bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice
Authors: Zhang Wenliang , Zhong Wei , Sun Qian , Sun Xinguo , Zhou Zhanxiang
Published: August 2017

Chronic alcohol feeding causes lipid accumulation and apoptosis in the liver. This study investigated the role of bioactive lipid metabolites in alcohol-induced liver damage and tested the potential of targeting arachidonate 15-lipoxygenase (ALOX15) in treating alcoholic liver disease (ALD). Results showed that chronic alcohol exposure induced hepatocyte apoptosis in association with increased hepatic 13-HODE. Exposure of 13-HODE to Hepa-1c1c7 cells induced oxidative stress, ER stress and apoptosis. 13-HODE also perturbed proteins related to lipid metabolism. HODE-generating ALOX15 was up-regulated by chronic alcohol exposure. Linoleic acid, but not ethanol or acetaldehyde, induced ALOX15 expression in Hepa-1c1c7 cells. ALOX15 knockout prevented alcohol-induced liver damage via attenuation of oxidative stress, ER stress, lipid metabolic disorder, and cell death signaling. ALOX15 inhibitor (PD146176) treatment also significantly alleviated alcohol-induced oxidative stress, lipid accumulation and liver damage. These results demonstrated that activation of ALOX15/13-HODE circuit critically mediates the pathogenesis of ALD. This study suggests that ALOX15 is a potential molecular target for treatment of ALD.
Attraction Effect in Risky Choice Can Be Explained by Subjective Distance Between Choice Alternatives
Authors: Mohr Peter N. C. , Heekeren Hauke R. , Rieskamp Jörg
Published: August 2017

Individuals make decisions under risk throughout daily life. Standard models of economic decision making typically assume that people evaluate choice options independently. There is, however, substantial evidence showing that this independence assumption is frequently violated in decision making without risk. The present study extends these findings to the domain of decision making under risk. To explain the independence violations, we adapted a sequential sampling model, namely Multialternative Decision Field Theory (MDFT), to decision making under risk and showed how this model can account for the observed preference shifts. MDFT not only better predicts choices compared with the standard Expected Utility Theory, but it also explains individual differences in the size of the observed context effect. Evidence in favor of the chosen option, as predicted by MDFT, was positively correlated with brain activity in the medial orbitofrontal cortex (mOFC) and negatively correlated with brain activity in the anterior insula (aINS). From a neuroscience perspective, the results of the present study show that specific brain regions, such as the mOFC and aINS, not only code the value or risk of a single choice option but also code the evidence in favor of the best option compared with other available choice options.
The mean and variance of climate change in the oceans: hidden evolutionary potential under stochastic environmental variability in marine sticklebacks
Authors: Shama Lisa N. S.
Published: August 2017

Increasing climate variability may pose an even greater risk to species than climate warming because temperature fluctuations can amplify adverse impacts of directional warming on fitness-related traits. Here, the influence of directional warming and increasing climate variability on marine stickleback fish (Gasterosteus aculeatus) offspring size variation was investigated by simulating changes to the mean and variance of ocean temperatures predicted under climate change. Reproductive traits of mothers and offspring size reaction norms across four climate scenarios were examined to assess the roles of standing genetic variation, transgenerational and within-generation plasticity in adaptive potential. Mothers acclimated to directional warming produced smaller eggs than mothers in constant, ambient temperatures, whereas mothers in a predictably variable environment (weekly change between temperatures) produced a range of egg sizes, possibly reflecting a diversified bet hedging strategy. Offspring size post-hatch was mostly influenced by genotype by environment interactions and not transgenerational effects. Offspring size reaction norms also differed depending on the type of environmental predictability (predictably variable vs. stochastic), with offspring reaching the largest sizes in the stochastic environment. Release of cryptic genetic variation for offspring size in the stochastic environment suggests hidden evolutionary potential in this wild population to respond to changes in environmental predictability.
Al-doped ZnO/Ag-nanowire Composite Electrodes for Flexible 3-Dimensional Nanowire Solar Cells
Authors: Pathirane Minoli K. , Hosseinzadeh Khaligh Hadi , Goldthorpe Irene A. , Wong William S.
Published: August 2017

Silver nanowires in conjunction with sputter-coated Al-doped ZnO (AZO) thin films were used as a composite transparent top electrode for hybrid radial-junction ZnO nanowire/a-Si:H p-i-n thin-film solar cells. Solar cells with the composite nanowire top contacts attained a short-circuit current density (Jsc) of 13.9 mA/cm2 and a fill factor (FF) of 62% on glass substrates while a Jsc of 13.0 mA/cm2 and FF of 62% was achieved on plastic substrates. The power conversion efficiency (PCE) of the 3-dimensional solar cells improved by up to 60% compared to using AZO electrodes alone due to enhanced coverage of the top electrode over the 3-D structures, decreasing the series resistance of the device by 5×. The composite layer also showed a 10× reduction in sheet resistance compared to the AZO thin-film contact under applied mechanical strain.
In vivo label-free structural and biochemical imaging of coronary arteries using an integrated ultrasound and multispectral fluorescence lifetime catheter system
Authors: Bec Julien , Phipps Jennifer E. , Gorpas Dimitris , Ma Dinglong , Fatakdawala Hussain , Margulies Kenneth B. , Southard Jeffrey A. , Marcu Laura
Published: August 2017

