bluuebunny/crossref_metadata_2025 huggingface dataset:
PU.1/microRNA-142-3p targets ATG5/ATG16L1 to inactivate autophagy and sensitize hepatocellular carcinoma cells to sorafenib
Authors: Zhang Kai , Chen Jing , Zhou Hao , Chen Ying , Zhi Yingru , Zhang Bei , Chen Longbang , Chu Xiaoyuan , Wang Rui , Zhang Chunni
Published: February 2018

Sorafenib is currently the only systemic agent approved for treatment of advanced hepatocellular carcinoma (HCC). However, intrinsic and acquired resistance to sorafenib remains a great challenge with respect to improving the prognoses of patients with HCC. The cyto-protective functions of autophagy have been suggested as a potential mechanism by which chemoresistance or targeted drug resistance occurs in tumour cells. In the present study, miR-142-3p was identified as a novel autophagy-regulating microRNA (miRNA) that plays a vital role in sorafenib resistance in HCC cells. Gain- and loss-of-function assays revealed that ectopic miR-142-3p upregulation sensitized HCC cells to sorafenib by reducing sorafenib-induced autophagy, enhancing sorafenib-induced apoptosis and inhibiting cell growth, whereas miR-142-3p inhibition exerted contrasting effects. Bioinformatics analysis and luciferase reporter and rescue assays showed that autophagy-related 5 (ATG5) and autophagy-related 16-like 1 (ATG16L1) are potential targets through which miR-142-3p regulates autophagy inhibition. Furthermore, we verified that PU.1 regulated the expression of miR-142-3p in conjunction with our cellular experiments and the related results in the literature. Our findings show that targeting the PU.1–miR-142-3p–ATG5/ATG16L1 axis may be a useful therapeutic strategy for preventing cyto-protective autophagy to overcome sorafenib resistance.
Warm Arctic episodes linked with increased frequency of extreme winter weather in the United States
Authors: Cohen Judah , Pfeiffer Karl , Francis Jennifer A.
Published: February 2018

Recent boreal winters have exhibited a large-scale seesaw temperature pattern characterized by an unusually warm Arctic and cold continents. Whether there is any physical link between Arctic variability and Northern Hemisphere (NH) extreme weather is an active area of research. Using a recently developed index of severe winter weather, we show that the occurrence of severe winter weather in the United States is significantly related to anomalies in pan-Arctic geopotential heights and temperatures. As the Arctic transitions from a relatively cold state to a warmer one, the frequency of severe winter weather in mid-latitudes increases through the transition. However, this relationship is strongest in the eastern US and mixed to even opposite along the western US. We also show that during mid-winter to late-winter of recent decades, when the Arctic warming trend is greatest and extends into the upper troposphere and lower stratosphere, severe winter weather—including both cold spells and heavy snows—became more frequent in the eastern United States.
Single cell polarity in liquid phase facilitates tumour metastasis
Authors: Lorentzen Anna , Becker Paul F. , Kosla Jan , Saini Massimo , Weidele Kathrin , Ronchi Paolo , Klein Corinna , Wolf Monika J. , Geist Felix , Seubert Bastian , Ringelhan Marc , Mihic-Probst Daniela , Esser Knud , Roblek Marko , Kuehne Felix , Bianco Gaia , O’Connor Tracy , Müller Quentin , Schuck Kathleen , Lange Sebastian , Hartmann Daniel , Spaich Saskia , Groß Olaf , Utikal Jochen , Haferkamp Sebastian , Sprick Martin R. , Damle-Vartak Amruta , Hapfelmeier Alexander , Hüser Norbert , Protzer Ulrike , Trumpp Andreas , Saur Dieter , Vartak Nachiket , Klein Christoph A. , Polzer Bernhard , Borsig Lubor , Heikenwalder Mathias
Published: February 2018

Dynamic polarisation of tumour cells is essential for metastasis. While the role of polarisation during dedifferentiation and migration is well established, polarisation of metastasising tumour cells during phases of detachment has not been investigated. Here we identify and characterise a type of polarisation maintained by single cells in liquid phase termed single-cell (sc) polarity and investigate its role during metastasis. We demonstrate that sc polarity is an inherent feature of cells from different tumour entities that is observed in circulating tumour cells in patients. Functionally, we propose that the sc pole is directly involved in early attachment, thereby affecting adhesion, transmigration and metastasis. In vivo, the metastatic capacity of cell lines correlates with the extent of sc polarisation. By manipulating sc polarity regulators and by generic depolarisation, we show that sc polarity prior to migration affects transmigration and metastasis in vitro and in vivo.
Chloroquine modulates antitumor immune response by resetting tumor-associated macrophages toward M1 phenotype
Authors: Chen Degao , Xie Jing , Fiskesund Roland , Dong Wenqian , Liang Xiaoyu , Lv Jiadi , Jin Xun , Liu Jinyan , Mo Siqi , Zhang Tianzhen , Cheng Feiran , Zhou Yabo , Zhang Huafeng , Tang Ke , Ma Jingwei , Liu Yuying , Huang Bo
Published: February 2018

