bluuebunny/crossref_metadata_2025 huggingface dataset:
SATB2/β-catenin/TCF-LEF pathway induces cellular transformation by generating cancer stem cells in colorectal cancer
Authors: Yu Wei , Ma Yiming , Shankar Sharmila , Srivastava Rakesh K.
Published: September 2017

Recent studies have demonstrated the involvement of colorectal cancer (CRC) stem cells (CSC) in transformation, cancer progression and metastasis. The main goal of this paper was to examine the molecular mechanisms by which SATB2 induced malignant transformation of colorectal epithelial cells. SATB2 induced malignant transformation and these transformed cells gained the characteristics of CSCs by expressing stem cell markers (CD44, CD133, LGR5 and DCLK1) and transcription factors (c-Myc, Nanog and Sox2). Overexpression of SATB2 in normal colorectal epithelial cells increased cell motility, migration and invasion, which were associated with an increase in N-cadherin and Zeb1, and decrease in E-cadherin expression. SATB2 overexpression also upregulated XIAP and cyclin D1, suggesting its role in cell survival and cell cycle. Furthermore, the expression of SATB2 was positively correlated with β-catenin expression in CRC. In contrary, depletion of SATB2 inhibited cell proliferation, colony formation, cell motility and expression of β-catenin, Snail, Slug, Zeb1 and N-cadherin, and upregulated E-cadherin. Furthermore, SATB2 silencing inhibited the expression of stem cell markers, pluripotency maintaining transcription factors, cell cycle and cell proliferation/survival genes and TCF/LEF targets. Finally, β-catenin/TCF-LEF pathway mediated the biological effects of SATB2 in CSCs. These studies support the role of SATB2/β-catenin/TCF-LEF pathway in transformation and carcinogenesis.
Hyaluronic acid based extracellular matrix regulates surface expression of GluN2B containing NMDA receptors
Authors: Schweitzer Barbara , Singh Jeet , Fejtova Anna , Groc Laurent , Heine Martin , Frischknecht Renato
Published: September 2017

Cortical areas of the juvenile rodent brain display a high degree of structural and functional plasticity, which disappears later in development. Coincident with the decline of plasticity 1) the hyaluronic acid-based extracellular matrix (ECM) of the brain, which stabilizes synapses and neuronal circuit is formed and 2) N-methyl-D-aspartate subtype of ionotropic glutamate receptors (NMDARs) implied in synaptic plasticity switch from mainly GluN2B to GluN2A subunit-containing receptors. Here we tested the hypothesis that ECM influences the NMDAR subunit composition in dissociated neuronal cultures. Experimental removal of ECM using hyaluronidase induced an increase in surface expression of GluN2B. This was due to decreased endocytosis of surface GluNB-containing receptors. We further found a reduction in phosphorylation at Tyr1472, which negatively regulates their binding to the endocytotic AP2 complex. We propose that maturation of ECM could induce switch in NMDAR composition necessary for normal adult synaptic plasticity and that increased expression of GluN2B contributes to rejuvenation of plasticity after ECM removal in vivo.
LNA effects on DNA binding and conformation: from single strand to duplex and triplex structures
Authors: Pabon-Martinez Y. Vladimir , Xu You , Villa Alessandra , Lundin Karin E. , Geny Sylvain , Nguyen Chi-Hung , Pedersen Erik B. , Jørgensen Per T. , Wengel Jesper , Nilsson Lennart , Smith C. I. Edvard , Zain Rula
Published: September 2017

The anti-gene strategy is based on sequence-specific recognition of double-strand DNA by triplex forming (TFOs) or DNA strand invading oligonucleotides to modulate gene expression. To be efficient, the oligonucleotides (ONs) should target DNA selectively, with high affinity. Here we combined hybridization analysis and electrophoretic mobility shift assay with molecular dynamics (MD) simulations to better understand the underlying structural features of modified ONs in stabilizing duplex- and triplex structures. Particularly, we investigated the role played by the position and number of locked nucleic acid (LNA) substitutions in the ON when targeting a c-MYC or FXN (Frataxin) sequence. We found that LNA-containing single strand TFOs are conformationally pre-organized for major groove binding. Reduced content of LNA at consecutive positions at the 3′-end of a TFO destabilizes the triplex structure, whereas the presence of Twisted Intercalating Nucleic Acid (TINA) at the 3′-end of the TFO increases the rate and extent of triplex formation. A triplex-specific intercalating benzoquinoquinoxaline (BQQ) compound highly stabilizes LNA-containing triplex structures. Moreover, LNA-substitution in the duplex pyrimidine strand alters the double helix structure, affecting x-displacement, slide and twist favoring triplex formation through enhanced TFO major groove accommodation. Collectively, these findings should facilitate the design of potent anti-gene ONs.
A global Staphylococcus aureus proteome resource applied to the in vivo characterization of host-pathogen interactions
Authors: Michalik Stephan , Depke Maren , Murr Annette , Gesell Salazar Manuela , Kusebauch Ulrike , Sun Zhi , Meyer Tanja C. , Surmann Kristin , Pförtner Henrike , Hildebrandt Petra , Weiss Stefan , Palma Medina Laura Marcela , Gutjahr Melanie , Hammer Elke , Becher Dörte , Pribyl Thomas , Hammerschmidt Sven , Deutsch Eric W. , Bader Samuel L. , Hecker Michael , Moritz Robert L. , Mäder Ulrike , Völker Uwe , Schmidt Frank
Published: September 2017

