bluuebunny/crossref_metadata_2025 huggingface dataset:
A Microvascularized Tumor-mimetic Platform for Assessing Anti-cancer Drug Efficacy
Authors: Pradhan Shantanu , Smith Ashley M. , Garson Charles J. , Hassani Iman , Seeto Wen J. , Pant Kapil , Arnold Robert D. , Prabhakarpandian Balabhaskar , Lipke Elizabeth A.
Published: February 2018

Assessment of anti-cancer drug efficacy in in vitro three-dimensional (3D) bioengineered cancer models provides important contextual and relevant information towards pre-clinical translation of potential drug candidates. However, currently established models fail to sufficiently recapitulate complex tumor heterogeneity. Here we present a chip-based tumor-mimetic platform incorporating a 3D in vitro breast cancer model with a tumor-mimetic microvascular network, replicating the pathophysiological architecture of native vascularized breast tumors. The microfluidic platform facilitated formation of mature, lumenized and flow-aligned endothelium under physiological flow recapitulating both high and low perfused tumor regions. Metastatic and non-metastatic breast cancer cells were maintained in long-term 3D co-culture with stromal fibroblasts in a poly(ethylene glycol)-fibrinogen hydrogel matrix within adjoining tissue chambers. The interstitial space between the chambers and endothelium contained pores to mimic the “leaky” vasculature found in vivo and facilitate cancer cell-endothelial cell communication. Microvascular pattern-dependent flow variations induced concentration gradients within the 3D tumor mass, leading to morphological tumor heterogeneity. Anti-cancer drugs displayed cell type- and flow pattern-dependent effects on cancer cell viability, viable tumor area and associated endothelial cytotoxicity. Overall, the developed microfluidic tumor-mimetic platform facilitates investigation of cancer-stromal-endothelial interactions and highlights the role of a fluidic, tumor-mimetic vascular network on anti-cancer drug delivery and efficacy for improved translation towards pre-clinical studies.
Adherence to antiretroviral therapy and factors affecting low medication adherence among incident HIV-infected individuals during 2009–2016: A nationwide study
Authors: Kim Jungmee , Lee Eunyoung , Park Byung-Joo , Bang Ji Hwan , Lee Jin Yong
Published: February 2018

For ideal clinical benefit, human immunodeficiency virus (HIV)-infected individuals should receive continuous medication. This is the first nationwide antiretroviral therapy (ART) adherence study in Asia, where medication monitoring at national level is systemically available. We estimated the ART adherence of incident HIV-infected individuals and investigated factors affecting low medication adherence using the national health insurance (NHI) claims data from 2007 to 2016. Medication possession ratio (MPR) was used to measure medication adherence and risk factors were identified by multivariable logistic regression analysis. Of the 8,501 newly diagnosed HIV-infected individuals during 2009–2016 with at least one ART prescription, 70.4% of HIV patients had adequate adherence to ART defined as MPR ≥95%. Requiring prophylactic antibiotics, female gender, age of 0–19 and same or over 50 s compared to 30–39, and having a history of malignancy, lower socioeconomic status, not visiting tertiary hospital, and being diagnosed in the earlier years were risk factors for lower adherence (Odds ratio 1.7, 1.6, 1.6, 1.4, 1.6, 2.1, 1.2, and 1.6 to 3.8 respectively). Health authority should take into consideration of these modifiable and unmodifiable barriers to establish sustainable monitoring system at national level and to improve adherence.
A novel flatworm-specific gene implicated in reproduction in Macrostomum lignano
Authors: Grudniewska Magda , Mouton Stijn , Grelling Margriet , Wolters Anouk H. G. , Kuipers Jeroen , Giepmans Ben N. G. , Berezikov Eugene
Published: February 2018

Free-living flatworms, such as the planarian Schmidtea mediterranea, are extensively used as model organisms to study stem cells and regeneration. The majority of flatworm studies so far focused on broadly conserved genes. However, investigating what makes these animals different is equally informative for understanding its biology and might have biomedical value. We re-analyzed the neoblast and germline transcriptional signatures of the flatworm M. lignano using an improved transcriptome assembly and show that germline-enriched genes have a high fraction of flatworm-specific genes. We further identified the Mlig-sperm1 gene as a member of a novel gene family conserved only in free-living flatworms and essential for producing healthy spermatozoa. In addition, we established a whole-animal electron microscopy atlas (nanotomy) to visualize the ultrastructure of the testes in wild type worms, but also as a reference platform for different ultrastructural studies in M. lignano. This work demonstrates that investigation of flatworm-specific genes is crucial for understanding flatworm biology and establishes a basis for such future research in M. lignano.
Scleraxis is a transcriptional activator that regulates the expression of Tenomodulin, a marker of mature tenocytes and ligamentocytes
Authors: Shukunami Chisa , Takimoto Aki , Nishizaki Yuriko , Yoshimoto Yuki , Tanaka Seima , Miura Shigenori , Watanabe Hitomi , Sakuma Tetsushi , Yamamoto Takashi , Kondoh Gen , Hiraki Yuji
Published: February 2018