Existing clinical intravascular imaging modalities are not capable of accurate detection of critical plaque pathophysiology in the coronary arteries. This study reports the first intravascular catheter combining intravascular ultrasound (IVUS) with multispectral fluorescence lifetime imaging (FLIm) that enables label-free simultaneous assessment of morphological and biochemical features of coronary vessels in vivo. A 3.7 Fr catheter with a fiber-optic channel was constructed based on a 40 MHz clinical IVUS catheter. The ability to safely acquire co-registered FLIm-IVUS data in vivo using Dextran40 solution flushing was demonstrated in swine coronary arteries. FLIm parameters from the arterial wall were consistent with the emission of fluorophores present in healthy arterial wall (collagen, elastin). Additionally, structural and biochemical features from atherosclerotic lesions were acquired in ex vivo human coronary samples and corroborated with histological findings. Current results show that FLIm parameters linked to the amount of structural proteins (e.g. collagen, elastin) and lipids (e.g. foam cells, extracellular lipids) in the first 200 μm of the intima provide important biochemical information that can supplement IVUS data for a comprehensive assessment of plaques pathophysiology. The unique FLIm-IVUS system evaluated here has the potential to provide a comprehensive insight into atherosclerotic lesion formation, diagnostics and response to therapy.
Classification of M1/M2-polarized human macrophages by label-free hyperspectral reflectance confocal microscopy and multivariate analysis
Authors: Bertani Francesca R. , Mozetic Pamela , Fioramonti Marco , Iuliani Michele , Ribelli Giulia , Pantano Francesco , Santini Daniele , Tonini Giuseppe , Trombetta Marcella , Businaro Luca , Selci Stefano , Rainer Alberto
Published: August 2017

The possibility of detecting and classifying living cells in a label-free and non-invasive manner holds significant theranostic potential. In this work, Hyperspectral Imaging (HSI) has been successfully applied to the analysis of macrophagic polarization, given its central role in several pathological settings, including the regulation of tumour microenvironment. Human monocyte derived macrophages have been investigated using hyperspectral reflectance confocal microscopy, and hyperspectral datasets have been analysed in terms of M1 vs. M2 polarization by Principal Components Analysis (PCA). Following PCA, Linear Discriminant Analysis has been implemented for semi-automatic classification of macrophagic polarization from HSI data. Our results confirm the possibility to perform single-cell-level in vitro classification of M1 vs. M2 macrophages in a non-invasive and label-free manner with a high accuracy (above 98% for cells deriving from the same donor), supporting the idea of applying the technique to the study of complex interacting cellular systems, such in the case of tumour-immunity in vitro models.
In vivo assessment of macula in eyes of healthy children 8 to 16 years old using optical coherence tomography angiography
Authors: Zhang Zhengwei , Huang Xiaoli , Meng Xiaomei , Chen Tiantian , Gu Yan , Wu Yan , Wu Zhifeng
Published: August 2017

The purpose of the present study was to investigate the vascular flow density (VD) of macular superficial (SCP), deep capillary plexus (DCP), and choriocapillaris and the size of the foveal avascular zone (FAZ) area in healthy children using optical coherence tomography angiography (OCTA). The potential associations of age, sex, intraocular pressure, body mass index, spherical equivalent, and axial length with OCTA parameters were also investigated. A total of 75 eyes from 75 healthy children were included for analysis, with the mean age 11.51 ± 1.91 years (range, 8–16 years). At the level of the SCP, mean VD and mean FAZ area were, respectively, 54.29 ± 2.25% and 0.290 ± 0.109 mm2. At the level of the DCP and choriocapillaris, mean VD were 60.19 ± 1.76% and 66.58 ± 1.33%, respectively. After adjustment on the signal strength index, there was no significant correlation between age and all OCTA parameters. Intra-observer repeatability was 0.91, 0.82, and 0.88 in the SCP, DCP and choriocapillaris, respectively. In healthy eyes of children, only sex has a significant influence on the FAZ area. OCTA may provide a noninvasive and reliable approach for evaluating macular perfusion in children, although sex-related variations should be considered.
Magnetic properties of individual Co2FeGa Heusler nanoparticles studied at room temperature by a highly sensitive co-resonant cantilever sensor
Authors: Körner Julia , Reiche Christopher F. , Ghunaim Rasha , Fuge Robert , Hampel Silke , Büchner Bernd , Mühl Thomas
Published: August 2017

The investigation of properties of nanoparticles is an important task to pave the way for progress and new applications in many fields of research like biotechnology, medicine and magnetic storage techniques. The study of nanoparticles with ever decreasing size is a challenge for commonly employed methods and techniques. It requires increasingly complex measurement setups, often low temperatures and a size reduction of the respective sensors to achieve the necessary sensitivity and resolution. Here, we present results on how magnetic properties of individual nanoparticles can be measured at room temperature and with a conventional scanning force microscopy setup combined with a co-resonant cantilever magnetometry approach. We investigate individual Co2FeGa Heusler nanoparticles with diameters of the order of 35 nm encapsulated in carbon nanotubes. We observed, for the first time, magnetic switching of these nanoparticles in an external magnetic field by simple laser deflection detection. Furthermore, we were able to deduce magnetic properties of these nanoparticles which are in good agreement with previous results obtained with large nanoparticle ensembles in other experiments. In order to do this, we expand the analytical description of the frequency shift signal in cantilever magnetometry to a more general formulation, taking unaligned sensor oscillation directions with respect to the magnetic field into account.
Development of a comprehensive set of tools for genome engineering in a cold- and thermo-tolerant Kluyveromyces marxianus yeast strain
Authors: Nambu-Nishida Yumiko , Nishida Keiji , Hasunuma Tomohisa , Kondo Akihiko
Published: August 2017

