speckle contrast imaging (LSCI) was performed to measure dynamic changes in cortical perfusion following reperfusion. Delivery of Ang-(1-7) did not have any effect on cortical perfusion following reperfusion however; it showed an indication to prevent the ‘steal phenomenon’ within the contralateral hemisphere. The comprehensive series of studies have demonstrated a moderate protective effect of Ang-(1-7) when given alongside reperfusion to increase tissue salvage.
Metabolic therapies inhibit tumor growth in vivo and in silico
Authors: da Veiga Moreira Jorgelindo , Hamraz Minoo , Abolhassani Mohammad , Schwartz Laurent , Jolicœur Mario , Peres Sabine
Published: February 2019

In the recent years, cancer research succeeded with sensitive detection methods, targeted drug delivery systems, and the identification of a large set of genes differently expressed. However, although most therapies are still based on antimitotic agents, which are causing wide secondary effects, there is an increasing interest for metabolic therapies that can minimize side effects. In the early 20th century, Otto Warburg revealed that cancer cells rely on the cytoplasmic fermentation of glucose to lactic acid for energy synthesis (called “Warburg effect”). Our investigations aim to reverse this effect in reprogramming cancer cells’ metabolism. In this work, we present a metabolic therapy specifically targeting the activity of specific enzymes of central carbon metabolism, combining the METABLOC bi-therapeutic drugs combination (Alpha Lipoic Acid and Hydroxycitrate) to Metformin and Diclofenac, for treating tumors implanted in mice. Furthermore, a dynamic metabolic model describing central carbon metabolism as well as fluxes targeted by the drugs allowed to simulate tumors progression in both treated and non-treated mice, in addition to draw hypotheses on the effects of the drugs on tumor cells metabolism. Our model predicts metabolic therapies-induced reversed Warburg effect on tumor cells.
Ecological indicator values reveal missing predictors of species distributions
Authors: Scherrer Daniel , Guisan Antoine
Published: February 2019

The questions of how much abiotic environment contributes to explain species distributions, and which abiotic factors are the most influential, are key when projecting species realized niches in space and time. Here, we show that answers to these questions can be obtained by using species’ ecological indicator values (EIVs). By calculating community averages of plant EIVs (397 plant species and 3988 vegetation plots), we found that substituting mapped environmental predictors with site EIVs led to a doubling of explained variation (22.5% to 44%). EIVs representing light and soil showed the highest model improvement, while EIVs representing temperature did not explain additional variance, suggesting that current temperature maps are already fairly accurate. Therefore, although temperature is frequently reported as having a dominant effect on species distributions over other factors, our results suggest that this might primarily result from limitations in our capacity to map other key environmental factors, such as light and soil properties, over large areas.
High genetic diversity and low differentiation retained in the European fragmented and declining Greater Spotted Eagle (Clanga clanga) population
Authors: Väli Ülo , Dombrovski Valery , Dzmitranok Marina , Maciorowski Grzegorz , Meyburg Bernd-Ulrich
Published: February 2019

Characterising genetic diversity and structure of populations is essential for effective conservation of threatened species. The Greater Spotted Eagle (Clanga clanga), a large and globally vulnerable raptor, is extinct or in severe decline in most of its previous range in Europe. We assessed whether the remnants of European population are genetically impoverished, and isolated from each other. We evaluated levels of genetic diversity and population structuring by sequencing mitochondrial pseudo-control region and 10 introns from various nuclear genes, and estimated length diversity in 23 microsatellite markers. The European population has expanded since the late Pleistocene, and does not exhibit signs of a recent population bottleneck. The global genetic diversity in Europe was rather similar to that detected in other similar species. Microsatellites suggested shallow but significant differentiation between the four extant populations in Estonia, Poland, Belarus and Russia (Upper Volga region) populations, but introns and mtDNA showed that only the Estonian population differed from the others. Mitochondrial diversity was highest in the northernmost Estonian population, introns suggested lower diversity in Upper Volga, microsatellites indicated equal diversity among populations. A recent bottleneck was detected in Poland, which is consistent with the observed repopulation of the region. We conclude that significant gene flow and high genetic diversity are retained in the fragmented Greater Spotted Eagle populations; there is currently no need for genetic augmentation in Europe.
One-year postoperative skeletal stability of 3D planned bimaxillary osteotomies: maxilla-first versus mandible-first surgery
Authors: Liebregts Jeroen , Baan Frank , van Lierop Pieter , de Koning Martien , Bergé Stefaan , Maal Thomas , Xi Tong
Published: February 2019