Tenomodulin (Tnmd) is a type II transmembrane glycoprotein predominantly expressed in tendons and ligaments. We found that scleraxis (Scx), a member of the Twist-family of basic helix-loop-helix transcription factors, is a transcriptional activator of Tnmd expression in tenocytes. During embryonic development, Scx expression preceded that of Tnmd. Tnmd expression was nearly absent in tendons and ligaments of Scx-deficient mice generated by transcription activator-like effector nucleases-mediated gene disruption. Tnmd mRNA levels were dramatically decreased during serial passages of rat tenocytes. Scx silencing by small interfering RNA significantly suppressed endogenous Tnmd mRNA levels in tenocytes. Mouse Tnmd contains five E-box sites in the ~1-kb 5′-flanking region. A 174-base pair genomic fragment containing a TATA box drives transcription in tenocytes. Enhancer activity was increased in the upstream region (−1030 to −295) of Tnmd in tenocytes, but not in NIH3T3 and C3H10T1/2 cells. Preferential binding of both Scx and Twist1 as a heterodimer with E12 or E47 to CAGATG or CATCTG and transactivation of the 5′-flanking region were confirmed by electrophoresis mobility shift and dual luciferase assays, respectively. Scx directly transactivates Tnmd via these E-boxes to positively regulate tenocyte differentiation and maturation.
Effects of timber harvesting on the genetic potential for carbon and nitrogen cycling in five North American forest ecozones
Authors: Cardenas Erick , Orellana Luis H. , Konstantinidis Konstantinos T. , Mohn William W.
Published: February 2018

Forest ecosystems are critical to global biogeochemical cycles but under pressure from harvesting and climate change. We investigated the effects of organic matter (OM) removal during forest harvesting on the genetic potential of soil communities for biomass decomposition and nitrogen cycling in five ecozones across North America. We analyzed 107 samples, representing four treatments with varied levels of OM removal, at Long-Term Soil Productivity Study sites. Samples were collected more than ten years after harvesting and replanting and were analyzed via shotgun metagenomics. High-quality short reads totaling 1.2 Tbp were compared to the Carbohydrate Active Enzyme (CAZy) database and a custom database of nitrogen cycle genes. Gene profile variation was mostly explained by ecozone and soil layer. Eleven CAZy and nine nitrogen cycle gene families were associated with particular soil layers across all ecozones. Treatment effects on gene profiles were mainly due to harvesting, and only rarely to the extent of OM removal. Harvesting generally decreased the relative abundance of CAZy genes while increasing that of nitrogen cycle genes, although these effects varied among ecozones. Our results suggest that ecozone-specific nutrient availability modulates the sensitivity of the carbon and nitrogen cycles to harvesting with possible consequences for long-term forest sustainability.
Time-dependent Enhanced Corrosion of Ti6Al4V in the Presence of H2O2 and Albumin
Authors: Zhang Yue , Addison Owen , Yu Fei , Troconis Brendy C. Rincon , Scully John R. , Davenport Alison J.
Published: February 2018

There is increasing concern regarding the biological consequences of metal release from implants. However, the mechanisms underpinning implant surface degradation, especially in the absence of wear, are often poorly understood. Here the synergistic effect of albumin and H2O2 on corrosion of Ti6Al4V in physiological saline is studied with electrochemical methods. It is found that albumin induces a time-dependent dissolution of Ti6Al4V in the presence of H2O2 in physiology saline. Potentiostatic polarisation measurements show that albumin supresses dissolution in the presence of H2O2 at short times (<24 h) but over longer time periods (120 h) it significantly accelerates corrosion, which is attributed to albumin-catalysed dissolution of the corrosion product layer resulting in formation of a thinner oxide film. Dissolution of Ti6Al4V in the presence of albumin and H2O2 in physiological saline is also found to be dependent on potential: the titanium ion release rate is found to be higher (0.57 µg/cm2) at a lower potential (90 mV), where the oxide capacitance and resistance inferred from Electrochemical Impedance Spectroscopy also suggests a less resistant oxide film. The study highlights the importance of using more realistic solutions, and considering behaviour over longer time periods when testing corrosion resistance of metallic biomaterials.
IL-2 Inducible Kinase ITK is Critical for HIV-1 Infection of Jurkat T-cells
Authors: Hain Anika , Krämer Melanie , Linka René M. , Nakhaei-Rad Saeideh , Ahmadian Mohammad Reza , Häussinger Dieter , Borkhardt Arndt , Münk Carsten
Published: February 2018

Successful replication of Human immunodeficiency virus (HIV)-1 depends on the expression of various cellular host factors, such as the interleukin-2 inducible T-cell kinase (ITK), a member of the protein family of TEC-tyrosine kinases. ITK is selectively expressed in T-cells and coordinates signaling pathways downstream of the T-cell receptor and chemokine receptors, including PLC-1 activation, Ca2+-release, transcription factor mobilization, and actin rearrangements. The exact role of ITK during HIV-1 infection is still unknown. We analyzed the function of ITK during HIV-1 replication and showed that attachment, fusion of virions with the cell membrane and entry into Jurkat T-cells was inhibited when ITK was knocked down. In contrast, reverse transcription and provirus expression were not affected by ITK deficiency. Inhibited ITK expression did not affect the CXCR4 receptor on the cell surface, whereas CD4 and LFA-1 integrin levels were slightly enhanced in ITK knockdown cells and heparan sulfate (HS) expression was completely abolished in ITK depleted T-cells. However, neither HS expression nor other attachment factors could explain the impaired HIV-1 binding to ITK-deficient cells, which suggests that a more complex cellular process is influenced by ITK or that not yet discovered molecules contribute to restriction of HIV-1 binding and entry.
A multiplex serologic platform for diagnosis of tick-borne diseases
Authors: Tokarz Rafal , Mishra Nischay , Tagliafierro Teresa , Sameroff Stephen , Caciula Adrian , Chauhan Lokendrasingh , Patel Jigar , Sullivan Eric , Gucwa Azad , Fallon Brian , Golightly Marc , Molins Claudia , Schriefer Martin , Marques Adriana , Briese Thomas , Lipkin W. Ian
Published: February 2018

