bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gabrb2-knockout mice displayed schizophrenia-like and comorbid phenotypes with interneuron–astrocyte–microglia dysregulation
Authors: Yeung Rigil K. , Xiang Zheng-Hua , Tsang Shui-Ying , Li Rui , Ho Timothy Y. C. , Li Qi , Hui Chok-King , Sham Pak-Chung , Qiao Ming-Qi , Xue Hong 
Published: July 2018

AbstractIntronic polymorphisms of the GABAA receptor β2 subunit gene (GABRB2) under adaptive evolution were associated with schizophrenia and reduced expression, especially of the long isoform which differs in electrophysiological properties from the short isoform. The present study was directed to examining the gene dosage effects of Gabrb2 in knockout mice of both heterozygous (HT) and homozygous (KO) genotypes with respect to possible schizophrenia-like and comorbid phenotypes. The KO mice, and HT mice to a lesser extent, were found to display prepulse inhibition (PPI) deficit, locomotor hyperactivity, stereotypy, sociability impairments, spatial-working and spatial-reference memory deficits, reduced depression and anxiety, and accelerated pentylenetetrazol (PTZ)-induced seizure. In addition, the KO mice were highly susceptible to audiogenic epilepsy. Some of the behavioral phenotypes showed evidence of imprinting, gender effect and amelioration by the antipsychotic risperidone, and the audiogenic epilepsy was inhibited by the antiepileptic diazepam. GABAergic parvalbumin (PV)-positive interneuron dystrophy, astrocyte dystrophy, and extensive microglia activation were observed in the frontotemporal corticolimbic regions, and reduction of newborn neurons was observed in the hippocampus by immunohistochemical staining. The neuroinflammation indicated by microglial activation was accompanied by elevated brain levels of oxidative stress marker malondialdehyde (MDA) and the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). These extensive schizophrenia-like and comorbid phenotypes brought about by Gabrb2 knockout, in conjunction with our previous findings on GABRB2 association with schizophrenia, support a pivotal role of GABRB2 in schizophrenia etiology.
RETRACTED ARTICLE: Annonacin promotes selective cancer cell death via NKA-dependent and SERCA-dependent pathways
Authors: Yiallouris Andreas , Patrikios Ioannis , Johnson Elizabeth O. , Sereti Evangelia , Dimas Konstantinos , De Ford Cristian , Fedosova Natalia U. , Graier Wolfgang F. , Sokratous Kleitos , Kyriakou Kyriakos , Stephanou Anastasis 
Published: July 2018

AbstractIn the healthcare sector, phytocompounds are known to be beneficial by contributing or alleviating a variety of diseases. Studies have demonstrated the progressive effects of phytocompounds on immune-related diseases and to exhibit anticancer effects. Graviola tree is an evergreen tree with its extracts (leafs and seeds) been reported having anticancer properties, but the precise target of action is not clear. Using an in silico approach, we predicted that annonacin, an Acetogenin, the active agent found in Graviola leaf extract (GLE) to potentially act as a novel inhibitor of both sodium/potassium (NKA) and sarcoplasmic reticulum (SERCA) ATPase pumps. We were able to validate and confirm the in silico studies by showing that GLE inhibited NKA and SERCA activity in intact cells. In the present study, we also demonstrated the antiproliferative and anticancer effects of GLE in a variety of cancer cell lines with limited toxic effects on non-transformed cells. Moreover, our results revealed that known inhibitors of both NKA and SERCA pumps could also promote cell death in several cancer cell lines. In addition, a mouse xenograft cancer model showed GLE as able to reduce tumor size and progression. Finally, bioprofiling studies indicated a strong correlation between overexpression of both NKA and SERCA gene expression vs. survival rates. Overall, our results demonstrated that GLE can promote selective cancer cell death via inhibiting NKA and SERCA, and thus can be considered as a potential novel treatment for cancer. After molecular analysis of GLE by liquid chromatography–mass spectrometry and ESI–QTOF–MS analysis, it was found that the MS spectrum of the high abundant chromatographic peak purified sample highly consisted of annonacin.
BET bromodomain inhibitor JQ1 preferentially suppresses EBV-positive nasopharyngeal carcinoma cells partially through repressing c-Myc
Authors: Li Ning , Yang Lu , Qi Xue-Kang , Lin Yu-Xin , Xie Xinhua , He Gui-Ping , Feng Qi-Sheng , Liu Ling-Rui , Xie Xiaoming , Zeng Yi-Xin , Feng Lin 
Published: July 2018