Data-independent acquisition mass spectrometry promises higher performance in terms of quantification and reproducibility compared to data-dependent acquisition mass spectrometry methods. To enable high-accuracy quantification of Staphylococcus aureus proteins, we have developed a global ion library for data-independent acquisition approaches employing high-resolution time of flight or Orbitrap instruments for this human pathogen. We applied this ion library resource to investigate the time-resolved adaptation of S. aureus to the intracellular niche in human bronchial epithelial cells and in a murine pneumonia model. In epithelial cells, abundance changes for more than 400 S. aureus proteins were quantified, revealing, e.g., the precise temporal regulation of the SigB-dependent stress response and differential regulation of translation, fermentation, and amino acid biosynthesis. Using an in vivo murine pneumonia model, our data-independent acquisition quantification analysis revealed for the first time the in vivo proteome adaptation of S. aureus. From approximately 2.15 × 105 
S. aureus cells, 578 proteins were identified. Increased abundance of proteins required for oxidative stress response, amino acid biosynthesis, and fermentation together with decreased abundance of ribosomal proteins and nucleotide reductase NrdEF was observed in post-infection samples compared to the pre-infection state.
Insulin, glucagon and somatostatin stores in the pancreas of subjects with type-2 diabetes and their lean and obese non-diabetic controls
Authors: Henquin Jean-Claude , Ibrahim Majeed M. , Rahier Jacques
Published: September 2017

In type-2 diabetes, both insufficient insulin and excessive glucagon secretion contribute to hyperglycemia. We compared insulin, glucagon and somatostatin stores in pancreas obtained at autopsy of 20 lean and 19 obese non-diabetic (ND), and 18 type-2 diabetic (T2D) subjects. From concentrations and pancreas weight, total content of hormones was calculated. Insulin content was 35% lower in T2D than ND subjects (7.4 versus 11.3 mg), whereas glucagon content was similar (0.76 versus 0.81 mg). The higher ratio of glucagon/insulin contents in T2D was thus explained by the decrease in insulin. With increasing BMI of ND subjects, insulin and glucagon contents respectively tended to increase and decrease, resulting in a lower glucagon/insulin ratio in obesity. With aging, insulin and glucagon contents did not significantly change in ND subjects but declined in T2D subjects, without association with the duration of diabetes or type of treatment. The somatostatin content was lower in T2D than ND subjects (0.027 versus 0.038 mg), but ratios somatostatin/insulin and somatostatin/glucagon were not different. In conclusion, insulin stores are about 1/3 lower in T2D than ND subjects, whereas glucagon stores are unchanged. Abnormal secretion of each hormone in type-2 diabetes cannot be attributed to major alterations in their pancreatic reserves.
The intestinal phosphate transporter NaPi-IIb (Slc34a2) is required to protect bone during dietary phosphate restriction
Authors: Knöpfel Thomas , Pastor-Arroyo Eva M. , Schnitzbauer Udo , Kratschmar Denise V. , Odermatt Alex , Pellegrini Giovanni , Hernando Nati , Wagner Carsten A.
Published: September 2017

NaPi-IIb/Slc34a2 is a Na+-dependent phosphate transporter that accounts for the majority of active phosphate transport into intestinal epithelial cells. Its abundance is regulated by dietary phosphate, being high during dietary phosphate restriction. Intestinal ablation of NaPi-IIb in mice leads to increased fecal excretion of phosphate, which is compensated by enhanced renal reabsorption. Here we compared the adaptation to dietary phosphate of wild type (WT) and NaPi-IIb−/− mice. High phosphate diet (HPD) increased fecal and urinary excretion of phosphate in both groups, though NaPi-IIb−/− mice still showed lower urinary excretion than WT. In both genotypes low dietary phosphate (LDP) resulted in reduced fecal excretion and almost undetectable urinary excretion of phosphate. Consistently, the expression of renal cotransporters after prolonged LDP was similar in both groups. Plasma phosphate declined more rapidly in NaPi-IIb−/− mice upon LDP, though both genotypes had comparable levels of 1,25(OH)2vitamin D3, parathyroid hormone and fibroblast growth factor 23. Instead, NaPi-IIb−/− mice fed LDP had exacerbated hypercalciuria, higher urinary excretion of corticosterone and deoxypyridinoline, lower bone mineral density and higher number of osteoclasts. These data suggest that during dietary phosphate restriction NaPi-IIb-mediated intestinal absorption prevents excessive demineralization of bone as an alternative source of phosphate.
Neonicotinoids act like endocrine disrupting chemicals in newly-emerged bees and winter bees
Authors: Baines Danica , Wilton Emily , Pawluk Abbe , de Gorter Michael , Chomistek Nora
Published: September 2017