Orthognathic surgery is carried out to correct jaw deformities and to improve facial aesthetics. However, controversy surrounds whether the maxilla- or mandible-first surgery approach leads to better surgical outcomes. In our previous study, we have shown that in most instances, the maxilla-first surgical approach yielded closer concordance with the 3D virtual treatment plan than a mandibular-first procedure. However, the post-operative stability of each approach has not been investigated. Therefore, this one-year follow-up study was set-up and investigated the postoperative skeletal stability of the 3D planned translations and rotations after either the maxilla- or mandible-first surgery. In total, 106 patients who underwent bimaxillary surgery and had an individualized 3D virtual operation plans, received either maxilla-first (n = 53) or mandible-first (n = 53) surgery. 3D printed interocclusal splints were used during surgery to position the jaws. One year postoperatively a cone-beam computed tomography (CBCT) scan was made to assess the effects using the OrthoGnathicAnalyser. The mean sagittal, vertical and transverse relapse was less than 1.8 mm and no significant differences were found in relapse between the maxilla-first or the mandibular-first surgical procedure. Overall, this study shows that 3D virtual planning in combination with an optimised sequencing of osteotomies provides predictable long-term results in bimaxillary surgery.
New electrical impedance methods for the in situ measurement of the complex permittivity of anisotropic skeletal muscle using multipolar needles
Authors: Kwon H. , Guasch M. , Nagy J. A. , Rutkove S. B. , Sanchez B.
Published: February 2019

This paper provides a rigorous analysis on the measurement of the permittivity of two-dimensional anisotropic biological tissues such as skeletal muscle using the four-electrode impedance technique. The state-of-the-art technique requires individual electrodes placed at the same depth in contact with the anisotropic material, e.g. using monopolar needles. In this case, the minimum of measurements in different directions needed to estimate the complex permittivity and its anisotropy direction is 3, which translates into 12 monopolar needle insertions (i.e. 3 directions × 4 electrodes in each direction). Here, we extend our previous work and equip the reader with 8 new methods for multipolar needles, where 2 or more electrodes are spaced along the needle’s shaft in contact with the tissue at different depths. Using multipolar needles, the new methods presented reduce the number of needle insertions by a factor of 2 with respect to the available methods. We illustrate the methods with numerical simulations and new experiments on ex vivo ovine skeletal muscle (n = 3). Multi-frequency longitudinal and transverse permittivity data from 30 kHz to 1 MHz is made publicly available in the supplementary material. The methods presented here for multipolar needles bring closer the application of needle electrical impedance to patients with neuromuscular diseases.
Assessing Sus scrofa diversity among continental United States, and Pacific islands populations using molecular markers from a gene banks collection
Authors: Faria D. A. , Wilson C. , Paiva Samuel , Blackburn H. D.
Published: February 2019

Human migration and trade facilitated domesticated livestock movement, gene flow and development of diverse populations upon which agriculture is based. In addition, varying USA ecological conditions has led to a diverse set of livestock populations to utilize. Quantifying genetic diversity of these populations is incomplete. This paper quantifies genetic diversity captured by the National Animal Germplasm Program and explores genetic structure and differences among 19 pig populations (feral populations from Pacific islands, continental US, and Chinese breeds) using 70,231 SNP from 500 animal samples. Among continental US breeds Fis was consistently low suggesting genetic variability is sufficiently available for breeders to use. A unique population structure using principal component analysis illustrated clear distinctions between Duroc, Yorkshire, Hampshire, breeds of Chinese origin, and feral Pacific Island populations were identified. Five Y chromosome haplotypes were evaluated and demonstrated migration patterns from European, central Asia, and potentially Polynesian waves of gene flow. Quantifying diversity and potential origin of Pacific populations provides insight for future uses, and the need for preservation. Viewing gene bank holdings in context of diversity measures we found a lack of inbreeding within breeds, suggesting the collection represents a wide sampling of individual breeds.
Distribution and Morphology of Cortical Terminals in the Cat Thalamus from the Anterior Ectosylvian Sulcus
Authors: Huppé-Gourgues F. , Abbas Farishta R. , Boire D. , Ptito M. , Casanova C.
Published: February 2019