Kluyveromyces marxianus, a non-conventional thermotolerant yeast, is potentially useful for production of ethanol and other products. This species has a strong tendency to randomly integrate transforming DNA fragments, making necessary the development of more precise methods for gene targeting. In this study, we first demonstrated thatK. marxianusNBRC1777 is cold-tolerant, and then established a highly efficient and precise technique for gene editing by introducing genes encoding deaminase-mediated targeted point mutagenesis (Target-AID) and clustered regularly interspaced short palindromic repeats (CRISPR) associated proteins (CRISPR-Cas9). We used Target-AID to introduce targeted point mutations that disruptedNej1orDnl4, genes that are involved in non-homologous end-joining (NHEJ). Both of the resulting mutant strains showed enhanced proportions of homology-mediated integration compared to the wild-type parent. In combination with target cleavage by CRISPR-Cas9, markerless integration was performed using short (~50 bp) flanking homologous sequences. Together, these tools render this species fully tractable for gene manipulation, permitting targeted genetic changes in the cold- and thermo-tolerant yeastK. marxianus.
The human IL-17A/F heterodimer: a two-faced cytokine with unique receptor recognition properties
Authors: Goepfert Arnaud , Lehmann Sylvie , Wirth Emmanuelle , Rondeau Jean-Michel
Published: August 2017

IL-17A and IL-17F are prominent members of the IL-17 family of cytokines that regulates both innate and adaptive immunity. IL-17A has been implicated in chronic inflammatory and autoimmune diseases, and anti-IL-17A antibodies have shown remarkable clinical efficacy in psoriasis and psoriatic arthritis patients. IL-17A and IL-17F are homodimeric cytokines that can also form the IL-17A/F heterodimer whose precise role in health and disease remains elusive. All three cytokines signal through the assembly of a ternary complex with the IL-17RA and IL-17RC receptors. Here we report the X-ray analysis of the human IL-17A/F heterodimer that reveals a two-faced cytokine closely mimicking IL-17A as well as IL-17F. We also present the crystal structure of its complex with the IL-17RA receptor. Unexpectedly in view of the much higher affinity of this receptor toward IL-17A, we find that IL-17RA is bound to the “F-face” of the heterodimer in the crystal. Using site-directed mutagenesis, we then demonstrate that IL-17RA can also bind to the “A-face” of IL-17A/F with similar affinity. Further, we show that IL-17RC does not discriminate between the two faces of the cytokine heterodimer either, thus enabling the formation of two topologically-distinct heterotrimeric complexes with potentially different signaling properties.
Microbial community analysis of apple rhizosphere around Bohai Gulf
Authors: Jiang Jihang , Song Zhen , Yang Xiaotong , Mao Zhiquan , Nie Xiaohong , Guo Hui , Peng Xiawei
Published: August 2017

Bohai Gulf is the main area for apple tree cultivation in China. Consecutive replanting significantly affects the yield and quality of apple trees in this area. Microecological imbalance in apple trees’ rhizospheres caused by variation in the soil microbial community is considered the primary cause of apple replant disease (ARD). This study analysed the microbial communities of the rhizospheres of perennial apple trees (PAT) and apple tree saplings under replanting (ATS) around Bohai Gulf using high-throughput sequencing. The results revealed increased populations of typical pathogenic fungi Verticillium and bacteria Xanthomonadaceae, and decreased populations of beneficial bacterial populations Pseudomonas and Bacillus with replanting, suggesting that competition between pathogens and beneficial microbes varies according to the ratio of pathogens to beneficial microbes in rhizosphere soil under the replanting system. Meanwhile, replanting was accompanied by an increase in the antagonistic bacteria Arthrobacter and fungus Chaetomium, suggesting that increased numbers of pathogens can lead to more instances of antagonism. Redundancy analysis (RDA) revealed site position and the main soil properties (pH, organic matter, available N, available K, available P, and moisture) affected the microbial community composition. It found clear differences in soil microbial communities and demonstrated a better understanding of the causes for ARD.
PDGF-BB enhances collagen gel contraction through a PI3K-PLCγ-PKC-cofilin pathway
Authors: Reyhani Vahid , Tsioumpekou Maria , van Wieringen Tijs , Rask Lars , Lennartsson Johan , Rubin Kristofer
Published: August 2017

Cell-mediated contraction of collagenous matrices is modulated by various growth factors and cytokines, such as platelet-derived growth factor-BB (PDGF-BB). Here we used a genetic cell model to delineate defined signaling pathways that enhance collagen gel contraction downstream of ligand-stimulated platelet-derived growth factor receptor-β (PDGF-Rβ). Our data show that PDGF BB-enhanced activations of phosphatidylinositol 3′-kinase (PI3K) and phospholipase Cγ (PLCγ) were necessary for PDGF-enhanced collagen gel contraction. Importantly, other defined signaling pathways down-stream of PDGF-Rβ were, however, dispensable. The decisive roles for PI3K and PLCγ were corroborated by experiments using selective inhibitors. Furthermore, we show that de-phosphorylation and thereby activation of cofilin that is important for the turnover of actin filaments, is depended on PI3K and PLCγ down-stream of PDGF-Rβ. Moreover, inhibition of protein kinase C (PKC) by GÖ6976 and bisindolylmaleimide-II abolished cofilin de-phosphorylation, as well as PDGF-enhanced contraction. In contrast, activation of the PKC protein family by 4β-phorbol 12-myristate 13-acetate (PMA) did not accelerate collagen gel contraction although it induced long-term cofilin de-phosphorylation, showing the need of a dynamic control of cofilin de-phosphorylation for PDGF-enhanced collagen gel contraction. Taken together, our data point to the involvement of a PI3K/PLCγ-PKC-cofilin pathway in both PDGF-enhanced cofilin de-phosphorylation and PDGF-enhanced collagen gel contraction.
Muscle and adipose tissue morphology, insulin sensitivity and beta-cell function in diabetic and nondiabetic obese patients: effects of bariatric surgery
Authors: Camastra Stefania , Vitali Alessandra , Anselmino Marco , Gastaldelli Amalia , Bellini Rosario , Berta Rossana , Severi Ilenia , Baldi Simona , Astiarraga Brenno , Barbatelli Giorgio , Cinti Saverio , Ferrannini Ele
Published: August 2017

