bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parasite motility is critical for virulence of African trypanosomes
Authors: Shimogawa Michelle M. , Ray Sunayan S. , Kisalu Neville , Zhang Yibo , Geng Quanjie , Ozcan Aydogan , Hill Kent L. 
Published: June 2018

AbstractAfrican trypanosomes, Trypanosoma brucei spp., are lethal pathogens that cause substantial human suffering and limit economic development in some of the world’s most impoverished regions. The name Trypanosoma (“auger cell”) derives from the parasite’s distinctive motility, which is driven by a single flagellum. However, despite decades of study, a requirement for trypanosome motility in mammalian host infection has not been established. LC1 is a conserved dynein subunit required for flagellar motility. Prior studies with a conditional RNAi-based LC1 mutant, RNAi-K/R, revealed that parasites with defective motility could infect mice. However, RNAi-K/R retained residual expression of wild-type LC1 and residual motility, thus precluding definitive interpretation. To overcome these limitations, here we generate constitutive mutants in which both LC1 alleles are replaced with mutant versions. These double knock-in mutants show reduced motility compared to RNAi-K/R and are viable in culture, but are unable to maintain bloodstream infection in mice. The virulence defect is independent of infection route but dependent on an intact host immune system. By comparing different mutants, we also reveal a critical dependence on the LC1 N-terminus for motility and virulence. Our findings demonstrate that trypanosome motility is critical for establishment and maintenance of bloodstream infection, implicating dynein-dependent flagellar motility as a potential drug target.
Highly-efficient three-dimensional waveguide couplers using impedance-tunable transformation optics
Authors: Cao Jun , Qi Fenghua , Yan Senlin , Zhang Lifa 
Published: June 2018

AbstractThere is growing interest in designing waveguide couplers with low reflections. Using impedance-tunable transformation optics, we propose a coordinate transformation technique in the design of compact three-dimensional waveguide couplers. To transmit electromagnetic waves between two coaxial waveguides with different inner and outer radii in the microwave range, a suitable impedance function is derived to reduce the impedance mismatch at the boundary, which make the fabrication process being simplified due to the reduced set of transformation media(dielectric response materials only). A larger refractive index is set to raise the coupling performance in the low frequency range. Next we apply impedance-tunable transformation optics to the design of dielectric waveguide couplers, where only the core region be contained in the transformed space; by selecting a tunable impedance function, waves can transmit efficiently through waveguides with quite different cross sections and background media. The proposed impedance-tunable three-dimensional waveguide couplers are confirmed by the 3-dimensional numerical simulation with good performances, which can have potential applications in fiber-to-chip coupling.
Realization of an ultrathin acoustic lens for subwavelength focusing in the megasonic range
Authors: Hyun Jaeyub , Kim Yong Tae , Doh Il , Ahn Bongyoung , Baik Kyungmin , Kim Se-Hwa 
Published: June 2018

AbstractIn this study, we report the first experimental realization of an ultrathin (0.14λ, λ = 1.482 mm means wavelength at 1 MHz in the water medium) subwavelength focusing acoustic lens that can surpass the Rayleigh diffraction limit (0.61λ/NA, NA means numerical aperture). It is termed a Super-Oscillatory Acoustic Lens (SOAL), and it operates in the megasonic range. The SOAL represents an interesting feature allowing the achievement of subwavelength focusing without the need to operate in close proximity to the object to be imaged. The optimal layout of the SOAL is obtained by utilizing a systematic design approach, referred to here as topology optimization. To this end, the optimization formulation is newly defined. The optimized SOAL is fabricated using a photo-etching process and its subwavelength focusing performance is verified experimentally via an acoustic intensity measurement system. From these measurements, we found that the proposed optimized SOAL can achieve superior focusing features with a Full Width at Half Maximum (FWHM) of ~0.40λ/NA ≃ 0.84 mm (for our SOAL, NA = 0.707) with the transmission efficiency of 26.5%.
On the thermal shock resistance and mechanical properties of novel unidirectional UHTCMCs for extreme environments
Authors: Zoli Luca , Vinci Antonio , Galizia Pietro , Melandri Cesare , Sciti Diletta 
Published: June 2018