Two main types of cortical terminals have been identified in the cat thalamus. Large (type II) have been proposed to drive the response properties of thalamic cells while smaller (type I) are believed to modulate those properties. Among the cat’s visual cortical areas, the anterior ectosylvian visual area (AEV) is considered as one of the highest areas in the hierarchical organization of the visual system. Whereas the connections from the AEV to the thalamus have been recognized, their nature (type I or II) is presently not known. In this study, we assessed and compared the relative contribution of type I and type II inputs to thalamic nuclei originating from the AEV. The anterograde tracer BDA was injected in the AEV of five animals. Results show that (1) both type I and II terminals from AEV are present in the Lateral Posterior- Pulvinar complex, the lateral median suprageniculate complex and the medial and dorsal geniculate nuclei (2) type I terminals significantly outnumber the type II terminals in almost all nuclei studied. Our results indicate that neurons in the AEV are more likely to modulate response properties in the thalamus rather than to determine basic organization of receptive fields of thalamic cells.
Unclear associations between small pelagic fish and jellyfish in several major marine ecosystems
Authors: Opdal Anders Frugård , Brodeur Richard D. , Cieciel Kristin , Daskalov Georgi M. , Mihneva Vesselina , Ruzicka James J. , Verheye Hans M. , Aksnes Dag L.
Published: February 2019

During the last 20 years, a series of studies has suggested trends of increasing jellyfish (Cnidaria and Ctenophora) biomass in several major ecosystems worldwide. Some of these systems have been heavily fished, causing a decline among their historically dominant small pelagic fish stocks, or have experienced environmental shifts favouring jellyfish proliferation. Apparent reduction in fish abundance alongside increasing jellyfish abundance has led to hypotheses suggesting that jellyfish in these areas could be replacing small planktivorous fish through resource competition and/or through predation on early life stages of fish. In this study, we test these hypotheses using extended and published data of jellyfish, small pelagic fish and crustacean zooplankton biomass from four major ecosystems within the period of 1960 to 2014: the Southeastern Bering Sea, the Black Sea, the Northern California Current and the Northern Benguela. Except for a negative association between jellyfish and crustacean zooplankton in the Black Sea, we found no evidence of jellyfish biomass being related to the biomass of small pelagic fish nor to a common crustacean zooplankton resource. Calculations of the energy requirements of small pelagic fish and jellyfish stocks in the most recent years suggest that fish predation on crustacean zooplankton is 2–30 times higher than jellyfish predation, depending on ecosystem. However, compared with available historical data in the Southeastern Bering Sea and the Black Sea, it is evident that jellyfish have increased their share of the common resource, and that jellyfish can account for up to 30% of the combined fish-jellyfish energy consumption. We conclude that the best available time-series data do not suggest that jellyfish are outcompeting, or have replaced, small pelagic fish on a regional scale in any of the four investigated ecosystems. However, further clarification of the role of jellyfish requires higher-resolution spatial, temporal and taxonomic sampling of the pelagic community.
Television viewing and cognitive decline in older age: findings from the English Longitudinal Study of Ageing
Authors: Fancourt Daisy , Steptoe Andrew
Published: February 2019

There has been significant interest in the effects of television on cognition in children, but much less research has been carried out into the effects in older adults. This study aimed to explore whether television viewing behaviours in adults aged 50 or over are associated with a decline in cognition. Using data from the English Longitudinal Study of Aging involving 3,662 adults aged 50+, we used multivariate linear regression models to explore longitudinal associations between baseline television watching (2008/2009) and cognition 6 years later (2014/2015) while controlling for demographic factors, socio-economic status, depression, physical health, health behaviours and a range of other sedentary behaviours. Watching television for more than 3.5 hours per day is associated with a dose-response decline in verbal memory over the following six years, independent of confounding variables. These results are found in particular amongst those with better cognition at baseline and are robust to a range of sensitivity analyses exploring reverse causality, differential non-response and stability of television viewing. Watching television is not longitudinally associated with changes in semantic fluency. Overall our results provide preliminary data to suggest that television viewing for more than 3.5 hours per day is related to cognitive decline.
Novel in situ visualisation of rat intestinal absorption of polyphenols via matrix-assisted laser desorption/ionisation mass spectrometry imaging
Authors: Nguyen Huu-Nghi , Tanaka Mitsuru , Li Baorui , Ueno Tomoya , Matsuda Hideki , Matsui Toshiro
Published: February 2019

Matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) is presently used in physiological evaluations for visualisation of targets in organs. In the present study, MALDI-MSI was used as a visualisation technique to investigate the intestinal absorption of polyphenols. Nifedipine/phytic acid-aided MALDI-MSI was performed to visualise theaflavin-3′-O-gallate (TF3′G) and epicatechin-3-O-gallate (ECG) in the rat jejunum for 50-µM, 60-min transport experiments. Non-absorbable TF3′G was successfully visualised at the apical region, whereas absorbable ECG was detected throughout the rat jejunum. MALDI-MSI was also performed to determine the transport routes of the target metabolites. Signals corresponding to TF3′G and ECG in the membranes were diminished following treatment with inhibitors targeting the monocarboxylic acid transporter and organic anion transporting polypeptides. Enhanced visualisation of TF3′G was achieved by inhibiting efflux routes. Our findings demonstrated that the present MALDI-MSI can provide critical spatial informations on intestinal absorption of targets, by which TF3′G and ECG were incorporated into intestinal tissues, followed by efflux back to the apical compartment. In addition, MALDI-MSI analyses suggested that TF3′G was resistant to phase II metabolism during the influx/efflux processes, whereas ECG was susceptible to methylation and sulphation reactions. In conclusion, inhibitor-aided MALDI-MSI could serve as a powerful in situ visualisation technique for verifying intestinal transport routes and investigating the metabolism of penetrants.
Gentisic acid prevents the transition from pressure overload-induced cardiac hypertrophy to heart failure
Authors: Sun Simei , Kee Hae Jin , Ryu Yuhee , Choi Sin Young , Kim Gwi Ran , Kim Hyung-Seok , Kee Seung-Jung , Jeong Myung Ho
Published: February 2019

We previously reported that gentisic acid attenuates cardiac hypertrophy and fibrosis in transverse aortic constriction (TAC)-induced cardiac hypertrophy. Here, we examined whether gentisic acid prevents the development of heart failure. Heart failure was induced in mice via chronic TAC. Mice were administered the vehicle, gentisic acid (10 and 100 mg∙kg−1∙day−1), or bisoprolol (0.5 mg∙kg−1∙day−1) orally for 3 weeks, beginning 3 weeks after TAC. After oral administration of gentisic acid (2000 mg∙kg−1), no significant differences in organ weight, histology, or analyzed serum and hematological parameters were observed between female mice in the control and gentisic acid-treated groups. Gentisic acid administration inhibited cardiac dysfunction in a dose-dependent manner, and reduced cardiac hypertrophy and fibrosis, as was revealed via western blotting, quantitative real-time PCR, and Masson’s trichrome staining. Gentisic acid dose-dependently reduced the expression of fibrosis marker genes, suppressed the renin-angiotensin-aldosterone system, and reduced lung size and pulmonary vascular remodeling. Our data indicate that gentisic acid prevents cardiac hypertrophy, fibrosis, cardiac dysfunction, and pulmonary pathology in TAC-induced heart failure. These findings suggest that supplementation with gentisic acid may provide an advantage in preventing the progression from cardiac hypertrophy to heart failure.
Measurement-Device-Independent Twin-Field Quantum Key Distribution
Authors: Yin Hua-Lei , Fu Yao
Published: February 2019

The ultimate aim of quantum key distribution (QKD) is improving the transmission distance and key generation speed. Unfortunately, it is believed to be limited by the secret-key capacity of quantum channel without quantum repeater. Recently, a novel twin-field QKD (TF-QKD) is proposed to break through the limit, where the key rate is proportional to the square-root of channel transmittance. Here, by using the vacuum and one-photon state as a qubit, we show that the TF-QKD can be regarded as a measurement-device-independent QKD (MDI-QKD) with single-photon Bell state measurement. Therefore, the MDI property of TF-QKD can be understood clearly. Importantly, the universal security proof theories can be directly used for TF-QKD, such as BB84 encoding, six-state encoding and reference-frame-independent scheme. Furthermore, we propose a feasible experimental scheme for the proof-of-principle experimental demonstration.
Tight clustering for large datasets with an application to gene expression data
Authors: Karmakar Bikram , Das Sarmistha , Bhattacharya Sohom , Sarkar Rohan , Mukhopadhyay Indranil
Published: February 2019

This article proposes a practical and scalable version of the tight clustering algorithm. The tight clustering algorithm provides tight and stable relevant clusters as output while leaving a set of points as noise or scattered points, that would not go into any cluster. However, the computational limitation to achieve this precise target of tight clusters prohibits it from being used for large microarray gene expression data or any other large data set, which are common nowadays. We propose a pragmatic and scalable version of the tight clustering method that is applicable to data sets of very large size and deduce the properties of the proposed algorithm. We validate our algorithm with extensive simulation study and multiple real data analyses including analysis of real data on gene expression.
Ovarian Hormone-dependent and Spinal ERK Activation-regulated Nociceptive Hypersensitivity in Female Rats with Acid Injection-induced Chronic Widespread Muscle Pain
Authors: Chang Ju-Hsin , Tsai Shih-Ying , Zeng Yen-Jing , Liu Yu-Cheng , Li Chi-Yuan , Chen Kuen-Bao , Wen Yeong-Ray
Published: February 2019

