bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex-specific deficits in neurite density and white matter integrity are associated with targeted disruption of exon 2 of the Disc1 gene in the rat
Authors: Barnett Brian R. , Torres-Velázquez Maribel , Yi Sue Y. , Rowley Paul A. , Sawin Emily A. , Rubinstein C. Dustin , Krentz Kathleen , Anderson Jacqueline M. , Bakshi Vaishali P. , Yu John-Paul J. 
Published: February 2019

AbstractDiffusion tensor imaging (DTI) has provided remarkable insight into our understanding of white matter microstructure and brain connectivity across a broad spectrum of psychiatric disease. While DTI and other diffusion weighted magnetic resonance imaging (MRI) methods have clarified the axonal contribution to the disconnectivity seen in numerous psychiatric diseases, absent from these studies are quantitative indices of neurite density and orientation that are especially important features in regions of high synaptic density that would capture the synaptic contribution to the psychiatric disease state. Here we report the application of neurite orientation dispersion and density imaging (NODDI), an emerging microstructure imaging technique, to a novel Disc1 svΔ2 rat model of psychiatric illness and demonstrate the complementary and more specific indices of tissue microstructure found in NODDI than those reported by DTI. Our results demonstrate global and sex-specific changes in white matter microstructural integrity and deficits in neurite density as a consequence of the Disc1 svΔ2 genetic variation and highlight the application of NODDI and quantitative measures of neurite density and neurite dispersion in psychiatric disease.
MEK inhibition suppresses K-Ras wild-type cholangiocarcinoma in vitro and in vivo via inhibiting cell proliferation and modulating tumor microenvironment
Authors: Wang Pan , Song Xinhua , Utpatel Kirsten , Shang Runze , Yang Yoon Mee , Xu Meng , Zhang Jie , Che Li , Gordan John , Cigliano Antonio , Seki Ekihiro , Evert Matthias , Calvisi Diego F. , Hu Xiaosong , Chen Xin 
Published: February 2019

AbstractPD901, a MEK inhibitor, has been demonstrated of therapeutic efficacy against cholangiocarcinoma (CCA) harboring K-Ras oncogenic mutations. However, most CCA exhibit no K-Ras mutations. In the current study, we investigated the therapeutic potential of PD901, either alone or in combination with the pan-mTOR inhibitor MLN0128, for the treatment of K-Ras wild-type CCA in vitro using human CCA cell lines, and in vivo using AKT/YapS127A CCA mouse model. We discovered that in vitro, PD901 treatment strongly inhibited CCA cell proliferation, and combined PD901 and MLN0128 therapy further increased growth inhibition. In vivo, treatment of PD901 alone triggered tumor regression, which was not further increased when the two drugs were administered simultaneously. Mechanistically, PD901 efficiently hampered ERK activation in vitro and in vivo, leading to strong inhibition of CCA tumor cell cycle progression. Intriguingly, we discovered that PD901, but not MLN0128 treatment resulted in changes affecting the vasculature and cancer-associated fibroblasts in AKT/YapS127A mouse lesions. It led to the decreased hypoxia within tumor lesions, which may further enhance the anti-cell proliferation activities of PD901. Altogether, our study demonstrates that MEK inhibitors could be effective for the treatment of K-Ras wild-type CCA via inhibiting cell proliferation and modulating tumor microenvironment.
Correspondence between cerebral glucose metabolism and BOLD reveals relative power and cost in human brain
Authors: Shokri-Kojori Ehsan , Tomasi Dardo , Alipanahi Babak , Wiers Corinde E. , Wang Gene-Jack , Volkow Nora D. 
Published: February 2019

AbstractThe correspondence between cerebral glucose metabolism (indexing energy utilization) and synchronous fluctuations in blood oxygenation (indexing neuronal activity) is relevant for neuronal specialization and is affected by brain disorders. Here, we define novel measures of relative power (rPWR, extent of concurrent energy utilization and activity) and relative cost (rCST, extent that energy utilization exceeds activity), derived from FDG-PET and fMRI. We show that resting-state networks have distinct energetic signatures and that brain could be classified into major bilateral segments based on rPWR and rCST. While medial-visual and default-mode networks have the highest rPWR, frontoparietal networks have the highest rCST. rPWR and rCST estimates are generalizable to other indexes of energy supply and neuronal activity, and are sensitive to neurocognitive effects of acute and chronic alcohol exposure. rPWR and rCST are informative metrics for characterizing brain pathology and alternative energy use, and may provide new multimodal biomarkers of neuropsychiatric disorders.
TRADD regulates perinatal development and adulthood survival in mice lacking RIPK1 and RIPK3
Authors: Dowling John P. , Alsabbagh Mohamed , Del Casale Christina , Liu Zheng-Gang , Zhang Jianke 
Published: February 2019

