bluuebunny/crossref_metadata_2025_split huggingface dataset:
PIM kinases mediate resistance of glioblastoma cells to TRAIL by a p62/SQSTM1-dependent mechanism
Authors: Serrano-Saenz Santiago , Palacios Carmen , Delgado-Bellido Daniel , López-Jiménez Laura , Garcia-Diaz Angel , Soto-Serrano Yolanda , Casal J. Ignacio , Bartolomé Rubén A. , Fernández-Luna José Luis , López-Rivas Abelardo , Oliver F. Javier 
Published: February 2019

AbstractGlioblastoma (GBM) is the most common and aggressive brain tumor and is associated with poor prognosis. GBM cells are frequently resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and finding new combinatorial therapies to sensitize glioma cells to TRAIL remains an important challenge. PIM kinases are serine/threonine kinases that promote cell survival and proliferation and are highly expressed in different tumors. In this work, we studied the role of PIM kinases as regulators of TRAIL sensitivity in GBM cells. Remarkably, PIM inhibition or knockdown facilitated activation by TRAIL of a TRAIL-R2/DR5-mediated and mitochondria-operated apoptotic pathway in TRAIL-resistant GBM cells. The sensitizing effect of PIM knockdown on TRAIL-induced apoptosis was mediated by enhanced caspase-8 recruitment to and activation at the death-inducing signaling complex (DISC). Interestingly, TRAIL-induced internalization of TRAIL-R2/DR5 was significantly reduced in PIM knockdown cells. Phospho-proteome profiling revealed a decreased phosphorylation of p62/SQSTM1 after PIM knockdown. Our results also showed an interaction between p62/SQSTM1 and the DISC that was reverted after PIM knockdown. In line with this, p62/SQSTM1 ablation increased TRAIL-R2/DR5 levels and facilitated TRAIL-induced caspase-8 activation, revealing an inhibitory role of p62/SQSTM1 in TRAIL-mediated apoptosis in GBM. Conversely, upregulation of TRAIL-R2/DR5 upon PIM inhibition and apoptosis induced by the combination of PIM inhibitor and TRAIL were abrogated by a constitutively phosphorylated p62/SQSTM1S332E mutant. Globally, our data represent the first evidence that PIM kinases regulate TRAIL-induced apoptosis in GBM and identify a specific role of p62/SQSTM1Ser332 phosphorylation in the regulation of the extrinsic apoptosis pathway activated by TRAIL.
Chemerin reverses neurological impairments and ameliorates neuronal apoptosis through ChemR23/CAMKK2/AMPK pathway in neonatal hypoxic–ischemic encephalopathy
Authors: Zhang Yixin , Xu Ningbo , Ding Yan , Doycheva Desislava Met , Zhang Yiting , Li Qian , Flores Jerry , Haghighiabyaneh Mina , Tang Jiping , Zhang John H. 
Published: February 2019

AbstractHypoxic–ischemic encephalopathy (HIE) is a devastating neurological event that contributes to the prolonged neurodevelopmental consequences in infants. Therapeutic strategies focused on attenuating neuronal apoptosis in the penumbra appears to be promising. Given the increasingly recognized neuroprotective roles of adipokines in HIE, we investigated the potential anti-apoptotic roles of a novel member of adipokines, Chemerin, in an experimental model of HIE. In the present study, 10-day-old rat pups underwent right common carotid artery ligation followed by 2.5 h hypoxia. At 1 h post hypoxia, pups were intranasally administered with human recombinant chemerin (rh-chemerin). Here, we showed that rh-chemerin prevented the neuronal apoptosis and degeneration as evidenced by the decreased expression of the pro-apoptotic markers, cleaved caspase 3 and Bax, as well as the numbers of Fluoro-Jade C and TUNEL-positive neurons. Furthermore, rh-Chemerin reversed neurological and morphological impairments induced by hypoxia–ischemia in neonatal rats at 24 h and 4 weeks after HIE. In addition, chemerin-mediated neuronal survival correlated with the elevation of chemerin receptor 23 (chemR23), phosphorylated calmodulin-dependent protein kinase kinase 2 (CAMKK2), as well as phosphorylated adenosine monophosphate-activated protein kinase (AMPK). Specific inhibition of chemR23, CAMKK2, and AMPK abolished the anti-apoptotic effects of rh-chemerin at 24 h after HIE, demonstrating that rh-chemerin ameliorated neuronal apoptosis partially via activating chemR23/CAMKK2/AMPK signaling pathway. Neuronal apoptosis is a well-established contributing factor of pathological changes and the neurological impairment after HIE. These results revealed mechanisms of neuroprotection by rh-chemerin, and indicated that activation of chemR23 might be harnessed to protect from neuronal apoptosis in HIE.
Pigment epithelium-derived factor mediates retinal ganglion cell neuroprotection by suppression of caspase-2
Authors: Vigneswara Vasanthy , Ahmed Zubair 
Published: February 2019