Tick-borne diseases are the most common vector-borne diseases in the United States, with serology being the primary method of diagnosis. We developed the first multiplex, array-based assay for serodiagnosis of tick-borne diseases called the TBD-Serochip. The TBD-Serochip was designed to discriminate antibody responses to 8 major tick-borne pathogens present in the United States, including Anaplasma phagocytophilum, Babesia microti, Borrelia burgdorferi, Borrelia miyamotoi, Ehrlichia chaffeensis, Rickettsia rickettsii, Heartland virus and Powassan virus. Each assay contains approximately 170,000 12-mer linear peptides that tile along the protein sequence of the major antigens from each agent with 11 amino acid overlap. This permits accurate identification of a wide range of specific immunodominant IgG and IgM epitopes that can then be used to enhance diagnostic accuracy and integrate differential diagnosis into a single assay. To test the performance of the TBD-Serochip, we examined sera from patients with confirmed Lyme disease, babesiosis, anaplasmosis, and Powassan virus disease. We identified a wide range of specific discriminatory epitopes that facilitated accurate diagnosis of each disease. We also identified previously undiagnosed infections. Our results indicate that the TBD-Serochip is a promising tool for a differential diagnosis not available with currently employed serologic assays for TBDs.
Diffusion mechanism in the sodium-ion battery material sodium cobaltate
Authors: Willis T. J. , Porter D. G. , Voneshen D. J. , Uthayakumar S. , Demmel F. , Gutmann M. J. , Roger M. , Refson K. , Goff J. P.
Published: February 2018

High performance batteries based on the movement of Li ions in Li
x
CoO2 have made possible a revolution in mobile electronic technology, from laptops to mobile phones. However, the scarcity of Li and the demand for energy storage for renewables has led to intense interest in Na-ion batteries, including structurally-related Na
x
CoO2. Here we have determined the diffusion mechanism for Na0.8CoO2 using diffuse x-ray scattering, quasi-elastic neutron scattering and ab-initio molecular dynamics simulations, and we find that the sodium ordering provides diffusion pathways and governs the diffusion rate. Above T ~ 290 K the so-called partially disordered stripe superstructure provides channels for quasi-1D diffusion, and melting of the sodium ordering leads to 2D superionic diffusion above T ~ 370 K. We obtain quantitative agreement between our microscopic study of the hopping mechanism and bulk self-diffusion measurements. Our approach can be applied widely to other Na- or Li-ion battery materials.
PREP1 tumor suppressor protects the late-replicating DNA by controlling its replication timing and symmetry
Authors: Palmigiano Angela , Santaniello Francesco , Cerutti Aurora , Penkov Dmitry , Purushothaman Divya , Makhija Ekta , Luzi Lucilla , di Fagagna Fabrizio d’Adda , Pelicci Pier Giuseppe , Shivashankar Viveswara , Dellino Gaetano Ivan , Blasi Francesco
Published: February 2018

The synthesis of middle-to-late-replicating DNA can be affected independently of the rest of the genome by down-regulating the tumor suppressor PREP1 (PKNOX1). Indeed, DNA combing shows that PREP1 down-regulation affects DNA replication rate, increases the number of simultaneously firing origins and the asymmetry of DNA replication, leading to DNA damage. Genome-wide analysis of replication timing by Repli-seq shows that, upon PREP1 down-regulation, 25% of the genome is replicated earlier in the S-phase. The targeted DNA sequences correspond to Lamin-Associated Domains (LADs), and include late-replicating (LRRs) and temporal transition regions (TTRs). Notably, the distribution of PREP1 DNA binding sites and of its target genes indicates that DNA replication defects are independent of the overall PREP1 transcriptional activity. Finally, PREP1 down-regulation causes a substantial decrease in Lamin B1 levels. This suggests that DNA is released from the nuclear lamina earlier than in the control cells and is available for replication, thus explaining timing defects and DNA damage.This is the first evidence that the replication timing of a specific fraction of the human genome is affected by PREP1 tumor suppressor. This previously unknown function might significantly contribute to the genomic instability observed in human tumors.
Working Memory And Brain Tissue Microstructure: White Matter Tract Integrity Based On Multi-Shell Diffusion MRI
Authors: Chung Sohae , Fieremans Els , Kucukboyaci Nuri E. , Wang Xiuyuan , Morton Charles J. , Novikov Dmitry S. , Rath Joseph F. , Lui Yvonne W.
Published: February 2018

