bluuebunny/crossref_metadata_2025_split huggingface dataset:
Checkpoint suppressor 1 suppresses transcriptional activity of ERα and breast cancer cell proliferation via deacetylase SIRT1
Authors: Xu Zhaowei , Yang Yangyang , Li Bowen , Li Yanan , Xia Kangkai , Yang Yuxi , Li Xiahui , Wang Miao , Li Shujing , Wu Huijian 
Published: May 2018

AbstractBreast cancer is a highly heterogeneous carcinoma in women worldwide, but the underlying mechanisms that account for breast cancer initiation and development have not been fully established. Mounting evidence indicates that Checkpoint suppressor 1 (CHES1) is tightly associated with tumorigenesis and prognosis in many types of cancer. However, the definitive function of CHES1 in breast cancer remains to be explored. Here we showed that CHES1 had a physical interaction with estrogen receptor-α (ERα) and repressed the transactivation of ERα in breast cancer cells. Mechanistically, the interaction between CHES1 and ERα enhanced the recruitment of nicotinamide adenine dinucleotide (NAD+) deacetylase Sirtuin 1 (SIRT1), and it further induced SIRT1-mediated ERα deacetylation and repression on the promoter-binding enrichment of ERα. In addition, we also found that the expression of CHES1 was repressed by estrogen-ERα signaling and the expression level of CHES1 was significantly downregulated in ERα-positive breast cancer. The detailed mechanism was that ERα may directly bind to CHES1 potential promoter via recognizing the conserved estrogen response element (ERE) motif in response to estrogen stimulation. Functionally, CHES1 inhibited ERα-mediated proliferation and tumorigenesis of breast cancer cells in vivo and in vitro. Totally, these results identified a negative cross-regulatory loop between ERα and CHES1 that was required for growth of breast cancer cells, it might uncover novel insight into molecular mechanism of CHES1 involved in breast cancer and provide new avenues for molecular-targeted therapy in hormone-regulated breast cancer.
Three previously unrecognised classes of biosynthetic enzymes revealed during the production of xenovulene A
Authors: Schor Raissa , Schotte Carsten , Wibberg Daniel , Kalinowski Jörn , Cox Russell J. 
Published: May 2018

AbstractXenovulene A is a complex fungal meroterpenoid, produced by the organism hitherto known as Acremonium strictum IMI 501407, for which limited biosynthetic evidence exists. Here, we generate a draft genome and show that the producing organism is previously unknown and should be renamed as Sarocladium schorii. A biosynthetic gene cluster is discovered which bears resemblance to those involved in the biosynthesis of fungal tropolones, with additional genes of unknown function. Heterologous reconstruction of the entire pathway in Aspergillus oryzae allows the chemical steps of biosynthesis to be dissected. The pathway shows very limited similarity to the biosynthesis of other fungal meroterpenoids. The pathway features: the initial formation of tropolone intermediates; the likely involvement of a hetero Diels–Alder enzyme; a terpene cyclase with no significant sequence homology to any known terpene cyclase and two enzymes catalysing oxidative-ring contractions.
Immunogene therapy with fusogenic nanoparticles modulates macrophage response to Staphylococcus aureus
Authors: Kim Byungji , Pang Hong-Bo , Kang Jinyoung , Park Ji-Ho , Ruoslahti Erkki , Sailor Michael J. 
Published: May 2018

AbstractThe incidence of adverse effects and pathogen resistance encountered with small molecule antibiotics is increasing. As such, there is mounting focus on immunogene therapy to augment the immune system’s response to infection and accelerate healing. A major obstacle to in vivo gene delivery is that the primary uptake pathway, cellular endocytosis, results in extracellular excretion and lysosomal degradation of genetic material. Here we show a nanosystem that bypasses endocytosis and achieves potent gene knockdown efficacy. Porous silicon nanoparticles containing an outer sheath of homing peptides and fusogenic liposome selectively target macrophages and directly introduce an oligonucleotide payload into the cytosol. Highly effective knockdown of the proinflammatory macrophage marker IRF5 enhances the clearance capability of macrophages and improves survival in a mouse model of Staphyloccocus aureus pneumonia.
Calreticulin and integrin alpha dissociation induces anti-inflammatory programming in animal models of inflammatory bowel disease
Authors: Ohkuro Masayoshi , Kim Jun-Dal , Kuboi Yoshikazu , Hayashi Yuki , Mizukami Hayase , Kobayashi-Kuramochi Hiroko , Muramoto Kenzo , Shirato Manabu , Michikawa-Tanaka Fumiko , Moriya Jun , Kozaki Teruya , Takase Kazuma , Chiba Kenichi , Agarwala Kishan Lal , Kimura Takayuki , Kotake Makoto , Kawahara Tetsuya , Yoneda Naoki , Hirota Shinsuke , Azuma Hiroshi , Ozasa-Komura Nobuko , Ohashi Yoshiaki , Muratani Masafumi , Kimura Keiji , Hishinuma Ieharu , Fukamizu Akiyoshi 
Published: May 2018

AbstractInflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a chronic intestinal inflammatory condition initiated by integrins-mediated leukocyte adhesion to the activated colonic microvascular endothelium. Calreticulin (CRT), a calcium-binding chaperone, is known as a partner in the activation of integrin α subunits (ITGAs). The relationship between their interaction and the pathogenesis of IBD is largely unknown. Here we show that a small molecule, orally active ER-464195-01, inhibits the CRT binding to ITGAs, which suppresses the adhesiveness of both T cells and neutrophils. Transcriptome analysis on colon samples from dextran sodium sulfate-induced colitis mice reveals that the increased expression of pro-inflammatory genes is downregulated by ER-464195-01. Its prophylactic and therapeutic administration to IBD mouse models ameliorates the severity of their diseases. We propose that leukocytes infiltration via the binding of CRT to ITGAs is necessary for the onset and development of the colitis and the inhibition of this interaction may be a novel therapeutic strategy for the treatment of IBD.
Clinical prediction models to support the diagnosis of asthma in primary care: a systematic review protocol
Authors: Daines L. , McLean S. , Buelo A. , Lewis S. , Sheikh A. , Pinnock H. 
Published: May 2018

AbstractSubstantial over-diagnosis and under-diagnosis of asthma in adults and children has recently been reported. As asthma is mostly diagnosed in non-specialist settings, a clinical prediction model (CPM) to aid the diagnosis of asthma in primary care may help improve diagnostic accuracy. We aim to systematically identify, describe, compare, and synthesise existing CPMs designed to support the diagnosis of asthma in children and adults presenting with symptoms suggestive of the disease, in primary care settings or equivalent populations. We will systematically search Medline, Embase and CINAHL from 1 January 1990 to present. Any CPM derived for use in a primary care population will be included. Equivalent populations in countries without a developed primary care service will also be included. The probability of asthma diagnosis will be the primary outcome. We will include CPMs designed for use in clinical practice to aid the diagnostic decision making of a healthcare professional during the assessment of an individual with symptoms suggestive of asthma. We will include derivation studies, and external model validation studies. Two reviewers will independently screen titles/abstracts and full texts for eligibility and extract data from included papers. The CHARMS checklist (or PROBAST if available) will be used to assess risk of bias within each study. Results will be summarised by narrative synthesis with meta-analyses completed if possible. This systematic review will provide comprehensive information about existing CPMs for the diagnosis of asthma in primary care and will inform the development of a future diagnostic model.
Circadian and Homeostatic Modulation of Multi-Unit Activity in Midbrain Dopaminergic Structures
Authors: Fifel Karim , Meijer Johanna H. , Deboer Tom 
Published: May 2018

AbstractAlthough the link between sleep disturbances and dopamine (DA)-related neurological and neuropsychiatric disorders is well established, the impact of sleep alterations on neuronal activity of midbrain DA-ergic structures is currently unknown. Here, using wildtype C57Bl mice, we investigated the circadian- and sleep-related modulation of electrical neuronal activity in midbrain ventral-tegmental-area (VTA) and substantia nigra (SN). We found no significant circadian modulation of activity in SN while VTA displayed a low amplitude but significant circadian modulation with increased firing rates during the active phase. Combining neural activity recordings with electroencephalogram (EEG) recordings revealed a strong vigilance state dependent modulation of neuronal activity with increased activity during wakefulness and rapid eye movement sleep relative to non-rapid eye movement sleep in both SN and VTA. Six-hours of sleep deprivation induced a significant depression of neuronal activity in both areas. Surprisingly, these alterations lasted for up to 48 hours and persisted even after the normalization of cortical EEG waves. Our results show that sleep and sleep disturbances significantly affect neuronal activity in midbrain DA structures. We propose that these changes in neuronal activity underlie the well-known relationship between sleep alterations and several disorders involving dysfunction of the DA circuitry such as addiction and depression.
New insights into mechanisms of material ejection in MALDI mass spectrometry for a wide range of spot sizes
Authors: Niehaus Marcel , Soltwisch Jens 
Published: May 2018

AbstractMatrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is widely used for the analysis of large biomolecules in numerous applications. The technique utilizes nanosecond-long laser pulses at various spot sizes to eject and ionize large molecules embedded in a highly absorptive chemical matrix. Despite the methods name, ‘molecular desorption’ from the matrix crystal surface is not the sole mechanism discussed for material ejection in MALDI, but additional ablation of larger clusters has been reported. Here we present results on the influence of laser fluence and spot size on the mechanisms of the initial material ejection in MALDI and subsequent plume development. We used a laser-based postionization (MALDI-2) as well as a complementary photoacoustic method to monitor the material ejection step. The photoacoustic data reveal a quasi-thermal sublimation process up to a transition fluence. Above this threshold fluence additional ablation processes are observed. Complementary investigations on plume dynamics by MALDI-2 showed an ejection of predominantly fast particles for desorption conditions while ablation produces considerably slower ejecta. Additionally the presented results revealed a peculiar influence of the spot size on analyte fragmentation as well as plume development and allows for new insights into the unexplained spot size effect reported for MALDI.
Origin of magnetic properties in carbon implanted ZnO nanowires
Authors: Wang Y. F. , Shao Y. C. , Hsieh S. H. , Chang Y. K. , Yeh P. H. , Hsueh H. C. , Chiou J. W. , Wang H. T. , Ray S. C. , Tsai H. M. , Pao C. W. , Chen C. H. , Lin H. J. , Lee J. F. , Wu C. T. , Wu J. J. , Chang Y. M. , Asokan K. , Chae K. H. , Ohigashi T. , Takagi Y. , Yokoyama T. , Kosugi N. , Pong W. F. 
Published: May 2018

AbstractVarious synchrotron radiation-based spectroscopic and microscopic techniques are used to elucidate the room-temperature ferromagnetism of carbon-doped ZnO-nanowires (ZnO-C:NW) via a mild C+ ion implantation method. The photoluminescence and magnetic hysteresis loops reveal that the implantation of C reduces the number of intrinsic surface defects and increases the saturated magnetization of ZnO-NW. The interstitial implanted C ions constitute the majority of defects in ZnO-C:NW as confirmed by the X-ray absorption spectroscopic studies. The X-ray magnetic circular dichroism spectra of O and C K-edge respectively indicate there is a reduction in the number of unpaired/dangling O 2p bonds in the surface region of ZnO-C:NW and the C 2p-derived states of the implanted C ions strongly affect the net spin polarization in the surface and bulk regions of ZnO-C:NW. Furthermore, these findings corroborate well with the first-principles calculations of C-implanted ZnO in surface and bulk regions, which highlight the stability of implanted C for the suppression and enhancement of the ferromagnetism of the ZnO-C:NW in the surface region and bulk phase, respectively.
Electrical synapses between inhibitory neurons shape the responses of principal neurons to transient inputs in the thalamus: a modeling study
Authors: Pham Tuan , Haas Julie S. 
Published: May 2018

AbstractAs multimodal sensory information proceeds to the cortex, it is intercepted and processed by the nuclei of the thalamus. The main source of inhibition within thalamus is the reticular nucleus (TRN), which collects signals both from thalamocortical relay neurons and from thalamocortical feedback. Within the reticular nucleus, neurons are densely interconnected by connexin36-based gap junctions, known as electrical synapses. Electrical synapses have been shown to coordinate neuronal rhythms, including thalamocortical spindle rhythms, but their role in shaping or modulating transient activity is less understood. We constructed a four-cell model of thalamic relay and TRN neurons, and used it to investigate the impact of electrical synapses on closely timed inputs delivered to thalamic relay cells. We show that the electrical synapses of the TRN assist cortical discrimination of these inputs through effects of truncation, delay or inhibition of thalamic spike trains. We expect that these are principles whereby electrical synapses play similar roles in regulating the processing of transient activity in excitatory neurons across the brain.
Identification of differentially accumulated proteins involved in regulating independent and combined osmosis and cadmium stress response in Brachypodium seedling roots
Authors: Chen Ziyan , Zhu Dong , Wu Jisu , Cheng Zhiwei , Yan Xing , Deng Xiong , Yan Yueming 
Published: May 2018