Resetting tumor-associated macrophages (TAMs) is a promising strategy to ameliorate the immunosuppressive tumor microenvironment and improve innate and adaptive antitumor immunity. Here we show that chloroquine (CQ), a proven anti-malarial drug, can function as an antitumor immune modulator that switches TAMs from M2 to tumor-killing M1 phenotype. Mechanistically, CQ increases macrophage lysosomal pH, causing Ca2+ release via the lysosomal Ca2+ channel mucolipin-1 (Mcoln1), which induces the activation of p38 and NF-κB, thus polarizing TAMs to M1 phenotype. In parallel, the released Ca2+ activates transcription factor EB (TFEB), which reprograms the metabolism of TAMs from oxidative phosphorylation to glycolysis. As a result, CQ-reset macrophages ameliorate tumor immune microenvironment by decreasing immunosuppressive infiltration of myeloid-derived suppressor cells and Treg cells, thus enhancing antitumor T-cell immunity. These data illuminate a previously unrecognized antitumor mechanism of CQ, suggesting a potential new macrophage-based tumor immunotherapeutic modality.
Characterizing the replicability of cell types defined by single cell RNA-sequencing data using MetaNeighbor
Authors: Crow Megan , Paul Anirban , Ballouz Sara , Huang Z. Josh , Gillis Jesse
Published: February 2018

Single-cell RNA-sequencing (scRNA-seq) technology provides a new avenue to discover and characterize cell types; however, the experiment-specific technical biases and analytic variability inherent to current pipelines may undermine its replicability. Meta-analysis is further hampered by the use of ad hoc naming conventions. Here we demonstrate our replication framework, MetaNeighbor, that quantifies the degree to which cell types replicate across datasets, and enables rapid identification of clusters with high similarity. We first measure the replicability of neuronal identity, comparing results across eight technically and biologically diverse datasets to define best practices for more complex assessments. We then apply this to novel interneuron subtypes, finding that 24/45 subtypes have evidence of replication, which enables the identification of robust candidate marker genes. Across tasks we find that large sets of variably expressed genes can identify replicable cell types with high accuracy, suggesting a general route forward for large-scale evaluation of scRNA-seq data.
Implication of liver enzymes on incident cardiovascular diseases and mortality: A nationwide population-based cohort study
Authors: Choi Kyung Mook , Han Kyungdo , Park Sanghyun , Chung Hye Soo , Kim Nam Hoon , Yoo Hye Jin , Seo Ji-A , Kim Sin Gon , Kim Nan Hee , Baik Sei Hyun , Park Yong Gyu , Kim Seon Mee
Published: February 2018

Although liver enzymes, such as γ-glutamyltransferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), have recently been suggested as risk factors for cardiovascular diseases (CVD), impact on mortality after myocardial infarction (MI) or ischemic stroke (IS) was not previously examined. Using a population-based, nationwide cohort database, we explored the implication of GGT and aminotransferases on the development of CVD and all-cause mortality during a median 9.1 years of follow-up. Among 16,624,006 Korean adults, both GGT and aminotransferases exhibited a positive relationship with MI, IS, and mortality in a multivariate adjusted model. ALT and AST showed U-shaped associations with mortality, whereas GGT showed a positive linear relationship with mortality. The risk of 1-year mortality after MI or IS was significantly higher in the highest quartile of GGT compared to the lowest quartile (HR, 1.46; 95% CI, 1.40-1.52). The implication of GGT on MI, IS, and mortality persisted regardless of traditional cardiovascular risk parameters. This study demonstrated the unique pattern of association of ALT, AST, and GGT with the development of CVD and all-cause mortality in the Korean population. In particular, GGT showed the most robust linear relationship with mortality before and after cardiovascular events independent of risk factors.
Simulated microgravity inhibits cell focal adhesions leading to reduced melanoma cell proliferation and metastasis via FAK/RhoA-regulated mTORC1 and AMPK pathways
Authors: Tan Xin , Xu Aizhang , Zhao Tuo , Zhao Qin , Zhang Jun , Fan Cuihong , Deng Yulin , Freywald Andrew , Genth Harald , Xiang Jim
Published: February 2018

Simulated microgravity (SMG) was reported to affect tumor cell proliferation and metastasis. However, the underlying mechanism is elusive. In this study, we demonstrate that clinostat-modelled SMG reduces BL6-10 melanoma cell proliferation, adhesion and invasiveness in vitro and decreases tumor lung metastasis in vivo. It down-regulates metastasis-related integrin α6β4, MMP9 and Met72 molecules. SMG significantly reduces formation of focal adhesions and activation of focal adhesion kinase (FAK) and Rho family proteins (RhoA, Rac1 and Cdc42) and of mTORC1 kinase, but activates AMPK and ULK1 kinases. We demonstrate that SMG inhibits NADH induction and glycolysis, but induces mitochondrial biogenesis. Interestingly, administration of a RhoA activator, the cytotoxic necrotizing factor-1 (CNF1) effectively converts SMG-triggered alterations and effects on mitochondria biogenesis or glycolysis. CNF1 also converts the SMG-altered cell proliferation and tumor metastasis. In contrast, mTORC inhibitor, rapamycin, produces opposite responses and mimics SMG-induced effects in cells at normal gravity. Taken together, our observations indicate that SMG inhibits focal adhesions, leading to inhibition of signaling FAK and RhoA, and the mTORC1 pathway, which results in activation of the AMPK pathway and reduced melanoma cell proliferation and metastasis. Overall, our findings shed a new light on effects of microgravity on cell biology and human health.
Disruption of the open conductance in the β-tongue mutants of Cytolysin A
Authors: Fahie Monifa A. , Liang Lucas , Avelino Alzira R. , Pham Bach , Limpikirati Patanachai , Vachet Richard W. , Chen Min
Published: February 2018

