bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin-like growth factor-1 attenuates oxidative stress-induced hepatocyte premature senescence in liver fibrogenesis via regulating nuclear p53–progerin interaction
Authors: Luo Xiaoying , Jiang Xiaoke , Li Jun , Bai Yangqiu , Li Zhen , Wei Peiru , Sun Suofeng , Liang Yuan , Han Shuangyin , Li Xiuling , Zhang Bingyong
Published: June 2019

Stress-induced premature senescence (SIPS), a state of cell growth arrest due to various stimuli, is implicated in the pathogeneses of hepatic fibrogenesis. Progerin, a permanently farnesylated mutant lamin A protein, likely leads to premature senescence to influent liver diseases. The previous reports showed that activation of insulin-like growth factor-1 (IGF-1) signaling could enhance cell longevity and attenuate liver fibrosis. However, the underlying mechanisms about hepatocyte premature senility in liver fibrosis, and how IGF-1 regulates cell premature aging and fibrogenesis, remain poorly understood. In the present study, we found the augment of hepatocyte oxidation and premature aging, along with the decrease of plasm IGF-1 level in patients with liver fibrosis and CCl4-induced liver injury rat models. Nevertheless, IGF-1 gene transfer to CCl4 rats to overexpress intrahepatic IGF-1 relieved hepatocyte oxidative stress and premature senescence, which was likely mediated by the p53/progerin pathway, to improve hepatic steatosis and fibrogenesis. In vitro, H2O2 caused abnormal accumulation of progerin in nuclear and activation of nuclear p53–progerin interaction to trigger primary rat hepatocyte premature senescence through the p21-independent pathway; while these effects were rescued by prolonged exogenous IGF-1 or the IGF-1 adenovirus vector. Furthermore, the IGF-1 adenovirus vector, transfected to H2O2-treated hepatocytes, reversed oxidative stress-induced premature senescence via enhancing cytoplasmic AKT1–p53 interaction and subsequently inhibiting nuclear p53–progerin interaction. Consequently, our data illuminate a novel role of IGF-1 in regulating stress-induced hepatocyte premature senescence in liver fibrosis: prolonged IGF-1 relieves oxidative stress-initiated hepatocyte premature senescence via inhibition of nuclear p53–progerin interaction to ameliorate hepatic steatosis and fibrogenesis.
Alcohol exposure alters pre-mRNA splicing of antiapoptotic Mcl-1L isoform and induces apoptosis in neural progenitors and immature neurons
Authors: Donadoni Martina , Cicalese Stephanie , Sarkar Dipak K. , Chang Sulie L. , Sariyer Ilker Kudret
Published: June 2019

Alternative splicing and expression of splice variants of genes in the brain may lead to the modulation of protein functions, which may ultimately influence behaviors associated with alcohol dependence and neurotoxicity. We recently showed that ethanol exposure can lead to pre-mRNA missplicing of Mcl-1, a pro-survival member of the Bcl-2 family, by downregulating the expression levels of serine/arginine rich splicing factor 1 (SRSF1). Little is known about the physiological expression of these isoforms in neuronal cells and their role in toxicity induced by alcohol exposure during the developmental period. In order to investigate the impact of alcohol exposure on alternative splicing of Mcl-1 pre-mRNA and its role in neurotoxicity, we developed a unique primary human neuronal culture model where neurospheres (hNSPs), neural progenitors (hNPCs), immature neurons, and mature neurons were cultured from the matching donor fetal brain tissues. Our data suggest that neural progenitors and immature neurons are highly sensitive to the toxic effects of ethanol, while mature neuron cultures showed resistance to ethanol exposure. Further analysis of Mcl-1 pre-mRNA alternative splicing by semi-quantitative and quantitative analysis revealed that ethanol exposure causes a significant decrease in Mcl-1L/Mcl-1S ratio in a dose and time dependent manner in neural progenitors. Interestingly, ectopic expression of Mcl-1L isoform in neural progenitors was able to recover the viability loss and apoptosis induced by alcohol exposure. Altogether, these observations suggest that alternative splicing of Mcl-1 may play a crucial role in neurotoxicity associated with alcohol exposure in the developing fetal brain.
Novel chitosan–cellulose nanofiber self-healing hydrogels to correlate self-healing properties of hydrogels with neural regeneration effects
Authors: Cheng Kun-Chih , Huang Chih-Feng , Wei Yen , Hsu Shan-hui
Published: June 2019

Biodegradable self-healing hydrogels are attractive materials for tissue repair; however, the impact of the self-healing abilities of hydrogels on tissue repair is not clear. In this study, we prepared novel chitosan–cellulose nanofiber (CS–CNF) composite self-healing hydrogels with the same modulus (approximately 2 kPa) but tunable self-healing properties. By adding a low amount of CNFs (0.06–0.15 wt%) in the pristine chitosan (CS) self-healing hydrogel, the reversible dynamic Schiff bonding, strain sensitivity, and self-healing of the hydrogel are obviously affected. Neural stem cells embedded in the CS–CNF hydrogel with better self-healing properties reveal significantly enhanced oxygen metabolism as well as neural differentiation. The differentiation of neural stem cells is highly correlated with their metabolic change in the self-healing hydrogel. Moreover, the neural regeneration effect of the optimized CS–CNF hydrogel with 0.09 wt% CNFs and the best self-healing properties show a 50% improvement over the pristine CS hydrogel in the zebrafish brain injury model. A mechanism is proposed to interpret the tunable self-healing properties of CS–CNF hydrogels with stiffness maintained in a similar range. The new self-healing hydrogels help to clarify the role of self-healing in the biological performance of hydrogels as well as provide design rationale for hydrogels with better injectability and tissue regeneration potential.
New approach to waste-heat energy harvesting: pyroelectric energy conversion
Authors: Pandya Shishir , Velarde Gabriel , Zhang Lei , Wilbur Joshua D. , Smith Andrew , Hanrahan Brendan , Dames Chris , Martin Lane W.
Published: June 2019

