bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multi-state model of chemoresistance to characterize phenotypic dynamics in breast cancer
Authors: Howard Grant R. , Johnson Kaitlyn E. , Rodriguez Ayala Areli , Yankeelov Thomas E. , Brock Amy 
Published: August 2018

AbstractThe development of resistance to chemotherapy is a major cause of treatment failure in breast cancer. While mathematical models describing the dynamics of resistant cancer cell subpopulations have been proposed, experimental validation has been difficult due to the complex nature of resistance that limits the ability of a single phenotypic marker to sufficiently identify the drug resistant subpopulations. We address this problem with a coupled experimental/modeling approach to reveal the composition of drug resistant subpopulations changing in time following drug exposure. We calibrate time-resolved drug sensitivity assays to three mathematical models to interrogate the models’ ability to capture drug response dynamics. The Akaike information criterion was employed to evaluate the three models, and it identified a multi-state model incorporating the role of population heterogeneity and cellular plasticity as the optimal model. To validate the model’s ability to identify subpopulation composition, we mixed different proportions of wild-type MCF-7 and MCF-7/ADR resistant cells and evaluated the corresponding model output. Our blinded two-state model was able to estimate the proportions of cell types with an R-squared value of 0.857. To the best of our knowledge, this is the first work to combine experimental time-resolved drug sensitivity data with a mathematical model of resistance development.
Effective soil erosion control represents a significant net carbon sequestration
Authors: Ran Lishan , Lu Xixi , Fang Nufang , Yang Xiankun 
Published: August 2018

AbstractThe debate over whether soil erosion is a carbon (C) sink or atmospheric CO2 source remains highly controversial. For the first time, we report the magnitude of C stabilization associated with soil erosion control for an entire large river basin. The soil erosion of the Yellow River basin in northern China is among the most severe worldwide. Progressive soil conservation has been implemented by the Chinese government since the 1970s, including the largest ever revegetation programme, the Grain-for-Green Project, which began in 1999. Based on compiled hydrological records and organic carbon (OC) data, together with primary production estimates, we evaluated the sequestered OC resulting from soil conservation. Compared with that at baseline in 1950–1970, in which significant soil conservation did not occur, the fate of erosion-induced OC was substantially altered in the period from 2000–2015. Approximately 20.6 Tg of OC were effectively controlled per year by soil conservation efforts. Simultaneously, the decomposition of erosion-induced soil organic carbon (SOC) declined from 8 Tg C yr−1 to current 5.3 Tg C yr−1. The reduced C emissions (2.7 Tg C yr−1) within the Yellow River basin alone account for 12.7% of the mean C accumulation acquired via forest expansion throughout all of China previously assessed. If the accumulated C in restored plants and soils was included, then 9.7 Tg C yr−1 was reduced from the atmospheric C pool during this period, which represents a tremendous C-capturing benefit. Thus, the increased C storage obtained via soil conservation should be considered in future C inventories.
Highly efficient capture of cancer cells expressing EGFR by microfluidic methods based on antigen-antibody association
Authors: Ohnaga Takashi , Takei Yoshinori , Nagata Takuya , Shimada Yutaka 
Published: August 2018

AbstractEpidermal growth factor receptor (EGFR) was evaluated as a target antigen for cancer cell capture by microfluidic methods based on antigen-antibody association. A polymer CTC-chip microfluidic device was surface-functionalized with three different anti-EGFR antibodies and used to capture EGFR-expressing cancer cells. Capture efficacy depended on the type of antibody used, and cetuximab efficiently captured cancer cell lines that had a wide range of EGFR expression. Capture efficiency was analyzed from the viewpoint of antigen-antibody association in a kinetic process, i.e., cell rolling well-known in leukocyte adhesion, and antibodies with a smaller dissociation constant were shown to result in more efficient capture. Moreover, a lower limit of cellular EGFR expression level for the capture was estimated and methods to decrease the limit were discussed based on densities of anti-EGFR antibody on the device surface.
Optimising complementary soft tissue synchrotron X-ray microtomography for reversibly-stained central nervous system samples
Authors: Strotton Merrick C. , Bodey Andrew J. , Wanelik Kazimir , Darrow Michele C. , Medina Esau , Hobbs Carl , Rau Christoph , Bradbury Elizabeth J. 
Published: August 2018