AbstractTRADD is an adaptor for TNFR1-induced apoptosis and NFκB activation. However, TRADD-deficient mice undergo normal development and contain normal lymphoid populations, which contrasts with an embryonic defect in mice lacking FADD, the shared adaptor mediating apoptosis. Recent studies indicate FADD suppresses embryonic necroptosis mediated by RIPK1. TRADD was suggested to also mediate necroptosis. Here we report that targeting TRADD fails to rescue Fadd−/− embryos from necroptosis, and ablation of TRADD rescues Ripk1−/− mice from perinatal lethality when RIPK3-mediated necroptosis is disabled. The resulting Ripk1−/−Ripk3−/−Tradd−/− mice survive until early adulthood, but die thereafter. A single allele of Tradd is optimal for survival of Ripk1−/−Ripk3−/−Tradd+/− mice. We show that TRADD plays a more dominating role in NFκB-signaling than RIPK1. While RIPK1 protects thymocytes from TNFα-induced apoptosis, TRADD promotes this process. The data demonstrate that TRADD is critical in perinatal and adult mice lacking RIPK1 and RIPK3, which has not been appreciated in prior studies.
Cation-swapped homogeneous nanoparticles in perovskite oxides for high power density
Authors: Joo Sangwook , Kwon Ohhun , Kim Kyeounghak , Kim Seona , Kim Hyunmin , Shin Jeeyoung , Jeong Hu Young , Sengodan Sivaprakash , Han Jeong Woo , Kim Guntae 
Published: February 2019

AbstractExsolution has been intensively studied in the fields of energy conversion and storage as a method for the preparation of catalytically active and durable metal nanoparticles. Under typical conditions, however, only a limited number of nanoparticles can be exsolved from the host oxides. Herein, we report the preparation of catalytic nanoparticles by selective exsolution through topotactic ion exchange, where deposited Fe guest cations can be exchanged with Co host cations in PrBaMn1.7Co0.3O5+δ. Interestingly, this phenomenon spontaneously yields the host PrBaMn1.7Fe0.3O5+δ, liberating all the Co cations from the host owing to the favorable incorporation energy of Fe into the lattice of the parent host (ΔEincorporation = −0.41 eV) and the cation exchange energy (ΔEexchange = −0.34 eV). Remarkably, the increase in the number of exsolved nanoparticles leads to their improved catalytic activity as a solid oxide fuel cell electrode and in the dry reforming of methane.
Automated microfluidic cell culture of stem cell derived dopaminergic neurons
Authors: Kane Khalid I. W. , Moreno Edinson Lucumi , Hachi Siham , Walter Moriz , Jarazo Javier , Oliveira Miguel A. P. , Hankemeier Thomas , Vulto Paul , Schwamborn Jens C. , Thoma Martin , Fleming Ronan M. T. 
Published: February 2019

AbstractParkinson’s disease is a slowly progressive neurodegenerative disease characterised by dysfunction and death of selectively vulnerable midbrain dopaminergic neurons and the development of human in vitro cellular models of the disease is a major challenge in Parkinson’s disease research. We constructed an automated cell culture platform optimised for long-term maintenance and monitoring of different cells in three dimensional microfluidic cell culture devices. The system can be flexibly adapted to various experimental protocols and features time-lapse imaging microscopy for quality control and electrophysiology monitoring to assess cellular activity. Using this system, we continuously monitored the differentiation of Parkinson’s disease patient derived human neuroepithelial stem cells into midbrain specific dopaminergic neurons. Calcium imaging confirmed the electrophysiological activity of differentiated neurons and immunostaining confirmed the efficiency of the differentiation protocol. This system is the first example of an automated Organ-on-a-Chip culture and has the potential to enable a versatile array of in vitro experiments for patient-specific disease modelling.
Enantiomeric Isoflavones with neuroprotective activities from the Fruits of Maclura tricuspidata
Authors: Hiep Nguyen Tuan , Kwon Jaeyoung , Hong Sungeun , Kim Nahyun , Guo Yuanqiang , Hwang Bang Yeon , Mar Woongchon , Lee Dongho 
Published: February 2019