Obesity is characterized by insulin-resistance (IR), enhanced lipolysis, and ectopic, inflamed fat. We related the histology of subcutaneous (SAT), visceral fat (VAT), and skeletal muscle to the metabolic abnormalities, and tested their mutual changes after bariatric surgery in type 2 diabetic (T2D) and weight-matched non-diabetic (ND) patients. We measured IR (insulin clamp), lipolysis (2H5-glycerol infusion), ß-cell glucose-sensitivity (ß-GS, mathematical modeling), and VAT, SAT, and rectus abdominis histology (light and electron microscopy). Presurgery, SAT and VAT showed signs of fibrosis/necrosis, small mitochondria, free interstitial lipids, thickened capillary basement membrane. Compared to ND, T2D had impaired ß-GS, intracapillary neutrophils and higher intramyocellular fat, adipocyte area in VAT, crown-like structures (CLS) in VAT and SAT with rare structures (cyst-like) ~10-fold larger than CLS. Fat expansion was associated with enhanced lipolysis and IR. VAT histology and intramyocellular fat were related to impaired ß-GS. Postsurgery, IR and lipolysis improved in all, ß-GS improved in T2D. Muscle fat infiltration was reduced, adipocytes were smaller and richer in mitochondria, and CLS density in SAT was reduced. In conclusion, IR improves proportionally to weight loss but remains subnormal, whilst SAT and muscle changes disappear. In T2D postsurgery, some VAT pathology persists and beta-cell dysfunction improves but is not normalized.
An integrated method for cell isolation and migration on a chip
Authors: Lv Xiaoqing , Geng Zhaoxin , Fan Zhiyuan , Wang Shicai , Pei WeiHua , Chen Hongda
Published: August 2017

Tumour cell migration has an important impact on tumour metastasis. Magnetic manipulation is an ascendant method for guiding and patterning cells. Here, a unique miniaturized microfluidic chip integrating cell isolation and migration assay was designed to isolate and investigate cell migration. The chip was fabricated and composed of a magnet adapter, a polytetrafluoroethylene(PDMS) microfluidic chip and six magnetic rings. This device was used to isolate MCF-7 cells from MDA-MB-231-RFP cells and evaluate the effects of TGF-β on MCF-7 cells. First, the two cell types were mixed and incubated with magnetic beads modified with an anti-EpCAM antibody. Then, they were slowly introduced into the chip. MCF-7 cells bond to the magnetic beads in a ring-shaped pattern, while MDA-MB-231-RFP cells were washed away by PBS. Cell viability was examined during culturing in the micro-channel. The effects of TGF-β on MCF-7 cells were evaluated by migration distance and protein expression. The integrated method presented here is novel, low-cost and easy for performing cell isolation and migration assay. The method could be beneficial for developing microfluidic device applications for cancer metastasis research and could provide a new method for biological experimentation.
SIRT1 reduction is associated with sex-specific dysregulation of renal lipid metabolism and stress responses in offspring by maternal high-fat diet
Authors: Nguyen Long The , Chen Hui , Pollock Carol , Saad Sonia
Published: August 2017

Rodent models of maternal obesity have been associated with kidney damage and dysfunction in offspring. However, the underlying mechanisms are yet to be elucidated. In this study, female rats were fed a high-fat diet (HFD) for 6 weeks prior to mating, throughout gestation and lactation; both male and female offspring were examined at weaning. Our results demonstrate that renal lipid deposition was increased in male offspring only, which is associated with reduced protein expression of Sirtuin (SIRT) 1, an essential regulator of lipid metabolism and stress response. Other components in its signalling network including phosphorylated 5′-AMP-activated protein kinase (pAMPKα), Forkhead box FOXO3a and Peroxisome proliferator-activated receptor (PPAR)γ coactivator 1-alpha (PGC-1α) were also downregulated. By contrast, in female offspring, renal fat/lipid distribution was unchanged in coupling with normal SIRT1 regulation. Specific autophagy and antioxidant markers were suppressed in both sexes. On the other hand, fibronectin and Collagen type IV protein expression was significantly higher in the offspring born HFD-fed dams, particularly in the males. Collectively, these findings suggest that maternal HFD consumption can induce sex-specific changes in offspring kidney lipid metabolism and stress responses at early ages, which may underpin the risk of kidney diseases later in life.
Molecular dynamics for linear polymer melts in bulk and confined systems under shear flow
Authors: Cho Soowon , Jeong Sohdam , Kim Jun Mo , Baig Chunggi
Published: August 2017