Working memory is a complex cognitive process at the intersection of sensory processing, learning, and short-term memory and also has a general executive attention component. Impaired working memory is associated with a range of neurological and psychiatric disorders, but very little is known about how working memory relates to underlying white matter (WM) microstructure. In this study, we investigate the association between WM microstructure and performance on working memory tasks in healthy adults (right-handed, native English speakers). We combine compartment specific WM tract integrity (WMTI) metrics derived from multi-shell diffusion MRI as well as diffusion tensor/kurtosis imaging (DTI/DKI) metrics with Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) subtests tapping auditory working memory. WMTI is a novel tool that helps us describe the microstructural characteristics in both the intra- and extra-axonal environments of WM such as axonal water fraction (AWF), intra-axonal diffusivity, extra-axonal axial and radial diffusivities, allowing a more biophysical interpretation of WM changes. We demonstrate significant positive correlations between AWF and letter-number sequencing (LNS), suggesting that higher AWF with better performance on complex, more demanding auditory working memory tasks goes along with greater axonal volume and greater myelination in specific regions, causing efficient and faster information process.
Toxicity Classification of Oxide Nanomaterials: Effects of Data Gap Filling and PChem Score-based Screening Approaches
Authors: Ha My Kieu , Trinh Tung Xuan , Choi Jang Sik , Maulina Desy , Byun Hyung Gi , Yoon Tae Hyun
Published: February 2018

Development of nanotoxicity prediction models is becoming increasingly important in the risk assessment of engineered nanomaterials. However, it has significant obstacles caused by the wide heterogeneities of published literature in terms of data completeness and quality. Here, we performed a meta-analysis of 216 published articles on oxide nanoparticles using 14 attributes of physicochemical, toxicological and quantum-mechanical properties. Particularly, to improve completeness and quality of the extracted dataset, we adapted two preprocessing approaches: data gap-filling and physicochemical property based scoring. Performances of nano-SAR classification models revealed that the dataset with the highest score value resulted in the best predictivity with compromise in its applicability domain. The combination of physicochemical and toxicological attributes was proved to be more relevant to toxicity classification than quantum-mechanical attributes. Overall, by adapting these two preprocessing methods, we demonstrated that meta-analysis of nanotoxicity literatures could provide an effective alternative for the risk assessment of engineered nanomaterials.
Biogeographical Differences in the Influence of Maternal Microbial Sources on the Early Successional Development of the Bovine Neonatal Gastrointestinal tract
Authors: Yeoman Carl J. , Ishaq Suzanne L. , Bichi Elena , Olivo Sarah K. , Lowe James , Aldridge Brian M.
Published: February 2018

The impact of maternal microbial influences on the early choreography of the neonatal calf microbiome were investigated. Luminal content and mucosal scraping samples were collected from ten locations in the calf gastrointestinal tract (GIT) over the first 21 days of life, along with postpartum maternal colostrum, udder skin, and vaginal scrapings. Microbiota were found to vary by anatomical location, between the lumen and mucosa at each GIT location, and differentially enriched for maternal vaginal, skin, and colostral microbiota. Most calf sample sites exhibited a gradual increase in α-diversity over the 21 days beginning the first few days after birth. The relative abundance of Firmicutes was greater in the proximal GIT, while Bacteroidetes were greater in the distal GIT. Proteobacteria exhibited greater relative abundances in mucosal scrapings relative to luminal content. Forty-six percent of calf luminal microbes and 41% of mucosal microbes were observed in at-least one maternal source, with the majority being shared with microbes on the skin of the udder. The vaginal microbiota were found to harbor and uniquely share many common and well-described fibrolytic rumen bacteria, as well as methanogenic archaea, potentially indicating a role for the vagina in populating the developing rumen and reticulum with microbes important to the nutrition of the adult animal.
Temporal structure in spiking patterns of ganglion cells defines perceptual thresholds in rodents with subretinal prosthesis
Authors: Ho Elton , Lorach Henri , Goetz Georges , Laszlo Florian , Lei Xin , Kamins Theodore , Mariani Jean-Charles , Sher Alexander , Palanker Daniel
Published: February 2018

Subretinal prostheses are designed to restore sight in patients blinded by retinal degeneration using electrical stimulation of the inner retinal neurons. To relate retinal output to perception, we studied behavioral thresholds in blind rats with photovoltaic subretinal prostheses stimulated by full-field pulsed illumination at 20 Hz, and measured retinal ganglion cell (RGC) responses to similar stimuli ex-vivo. Behaviorally, rats exhibited startling response to changes in brightness, with an average contrast threshold of 12%, which could not be explained by changes in the average RGC spiking rate. However, RGCs exhibited millisecond-scale variations in spike timing, even when the average rate did not change significantly. At 12% temporal contrast, changes in firing patterns of prosthetic response were as significant as with 2.3% contrast steps in visible light stimulation of healthy retinas. This suggests that millisecond-scale changes in spiking patterns define perceptual thresholds of prosthetic vision. Response to the last pulse in the stimulation burst lasted longer than the steady-state response during the burst. This may be interpreted as an excitatory OFF response to prosthetic stimulation, and can explain behavioral response to decrease in illumination. Contrast enhancement of images prior to delivery to subretinal prosthesis can partially compensate for reduced contrast sensitivity of prosthetic vision.
Human neutrophils can mimic myeloid-derived suppressor cells (PMN-MDSC) and suppress microbead or lectin-induced T cell proliferation through artefactual mechanisms
Authors: Negorev Dmitri , Beier Ulf H. , Zhang Tianyi , Quatromoni Jon G. , Bhojnagarwala Pratik , Albelda Steven M. , Singhal Sunil , Eruslanov Evgeniy , Lohoff Falk W. , Levine Matthew H. , Diamond Joshua M. , Christie Jason D. , Hancock Wayne W. , Akimova Tatiana
Published: February 2018