Accumulating evidence suggests that neonicotinoids may have long-term adverse effects on bee health, yet our understanding of how this could occur is incomplete. Pesticides can act as endocrine disrupting chemicals (EDCs) in animals providing characteristic multiphasic dose-response curves and non-lethal endpoints in toxicity studies. However, it is not known if neonicotinoids act as EDCs in bees. To address this issue, we performed oral acute and chronic toxicity studies including concentrations recorded in nectar and pollen, applying acetamiprid, clothianidin, imidacloprid, and thiamethoxam to bumble bees, honey bees and leafcutter bees, the three most common bee species managed for pollination. In acute toxicity studies, late-onset symptoms, such as ataxia, were recorded as non-lethal endpoints for all three bee species. Clothianidin and thiamethoxam produced biphasic dose-response curves for all three bee species. Clothianidin and thiamethoxam were extremely toxic to winter worker honey bees prior to brood production in spring, making this the most sensitive bee stage identified to date. Chronic exposure to field-realistic levels of neonicotinoids reduced bee survival and caused significant late-onset symptoms for all three bee species. Given these findings, neonicotinoid risk should be reevaluated to address the EDC-like behavior and the sensitivity of winter worker honey bees.
Thin zeolite laminates for rapid and energy-efficient carbon capture
Authors: Akhtar Farid , Ogunwumi Steven , Bergström Lennart
Published: September 2017

Thin, binder-less zeolite NaX laminates, with thicknesses ranging between 310 to 750 μm and widths exceeding 50 mm and biaxial tensile strength in excess of 3 MPa, were produced by pulsed current processing. The NaX laminates displayed a high CO2 adsorption capacity and high binary CO2-over-N2 and CO2-over-CH4 selectivity, suitable for CO2 capture from flue gas and upgrading of raw biogas. The thin laminates displayed a rapid CO2 uptake; NaX laminates with a thickness of 310 μm were saturated to 40% of their CO2 capacity within 24 seconds. The structured laminates of 310 μm thickness and 50 mm thickness would offer low pressure drop and efficient carbon capture performance in a laminate-based swing adsorption technology.
Evaluating strategies for reversing CRISPR-Cas9 gene drives
Authors: Vella Michael R. , Gunning Christian E. , Lloyd Alun L. , Gould Fred
Published: September 2017

A gene drive biases inheritance of a gene so that it increases in frequency within a population even when the gene confers no fitness benefit. There has been renewed interest in environmental releases of engineered gene drives due to recent proof of principle experiments with the CRISPR-Cas9 system as a drive mechanism. Release of modified organisms, however, is controversial, especially when the drive mechanism could theoretically alter all individuals of a species. Thus, it is desirable to have countermeasures to reverse a drive if a problem arises. Several genetic mechanisms for limiting or eliminating gene drives have been proposed and/or developed, including synthetic resistance, reversal drives, and immunizing reversal drives. While predictions about efficacy of these mechanisms have been optimistic, we lack detailed analyses of their expected dynamics. We develop a discrete time model for population genetics of a drive and proposed genetic countermeasures. Efficacy of drive reversal varies between countermeasures. For some parameter values, the model predicts unexpected behavior including polymorphic equilibria and oscillatory dynamics. The timing and number of released individuals containing a genetic countermeasure can substantially impact outcomes. The choice among countermeasures by researchers and regulators will depend on specific goals and population parameters of target populations.
Rapid synthesis and decoration of reduced graphene oxide with gold nanoparticles by thermostable peptides for memory device and photothermal applications
Authors: Otari Sachin V. , Kumar Manoj , Anwar Muhammad Zahid , Thorat Nanasaheb D. , Patel Sanjay K. S. , Lee Dongjin , Lee Jai Hyo , Lee Jung-Kul , Kang Yun Chan , Zhang Liaoyuan
Published: September 2017

This article presents novel, rapid, and environmentally benign synthesis method for one-step reduction and decoration of graphene oxide with gold nanoparticles (NAuNPs) by using thermostable antimicrobial nisin peptides to form a gold-nanoparticles-reduced graphene oxide (NAu-rGO) nanocomposite. The formed composite material was characterized by UV/Vis spectroscopy, X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, field emission scanning electron microscopy, and high-resolution transmission electron microscopy (HR-TEM). HR-TEM analysis revealed the formation of spherical AuNPs of 5–30 nm in size on reduced graphene oxide (rGO) nanosheets. A non-volatile-memory device was prepared based on a solution-processed ZnO thin-film transistor fabricated by inserting the NAu-rGO nanocomposite in the gate dielectric stack as a charge trapping medium. The transfer characteristic of the ZnO thin-film transistor memory device showed large clockwise hysteresis behaviour because of charge carrier trapping in the NAu-rGO nanocomposite. Under positive and negative bias conditions, clear positive and negative threshold voltage shifts occurred, which were attributed to charge carrier trapping and de-trapping in the ZnO/NAu-rGO/SiO2 structure. Also, the photothermal effect of the NAu-rGO nanocomposites on MCF7 breast cancer cells caused inhibition of ~80% cells after irradiation with infrared light (0.5 W cm−2) for 5 min.
The syntactic organization of pasta-eating and the structure of reach movements in the head-fixed mouse
Authors: Whishaw Ian Q. , Faraji Jamshid , Kuntz Jessica R. , Mirza Agha Behroo , Metz Gerlinde A. S. , Mohajerani Majid H.
Published: September 2017