In this work, we analyzed the individual chain dynamics for linear polymer melts under shear flow for bulk and confined systems using atomistic nonequilibrium molecular dynamics simulations of unentangled (C50H102) and slightly entangled (C178H358) polyethylene melts. While a certain similarity appears for the bulk and confined systems for the dynamic mechanisms of polymer chains in response to the imposed flow field, the interfacial chain dynamics near the boundary solid walls in the confined system are significantly different from the corresponding bulk chain dynamics. Detailed molecular-level analysis of the individual chain motions in a wide range of flow strengths are carried out to characterize the intrinsic molecular mechanisms of the bulk and interfacial chains in three flow regimes (weak, intermediate, and strong). These mechanisms essentially underlie various macroscopic structural and rheological properties of polymer systems, such as the mean-square chain end-to-end distance, probability distribution of the chain end-to-end distance, viscosity, and the first normal stress coefficient. Further analysis based on the mesoscopic Brightness method provides additional structural information about the polymer chains in association with their molecular mechanisms.
Cellular internalization of alpha-synuclein aggregates by cell surface heparan sulfate depends on aggregate conformation and cell type
Authors: Ihse Elisabet , Yamakado Hodaka , van Wijk Xander M. , Lawrence Roger , Esko Jeffrey D. , Masliah Eliezer
Published: August 2017

Amyloid aggregates found in the brain of patients with neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, are thought to spread to increasingly larger areas of the brain through a prion-like seeding mechanism. Not much is known about which cell surface receptors may be involved in the cell-to-cell transfer, but proteoglycans are of interest due to their well-known propensity to interact with amyloid aggregates. In this study, we investigated the involvement of plasma membrane-bound heparan and chondroitin sulfate proteoglycans in cellular uptake of aggregates consisting of α-synuclein, a protein forming amyloid aggregates in Parkinson’s disease. We show, using a pH-sensitive probe, that internalization of α-synuclein amyloid fibrils in neuroblastoma cells is dependent on heparan sulfate, whereas internalization of smaller non-amyloid oligomers is not. We also show that α-synuclein fibril uptake in an oligodendrocyte-like cell line is equally dependent on heparan sulfate, while astrocyte- and microglia-like cell lines have other means to internalize the fibrils. In addition, we analyzed the interaction between the α-synuclein amyloid fibrils and heparan sulfate and show that overall sulfation of the heparan sulfate chains is more important than sulfation at particular sites along the chains.
MatCol: a tool to measure fluorescence signal colocalisation in biological systems
Authors: Khushi Matloob , Napier Christine E. , Smyth Christine M. , Reddel Roger R. , Arthur Jonathan W.
Published: August 2017

Protein colocalisation is often studied using pixel intensity-based coefficients such as Pearson, Manders, Li or Costes. However, these methods cannot be used to study object-based colocalisations in biological systems. Therefore, a novel method is required to automatically identify regions of fluorescent signal in two channels, identify the co-located parts of these regions, and calculate the statistical significance of the colocalisation. We have developed MatCol to address these needs. MatCol can be used to visualise protein and/or DNA colocalisations and fine tune user-defined parameters for the colocalisation analysis, including the application of median or Wiener filtering to improve the signal to noise ratio. Command-line execution allows batch processing of multiple images. Users can also calculate the statistical significance of the observed object colocalisations compared to overlap by random chance using Student’s t-test. We validated MatCol in a biological setting. The colocalisations of telomeric DNA and TRF2 protein or TRF2 and PML proteins in >350 nuclei derived from three different cell lines revealed a highly significant correlation between manual and MatCol identification of colocalisations (linear regression R2 = 0.81, P < 0.0001). MatCol has the ability to replace manual colocalisation counting, and the potential to be applied to a wide range of biological areas.
RNA interference in the Asian Longhorned Beetle:Identification of Key RNAi Genes and Reference Genes for RT-qPCR
Authors: Rodrigues Thais B. , Dhandapani Ramesh Kumar , Duan Jian J. , Palli Subba Reddy
Published: August 2017

Asian Longhorned Beetle (ALB) Anoplophora glabripennis is a serious invasive forest pest in several countries including the United States, Canada, and Europe. RNA interference (RNAi) technology is being developed as a novel method for pest management. Here, we identified the ALB core RNAi genes including those coding for Dicer, Argonaute, and double-stranded RNA-binding proteins (dsRBP) as well as for proteins involved in dsRNA transport and the systemic RNAi. We also compared expression of six potential reference genes that could be used to normalize gene expression and selected gapdh and rpl32 as the most reliable genes among different tissues and stages of ALB. Injection of double-stranded RNA (dsRNA) targeting gene coding for inhibitor of apoptosis (IAP) into larvae and adults resulted in a significant knockdown of this gene and caused the death of 90% of the larvae and 100% of adults. No mortality of both larvae and adults injected with dsRNA targeting gene coding for green fluorescence protein (GFP, as a negative control) was observed. These data suggest that functional RNAi machinery exists in ALB and a potential RNAi-based method could be developed for controlling this insect.
Cognitive fatigue in individuals with traumatic brain injury is associated with caudate activation
Authors: Wylie G. R. , Dobryakova E. , DeLuca J. , Chiaravalloti N. , Essad K. , Genova H.
Published: August 2017