AbstractAerospace provides a strong driving force for technological development. Recently a novel class of composites for harsh environments, based on ultra-high temperature ceramic composites reinforced with continuous fibers (UHTCMC), is being developed. The goal of this work is to overcome the current data patchwork about their microstructural optimization and structural behavior, by showing a consistent mechanical characterization of well-defined and developed UHTCMCs based on ZrB2-matrix. The obtained composites have a density of 3.7 g/cm3 and porosity of less than 10%. The flexural strength increased from 360 to 550 MPa from room temperature to 1500 °C, showing a non-brittle behaviour. The composites were able to sustain a thermal shock severity as high as 1500 °C. The maximum decrease of strength at 1400 °C was 16% of the initial value, indicating that the samples could be shocked at even higher temperature. Flexural strength, Young’s modulus and coefficient of thermal expansions (CTE) of the composites were measured both along transverse and longitudinal direction and correlated to the microstructural features. The presented microstructural and mechanical characterization well defines the potentiality of the UHTCMCs and can be used as reference for the design and development of novel thermal protection systems and other structural components for harsh environments.
Pharmacological activation of epidermal growth factor receptor signaling inhibits colitis-associated cancer in mice
Authors: Dubé Philip E. , Liu Cambrian Y. , Girish Nandini , Washington M. Kay , Polk D. Brent 
Published: June 2018

AbstractCurrent treatments for inflammatory bowel disease (IBD) target the overactive immune response of the intestinal mucosa. However, epidermal growth factor (EGF), an activating ligand of the EGF receptor (EGFR), has been shown to induce disease remission through direct targeting of intestinal mucosal healing. Despite promising preclinical and clinical results, this EGFR-activating therapy has not progressed, in part due to the potential for carcinogenesis associated with long-term use and the increased risk of colitis-associated cancer (CAC) in IBD. Here we tested whether pharmacological modulation of EGFR altered outcomes of CAC in the murine azoxymethane/dextran sulfate sodium model. We found that administering EGF during the period of maximum colitis severity (“early”), coincident with the initiation and early promotion of tumors, improved outcomes of colitis and reduced tumor size. In contrast, daily EGF administration beginning ~2 months after tumor initiation (“late”) increased tumor size. Administration of the EGFR kinase inhibitor gefitinib increased the tumor size when the drug was given early and decreased the tumor size when the drug was administered late. EGF administration not only reduced colonic cytokine and chemokine expression during injury, but also baseline chemokine expression in homeostasis. These results suggest that EGFR activation during acute bouts of colitis may reduce the long-term burden of CAC.
The role of miR-122 in the dysregulation of glucose-6-phosphate dehydrogenase (G6PD) expression in hepatocellular cancer
Authors: Barajas Juan M. , Reyes Ryan , Guerrero Maria J. , Jacob Samson T. , Motiwala Tasneem , Ghoshal Kalpana 
Published: June 2018

AbstractHepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Thus, a better understanding of molecular aberrations involved in HCC pathogenesis is necessary for developing effective therapy. It is well established that cancer cells metabolize energy sources differently to rapidly generate biomass. Glucose-6-phosphate-dehydrogenase (G6PD), the rate-limiting enzyme of the Pentose Phosphate Pathway (PPP), is often activated in human malignancies to generate precursors for nucleotide and lipid synthesis. Here, we determined the clinical significance of G6PD in primary human HCC by analyzing RNA-seq and clinical data in The Cancer Genome Atlas. We found that the upregulation of G6PD correlates with higher tumor grade, increased tumor recurrence, and poor patient survival. Notably, liver-specific miR-122, which is essential for metabolic homeostasis, suppresses G6PD expression by directly interacting with its 3′UTR. Luciferase reporter assay confirmed two conserved functional miR-122 binding sites located in the 3′-UTR of G6PD. Furthermore, we show that ectopic expression of miR-122 and miR-1, a known regulator of G6PD expression coordinately repress G6PD expression in HCC cells. These miRNAs also reduced G6PD activity in HepG2 cells that express relatively high activity of this enzyme. Collectively, this study provides evidence that anti-HCC efficacy of miR122 and miR-1 could be mediated, at least in part, through inhibition of PPP by suppressing the expression of G6PD.
Complex history of dog (Canis familiaris) origins and translocations in the Pacific revealed by ancient mitogenomes
Authors: Greig K. , Gosling A. , Collins C. J. , Boocock J. , McDonald K. , Addison D. J. , Allen M. S. , David B. , Gibbs M. , Higham C. F. W. , Liu F. , McNiven I. J. , O’Connor S. , Tsang C. H. , Walter R. , Matisoo-Smith E. 
Published: June 2018