Cytolysin A (ClyA) is a water-soluble alpha pore-forming toxin that assembles to form an oligomeric pore on host cell membranes. The ClyA monomer possesses an α-helical bundle with a β-sheet subdomain (the β-tongue) previously believed to be critical for pore assembly and/or insertion. Oligomerization of ClyA pores transforms the β-tongue into a helix-turn-helix that embeds into the lipid bilayer. Here, we show that mutations of the β-tongue did not prevent oligomerization or transmembrane insertion. Instead, β-tongue substitution mutants yielded pores with decreased conductance while a deletion mutation resulted in pores that rapidly closed following membrane association. Our results suggest that the β-tongue may play an essential structural role in stabilizing the open conformation of the transmembrane domain.
The circadian regulator BMAL1 programmes responses to parasitic worm infection via a dendritic cell clock
Authors: Hopwood Thomas W. , Hall Sarah , Begley Nicola , Forman Ruth , Brown Sheila , Vonslow Ryan , Saer Ben , Little Matthew C. , Murphy Emma A. , Hurst Rebecca J. , Ray David W. , MacDonald Andrew S. , Brass Andy , Bechtold David A. , Gibbs Julie E. , Loudon Andrew S. , Else Kathryn J.
Published: February 2018

Resistance to the intestinal parasitic helminth Trichuris muris requires T-helper 2 (TH2) cellular and associated IgG1 responses, with expulsion typically taking up to 4 weeks in mice. Here, we show that the time-of-day of the initial infection affects efficiency of worm expulsion, with strong TH2 bias and early expulsion in morning-infected mice. Conversely, mice infected at the start of the night show delayed resistance to infection, and this is associated with feeding-driven metabolic cues, such that feeding restriction to the day-time in normally nocturnal-feeding mice disrupts parasitic expulsion kinetics. We deleted the circadian regulator BMAL1 in antigen-presenting dendritic cells (DCs) in vivo and found a loss of time-of-day dependency of helminth expulsion. RNAseq analyses revealed that IL-12 responses to worm antigen by circadian-synchronised DCs were dependent on BMAL1. Therefore, we find that circadian machinery in DCs contributes to the TH1/TH2 balance, and that environmental, or genetic perturbation of the DC clock results in altered parasite expulsion kinetics.
Stable N-doped & FeNi-decorated graphene non-precious electrocatalyst for Oxygen Reduction Reaction in Acid Medium
Authors: Barakat Nasser A. M. , El-Deen Ahmed G. , Ghouri Zafar Khan , Al-Meer Saeed
Published: February 2018

NiFe nanoparticles-decorated & N-doped graphene is introduced as an effective and stable non-precious electrocatalyst for ORR in the acid medium. Compared to conventional Pt/C electrodes under the same conditions, the proposed nanocatalyst shows closer onset potential and current density. Typically, the observed onset potentials and current densities for the synthesized and Pt/C electrodes are 825 and 910 mV (vs. NHE) and −3.65 and −4.31 mA.cm−2 (at 5 mV.s−1), respectively. However, the most important advantage of the introduced metallic alloy-decorated graphene is its distinct stability in acid medium; the retention in the electrocatalytic performance after 1,000 successive cycles is approximately 98%. This finding is attributed to the high corrosion resistance of the NiFe alloy. The kinetic study indicates that the number of the transferred electrons is 3.46 and 3.89 for the introduced and Pt/C (20 wt%) electrodes, respectively which concludes a high activity for the proposed nanocomposite. The suggested decorated graphene can be synthesized using a multi-thermal method. Typically, nickel acetate, iron acetate, graphene oxide and urea are subjected to MW heating. Then, sintering with melamine in an Argon atmosphere at 750 °C is required to produce the final electrocatalyst. Overall, the introduced NiFe@ N-doped Gr nanocomposite shows remarkable electrochemical activity in the acid medium with long-term stability.
Current-induced magnetic switching with spin-orbit torque in an interlayer-coupled junction with a Ta spacer layer
Authors: Kwak W.-Y. , Kwon J.-H. , Grünberg P. , Han S. H. , Cho B. K.
Published: February 2018

Spin-orbit torque has attracted considerable attention as a means to overcome limits of devices based on spin-transfer torque. However, a small magnetic field that is collinear to the current flow must be applied to break symmetry and induce deterministic current-induced magnetization switching. Recently, a junction utilizing interlayer coupling mediated by a Ru spacer layer between two CoFe layers was designed for symmetry breaking and exhibited current-induced magnetization switching without a magnetic field. Here, we demonstrate zero-field current-induced switching of the perpendicular magnetization of a Co layer that is indirectly coupled with a CoFe layer via a Ta spacer. The weak interlayer coupling exhibited by Ta allows the layer thickness to be relatively small (≈0.5 nm), enabling appropriate interlayer coupling to induce spin-orbit torque for current-induced magnetic switching. External magnetic field effects on switching characteristics show that the current switching process is quite stable against external environments.
Gut microbial composition in patients with psoriasis
Authors: Codoñer Francisco M. , Ramírez-Bosca Ana , Climent Eric , Carrión-Gutierrez Miguel , Guerrero Mariano , Pérez-Orquín Jose Manuel , Horga de la Parte José , Genovés Salvador , Ramón Daniel , Navarro-López Vicente , Chenoll Empar
Published: February 2018

Since the last 5–10 years the relevance of the gut microbiome on different intestinal illnesses has been revealed. Recent findings indicate the effect of gut microbiome on certain dermatological diseases such as atopic dermatitis. However, data on other skin diseases such as psoriasis are limited. This is the first time attempting to reveal the gut microbiome composition of psoriatic patients with a prospective study including a group of patients with plaque psoriasis, analyzing their gut microbiome and the relationship between the microbiome composition and bacterial translocation. The microbiome of a cohort of 52 psoriatic patients (PASI score ≥6) was obtained by 16s rRNA massive sequencing with MiSeq platform (Illumina inc, San Diego) with an average of 85,000 sequences per sample. The study of the gut microbiome and enterotype shows from the first time a specific “psoriatic core intestinal microbiome” that clearly differs from the one present in healthy population. In addition, those psoriatic patients classified as belonging to enterotype 2 tended to experience more frequent bacterial translocation and higher inflammatory status (71%) than patients with other enterotypes (16% for enterotype 1; and 21% for enterotype 3).
Estimating the nutrient thresholds of a typical tributary in the Liao River basin, Northeast China
Authors: Chen Jiabo , Li Fayun , Wang Yanjie , Kong Yun
Published: February 2018