Symptoms of chronic widespread muscle pain (CWP) meet most of the diagnostic criteria for fibromyalgia syndrome, which is prevalent in females. We used an acid injection-induced muscle pain (AIMP) model to mimic CWP. After female rats received an ovariectomy (OVX), acid saline solution was injected into the left gastrocnemius muscle. Time courses of changes in pain behaviours and p-ERK in the spinal cord were compared between groups. Intrathecal injections of oestradiol (E2) to the OVX group before two acid injections and E2 or progesterone (P4) injections in male rats were compared to evaluate hormone effects. We found that repeated acid injections produced mechanical hypersensitivity and enhanced p-ERK expression in the spinal dorsal horn. OVX rats exhibited significantly less tactile allodynia than did the rats in the other groups. The ERK inhibitor U0126 alleviated mechanical allodynia with lower p-ERK expression in the sham females but did not affect the OVX rats. Intrathecal E2 reversed the attenuated mechanical hypersensitivity in the OVX group, and E2 or P4 induced transient hyperalgesia in male rats. Accordingly, our results suggested that ovarian hormones contribute to AIMP through a spinal p-ERK-mediated pathway. These findings may partially explain the higher prevalence of fibromyalgia in females than males.
Mixed stock analysis of juvenile green turtles aggregating at two foraging grounds in Fiji reveals major contribution from the American Samoa Management Unit
Authors: Piovano Susanna , Batibasaga Aisake , Ciriyawa Ana , LaCasella Erin L. , Dutton Peter H.
Published: February 2019

In this study we assessed the breeding population, or Management Unit (MU), origin of green turtles (Chelonia mydas) present at Yadua Island and Makogai Island foraging grounds in Fiji, central South Pacific. Based on analysis of mitochondrial (mt) DNA sequences from 150 immature green turtles caught during surveys carried out in 2015–2016, we identified a total of 18 haplotypes, the most common being CmP22.1 (44%) which is a primary haplotype characterizing the American Samoa breeding population. Results of a Bayesian mixed-stock analysis reveals that the two foraging grounds are used by green turtles from the American Samoa MU (72%, Credible Interval (CI): 56–87%), New Caledonia MU (17%, CI: 6–26%) and French Polynesia MU (7%, CI: 0–23%). The prominence of the contribution we found from the American Samoa MU compared to that of French Polynesia, both which have historic telemetry and tagging data showing connectivity with Fijian foraging areas, may reflect the current relative abundance of these two nesting populations and draws attention to a need to update population surveys and identify any significant nesting in Fiji that may have been overlooked.
Proteasome β5 subunit overexpression improves proteostasis during aging and extends lifespan in Drosophila melanogaster
Authors: Nguyen Nga N. , Rana Anil , Goldman Camille , Moore Rhiannon , Tai Justin , Hong Yongchan , Shen Jingyi , Walker David W. , Hur Jae H.
Published: February 2019

The β5 subunit of the proteasome has been shown in worms and in human cell lines to be regulatory. In these models, β5 overexpression results in upregulation of the entire proteasome complex which is sufficient to increase proteotoxic stress resistance, improve metabolic parameters, and increase longevity. However, fundamental questions remain unanswered, including the temporal requirements for β5 overexpression and whether β5 overexpression can extend lifespan in other species. To determine if adult-only overexpression of the β5 subunit can increase proteasome activity in a different model, we characterized phenotypes associated with β5 overexpression in Drosophila melanogaster adults. We find that adult-only overexpression of the β5 subunit does not result in transcriptional upregulation of the other subunits of the proteasome as they do in nematodes and human cell culture. Despite this lack of a regulatory role, boosting β5 expression increases the chymotrypsin-like activity associated with the proteasome, reduces both the size and number of ubiquitinated protein aggregates in aged flies, and increases longevity. Surprisingly, these phenotypes were not associated with increased resistance to acute proteotoxic insults or improved metabolic parameters.
deMix: Decoding Deuterated Distributions from Heterogeneous Protein States via HDX-MS
Authors: Na Seungjin , Lee Jae-Jin , Joo Jong Wha J. , Lee Kong-Joo , Paek Eunok
Published: February 2019