AbstractArchaeological evidence suggests that dogs were introduced to the islands of Oceania via Island Southeast Asia around 3,300 years ago, and reached the eastern islands of Polynesia by the fourteenth century AD. This dispersal is intimately tied to human expansion, but the involvement of dogs in Pacific migrations is not well understood. Our analyses of seven new complete ancient mitogenomes and five partial mtDNA sequences from archaeological dog specimens from Mainland and Island Southeast Asia and the Pacific suggests at least three dog dispersal events into the region, in addition to the introduction of dingoes to Australia. We see an early introduction of dogs to Island Southeast Asia, which does not appear to extend into the islands of Oceania. A shared haplogroup identified between Iron Age Taiwanese dogs, terminal-Lapita and post-Lapita dogs suggests that at least one dog lineage was introduced to Near Oceania by or as the result of interactions with Austronesian language speakers associated with the Lapita Cultural Complex. We did not find any evidence that these dogs were successfully transported beyond New Guinea. Finally, we identify a widespread dog clade found across the Pacific, including the islands of Polynesia, which likely suggests a post-Lapita dog introduction from southern Island Southeast Asia.
Recurrence Quantification Analysis at work: Quasi-periodicity based interpretation of gait force profiles for patients with Parkinson disease
Authors: Afsar Ozgur , Tirnakli Ugur , Marwan Norbert 
Published: June 2018

AbstractIn this letter, making use of real gait force profiles of healthy and patient groups with Parkinson disease which have different disease severity in terms of Hoehn-Yahr stage, we calculate various heuristic complexity measures of the recurrence quantification analysis (RQA). Using this technique, we are able to evince that entropy, determinism and average diagonal line length (divergence) measures decrease (increases) with increasing disease severity. We also explain these tendencies using a theoretical model (based on the sine-circle map), so that we clearly relate them to decreasing degree of irrationality of the system as a course of gait’s nature. This enables us to interpret the dynamics of normal/pathological gait and is expected to increase further applications of this technique on gait timings, gait force profiles and combinations of them with various physiological signals.
WNK1 regulates skeletal muscle cell hypertrophy by modulating the nuclear localization and transcriptional activity of FOXO4
Authors: Mandai Shintaro , Mori Takayasu , Nomura Naohiro , Furusho Taisuke , Arai Yohei , Kikuchi Hiroaki , Sasaki Emi , Sohara Eisei , Rai Tatemitsu , Uchida Shinichi 
Published: June 2018

AbstractWith-no-lysine (K) (WNK) kinases, which are mutated in the inherited form of hypertension pseudohypoaldosteronism type II, are essential regulators of membrane ion transporters. Here, we report that WNK1 positively regulates skeletal muscle cell hypertrophy via mediating the function of the pro-longevity transcription factor forkhead box protein O4 (FOXO4) independent of the conventional WNK signaling pathway linking SPS/STE20-related proline-alanine–rich kinase (SPAK)/oxidative stress response kinase 1 (OSR1) to downstream effector ion transporters. Small interfering RNA (siRNA)-mediated silencing of WNK1, but not SPAK/OSR1 kinases, induced myotube atrophy and remarkable increases in the mRNA expression of the muscle atrophy ubiquitin ligases MAFbx and MuRF1 in C2C12 mouse skeletal muscle cells. WNK1 silencing also increased FOXO4 nuclear localization, and co-transfection of Foxo4-targeted siRNA completely reversed the myotube atrophy and upregulation of atrogene transcription induced by WNK1 silencing. We further illustrated that WNK1 protein abundance in skeletal muscle was increased by chronic voluntary wheel running exercise (hypertrophic stimulus) and markedly decreased by adenine-induced chronic kidney disease (atrophic stimulus) in mice. These findings suggest that WNK1 is involved in the physiological regulation of mammalian skeletal muscle hypertrophy and atrophy via interactions with FOXO4. The WNK1-FOXO4 axis may be a potential therapeutic target in human diseases causing sarcopenia.
Fludarabine as a cost-effective adjuvant to enhance engraftment of human normal and malignant hematopoiesis in immunodeficient mice
Authors: Pievani A. , Michelozzi I. M. , Rambaldi B. , Granata V. , Corsi A. , Dazzi F. , Biondi A. , Serafini M. 
Published: June 2018