AbstractRetinal ganglion cells (RGCs) undergo rapid cell death by apoptosis after injury but can be rescued by suppression of caspase-2 (CASP2) using an siRNA to CASP2 (siCASP2). Pigment epithelium-derived factor (PEDF), has neuroprotective and anti-angiogenic functions and protects RGC from death. The purpose of this study was to investigate if suppression of CASP2 is a possible mechanism of neuroprotection by PEDF in RGC. Adult rat retinal cells were treated in vitro with sub-optimal and optimal concentrations of siCASP2 and PEDF and levels of CASP2 mRNA and RGC survival were then quantified. Optic nerve crush (ONC) injury followed by intravitreal injections of siCASP2 or PEDF and eye drops of PEDF-34 were also used to determine CASP2 mRNA and protein reduction. Results showed that PEDF and PEDF-34 significantly suppressed CASP2 mRNA in culture, by 1.85- and 3.04-fold, respectively, and increased RGC survival by 63.2 ± 3.8% and 81.9 ± 6.6%, respectively compared to cells grown in Neurobasal-A alone. RGC survival was significantly reduced in glial proliferation inhibited and purified RGC cultures suggesting that some of the effects of PEDF were glia-mediated. In addition, intravitreal injection of PEDF and eye drops of PEDF-34 after ONC also suppressed CASP2 mRNA levels by 1.82- and 3.89-fold and cleaved caspase-2 (C-CASP2) protein levels by 4.98- and 8.93-fold compared to ONC + PBS vehicle groups, respectively, without affecting other executioner caspases. Treatment of retinal cultures with PEDF and PEDF-34 promoted the secretion of neurotrophic factors (NTF) into the culture media, of which brain-derived neurotrophic factor (BDNF) caused the greatest reduction in CASP2 mRNA and C-CASP2 protein. The neuroprotective effects of PEDF were blocked by a polyclonal antibody and PEDF suppressed key elements in the apoptotic pathway. In conclusion, this study shows that some of the RGC neuroprotective effects of PEDF is regulated through suppression of CASP2 and downstream apoptotic signalling molecules.
Single-molecule sequencing detection of N6-methyladenine in microbial reference materials
Authors: McIntyre Alexa B. R. , Alexander Noah , Grigorev Kirill , Bezdan Daniela , Sichtig Heike , Chiu Charles Y. , Mason Christopher E. 
Published: February 2019

AbstractThe DNA base modification N6-methyladenine (m6A) is involved in many pathways related to the survival of bacteria and their interactions with hosts. Nanopore sequencing offers a new, portable method to detect base modifications. Here, we show that a neural network can improve m6A detection at trained sequence contexts compared to previously published methods using deviations between measured and expected current values as each adenine travels through a pore. The model, implemented as the mCaller software package, can be extended to detect known or confirm suspected methyltransferase target motifs based on predictions of methylation at untrained contexts. We use PacBio, Oxford Nanopore, methylated DNA immunoprecipitation sequencing (MeDIP-seq), and whole-genome bisulfite sequencing data to generate and orthogonally validate methylomes for eight microbial reference species. These well-characterized microbial references can serve as controls in the development and evaluation of future methods for the identification of base modifications from single-molecule sequencing data.
SMARCA4 loss is synthetic lethal with CDK4/6 inhibition in non-small cell lung cancer
Authors: Xue Yibo , Meehan Brian , Fu Zheng , Wang Xue Qing D. , Fiset Pierre Olivier , Rieker Ralf , Levins Cameron , Kong Tim , Zhu Xianbing , Morin Geneviève , Skerritt Lashanda , Herpel Esther , Venneti Sriram , Martinez Daniel , Judkins Alexander R. , Jung Sungmi , Camilleri-Broet Sophie , Gonzalez Anne V. , Guiot Marie-Christine , Lockwood William W. , Spicer Jonathan D. , Agaimy Abbas , Pastor William A. , Dostie Josée , Rak Janusz , Foulkes William D. , Huang Sidong 
Published: February 2019