Estimating regional nutrient criteria for streams and rivers is a key step toward protecting river water quality and restoring the health of aquatic ecosystems. Using a multivariable statistical analysis technique, nutrients were identified as the main factor influencing the degradation of the benthic macroinvertebrate community. Three chemical methods (the reference stream distribution approach, all-streams distribution approach and Y-intercept approach) and one biological method (the stress-response approach) were applied to evaluate the nutrient thresholds in the Qing River basin. The reference stream distribution approach and all-streams distribution approach were based on calculating a predetermined percentile of reference streams and all-streams water quality data set, respectively. The Y-intercept approach was based on determining the influence of human activity on water quality by linear regression models. The biological method was based on the response of the benthic macroinvertebrate community structure to changes in water quality. The chemical thresholds were 0.750–1.288 mg/L for total nitrogen (TN) and 0.035–0.046 mg/L for total phosphorus (TP); the biological thresholds were 1.050–1.655 for TN and 0.052–0.101 for TP. The results from the chemical approaches were verified using the biological method, resulting in preliminarily recommended thresholds of 1.000 mg/L TN and 0.040 mg/L TP in the Qing River system.
Bioprocessing strategies for cost-effective large-scale biogenic synthesis of nano-MgO from endophytic Streptomyces coelicolor strain E72 as an anti-multidrug-resistant pathogens agent
Authors: EL-Moslamy Shahira H.
Published: February 2018

In this report, the local nano-MgO synthesizer strain has been isolated from Ocimum sanctum plant and deposited in GenBank as endophytic Streptomyces coelicolor strain E72. Its intracellular metabolic fraction that contains 7.2 μg/μl of carbohydrate, 6.3 g/l of protein and 5.2 nmol/hr/ml of nitrate reductase used to produce multi-surface shaped nano-MgO with diameter ~25 nm. To the best of our knowledge, this is the first report using statistical nanobiotechnological strategies (Plackett -Burman, Box-Behnken and Taguchi experimental designs) to study and evaluate the endophytic S. coelicolor biomass production (123.3 g/l) and extract the highest bioactive metabolites that used for biogenic synthesis of nano-MgO (320 g/l) through exponential sucrose pulses feeding fermentation strategy after 192 hr in semi industrial scale bioreactor (7 L). Purified nano-MgO applied in vitro against multi-drug resistant human pathogens and the large inhibition zone recorded against Shigella flexneri (108 ± 10.53 mm). The average of MICs was recorded as 25 µg/ml that inhibited 90% of the pathogenic living cells and compared with 100 mg/ml ampicilin/sulbactam solution that killed 40% of the same pathogen. These results are expected to gather sufficient knowledge to discover and develop a new cheap and eco-friendly nano-MgO as an extremely strong antimicrobial agent used in biomedical applications.
Visual stimulation-induced mild stress enhances cognitive behavior in cynomolgus monkey
Authors: Woo Dong Ho , Koh Eun Ha , Shin Seung-Hyuk , Yang Young-Su , Choe Jae Chun , Lee C. Justin , Han Su-Cheol
Published: February 2018

Cortisol is a well-known endogenous glucocorticoid that serves as a stress indicator. It is normally released under stressful condition to warn about imminent danger and thus is critical for survival of the species. However, it is unclear how cortisol relates to cognitive process under physiological condition in high-order primates such as non-human primates (NHP). Here, we report that a slight but significant increase in blood cortisol level by mild stress is positively correlated with the cognitive function in cynomolgus monkey. We stimulated 3 groups of monkeys by viewing consecutive series of pictures of monkeys, pictures of humans, or animation still pictures. We first found that the blood cortisol level was significantly higher during the stimulation session and returned to normal after stimulation session. Among the three types of pictures, the monkeys which were stimulated with monkey pictures showed the most significant increase in cortisol level during stimulation. Furthermore, the monkeys showed significantly enhanced manipulation, suggesting that cortisol affected cognitive processes. Overall, our study demonstrates that visual stimulation both increases blood cortisol and enhances manipulating behavior. Therefore, unlike the common notion that cortisol is a stress indicator, our data supports that a mild increase of cortisol enhances cognition in NHP.
Pathways of cellular internalisation of liposomes delivered siRNA and effects on siRNA engagement with target mRNA and silencing in cancer cells
Authors: Alshehri Abdullah , Grabowska Anna , Stolnik Snow
Published: February 2018

Design of an efficient delivery system is a generally recognised bottleneck in translation of siRNA technology into clinic. Despite research efforts, cellular processes that determine efficiency of siRNA silencing achieved by different delivery formulations remain unclear. Here, we investigated the mechanism(s) of cellular internalisation of a model siRNA-loaded liposome system in a correlation to the engagement of delivered siRNA with its target and consequent silencing by adopting siRNA molecular beacon technology. Probing of cellular internalisation pathways by a panel of pharmacological inhibitors indicated that clathrin-mediated (dynamin-dependent) endocytosis, macropinocytosis (dynamine independent), and cell membrane cholesterol dependent process(es) (clathrin and caveolea-independent) all play a role in the siRNA-liposomes internalization. The inhibition of either of these entry routes was, in general, mirrored by a reduction in the level of siRNA engagement with its target mRNA, as well as in a reduction of the target gene silencing. A dramatic increase in siRNA engagement with its target RNA was observed on disruption of endosomal membrane (by chloroquine), accompanied with an increased silencing. The work thus illustrates that employing molecular beacon siRNA technology one can start to assess the target RNA engagement – a stage between initial cellular internalization and final gene silencing of siRNA delivery systems.
Biodegradation of 17β-estradiol by Bacterial Co-culture Isolated from Manure
Authors: Li Mingtang , Zhao Xingmin , Zhang Xiufang , Wu Di , Leng Su
Published: February 2018