Harvesting waste heat for useful purposes is an essential component of improving the efficiency of primary energy utilization. Today, approaches such as pyroelectric energy conversion are receiving renewed interest for their ability to turn wasted energy back into useful energy. From this perspective, the need for these approaches, the basic mechanisms and processes underlying their operation, and the material and device requirements behind pyroelectric energy conversion are reviewed, and the potential for advances in this area is also discussed.
PRL3-zumab as an immunotherapy to inhibit tumors expressing PRL3 oncoprotein
Authors: Thura Min , Al-Aidaroos Abdul Qader , Gupta Abhishek , Chee Cheng Ean , Lee Soo Chin , Hui Kam Man , Li Jie , Guan Yeoh Khay , Yong Wei Peng , So Jimmy , Chng Wee Joo , Ng Chin Hin , Zhou Jianbiao , Wang Ling Zhi , Yuen John Shyi Peng , Ho Henry Sun Sien , Yi Sim Mei , Chiong Edmund , Choo Su Pin , Ngeow Joanne , Ng Matthew Chau Hsien , Chua Clarinda , Yeo Eugene Shen Ann , Tan Iain Bee Huat , Sng Joel Xuan En , Tan Nicholas Yan Zhi , Thiery Jean Paul , Goh Boon Cher , Zeng Qi
Published: June 2019

Tumor-specific antibody drugs can serve as cancer therapy with minimal side effects. A humanized antibody, PRL3-zumab, specifically binds to an intracellular oncogenic phosphatase PRL3, which is frequently expressed in several cancers. Here we show that PRL3-zumab specifically inhibits PRL3+cancer cells in vivo, but not in vitro. PRL3 antigens are detected on the cell surface and outer exosomal membranes, implying an ‘inside-out’ externalization of PRL3. PRL3-zumab binds to surface PRL3 in a manner consistent with that in classical antibody-dependent cell-mediated cytotoxicity or antibody-dependent cellular phagocytosis tumor elimination pathways, as PRL3-zumab requires an intact Fc region and host FcγII/III receptor engagement to recruit B cells, NK cells and macrophages to PRL3+tumor microenvironments. PRL3 is overexpressed in 80.6% of 151 fresh-frozen tumor samples across 11 common cancers examined, but not in patient-matched normal tissues, thereby implicating PRL3 as a tumor-associated antigen. Targeting externalized PRL3 antigens with PRL3-zumab may represent a feasible approach for anti-tumor immunotherapy.
Gene expression dysregulation domains are not a specific feature of Down syndrome
Authors: Ahlfors Helena , Anyanwu Nneka , Pakanavicius Edvinas , Dinischiotu Natalia , Lana-Elola Eva , Watson-Scales Sheona , Tosh Justin , Wiseman Frances , Briscoe James , Page Karen , Fisher Elizabeth M. C. , Tybulewicz Victor L. J.
Published: June 2019

Down syndrome (DS), trisomy of human chromosome 21 (Hsa21), results in a broad range of phenotypes. A recent study reported that DS cells show genome-wide transcriptional changes in which up- or down-regulated genes are clustered in gene expression dysregulation domains (GEDDs). GEDDs were also reported in fibroblasts derived from a DS mouse model duplicated for some Hsa21-orthologous genes, indicating cross-species conservation of this phenomenon. Here we investigate GEDDs using the Dp1Tyb mouse model of DS, which is duplicated for the entire Hsa21-orthologous region of mouse chromosome 16. Our statistical analysis shows that GEDDs are present both in DS cells and in Dp1Tyb mouse fibroblasts and hippocampus. However, we find that GEDDs do not depend on the DS genotype but occur whenever gene expression changes. We conclude that GEDDs are not a specific feature of DS but instead result from the clustering of co-regulated genes, a function of mammalian genome organisation.
Spinal neural tube closure depends on regulation of surface ectoderm identity and biomechanics by Grhl2
Authors: Nikolopoulou Evanthia , Hirst Caroline S. , Galea Gabriel , Venturini Christina , Moulding Dale , Marshall Abigail R. , Rolo Ana , De Castro Sandra C. P. , Copp Andrew J. , Greene Nicholas D. E.
Published: June 2019

Lack or excess expression of the surface ectoderm-expressed transcription factor Grainyhead-like2 (Grhl2), each prevent spinal neural tube closure. Here we investigate the causative mechanisms and find reciprocal dysregulation of epithelial genes, cell junction components and actomyosin properties in Grhl2 null and over-expressing embryos. Grhl2 null surface ectoderm shows a shift from epithelial to neuroepithelial identity (with ectopic expression of N-cadherin and Sox2), actomyosin disorganisation, cell shape changes and diminished resistance to neural fold recoil upon ablation of the closure point. In contrast, excessive abundance of Grhl2 generates a super-epithelial surface ectoderm, in which up-regulation of cell-cell junction proteins is associated with an actomyosin-dependent increase in local mechanical stress. This is compatible with apposition of the neural folds but not with progression of closure, unless myosin activity is inhibited. Overall, our findings suggest that Grhl2 plays a crucial role in regulating biomechanical properties of the surface ectoderm that are essential for spinal neurulation.
Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells
Authors: Haythorne Elizabeth , Rohm Maria , van de Bunt Martijn , Brereton Melissa F. , Tarasov Andrei I. , Blacker Thomas S. , Sachse Gregor , Silva dos Santos Mariana , Terron Exposito Raul , Davis Simon , Baba Otto , Fischer Roman , Duchen Michael R. , Rorsman Patrik , MacRae James I. , Ashcroft Frances M.
Published: June 2019