AbstractThere is still an unmet need for xenotransplantation models that efficiently recapitulate normal and malignant human hematopoiesis. Indeed, there are a number of strategies to generate humanized mice and specific protocols, including techniques to optimize the cytokine environment of recipient mice and drug alternatives or complementary to the standard conditioning regimens, that can be significantly modulated. Unfortunately, the high costs related to the use of sophisticated mouse models may limit the application of these models to studies that require an extensive experimental design. Here, using an affordable and convenient method, we demonstrate that the administration of fludarabine (FludaraTM) promotes the extensive and rapid engraftment of human normal hematopoiesis in immunodeficient mice. Quantification of human CD45+cells in bone marrow revealed approximately a 102-fold increase in mice conditioned with irradiation plus fludarabine. Engrafted cells in the bone marrow included hematopoietic stem cells, as well as myeloid and lymphoid cells. Moreover, this model proved to be sufficient for robust reconstitution of malignant myeloid hematopoiesis, permitting primary acute myeloid leukemia cells to engraft as early as 8 weeks after the transplant. Overall, these results present a novel and affordable model for engraftment of human normal and malignant hematopoiesis in immunodeficient mice.
Role of disorder when upscaling magnetocaloric Ni-Co-Mn-Al Heusler alloys from thin films to ribbons
Authors: Weise B. , Dutta B. , Teichert N. , Hütten A. , Hickel T. , Waske A. 
Published: June 2018

AbstractResearch in functional magnetic materials often employs thin films as model systems for finding new chemical compositions with promising properties. However, the scale-up of thin films towards bulk-like structures is challenging, since the material synthesis conditions are entirely different for thin films and e.g. rapid quenching methods. As one of the consequences, the type and degree of order in thin films and melt-spun ribbons are usually different, leading to different magnetic properties. In this work, using the example of magnetocaloric Ni-Co-Mn-Al melt-spun ribbons and thin films, we show that the excellent functional properties of the films can be reproduced also in ribbons, if an appropriate heat treatment is applied, that installs the right degree of order in the ribbons. We show that some chemical disorder is needed to get a pronounced and sharp martensitic transition. Increasing the order with annealing improves the magnetic properties only up to a point where selected types of disorder survive, which in turn compromise the magnetic properties. These findings allow us to understand the impact of the type and degree of disorder on the functional properties, paving the way for a faster transfer of combinatorial thin film research towards bulk-like materials for magnetic Heusler alloys.
DPubChem: a web tool for QSAR modeling and high-throughput virtual screening
Authors: Soufan Othman , Ba-alawi Wail , Magana-Mora Arturo , Essack Magbubah , Bajic Vladimir B. 
Published: June 2018

AbstractHigh-throughput screening (HTS) performs the experimental testing of a large number of chemical compounds aiming to identify those active in the considered assay. Alternatively, faster and cheaper methods of large-scale virtual screening are performed computationally through quantitative structure-activity relationship (QSAR) models. However, the vast amount of available HTS heterogeneous data and the imbalanced ratio of active to inactive compounds in an assay make this a challenging problem. Although different QSAR models have been proposed, they have certain limitations, e.g., high false positive rates, complicated user interface, and limited utilization options. Therefore, we developed DPubChem, a novel web tool for deriving QSAR models that implement the state-of-the-art machine-learning techniques to enhance the precision of the models and enable efficient analyses of experiments from PubChem BioAssay database. DPubChem also has a simple interface that provides various options to users. DPubChem predicted active compounds for 300 datasets with an average geometric mean and F1 score of 76.68% and 76.53%, respectively. Furthermore, DPubChem builds interaction networks that highlight novel predicted links between chemical compounds and biological assays. Using such a network, DPubChem successfully suggested a novel drug for the Niemann-Pick type C disease. DPubChem is freely available at www.cbrc.kaust.edu.sa/dpubchem.
Intra-individual Gene Expression Variability of Histologically Normal Breast Tissue
Authors: Sun Xuezheng , Shan Yue , Li Quefeng , Chollet-Hinton Lynn , Kirk Erin L. , Gierach Gretchen L. , Troester Melissa A. 
Published: June 2018

