bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Core Regulatory Circuit in Glioblastoma Stem Cells Links MAPK Activation to a Transcriptional Program of Neural Stem Cell Identity
Authors: Riddick Gregory , Kotliarova Svetlana , Rodriguez Virginia , Kim H. S. , Linkous Amanda , Storaska Andrew J. , Ahn Susie , Walling Jennifer , Belova Galina , Fine Howard A. 
Published: March 2017

AbstractGlioblastoma, the most common primary malignant brain tumor, harbors a small population of tumor initiating cells (glioblastoma stem cells) that have many properties similar to neural stem cells. To investigate common regulatory networks in both neural and glioblastoma stem cells, we subjected both cell types to in-vitro differentiation conditions and measured global gene-expression changes using gene expression microarrays. Analysis of enriched transcription factor DNA-binding sites in the promoters of differentially expressed genes was used to reconstruct regulatory networks involved in differentiation. Computational predictions, which were biochemically validated, show an extensive overlap of regulatory circuitry between cell types including a network centered on the transcription factor KLF4. We further demonstrate that EGR1, a transcription factor previously shown to be downstream of the MAPK pathway, regulates KLF4 expression and that KLF4 in turn transcriptionally activates NOTCH as well as SOX2. These results demonstrate how known genomic alterations in glioma that induce constitutive activation of MAPK are transcriptionally linked to master regulators essential for neural stem cell identify.
Higher-order power harmonics of pulsed electrical stimulation modulates corticospinal contribution of peripheral nerve stimulation
Authors: Chen Chiun-Fan , Bikson Marom , Chou Li-Wei , Shan Chunlei , Khadka Niranjan , Chen Wen-Shiang , Fregni Felipe 
Published: March 2017

AbstractIt is well established that electrical-stimulation frequency is crucial to determining the scale of induced neuromodulation, particularly when attempting to modulate corticospinal excitability. However, the modulatory effects of stimulation frequency are not only determined by its absolute value but also by other parameters such as power at harmonics. The stimulus pulse shape further influences parameters such as excitation threshold and fiber selectivity. The explicit role of the power in these harmonics in determining the outcome of stimulation has not previously been analyzed. In this study, we adopted an animal model of peripheral electrical stimulation that includes an amplitude-adapted pulse train which induces force enhancements with a corticospinal contribution. We report that the electrical-stimulation-induced force enhancements were correlated with the amplitude of stimulation power harmonics during the amplitude-adapted pulse train. In an exploratory analysis, different levels of correlation were observed between force enhancement and power harmonics of 20–80 Hz (r = 0.4247, p = 0.0243), 100–180 Hz (r = 0.5894, p = 0.0001), 200–280 Hz (r = 0.7002, p < 0.0001), 300–380 Hz (r = 0.7449, p < 0.0001), 400–480 Hz (r = 0.7906, p < 0.0001), 500–600 Hz (r = 0.7717, p < 0.0001), indicating a trend of increasing correlation, specifically at higher order frequency power harmonics. This is a pilot, but important first demonstration that power at high order harmonics in the frequency spectrum of electrical stimulation pulses may contribute to neuromodulation, thus warrant explicit attention in therapy design and analysis.
PD-L1 predicts poor prognosis for nasopharyngeal carcinoma irrespective of PD-1 and EBV-DNA load
Authors: Zhou Yajuan , Shi Dingbo , Miao Jingjing , Wu Haijun , Chen Jiewei , Zhou Xiaoyi , Hu Desheng , Zhao Chong , Deng Wuguo , Xie Conghua 
Published: March 2017

AbstractProgrammed death-1 (PD-1) is an immunosuppressive receptor functionally bound with programmed death-ligand 1 (PD-L1), which has been reported in various malignancies. However, only a few studies are available for the clinical significance of PD-1/PD-L1 in nasopharyngeal carcinoma (NPC). In this study, we aim to investigate alterations in PD-1/PD-L1 by using immunohistochemistry analysis in a cohort of consecutively enrolled NPC patients (n = 99). To further analyse the correlation between PD-1/PD-L1 and factors involved in clinico-pathology, haematologic biomarkers, EBV-DNA load and outcomes, we collected clinical data for statistical analysis. We observed that lower haemoglobin (HB) and Body Mass Index (BMI) levels were associated with high levels of PD-L1 staining in NPC patients. Importantly, our results suggested that PD-L1 might be a negative indicator for NPC patients. In contrast, a correlation between the PD-1/PD-L1 level and EBV load was not identified. Moreover, PD-1 positivity was suggested to not be significantly correlated with clinical outcomes. Taken together, our results revealed that PD-L1 might be a potential prognostic biomarker for NPC patients. However, further studies are needed to clarify the underlying mechanism of EBV status in the immunosuppression process induced by the PD-1/PD-L1 axis.
Predicting bone strength with ultrasonic guided waves
Authors: Bochud Nicolas , Vallet Quentin , Minonzio Jean-Gabriel , Laugier Pascal 
Published: March 2017