Animal wastes are potential sources of natural and steroidal estrogen hormones into the environment. These hormones can be removed by microorganisms with induced enzymes. Two strains of 17β-estradiol-degrading bacteria (LM1 and LY1) were isolated from animal wastes. Based on biochemical characteristics and 16 S rDNA gene sequences, we identified strains LM1 and LY1 as belonging to the genus of Acinetobacter and Pseudomonas, respectively. Bacterial co-culture containing LM1 and LY1 bacterial strains could rapidly remove approximately 98% of E2 (5 mg L−1) within 7 days. However, strains LM1 and LY1 degraded 77% and 68% of E2 when they were incubated alone, respectively. More than 90% of 17β-estradiol (E2, ≤ 20 mg L−1) could be removed by bacterial co-culture. Low C/N ratio (1:35) was more suitable for bacterial growth and E2 degradation. The optimal pH for bacterial co-culture to degrade E2 ranged from 7.00 to 9.00. Coexisting sodium acetate, glucose and sodium citrate decreased E2 degradation in the first 4 days, but more E2 was removed when they were depleted. The growth of the bacterial co-culture was not significantly decreased by Ni, Pb, Cd or Cu at or below 0.8, 1.2, 1.6 or 0.8 mg L−1, respectively. These data highlight the usefulness of bacterial co-culture in the bioremediation of estrogen-contaminated environments.
Genome-wide analysis revealed that DZNep reduces tubulointerstitial fibrosis via down-regulation of pro-fibrotic genes
Authors: Mimura Imari , Hirakawa Yosuke , Kanki Yasuharu , Nakaki Ryo , Suzuki Yutaka , Tanaka Tetsuhiro , Aburatani Hiroyuki , Nangaku Masaomi
Published: February 2018

Tubulointerstitial fibrosis has been recently reported to be caused by the collapse of the epigenetic regulation of kidney diseases. We examined whether pharmacological inhibition of histone modification is effective against renal fibrosis. DZNep (3-deazaneplanocin A) was originally developed as an anti-cancer drug to inhibit the repressive histone mark, H3K27me3. We used a model of chronic tubulointerstitial fibrosis induced by unilateral ischaemia/reperfusion and administered DZNep intravenously to the mice for 8 weeks. We found DZNep contributes to the reduction of tubulointerstitial fibrosis. We selected only tubular cells from in vivo samples using laser-capture microdissection because epigenetic regulation is specific to the cell types, and we focused on the changes in the tubular cells. We performed a genome-wide analysis of tubular cells using high-throughput sequencing (RNA-seq) to identify novel epigenetic factors associated with renal fibrosis. We found that pro-fibrotic genes such as COL3A1 (collagen type 3a1) and TIMP2 (tissue inhibitor of metalloproteinase 2) were suppressed by DZNep in vivo. In addition, pro-fibrotic genes such as COL4A1 (collagen type 4a1), TIMP2 and MMP14 were down-regulated by DZNep in vitro. In conclusion, we found that pharmacological epigenetic modification by DZNep decreased the expression levels of fibrogenic genes in tubular cells and inhibited tubulointerstitial fibrosis.
Post-epizootic salamander persistence in a disease-free refugium suggests poor dispersal ability of Batrachochytrium salamandrivorans
Authors: Spitzen - van der Sluijs Annemarieke , Stegen Gwij , Bogaerts Sergé , Canessa Stefano , Steinfartz Sebastian , Janssen Nico , Bosman Wilbert , Pasmans Frank , Martel An
Published: February 2018

Lack of disease spill-over between adjacent populations has been associated with habitat fragmentation and the absence of population connectivity. We here present a case which describes the absence of the spill-over of the chytrid fungus Batrachochytrium salamandrivorans (Bsal) between two connected subpopulations of fire salamanders (Salamandra salamandra). Based on neutrally evolving microsatellite loci, both subpopulations were shown to form a single genetic cluster, suggesting a shared origin and/or recent gene flow. Alpine newts (Ichthyosaura alpestris) and fire salamanders were found in the landscape matrix between the two sites, which are also connected by a stream and separated by no obvious physical barriers. Performing a laboratory trial using alpine newts, we confirmed that Bsal is unable to disperse autonomously. Vector-mediated dispersal may have been impeded by a combination of sub-optimal connectivity, limited dispersal ability of infected hosts and a lack of suitable dispersers following the rapid, Bsal-driven collapse of susceptible hosts at the source site. Although the exact cause remains unclear, the aggregate evidence suggests that Bsal may be a poorer disperser than previously hypothesized. The lack of Bsal dispersal between neighbouring salamander populations opens perspectives for disease management and stresses the necessity of implementing biosecurity measures preventing human-mediated spread.
Gene expression models based on a reference laboratory strain are poor predictors of Mycobacterium tuberculosis complex transcriptional diversity
Authors: Chiner-Oms Álvaro , González-Candelas Fernando , Comas Iñaki
Published: February 2018