AbstractSeven pairs of enantiomeric isoflavones (1a/1b–7a/7b) were obtained from the ethyl acetate extract of the fruits of Maclura tricuspidata (syn. Cudrania tricuspidata), and successfully separated by chiral high-pressure liquid chromatography (HPLC). The structures and absolute configurations of the enantiomeric isoflavones were established on the basic of comprehensive spectroscopic analyses and quantum chemical calculation methods. Compounds 1, 1a, and 1b exhibited neuroprotective activities against oxygen-glucose deprivation/reoxygenation (ODG/R)-induced SH-SY5Y cells death with EC50 values of 5.5 µM, 4.0 µM, and 10.0 µM, respectively. Furthermore, 1, 1a, and 1b inhibited OGD/R-induced reactive oxygen species generation in SH-5Y5Y cells with IC50 values of 6.9 µM, 4.5 µM, and 9.5 µM, respectively.
Colour lightness of butterfly assemblages across North America and Europe
Authors: Stelbrink Pablo , Pinkert Stefan , Brunzel Stefan , Kerr Jeremy , Wheat Christopher W. , Brandl Roland , Zeuss Dirk 
Published: February 2019

AbstractMelanin-based dark colouration is beneficial for insects as it increases the absorption of solar energy and protects against pathogens. Thus, it is expected that insect colouration is darker in colder regions and in regions with high humidity, where it is assumed that pathogen pressure is highest. These relationships between colour lightness, insect distribution, and climate between taxa and subtaxa across continents have never been tested and compared. Here we analysed the colour lightness of nearly all butterfly species of North America and Europe using the average colour lightness of species occurring within 50 km × 50 km grid cells across both continents as the dependent variable and average insolation, temperature and humidity within grid cells as explanatory variables. We compared the direction, strength and shape of these relationships between butterfly families and continents. On both continents, butterfly assemblages in colder and more humid regions were generally darker coloured than assemblages in warmer and less humid regions. Although these relationships differed in detail between families, overall trends within families on both continents were similar. Our results add further support for the importance of insect colour lightness as a mechanistic adaptation to climate that influences biogeographical patterns of species distributions.
Clinical relevance of non-tuberculous mycobacteria isolated from respiratory specimens: seven year experience in a UK hospital
Authors: Schiff H. F. , Jones S. , Achaiah A. , Pereira A. , Stait G. , Green B. 
Published: February 2019

AbstractThe frequency of isolation of non-tuberculous mycobacteria (NTM) species from respiratory specimens is increasing, however the clinical relevance of such identifications vary by mycobacterial species and geographical location. A retrospective study of 853 NTM isolates from respiratory samples from 386 patients over seven years was performed. Clinical records and radiographic information were examined. Clinical significance was assessed by American Thoracic Society diagnostic criteria. 25% of all patients with respiratory isolates met criteria for non-tuberculous mycobacterial pulmonary disease (NTM-PD). Significant symptoms were weight loss, fever, night sweats, productive cough and haemoptysis. HIV co-infection was a significant risk factor for disease. Cavities, nodules and tree-in-bud were significant radiographic findings. Mycobacterium avium complex (MAC) were the dominant species isolated from this patient cohort. Mycobacterium abscessus (M. abscessus) was the species most likely to cause clinically significant disease and be sputum smear positive, thus warranting particular attention.
CARS spectroscopy of Aspergillus nidulans spores
Authors: D. Strycker Benjamin , Han Zehua , Commer Blake , D. Shaw Brian , V. Sokolov Alexei , O. Scully Marlan 
Published: February 2019

AbstractCoherent Anti-Stokes Raman Spectroscopy (CARS) is performed on single spores (conidia) of the fungus Aspergillus nidulans in order to establish a baseline measurement for fungal spores. Chemical maps of single spores are generated and spectral differentiation between the cell wall and the cytoplasm is achieved. Principal Component Analysis of the measured spectra is then completed as a means to quantify spore heterogeneity. Applications range from the quick and accurate diagnosis of public health concerns to real-time agricultural and environmental sensing of fungal symbionts and pathogens.
A mutation in the AdhE alcohol dehydrogenase of Clostridium thermocellum increases tolerance to several primary alcohols, including isobutanol, n-butanol and ethanol
Authors: Tian Liang , Cervenka Nicholas D. , Low Aidan M. , Olson Daniel G. , Lynd Lee R. 
Published: February 2019