Characterization of protein structural changes in response to protein modifications, ligand or chemical binding, or protein-protein interactions is essential for understanding protein function and its regulation. Amide hydrogen/deuterium exchange (HDX) coupled with mass spectrometry (MS) is one of the most favorable tools for characterizing the protein dynamics and changes of protein conformation. However, currently the analysis of HDX-MS data is not up to its full power as it still requires manual validation by mass spectrometry experts. Especially, with the advent of high throughput technologies, the data size grows everyday and an automated tool is essential for the analysis. Here, we introduce a fully automated software, referred to as ‘deMix’, for the HDX-MS data analysis. deMix deals directly with the deuterated isotopic distributions, but not considering their centroid masses and is designed to be robust over random noises. In addition, unlike the existing approaches that can only determine a single state from an isotopic distribution, deMix can also detect a bimodal deuterated distribution, arising from EX1 behavior or heterogeneous peptides in conformational isomer proteins. Furthermore, deMix comes with visualization software to facilitate validation and representation of the analysis results.
Peri-hand space expands beyond reach in the context of walk-and-reach movements
Authors: Berger Michael , Neumann Peter , Gail Alexander
Published: February 2019

The brain incorporates sensory information across modalities to be able to interact with our environment. The peripersonal space (PPS), defined by a high level of crossmodal interaction, is centered on the relevant body part, e.g. the hand, but can spatially expand to encompass tools or reach targets during goal-directed behavior. Previous studies considered expansion of the PPS towards goals within immediate or tool-mediated reach, but not the translocation of the body as during walking. Here, we used the crossmodal congruency effect (CCE) to quantify the extension of the PPS and test if PPS can also expand further to include far located walk-and-reach targets accessible only by translocation of the body. We tested for orientation specificity of the hand-centered reference frame, asking if the CCE inverts with inversion of the hand orientation during reach. We show a high CCE with onset of the movement not only towards reach targets but also walk-and-reach targets. When participants must change hand orientation, the CCE decreases, if not vanishes, and does not simply invert. We conclude that the PPS can expand to the action space beyond immediate or tool-mediated reaching distance but is not purely hand-centered with respect to orientation.
Cancer associated fibroblasts sculpt tumour microenvironment by recruiting monocytes and inducing immunosuppressive PD-1+ TAMs
Authors: Gok Yavuz Betul , Gunaydin Gurcan , Gedik M. Emre , Kosemehmetoglu Kemal , Karakoc Derya , Ozgur Figen , Guc Dicle
Published: February 2019

Fibroblasts turn into cancer associated fibroblasts (CAFs) in the tumour microenvironment. CAFs have recently attracted attention for their function as a regulator of immune cell recruitment and function in addition to their tumour-promoting roles. In this study, we aimed to determine the role of CAFs on monocyte recruitment and macrophage polarization in breast cancer. CAFs, which were α-SMA expressing fibroblasts in contrast to normal fibroblasts (NFs), effectively recruited monocytes. Recruitment of monocytes by CAFs might be mediated by monocyte chemotactic protein-1 (MCP-1) as well as stromal cell-derived factor-1 (SDF-1) cytokines. CAFs differentiated the recruited monocytes into M2-like macrophages which are capable of exerting their immunosuppressive roles via the PD-1 axis. CAF-educated monocytes exhibited strong immune suppression unlike NF-educated monocytes and enhanced the motility/invasion of breast cancer cells in addition to increasing the expressions of epithelial–mesenchymal transition (EMT)-related genes and vimentin protein in cancer cells. CAF-educated M1 macrophages displayed increased expression of M2 markers and production of anti-inflammatory cytokine IL-10 in contrast to decreased production of pro-inflammatory cytokine IL-12 compared with control M1 macrophages; suggesting that CAFs were also able to induce the trans-differentiation of M1 macrophages to M2 macrophages. We then investigated the relationship between the infiltration of CAFs and tumour associated macrophages (TAMs) using tissue samples obtained from breast cancer patients. High grade of CAFs significantly correlated with the number of TAMs in human breast cancer tissue samples. It was also associated with higher Ki-67 proliferation index, and higher tumour volume. This result is in line with our finding of increased breast cancer cell proliferation due to the effects of CAF-educated monocytes in vitro. Our results concluded that CAFs play pivotal roles in sculpturing the tumour microenvironment in breast cancer, and therapeutic strategies to reverse the CAF-mediated immunosuppressive microenvironment should be taken into consideration.
Low density lipoprotein mimics insulin action on autophagy and glucose uptake in endothelial cells
Authors: Zhu Lin , Wu Guangjie , Yang Xiaoyan , Jia Xiong , Li Juyi , Bai Xiangli , Li Wenjing , Zhao Ying , Li Ye , Cheng Wenzhuo , Liu Shuli , Jin Si
Published: February 2019