AbstractTumor suppressor SMARCA4 (BRG1), a key SWI/SNF chromatin remodeling gene, is frequently inactivated in cancers and is not directly druggable. We recently uncovered that SMARCA4 loss in an ovarian cancer subtype causes cyclin D1 deficiency leading to susceptibility to CDK4/6 inhibition. Here, we show that this vulnerability is conserved in non-small cell lung cancer (NSCLC), where SMARCA4 loss also results in reduced cyclin D1 expression and selective sensitivity to CDK4/6 inhibitors. In addition, SMARCA2, another SWI/SNF subunit lost in a subset of NSCLCs, also regulates cyclin D1 and drug response when SMARCA4 is absent. Mechanistically, SMARCA4/2 loss reduces cyclin D1 expression by a combination of restricting CCND1 chromatin accessibility and suppressing c-Jun, a transcription activator of CCND1. Furthermore, SMARCA4 loss is synthetic lethal with CDK4/6 inhibition both in vitro and in vivo, suggesting that FDA-approved CDK4/6 inhibitors could be effective to treat this significant subgroup of NSCLCs.
Just add sugar for carbohydrate induced self-assembly of curcumin
Authors: Wong Sandy , Zhao Jiacheng , Cao Cheng , Wong Chin Ken , Kuchel Rhiannon P. , De Luca Sergio , Hook James M. , Garvey Christopher J. , Smith Sean , Ho Junming , Stenzel Martina H. 
Published: February 2019

AbstractIn nature, self-assembly processes based on amphiphilic molecules play an integral part in the design of structures of higher order such as cells. Among them, amphiphilic glycoproteins or glycolipids take on a pivotal role due to their bioactivity. Here we show that sugars, in particular, fructose, are capable of directing the self-assembly of highly insoluble curcumin resulting in the formation of well-defined capsules based on non-covalent forces. Simply by mixing an aqueous solution of fructose and curcumin in an open vessel leads to the generation of capsules with sizes ranging between 100 and 150 nm independent of the initial concentrations used. Our results demonstrate that hydrogen bonding displayed by fructose can induce the self-assembly of hydrophobic molecules such as curcumin into well-ordered structures, and serving as a simple and virtually instantaneous way of making nanoparticles from curcumin in water with the potential for template polymerization and nanocarriers.
Pioneer axons employ Cajal’s battering ram to enter the spinal cord
Authors: Nichols Ev L. , Smith Cody J. 
Published: February 2019

AbstractSensory axons must traverse a spinal cord glia limitans to connect the brain with the periphery. The fundamental mechanism of how these axons enter the spinal cord is still debatable; both Ramon y Cajal’s battering ram hypothesis and a boundary cap model have been proposed. To distinguish between these hypotheses, we visualized the entry of pioneer axons into the dorsal root entry zone (DREZ) with time-lapse imaging in zebrafish. Here, we identify that DRG pioneer axons enter the DREZ before the arrival of neural crest cells at the DREZ. Instead, actin-rich invadopodia in the pioneer axon are necessary and sufficient for DREZ entry. Using photoactivable Rac1, we demonstrate cell-autonomous functioning of invasive structures in pioneer axon spinal entry. Together these data support the model that actin-rich invasion structures dynamically drive pioneer axon entry into the spinal cord, indicating that distinct pioneer and secondary events occur at the DREZ.
The meiotic TERB1-TERB2-MAJIN complex tethers telomeres to the nuclear envelope
Authors: Wang Yan , Chen Yanyan , Chen Juan , Wang Lijun , Nie Leitong , Long Juanjuan , Chang Haishuang , Wu Jian , Huang Chenhui , Lei Ming 
Published: February 2019