Mice are adept in the use of their hands for activities such as feeding, which has led to their use in investigations of the neural basis of skilled-movements. We describe the syntactic organization of pasta-eating and the structure of hand movements used for pasta manipulation by the head-fixed mouse. An ethogram of mice consuming pieces of spaghetti reveals that they eat in bite/chew bouts. A bout begins with pasta lifted to the mouth and then manipulated with hand movements into a preferred orientation for biting. Manipulation involves many hand release-reach movements, each with a similar structure. A hand is advanced from a digit closed and flexed (collect) position to a digit extended and open position (overgrasp) and then to a digit closed and flexed (grasp) position. Reach distance, hand shaping, and grasp patterns featuring precision grasps or whole hand grasps are related. To bite, mice display hand preference and asymmetric grasps; one hand (guide grasp) directs food into the mouth and the other stabilizes the pasta for biting. When chewing after biting, the hands hold the pasta in a symmetric resting position. Pasta-eating is organized and features structured hand movements and so lends itself to the neural investigation of skilled-movements.
Direct comparison of performance of single nucleotide variant calling in human genome with alignment-based and assembly-based approaches
Authors: Wu Leihong , Yavas Gokhan , Hong Huixiao , Tong Weida , Xiao Wenming
Published: September 2017

Complementary to reference-based variant detection, recent studies revealed that many novel variants could be detected with de novo assembled genomes. To evaluate the effect of reads coverage and the accuracy of assembly-based variant calling, we simulated short reads containing more than 3 million of single nucleotide variants (SNVs) from the whole human genome and compared the efficiency of SNV calling between the assembly-based and alignment-based calling approaches. We assessed the quality of the assembled contig and found that a minimum of 30X coverage of short reads was needed to ensure reliable SNV calling and to generate assembled contigs with a good coverage of genome and genes. In addition, we observed that the assembly-based approach had a much lower recall rate and precision comparing to the alignment-based approach that would recover 99% of imputed SNVs. We observed similar results with experimental reads for NA24385, an individual whose germline variants were well characterized. Although there are additional values for SNVs detection, the assembly-based approach would have great risk of false discovery of novel SNVs. Further improvement of de novo assembly algorithms are needed in order to warrant a good completeness of genome with haplotype resolved and high fidelity of assembled sequences.
Near-optimal integration of facial form and motion
Authors: Dobs Katharina , Ma Wei Ji , Reddy Leila
Published: September 2017

Human perception consists of the continuous integration of sensory cues pertaining to the same object. While it has been fairly well shown that humans use an optimal strategy when integrating low-level cues proportional to their relative reliability, the integration processes underlying high-level perception are much less understood. Here we investigate cue integration in a complex high-level perceptual system, the human face processing system. We tested cue integration of facial form and motion in an identity categorization task and found that an optimal model could successfully predict subjects’ identity choices. Our results suggest that optimal cue integration may be implemented across different levels of the visual processing hierarchy.
The Role of High Frequency Ultrasonography in Diagnosis of Acute Closed Mallet Finger Injury
Authors: Wang Tiezheng , Qi Hengtao , Teng Jianbo , Wang Zengtao , Zhao Bin
Published: September 2017

To evaluate the role of high frequency ultrasonography in diagnosis of acute closed mallet finger injury. 36 patients diagnosed with mallet finger were included in this study. All patients underwent ultrasonography, magnetic resonance imaging(MRI) and X-ray examinations. A new kind of classification of acute mallet finger injury based on ultrasonography findings was described. The difference in terms of extensor tendon injury and bony fragment identification ability among the three types of examinations were described respectively. Either an injury of extensor digital tendon or an avulsion fracture of distal phalangeal base was identified clearly on ultrasonography. Among the 36 cases, avulsion fracture of the distal phalangeal base was found without extensor tendon rupture in Type A, complete rupture of the extensor tendon was found without avulsion fracture in Type B, and contusion of the extensor tendon was found in Type C. Compared with X-ray, ultrasonography and MRI could show the extensor tendon injury clearly. While compared with MRI, ultrasonography and X-ray was more sensitive in showing bony fragment. High frequency ultrasonography could be an accurate, reliable, and non-invasive diagnostic imaging method in diagnosis of acute close mallet finger injury.
The network of plants volatile organic compounds
Authors: Vivaldo Gianna , Masi Elisa , Taiti Cosimo , Caldarelli Guido , Mancuso Stefano
Published: September 2017

Plants emission of Volatile Organic Compounds (VOCs) is involved in a wide class of ecological functions, as VOCs play a crucial role in plants interactions with biotic and abiotic factors. Accordingly, they vary widely across species and underpin differences in ecological strategy. In this paper, VOCs spontaneously emitted by 109 plant species (belonging to 56 different families) have been qualitatively and quantitatively analysed in order to provide an alternative classification of plants species. In particular, by using bipartite networks methodology from Complex Network Theory, and through the application of community detection algorithms, we show that is possible to classify species according to chemical classes such as terpenes and sulfur compounds. Such complex network analysis allows to uncover hidden plants relationships related to their evolutionary and adaptation to the environment story.
Hardware emulation of stochastic p-bits for invertible logic
Authors: Pervaiz Ahmed Zeeshan , Ghantasala Lakshmi Anirudh , Camsari Kerem Yunus , Datta Supriyo
Published: September 2017

The common feature of nearly all logic and memory devices is that they make use of stable units to represent 0’s and 1’s. A completely different paradigm is based on three-terminal stochastic units which could be called “p-bits”, where the output is a random telegraphic signal continuously fluctuating between 0 and 1 with a tunable mean. p-bits can be interconnected to receive weighted contributions from others in a network, and these weighted contributions can be chosen to not only solve problems of optimization and inference but also to implement precise Boolean functions in an inverted mode. This inverted operation of Boolean gates is particularly striking: They provide inputs consistent to a given output along with unique outputs to a given set of inputs. The existing demonstrations of accurate invertible logic are intriguing, but will these striking properties observed in computer simulations carry over to hardware implementations? This paper uses individual micro controllers to emulate p-bits, and we present results for a 4-bit ripple carry adder with 48 p-bits and a 4-bit multiplier with 46 p-bits working in inverted mode as a factorizer. Our results constitute a first step towards implementing p-bits with nano devices, like stochastic Magnetic Tunnel Junctions.
On the consistency of seismically imaged lower mantle slabs
Authors: Shephard G. E. , Matthews K. J. , Hosseini K. , Domeier M.
Published: September 2017