AbstractThe management of advanced nasopharyngeal carcinoma (NPC) remains a challenge. The ubiquitous nature of Epstein–Barr virus (EBV) infection in nonkeratinizing NPC has forced us to investigate novel drugs for NPC in the presence of EBV. In this study, we performed a small-scale screening of a library of compounds that target epigenetic regulators in paired EBV-positive and EBV-negative NPC cell lines. We found that bromodomain and extra-terminal (BET) inhibitor JQ1 preferentially inhibits the growth of EBV-positive NPC cells. JQ1 induces apoptosis, decreases cell proliferation and enhances the radiosensitivity in NPC cells, especially EBV-positive cells. Significantly, JQ1-induced cell death is c-Myc-dependent. Notably, RNA-seq analysis demonstrated that JQ1 represses TP63, TP53 and their targets. JQ1 also lessens the expression of PD-L1 in NPC. Moreover, the high potency of JQ1 in NPC cells was further confirmed in vivo in CNE2-EBV+ tumor-bearing mice. These findings indicate that JQ1 is a promising therapeutic candidate for advanced NPC.
Glutathione depletion induces ferroptosis, autophagy, and premature cell senescence in retinal pigment epithelial cells
Authors: Sun Yun , Zheng Yingfeng , Wang Chunxiao , Liu Yizhi 
Published: July 2018

AbstractGlutathione (GSH) protects against oxidative damage in many tissues, including retinal pigment epithelium (RPE). Oxidative stress-mediated senescence and death of RPE and subsequent death of photoreceptors have been observed in age-related macular degeneration (AMD). Although the consequences of GSH depletion have been described previously, questions remain regarding the molecular mechanisms. We herein examined the downstream effects of GSH depletion on stress-induced premature senescence (SIPS) and cell death in human RPE cells. Briefly, cultured ARPE-19 cells were depleted of GSH using: (1) incubation in cystine (Cys2)-free culture medium; (2) treatment with buthionine sulphoximine (BSO, 1000 µM) to block de novo GSH synthesis for 24–48 h; or (3) treatment with erastin (10 µM for 12–24 h) to inhibit Cys2/glutamate antiporter (system xc−). These treatments decreased cell viability and increased both soluble and lipid reactive oxygen species (ROS) generation but did not affect mitochondrial ROS or mitochondrial mass. Western blot analysis revealed decreased expression of ferroptotic modulator glutathione peroxidase 4 (GPX4). Increased autophagy was apparent, as reflected by increased LC3 expression, autophagic vacuoles, and autophagic flux. In addition, GSH depletion induced SIPS, as evidenced by increased percentage of the senescence-associated β-galactosidase-positive cells, increased senescence-associated heterochromatin foci (SAHF), as well as cell cycle arrest at the G1 phase. GSH depletion-dependent cell death was prevented by selective ferroptosis inhibitors (8 μM Fer-1 and 600 nM Lip-1), iron chelator DFO (80 μM), as well as autophagic inhibitors Baf-A1 (75 nM) and 3-MA (10 mM). Inhibiting autophagy with Baf-A1 (75 nM) or 3-MA (10 mM) promoted SIPS. In contrast, inducing autophagy with rapamycin (100 nM) attenuated SIPS. Our findings suggest that GSH depletion induces ferroptosis, autophagy, and SIPS. In addition, we found that autophagy is activated in the process of ferroptosis and reduces SIPS, suggesting an essential role of autophagy in ferroptosis and SIPS.
Exosomal secretion of α-synuclein as protective mechanism after upstream blockage of macroautophagy
Authors: Fussi Natascha , Höllerhage Matthias , Chakroun Tasnim , Nykänen Niko-Petteri , Rösler Thomas W. , Koeglsperger Thomas , Wurst Wolfgang , Behrends Christian , Höglinger Günter U. 
Published: July 2018