Every year, species of theMycobacterium tuberculosiscomplex (MTBC) kill more people than any other infectious disease caused by a single agent. As a consequence of its global distribution and parallel evolution with the human host the bacteria is not genetically homogeneous. The observed genetic heterogeneity has relevance at different phenotypic levels, from gene expression to epidemiological dynamics. However, current systems biology datasets have focused on the laboratory reference strain H37Rv. By using large expression datasets testing the role of almost two hundred transcription factors, we have constructed computational models to grab the expression dynamics ofMycobacterium tuberculosisH37Rv genes. However, we have found that many of those transcription factors are deleted or likely dysfunctional across strains of the MTBC. As a result, we failed to predict expression changes in strains with a different genetic background when compared with experimental data. These results highlight the importance of designing systems biology approaches that take into account the genetic diversity of tubercle bacilli, or any other pathogen, if we want to identify universal targets for vaccines, diagnostics and treatments.
Electrical devices from top-down structured platinum diselenide films
Authors: Yim Chanyoung , Passi Vikram , Lemme Max C. , Duesberg Georg S. , Ó Coileáin Cormac , Pallecchi Emiliano , Fadil Dalal , McEvoy Niall
Published: February 2018

Platinum diselenide (PtSe2) is an exciting new member of the two-dimensional (2D) transition metal dichalcogenide (TMD) family. It has a semimetal to semiconductor transition when approaching monolayer thickness and has already shown significant potential for use in device applications. Notably, PtSe2 can be grown at low temperature making it potentially suitable for industrial usage. Here, we address thickness-dependent transport properties and investigate electrical contacts to PtSe2, a crucial and universal element of TMD-based electronic devices. PtSe2 films have been synthesized at various thicknesses and structured to allow contact engineering and the accurate extraction of electrical properties. Contact resistivity and sheet resistance extracted from transmission line method (TLM) measurements are compared for different contact metals and different PtSe2 film thicknesses. Furthermore, the transition from semimetal to semiconductor in PtSe2 has been indirectly verified by electrical characterization in field-effect devices. Finally, the influence of edge contacts at the metal–PtSe2 interface has been studied by nanostructuring the contact area using electron beam lithography. By increasing the edge contact length, the contact resistivity was improved by up to 70% compared to devices with conventional top contacts. The results presented here represent crucial steps toward realizing high-performance nanoelectronic devices based on group-10 TMDs.
Accumulation of persistent tungsten in bone as in situ generated polytungstate
Authors: VanderSchee Cassidy R. , Kuter David , Bolt Alicia M. , Lo Feng-Chun , Feng Renfei , Thieme Juergen , Chen-Wiegart Yu-chen Karen , Williams Garth , Mann Koren K. , Bohle D. Scott
Published: February 2018

Tungsten accumulates in bone but is neither labile nor inert once absorbed. Tungsten’s relatively high cytosolic solubility and availability are problematic given its association with childhood lymphocytic leukemia. In light of tungsten’s technological prevalence, and the increased concern of regulatory agencies, here we characterize the chemical form and localization in mice exposed to tungsten through drinking water. Using X-ray fluorescence spectroscopy, we report accumulation of tungsten in bone tissue with some sites having ~10-fold greater intensities than background levels. The long bone tissue studied includes cortical, cancellous and bone marrow. Persistence of tungsten in cortical bone tissue following removal of the source indicates that it is retained in an insoluble form. The X-ray absorption near-edge structure spectra for tungsten in these tissues indicate that it is no longer in the originally administered form, orthotungstate, but rather resembles the heteropolytungsate species, phosphotungstate.
Advances in point-of-care diagnostic devices in cancers
Authors: Sandbhor Gaikwad Puja , Banerjee Rinti
Published: February 2018

The early diagnosis and monitoring of the progress of cancers are limited due to the lack of adequate screening tools.
Enhancing anticancer cytotoxicity through bimodal drug delivery from ultrasmall Zr MOF nanoparticles
Authors: Abánades Lázaro Isabel , Abánades Lázaro Sandra , Forgan Ross S.
Published: February 2018

Dual delivery of dichloroacetate and 5-fluorouracil from Zr MOFs into cancer cells is found to enhance in vitro cytotoxicity.
Size-dependent modulation of fluorescence and light scattering: a new strategy for development of ratiometric sensing
Authors: Liu Shi Gang , Li Na , Han Lei , Li Ling Jie , Li Nian Bing , Luo Hong Qun
Published: February 2018

A new size-dependent modulation strategy to design ratiometric sensors is proposed by combining fluorescence and light scattering.
Universality of the giant Seebeck effect in organic small molecules
Authors: Kojima Hirotaka , Abe Ryo , Fujiwara Fumiya , Nakagawa Mario , Takahashi Kohtaro , Kuzuhara Daiki , Yamada Hiroko , Yakiyama Yumi , Sakurai Hidehiro , Yamamoto Tatsuya , Yakushiji Hidenori , Ikeda Masaaki , Nakamura Masakazu
Published: February 2018

Various pure organic semiconducting molecules exhibit extraordinarily large Seebeck coefficient which cannot be elucidated by conventional physical models of thermoelectricity.
The investigation of an organic acid assisted sol–gel method for preparing monolithic zirconia aerogels
Authors: Wang Xiaoqing , Li Chengyuan , Shi Zhenyu , Zhi Mingjia , Hong Zhanglian
Published: February 2018

The mechanism of the organic acid assisted sol–gel method free of propylene oxide for preparing monolithic zirconia aerogels was investigated in detail.
A first-principles prediction on the “healing effect” of graphene preventing carrier trapping near the surface of metal halide perovskites
Authors: Wang W.-W. , Dang J.-S. , Jono R. , Segawa H. , Sugimoto M.
Published: February 2018

We introduce a healing effect of graphene preventing carrier trapping by the defects near the surface of metal halide perovskites.
Two dimensional semiconductors for ultrasound-mediated cancer therapy: the case of black phosphorus nanosheets
Authors: Ouyang Jiang , Deng Liu , Chen Wansong , Sheng Jianping , Liu Zhenjun , Wang Liqiang , Liu You-Nian
Published: February 2018