The geoscience community is increasingly utilizing seismic tomography to interpret mantle heterogeneity and its links to past tectonic and geodynamic processes. To assess the robustness and distribution of positive seismic anomalies, inferred as subducted slabs, we create a set of vote maps for the lower mantle with 14 global P-wave or S-wave tomography models. Based on a depth-dependent threshold metric, an average of 20% of any given tomography model depth is identified as a potential slab. However, upon combining the 14 models, the most consistent positive wavespeed features are identified by an increasing vote count. An overall peak in the most robust anomalies is found between 1000–1400 km depth, followed by a decline to a minimum around 2000 km. While this trend could reflect reduced tomographic resolution in the middle mantle, we show that it may alternatively relate to real changes in the time-dependent subduction flux and/or a mid-lower mantle viscosity increase. An apparent secondary peak in agreement below 2500 km depth may reflect the degree-two lower mantle slow seismic structures. Vote maps illustrate the potential shortcomings of using a limited number or type of tomography models and slab threshold criteria.
Noble UV protective agent for Bacillus thuringiensis based on a combination of graphene oxide and olive oil
Authors: Maghsoudi Shahab , Jalali Elham
Published: September 2017

The focus of this study is investigating the performance of graphene oxide (GO) in the protective effect of olive oil on Bacillus thuringiensis (Bt) after being exposed to UV radiations. Biological pesticides Bt subsp. Kurstaki is one of the most important biological control agents. We compared the protective effect of two UV protectant; GO and olive oil and also the combination of both, on the stability of the formulation of Bt after exposure to UV radiations. Spore viability was measured for protective effect and bioassay test was performed on the formulations of Bt. The combination of GO and olive oil revealed the highest viabilities of 50.62% after 96 h exposure to UV radiation, while viabilities of free spore, olive oil formulation and GO formulation were 32.54%, 37.19%,and 45.20%, respectively. The mortality of irradiated combination formulation on second-instar larvae Ephestia Kuehniella was 68.89%, while the same parameter for free spore, olive oil formulation and GO formulation were 40%, 46.66%,and 56%, respectively.
Linking primary producer diversity and food quality effects on herbivores: A biochemical perspective
Authors: Marzetz Vanessa , Koussoroplis Apostolos-Manuel , Martin-Creuzburg Dominik , Striebel Maren , Wacker Alexander
Published: September 2017

Biodiversity can strongly influence trophic interactions. The nutritional quality of prey communities and how it is related to the prey diversity is suspected to be a major driver of biodiversity effects. As consumer growth can be co-limited by the supply of several biochemical components, biochemically diverse prey communities should promote consumer growth. Yet, there is no clear consensus on how prey specific diversity is linked to community biochemical diversity since previous studies have considered only single nutritional quality traits. Here, we demonstrate that phytoplankton biochemical traits (fatty acids and sterols) can to a large extent explain Daphnia magna growth and its apparent dependence on phytoplankton species diversity. We find strong correlative evidence between phytoplankton species diversity, biochemical diversity, and growth. The relationship between species diversity and growth was partially explained by the fact that in many communities Daphnia was co-limited by long chained polyunsaturated fatty acids and sterols, which was driven by different prey taxa. We suggest that biochemical diversity is a good proxy for the presence of high food quality taxa, and a careful consideration of the distribution of the different biochemical traits among species is necessary before concluding about causal links between species diversity and consumer performance.
Phylogeographic studies of schizothoracine fishes on the central Qinghai-Tibet Plateau reveal the highest known glacial microrefugia
Authors: Liang Yangyang , He Dekui , Jia Yintao , Sun Heying , Chen Yifeng
Published: September 2017

Pleistocene climatic oscillations have greatly influenced the evolutionary history and distribution pattern of most extant species. However, their effects on species on the Qinghai-Tibet Plateau (QTP) are not well understood. To investigate the effects of past climatic shifts, particularly the Last Glacial Maximum (LGM), on plateau fish, we analysed the phylogeographic structure and demographic history of five closely related taxa of the subfamily Schizothoracinae, a representative endemic taxon of the QTP, from nine endorheic lakes on the central QTP and three peripheral exorheic rivers using the mitochondrial control region (D-loop) sequence and 12 microsatellite (SSR) markers. Phylogram from D-loop haplotypes revealed two well-supported lineages (North and South) separated by the Tanggula Mountains. The results from the D-loop and SSR revealed that endorheic populations possess high genetic diversity and a unique genetic structure. The most recent demographic expansion occurred post-LGM for most endorheic populations and in the last interglacial period for Siling Co and all exorheic populations. Phylogeographic structure, together with species distribution modelling, supports the scenario of multiple glacial refugia on the QTP during the LGM and suggests that Siling Co (4540 m asl) is a cryptic glacial microrefugia for plateau fish, which would be the highest glacial microrefugia known.
Responses of plant species diversity and soil physical-chemical-microbial properties to Phragmites australis invasion along a density gradient
Authors: Uddin MD Nazim , Robinson Randall William
Published: September 2017