AbstractAccumulation of pathological α-synuclein aggregates plays a major role in Parkinson’s disease. Macroautophagy is a mechanism to degrade intracellular protein aggregates by wrapping them into autophagosomes, followed by fusion with lysosomes. We had previously shown that pharmacological activation of macroautophagy protects against α-synuclein-induced toxicity in human neurons. Here, we hypothesized that inhibition of macroautophagy would aggravate α-synuclein-induced cell death.Unexpectedly, inhibition of autophagosome formation by silencing of ATG5 protected from α-synuclein-induced toxicity. Therefore, we studied alternative cellular mechanisms to compensate for the loss of macroautophagy. ATG5 silencing did not affect the ubiquitin–proteasome system, chaperone systems, chaperone-mediated autophagy, or the unfolded protein response. However, ATG5 silencing increased the secretion of α-synuclein via exosomes. Blocking exosomal secretion exacerbated α-synuclein-induced cell death.We conclude that exosomal secretion of α-synuclein is increased after impaired formation of autophagosomes to reduce the intracellular α-synuclein burden. This compensatory mechanism prevents α-synuclein-induced neuronal cell death.
Single neurons may encode simultaneous stimuli by switching between activity patterns
Authors: Caruso Valeria C. , Mohl Jeff T. , Glynn Christopher , Lee Jungah , Willett Shawn M. , Zaman Azeem , Ebihara Akinori F. , Estrada Rolando , Freiwald Winrich A. , Tokdar Surya T. , Groh Jennifer M. 
Published: July 2018

AbstractHow the brain preserves information about multiple simultaneous items is poorly understood. We report that single neurons can represent multiple stimuli by interleaving signals across time. We record single units in an auditory region, the inferior colliculus, while monkeys localize 1 or 2 simultaneous sounds. During dual-sound trials, we find that some neurons fluctuate between firing rates observed for each single sound, either on a whole-trial or on a sub-trial timescale. These fluctuations are correlated in pairs of neurons, can be predicted by the state of local field potentials prior to sound onset, and, in one monkey, can predict which sound will be reported first. We find corroborating evidence of fluctuating activity patterns in a separate dataset involving responses of inferotemporal cortex neurons to multiple visual stimuli. Alternation between activity patterns corresponding to each of multiple items may therefore be a general strategy to enhance the brain processing capacity, potentially linking such disparate phenomena as variable neural firing, neural oscillations, and limits in attentional/memory capacity.
Bottle-grade polyethylene furanoate from ring-opening polymerisation of cyclic oligomers
Authors: Rosenboom Jan-Georg , Hohl Diana Kay , Fleckenstein Peter , Storti Giuseppe , Morbidelli Massimo 
Published: July 2018

AbstractPolyethylene furanoate (PEF) represents a promising renewable resource-based bioplastic as replacement for fossil-based polyethylene terephthalate (PET) with improved material properties. However, the synthesis of PEF through conventional polycondensation remains challenging, since the time-intensive reaction leads to degradation and undesired discolouration of the product. Here we show the successful rapid synthesis of bottle-grade PEF via ring-opening polymerisation (ROP) from cyclic PEF oligomers within minutes, thereby avoiding degradation and discolouration. The melting point of such mixture of cyclic oligomers lies around 370 °C, well above the degradation temperature of PEF (~329 °C). This challenge can be overcome, exploiting the self-plasticising effect of the forming polymer itself (which melts around 220 °C) by initiation in the presence of a high boiling, yet removable, and inert liquid plasticiser. This concept yields polymer grades required for bottle applications (Mn > 30 kg mol−1, conversion > 95%, colour-free products), and can be extended to other diffusion-limited polymer systems.
Single-molecule insights into surface-mediated homochirality in hierarchical peptide assembly
Authors: Chen Yumin , Deng Ke , Lei Shengbin , Yang Rong , Li Tong , Gu Yuantong , Yang Yanlian , Qiu Xiaohui , Wang Chen 
Published: July 2018

AbstractHomochirality is very important in the formation of advanced biological structures, but the origin and evolution mechanisms of homochiral biological structures in complex hierarchical process is not clear at the single-molecule level. Here we demonstrate the single-molecule investigation of biological homochirality in the hierarchical peptide assembly, regarding symmetry break, chirality amplification, and chirality transmission. We find that homochirality can be triggered by the chirality unbalance of two adsorption configuration monomers. Co-assembly between these two adsorption configuration monomers is very critical for the formation of homochiral assemblies. The site-specific recognition is responsible for the subsequent homochirality amplification and transmission in their hierarchical assembly. These single-molecule insights open up inspired thoughts for understanding biological homochirality and have general implications for designing and fabricating artificial biomimetic hierarchical chiral materials.
Highly efficient RNA-guided base editing in rabbit
Authors: Liu Zhiquan , Chen Mao , Chen Siyu , Deng Jichao , Song Yuning , Lai Liangxue , Li Zhanjun 
Published: July 2018