AbstractIn this study, we aimed to identify differentially accumulated proteins (DAPs) involved in PEG mock osmotic stress, cadmium (Cd2+) stress, and their combined stress responses in Brachypodium distachyon seedling roots. The results showed that combined PEG and Cd2+ stresses had more significant effects on Brachypodium seedling root growth, physiological traits, and ultrastructures when compared with each individual stress. Totally, 106 DAPs were identified that are responsive to individual and combined stresses in roots. These DAPs were mainly involved in energy metabolism, detoxification and stress defense and protein metabolism. Principal component analysis revealed that DAPs from Cd2+ and combined stress treatments were grouped closer than those from osmotic stress treatment, indicating that Cd2+ and combined stresses had more severe influences on the root proteome than osmotic stress alone. Protein–protein interaction analyses highlighted a 14-3-3 centered sub-network that synergistically responded to osmotic and Cd2+ stresses and their combined stresses. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis of 14 key DAP genes revealed that most genes showed consistency between transcriptional and translational expression patterns. A putative pathway of proteome metabolic changes in Brachypodium seedling roots under different stresses was proposed, which revealed a complicated synergetic responsive network of plant roots to adverse environments.
Auxin decreases chromatin accessibility through the TIR1/AFBs auxin signaling pathway in proliferative cells
Authors: Hasegawa Junko , Sakamoto Takuya , Fujimoto Satoru , Yamashita Tomoe , Suzuki Takamasa , Matsunaga Sachihiro 
Published: May 2018

AbstractChromatin accessibility is closely associated with chromatin functions such as gene expression, DNA replication, and maintenance of DNA integrity. However, the relationship between chromatin accessibility and plant hormone signaling has remained elusive. Here, based on the correlation between chromatin accessibility and DNA damage, we used the sensitivity to DNA double strand breaks (DSBs) as an indicator of chromatin accessibility and demonstrated that auxin regulates chromatin accessibility through the TIR1/AFBs signaling pathway in proliferative cells. Treatment of proliferating plant cells with an inhibitor of the TIR1/AFBs auxin signaling pathway, PEO-IAA, caused chromatin loosening, indicating that auxin signaling functions to decrease chromatin accessibility. In addition, a transcriptome analysis revealed that severalhistone H4genes and a histone chaperone gene,FAS1, are positively regulated through the TIR1/AFBs signaling pathway, suggesting that auxin plays a role in promoting nucleosome assembly. Analysis of thefas1mutant ofArabidopsis thalianaconfirmed that FAS1 is required for the auxin-dependent decrease in chromatin accessibility. These results suggest that the positive regulation of chromatin-related genes mediated by the TIR1/AFBs auxin signaling pathway enhances nucleosome assembly, resulting in decreased chromatin accessibility in proliferative cells.
Nanojunction Effects on Water Flow in Carbon Nanotubes
Authors: Ebrahimi Fatemeh , Ramazani Farzaneh , Sahimi Muhammad 
Published: May 2018

AbstractWe report on the results of extensive molecular dynamics simulation of water imbibition in carbon nanotubes (CNTs), connected together by converging or diverging nanojunctions in various configurations. The goal of the study is to understand the effect of the nanojunctions on the interface motion, as well as the differences between what we study and water imbibition in microchannels. While the dynamics of water uptake in the entrance CNT is the same as that of imbibition in straight CNTs, with the main source of energy dissipation being the friction at the entrance, water uptake in the exit CNT is more complex due to significant energy loss in the nanojunctions. We derive an approximate but accurate expression for the pressure drop in the nanojunction. A remarkable difference between dynamic wetting of nano- and microjunctions is that, whereas water absorption time in the latter depends only on the ratios of the radii and of the lengths of the channels, the same is not true about the former, which is shown to be strongly dependent upon the size of each segment of the nanojunction. Interface pinning-depinning also occurs at the convex edges.
Melanopsin-mediated pupil function is impaired in Parkinson’s disease
Authors: Joyce Daniel S. , Feigl Beatrix , Kerr Graham , Roeder Luisa , Zele Andrew J. 
Published: May 2018