AbstractSynchrotron radiation microtomography (SRμCT) is a nominally non-destructive 3D imaging technique which can visualise the internal structures of whole soft tissues. As a multi-stage technique, the cumulative benefits of optimising sample preparation, scanning parameters and signal processing can improve SRμCT imaging efficiency, image quality, accuracy and ultimately, data utility. By evaluating different sample preparations (embedding media, tissue stains), imaging (projection number, propagation distance) and reconstruction (artefact correction, phase retrieval) parameters, a novel methodology (combining reversible iodine stain, wax embedding and inline phase contrast) was optimised for fast (~12 minutes), high-resolution (3.2–4.8 μm diameter capillaries resolved) imaging of the full diameter of a 3.5 mm length of rat spinal cord. White-grey matter macro-features and micro-features such as motoneurons and capillary-level vasculature could then be completely segmented from the imaged volume for analysis through the shallow machine learning SuRVoS Workbench. Imaged spinal cord tissue was preserved for subsequent histology, establishing a complementary SRμCT methodology that can be applied to study spinal cord pathologies or other nervous system tissues such as ganglia, nerves and brain. Further, our ‘single-scan iterative downsampling’ approach and side-by-side comparisons of mounting options, sample stains and phase contrast parameters should inform efficient, effective future soft tissue SRμCT experiment design.
Social support rescues acute stress-induced cognitive impairments by modulating ERK1/2 phosphorylation in adolescent mice
Authors: Kim Ji-Woon , Ko Mee Jung , Gonzales Edson Luck , Kang Ri Jin , Kim Do Gyeong , Kim Yujeong , Seung Hana , Oh Hyun A , Eun Pyeong Hwa , Shin Chan Young 
Published: August 2018

AbstractSocial support can relieve stress-induced behavioural outcomes, although its underlying molecular mechanisms are not fully understood. Here, we evaluated whether social interactions can prevent the restraint stress (RS)-induced cognitive impairments in male adolescent mice by utilizing molecular, cellular, and behavioural approaches. Acute RS in adolescent ICR mice impaired the working memory in the Y-maze test and memory consolidation and retrieval in the novel-object-recognition test (NORT). In addition, RS increased the extracellular signal-regulated kinases 1/2 phosphorylation (p-ERK1/2) in the prefrontal cortex (PFC) and corticosterone levels in the plasma. Interestingly, these outcomes were normalized by the presence of a conspecific animal (social support) during RS. RS also significantly upregulated the expression levels of known stress-relevant genes such as Egr1, Crh, and Crhr1, which were normalized by social support. Systemic injection of SL327 (an inhibitor of MEK1/2 that also blocks its downstream signal ERK1/2) prior to RS rescued the working memory impairments and the increased p-ERK1/2 while normalizing the expression of Egr1. Our results suggest that social support can alleviate the RS-induced cognitive impairments partly by modulating ERK1/2 phosphorylation and gene transcription in the PFC, and provide novel insights into the molecular mechanisms of the stress-buffering effects of social support.
Cancer stem cells as targets for DC-based immunotherapy of colorectal cancer
Authors: Szaryńska Magdalena , Olejniczak Agata , Kobiela Jarosław , Łaski Dariusz , Śledziński Zbigniew , Kmieć Zbigniew 
Published: August 2018

AbstractThe therapy of colorectal cancer (CRC) patients is often unsuccessful because of the presence of cancer stem cells (CSCs) resistant to conventional approaches. Dendritic cells (DC)-based protocols are believed to effectively supplement CRC therapy. Our study was aimed to assess how the number and properties of CSCs isolated from tumor tissue of CRC patients will affect the biological characteristics of in vitro modified DCs. Similar procedures were conducted with the using of CRC HCT116 and HT29 cell lines. We found that the detailed configuration of CSC-like markers significantly influenced the maturation and activation of DCs after stimulation with cancer cells lysates or culture supernatants. This basic stimulatory effect was enhanced by LPS that is normally present in CRC CSCs niche. The increased number of CD29+ and CD44+ CSCs presented the opposite impact on treated DCs as showed by many significant correlations. The CD133+ CSCs seemed to impair the functions of DCs. The more CD133+ CSCs in tumor sample the lower number of activated DCs evidenced after stimulation. Moreover, our results showed superiority of the spherical culture model over the adherent one since spherical HCT116 and HT29 cells presented similar influence on DCs properties as CRC patients cancer cells. We concluded that the DCs features may depend directly on the properties of CSCs affected by progression status of tumor.
Automated Gleason grading of prostate cancer tissue microarrays via deep learning
Authors: Arvaniti Eirini , Fricker Kim S. , Moret Michael , Rupp Niels , Hermanns Thomas , Fankhauser Christian , Wey Norbert , Wild Peter J. , Rüschoff Jan H. , Claassen Manfred 
Published: August 2018