Elevated plasma low density lipoprotein (LDL) is an established risk factor for cardiovascular disease. In addition to being able to cross the endothelial barrier to become accumulated in subendothelial space and thereby initiate atherosclerosis, LDL may exert a direct effect on vascular endothelial cells through activation of LDL receptor and its downstream signaling. Whether LDL can modulate the signaling for autophagy in endothelial cells is not clear. The present study firstly demonstrated that LDL can suppress endothelial autophagy through activation of the PI3K/Akt/mTOR signaling pathway and can promote glucose uptake by translocating glucose transporter 1 (GLUT1) from cytoplasm to cell membrane, actions similar to those of insulin. A co-immunoprecipitation assay found that LDL receptor (LDLR) and insulin receptor (IR) formed a complex in HUVECs. Knock down of the insulin receptor by small interfering RNA blocked the suppression of autophagy by LDL, as well as the signaling pathway involved. We conclude that LDL may mimic the action of insulin in endothelial cells, which might partly explain the increased incidence of diabetes in patients receiving some LDL-lowering therapy.
Streptomyces monashensis sp. nov., a novel mangrove soil actinobacterium from East Malaysia with antioxidative potential
Authors: Law Jodi Woan-Fei , Ser Hooi-Leng , Ab Mutalib Nurul-Syakima , Saokaew Surasak , Duangjai Acharaporn , Khan Tahir Mehmood , Chan Kok-Gan , Goh Bey-Hing , Lee Learn-Han
Published: February 2019

A new Streptomyces species discovered from Sarawak mangrove soil is described, with the proposed name – Streptomyces monashensis sp. nov. (strain MUSC 1JT). Taxonomy status of MUSC 1JT was determined via polyphasic approach. Phylogenetic and chemotaxonomic properties of strain MUSC 1JT were in accordance with those known for genus Streptomyces. Based on phylogenetic analyses, the strains closely related to MUSC 1JT were Streptomyces corchorusii DSM 40340T (98.7%), Streptomyces olivaceoviridis NBRC 13066T (98.7%), Streptomyces canarius NBRC 13431T (98.6%) and Streptomyces coacervatus AS-0823T (98.4%). Outcomes of DNA–DNA relatedness between strain MUSC 1JT and its closely related type strains covered from 19.7 ± 2.8% to 49.1 ± 4.3%. Strain MUSC 1JT has genome size of 10,254,857 bp with DNA G + C content of 71 mol%. MUSC 1JT extract exhibited strong antioxidative activity up to 83.80 ± 4.80% in the SOD assay, with significant cytotoxic effect against colon cancer cell lines HCT-116 and SW480. Streptomyces monashensis MUSC 1JT (=DSM 103626T = MCCC 1K03219T) could potentially be a producer of novel bioactive metabolites; hence discovery of this new species may be highly significant to the biopharmaceutical industry as it could lead to development of new and useful chemo-preventive drugs.
Peer effects on control-averse behavior
Authors: Rudorf Sarah , Baumgartner Thomas , Knoch Daria
Published: February 2019

The urge to rebel against external control affects social interactions in many domains of our society with potentially far-reaching consequences. Nevertheless, it has remained unclear to what degree this control-averse behavior might be influenced by the people in our surroundings, our peers. In an experimental paradigm with real restrictions of the subjects’ freedom of choice and no systematic incentives to follow the peer, we are able to demonstrate both negative and positive peer effects on control-averse behavior. First, we find that information about a peer’s strongly control-averse behavior, although irrelevant for the subjects’ outcome, increases the subjects’ individual control-averse behavior. Second, we find that information about a peer’s more generous and only weakly control-averse behavior increases subjects’ generous behavior, even though it is associated with greater costs for the subjects. Critically, each subject’s behavior determined the monetary payoff of both the subject and a third person, thereby constituting a social behavior with actual consequences. Interestingly, these peer effects are not moderated by self-assessments of the general resistance to peer influence or the general tendency to rebel against restrictions of one’s freedom of choice. Contributing new insights into a complex and highly relevant social phenomenon, our results indicate that information about a single peer’s behavior can influence individual control-averse behavior.
The impact of cation concentration on Microcystis (cyanobacteria) scum formation
Authors: Drugă Bogdan , Buda Doriana-Mădălina , Szekeres Edina , Chiş Ciprian , Chiş Iuliana , Sicora Cosmin
Published: February 2019