AbstractDuring meiotic prophase I, telomeres attach to and move on the nuclear envelope (NE), regulating chromosome movement to promote homologous pairing. Meiosis-specific proteins TERB1, TERB2 and MAJIN play a key role in this process. Here, we report the crystal structures of human TERB1-TERB2 and TERB2-MAJIN subcomplexes. Specific disruption of the TERB1-TERB2 or the TERB2-MAJIN interaction in the mouse Terb2 gene abolishes the telomere attachment to the NE and causes aberrant homologous pairing and disordered synapsis. In addition, depletion of SUN1 also partially disrupts the telomere-NE connection. We propose that the telomere-TRF1-TERB1-TERB2-MAJIN-NE interaction network and the telomere-LINC complex connection are likely two separate but cooperative pathways to stably recruit telomeres to the NE in meiosis prophase I. Our work provides a molecular model of the connection between telomeres and the NE and reveals the correlation between aberrant synapsis and the defective telomere attachment to the NE.
Phosphoric acid-catalyzed atroposelective construction of axially chiral arylpyrroles
Authors: Zhang Lei , Xiang Shao-Hua , Wang Jun , Xiao Jian , Wang Jun-Qi , Tan Bin 
Published: February 2019

AbstractAxially chiral arylpyrroles are key components of pharmaceuticals and natural products as well as chiral catalysts and ligands for asymmetric transformations. However, the catalytic enantioselective construction of optically active arylpyrroles remains a formidable challenge. Here we disclose a highly efficient strategy to access enantioenriched axially chiral arylpyrroles by means of organocatalytic atroposelective desymmetrization and kinetic resolution. Depending on the remote control of chiral catalyst, the arylpyrroles were obtained in high yields and excellent enantioselectivities under mild reaction conditions. This strategy tolerates a wide range of functional groups, providing a facile avenue to approach axially chiral arylpyrroles from simple and readily available starting materials. Selected arylpyrrole products proved to be efficient chiral ligands in asymmetric catalysis and also important precursors for further synthetic transformations into highly functionalized pyrroles with potential bioactivity, especially the axially chiral fully substituted arylpyrroles.
Ocean colour signature of climate change
Authors: Dutkiewicz Stephanie , Hickman Anna E. , Jahn Oliver , Henson Stephanie , Beaulieu Claudie , Monier Erwan 
Published: February 2019

AbstractMonitoring changes in marine phytoplankton is important as they form the foundation of the marine food web and are crucial in the carbon cycle. Often Chlorophyll-a (Chl-a) is used to track changes in phytoplankton, since there are global, regular satellite-derived estimates. However, satellite sensors do not measure Chl-a directly. Instead, Chl-a is estimated from remote sensing reflectance (RRS): the ratio of upwelling radiance to the downwelling irradiance at the ocean’s surface. Using a model, we show that RRS in the blue-green spectrum is likely to have a stronger and earlier climate-change-driven signal than Chl-a. This is because RRS has lower natural variability and integrates not only changes to in-water Chl-a, but also alterations in other optically important constituents. Phytoplankton community structure, which strongly affects ocean optics, is likely to show one of the clearest and most rapid signatures of changes to the base of the marine ecosystem.
Combining attentional bias modification with dorsolateral prefrontal rTMS does not attenuate maladaptive attentional processing
Authors: Bovy Leonore , Möbius Martin , Dresler Martin , Fernández Guillén , Sanfey Alan , Becker Eni , Tendolkar Indira 
Published: February 2019

AbstractHigh frequency repetitive Transcranial Magnetic Stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) has been shown to reduce depressive symptoms and improve cognitive biases such as attentional bias. One promising technique that may complement rTMS treatment is attentional bias modification (ABM) training, given the similarity in modulating attentional bias and affecting neuronal activity. We tested whether the combination of rTMS treatment and ABM training in a single session would attenuate maladaptive attentional processing and improve mood in participants with subclinical depressive symptoms. To this end, 122 healthy participants were randomly assigned to one of four groups, receiving either a single rTMS treatment, a single ABM treatment, a combination of rTMS and ABM or a sham treatment. Of these 122 participants, 72 showed a heightened BDI-II score (between 9 and 25) and were included in our main analyses. In our subclinical (≥9 and ≤25 BDI-II) sample, a single combination treatment of rTMS and ABM training induced no significant changes in attentional bias, attentional control or mood, nor did rTMS alone affect attentional bias systematically. We discuss these null findings in light of the task specifics and relate them to the ongoing discussion on ABM training in depression.
The effect of ILs as co-salts in electrolytes for high voltage supercapacitors
Authors: Kwon Ha-Na , Jang Su-Jin , Kang Yun Chan , Roh Kwang Chul 
Published: February 2019