AbstractThe Gleason grading system remains the most powerful prognostic predictor for patients with prostate cancer since the 1960s. Its application requires highly-trained pathologists, is tedious and yet suffers from limited inter-pathologist reproducibility, especially for the intermediate Gleason score 7. Automated annotation procedures constitute a viable solution to remedy these limitations. In this study, we present a deep learning approach for automated Gleason grading of prostate cancer tissue microarrays with Hematoxylin and Eosin (H&E) staining. Our system was trained using detailed Gleason annotations on a discovery cohort of 641 patients and was then evaluated on an independent test cohort of 245 patients annotated by two pathologists. On the test cohort, the inter-annotator agreements between the model and each pathologist, quantified via Cohen’s quadratic kappa statistic, were 0.75 and 0.71 respectively, comparable with the inter-pathologist agreement (kappa = 0.71). Furthermore, the model’s Gleason score assignments achieved pathology expert-level stratification of patients into prognostically distinct groups, on the basis of disease-specific survival data available for the test cohort. Overall, our study shows promising results regarding the applicability of deep learning-based solutions towards more objective and reproducible prostate cancer grading, especially for cases with heterogeneous Gleason patterns.
Cardiomyocytes Derived from Human CardiopoieticAmniotic Fluids
Authors: Di Baldassarre Angela , D’Amico Maria A , Izzicupo Pascal , Gaggi Giulia , Guarnieri Simone , Mariggiò Maria A , Antonucci Ivana , Corneo Barbara , Sirabella Dario , Stuppia Liborio , Ghinassi Barbara 
Published: August 2018

AbstractHuman amniotic fluid (hAF) cells share characteristics of both embryonic and adult stem cells. They proliferate rapidly and can differentiate into cells of all embryonic germ layers but do not form teratomas. Embryoid-bodies obtained from hAF have cardiac differentiation potential, but terminal differentiation to cardiomyocytes (CMs) has not yet been described. Our purpose was to promote cardiac differentiation in hAFcells. Cells were exposed to inducing factors for up to 15 days. Only the subset of hAF cells expressing the multipotency markers SSEA4, OCT4 and CD90 (CardiopoieticAF cells) responded to the differentiation process by increasing the expression of the cardiac transcription factors Nkx2.5 and GATA4, sarcomeric proteins (cTnT, α-MHC, α-SA), Connexin43 and atrial and ventricular markers. Furthermore, differentiated cells were positive for the calcium pumps CACNA1C and SERCA2a, with approximately 30% of CardiopoieticAF-derived CM-like cells responding to caffeine or adrenergic stimulation. Some spontaneous rare beating foci were also observed. In conclusion, we demonstrated that CardiopoieticAF cells might differentiate toward the cardiac lineage giving rise to CM-like cells characterized by several cardiac-specific molecular, structural, and functional properties.
Highly-stable write-once-read-many-times switching behaviors of 1D–1R memristive devices based on graphene quantum dot nanocomposites
Authors: Sung Sihyun , Wu Chaoxing , Jung Hyun Soo , Kim Tae Whan 
Published: August 2018

AbstractOne diode and one resistor (1D–1R) memristive devices based on inorganic Schottky diodes and poly(methylsilsesquioxane) (PMSSQ):graphene quantum dot (GQD) hybrid nanocomposites were fabricated to achieve stable memory characteristics. Current-voltage (I-V) curves for the Al/PMSSQ:GQDs/Al/p-Si/Al devices at room temperature exhibited write-once, read-many-times memory (WORM) characteristics with an ON/OFF ratio of as large as 104 resulting from the formation of a 1D–1R structure. I-V characteristics of the WORM 1D–1R device demonstrated that the memory and the diode behaviors of the 1D–1R device functioned simultaneously. The retention time of the WORM 1D–1R devices could be maintained at a value larger than 104 s under ambient conditions. The operating mechanisms of the devices were analyzed on the basis of the I–V results and with the aid of the energy band diagram.
Distribution of oxidized DJ-1 in Parkinson’s disease-related sites in the brain and in the peripheral tissues: effects of aging and a neurotoxin
Authors: Mita Yuichiro , Kataoka Yuto , Saito Yoshiro , Kashi Takuma , Hayashi Kojiro , Iwasaki Asa , Imanishi Takanori , Miyasaka Tomohiro , Noguchi Noriko 
Published: August 2018