The invasion of ecosystems by strongly colonising plants such as Phragmites australis is viewed as one of the greatest threats to plant diversity and soil properties. This study compared a range of diversity measures including soil properties and mycorrhizal potential under different degrees of Phragmites density among three populations in coastal wetland, Victoria, Australia. Species richness, evenness and Shanon-Wiener index had significantly higher values in low degree of Phragmites density in all populations. Higher densities had the lowest diversity, with Shannon-Wiener index = 0 and Simpson’s index = 1 indicating its mono-specificity. Significant alterations in soil properties associated with different degrees of Phragmites density were noticed. These had interactive effects (population × density) on water content, dehydrogenase activity, microbial biomass (C, N and P) but not on pH, electrical conductivity, phenolics, organic carbon, and spore density. Furthermore, the study elucidated decrease of competitive abilities of native plants, by interfering with formation of mycorrhizal associations and biomass. Overall, our results suggest that significant ecological alterations in vegetation and soil variables (including mycorrhizal potential) were strongly dependent on Phragmites density. Such changes may lead to an important role in process of Phragmites invasion through disruption of functional relationships amongst those variables.
Glycosylation-dependent galectin-1/neuropilin-1 interactions promote liver fibrosis through activation of TGF-β- and PDGF-like signals in hepatic stellate cells
Authors: Wu Ming-Heng , Chen Yuh-Ling , Lee Kuen-Haur , Chang Che-Chang , Cheng Tsai-Mu , Wu Szu-Yuan , Tu Chao-Chiang , Tsui Wan-Lin
Published: September 2017

Concomitant expressions of glycan-binding proteins and their bound glycans regulate many pathophysiologic processes, but this issue has not been addressed in liver fibrosis. Activation of hepatic stellate cells (HSCs) is a rate-limiting step in liver fibrosis and is an important target for liver fibrosis therapy. We previously reported that galectin (Gal)-1, a β-galactoside-binding protein, regulates myofibroblast homeostasis in oral carcinoma and wound healing, but the role of Gal-1 in HSC migration and activation is unclear. Herein, we report that Gal-1 and its bound glycans were highly expressed in fibrotic livers and activated HSCs. The cell-surface glycome of activated HSCs facilitated Gal-1 binding, which upon recognition of the N-glycans on neuropilin (NRP)-1, activated platelet-derived growth factor (PDGF)- and transforming growth factor (TGF)-β-like signals to promote HSC migration and activation. In addition, blocking endogenous Gal-1 expression suppressed PDGF- and TGF-β1-induced signaling, migration, and gene expression in HSCs. Methionine and choline-deficient diet (MCD)-induced collagen deposition and HSC activation were attenuated in Gal-1-null mice compared to wild-type mice. In summary, we concluded that glycosylation-dependent Gal-1/NRP-1 interactions activate TGF-β and PDGF-like signaling to promote the migration and activation of HSCs. Therefore, targeting Gal-1/NRP-1 interactions could be developed into liver fibrosis therapy.
Lattice light sheet imaging of membrane nanotubes between human breast cancer cells in culture and in brain metastases
Authors: Parker Ian , Evans Katrina T. , Ellefsen Kyle , Lawson Devon A. , Smith Ian F.
Published: September 2017

Membrane nanotubes are cytosolic protrusions with diameters <1 µm that extend between cells separated by tens of µm. They mediate several forms of intercellular communication and are upregulated in diverse diseases. Difficulties in visualizing and studying nanotubes within intact tissues have, however, prompted skepticism regarding their in vivo relevance, and most studies have been confined to cell culture systems. Here, we introduce lattice-light sheet imaging of MDA-MB-231 human breast cancer cells genetically engineered to brightly express membrane–targeted GFP as a promising approach to visualize membrane nanotubes in vitro and in situ. We demonstrate that cultured cells form multiple nanotubes that mediate intercellular communication of Ca2+ signals and actively traffic GFP-tagged membrane vesicles along their length. Furthermore, we directly visualize nanotubes in situ, interconnecting breast cancer cells in live acute brain slices from an experimental mouse model of breast cancer brain metastasis. This amenable experimental system should facilitate the transition of the study of intercellular communication by membrane nanotubes from cell culture to the whole animal.
The Chemical Form of Metal Species Released from Corroded Taper Junctions of Hip Implants: Synchrotron Analysis of Patient Tissue
Authors: Di Laura Anna , Quinn Paul D. , Panagiotopoulou Vasiliki C. , Hothi Harry S. , Henckel Johann , Powell Jonathan J. , Berisha Fitim , Amary Fernanda , Mosselmans J. Fred W. , Skinner John A. , Hart Alister J.
Published: September 2017