Diabetes is a global health problem caused primarily by the inability of pancreatic β-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of β-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic βV59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 β-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in β-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of β-cells in diabetes.
Low viscosity of the Earth’s inner core
Authors: Belonoshko Anatoly B. , Fu Jie , Bryk Taras , Simak Sergei I. , Mattesini Maurizio
Published: June 2019

The Earth’s solid inner core is a highly attenuating medium. It consists mainly of iron. The high attenuation of sound wave propagation in the inner core is at odds with the widely accepted paradigm of hexagonal close-packed phase stability under inner core conditions, because sound waves propagate through the hexagonal iron without energy dissipation. Here we show by first-principles molecular dynamics that the body-centered cubic phase of iron, recently demonstrated to be thermodynamically stable under the inner core conditions, is considerably less elastic than the hexagonal phase. Being a crystalline phase, the body-centered cubic phase of iron possesses the viscosity close to that of a liquid iron. The high attenuation of sound in the inner core is due to the unique diffusion characteristic of the body-centered cubic phase. The low viscosity of iron in the inner core enables the convection and resolves a number of controversies.
Vibrio sp. dhg as a platform for the biorefinery of brown macroalgae
Authors: Lim Hyun Gyu , Kwak Dong Hun , Park Sungwoo , Woo Sunghwa , Yang Jae-Seong , Kang Chae Won , Kim Beomhee , Noh Myung Hyun , Seo Sang Woo , Jung Gyoo Yeol
Published: June 2019

Although brown macroalgae holds potential as an alternative feedstock, its utilization by conventional microbial platforms has been limited due to the inability to metabolize one of the principal sugars, alginate. Here, we isolate Vibrio sp. dhg, a fast-growing bacterium that can efficiently assimilate alginate. Based on systematic characterization of the genomic information of Vibrio sp. dhg, we establish a genetic toolbox for its engineering. We also demonstrate its ability to rapidly produce ethanol, 2,3-butanediol, and lycopene from brown macroalgae sugar mixture with high productivities and yields. Collectively, Vibrio sp. dhg can be used as a platform for the efficient conversion of brown macroalgae sugars into diverse value-added biochemicals.
Theory of the field-revealed Kitaev spin liquid
Authors: Gordon Jacob S. , Catuneanu Andrei , Sørensen Erik S. , Kee Hae-Young
Published: June 2019

Elementary excitations in entangled states such as quantum spin liquids may exhibit exotic statistics different from those obeyed by fundamental bosons and fermions. Non-Abelian anyons exist in a Kitaev spin liquid—the ground state of an exactly solvable model. A smoking-gun signature of these excitations, namely a half-integer quantized thermal Hall conductivity, was recently reported in α-RuCl3. While fascinating, a microscopic theory for this phenomenon remains elusive because the pure Kitaev model cannot display this effect in an intermediate magnetic field. Here we present a microscopic theory of the Kitaev spin liquid emerging between the low- and high-field states. Essential to this result is an antiferromagnetic off-diagonal symmetric interaction which allows the Kitaev spin liquid to protrude from the ferromagnetic Kitaev limit under a magnetic field. This generic model displays a strong field anisotropy, and we predict a wide spin liquid regime when the field is perpendicular to the honeycomb plane.
Factors other than hTau overexpression that contribute to tauopathy-like phenotype in rTg4510 mice
Authors: Gamache Julia , Benzow Kellie , Forster Colleen , Kemper Lisa , Hlynialuk Chris , Furrow Eva , Ashe Karen H. , Koob Michael D.
Published: June 2019

The tauopathy-like phenotype observed in the rTg4510 mouse line, in which human tauP301L expression specifically within the forebrain can be temporally controlled, has largely been attributed to high overexpression of mutant human tau in the forebrain region. Unexpectedly, we found that in a different mouse line with a targeted-insertion of the same transgene driven by the same tetracycline-TransActivator (tTA) allele, but with even higher overexpression of tauP301L than rTg4510, atrophy and tau histopathology are delayed, and a different behavioral profile is observed. This suggests that it is not overexpression of mutant human tau alone that contributes to the phenotype in rTg4510 mice. Furthermore we show that the tauopathy-like phenotype seen in rTg4510 requires a ~70-copy tau-transgene insertion in a 244 kb deletion in Fgf14, a ~7-copy tTA-transgene insertion in a 508 kb deletion that disrupts another five genes, in addition to high transgene overexpression. We propose that these additional effects need to be accounted for in any studies using rTg4510.
Simplicial models of social contagion
Authors: Iacopini Iacopo , Petri Giovanni , Barrat Alain , Latora Vito
Published: June 2019

Complex networks have been successfully used to describe the spread of diseases in populations of interacting individuals. Conversely, pairwise interactions are often not enough to characterize social contagion processes such as opinion formation or the adoption of novelties, where complex mechanisms of influence and reinforcement are at work. Here we introduce a higher-order model of social contagion in which a social system is represented by a simplicial complex and contagion can occur through interactions in groups of different sizes. Numerical simulations of the model on both empirical and synthetic simplicial complexes highlight the emergence of novel phenomena such as a discontinuous transition induced by higher-order interactions. We show analytically that the transition is discontinuous and that a bistable region appears where healthy and endemic states co-exist. Our results help explain why critical masses are required to initiate social changes and contribute to the understanding of higher-order interactions in complex systems.
Introducing risk inequality metrics in tuberculosis policy development
Authors: Gomes M. Gabriela M. , Oliveira Juliane F. , Bertolde Adelmo , Ayabina Diepreye , Nguyen Tuan Anh , Maciel Ethel L. , Duarte Raquel , Nguyen Binh Hoa , Shete Priya B. , Lienhardt Christian
Published: June 2019