AbstractClostridium thermocellum is a good candidate organism for producing cellulosic biofuels due to its native ability to ferment cellulose, however its maximum biofuel titer is limited by tolerance. Wild type C. thermocellum is inhibited by 5 g/L n-butanol. Using growth adaptation in a chemostat, we increased n-butanol tolerance to 15 g/L. We discovered that several tolerant strains had acquired a D494G mutation in the adhE gene. Re-introducing this mutation recapitulated the n-butanol tolerance phenotype. In addition, it increased tolerance to several other primary alcohols including isobutanol and ethanol. To confirm that adhE is the cause of inhibition by primary alcohols, we showed that deleting adhE also increases tolerance to several primary alcohols.
Laser sintering of gravure printed indium tin oxide films on polyethylene terephthalate for flexible electronics
Authors: Serkov A. A. , Snelling H. V. , Heusing S. , Amaral T. Martins 
Published: February 2019

AbstractTin doped indium oxide (ITO) thin films provide excellent transparency and conductivity for electrodes in displays and photovoltaic systems. Current advances in producing printable ITO inks are reducing the volume of wasted indium during thin film patterning. However, their applicability to flexible electronics is hindered by the need for high temperature processing that results in damage to conventional polymer substrates. Here, we detail the conditions under which laser heating can be used as a replacement for oven and furnace treatments. Measurements of the optical properties of both the printed ITO film and the polymer substrate (polyethylene terephthalate, PET) identify that in the 1.5–2.0 μm wavelength band there is absorption in the ITO film but good transparency in PET. Hence, laser light that is not absorbed in the film does not go on to add a deleterious energy loading to the substrate. Localization of the energy deposition in the film is further enhanced by using ultrashort laser pulses (~1 ps) thus limiting heat flow during the interaction. Under these conditions, laser processing of the printed ITO films results in an improvement of the conductivity without damage to the PET.
Atypical biological features of a new cold seep site on the Lofoten-Vesterålen continental margin (northern Norway)
Authors: Sen Arunima , Himmler Tobias , Hong Wei Li , Chitkara Cheshtaa , Lee Raymond W. , Ferré Benedicte , Lepland Aivo , Knies Jochen 
Published: February 2019

AbstractA newly discovered cold seep from the Lofoten-Vesterålen margin (Norwegian Sea) is dominated by the chemosymbiotrophic siboglinidOligobrachia haakonmosbiensislike other high latitude seeps, but additionally displays uncharacteristic features. Sulphidic bottom water likely prevents colonization by cnidarians and sponges, resulting in fewer taxa than deeper seeps in the region, representing a deviation from depth-related trends seen among seeps elsewhere.O. haakonmosbiensiswas present among carbonate and barite crusts, constituting the first record of frenulates among hard substrates. The presence of both adults and egg cases indicate thatAmbylraja hyperboreaskates use the site as an egg case nursery ground. Due to sub-zero ambient temperatures (−0.7 °C), we hypothesize that small, seepage related heat anomalies aid egg incubation and prevent embryo mortality. We place our results within the context of high–latitude seeps and suggest they exert evolutionary pressure on benthic species, thereby selecting for elevated exploitation and occupancy of high-productivity habitats.
Modeling the Effects of Multiple Myeloma on Kidney Function
Authors: Walk Julia C. , Ayati Bruce P. , Holstein Sarah A. 
Published: February 2019

AbstractMultiple myeloma (MM), a plasma cell cancer, is associated with many health challenges, including damage to the kidney by tubulointerstitial fibrosis. We develop a mathematical model which captures the qualitative behavior of the cell and protein populations involved. Specifically, we model the interaction between cells in the proximal tubule of the kidney, free light chains, renal fibroblasts, and myeloma cells. We analyze the model for steady-state solutions to find a mathematically and biologically relevant stable steady-state solution. This foundational model provides a representation of dynamics between key populations in tubulointerstitial fibrosis that demonstrates how these populations interact to affect patient prognosis in patients with MM and renal impairment.
Piwi-like 1 protein expression is a prognostic factor for renal cell carcinoma patients
Authors: Stöhr Christine G. , Steffens Sandra , Polifka Iris , Jung Rudolf , Kahlmeyer Andreas , Ivanyi Philipp , Weber Florian , Hartmann Arndt , Wullich Bernd , Wach Sven , Taubert Helge 
Published: February 2019