We investigated differences in brain activation associated with cognitive fatigue between persons with traumatic brain injury (TBI) and healthy controls (HCs). Twenty-two participants with moderate-severe TBI and 20 HCs performed four blocks of a difficult working memory task and four blocks of a control task during fMRI imaging. Cognitive fatigue, assessed before and after each block, was used as a covariate to assess fatigue-related brain activation. The TBI group reported more fatigue than the HCs, though their performance was comparable. Regarding brain activation, the TBI group showed a Task X Fatigue interaction in the caudate tail resulting from a positive correlation between fatigue and brain activation for the difficult task and a negative relationship for the control task. The HC group showed the same Task X Fatigue interaction in the caudate head. Because we had prior hypotheses about the caudate, we performed a confirmatory analysis of a separate dataset in which the same subjects performed a processing speed task. A relationship between Fatigue and brain activation was evident in the caudate for this task as well. These results underscore the importance of the caudate nucleus in relation to cognitive fatigue.
Ecological effects of full and partial protection in the crowded Mediterranean Sea: a regional meta-analysis
Authors: Giakoumi Sylvaine , Scianna Claudia , Plass-Johnson Jeremiah , Micheli Fiorenza , Grorud-Colvert Kirsten , Thiriet Pierre , Claudet Joachim , Di Carlo Giuseppe , Di Franco Antonio , Gaines Steven D. , García-Charton José A. , Lubchenco Jane , Reimer Jessica , Sala Enric , Guidetti Paolo
Published: August 2017

Marine protected areas (MPAs) are a cornerstone of marine conservation. Globally, the number and coverage of MPAs are increasing, but MPA implementation lags in many human-dominated regions. In areas with intense competition for space and resources, evaluation of the effects of MPAs is crucial to inform decisions. In the human-dominated Mediterranean Sea, fully protected areas occupy only 0.04% of its surface. We evaluated the impacts of full and partial protection on biomass and density of fish assemblages, some commercially important fishes, and sea urchins in 24 Mediterranean MPAs. We explored the relationships between the level of protection and MPA size, age, and enforcement. Results revealed significant positive effects of protection for fisheries target species and negative effects for urchins as their predators benefited from protection. Full protection provided stronger effects than partial protection. Benefits of full protection for fish biomass were only correlated with the level of MPA enforcement; fish density was higher in older, better enforced, and —interestingly— smaller MPAs. Our finding that even small, well-enforced, fully protected areas can have significant ecological effects is encouraging for “crowded” marine environments. However, more data are needed to evaluate sufficient MPA sizes for protecting populations of species with varying mobility levels.
Expansion of C9ORF72 in amyotrophic lateral sclerosis correlates with brain-computer interface performance
Authors: Geronimo Andrew , Sheldon Kathryn E. , Broach James R. , Simmons Zachary , Schiff Steven J.
Published: August 2017

Abnormal expansion of hexanucleotide GGGGCC (G4C2) in the C9ORF72 gene has been associated with multiple neurodegenerative disorders, with particularly high prevalence in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Repeat expansions of this type have been associated with altered pathology, symptom rate and severity, as well as psychological changes. In this study, we enrolled twenty-five patients with ALS and fifteen neurologically healthy controls in a P300 brain-computer interface (BCI) training procedure. Four of the patients were found to possess an expanded allele, which was associated with a reduction in the quality of evoked potentials that led to reduced performance on the BCI task. Our findings warrant further exploration of the relationship between brain function and G4C2 repeat length. Such a relationship suggests that personalized assessment of suitability of BCI as a communication device in patients with ALS may be feasible.
Octacosanol restores stress-affected sleep in mice by alleviating stress
Authors: Kaushik Mahesh K. , Aritake Kosuke , Takeuchi Atsuko , Yanagisawa Masashi , Urade Yoshihiro
Published: August 2017

Octacosanol, a component of various food materials, possesses prominent biological activities and functions. It fights against cellular stress by increasing glutathione level and thus scavenging oxygen reactive species. However, its anti-stress activity and role in sleep induction remained elusive. We hypothesize that octacosanol can restore stress-affected sleep by mitigating stress. Cage change strategy was used to induce mild stress and sleep disturbance in mice, and effects of octacosanol administration on amount of sleep and stress were investigated. Results showed that octacosanol did not change rapid eye movement (REM) or non-REM (NREM) sleep compared to vehicle in normal mice. However, in cage change experiment, octacosanol induces significant increase in NREM sleep at doses of 100 and 200 mg/kg (75.7 ± 14.9 and 82.7 ± 9.3 min/5 h) compared to vehicle (21.2 ± 5.1 min/5 h), and decreased sleep latency. Octacosanol induced sleep by increasing number of sleep episodes and decreasing wake episode duration. Plasma corticosterone levels were significantly reduced after octacosanol (200 mg/kg) administration, suggesting a decrease in stress level. Octacosanol-induced changes in sleep-wake parameters in stressed-mice were comparable to the values in normal mice. Together, these data clearly showed that, though octacosanol does not alter normal sleep, it clearly alleviates stress and restore stress-affected sleep.
Polymer encapsulated microcavity optomechanical magnetometer
Authors: Zhu Jiangang , Zhao Guangming , Savukov Igor , Yang Lan
Published: August 2017

