bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noninvasive optical activation of Flp recombinase for genetic manipulation in deep mouse brain regions
Authors: Jung Hyunjin , Kim Seong-Wook , Kim Minsoo , Hong Jongryul , Yu Daseuli , Kim Ji Hye , Lee Yunju , Kim Sungsoo , Woo Doyeon , Shin Hee-Sup , Park Byung Ouk , Heo Won Do 
Published: January 2019

AbstractSpatiotemporal control of gene expression or labeling is a valuable strategy for identifying functions of genes within complex neural circuits. Here, we develop a highly light-sensitive and efficient photoactivatable Flp recombinase (PA-Flp) that is suitable for genetic manipulation in vivo. The highly light-sensitive property of PA-Flp is ideal for activation in deep mouse brain regions by illumination with a noninvasive light-emitting diode. In addition, PA-Flp can be extended to the Cre-lox system through a viral vector as Flp-dependent Cre expression platform, thereby activating both Flp and Cre. Finally, we demonstrate that PA-Flp–dependent, Cre-mediated Cav3.1 silencing in the medial septum increases object-exploration behavior in mice. Thus, PA-Flp is a noninvasive, highly efficient, and easy-to-use optogenetic module that offers a side-effect-free and expandable genetic manipulation tool for neuroscience research.
Tadalafil treatment in mice for preeclampsia with fetal growth restriction has neuro-benefic effects in offspring through modulating prenatal hypoxic conditions
Authors: Tachibana Ryota , Umekawa Takashi , Yoshikawa Kento , Owa Takao , Magawa Shoichi , Furuhashi Fumi , Tsuji Makoto , Maki Shintaro , Shimada Kyoko , Kaneda Michiko K. , Nii Masafumi , Tanaka Hiroaki , Tanaka Kayo , Kamimoto Yuki , Kondo Eiji , Kato Ineko , Ikemura Kenji , Okuda Masahiro , Ma Ning , Miyoshi Takekazu , Hosoda Hiroshi , Endoh Masayuki , Kimura Tadashi , Ikeda Tomoaki 
Published: January 2019

AbstractWe have demonstrated that tadalafil facilitates fetal growth in mice with L-NG-nitroarginine methyl ester (L-NAME)-induced preeclampsia (PE) with fetal growth restriction (FGR). Tadalafil is a selective phosphodiesterase 5 inhibitor that dilates the maternal blood sinuses in the placenta, thereby facilitating the growth of the fetus. The purpose of this study was to investigate the effects of tadalafil treatment for PE and FGR on the developing brain in FGR offspring using an L-NAME-induced mouse model of PE with FGR. A control group of dams received carboxymethylcellulose (CMC). L-NAME-treated groups received L-NAME dissolved in CMC from 11 days post coitum (d.p.c.). The L-NAME-treated dams were divided into two subgroups 14 d.p.c. One subgroup continued to receive L-NAME. The other subgroup received L-NAME with tadalafil suspended in CMC. Tadalafil treatment for PE with FGR reduced the expression of hypoxia-inducible factor-2α in the placenta and in the brain of the FGR fetus. Moreover, tadalafil treatment in utero shows improved synaptogenesis and myelination in FGR offspring on postnatal day 15 (P15) and P30. These results suggest that tadalafil treatment for PE with FGR not only facilitates fetal growth, but also has neuroprotective effects on the developing brain of FGR offspring through modulating prenatal hypoxic conditions.
Arx Expression Suppresses Ventralization of the Developing Dorsal Forebrain
Authors: Lim Youngshin , Cho Il-Taeg , Shi Xiuyu , Grinspan Judith B. , Cho Ginam , Golden Jeffrey A. 
Published: January 2019

AbstractEarly brain development requires a tight orchestration between neural tube patterning and growth. How pattern formation and brain growth are coordinated is incompletely understood. Previously we showed that aristaless-related homeobox (ARX), a paired-like transcription factor, regulates cortical progenitor pool expansion by repressing an inhibitor of cell cycle progression. Here we show that ARX participates in establishing dorsoventral identity in the mouse forebrain. In Arx mutant mice, ventral genes, including Olig2, are ectopically expressed dorsally. Furthermore, Gli1 is upregulated, suggesting an ectopic activation of SHH signaling. We show that the ectopic Olig2 expression can be repressed by blocking SHH signaling, implicating a role for SHH signaling in Olig2 induction. We further demonstrate that the ectopic Olig2 accounts for the reduced Pax6 and Tbr2 expression, both dorsal specific genes essential for cortical progenitor cell proliferation. These data suggest a link between the control of dorsoventral identity of progenitor cells and the control of their proliferation. In summary, our data demonstrate that ARX functions in a gene regulatory network integrating normal forebrain patterning and growth, providing important insight into how mutations in ARX can disrupt multiple aspects of brain development and thus generate a wide spectrum of neurodevelopmental phenotypes observed in human patients.
Recovering metals from aqueous solutions by biosorption onto phosphorylated dry baker’s yeast
Authors: Ojima Yoshihiro , Kosako Shogo , Kihara Maya , Miyoshi Norikazu , Igarashi Koichi , Azuma Masayuki 
Published: January 2019