We report that human conventional CD15+neutrophils can be isolated in the peripheral blood mononuclear cell (PBMC) layer during Ficoll gradient separation, and that they can impair T cell proliferationin vitrowithout concomitant neutrophil activation and killing. This effect was observed in a total of 92 patients with organ transplants, lung cancer or anxiety/depression, and in 18 healthy donors. Although such features are typically associated in the literature with the presence of certain myeloid-derived suppressor cell (PMN-MDSC) populations, we found that commercial centrifuge tubes that contained membranes or gels for PBMC isolation led to up to 70% PBMC contamination by CD15+neutrophils, with subsequent suppressive effects in certain cellular assays. In particular, the suppressive activity of human MDSC should not be evaluated using lectin or microbead stimulation, whereas assays involving soluble or plate-bound antibodies or MLR are unaffected. We conclude that CD15+neutrophil contamination, and associated effects on suppressor assays, can lead to significant artefacts in studies of human PMN-MDSC.
Functional analysis of SLC39A8 mutations and their implications for manganese deficiency and mitochondrial disorders
Authors: Choi Eun-Kyung , Nguyen Trang-Tiffany , Gupta Neil , Iwase Shigeki , Seo Young Ah
Published: February 2018

SLC39A8 encodes ZIP8, a divalent metal ion transporter. Mutations in the SLC39A8 gene are associated with congenital disorder of glycosylation type II and Leigh syndrome. Notably, affected patients with both disorders exhibited severe manganese (Mn) deficiency. The cellular function of human SLC39A8 (hSLC39A8) and the mechanisms by which mutations in this protein lead to human diseases are unclear. Herein, we show that hSLC39A8 mediates 54Mn uptake by the cells, and its expression is regulated by Mn. While expression of wild-type hSLC39A8 increased 54Mn uptake activity, disease-associated mutations abrogated the ability of the transporter to mediate Mn uptake into the cells, thereby providing a causal link to severe Mn deficiency. All mutants failed to localize on the cell surface and were retained within the endoplasmic reticulum. Interestingly, expression of hSLC39A8 mutants of both CDG type II and Leigh syndrome reduced mitochondrial 54Mn levels and activity of Mn-dependent mitochondrial superoxide dismutase MnSOD, and in turn increased oxidative stress. The expression of wild-type hSLC39A8, but not the disease-associated mutants, promoted mitochondrial functions. Moreover, loss of function analyses further corroborate hSLC39A8’s critical role in mediating Mn uptake and mitochondrial function. Our results provide a potential pathogenic mechanism of diseases that are associated with hSLC39A8 mutations.
High fidelity heralded single-photon source using cavity quantum electrodynamics
Authors: Zhang Xin , Xu Chang , Ren Zhongzhou
Published: February 2018

Demands for single-photon sources are ubiquitous in quantum information processing as well as in quantum metrology. In many protocols for producing single photons, a cavity-emitter configuration is used. In such cavity quantum electrodynamical systems, the cavity can enforce a well-defined output mode for the photon and enhance its collection efficiency, while the emitter is indispensable for single photon emission. Here we show the two cavity-one two-level emitter configuration can be used to produce exclusively photon pairs, with each photon in a separate mode. Conditioning on detecting a photon in one of the modes, one heralds with high fidelity a single photon in the other mode. Counterintuitively, upon decreasing the coupling of the emitter to one of the modes, the heralding fidelity can further increase.
Systematic and stochastic influences on the performance of the MinION nanopore sequencer across a range of nucleotide bias
Authors: Krishnakumar Raga , Sinha Anupama , Bird Sara W. , Jayamohan Harikrishnan , Edwards Harrison S. , Schoeniger Joseph S. , Patel Kamlesh D. , Branda Steven S. , Bartsch Michael S.
Published: February 2018

Emerging sequencing technologies are allowing us to characterize environmental, clinical and laboratory samples with increasing speed and detail, including real-time analysis and interpretation of data. One example of this is being able to rapidly and accurately detect a wide range of pathogenic organisms, both in the clinic and the field. Genomes can have radically different GC content however, such that accurate sequence analysis can be challenging depending upon the technology used. Here, we have characterized the performance of the Oxford MinION nanopore sequencer for detection and evaluation of organisms with a range of genomic nucleotide bias. We have diagnosed the quality of base-calling across individual reads and discovered that the position within the read affects base-calling and quality scores. Finally, we have evaluated the performance of the current state-of-the-art neural network-based MinION basecaller, characterizing its behavior with respect to systemic errors as well as context- and sequence-specific errors. Overall, we present a detailed characterization the capabilities of the MinION in terms of generating high-accuracy sequence data from genomes with a wide range of nucleotide content. This study provides a framework for designing the appropriate experiments that are the likely to lead to accurate and rapid field-forward diagnostics.
Short-term acclimation in adults does not predict offspring acclimation potential to hypoxia
Authors: Truebano Manuela , Tills Oliver , Collins Michael , Clarke Charlotte , Shipsides Emma , Wheatley Charlotte , Spicer John I.
Published: February 2018