Global stakeholders including the World Health Organization rely on predictive models for developing strategies and setting targets for tuberculosis care and control programs. Failure to account for variation in individual risk leads to substantial biases that impair data interpretation and policy decisions. Anticipated impediments to estimating heterogeneity for each parameter are discouraging despite considerable technical progress in recent years. Here we identify acquisition of infection as the single process where heterogeneity most fundamentally impacts model outputs, due to selection imposed by dynamic forces of infection. We introduce concrete metrics of risk inequality, demonstrate their utility in mathematical models, and pack the information into a risk inequality coefficient (RIC) which can be calculated and reported by national tuberculosis programs for use in policy development and modeling.
Cellular advective-diffusion drives the emergence of bacterial surface colonization patterns and heterogeneity
Authors: Rossy Tamara , Nadell Carey D. , Persat Alexandre
Published: June 2019

Microorganisms navigate and divide on surfaces to form multicellular structures called biofilms, the most widespread survival strategy found in the bacterial world. One common assumption is that cellular components guide the spatial architecture and arrangement of multiple species in a biofilm. However, bacteria must contend with mechanical forces generated through contact with surfaces and under fluid flow, whose contributions to colonization patterns are poorly understood. Here, we show how the balance between motility and flow promotes the emergence of morphological patterns in Caulobacter crescentus biofilms. By modeling transport of single cells by flow and Brownian-like swimming, we show that the emergence of these patterns is guided by an effective Péclet number. By analogy with transport phenomena we show that, counter-intuitively, fluid flow represses mixing of distinct clonal lineages, thereby affecting the interaction landscapes between biofilm-dwelling bacteria. This demonstrates that hydrodynamics influence species interaction and evolution within surface-associated communities.
High-throughput prediction of the ground-state collinear magnetic order of inorganic materials using Density Functional Theory
Authors: Horton Matthew Kristofer , Montoya Joseph Harold , Liu Miao , Persson Kristin Aslaug
Published: June 2019

We present a robust, automatic high-throughput workflow for the calculation of magnetic ground state of solid-state inorganic crystals, whether ferromagnetic, antiferromagnetic or ferrimagnetic, and their associated magnetic moments within the framework of collinear spin-polarized Density Functional Theory. This is done through a computationally efficient scheme whereby plausible magnetic orderings are first enumerated and prioritized based on symmetry, and then relaxed and their energies determined through conventional DFT + U calculations. This automated workflow is formalized using the atomate code for reliable, systematic use at a scale appropriate for thousands of materials and is fully customizable. The performance of the workflow is evaluated against a benchmark of 64 experimentally known mostly ionic magnetic materials of non-trivial magnetic order and by the calculation of over 500 distinct magnetic orderings. A non-ferromagnetic ground state is correctly predicted in 95% of the benchmark materials, with the experimentally determined ground state ordering found exactly in over 60% of cases. Knowledge of the ground state magnetic order at scale opens up the possibility of high-throughput screening studies based on magnetic properties, thereby accelerating discovery and understanding of new functional materials.
Model of a Support Vector Machine to Assess the Functional Cure for Surgery of Intermittent Exotropia
Authors: Liu Yanli , Liu Chungao , Zhang Wei , Chen Xia , Zhao Kanxing
Published: June 2019

In this paper the optimum timing for the postoperative functional cure of basic intermittent exotropia is explored based on support vector machine (SVM). One hundred and thirty-two patients were recruited in this prospective cross-sectional study with 6 months of follow-up. Examinations included angle of deviation, central and peripheral fusion, controllability, and near and distance stereopsis. Influencing factors of postoperative alignment and stereopsis were analyzed with a chi-squared test and univariate and multivariate logistic regression analyses. At 6 months post-operation, there were 84 successful procedures for the angle of deviation, with 4 overcorrections and 44 undercorrections. The success rate was 63.6%. The angle of deviation on postoperative day 1 was the only significant associated factor. One hundred and thirty patients had normal near stereoacuity, 60 had normal distance stereoacuity according to a Functional Visual Analyzer assessment, and 108 had normal stereoacuity as assessed by the Frisby Davis Distance (FD2) stereotest. The age of onset and preoperative distance stereoacuity with FD2 were the influencing factors of postoperative distance stereopsis restoration. The accuracy of this method of SVM was 82.1%. The angle of deviation for distance on postoperative day 1 was the only significant factor that correlated with alignment at 6 months post-operation, and the model of SVM was useful to determine the optimal time of the postoperative functional cure.
Publisher Correction: Protein expression changes caused by spaceflight as measured for 18 Russian cosmonauts
Authors: Larina Irina M. , Percy Andrew J. , Yang Juncong , Borchers Christoph H. , Nosovsky Andrei M. , Grigoriev Anatoli I. , Nikolaev Evgeny N.
Published: June 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Author Correction: A comprehensive analysis of the faecal microbiome and metabolome of Strongyloides stercoralis infected volunteers from a non-endemic area
Authors: Jenkins Timothy P. , Formenti Fabio , Castro Cecilia , Piubelli Chiara , Perandin Francesca , Buonfrate Dora , Otranto Domenico , Griffin Julian L. , Krause Lutz , Bisoffi Zeno , Cantacessi Cinzia
Published: June 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Human osteogenic differentiation in Space: proteomic and epigenetic clues to better understand osteoporosis
Authors: Gambacurta Alessandra , Merlini Giulia , Ruggiero Cristina , Diedenhofen Giacomo , Battista Natalia , Bari Monica , Balsamo Michele , Piccirillo Sara , Valentini Giovanni , Mascetti Gabriele , Maccarrone Mauro
Published: June 2019