The mechanisms of metal release from the articulation at the head cup bearing and the tapered junctions of orthopaedic hip implants are known to differ and the debris generated varies in size, shape and volume. Significantly less metal is lost from the taper junction between Cobalt-Chromium-Molybdenum (CoCrMo) and Titanium (Ti) components (fretting-corrosion dominant mechanism), when compared to the CoCrMo bearing surfaces (wear-corrosion dominant mechanism). Corrosion particles from the taper junction can lead to Adverse Reactions to Metal Debris (ARMD) similar to those seen with CoCrMo bearings. We used synchrotron methods to understand the modes underlying clinically significant tissue reactions to Co, Cr and Ti by analysing viable peri-prosthetic tissue. Cr was present as Cr2O3 in the corroded group in addition to CrPO4 found in the metal-on-metal (MoM) group. Interestingly, Ti was present as TiO2 in an amorphous rather than rutile or anatase physical form. The metal species were co-localized in the same micron-scale particles as result of corrosion processes and in one cell type, the phagocytes. This work gives new insights into the degradation products from metal devices as well as guidance for toxicological studies in humans.
Stat3 as a potential therapeutic target for rheumatoid arthritis
Authors: Oike Takatsugu , Sato Yuiko , Kobayashi Tami , Miyamoto Kana , Nakamura Satoshi , Kaneko Yosuke , Kobayashi Shu , Harato Kengo , Saya Hideyuki , Matsumoto Morio , Nakamura Masaya , Niki Yasuo , Miyamoto Takeshi
Published: September 2017

Rheumatoid arthritis (RA) is a multi-factorial disease characterized by chronic inflammation and destruction of multiple joints. To date, various biologic treatments for RA such as anti-tumor necrosis factor alpha antibodies have been developed; however, mechanisms underlying RA development remain unclear and targeted therapy for this condition has not been established. Here, we provide evidence that signal transducer and activator of transcription 3 (Stat3) promotes inflammation and joint erosion in a mouse model of arthritis. Stat3 global KO mice show early embryonic lethality; thus, we generated viable Stat3 conditional knockout adult mice and found that they were significantly resistant to collagen-induced arthritis (CIA), the most common RA model, compared with controls. We then used anin vitroculture system to screen ninety-six existing drugs to select Stat3 inhibitors and selected five candidate inhibitors. Among them, three significantly inhibited development of arthritis and joint erosion in CIA wild-type mice. These findings suggest that Stat3 inhibitors may serve as promising drugs for RA therapy.
Signatures of the Kondo effect in VSe2
Authors: Barua Sourabh , Hatnean M. Ciomaga , Lees M. R. , Balakrishnan G.
Published: September 2017

VSe2 is a transition metal dichaclogenide which has a charge- density wave transition that has been well studied. We report on a low-temperature upturn in the resistivity and, at temperatures below this resistivity minimum, an unusual magnetoresistance which is negative at low fields and positive at higher fields, in single crystals of VSe2. The negative magnetoresistance has a parabolic dependence on the magnetic field and shows little angular dependence. The magnetoresistance at temperatures above the resistivity minimum is always positive. We interpret these results as signatures of the Kondo effect in VSe2. An upturn in the susceptibility indicates the presence of interlayer V ions which can provide the localized magnetic moments required for scattering the conduction electrons in the Kondo effect. The low-temperature behaviour of the heat capacity, including a high value of γ, along with a deviation from a Curie-Weiss law observed in the low-temperature magnetic susceptibility, are consistent with the presence of magnetic interactions between the paramagnetic interlayer V ions and a Kondo screening of these V moments.
Enhancement of extinction memory by pharmacological and behavioral interventions targeted to its reactivation
Authors: Haubrich Josué , Machado Adriano , Boos Flávia Zacouteguy , Crestani Ana P. , Sierra Rodrigo O. , Alvares Lucas de Oliveira , Quillfeldt Jorge A.
Published: September 2017

Extinction is a process that involves new learning that inhibits the expression of previously acquired memories. Although temporarily effective, extinction does not erase an original fear association. Since the extinction trace tends to fade over time, the original memory can resurge. On the other hand, strengthening effects have been described in several reconsolidation studies using different behavioral and pharmacological manipulations. In order to know whether an extinction memory can be strengthened by reactivation-based interventions in the contextual fear conditioning task, we began by replicating the classic phenomenon of spontaneous recovery to show that brief reexposure sessions can prevent the decay of the extinction trace over time in a long-lasting way. This fear attenuation was shown to depend both on L-type calcium channels and protein synthesis, which suggests a reconsolidation process behind the reactivation-induced strengthening effect. The extinction trace was also susceptible to enhancement by a post-reactivation infusion of a memory-enhancing drug (NaB), which was also able to prevent rapid fear reacquisition (savings). These findings point to new reactivation-based approaches able to strengthen an extinction memory to promote its persistence. The constructive interactions between extinction and reconsolidation may represent a promising novel approach in the realm of fear-related disorder treatments.
Transcription factors NRF2 and HSF1 have opposing functions in autophagy
Authors: Dayalan Naidu Sharadha , Dikovskaya Dina , Gaurilcikaite Egle , Knatko Elena V. , Healy Zachary R. , Mohan Hema , Koh Glenn , Laurell Axel , Ball Graeme , Olagnier David , de la Vega Laureano , Ganley Ian G. , Talalay Paul , Dinkova-Kostova Albena T.
Published: September 2017