AbstractBiosorption is a cost-effective and simple technique for removing heavy metals and rare earth elements from aqueous solution. Here, metals were recovered from aqueous solutions using phosphorylated dry baker’s yeast cells. The cells were phosphorylated using cyclo-triphosphate, Na3P3O9. The total P content of the phosphorylated cells was ~1.0 mmol/g dry cell weight (DCW). The zeta potential of the phosphorylated cells was −45 mV, two times higher than for the non-phosphorylated cells. The strong negative charges of the phosphorylated cells allowed the cells to adsorb heavy metal ions such as Cd2+, Cu2+, Pb2+, and Zn2+, the adsorption capacities of which reached ~1.0 mmol/g DCW. This adsorption capacity was the highest level found in the previous studies using yeast dead biomass. The adsorbed metal ions were easily desorbed in 0.1 M HCl. The phosphorylated cells also adsorbed rare earth ions including Ce3+, Dy3+, Gd3+, La3+, Nd3+, Y3+, and Yb3+ with high efficiency. Furthermore, the phosphorylated yeast cells selectively adsorbed the rare earth ions (Nd3+ and Yb3+) from a solution containing heavy metals and rare earth ions because trivalent positively charged ions were adsorbed preferentially over divalent ions. Thus, phosphorylated yeast cells therefore have great potential for use as novel bioadsorbents. It is also expected that this technique can be applied to many microbial materials as well as yeast.
Effects of smoking on cognition and BDNF levels in a male Chinese population: relationship with BDNF Val66Met polymorphism
Authors: Xia Haisen , Du Xiangdong , Yin Guangzhong , Zhang Yingyang , Li Xiaosi , Cai Junyi , Huang Xingbing , Ning Yuping , Soares Jair C. , Wu Fengchun , Zhang Xiang Yang 
Published: January 2019

AbstractRecent studies demonstrate that brain-derived neurotrophic factor (BDNF) might be associated with nicotine addiction, and circulating BDNF is a biomarker of memory and general cognitive function. Moreover, studies suggest that a functional polymorphism of the BDNF Val66Met may mediate hippocampal-dependent cognitive functions. We aimed to explore the relationships between smoking, cognitive performance and BDNF in a normal Chinese Han population. We recruited 628 male healthy subjects, inducing 322 smokers and 306 nonsmokers, and genotyped them the BDNF Val66Met polymorphism. Of these, we assessed 114 smokers and 98 nonsmokers on the repeatable battery for the assessment of neuropsychological status (RBANS), and 103 smokers and 89 nonsmokers on serum BDNF levels. Smokers scored lower than the nonsmokers on RBANS total score (p = 0.002), immediate memory (p = 0.003) and delayed memory (p = 0.021). BDNF levels among the smokers who were Val allele carriers were correlated with the degree of cognitive impairments, especially attention, as well as with the carbon monoxide concentrations. Our findings suggest that smoking is associated with cognitive impairment in a male Chinese Han population. The association between higher BDNF levels and cognitive impairment, mainly attention in smokers appears to be dependent on the BDNF Val66Met polymorphism.
Temporal trends and inequalities in coronary angiography utilization in the management of non-ST-Elevation acute coronary syndromes in the U.S.
Authors: Rashid Muhammad , Fischman David L. , Gulati Martha , Tamman Khalid , Potts Jessica , Kwok Chun Shing , Ensor Joie , Shoaib Ahmad , Mansour Hossam , Zaman Azfar , Savage Michael P. , Mamas Mamas A. 
Published: January 2019

AbstractCoronary angiography (CA) is the basis of an invasive management strategy in non-ST elevation acute coronary syndromes (NSTEACS). There are limited contemporary data on national temporal trends in utilization of CA in different patient subgroups. We sought to investigate temporal trends, predictors and clinical outcomes associated with the use of CA in the US. Using the Nationwide Inpatient Sample (NIS) from 2004–2014, we identified all inpatient admissions, age ≥18, with a primary diagnosis of NSTEACS. Descriptive statistics and multivariable logistic regression models were used to investigate temporal trends, predictors and clinical outcomes associated with CA. From a total of 4,380,827 patients, 57.5% received CA during the study period and were more likely to be male, younger and less comorbid as defined per Charlson comorbidity index. The proportion of patients receiving CA increased from 48.5% to 68.5%, however, higher proportional increase was observed in males (53.9% to 69.4% Ptrend < 0.001) and those age ≤60 years (59.0% to 77.9% Ptrend < 0.001). Prior history of CABG (OR 0.33 95%CI 0.35–0.36), previous PCI (OR 0.84 95%CI 0.83–0.86) and previous AMI (OR 0.65 95%CI 0.64–0.67) were inversely related with receipt of CA. Receipt of CA was strongly associated with decreased odds of in-hospital mortality (OR 0.38 95%CI 0.36–0.40). In this national analysis, we observed a temporal increase in utilization of CA albeit slower adoption was noted in older, women and more comorbid patients. The risk-treatment paradox wherein patients who are most likely to benefit were less likely to receive CA persists even in contemporary practice.
Considerations for high-yield, high-throughput cell enrichment: fluorescence versus magnetic sorting
Authors: Sutermaster Bryan A. , Darling Eric M. 
Published: January 2019