We demonstrate a magnetometer using polymer encapsulated whispering-gallery-mode microcavity actuated by a micro-magnet. The magnetic field induces force on the micro-magnet causing deformation in the polymer around the microcavity. Subsequently the microcavity detects the change in the refractive index of the polymer resulted from the deformation. This magnetometer works in the frequency range of hertz-to-kilohertz range and achieves a sensitivity of 880 pT/Hz1/2 at 200 Hz in a micro-scale sensor volume. Polymer encapsulation of the magnetometer and fiber optical connection ensures environmental robustness and practicality of the sensor.
Chilling temperature remodels phospholipidome of Zea mays seeds during imbibition
Authors: Noblet Agathe , Leymarie Juliette , Bailly Christophe
Published: August 2017

Global warming is a major agricultural issue in the Northern hemisphere where higher temperatures are expected to be associated with restricted water availability. In Europe, for maize, earlier and further northward sowings are forecasted in order to avoid water deficit periods in the crop life cycle. However these conditions may compromise seed germination and stand establishment since they will take place at cold temperatures. It is urgent to better understand the molecular bases of response of germinating maize seeds to cold in order to design genotypes adapted to these novel agricultural practices. Here we have performed a global phospholipidomic study to profile changes in membrane reorganisation during seed imbibition at 10 °C of cold-tolerant and -sensitive maize hybrids. Using a Multiple Reaction Monitoring (MRM-MS/MS) method coupled with HPLC we have identified 80 distinct phospholipids. We show that seed sensitivity to cold temperatures during imbibition relies on the accumulation of saturated or poorly unsaturated fatty acids, whatever the phospholipid class. In contrast seeds of cold-tolerant hybrid accumulated polyunsaturated chains which was associated with lower electrolyte leakage during imbibition at 10 °C. The expression of fatty acid desaturase genes provides a molecular model of maize seed sensitivity to imbibitional chilling damage.
T cell specific Cxcr5 deficiency prevents rheumatoid arthritis
Authors: Moschovakis Georgios L. , Bubke Anja , Friedrichsen Michaela , Falk Christine S. , Feederle Regina , Förster Reinhold
Published: August 2017

The chemokine receptor CXCR5 is primarily expressed on B cells and Tfh cells and facilitates their migration towards B cell follicles. In the present study we investigated the role of the CXCL13/CXCR5 axis in the pathogenesis of rheumatoid arthritis (RA) and specifically addressed the impact of CXCR5-mediated T and B cell migration in this disease. Employing collagen-induced arthritis (CIA) we identify CXCR5 as an absolutely essential factor for the induction of inflammatory autoimmune arthritis. Cxcr5-deficient mice and mice selectively lacking Cxcr5 on T cells were completely resistant to CIA, showed impaired germinal center responses and failed to mount an IgG1 antibody response to collagen II. Selective ablation of CXCR5 expression in B cells also led to suppression of CIA owing to diminished GC responses in secondary lymphoid organs (SLO) and impaired anti-collagen II antibody production. Chimeric mice harboring Cxcr5-proficient and Cxcr5-deficient immune cells revealed SLO and not the synovial tissue as the compartment where CXCR5-mediated cell migration induces autoimmune inflammation in arthritis. Thus our data demonstrate that CXCR5-mediated co-localization of Tfh cells and B cells in SLOs is absolutely essential for the induction of RA and identify CXCR5 and Tfh cells as promising therapeutic targets for the treatment of RA.
Structural stability and mechanism of compression of stoichiometric B13C2 up to 68GPa
Authors: Chuvashova Irina , Bykova Elena , Bykov Maxim , Svitlyk Volodymyr , Dubrovinsky Leonid , Dubrovinskaia Natalia
Published: August 2017

Boron carbide is a ceramic material with unique properties widely used in numerous, including armor, applications. Its mechanical properties, mechanism of compression, and limits of stability are of both scientific and practical value. Here, we report the behavior of the stoichiometric boron carbide B13C2 studied on single crystals up to 68 GPa. As revealed by synchrotron X-ray diffraction, B13C2 maintains its crystal structure and does not undergo phase transitions. Accurate measurements of the unit cell and B12 icosahedra volumes as a function of pressure led to conclusion that they reduce similarly upon compression that is typical for covalently bonded solids. A comparison of the compressional behavior of B13C2 with that of α–B, γ–B, and B4C showed that it is determined by the types of bonding involved in the course of compression. Neither ‘molecular-like’ nor ‘inversed molecular-like’ solid behavior upon compression was detected that closes a long-standing scientific dispute.
Low-dose tamoxifen treatment in juvenile males has long-term adverse effects on the reproductive system: implications for inducible transgenics
Authors: Patel Saloni H. , O’Hara Laura , Atanassova Nina , Smith Sarah E. , Curley Michael K. , Rebourcet Diane , Darbey Annalucia L. , Gannon Anne-Louise , Sharpe Richard M. , Smith Lee B.
Published: August 2017

The tamoxifen-inducible Cre system is a popular transgenic method for controlling the induction of recombination by Cre at a specific time and in a specific cell type. However, tamoxifen is not an inert inducer of recombination, but an established endocrine disruptor with mixed agonist/antagonist activity acting via endogenous estrogen receptors. Such potentially confounding effects should be controlled for, but >40% of publications that have used tamoxifen to generate conditional knockouts have not reported even the minimum appropriate controls. To highlight the importance of this issue, the present study investigated the long-term impacts of different doses of a single systemic tamoxifen injection on the testis and the wider endocrine system. We found that a single dose of tamoxifen less than 10% of the mean dose used for recombination induction, caused adverse effects to the testis and to the reproductive endocrine system that persisted long-term. These data raise significant concerns about the widespread use of tamoxifen induction of recombination, and highlight the importance of including appropriate controls in all pathophysiological studies using this means of induction.
Contributions of relative linear growth and adiposity accretion from birth to adulthood to adult hypertension
Authors: Ferraro Alexandre Archanjo , Barbieri Marco Antônio , da Silva Antonio Augusto Moura , Grandi Carlos , Cardoso Viviane Cunha , Stein Aryeh D. , Bettiol Heloisa
Published: August 2017