The prevalence of hypoxic areas in coastal waters is predicted to increase and lead to reduced biodiversity. While the adult stages of many estuarine invertebrates can cope with short periods of hypoxia, it remains unclear whether that ability is present if animals are bred and reared under chronic hypoxia. We firstly investigated the effect of moderate, short-term environmental hypoxia (40% air saturation for one week) on metabolic performance in adults of an estuarine amphipod, and the fitness consequences of prolonged exposure. We then reared the offspring of hypoxia-exposed parents under hypoxia, and assessed their oxyregulatory ability under declining oxygen tensions as juveniles and adults. Adults from the parental generation were able to acclimate their metabolism to hypoxia after one week, employing mechanisms typically associated with prolonged exposure. Their progeny, however, did not develop the adult pattern of respiratory regulation when reared under chronic hypoxia, but instead exhibited a poorer oxyregulatory ability than their parents. We conclude that species apparently hypoxia-tolerant when tested in short-term experiments, could be physiologically compromised as adults if they develop under hypoxia. Consequently, we propose that the increased prevalence of hypoxia in coastal regions will have marked effects in some species currently considered hypoxia tolerant.
Temperature Dependence of the Dielectric Function of Monolayer MoSe2
Authors: Park Han Gyeol , Kim Tae Jung , Ullah Farman , Le Van Long , Nguyen Hoang Tung , Kim Yong Soo , Kim Young Dong
Published: February 2018

The dielectric function $${\boldsymbol{\varepsilon }}{\boldsymbol{=}}{{\boldsymbol{\varepsilon }}}_{{\bf{1}}}{\boldsymbol{+}}{\bf{i}}{{\boldsymbol{\varepsilon }}}_{{\bf{2}}}$$
ε
=

ε

1

+
i

ε

2

of monolayer molybdenum diselenide (MoSe2) is obtained and analyzed at temperatures from 31 to 300 K and at energies from 0.74 to 6.42 eV. The sample is a large-area, partially discontinuous monolayer (submonolayer) film of MoSe2 grown on a sapphire substrate by selenization of pulsed laser deposited MoO3 film. Morphological and optical characterizations verified the excellent quality of the film. The MoSe2 data were analyzed using the effective medium approximation, which treats the film and bare substrate regions as a single layer. Second derivatives of ε with respect to energy were numerically calculated and analyzed with standard lineshapes to extract accurate critical-point (CP) energies. We find only 6 CPs for monolayer MoSe2 at room temperature. At cryogenic temperatures 6 additional structures are resolved. The separations in the B- and C-excitonic peaks are also observed. All structures blue-shift and sharpen with decreasing temperature as a result of the reducing lattice constant and electron-phonon interactions. The temperature dependences of the CP energies were determined by fitting the data to the phenomenological expression that contains the Bose-Einstein statistical factor and the temperature coefficient.
Biosignals reflect pair-dynamics in collaborative work: EDA and ECG study of pair-programming in a classroom environment
Authors: Ahonen Lauri , Cowley Benjamin Ultan , Hellas Arto , Puolamäki Kai
Published: February 2018

Collaboration is a complex phenomenon, where intersubjective dynamics can greatly affect the productive outcome. Evaluation of collaboration is thus of great interest, and can potentially help achieve better outcomes and performance. However, quantitative measurement of collaboration is difficult, because much of the interaction occurs in the intersubjective space between collaborators. Manual observation and/or self-reports are subjective, laborious, and have a poor temporal resolution. The problem is compounded in natural settings where task-activity and response-compliance cannot be controlled. Physiological signals provide an objective mean to quantify intersubjective rapport (as synchrony), but require novel methods to support broad deployment outside the lab. We studied 28 student dyads during a self-directed classroom pair-programming exercise. Sympathetic and parasympathetic nervous system activation was measured during task performance using electrodermal activity and electrocardiography. Results suggest that (a) we canisolate cognitive processes(mental workload)from confounding environmental effects, and (b)electrodermal signals show role-specific but correlated affective response profiles. We demonstrate the potential for social physiological compliance to quantify pair-work in natural settings, with no experimental manipulation of participants required. Our objective approach has a high temporal resolution, is scalable, non-intrusive, and robust.
The effect of fidget spinners on fine motor control
Authors: Cohen Erez James , Bravi Riccardo , Minciacchi Diego
Published: February 2018

Fidgeting, defined as the generation of small movements through nervousness or impatience, is one of cardinal characteristic of ADHD. While fidgeting is, by definition, a motor experience still nothing is known about the effects of fidgeting on motor control. Some forms of fidgeting involve also the manipulation of external objects which, through repetition, may become automatic and second nature. Both repetition and practice are important for the acquisition of motor skills and, therefore, it is plausible that the repetitive manipulation of objects may influence motor control and performance. As such, fidget spinners, by being diffuse and prone to repetitive usage, may represent interesting tool for improving motor control. In this study we examine the effect of fidget spinners on fine motor control, evaluated by a spiral-tracing task. We show that the use of fidget spinner indeed seems to have a favorable effect on fine motor control, at least in the short term, although this effect does not seem to be in any way inherent to fidget spinners themselves as much as to object manipulation in general. However, due to their widespread usage, fidget spinner may have the advantage of being an enjoyable means for improving fine motor control.
Quantitative Analysis of Charge Distribution in Bi-Emissive layer White Organic Light-Emitting Diodes with Two Fluorescent Dopants
Authors: Kim Ji Young , Kim Woo Young , Cheah Kok Wai
Published: February 2018