AbstractIonic liquids (ILs) which have electrical stability are attractive materials to enhance the potential window of electrolyte. According to the potential window is extended, available voltage for supercapacitor is broaden. In this study, the addition of ILs which is 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIBF4) and 1-ethyl-3-methylimidazolium bis(trifluoromethylesulfonyl) imide (EMITFSI) as co-salts, to a supercapacitor electrolyte increases the ionic conductivity and stability of it due to inhibition of electrolyte decomposition. As a result, the electrochemical stability potential windows (ESPWs) of supercapacitor is improved and the supercapacitor exhibited increased cycling stability. The loss of specific capacitance upon addition of 7 wt% EMIBF4 or EMITFSI to the electrolyte was 2.5% and 8.7%, respectively, after 10,000 cycles at 3.5 V, compared to the specific capacitance of the initial discharge.
Inferring Gene Regulatory Networks from a Population of Yeast Segregants
Authors: Chen Chen , Zhang Dabao , Hazbun Tony R. , Zhang Min 
Published: February 2019

AbstractConstructing gene regulatory networks is crucial to unraveling the genetic architecture of complex traits and to understanding the mechanisms of diseases. On the basis of gene expression and single nucleotide polymorphism data in the yeast, Saccharomyces cerevisiae, we constructed gene regulatory networks using a two-stage penalized least squares method. A large system of structural equations via optimal prediction of a set of surrogate variables was established at the first stage, followed by consistent selection of regulatory effects at the second stage. Using this approach, we identified subnetworks that were enriched in gene ontology categories, revealing directional regulatory mechanisms controlling these biological pathways. Our mapping and analysis of expression-based quantitative trait loci uncovered a known alteration of gene expression within a biological pathway that results in regulatory effects on companion pathway genes in the phosphocholine network. In addition, we identify nodes in these gene ontology-enriched subnetworks that are coordinately controlled by transcription factors driven by trans-acting expression quantitative trait loci. Altogether, the integration of documented transcription factor regulatory associations with subnetworks defined by a system of structural equations using quantitative trait loci data is an effective means to delineate the transcriptional control of biological pathways.
Limiting the Spectral Diffusion of Nano-Scale Light Emitters using the Purcell effect in a Photonic-Confined Environment
Authors: Lyasota A. , Jarlov C. , Rudra A. , Dwir B. , Kapon E. 
Published: February 2019

AbstractPartial suppression of the spectral diffusion of quantum dot (QD) excitons tuned to resonance of a nano-photonic cavity is reported. The suppression is caused by the Purcell enhancement of the QD-exciton recombination rate, which alters the rate of charging of the solid-state environment by the QD itself. The effect can be used to spectrally-stabilize solid-state emitters of single photons and other non-classical states of light.
Lignocellulose utilization and bacterial communities of millet straw based mushroom (Agaricus bisporus) production
Authors: Zhang Hao-Lin , Wei Jin-Kang , Wang Qing-Hui , Yang Rui , Gao Xiao-Jing , Sang Yu-Xi , Cai Pan-Pan , Zhang Guo-Qing , Chen Qing-Jun 
Published: February 2019

AbstractAgaricus bisporus is in general cultivated on wheat and rice straw in China. However, millet straw is a potential alternative resource for Agaricus bisporus cultivation, but this has hardly been studied. In the present study, the feasibility of millet straw based mushroom production was analyzed by three successive trials. Mature compost demonstrated high quality with total nitrogen, pH, and C/N ratio of 2.0%, 7.5, and 18:1 respectively, which was suitable for mushroom mycelia growth. During composting, 47–50% of cellulose, 63–65% of hemicellulose, and 8–17% lignin were degraded, while 22–27% of cellulose, 14–16% of hemicellulose, and 15–21% of lignin were consumed by A. bisporus mycelia during cultivation. The highest FPUase and CMCase were observed during mushroom flushes. Endo-xylanase had the key role in hemicellulose degradation with high enzyme activity during cultivation stages. Laccase participated in lignin degradation with the highest enzyme activity in Pinning stage followed by a sharp decline at the first flush. Yield was up to 20 kg/m2, as this is similar to growth on wheat straw, this shows that millet straw is an effective resource for mushroom cultivation. Actinobacteria, Bacteroidetes, Chloroflexi, Deinococcus-Thermus, Firmicutes, and Proteobacteria were the dominant phyla, based on 16S rRNA gene sequencing during composting. The key environmental factors dominating bacterial communities of the samples were determined to be pH value, cellulose content, and hemicellulose content for prewetting and premixed phase of basic mixture (P0); moisture content for phase I (PI); and nitrogen content, lignin content, and ash content for phase II (PII), respectively.