While birth weight and weight gain have been associated with hypertension (HT), the association of linear growth, independently of weight gains, has been less well studied. We assessed the independent association of body mass index (BMI) and length at birth and changes in BMI and height during the first two decades of life with adult blood pressure (BP). A birth cohort (n = 1141) was assembled in 1978–79, and followed up at school-age and adulthood. We used conditional length and BMI measures. BMI at birth was inversely associated with HT; c-BMI from school age to adulthood and c-height from birth to school age were positively associated with hypertension. Early adiposity accretion from birth to 9 years and late linear growth from 9 to 24 years were not associated with increased HT. Regarding BP, systolic and diastolic BP presented similar partterns: the lower the BMI at birth the higher the adult BP; the higher the BMI gains in the first 2 decades of life the higher the adult BP; linear accretion only in the first decade of life was associated with adult BP. Linear growth in the first decade of life and fat accretion in the second decade are associated with adults HT.
Immune system deregulation in hypertensive patients chronically RAS suppressed developing albuminuria
Authors: Martin-Lorenzo Marta , Gonzalez-Calero Laura , Martinez Paula J. , Baldan-Martin Montserrat , Lopez Juan Antonio , Ruiz-Hurtado Gema , de la Cuesta Fernando , Segura Julián , Vazquez Jesús , Vivanco Fernando , Barderas Maria G. , Ruilope Luis M. , Alvarez-Llamas Gloria
Published: August 2017

Albuminuria development in hypertensive patients is an indicator of higher cardiovascular (CV) risk and renal damage. Chronic renin-angiotensin system (RAS) suppression facilitates blood pressure control but it does not prevent from albuminuria development. We pursued the identification of protein indicators in urine behind albuminuria development in hypertensive patients under RAS suppression. Urine was collected from 100 patients classified in three groups according to albuminuria development: (a) patients with persistent normoalbuminuria; (b) patients developing de novo albuminuria; (c) patients with maintained albuminuria. Quantitative analysis was performed in a first discovery cohort by isobaric labeling methodology. Alterations of proteins of interest were confirmed by target mass spectrometry analysis in an independent cohort. A total of 2416 proteins and 1223 functional categories (coordinated protein responses) were identified. Immune response, adhesion of immune and blood cells, and phagocytosis were found significantly altered in patients with albuminuria compared to normoalbuminuric individuals. The complement system C3 increases, while Annexin A1, CD44, S100A8 and S100A9 proteins showed significant diminishment in their urinary levels when albuminuria is present. This study reveals specific links between immune response and controlled hypertension in patients who develop albuminuria, pointing to potential protein targets for novel and future therapeutic interventions.
Theoretical and NMR-based Conformational Analysis of Phosphodiester-linked Disaccharides
Authors: Gerbst Alexey G. , Nikolaev Andrei V. , Yashunsky Dmitry V. , Shashkov Alexander S. , Dmitrenok Andrey S. , Nifantiev Nikolay E.
Published: August 2017

The conformational behaviour of three phosphate-bridged dimannosides was studied by means of NMR and computational molecular modelling. First, the conformations of the phosphodiester linker were determined by quantum chemistry methods using dimethyl phosphate as a model. Then, a series of conformations was constructed for each of the studied molecules. Preliminary molecular dynamics (MD) simulations revealed that the inclusion of a cation had a drastic influence on the obtained results. Additionally, triethylammonium had the same effect as sodium as the counter-ion. After that, another series of MD simulations was run. The resulting MD trajectories were used to define the conformations responsible for the observed nuclear Overhauser effects and inter-nuclear coupling.
Histological Evaluation of Diabetic Neurodegeneration in the Retina of Zucker Diabetic Fatty (ZDF) Rats
Authors: Szabó Klaudia , Énzsöly Anna , Dékány Bulcsú , Szabó Arnold , Hajdú Rozina I. , Radovits Tamás , Mátyás Csaba , Oláh Attila , Laurik Lenke K. , Somfai Gábor M. , Merkely Béla , Szél Ágoston , Lukáts Ákos
Published: August 2017

In diabetes, retinal dysfunctions exist prior to clinically detectable vasculopathy, however the pathology behind these functional deficits is still not fully established. Previously, our group published a detailed study on the retinal histopathology of type 1 diabetic (T1D) rat model, where specific alterations were detected. Although the majority of human diabetic patients have type 2 diabetes (T2D), similar studies on T2D models are practically absent. To fill this gap, we examined Zucker Diabetic Fatty (ZDF) rats - a model for T2D - by immunohistochemistry at the age of 32 weeks. Glial reactivity was observed in all diabetic specimens, accompanied by an increase in the number of microglia cells. Prominent outer segment degeneration was detectable with changes in cone opsin expression pattern, without a decrease in the number of labelled elements. The immunoreactivity of AII amacrine cells was markedly decreased and changes were detectable in the number and staining of some other amacrine cell subtypes, while most other cells examined did not show any major alterations. Overall, the retinal histology of ZDF rats shows a surprising similarity to T1D rats indicating that despite the different evolution of the disease, the neuroretinal cells affected are the same in both subtypes of diabetes.