This work seeks to establish a quantitative method which can estimate the holes and electrons ratio in the emission zones. We fabricated multilayered white organic light-emitting diodes (WOLEDs) with the device structure of ITO/NPB(80 nm)/MADN:BUBD-1(7%)(20 nm)/MADN:DCJTB(0.3%)(20 nm)/TPBi(X nm)/LiF(2 nm)/Al as a case study on the charge recombination distribution in the emissive layer. The result shows a trend in the charge recombination ratio depending on the electron transport layer thickness. We obtained an empirical relationship between electron transport layer thicknesses and emission ratio in EML. In addition, the electroluminescent spectra were analyzed by fitting a Gaussian distribution for the two emissive layers to calculate the intensity ratio of the energy transitions. The arrival time of hole and electrons from each electrode was determined using the thickness and mobility of TPBi as electron transport layer. From these initial results, we derived an empirical mechanism to meet with a linear relationship that can allow us to design custom- made WOLEDs.
The genes of the sulphoquinovose catabolism in Escherichia coli are also associated with a previously unknown pathway of lactose degradation
Authors: Kaznadzey Anna , Shelyakin Pavel , Belousova Evgeniya , Eremina Aleksandra , Shvyreva Uliana , Bykova Darya , Emelianenko Vera , Korosteleva Anastasiya , Tutukina Maria , Gelfand Mikhail S.
Published: February 2018

Comparative genomics analysis of conserved gene cassettes demonstrated resemblance between a recently described cassette of genes involved in sulphoquinovose degradation in Escherichia coli K-12 MG1655 and a Bacilli cassette linked with lactose degradation. Six genes from both cassettes had similar functions related to carbohydrate metabolism, namely, hydrolase, aldolase, kinase, isomerase, transporter, and transcription factor. The Escherichia coli sulphoglycolysis cassette was thus predicted to be associated with lactose degradation. This prediction was confirmed experimentally: expression of genes coding for aldolase (yihT), isomerase (yihS), and kinase (yihV) was dramatically increased during growth on lactose. These genes were previously shown to be activated during growth on sulphoquinovose, so our observation may indicate multi-functional capabilities of the respective proteins. Transcription starts for yihT, yihV and yihW were mapped in silico, in vitro and in vivo. Out of three promoters for yihT, one was active only during growth on lactose. We further showed that switches in yihT transcription are controlled by YihW, a DeoR-family transcription factor in the Escherichia coli cassette. YihW acted as a carbon source-dependent dual regulator involved in sustaining the baseline growth in the absence of lac-operon, with function either complementary, or opposite to a global regulator of carbohydrate metabolism, cAMP-CRP.
Ultrasound and shock-wave stimulation to promote axonal regeneration following nerve surgery: a systematic review and meta-analysis of preclinical studies
Authors: Daeschler Simeon C. , Harhaus Leila , Schoenle Philipp , Boecker Arne , Kneser Ulrich , Bergmeister Konstantin D.
Published: February 2018

Limited regeneration after nerve injury often leads to delayed or incomplete reinnervation and consequently insufficient muscle function. Following nerve surgery, application of low-intensity ultrasound or extracorporeal shock waves may promote nerve regeneration and improve functional outcomes. Because currently clinical data is unavailable, we performed a meta-analysis following the PRISMA-guidelines to investigate the therapeutic effect of ultrasound and shock wave therapies on motor nerve regeneration. Ten ultrasound-studies (N = 445 rats) and three shock-wave studies (N = 110 rats) were identified from multiple databases. We calculated the difference in means or standardized mean difference with 95% confidence intervals for motor function, nerve conduction velocity and histomorphological parameters of treated versus sham or non-treated animals. Ultrasound treatment showed significantly faster nerve conduction, increased axonal regeneration with thicker myelin and improved motor function on sciatic functional index scale (week two: DM[95%CI]: 19,03[13,2 to 25,6], 71 animals; week four: 7,4[5,4 to 9,5], 47 animals). Shock wave induced recovery improvements were temporarily significant. In conclusion, there is significant evidence for low-intensity ultrasound but not for extracorporeal shock wave treatment to improve nerve regeneration. Prospective clinical trials should therefore investigate available FDA-approved ultrasound devices as adjunct postoperative treatment following nerve surgery.
Allocation of photosynthesized carbon in an intensively farmed winter wheat–soil system as revealed by 14CO2 pulse labelling
Authors: Sun Zhaoan , Chen Qing , Han Xiao , Bol Roland , Qu Bo , Meng Fanqiao
Published: February 2018

Understanding the rhizodeposited carbon (C) dynamics of winter wheat (Triticum aestivum L.), is crucial for soil fertility and C sequestration. Pot-grown winter wheat was pulse labelled with 14CO2 at the key growth stages. 14C in the shoots, roots and soil was measured at 5 or 2 days after 14C-labelling (DAL 5/2) at each growth stage and at harvest. The 14C in the shoots increased from 4% of the net 14C recovered (shoots + roots + soil) during tillering to 53% at harvest. Approximately 14–34% of the net 14C recovered was incorporated into the soil. Allocation of photosynthesized C was extrapolated from the pot experiment to field condition, assuming a planting density of 1.8 million plants ha−1. The estimated C input to the soil was 1.7 t C ha−1, and 0.7 t C ha−1 of root residues was retained after wheat harvest; both values were higher than those previously reported (0.6 and 0.4 t C ha−1, respectively). Our findings highlight that C tracing during the entire crop season is necessary to quantify the temporal allocation of photosynthesized C, especially the contribution to soil carbon in intensified farming system.
Prediction of Advanced Axillary Lymph Node Metastases (ypN2-3) Using Breast MR imaging and PET/CT after Neoadjuvant Chemotherapy in Invasive Ductal Carcinoma Patients
Authors: Kim Won Hwa , Lee Sang-Woo , Kim Hye Jung , Chae Yee Soo , Jeong Shin Young , Jung Jin Hyang , Park Ho Yong , Lee Won Kee
Published: February 2018