AbstractRecent bone quantitative ultrasound approaches exploit the multimode waveguide response of long bones for assessing properties such as cortical thickness and stiffness. Clinical applications remain, however, challenging, as the impact of soft tissue on guided waves characteristics is not fully understood yet. In particular, it must be clarified whether soft tissue must be incorporated in waveguide models needed to infer reliable cortical bone properties. We hypothesize that an inverse procedure using a free plate model can be applied to retrieve the thickness and stiffness of cortical bone from experimental data. This approach is first validated on a series of laboratory-controlled measurements performed on assemblies of bone- and soft tissue mimicking phantoms and then onin vivomeasurements. The accuracy of the estimates is evaluated by comparison with reference values. To further support our hypothesis, these estimates are subsequently inserted into a bilayer model to test its accuracy. Our results show that the free plate model allows retrieving reliable waveguide properties, despite the presence of soft tissue. They also suggest that the more sophisticated bilayer model, although it is more precise to predict experimental data in the forward problem, could turn out to be hardly manageable for solving the inverse problem.
Altered intestinal microbiota in patients with chronic pancreatitis: implications in diabetes and metabolic abnormalities
Authors: Jandhyala Sai Manasa , Madhulika A. , Deepika G. , Rao G. Venkat , Reddy D. Nageshwar , Subramanyam Chivukula , Sasikala Mitnala , Talukdar Rupjyoti 
Published: March 2017

AbstractIntestinal dysbiosis and its functional implications in chronic pancreatitis (CP) have not been elaborately studied. We evaluated the taxonomic and functional alterations in intestinal microbiota in 30 well-characterised patients with CP (16 without, 14 with diabetes) and 10 healthy controls. The patients with CP and diabetes had significantly longer disease duration and greater degree of malnutrition. There was increase in plasma endotoxin concentrations from controls to CP non-diabetics to CP diabetics. We observed significant differences in richness and alpha diversity between the groups. We also observed increase in the Firmicutes:Bacteroidetes ratio in CP patients without and with diabetes. There was reduction in abundance of Faecalibacterium prausnitzii and Ruminococcus bromii from controls to CP non-diabetics to CP diabetics. On the other hand, there was increase in LPS (endotoxin) synthetic pathways (KEGG orthology) in the groups. Faecalibacterium prausnitzii abundance correlated negatively with plasma endotoxin and glycemic status; while plasma endotoxin correlated positively with blood glucose and negatively with plasma insulin. Our results have important implications for future studies exploring mechanistic insights on secondary diabetes in CP.
Reaching back: the relative strength of the retroactive emotional attentional blink
Authors: Ní Choisdealbha Áine , Piech Richard M. , Fuller John K. , Zald David H. 
Published: March 2017

AbstractVisual stimuli with emotional content appearing in close temporal proximity either before or after a target stimulus can hinder conscious perceptual processing of the target via an emotional attentional blink (EAB). This occurs for targets that appear after the emotional stimulus (forward EAB) and for those appearing before the emotional stimulus (retroactive EAB). Additionally, the traditional attentional blink (AB) occurs because detection of any target hinders detection of a subsequent target. The present study investigated the relations between these different attentional processes. Rapid sequences of landscape images were presented to thirty-one male participants with occasional landscape targets (rotated images). For the forward EAB, emotional or neutral distractor images of people were presented before the target; for the retroactive EAB, such images were also targets and presented after the landscape target. In the latter case, this design allowed investigation of the AB as well. Erotic and gory images caused more EABs than neutral images, but there were no differential effects on the AB. This pattern is striking because while using different target categories (rotated landscapes, people) appears to have eliminated the AB, the retroactive EAB still occurred, offering additional evidence for the power of emotional stimuli over conscious attention.
Differences in electroencephalographic non-rapid-eye movement sleep slow-wave characteristics between young and old mice
Authors: Panagiotou Maria , Vyazovskiy Vladyslav V. , Meijer Johanna H. , Deboer Tom 
Published: March 2017