The potential of two dimensional semiconductors in sonodynamic cancer therapy is firstly investigated on black phosphorus nanosheets.
Water-based synthesis of gold and silver nanoparticles with cuboidal and spherical shapes using luteolin tetraphosphate at room temperature
Authors: Osonga Francis J. , Le Phuong , Luther David , Sakhaee Laura , Sadik Omowunmi A.
Published: February 2018

The demand for eco-friendly synthetic methods of metal nanoparticles is on the rise.
Mesoporous-silica induced doped carbon nanotube growth from metal–organic frameworks
Authors: Zhou Huang , He Daping , Saana Amiinu Ibrahim , Yang Jinlong , Wang Zhe , Zhang Jian , Liang Qirui , Yuan Shuai , Zhu Jiawei , Mu Shichun
Published: February 2018

Small diameter cobalt and nitrogen co-doped carbon nanotubes (Co/N-CNTs) were grown from a mesoporous-silica (mSiO2) covered Co-based MOF (ZIF-67).
A hybrid inorganic–organic light-emitting diode using Ti-doped ZrO2 as an electron-injection layer
Authors: Jayabharathi Jayaraman , Panimozhi Sekar , Thanikachalam Venugopal , Prabhakaran Annadurai , Jeeva Palanivel
Published: February 2018

Ti-doped ZrO2 facilitates electron injection effectively, leading to enhanced current efficiency of 2.84 cd A−1 and power efficiency of 1.32 lm W−1
Sequential electron transfer governs the UV-induced self-repair of DNA photolesions
Authors: Szabla Rafał , Kruse Holger , Stadlbauer Petr , Šponer Jiří , Sobolewski Andrzej L.
Published: February 2018

QM/MM simulations elucidate the self-repair mechanism of the cyclobutane pyrimidine dimer.
Development of a mitochondria targetable ratiometric time-gated luminescence probe for biothiols based on lanthanide complexes
Authors: Liu Xiangli , Song Bo , Ma Hua , Tang Zhixin , Yuan Jingli
Published: February 2018

A mitochondria targetable ratiometric luminescence probe based on a mixture of Eu3+ and Tb3+ complexes has been developed for the specific recognition and ratiometric time-gated luminescence detection of biothiols in aqueous and living samples.
Cyclic mechanical stretch up-regulates hepatoma-derived growth factor expression in cultured rat aortic smooth muscle cells
Authors: Kao Ying-Hsien , Chen Po-Han , Sun Cheuk-Kwan , Chang Yo-Chen , Lin Yu-Chun , Tsai Ming-Shian , Lee Po-Huang , Cheng Cheng-I
Published: February 2018

Hepatoma-derived growth factor (HDGF) is a potent mitogen for vascular smooth muscle cells (SMCs) during embryogenesis and injury repair of vessel walls. Whether mechanical stimuli modulate HDGF expression remains unknown. The present study aimed at investigating whether cyclic mechanical stretch plays a regulatory role in HDGF expression and regenerative cytokine production in aortic SMCs. A SMC cell line was grown on a silicone-based elastomer chamber with extracellular matrix coatings (either type I collagen or fibronectin) and received cyclic and uniaxial mechanical stretches with 10% deformation at frequency 1 Hz. Morphological observation showed that fibronectin coating provided better cell adhesion and spreading and that consecutive 6 h of cyclic mechanical stretch remarkably induced reorientation and realignment of SMCs. Western blotting detection demonstrated that continuous mechanical stimuli elicited up-regulation of HDGF and proliferative cell nuclear antigen, a cell proliferative marker. Signal kinetic profiling study indicated that cyclic mechanical stretch induced signaling activity in RhoA/ROCK and PI3K/Akt cascades. Kinase inhibition study further showed that blockade of PI3K activity suppressed the stretch-induced tumor necrosis factor-α (TNF-α), whereas RhoA/ROCK inhibition significantly blunted the interleukin-6 (IL-6) production and HDGF overexpression. Moreover, siRNA-mediated HDGF gene silencing significantly suppressed constitutive expression of IL-6, but not TNF-α, in SMCs. These findings support the role of HDGF in maintaining vascular expression of IL-6, which has been regarded a crucial regenerative factor for acute vascular injury. In conclusion, cyclic mechanical stretch may maintain constitutive expression of HDGF in vascular walls and be regarded an important biophysical regulator in vascular regeneration.
Deep Brain Stimulation of the Subthalamic Nucleus Parameter Optimization for Vowel Acoustics and Speech Intelligibility in Parkinson's Disease
Authors: Knowles Thea , Adams Scott , Abeyesekera Anita , Mancinelli Cynthia , Gilmore Greydon , Jog Mandar
Published: February 2018

Purpose

The settings of 3 electrical stimulation parameters were adjusted in 12 speakers with Parkinson's disease (PD) with deep brain stimulation of the subthalamic nucleus (STN-DBS) to examine their effects on vowel acoustics and speech intelligibility.

Method

Participants were tested under permutations of low, mid, and high STN-DBS frequency, voltage, and pulse width settings. At each session, participants recited a sentence. Acoustic characteristics of vowel production were extracted, and naive listeners provided estimates of speech intelligibility.

Results

Overall, lower-frequency STN-DBS stimulation (60 Hz) was found to lead to improvements in intelligibility and acoustic vowel expansion. An interaction between speaker sex and STN-DBS stimulation was found for vowel measures. The combination of low frequency, mid to high voltage, and low to mid pulse width led to optimal speech outcomes; however, these settings did not demonstrate significant speech outcome differences compared with the standard clinical STN-DBS settings, likely due to substantial individual variability.