AbstractThe Piwi-like genes belong to the Argonaute gene family and are conserved in plants, animals and humans. In addition to their essential role in the germ line and as stem cell-associated genes, Piwi-like proteins play a role in different cancer types but have yet to be studied in renal cell carcinoma (RCC). We investigated tissue micro arrays (TMAs) with tumor samples of two independent cohorts of RCC patients (N = 265 and N = 345); we used immunohistochemistry to assess the protein expression of Piwi-like 1. Applying an immunoreactive score (IRS), we found Piwi-like 1 positivity (IRS > 0) in 28.3% and 14.8% of the tumors in cohorts 1 and 2, respectively. Piwi-like 1 positivity was correlated with Fuhrman grade, tumor stage and the presence of distant metastasis (P < 0.005). Moreover, in univariate and multivariate analyses (adjusted to Fuhrman grade and tumor stage), Piwi-like 1 positivity was associated with a shorter cancer-specific survival in the patients in the second cohort. In addition, Piwi-like 1 expression allowed to further distinguish the RCC patients with high Fuhrman grade, high tumor stage, distant metastasis or high pre-operative levels of C-reactive protein, as Piwi-like 1 positivity was associated with a shorter cancer-specific survival in both cohorts. Our data encourage further investigations to enlighten the role of Piwi-like 1 and its function as a marker of poor prognosis in RCC patients.
Increasing trends in fecundity and calf survival of bottlenose dolphins in a marine protected area
Authors: Cheney Barbara J. , Thompson Paul M. , Cordes Line S. 
Published: February 2019

AbstractEstimates of temporal variation in demographic rates are critical for identifying drivers of population change and supporting conservation. However, for inconspicuous wide-ranging species, births may be missed and fecundity rates underestimated. We address this issue using photo-identification data and a novel robust design multistate model to investigate changes in bottlenose dolphin fecundity and calf survival. The model allows for uncertainty in breeding status, and seasonal effects. The best model estimated an increase in the proportion of females with newborn calves from 0.16 (95% CI = 0.11–0.24) in 2001 to 0.28 (95% CI = 0.22–0.36) in 2016. First year calf survival also increased over this period from 0.78 (95% CI = 0.53–0.92) to 0.93 (95% CI = 0.82–0.98). Second year calf survival remained lower, but also showed an increase from 0.32 (95% CI = 0.19–0.48) to 0.55 (95% CI = 0.44–0.65). Females with newborn calves had a slightly higher mortality than those with older calves, but further work is required to evaluate potential costs of reproduction. This study presents a rare example of empirical evidence of a positive trend in reproduction and survival for a cetacean population using a Marine Protected Area.
Fabricating Paper Based Devices Using Correction Pens
Authors: Mani Naresh Kumar , Prabhu Anusha , Biswas Sujay Kumar , Chakraborty Suman 
Published: February 2019

AbstractWe present a rapid (<10 s), cost-effective, unique single-step method for fabricating paper-based devices without necessitating any expensive instrumentation, simply by deploying correction pens that are otherwise commonly used for masking typos in printed or written matters. The marked regions formed by deposits from the correction pen demonstrate ubiquitous flow resistances to typical aqueous solutions and organic solvents in the transverse direction, resulting in a preferential bulk flow along the axial direction of the paper channels ‘fabricated’ in the process. Considering the simplicity and cost-effectiveness of this platform, it is deemed to be ideal for (bio) chemical sensing and point-of-care diagnostics in resource-limited settings.
Lamina Cribrosa Curvature in Healthy Korean Eyes
Authors: Lee Seung Hyen , Kim Tae-Woo , Lee Eun Ji , Girard Michaël J. A. , Mari Jean Martial 
Published: February 2019

AbstractGiven that posterior bowing of the lamina cribrosa (LC) is a principle event in the development of glaucomatous damage, assessment of the LC morphology may have clinical utility in diagnosing and managing glaucoma patients. LC curvature has been suggested as an index to evaluate the LC morphology. To apply LC morphology in clinical practice, it is necessary to know normal profiles of LC curvature in healthy population. This study was performed to investigate the characteristics of LC curvature in healthy eyes using enhanced depth imaging spectral-domain optical coherence tomography in a total of 250 eyes of 125 healthy Korean subjects. The lamina cribrosa curvature index (LCCI) values at seven locations spaced equidistantly across the vertical optic disc diameter were measured on serial horizontal B-scan images. The mean value of the seven measurements was defined as the average LCCI. The average LCCI was 7.46 ± 1.22 (range, 4.29–10.48) and did not differ significantly between the right and left eyes. There was a strong inter-eye correlation within subjects. LCCI was significantly larger in eyes with shorter axial length (P < 0.001). The observed range of LCCI in healthy subjects may be used as a reference for evaluating LC curvature in glaucomatous eyes.