Cyanobacterial scums at the surface of the lakes are potentially harmful phenomena with increasing occurrence in the last decades, and the causes that lead to their formation are still an unresolved issue. In order to better understand what triggers the scums, we investigated the effect of several Mg2+ and Ca2+ ion concentrations in promoting them in eight Microcystis aeruginosa strains. The possibility to prevent scum formation by using the ion chelator EDTA was also explored. We found that in some strains the cell aggregation takes place under lower ion source concentrations (20 mM MgSO4 or CaCl2), while in others this phenomenon does not occur even at 60 mM concentration. The scum formation correlated to the amount of extracellular polymeric substances (between 234 and 351 µg/cell). EDTA failed to prevent the scum formation in most strains, and in turn it caused cell lysis followed by the release of cellular content into the culture medium. We emphasize the relevance of these results for cyanobacterial scum formation in the environment and we also suggest that controlling the salinity of the medium (by manipulating the ion concentration) is a potentially efficient method for biomass harvesting in large ponds/tanks.
Diverse nature of femtosecond laser ablation of poly(L-lactide) and the influence of filamentation on the polymer crystallization behaviour
Authors: Stępak Bogusz , Gazińska Małgorzata , Nejbauer Michał , Stepanenko Yuriy , Antończak Arkadiusz
Published: February 2019

Over the past few years we have witnessed growing interest in ultrafast laser micromachining of bioresorbable polymers for fabrication of medical implants and surface modification. In this paper we show that surface structuring of poly(L-lactide) with 300 fs laser pulses at 515 and 1030 nm wavelength leads to formation of defects inside the polymer as a result of laser beam filamentation. Filament-induced channels have diameter around 1 μm and length of hundreds of micrometers. SEM images of microchannels cross-sections are presented. The influence of wavelength and pulse spacing on bulk modification extent was investigated and parameters limiting filamentation were determined. We show that filamentation can be used for controlling properties of PLLA. The presence of filament-induced modifications such as empty microchannels and pressure wave-induced stress lead to increased ability of polymer to crystallize at lower temperature. Crystallization behaviour and crystal morphology after laser treatment was investigated in details using different analytical techniques such as WAXD, DSC and FTIR/ATR. Hydrolytic degradation experiment was performed. Presented method can be applied for controllable, spatially distributed modification of polymer crystallinity, crystalline phase structure and hydrolytic degradation profile.
Air pollutants associated with smoking in indoor/outdoor of waterpipe cafés in Tehran, Iran: Concentrations, affecting factors and health risk assessment
Authors: Masjedi Mohammad Reza , Taghizadeh Farhad , Hamzehali Sanaz , Ghaffari Sonia , Fazlzadeh Mehdi , Jafari Ahmad Jonidi , Niazi Sadegh , Mehrizi Ehsan Abouee , Moradi Masoud , Pasalari Hasan , Arfaeinia Hossein
Published: February 2019

Despite increasingly growth in waterpipe smoking in Tehran, so far no study has been conducted on the air quality of the waterpipe and cigarette cafés. Thirty-six cafés were selected and the concentration of three pollutants including formaldehyde, carbon monoxide and nicotine were measured in both indoor and outdoor air of cafés two times (week-day and weekend’s session). Air sampling was performed for 180 min for each pollutant. It was observed that the concentration of pollutants inside the cafés was higher during weekend session (with a higher number of “active waterpipe heads”) compared with findings during the week-day sessions. Furthermore, the concentration of pollutants in the indoor air of the cafés was significantly higher than that of the outdoors (p < 0.05). According to path analysis, the number of “active waterpipe heads” had the maximum impact on generation of pollutants inside the cafés, followed by the type of tobacco as the second influential factor. The average of lifetime cancer risk (LTCR) resulted by formaldehyde exposure through inhalation in waterpipe (WS), cigarette (CS), waterpipe and cigarette (WCS) and none-smoking (NS) cafés in week-day and weekend sessions were estimated to be 111 × 10−5 and 61.2 × 10−5, 33.7 × 10−5 and 39.4 × 10−5, 271 × 10−5 and 322 × 10−5, and 4.80 × 10−5 and 5.90 × 10−5, respectively, which exceed the limit value by the U.S.EPA and WHO. The concentration of pollutants in the indoor air of smoking cafés in Tehran is significantly high, such that it can pose serious risks for the health of both personnel and customers. Therefore, decision makers are expected to enact applicable and strict policies so as to abate this public health risk.