In the frame of the VITA mission of the Italian Space Agency (ASI), we addressed the problem of Space osteoporosis by using human blood-derived stem cells (BDSCs) as a suitable osteogenic differentiation model. In particular, we investigated proteomic and epigenetic changes in BDSCs during osteoblastic differentiation induced by rapamycin under microgravity conditions. A decrease in the expression of 4 embryonic markers (Sox2, Oct3/4, Nanog and E-cadherin) was found to occur to a larger extent on board the ISS than on Earth, along with an earlier activation of the differentiation process towards the osteogenic lineage. The changes in the expression of 4 transcription factors (Otx2, Snail, GATA4 and Sox17) engaged in osteogenesis supported these findings. We then ascertained whether osteogenic differentiation of BDSCs could depend on epigenetic regulation, and interrogated changes of histone H3 that is crucial in this type of gene control. Indeed, we found that H3K4me3, H3K27me2/3, H3K79me2/3 and H3K9me2/3 residues are engaged in cellular reprogramming that drives gene expression. Overall, we suggest that rapamycin induces transcriptional activation of BDSCs towards osteogenic differentiation, through increased GATA4 and Sox17 that modulate downstream transcription factors (like Runx2), critical for bone formation. Additional studies are warranted to ascertain the possible exploitation of these data to identify new biomarkers and therapeutic targets to treat osteoporosis, not only in Space but also on Earth.
Morphological organization of point-to-point transport in complex networks
Authors: Kang Min-Yeong , Berthelot Geoffroy , Tupikina Liubov , Nicolaides Christos , Colonna Jean-Francois , Sapoval Bernard , Grebenkov Denis S.
Published: June 2019

We investigate the structural organization of the point-to-point electric, diffusive or hydraulic transport in complex scale-free networks. The random choice of two nodes, a source and a drain, to which a potential difference is applied, selects two tree-like structures, one emerging from the source and the other converging to the drain. These trees merge into a large cluster of the remaining nodes that is found to be quasi-equipotential and thus presents almost no resistance to transport. Such a global “tree-cluster-tree” structure is universal and leads to a power law decay of the currents distribution. Its exponent, −2, is determined by the multiplicative decrease of currents at successive branching points of a tree and is found to be independent of the network connectivity degree and resistance distribution.
Humans Use Predictive Gaze Strategies to Target Waypoints for Steering
Authors: Tuhkanen Samuel , Pekkanen Jami , Rinkkala Paavo , Mole Callum , Wilkie Richard M. , Lappi Otto
Published: June 2019

A major unresolved question in understanding visually guided locomotion in humans is whether actions are driven solely by the immediately available optical information (model-free online control mechanisms), or whether internal models have a role in anticipating the future path. We designed two experiments to investigate this issue, measuring spontaneous gaze behaviour while steering, and predictive gaze behaviour when future path information was withheld. In Experiment 1 participants (N = 15) steered along a winding path with rich optic flow: gaze patterns were consistent with tracking waypoints on the future path 1–3 s ahead. In Experiment 2, participants (N = 12) followed a path presented only in the form of visual waypoints located on an otherwise featureless ground plane. New waypoints appeared periodically every 0.75 s and predictably 2 s ahead, except in 25% of the cases the waypoint at the expected location was not displayed. In these cases, there were always other visible waypoints for the participant to fixate, yet participants continued to make saccades to the empty, but predictable, waypoint locations (in line with internal models of the future path guiding gaze fixations). This would not be expected based upon existing model-free online steering control models, and strongly points to a need for models of steering control to include mechanisms for predictive gaze control that support anticipatory path following behaviours.
Modeling the Effect of the Metastatic Microenvironment on Phenotypes Conferred by Estrogen Receptor Mutations Using a Human Liver Microphysiological System
Authors: Miedel Mark T. , Gavlock Dillon C. , Jia Shanhang , Gough Albert , Taylor D. Lansing , Stern Andrew M.
Published: June 2019

Reciprocal coevolution of tumors and their microenvironments underlies disease progression, yet intrinsic limitations of patient-derived xenografts and simpler cell-based models present challenges towards a deeper understanding of these intercellular communication networks. To help overcome these barriers and complement existing models, we have developed a human microphysiological system (MPS) model of the human liver acinus, a common metastatic site, and have applied this system to estrogen receptor (ER)+ breast cancer. In addition to their hallmark constitutive (but ER-dependent) growth phenotype, different ESR1 missense mutations, prominently observed during estrogen deprivation therapy, confer distinct estrogen-enhanced growth and drug resistant phenotypes not evident under cell autonomous conditions. Under low molecular oxygen within the physiological range (~5–20%) of the normal liver acinus, the estrogen-enhanced growth phenotypes are lost, a dependency not observed in monoculture. In contrast, the constitutive growth phenotypes are invariant within this range of molecular oxygen suggesting that ESR1 mutations confer a growth advantage not only during estrogen deprivation but also at lower oxygen levels. We discuss the prospects and limitations of implementing human MPS, especially in conjunction with in situ single cell hyperplexed computational pathology platforms, to identify biomarkers mechanistically linked to disease progression that inform optimal therapeutic strategies for patients.
Comparative genomics provides new insights into the remarkable adaptations of the African wild dog (Lycaon pictus)
Authors: Chavez Daniel E. , Gronau Ilan , Hains Taylor , Kliver Sergei , Koepfli Klaus-Peter , Wayne Robert K.
Published: June 2019