AbstractSeveral studies have sought to identify novel transcriptional biomarkers in normal breast or breast microenvironment to predict tumor risk and prognosis. However, systematic efforts to evaluate intra-individual variability of gene expression within normal breast have not been reported. This study analyzed the microarray gene expression data of 288 samples from 170 women in the Normal Breast Study (NBS), wherein multiple histologically normal breast samples were collected from different block regions and different sections at a given region. Intra-individual differences in global gene expression and selected gene expression signatures were quantified and evaluated in association with other patient-level factors. We found that intra-individual reliability was relatively high in global gene expression, but differed by signatures, with composition-related signatures (i.e., stroma) having higher intra-individual variability and tumorigenesis-related signatures (i.e., proliferation) having lower intra-individual variability. Histological stroma composition was the only factor significantly associated with heterogeneous breast tissue (defined as > median intra-individual variation; high nuclear density, odds ratio [OR] = 3.42, 95% confidence interval [CI] = 1.15–10.15; low area, OR = 0.29, 95% CI = 0.10–0.86). Other factors suggestively influencing the variability included age, BMI, and adipose nuclear density. Our results underscore the importance of considering intra-individual variability in tissue-based biomarker development, and have important implications for normal breast research.
Response inhibition on the stop signal task improves during cardiac contraction
Authors: Rae Charlotte L. , Botan Vanessa E. , Gould van Praag Cassandra D. , Herman Aleksandra M. , Nyyssönen Jasmina A. K. , Watson David R. , Duka Theodora , Garfinkel Sarah N. , Critchley Hugo D. 
Published: June 2018

AbstractMotor actions can be facilitated or hindered by psychophysiological states of readiness, to guide rapid adaptive action. Cardiovascular arousal is communicated by cardiac signals conveying the timing and strength of individual heartbeats. Here, we tested how these interoceptive signals facilitate control of motor impulsivity. Participants performed a stop signal task, in which stop cues were delivered at different time points within the cardiac cycle: at systole when the heart contracts (T-wave peak, approximately 300 ms following the R-wave), or at diastole between heartbeats (R-wave peak). Response inhibition was better at systole, indexed by a shorter stop signal reaction time (SSRT), and longer stop signal delay (SSD). Furthermore, parasympathetic control of cardiovascular tone, and subjective sensitivity to interoceptive states, predicted response inhibition efficiency, although these cardiovascular and interoceptive correlations did not survive correction for multiple comparisons. This suggests that response inhibition capacity is influenced by interoceptive physiological cues, such that people are more likely to express impulsive actions during putative states of lower cardiovascular arousal, when frequency and strength of cardiac afferent signalling is reduced.
Conic shapes have higher sensitivity than cylindrical ones in nanopore DNA sequencing
Authors: Tu Bin , Bai Shiyang , Lu Benzhuo , Fang Qiaojun 
Published: June 2018

AbstractNanopores have emerged as helpful research tools for single molecule detection. Through continuum modeling, we investigated the effects of membrane thickness, nanopore size, and pore shape on current signal characteristics of DNA. The simulation results showed that, when reducing the pore diameter, the amplitudes of current signals of DNA increase. Moreover, we found that, compared to cylindrically shaped nanopores, conical-shaped nanopores produce greater signal amplitudes from biomolecules translocation. Finally, we demonstrated that continuum model simulations for the discrimination of DNA and RNA yield current characteristics approximately consistent with experimental measurements and that A-T and G-C base pairs can be distinguished using thin conical solid-state nanopores. Our study not only suggests that computational approaches in this work can be used to guide the designs of nanopore for single molecule detection, but it also provides several possible ways to improve the current amplitudes of nanopores for better resolution.