Autophagy plays a critical role in the maintenance of cellular homeostasis by degrading proteins, lipids and organelles. Autophagy is activated in response to stress, but its regulation in the context of other stress response pathways, such as those mediated by heat shock factor 1 (HSF1) and nuclear factor-erythroid 2 p45-related factor 2 (NRF2), is not well understood. We found that the Michael acceptor bis(2-hydoxybenzylidene)acetone (HBB2), a dual activator of NRF2 and HSF1, protects against the development of UV irradiation-mediated cutaneous squamous cell carcinoma in mice. We further show that HBB2 is an inducer of autophagy. In cells, HBB2 increases the levels of the autophagy-cargo protein p62/sequestosome 1, and the lipidated form of microtubule-associated protein light chain 3 isoform B. Activation of autophagy by HBB2 is impaired in NRF2-deficient cells, which have reduced autophagic flux and low basal and induced levels of p62. Conversely, HSF1-deficient cells have increased autophagic flux under both basal as well as HBB2-induced conditions, accompanied by increased p62 levels. Our findings suggest that NRF2 and HSF1 have opposing roles during autophagy, and illustrate the existence of tight mechanistic links between the cellular stress responses.
Dramatically Enhanced Superconductivity in Elemental Bismuth from Excitonic Fluctuation Exchange
Authors: Koley S. , Laad M. S. , Taraphder A.
Published: September 2017

Motivated by the remarkable discovery of superconductivity in elemental Bismuth at ambient pressure, we study its normal state in detail using a combination of tight-binding (TB) band-structure supplemented by dynamical mean-field theory (DMFT). We show that a two-fluid model composed of preformed and dynamically fluctuating excitons coupled to a tiny number of carriers provides a unified rationalization of a range of ill-understood normal state spectral and transport data. Based on these, we propose that resonant scattering involving a very low density of renormalized carriers and the excitonic liquid drives logarithmic enhancement of vertex corrections, boosting superconductivity in Bi. A confirmatory test for our proposal would be the experimental verification of an excitonic semiconductor with electronic nematicity as a ‘competing order’ on inducing a semi-metal-to semiconductor transition in Bi by an external perturbation like pressure
Gene expression of NOX family members and their clinical significance in hepatocellular carcinoma
Authors: Eun Hyuk Soo , Cho Sang Yeon , Joo Jong Seok , Kang Sun Hyung , Moon Hee Seok , Lee Eaum Seok , Kim Seok Hyun , Lee Byung Seok
Published: September 2017

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex-derived reactive oxygen species (ROS) promote chronic liver inflammation and remodeling that can drive hepatocellular carcinoma development. The role of NOX expression in hepatocellular carcinoma (HCC) has been partially investigated; however, the clinical relevance of collective or individual NOX family member expression for HCC survival remains unclear. Here, we obtained NOX mRNA expression data for 377 HCC samples and 21 normal liver controls from the TCGA data portal and performed Kaplan-Meier survival, gene ontology functional enrichment, and gene set enrichment analyses. Although most NOX genes exhibited little change, some were significantly induced in HCC compared to that in normal controls. In addition, HCC survival analyses indicated better overall survival in patients with high NOX4 and DUOX1 expression, whereas patients with high NOX1/2/5 expression showed poor prognoses. Gene-neighbour and gene set enrichment analyses revealed that NOX1/2/5 were strongly correlated with genes associated with cancer cell survival and metastasis, whereas increased NOX4 and DUOX1 expression was associated with genes that inhibit tumour progression. On the basis of these data, NOX family gene expression analysis could be a predictor of survival and identify putative therapeutic targets in HCC.
Neuropilin-1 is upregulated by Wnt/β-catenin signaling and is important for mammary stem cells
Authors: Liu Wei , Wu Ting , Dong Xiaobing , Zeng Yi Arial
Published: September 2017

Wnt/β-catenin signaling is instrumental for the development of mammary gland and the properties of mammary stem cells (MaSCs). The Wnt signaling downstream effectors that engage in regulating MaSCs have not been extensively studied. Here, we report that Neuropilin-1 (Nrp1) expression is induced by Wnt/β-catenin signaling in MaSCs, and its function is critical for the activity of MaSCs. Nrp1 is particularly expressed in MaSCs that are marked by the expression of Protein C Receptor (Procr). Knockdown of Nrp1 by shRNA diminishes MaSCs’ in vitro colony formation and in vivo mammary gland reconstitution ability. Similar results are seen when antagonizing Nrp1 using a dominant negative peptide. In genetic experiments, deletion of Nrp1 results in delay of mammary development. In addition, knockdown of Nrp1 inhibits MMTV-Wnt1 tumor growth in xenograft. Our data demonstrate that Nrp1 is critical for mammary development and tumorigenesis, revealing new insights into MaSC regulation and targeting stem cells in treatment of breast cancer.
Selective uptake of epidermal growth factor-conjugated gold nanoparticle (EGF-GNP) facilitates non-thermal plasma (NTP)-mediated cell death
Authors: Kim Wanil , Na Kyung-Yoon , Lee Kyung-Ha , Lee Hyun Wook , Lee Jae Koo , Kim Kyong-Tai
Published: September 2017

Non-thermal atmospheric pressure plasma (NTP) has been shown to induce cell death in various mammalian cancer cells. Accumulated evidence also shows that NTP could be clinically used in cancer therapy. However, the current NTP-based applications lack target specificity. Here, a novel method in NTP-mediated cancer therapeutics was described with enhanced target specificity by treating EGF (epidermal growth factor)-conjugated GNP (gold nanoparticle). The treatment with EGF-conjugated GNP complex, followed by NTP irradiation showed selective apoptosis of cells having receptor-mediated endocytosis. NTP triggered γ–H2AX elevation which is a typical response elicited by DNA damage. These results suggest that EGF-conjugated GNP functions as an important adjuvant which gives target specificity in applications of conventional plasma therapy.