Within the Canidae, the African wild dog (Lycaon pictus) is the most specialized with regards to cursorial adaptations (specialized for running), having only four digits on their forefeet. In addition, this species is one of the few canids considered to be an obligate meat-eater, possessing a robust dentition for taking down large prey, and displays one of the most variable coat colorations amongst mammals. Here, we used comparative genomic analysis to investigate the evolutionary history and genetic basis for adaptations associated with cursoriality, hypercanivory, and coat color variation in African wild dogs. Genome-wide scans revealed unique amino acid deletions that suggest a mode of evolutionary digit loss through expanded apoptosis in the developing first digit. African wild dog-specific signals of positive selection also uncovered a putative mechanism of molar cusp modification through changes in genes associated with the sonic hedgehog (SHH) signaling pathway, required for spatial patterning of teeth, and three genes associated with pigmentation. Divergence time analyses suggest the suite of genomic changes we identified evolved ~1.7 Mya, coinciding with the diversification of large-bodied ungulates. Our results show that comparative genomics is a powerful tool for identifying the genetic basis of evolutionary changes in Canidae.
Ligand induced switching of the band alignment in aqueous synthesized CdTe/CdS core/shell nanocrystals
Authors: Vale Brener R. C. , Mourão Rafael S. , Bettini Jefferson , Sousa José C. L. , Ferrari Jefferson L. , Reiss Peter , Aldakov Dmitry , Schiavon Marco A.
Published: June 2019

CdTe/CdS core/shell quantum dots (QDs) are formed in aqueous synthesis via the partial decomposition of hydrophilic thiols, used as surface ligands. In this work, we investigate the influence of the chemical nature (functional group and chain length) of the used surface ligands on the shell formation. Four different surface ligands are compared: 3-mercaptopropionic acid, MPA, thioglycolic acid, TGA, sodium 3-mercaptopropanesulfonate, MPS, and sodium 2-mercaptoethanesulfonate, MES. The QD growth rate increases when the ligand aliphatic chain length decreases due to steric reasons. At the same time, the QDs stabilized with carboxylate ligands grow faster and achieve higher photoluminescence quantum yields compared to those containing sulfonate ligands. The average PL lifetime of TGA and MPA capped QDs is similar (≈20 ns) while in the case of MPS shorter (≈15 ns) and for MES significantly longer (≈30 ns) values are measured. A detailed structural analysis combining powder X-ray diffraction, and X-ray photoelectron spectroscopy (XPS) indicates the existence of two novel regimes of band alignment: in the case of the mercaptocarboxylate ligands the classic type I band alignment between the core and shell materials is predominant, while the mercaptosulfonate ligands induce a quasi-type II alignment (MES) or an inverted type I alignment (MPS). Finally, the effect of the pH value on the optical properties was evaluated: using a ligand excess in solution allows achieving better stability of the QDs while maintaining high photoluminescence intensity at low pH.
Efficient preparation of kaolinite/methanol intercalation composite by using a Soxhlet extractor
Authors: Qu Hao , He Sihui , Su Haiquan
Published: June 2019

Kaolinite/methanol intercalation composite (KMe) is a key precursor for preparing clay-based inorganic/organic hybrid materials and kaolinite nanoscrolls. However, synthesis of KMe is a time and methanol dissipative process and the complexity of this process also limits its further applications. In this study, Soxhlet extractor was introduced to synthesize an intercalation composite and KMe was efficiently synthesized in a Soxhlet extractor through a continuous displacement process by using kaolinite/DMSO intercalation composite (KD) as a precursor. The formation process of kaolinite/methanol intercalation composite was studied by X-ray diffraction (XRD) and infrared spectroscopy (IR). The results showed that the DMSO in kaolinite could be completely displaced by methanol in this process and the preparation of KMe could be completed in 8 hours, which was far faster than the reported methods. Moreover, methanol used in this process could be recycled. Furthermore, the resulting material could be successfully used to prepare kaolinite nanoscrolls in high yield.
Amide Proton Transfer-weighted MRI in the Diagnosis of Major Salivary Gland Tumors
Authors: Bae Yun Jung , Choi Byung Se , Jeong Woo-Jin , Jung Young Ho , Park Jung Hyun , Sunwoo Leonard , Jung Cheolkyu , Kim Jae Hyoung
Published: June 2019

Amide proton transfer-weighted magnetic resonance imaging (APTw-MRI), which is effective in tumor characterization, has expanded its role in the head and neck. We aimed to evaluate the diagnostic ability of APTw-MRI in differentiating malignant from benign major salivary gland tumors compared with diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE)-MRI. Between December 2017 and November 2018, 38 subjects, who were diagnosed with major salivary gland tumors and who underwent preoperative 3 T MRI, including APTw-MRI, DWI, and DCE-MRI, were included in this retrospective study. Twenty-three subjects had benign tumors, and fifteen had malignancies. APTw-signals of the tumors were measured and compared according to the histopathological diagnosis. Using receiver operating characteristic curve analysis, diagnostic performance of APTw-MRI was evaluated and compared with DWI and DCE-MRI using DeLong test. The maximum, mean, and median APTw-signals were significantly higher in malignant than in benign tumors (P < 0.001). The mean and maximum APTw-signals showed excellent area under the curve for predicting malignant tumors (0.948 and 0.939), which were significantly higher than the combining use of DWI and DCE-MRI (0.780) (P = 0.021 and 0.028). Therefore, APTw-MRI could be a useful tool for differentiating malignant from benign major salivary gland tumors, and can be applicable in the clinical setting.
Mycobacterial phosphatase PstP regulates global serine threonine phosphorylation and cell division
Authors: Iswahyudi  , Mukamolova Galina V. , Straatman-Iwanowska Anna A. , Allcock Natalie , Ajuh Paul , Turapov Obolbek , O’Hare Helen M.
Published: June 2019