We aimed to investigate the value of breast magnetic resonance (MR) imaging and positron emission tomography-computed tomography (PET/CT) in predicting advanced axillary lymph node (ALN) metastases (ypN2-3) after neoadjuvant chemotherapy (NAC) in invasive ductal carcinoma patients. A total of 108 patients with invasive ductal carcinoma underwent breast MR imaging and PET/CT both before and after NAC (termed initial staging and restaging, respectively). The number of positive ALNs and the short diameter (SD) of the largest ALN on breast MR imaging and maximal standardized uptake value (SUVmax) in the ALNs on PET/CT were evaluated. Odds ratio (OR) for prediction of advanced ALN metastases was calculated. The negative predictive value (NPV) of restaging imaging for exclusion of advanced ALN metastases was also calculated. Patients with advanced ALN metastases were more likely to have a higher number (≥2) of positive LNs (OR, 8.06; P = 0.015) on restaging MR imaging. No clinico-pathological factors were significantly associated with advanced ALN metastases. With restaging MR imaging, PET/CT, and MR imaging plus PET/CT, the NPV for excluding advanced ALN metastases was 97.3%, 94.4%, and 100.0%. A higher number of positive ALNs on restaging MR imaging was an independent predictor for advanced ALN metastases after NAC.
Intratesticular injection followed by electroporation allows gene transfer in caprine spermatogenic cells
Authors: Pramod R. Kumar , Mitra Abhijit
Published: February 2018

The production of transgenic livestock is constrained due to the limited success of currently available methods for transgenesis. Testis mediated gene transfer (TMGT) is an emerging method that shows a high success rate in generating transgenic mice. In this study, we report a newly developed protocol for electroporation-aided TMGT to produce a transgenic goat. The injectable volume and concentration of the transgene were first standardized, and then electroporation conditions were optimizedin vitro.In vivoexperiments were performed by injecting a transgenic construct (pIRES2-EGFP; enhanced green fluorescent protein) into the testicular interstitium followed by electroporation. Immunohistochemistry, quantitative real-time PCR (qPCR) and western blotting analyses confirmed the successful transfer of the transgene into seminiferous tubules and testicular cells. Furthermore, chromosomal integration of the transgene and its expression in sperm were evaluated d60 and d120 post-electroporation. Our protocol neither altered the seminal characteristics nor the fertilization capacity of the sperm cells.In vitrofertilization using transgenic sperm generated fluorescent embryos. Finally, natural mating of a pre-founder buck produced a transgenic baby goat. The present study demonstrates the first successful report of an electroporation-aided TMGT method for gene transfer in goats.
CRISPR-Cas9, a tool to efficiently increase the development of recombinant African swine fever viruses
Authors: Borca Manuel V. , Holinka Lauren G. , Berggren Keith A. , Gladue Douglas P.
Published: February 2018

African swine fever virus (ASFV) causes a highly contagious disease called African swine fever. This disease is often lethal for domestic pigs, causing extensive losses for the swine industry. ASFV is a large and complex double stranded DNA virus. Currently there is no commercially available treatment or vaccine to prevent this devastating disease. Development of recombinant ASFV for producing live-attenuated vaccines or studying the involvement of specific genes in virus virulence has relied on the relatively rare event of homologous recombination in primary swine macrophages, causing difficulty to purify the recombinant virus from the wild-type parental ASFV. Here we present the use of the CRISPR-Cas9 gene editing system as a more robust and efficient system to produce recombinant ASFVs. Using CRISPR-Cas9 a recombinant virus was efficiently developed by deleting the non-essential gene 8-DR from the genome of the highly virulent field strain Georgia07 using swine macrophages as cell substrate.
A role for tau in learning, memory and synaptic plasticity
Authors: Biundo Fabrizio , Del Prete Dolores , Zhang Hong , Arancio Ottavio , D’Adamio Luciano
Published: February 2018

Tau plays a pivotal role in the pathogenesis of neurodegenerative disorders: mutations in the gene encoding for tau (MAPT) are linked to Fronto-temporal Dementia (FTD) and hyper-phosphorylated aggregates of tau forming neurofibrillary tangles (NFTs) that constitute a pathological hallmark of Alzheimer disease (AD) and FTD. Accordingly, tau is a favored therapeutic target for the treatment of these diseases. Given the criticality of tau to dementia’s pathogenesis and therapy, it is important to understand the physiological function of tau in the central nervous system. Analysis of Mapt knock out (Mapt−/−) mice has yielded inconsistent results. Some studies have shown that tau deletion does not alter memory while others have described synaptic plasticity and memory alterations in Mapt−/− mice. To help clarifying these contrasting results, we analyzed a distinct Mapt−/− model on a B6129PF3/J genetic background. We found that tau deletion leads to aging-dependent short-term memory deficits, hyperactivity and synaptic plasticity defects. In contrast, Mapt+/− mice only showed a mild short memory deficit in the novel object recognition task. Thus, while tau is important for normal neuronal functions underlying learning and memory, partial reduction of tau expression may have fractional deleterious effects.