Conclusions

Although lower-frequency STN-DBS stimulation was found to yield consistent improvements in speech outcomes, it was not found to necessarily lead to the best speech outcomes for all participants. Nevertheless, frequency may serve as a starting point to explore settings that will optimize an individual's speech outcomes following STN-DBS surgery.

Supplemental Material

https://doi.org/10.23641/asha.5899228
Communicative Function Use of Preschoolers and Mothers From Differing Racial and Socioeconomic Groups
Authors: Fannin Danai Kasambira , Barbarin Oscar A. , Crais Elizabeth R.
Published: February 2018

Purpose

This study explores whether communicative function (CF: reasons for communicating) use differs by socioeconomic status (SES), race/ethnicity, or gender among preschoolers and their mothers.

Method

Mother–preschooler dyads (
N
= 95) from the National Center for Early Development and Learning's (2005) study of family and social environments were observed during 1 structured learning and free-play interaction. CFs were coded by trained independent raters.

Results

Children used all CFs at similar rates, but those from low SES homes produced fewer utterances and less reasoning, whereas boys used less self-maintaining and more predicting. African American mothers produced more directing and less responding than European American and Latino American mothers, and Latino American mothers produced more utterances than European American mothers. Mothers from low SES homes did more directing and less responding.

Conclusions

Mothers exhibited more sociocultural differences in CFs than children; this suggests that maternal demographic characteristics may influence CF production more than child demographics at school entry. Children from low SES homes talking less and boys producing less self-maintaining coincided with patterns previously detected in pragmatic literature. Overall, preschoolers from racial/ethnic minority and low SES homes were not less deft with CF usage, which may inform how their pragmatic skills are described.

Supplemental Material

https://doi.org/10.23641/asha.5890255
Switched‐bandwidth SAW‐based bandpass filters with flat group delay
Authors: Psychogiou D. , Gómez‐García R.
Published: February 2018

Tunable surface‐acoustic‐wave‐(SAW)‐based bandpass filters (BPFs) with flat in‐band group delay (τg) and variable passband bandwidth (BW) are reported. They are based on N hybrid acoustic‐wave‐lumped‐element‐resonator (AWLR) modules shaped by one lumped‐element resonator and K RF‐switched SAW resonators that are arranged in a Gaussian‐type source‐to‐load impedance‐inverter network. Fractional bandwidth (FBW) tuning is achieved by reconfiguring the number of SAW resonators within the AWLR modules. Major advantages of the proposed filter concept when compared to conventional SAW BPFs are as follows: (i) they do not depend on the electromechanical coupling coefficient (kt2) of the SAW resonators – FBW>kt2 can be realised –, (ii) they do not require lossy elements or SAW resonators with different frequencies, and (iii) they can be tuned. For experimental‐validation purposes, a 433.9 MHz two‐pole/four‐transmission‐zero prototype was built and measured. It exhibited flat‐in‐band‐τg passbands with discretely‐tunable BW between 0.18 and 0.45 MHz (i.e. 2.5:1 tuning ratio).
Impacts of the model uncertainty on the voltage regulation problem of medium‐voltage distribution systems
Authors: Bakhshideh Zad Bashir , Lobry Jacques , Vallée François
Published: February 2018

In this paper, a novel framework is proposed in order to evaluate impacts of the uncertain models of the system components on the voltage regulation problem of the medium‐voltage distribution systems. The investigation focuses on the model uncertainty associated with voltage dependency of loads, power factor of loads, thermal dependency of lines, shunt admittances of lines and internal resistance of substation transformer. To this end, firstly, voltage constraints are managed using a centralised voltage control algorithm (VCA) by relying on the simplified models of the system components. The system loads and lines as well as the substation transformer are then modelled with the uncertain variables which are bounded in the predefined ranges. Monte Carlo (MC) simulations are used to create wide series of scenarios that cover the possible values that the parameters of the system components can take due to their uncertain nature. The model uncertainty impacts on the voltage regulation problem are finally evaluated by the load flow calculations considering the scenarios created by the MC simulations and the set‐point obtained by the VCA. The proposed investigation brings useful information regarding the possible deviations that the node voltages can have due to the uncertain models of the studied components.
Scenario modules, ray‐tracing simulations and analysis of millimetre wave and terahertz channels for smart rail mobility
Authors: Guan Ke , Ai Bo , Peng Bile , He Danping , Lin Xue , Wang Longhe , Zhong Zhangdui , Kürner Thomas
Published: February 2018

Millimeter wave (mmWave) and Terahertz (THz) technologies are the enabler of providing high‐data rate communications for ‘smart rail mobility’. In this paper, six scenario modules for mmWave and THz train‐to‐infrastructure channels are defined and constructed. All the main objects, such as tracks, stations, crossing bridges, tunnels, cuttings, barriers, pylons, buildings, vegetation, traffic signs, billboards, trains, etc., are modeled according to the typical geometries and materials in reality. The three‐dimensional (3D) models of these six modules are publicly available and freely downloadable. Furthermore, extensive ray‐tracing simulations in the 60 GHz band with 8 GHz bandwidth are made in all the six modules with two antenna setups. Path loss exponent, shadow factor, Ricean K‐factor, root‐mean‐square (RMS) delay spread, and coherence bandwidth are extracted and analyzed. These channel characteristics show that the objects that might not be so impacting on lower frequency channels indeed influence mmWave channel properties, and therefore, they can even play a more important role in the channels at higher frequency bands – THz. The channel characteristics analyzed in this study provide the foundation for future work that aims to streamline the design, simulation, and development of mmWave and THz communications enabling smart rail mobility.