AbstractDJ-1 plays an important role in antioxidant defenses, and a reactive cysteine at position 106 (Cys106) of DJ-1, a critical residue of its biological function, is oxidized under oxidative stress. DJ-1 oxidation has been reported in patients with Parkinson’s disease (PD), but the relationship between DJ-1 oxidation and PD is still unclear. In the present study using specific antibody for Cys106-oxidized DJ-1 (oxDJ-1), we analyzed oxDJ-1 levels in the brain and peripheral tissues in young and aged mice and in a mouse model of PD induced using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). OxDJ-1 levels in the brain, heart, and skeletal muscle were high compared with other tissues. In the brain, oxDJ-1 was detected in PD-related brain sites such as the substantia nigra (SN) of the midbrain, olfactory bulb (OB), and striatum. In aged wild-type mice, oxDJ-1 levels in the OB, striatum, and heart tended to decrease, while those in the skeletal muscle increased significantly. Expression of dopamine-metabolizing enzymes significantly increased in the SN and OB of aged DJ-1−/− mice, accompanied by a complementary increase in glutathione peroxidase 1. MPTP treatment concordantly changed oxDJ-1 levels in PD-related brain sites and heart. These results indicate that the effects of physiological metabolism, aging, and neurotoxin change oxDJ-1 levels in PD-related brain sites, heart, and skeletal muscle where mitochondrial load is high, suggesting a substantial role of DJ-1 in antioxidant defenses and/or dopamine metabolism in these tissues.
Delay-Induced Multistability and Loop Formation in Neuronal Networks with Spike-Timing-Dependent Plasticity
Authors: Madadi Asl Mojtaba , Valizadeh Alireza , Tass Peter A. 
Published: August 2018

AbstractSpike-timing-dependent plasticity (STDP) adjusts synaptic strengths according to the precise timing of pre- and postsynaptic spike pairs. Theoretical and computational studies have revealed that STDP may contribute to the emergence of a variety of structural and dynamical states in plastic neuronal populations. In this manuscript, we show that by incorporating dendritic and axonal propagation delays in recurrent networks of oscillatory neurons, the asymptotic connectivity displays multistability, where different structures emerge depending on the initial distribution of the synaptic strengths. In particular, we show that the standard deviation of the initial distribution of synaptic weights, besides its mean, determines the main properties of the emergent structural connectivity such as the mean final synaptic weight, the number of two-neuron loops and the symmetry of the final structure. We also show that the firing rates of the neurons affect the evolution of the network, and a more symmetric configuration of the synapses emerges at higher firing rates. We justify the network results based on a two-neuron framework and show how the results translate to large recurrent networks.
DAF-21/Hsp90 is required for C. elegans longevity by ensuring DAF-16/FOXO isoform A function
Authors: Somogyvári Milán , Gecse Eszter , Sőti Csaba 
Published: August 2018

AbstractThe FOXO transcription factor family is a conserved regulator of longevity and the downstream target of insulin/insulin-like signaling. In Caenorhabditis elegans, the FOXO ortholog DAF-16A and D/F isoforms extend lifespan in daf-2 insulin-like receptor mutants. Here we identify the DAF-21/Hsp90 chaperone as a longevity regulator. We find that reducing DAF-21 capacity by daf-21(RNAi) initiated either at the beginning or at the end of larval development shortens wild-type lifespan. daf-21 knockdown employed from the beginning of larval development also decreases longevity of daf-2 mutant and daf-2 silenced nematodes. daf-16 loss-of-function mitigates the lifespan shortening effect of daf-21 silencing. We demonstrate that DAF-21 specifically promotes daf-2 and heat-shock induced nuclear translocation of DAF-16A as well as the induction of DAF-16A-specific mRNAs, without affecting DAF-16D/F localization and transcriptional function. DAF-21 is dispensable for the stability and nuclear import of DAF-16A, excluding a chaperone-client interaction and suggesting that DAF-21 regulates DAF-16A activation upstream of its cellular traffic. Finally, we show a selective requirement for DAF-21 to extend lifespan of DAF-16A, but not DAF-16D/F, transgenic daf-2 mutant strains. Our findings indicate a spatiotemporal determination of multiple DAF-21 roles in fertility, development and longevity and reveal an isoform-specific regulation of DAF-16 activity.
Assessment of physical inactivity and locomotor dysfunction in adults with visual impairment
Authors: Inoue Sachiko , Kawashima Motoko , Hiratsuka Yoshimune , Nakano Tadashi , Tamura Hiroshi , Ono Koichi , Murakami Akira , Tsubota Kazuo , Yamada Masakazu 
Published: August 2018