Protein phosphatase PstP is conserved throughout the Actinobacteria in a genetic locus related to cell wall synthesis and cell division. In many Actinobacteria it is the sole annotated serine threonine protein phosphatase to counter the activity of multiple serine threonine protein kinases. We used transcriptional knockdown, electron microscopy and comparative phosphoproteomics to investigate the putative dual functions of PstP as a specific regulator of cell division and as a global regulator of protein phosphorylation. Comparative phosphoproteomics in the early stages of PstP depletion showed hyperphosphorylation of protein kinases and their substrates, confirming PstP as a negative regulator of kinase activity and global serine and threonine phosphorylation. Analysis of the 838 phosphorylation sites that changed significantly, suggested that PstP may regulate diverse phosphoproteins, preferentially at phosphothreonine near acidic residues, near the protein termini, and within membrane associated proteins. Increased phosphorylation of the activation loop of protein kinase B (PknB) and of the essential PknB substrate CwlM offer possible explanations for the requirement for pstP for growth and for cell wall defects when PstP was depleted.
A systematic review of feasibility studies promoting the use of mobile technologies in clinical research
Authors: Bakker Jessie P. , Goldsack Jennifer C. , Clarke Michael , Coravos Andrea , Geoghegan Cynthia , Godfrey Alan , Heasley Matthew G. , Karlin Daniel R. , Manta Christine , Peterson Barry , Ramirez Ernesto , Sheth Nirav , Bruno Antonia , Bullis Emilia , Wareham Kirsten , Zimmerman Noah , Forrest Annemarie , Wood William A.
Published: June 2019

Mobile technologies, such as smart phone applications, wearables, ingestibles, and implantables, are increasingly used in clinical research to capture study endpoints. On behalf of the Clinical Trials Transformation Initiative, we aimed to conduct a systematic scoping review and compile a database summarizing pilot studies addressing mobile technology sensor performance, algorithm development, software performance, and/or operational feasibility, in order to provide a resource for guiding decisions about which technology is most suitable for a particular trial. Our systematic search identified 275 publications meeting inclusion criteria. From these papers, we extracted data including the medical condition, concept of interest captured by the mobile technology, outcomes captured by the digital measurement, and details regarding the sensors, algorithms, and study sample. Sixty-seven percent of the technologies identified were wearable sensors, with the remainder including tablets, smartphones, implanted sensors, and cameras. We noted substantial variability in terms of reporting completeness and terminology used. The data have been compiled into an online database maintained by the Clinical Trials Transformation Initiative that can be filtered and searched electronically, enabling a user to find information most relevant to their work. Our long-term goal is to maintain and update the online database, in order to promote standardization of methods and reporting, encourage collaboration, and avoid redundant studies, thereby contributing to the design and implementation of efficient, high-quality trials.
Stereo- and regioselective glycosylation with protection-less sugar derivatives: an alluring strategy to access glycans and natural products
Authors: Báti Gábor , He Jing-Xi , Pal Kumar Bhaskar , Liu Xue-Wei
Published: June 2019

This review delivers insights for dedicated chemists into the development of efficient methods in accessing carbohydrates at a lower cost.
Detection of Escherichia coli O157:H7 and Salmonella enterica serotype Typhimurium based on cell elongation induced by beta-lactam antibiotics
Authors: Jia Min , Liu Zhaochen , Wu Chuanchen , Zhang Zhen , Ma Luyao , Lu Xiaonan , Mao Yifei , Zhang Hongyan
Published: June 2019

A novel Gram-negative bacteria detection method based on cell elongation combined with membrane filtration and magnetic separation was established.
Versatile “on–off” biosensing of thrombin and miRNA based on Ag(i) ion-enhanced or Ag nanocluster-quenched electrochemiluminescence coupled with hybridization chain reaction amplification
Authors: Ge Junjun , Li Chunli , Zhao Yu , Yu Xijuan , Jie Guifen
Published: June 2019

A novel biosensing platform based on Ag(i) ion-enhanced or Ag nanoclusters (NCs)-quenched electrochemiluminescence (ECL) of CdSe quantum dots (QDs) was designed for versatile “on–off” assays of thrombin (TB) and miRNA.
Aromatic guanidines as highly active binary catalytic systems for the fixation of CO2 into cyclic carbonates under mild conditions
Authors: Mesías-Salazar Ángela , Martínez Javier , Rojas René S. , Carrillo-Hermosilla Fernando , Ramos Alberto , Fernández-Galán Rafael , Antiñolo Antonio
Published: June 2019

The formation of hydrogen bonding causes a considerable decrease in the reaction temperature and CO2 pressure used in this process.
Surface-modified Pt1Ni1–Ni(OH)2nanoparticles with abundant Pt–Ni(OH)2interfaces enhance electrocatalytic properties
Authors: Qin Yuchen , Zhuo Hongying , Liang Xiaoyu , Yu Kuomiao , Wang Yao , Gao Daowei , Zhang Xin
Published: June 2019