AbstractChanges in sleep pattern are typical for the normal aging process. However, aged mice show an increase in the amount of sleep, whereas humans show a decrease when aging. Mice are considered an important model in aging studies, and this divergence warrants further investigation. Recently, insights into the network dynamics of cortical activity during sleep were obtained by investigating characteristics of individual electroencephalogram (EEG) slow waves in young and elderly humans. In this study, we investigated, for the first time, the parameters of EEG slow waves, including their incidence, amplitude, duration and slopes, in young (6 months) and older (18–24 months) C57BL/6J mice during undisturbed 24 h, and after a 6-h sleep deprivation (SD). As expected, older mice slept more but, in contrast to humans, absolute NREM sleep EEG slow-wave activity (SWA, spectral power density between 0.5–4 Hz) was higher in the older mice, as compared to the young controls. Furthermore, slow waves in the older mice were characterized by increased amplitude, steeper slopes and fewer multipeak waves, indicating increased synchronization of cortical neurons in aging, opposite to what was found in humans. Our results suggest that older mice, in contrast to elderly humans, live under a high sleep pressure.
High intensity aerobic exercise training improves chronic intermittent hypoxia-induced insulin resistance without basal autophagy modulation
Authors: Pauly Marion , Assense Allan , Rondon Aurélie , Thomas Amandine , Dubouchaud Hervé , Freyssenet Damien , Benoit Henri , Castells Josiane , Flore Patrice 
Published: March 2017

AbstractChronic intermittent hypoxia (IH) associated with obstructive sleep apnea (OSA) is a major risk factor for cardiovascular and metabolic diseases (insulin resistance: IR). Autophagy is involved in the pathophysiology of IR and high intensity training (HIT) has recently emerged as a potential therapy. We aimed to confirm IH-induced IR in a tissue-dependent way and to explore the preventive effect of HIT on IR-induced by IH. Thirty Swiss 129 male mice were randomly assigned to Normoxia (N), Intermittent Hypoxia (IH: 21–5% FiO2, 30 s cycle, 8 h/day) or IH associated with high intensity training (IH HIT). After 8 days of HIT (2*24 min, 50 to 90% of Maximal Aerobic Speed or MAS on a treadmill) mice underwent 14 days IH or N. We found that IH induced IR, characterized by a greater glycemia, an impaired insulin sensitivity and lower AKT phosphorylation in adipose tissue and liver. Nevertheless, MAS and AKT phosphorylation were greater in muscle after IH. IH associated with HIT induced better systemic insulin sensitivity and AKT phosphorylation in liver. Autophagy markers were not altered in both conditions. These findings suggest that HIT could represent a preventive strategy to limit IH-induced IR without change of basal autophagy.
Multiscale image analysis reveals structural heterogeneity of the cell microenvironment in homotypic spheroids
Authors: Schmitz Alexander , Fischer Sabine C. , Mattheyer Christian , Pampaloni Francesco , Stelzer Ernst H. K. 
Published: March 2017

AbstractThree-dimensional multicellular aggregates such as spheroids provide reliable in vitro substitutes for tissues. Quantitative characterization of spheroids at the cellular level is fundamental. We present the first pipeline that provides three-dimensional, high-quality images of intact spheroids at cellular resolution and a comprehensive image analysis that completes traditional image segmentation by algorithms from other fields. The pipeline combines light sheet-based fluorescence microscopy of optically cleared spheroids with automated nuclei segmentation (F score: 0.88) and concepts from graph analysis and computational topology. Incorporating cell graphs and alpha shapes provided more than 30 features of individual nuclei, the cellular neighborhood and the spheroid morphology. The application of our pipeline to a set of breast carcinoma spheroids revealed two concentric layers of different cell density for more than 30,000 cells. The thickness of the outer cell layer depends on a spheroid’s size and varies between 50% and 75% of its radius. In differently-sized spheroids, we detected patches of different cell densities ranging from 5 × 105 to 1 × 106cells/mm3. Since cell density affects cell behavior in tissues, structural heterogeneities need to be incorporated into existing models. Our image analysis pipeline provides a multiscale approach to obtain the relevant data for a system-level understanding of tissue architecture.
Consequences of biodiversity loss diverge from expectation due to post-extinction compensatory responses
Authors: Thomsen Matthias S. , Garcia Clement , Bolam Stefan G. , Parker Ruth , Godbold Jasmin A. , Solan Martin 
Published: March 2017