AbstractParkinson’s disease (PD) is characterised by non-motor symptoms including sleep and circadian disruption. Melanopsin-expressing intrinsically photosensitive Retinal Ganglion Cells (ipRGC) transmit light signals to brain areas controlling circadian rhythms and the pupil light reflex. To determine if non-motor symptoms observed in PD are linked to ipRGC dysfunction, we evaluated melanopsin and rod/cone contributions to the pupil response in medicated participants with PD (n = 17) and controls (n = 12). Autonomic tone was evaluated by measuring pupillary unrest in darkness. In the PD group, there is evidence for an attenuated post-illumination pupil response (PIPR) amplitude and reduced pupil constriction amplitude, and PIPR amplitudes did not correlate with measures of sleep quality, retinal nerve fibre layer thickness, disease severity, or medication dosage. Both groups exhibited similar pupillary unrest. We show that melanopsin- and the rod/cone-photoreceptor contributions to the pupil control pathway are impaired in people with early-stage PD who have no clinically observable ophthalmic abnormalities. Given that ipRGCs project to brain targets involved in arousal, sleep and circadian rhythms, ipRGC dysfunction may underpin some of the non-motor symptoms observed in PD.
Loss of live coral compromises predator-avoidance behaviour in coral reef damselfish
Authors: Boström-Einarsson Lisa , Bonin Mary C. , Munday Philip L. , Jones Geoffrey P. 
Published: May 2018

AbstractTropical reefs have experienced an unprecedented loss of live coral in the past few decades and the biodiversity of coral-dependent species is under threat. Many reef fish species decline in abundance as coral cover is lost, yet the mechanisms responsible for these losses are largely unknown. A commonly hypothesised cause of fish decline is the loss of shelter space between branches as dead corals become overgrown by algae. Here we tested this hypothesis by quantifying changes in predator-avoidance behaviour of a common damselfish, Pomacentrus moluccensis, before and after the death of their coral colony. Groups of P. moluccensis were placed on either healthy or degraded coral colonies, startled using a visual stimulus and their sheltering responses compared over a 7-week period. P. moluccensis stopped sheltering amongst the coral branches immediately following the death of the coral, despite the presence of ample shelter space. Instead, most individuals swam away from the dead coral, potentially increasing their exposure to predators. It appears that the presence of live coral rather than shelter per se is the necessary cue that elicits the appropriate behavioural response to potential predators. The disruption of this link poses an immediate threat to coral-associated fishes on degrading reefs.
DNAJC17 is localized in nuclear speckles and interacts with splicing machinery components
Authors: Pascarella A. , Ferrandino G. , Credendino S. C. , Moccia C. , D’Angelo F. , Miranda B. , D’Ambrosio C. , Bielli P. , Spadaro O. , Ceccarelli M. , Scaloni A. , Sette C. , De Felice M. , De Vita G. , Amendola E. 
Published: May 2018

AbstractDNAJC17 is a heat shock protein (HSP40) family member, identified in mouse as susceptibility gene for congenital hypothyroidism. DNAJC17 knockout mouse embryos die prior to implantation. In humans, germline homozygous mutations in DNAJC17 have been found in syndromic retinal dystrophy patients, while heterozygous mutations represent candidate pathogenic events for myeloproliferative disorders. Despite widespread expression and involvement in human diseases, DNAJC17 function is still poorly understood. Herein, we have investigated its function through high-throughput transcriptomic and proteomic approaches. DNAJC17-depleted cells transcriptome highlighted genes involved in general functional categories, mainly related to gene expression. Conversely, DNAJC17 interactome can be classified in very specific functional networks, with the most enriched one including proteins involved in splicing. Furthermore, several splicing-related interactors, were independently validated by co-immunoprecipitation and in vivo co-localization. Accordingly, co-localization of DNAJC17 with SC35, a marker of nuclear speckles, further supported its interaction with spliceosomal components. Lastly, DNAJC17 up-regulation enhanced splicing efficiency of minigene reporter in live cells, while its knockdown induced perturbations of splicing efficiency at whole genome level, as demonstrated by specific analysis of RNAseq data. In conclusion, our study strongly suggests a role of DNAJC17 in splicing-related processes and provides support to its recognized essential function in early development.