AbstractCytidine base editors (CBEs) and adenine base editors (ABEs), composed of a cytidine deaminase or an evolved adenine deaminase fused to Cas9 nickase, enable the conversion of C·G to T·A or A·T to G·C base pair in organisms, respectively. Here, we show that BE3 and ABE7.10 systems can achieve a targeted mutation efficiency of 53–88% and 44–100%, respectively, in both blastocysts and Founder (F0) rabbits. Meanwhile, this strategy can be used to precisely mimic human pathologies by efficiently inducing nonsense or missense mutations as well as RNA mis-splicing in rabbit. In addition, the reduced frequencies of indels with higher product purity are also determined in rabbit blastocysts by BE4-Gam, which is an updated version of the BE3 system. Collectively, this work provides a simple and efficient method for targeted point mutations and generation of disease models in rabbit.
Aberrant imprinting may underlie evolution of parthenogenesis
Authors: Kirioukhova Olga , Shah Jubin N. , Larsen Danaé S. , Tayyab Muhammad , Mueller Nora E. , Govind Geetha , Baroux Célia , Federer Michael , Gheyselinck Jacqueline , Barrell Philippa J. , Ma Hong , Sprunck Stefanie , Huettel Bruno , Wallace Helen , Grossniklaus Ueli , Johnston Amal J. 
Published: July 2018

AbstractGenomic imprinting confers parent-of-origin-specific gene expression, thus non-equivalent and complementary function of parental genomes. As a consequence, genomic imprinting poses an epigenetic barrier to parthenogenesis in sexual organisms. We report aberrant imprinting in Boechera, a genus in which apomicts evolved from sexuals multiple times. Maternal activation of a MADS-box gene, a homolog of which is imprinted and paternally expressed in the sexual relative Arabidopsis, is accompanied by locus-specific DNA methylation changes in apomicts where parental imprinting seems to be relaxed.
Effect of temperature on the oxidation of Cu nanowires and development of an easy to produce, oxidation-resistant transparent conducting electrode using a PEDOT:PSS coating
Authors: Mardiansyah Dedi , Badloe Trevon , Triyana Kuwat , Mehmood Muhammad Q. , Raeis-Hosseini Niloufar , Lee Yoonkyung , Sabarman Harsojo , Kim Kyunghoon , Rho Junsuk 
Published: July 2018

AbstractOxidation can strongly influence the performance of Cu nanowires (CuNWs) by decreasing their conductivity. Here, we identify and investigate a way to prevent the oxidation process of CuNWs to maintain the high conducting performance of CuNWs as transparent electrodes. CuNWs were synthesised using an aqueous method. We prepared several temperature treatments (from 0–300 °C) to represent oxidation of CuNWs in different environments, to study the oxidation process and changes in morphology in detail. Depending on the temperature, smooth and uniform CuNWs exposed to oxidation produced rough Cu2O and CuO nanowires. We then suggest a method of protecting nanowires from oxidation, using the Mayer rod coating method to apply a layer of PEDOT:PSS to a transparent conducting film of CuNWs. The result indicates that this method of protection can protect the film, and maintain a stable, and constant resistance over of time, without effecting the excellent conductivity properties of pure CuNWs.
Simple Physical Model Unravels Influences of Chemokine on Shape Deformation and Migration of Human Hematopoietic Stem Cells
Authors: Ohta Takao , Monzel Cornelia , Becker Alexandra S. , Ho Anthony D. , Tanaka Motomu 
Published: July 2018

AbstractWe studied the dynamic behavior of human hematopoietic stem cells (HSC) on the in vitro model of bone marrow surfaces in the absence and presence of chemokine (SDF1α). The deformation and migration of cells were investigated by varying the chemokine concentration and surface density of ligand molecules. Since HSC used in this study were primary cells extracted from the human umbilical cord blood, it is not possible to introduce molecular reporter systems before or during the live cell imaging. To account for the experimental observations, we propose a simple and general theoretical model for cell crawling. In contrast to other theoretical models reported previously, our model focuses on the nonlinear coupling between shape deformation and translational motion and is free from any molecular-level process. Therefore, it is ideally suited for the comparison with our experimental results. We have demonstrated that the results in the absence of SDF1α were well recapitulated by the linear model, while the nonlinear model is necessary to reproduce the elongated migration observed in the presence of SDF1α. The combination of the simple theoretical model and the label-free, live cell observations of human primary cells opens a large potential to numerically identify the differential effects of extrinsic factors such as chemokines, growth factors, and clinical drugs on dynamic phenotypes of primary cells.
The Drosophila microbiome has a limited influence on sleep, activity, and courtship behaviors
Authors: Selkrig Joel , Mohammad Farhan , Ng Soon Hwee , Chua Jia Yi , Tumkaya Tayfun , Ho Joses , Chiang Yin Ning , Rieger Dirk , Pettersson Sven , Helfrich-Förster Charlotte , Yew Joanne Y. , Claridge-Chang Adam 
Published: July 2018