AbstractTo evaluate the association between vision-related quality of life (QoL), physical inactivity, and locomotor dysfunction in subjects with visual impairment.This cross-sectional study included 215 visually impaired subjects recruited from six ophthalmology departments in Japan. The physical inactivity and locomotor dysfunction associated with their visual impairment was investigated. The physical activity level was assessed using the short form of the International Physical Activity Questionnaire and classified as high, moderate, or low. Locomotor function was evaluated with the Geriatric Locomotive Function Scale. Vision-related QoL was evaluated using the 25-item National Eye Institute Visual Function Questionnaire. Background data, including for age, sex, best-corrected visual acuity for each eye, causative eye diseases, systemic comorbidities, and body mass index, were also collected.The average patient age was 69.6 (range, 20–93 years; standard deviation, 14.5 years) and 118 patients (54.9%) were men. Multivariate analysis showed that vision-related QoL and best-corrected visual acuity in the worse eye were significantly associated with physical inactivity and that vision-related QoL, female sex, age, and presence of systemic comorbidity were significantly associated with locomotor dysfunction. Vision-related quality of life is associated with physical inactivity and locomotor dysfunction.
Floral evolution by simplification in Monanthotaxis (Annonaceae) and hypotheses for pollination system shifts
Authors: Hoekstra Paul H. , Wieringa Jan J. , Smets Erik , Chatrou Lars W. 
Published: August 2018

AbstractSimplification by reduction has occurred many times independently in the floral evolution of angiosperms. These reductions have often been attributed to changes in reproductive biology. In the angiosperm plant family Annonaceae, most species have flowers with six petals, and many stamens and carpels. In the genus Monanthotaxis several deviations from this pattern have been observed, including flowers that contain three petals and three stamens only. New DNA sequences were generated for 42 specimens of Monanthotaxis. Five chloroplast markers and two nuclear markers for 72 out of 94 species of Monanthotaxis were used to reconstruct a phylogeny of the genus, which revealed several well-supported, morphologically distinct clades. The evolution of four quantitative and two qualitative floral characters was mapped onto this phylogeny, demonstrating a reduction in flower size and number of flower parts in Monanthotaxis. A large variation in stamen forms and numbers, strong correlations between petal size, stamen and carpel number, combined with a non-gradual mode of evolution and the sympatric co-occurrence of Monanthotaxis species from different clades suggest that the high diversity in the African rainforest of this genus is caused by switches in pollination systems.
Myocardial fatty acid uptake through CD36 is indispensable for sufficient bioenergetic metabolism to prevent progression of pressure overload-induced heart failure
Authors: Umbarawan Yogi , Syamsunarno Mas Rizky A. A. , Koitabashi Norimichi , Obinata Hideru , Yamaguchi Aiko , Hanaoka Hirofumi , Hishiki Takako , Hayakawa Noriyo , Sano Motoaki , Sunaga Hiroaki , Matsui Hiroki , Tsushima Yoshito , Suematsu Makoto , Kurabayashi Masahiko , Iso Tatsuya 
Published: August 2018

AbstractThe energy metabolism of the failing heart is characterized by reduced fatty acid (FA) oxidation and an increase in glucose utilization. However, little is known about how energy metabolism-function relationship is relevant to pathophysiology of heart failure. Recent study showed that the genetic deletion of CD36 (CD36KO), which causes reduction in FA use with an increased reliance on glucose, accelerates the progression from compensated hypertrophy to heart failure. Here, we show the mechanisms by which CD36 deletion accelerates heart failure in response to pressure overload. CD36KO mice exhibited contractile dysfunction and death from heart failure with enhanced cardiac hypertrophy and interstitial fibrosis when they were subjected to transverse aortic constriction (TAC). The pool size in the TCA cycle and levels of high-energy phosphate were significantly reduced in CD36KO-TAC hearts despite an increase in glycolytic flux. De novo synthesis of non-essential amino acids was facilitated in CD36KO-TAC hearts, which could cause a further decline of the pool size. The ingestion of a diet enriched in medium-chain FA improved cardiac dysfunction in CD36KO-TAC hearts. These findings suggest that myocardial FA uptake through CD36 is indispensable for sufficient ATP production and for preventing an increased glycolytic flux-mediated structural remodeling during pressure overload-induced hypertrophy.