AbstractConsensus has been reached that global biodiversity loss impairs ecosystem functioning and the sustainability of services beneficial to humanity. However, the ecosystem consequences of extinction in natural communities are moderated by compensatory species dynamics, yet these processes are rarely accounted for in impact assessments and seldom considered in conservation programmes. Here, we use marine invertebrate communities to parameterise numerical models of sediment bioturbation – a key mediator of biogeochemical cycling – to determine whether post-extinction compensatory mechanisms alter biodiversity-ecosystem function relations following non-random extinctions. We find that compensatory dynamics lead to trajectories of sediment mixing that diverge from those without compensation, and that the form, magnitude and variance of each probabilistic distribution is highly influenced by the type of compensation and the functional composition of surviving species. Our findings indicate that the generalized biodiversity-function relation curve, as derived from multiple empirical investigations of random species loss, is unlikely to yield representative predictions for ecosystem properties in natural systems because the influence of post-extinction community dynamics are under-represented. Recognition of this problem is fundamental to management and conservation efforts, and will be necessary to ensure future plans and adaptation strategies minimize the adverse impacts of the biodiversity crisis.
Effective Removal of Tetracycline Antibiotics from Water using Hybrid Carbon Membranes
Authors: Liu Ming-kai , Liu Ying-ya , Bao Dan-dan , Zhu Gen , Yang Guo-hai , Geng Jun-feng , Li Hai-tao 
Published: March 2017

AbstractAntibiotic residues in drinking water have become a global problem, especially in developing countries. However, effective purification of water contaminated by antibiotics remains a great challenge. Here, we investigated the removing of tetracycline by carbon nanomaterials with different structures and surface functionalities. The result shows that a membrane of thick graphene oxide (GO) and activated carbon (AC) with a thickness of 15 μm can effectively remove 98.9% of tetracycline hydrochloride (TCH) from water by vacuum filtration. Structural analysis indicated that the AC nanoparticles were uniformly inserted into the GO interstitial sites without any aggregations. Also, GO sheets were loosened by the encapsulated AC nanoparticles, leading to the formation of numerous tiny pores (3–10 nm) that acted as channels for fluid passage, whereas the carbons and chemical groups on the GO surface adsorbed TCH. GO/AC membrane exhibits the best adsorption efficiency among the investigated materials, including pure GO, AC, carbon nanotube (CNT), and CNT/AC and GO/CNT hybrids.
Consecutive record-breaking high temperatures marked the handover from hiatus to accelerated warming
Authors: Su Jingzhi , Zhang Renhe , Wang Huijun 
Published: March 2017

AbstractClosely following the hiatus warming period, two astonishing high temperature records reached in 2014 and 2015 consecutively. To investigate the occurrence features of record-breaking high temperatures in recent years, a new index focusing the frequency of the top 10 high annual mean temperatures was defined in this study. Analyses based on this index shown that record-breaking high temperatures occurred over most regions of the globe with a salient increasing trend after 1960 s, even during the so-called hiatus period. Overlapped on the ongoing background warming trend and the interdecadal climate variabilities, the El Niño events, particularly the strong ones, can make a significant contribution to the occurrence of high temperatures on interannual timescale. High temperatures associated with El Niño events mainly occurred during the winter annual period. As the Pacific Decadal Oscillation (PDO) struggled back to its positive phase since 2014, the global warming returned back to a new accelerated warming period, marked by the record-breaking high temperatures in 2014. Intensified by the super strong El Niño, successive high records occurred in 2015 and 2016. Higher frequencies of record high temperatures would occur in the near future because the PDO tends to maintain a continuously positive phase.
Land-based salmon aquacultures change the quality and bacterial degradation of riverine dissolved organic matter
Authors: Kamjunke Norbert , Nimptsch Jorge , Harir Mourad , Herzsprung Peter , Schmitt-Kopplin Philippe , Neu Thomas R. , Graeber Daniel , Osorio Sebastian , Valenzuela Jose , Carlos Reyes Juan , Woelfl Stefan , Hertkorn Norbert 
Published: March 2017