AbstractIn animals, commensal microbes modulate various physiological functions, including behavior. While microbiota exposure is required for normal behavior in mammals, it is not known how widely this dependency is present in other animal species. We proposed the hypothesis that the microbiome has a major influence on the behavior of the vinegar fly (Drosophila melanogaster), a major invertebrate model organism. Several assays were used to test the contribution of the microbiome on some well-characterized behaviors: defensive behavior, sleep, locomotion, and courtship in microbe-bearing, control flies and two generations of germ-free animals. None of the behaviors were largely influenced by the absence of a microbiome, and the small or moderate effects were not generalizable between replicates and/or generations. These results refute the hypothesis, indicating that the Drosophila microbiome does not have a major influence over several behaviors fundamental to the animal’s survival and reproduction. The impact of commensal microbes on animal behaviour may not be broadly conserved.
Hemostatic nanoparticles increase survival, mitigate neuropathology and alleviate anxiety in a rodent blast trauma model
Authors: Hubbard W. Brad , Lashof-Sullivan Margaret , Greenberg Shaylen , Norris Carly , Eck Joseph , Lavik Erin , VandeVord Pamela 
Published: July 2018

AbstractExplosions account for 79% of combat related injuries and often lead to polytrauma, a majority of which include blast-induced traumatic brain injuries (bTBI). These injuries lead to internal bleeding in multiple organs and, in the case of bTBI, long term neurological deficits. Currently, there are no treatments for internal bleeding beyond fluid resuscitation and surgery. There is also a dearth of treatments for TBI. We have developed a novel approach using hemostatic nanoparticles that encapsulate an anti-inflammatory, dexamethasone, to stop the bleeding and reduce inflammation after injury. We hypothesize that this will improve not only survival but long term functional outcomes after blast polytrauma. Poly(lactic-co-glycolic acid) hemostatic nanoparticles encapsulating dexamethasone (hDNPs) were fabricated and tested following injury along with appropriate controls. Rats were exposed to a single blast wave using an Advanced Blast Simulator, inducing primary blast lung and bTBI. Survival was elevated in the hDNPs group compared to controls. Elevated anxiety parameters were found in the controls, compared to hDNPs. Histological analysis indicated that apoptosis and blood-brain barrier disruption in the amygdala were significantly increased in the controls compared to the hDNPs and sham groups. Immediate intervention is crucial to mitigate injury mechanisms that contribute to emotional deficits.
Down-regulation of vascular GLP-1 receptor expression in human subjects with obesity
Authors: Kimura Tomohiko , Obata Atsushi , Shimoda Masashi , Shimizu Ikki , da Silva Xavier Gabriela , Okauchi Seizo , Hirukawa Hidenori , Kohara Kenji , Mune Tomoatsu , Moriuchi Saeko , Hiraoka Arudo , Tamura Kentaro , Chikazawa Genta , Ishida Atsuhisa , Yoshitaka Hidenori , Rutter Guy A. , Kaku Kohei , Kaneto Hideaki 
Published: July 2018

AbstractIt has been thought that incretin signaling prevents arteriosclerosis, and very recently anti-arteriosclerotic effects through GLP-1 receptor were finally demonstrated in clinical human study. The purpose of this study was to investigate how vascular GLP-1 receptor expression is influenced in human subjects. First, we evaluated GLP-1 receptor expression in human arteries in immunostaining. Next, we separated the artery into the intima and media, and evaluated gene expression levels of various factors. We divided the subjects into obesity and non-obesity group and compared their expression levels between them. Finally, we evaluated which factors determine vascular GLP-1 receptor expression. GLP-1 receptor expression in intima and media was lower in obesity group compared to non-obesity group which was correlated with the alteration of TCF7L2 expression. Multiple regression analyses showed that BMI was an independent determining factor for GLP-1 receptor expression in the intima and media. Furthermore, using small interfering RNA method and TCF7L2-EGFP adenovirus, we showed that TCF7L2 was involved in GLP-1 receptor expression in human vascular cells. Taken together, vascular GLP-1 receptor and TCF7L2 expression was significantly down-regulated in human subjects with obesity. In addition, it is likely that TCF7L2 functions as a modulator of vascular GLP-1 receptor expression.