Pt1Ni1–Ni(OH)2NPs with abundant Pt–Ni(OH)2interfaces exhibit a rather high activity and stability for the MOR in alkaline electrolytes.
Cinnamaldehyde attenuates atherosclerosis via targeting the IκB/NF-κB signaling pathway in high fat diet-induced ApoE−/− mice
Authors: Li Weifeng , Zhi Wenbing , Zhao Jinmeng , Li Wenqi , Zang Lulu , Liu Fang , Niu Xiaofeng
Published: June 2019

Cinnamaldehyde is a flavor isolated from the bark of Cinnamomum cassia Presl and exerts anti-inflammation effects in various diseases.
Integrating user behavior with engineering design of point-of-care diagnostic devices: theoretical framework and empirical findings
Authors: Nayak Samiksha , Guo Tiffany , Lopez-Rios Javier , Lentz Cody , Arumugam Siddarth , Hughes Joshua , Dolezal Curtis , Linder Vincent , Carballo-Diéguez Alex , Balán Iván C. , Sia Samuel K.
Published: June 2019

As point-of-care diagnostic devices become increasingly available to untrained users, it will be critical to understand how user behavior can best guide the engineering design process.
Effect of symmetric and asymmetric substitution on the optoelectronic properties of 9,10-dicyanoanthracene
Authors: Glöcklhofer Florian , Rosspeintner Arnulf , Pasitsuparoad Pakorn , Eder Simon , Fröhlich Johannes , Angulo Gonzalo , Vauthey Eric , Plasser Felix
Published: June 2019

Six newly synthesised 9,10-dicyanoanthracene derivatives exhibit high two-photon absorption cross sections particularly upon symmetric substitution with strong electron donors.
On the nucleophilic derivatization of 4,7-dibromo-[1,2,5]thiadiazolo[3,4-c]pyridine: basis for biologically interesting species and building blocks for organic materials
Authors: González-Antonio Oscar , Navarro Villalobos Mauricio , Vázquez-Alvarado María Magdalena , Santillan Rosa , Flores-Pérez Blas , Romero-Ávila Margarita , Farfán Norberto
Published: June 2019

Eleven new thiadiazolopyridine-derived building blocks were synthesized through a selective SNAr reaction and the key steps of their reaction mechanism and spectroscopic properties were studied.
Reconfigurable parity-time symmetry transition in phase change metamaterials
Authors: Cao Tun , Cao Ying , Fang Linhan
Published: June 2019

Reconfigurable parity-time symmetry transition in GeTe based metamaterials by switching the structural state of GeTe between amorphous and crystalline.
A new etching process for zinc oxide with etching rate and crystal plane control: experiment, calculation, and membrane application
Authors: Chung Jiyong , Lee Jeong Hee , Kim Kyeounghak , Lee Jaeyoung , Yoo Sung Jong , Han Jeong Woo , Kim Jinsoo , Yu Taekyung
Published: June 2019

The etching process can be a useful method for the morphology control of nanostructures.
Tunable bimetallic Au–Pd@CeO2 for semihydrogenation of phenylacetylene by ammonia borane
Authors: Liu Yu , Wang Qishun , Wu Lanlan , Long Yan , Li Jian , Song Shuyan , Zhang Hongjie
Published: June 2019

The bimetallic core ceria shell Au–Pd@CeO2 has been successfully fabricated through a one pot autoredox reaction, which shows high activity and selectivity towards the semihydrogenation of phenylacetylene by ammonia borane.
Miniaturized nanohole array based plasmonic sensor for the detection of acetone and ethanol with insights into the kinetics of adsorptive plasmonic sensing
Authors: Zhao Yangyang , Mukherjee Kalisadhan , Benkstein Kurt D. , Sun Libin , Steffens Kristen L. , Montgomery Christopher B. , Guo Shiqi , Semancik Steve , Zaghloul Mona E.
Published: June 2019

MOF-coated NHA plasmonic gas sensor with high sensitivity and temperature-induced analyte discrimination.
Reversible photo-cross-linking of the GCN4 peptide containing 3-cyanovinylcarbazole amino acid to double-stranded DNA
Authors: Qiu Zhiyong , Nakamura Shigetaka , Fujimoto Kenzo
Published: June 2019

Interaction analysis in vivo greatly promotes the analyses and understanding of biological functions.
A thio-β-cyclodextrin functionalized graphene/gold nanoparticle electrochemical sensor: a study of the size effect of the gold nanoparticles and the determination of tetrabromobisphenol A
Authors: Luo Suxing , Wu Yuanhui , Mou Qingsong , Li Jinhai , Luo Xiaoxue
Published: June 2019

In this study, a novel tetrabromobisphenol A (TBBPA) sensor was fabricated based on a CTAB-capped gold nanoparticle (AuNP)-thio-β-cyclodextrin (SH-β-CD)/graphene oxide modified glassy carbon electrode (GCE).
Reaction kinetics of a water-soluble palladium–β-cyclodextrin catalyst for a Suzuki–Miyaura cross-coupling in continuous flow
Authors: Liu Yukun , Hartman Ryan L.
Published: June 2019

An experimental and theoretical investigation on the reaction kinetics of a Suzuki–Miyaura cross-coupling catalyzed using the Pd–β-cyclodextrin ligand in continuous flow.
Definitive screening designs for multistep kinetic models in flow
Authors: Hone Christopher A. , Boyd Alistair , O'Kearney-McMullan Anne , Bourne Richard A. , Muller Frans L.
Published: June 2019

A definitive screening design (DSD) combined with reaction profiling was conducted using a flow reactor, in a short time frame, for the accurate estimation of kinetic parameters.