AbstractAquacultures are of great economic importance worldwide but pollute pristine headwater streams, lakes, and estuaries. However, there are no in-depth studies of the consequences of aquacultures on dissolved organic matter (DOM) composition and structure. We performed a detailed molecular level characterization of aquaculture DOM quality and its bacterial degradation using four salmon aquacultures in Chile. Fluorescence measurements, ultrahigh-resolution mass spectrometry, and nuclear magnetic resonance spectroscopy of the DOM revealed specific and extensive molecular alterations caused by aquacultures. Aquacultures released large quantities of readily bioavailable metabolites (primarily carbohydrates and peptides/proteins, and lipids), causing the organic matter downstream of all the investigated aquacultures to deviate strongly from the highly processed, polydisperse and molecularly heterogeneous DOM found in pristine rivers. However, the upstream individual catchment DOM signatures remained distinguishable at the downstream sites. The benthic algal biovolume decreased and the bacterial biovolume and production increased downstream of the aquacultures, shifting stream ecosystems to a more heterotrophic state and thus impairing the ecosystem health. The bacterial DOM degradation rates explain the attenuation of aquaculture DOM within the subsequent stream reaches. This knowledge may aid the development of improved waste processing facilities and may help to define emission thresholds to protect sensitive stream ecosystems.
Characterization of the Dynamic Transcriptome of a Herpesvirus with Long-read Single Molecule Real-Time Sequencing
Authors: Tombácz Dóra , Balázs Zsolt , Csabai Zsolt , Moldován Norbert , Szűcs Attila , Sharon Donald , Snyder Michael , Boldogkői Zsolt 
Published: March 2017

AbstractHerpesvirus gene expression is co-ordinately regulated and sequentially ordered during productive infection. The viral genes can be classified into three distinct kinetic groups: immediate-early, early, and late classes. In this study, a massively parallel sequencing technique that is based on PacBio Single Molecule Real-time sequencing platform, was used for quantifying the poly(A) fraction of the lytic transcriptome of pseudorabies virus (PRV) throughout a 12-hour interval of productive infection on PK-15 cells. Other approaches, including microarray, real-time RT-PCR and Illumina sequencing are capable of detecting only the aggregate transcriptional activity of particular genomic regions, but not individual herpesvirus transcripts. However, SMRT sequencing allows for a distinction between transcript isoforms, including length- and splice variants, as well as between overlapping polycistronic RNA molecules. The non-amplified Isoform Sequencing (Iso-Seq) method was used to analyse the kinetic properties of the lytic PRV transcripts and to then classify them accordingly. Additionally, the present study demonstrates the general utility of long-read sequencing for the time-course analysis of global gene expression in practically any organism.
Cholesterol depletion impairs contractile machinery in neonatal rat cardiomyocytes
Authors: Hissa Barbara , Oakes Patrick W. , Pontes Bruno , Ramírez-San Juan Guillermina , Gardel Margaret L. 
Published: March 2017

AbstractCholesterol regulates numerous cellular processes. Depleting its synthesis in skeletal myofibers induces vacuolization and contraction impairment. However, little is known about how cholesterol reduction affects cardiomyocyte behavior. Here, we deplete cholesterol by incubating neonatal cardiomyocytes with methyl-beta-cyclodextrin. Traction force microscopy shows that lowering cholesterol increases the rate of cell contraction and generates defects in cell relaxation. Cholesterol depletion also increases membrane tension, Ca2+ spikes frequency and intracellular Ca2+ concentration. These changes can be correlated with modifications in caveolin-3 and L-Type Ca2+ channel distributions across the sarcolemma. Channel regulation is also compromised since cAMP-dependent PKA activity is enhanced, increasing the probability of L-Type Ca2+ channel opening events. Immunofluorescence reveals that cholesterol depletion abrogates sarcomeric organization, changing spacing and alignment of α-actinin bands due to increase in proteolytic activity of calpain. We propose a mechanism in which cholesterol depletion triggers a signaling cascade, culminating with contraction impairment and myofibril disruption in cardiomyocytes.