AbstractEfficient sorting methods are required for the isolation of cellular subpopulations in basic science and translational applications. Despite this, throughputs, yields, viabilities, and processing times of common sorting methods like fluorescence-activated cell sorting (FACS) and magnetic-activated cell sorting (MACS) are underreported. In the current study, we set out to quantify the ability of these sorting methods to separate defined mixtures of alkaline phosphatase liver/bone/kidney (ALPL)-expressing and non-expressing cell types. Results showed that initial MACS runs performed using manufacturer’s recommended antibody and microbead concentrations produced inaccurate ALPL+ vs. ALPL− cell splits compared to FACS when ALPL+ cells were present in larger proportions (>~25%). Accuracy at all proportions could be achieved by using substantially higher concentrations of labeling reagents. Importantly, MACS sorts resulted in only 7–9% cell loss compared to ~70% cell loss for FACS. Additionally, MACS processing was 4–6 times faster than FACS for single, low proportion samples but took similar time for single, high-proportion samples. When processing multiple samples, MACS was always faster overall due to its ability to run samples in parallel. Average cell viability for all groups remained high (>83%), regardless of sorting method. Despite requiring substantial optimization, the ability of MACS to isolate increased cell numbers in less time than FACS may prove valuable in both basic science and translational, cell-based applications.
Effects of Mo addition on crack tip opening displacement (CTOD) in heat affected zones (HAZs) of high-strength low-alloy (HSLA) steels
Authors: Lee Seok Gyu , Kim Bohee , Kim Woo Gyeom , Um Kyung-Keun , Lee Sunghak 
Published: January 2019

AbstractEffects of Mo addition on microstructures and crack tip opening displacement (CTOD) in heat affected zones (HAZs) of three high-strength low-alloy (HSLA) steels were investigated in this study, and the correlation between them was explained by fracture mechanisms related with martensite-austenite constituent (MA) characteristics. The coarse-grained HAZ (CGHAZ) consisted of acicular ferrite (AF), granular bainite (GB), and bainitic ferrite (BF), whereas the inter-critically heated HAZ (ICHAZ) consisted of quasi-polygonal ferrite (QPF), GB, and MA. Since Mo promoted the formation of GB, BF, and MA and prevented the formation of AF and QPF, the CTOD decreased in both HAZs with increasing Mo content. According to the interrupted three-point bending test results of the ICHAZ where many MAs were distributed in the QPF or GB matrix, many voids were observed mainly at MA/QPF interfaces, which implied that the void initiation at the interfaces was a major fracture mechanism. The atomic probe data of MAs indicated the segregation of C, Mn, Mo, and P at MA/QPF interfaces, which could result in the easy MA/matrix interfacial debonding to initiate voids. Thus, characteristics of MA/QPF interfaces might affect more importantly the CTOD than the MA volume fraction or size.
Long-lived water clusters in hydrophobic solvents investigated by standard NMR techniques
Authors: Oka Kouki , Shibue Toshimichi , Sugimura Natsuhiko , Watabe Yuki , Winther-Jensen Bjorn , Nishide Hiroyuki 
Published: January 2019

AbstractUnusual physical characteristics of water can be easier explained and understood if properties of water clusters are revealed. Experimental investigation of water clusters has been reported by highly specialized equipment and/or harsh experimental conditions and has not determined the properties and the formation processes. In the current work, we used standard 1H-NMR as a versatile and facile tool to quantitatively investigate water clusters in the liquid phase under ambient conditions. This approach allows collection of data regarding the formation, long lifetime, stability, and physical properties of water clusters, as a cubic octamer in the liquid phase.
Temporal dynamics of access to amodal representations of category-level conceptual information
Authors: Leonardelli Elisa , Fait Elisa , Fairhall Scott L. 
Published: January 2019

AbstractCategories describe semantic divisions between classes of objects and category-based models are widely used for investigation of the conceptual system. One critical issue in this endeavour is the isolation of conceptual from perceptual contributions to category-differences. An unambiguous way to address this confound is combining multiple input-modalities. To this end, we showed participants person/place stimuli using name and picture modalities. Using multivariate methods, we searched for category-sensitive neural patterns shared across input-modalities and thus independent from perceptual properties. The millisecond temporal resolution of magnetoencephalography (MEG) allowed us to consider the precise timing of conceptual access and, by confronting latencies between the two modalities (“time generalization”), how latencies of processing depends on the input-modality. Our results identified category-sensitive conceptual representations common between modalities at three stages and that conceptual access for words was delayed by about 90 msec with respect to pictures. We also show that for pictures, the first conceptual pattern of activity (shared between both words and pictures) occurs as early as 110 msec. Collectively, our results indicated that conceptual access at the category-level is a multistage process and that different delays in access across these two input-modalities determine when these representations are activated.
Monitoring ultrafast metallization in LaCoO3 with femtosecond soft x-ray spectroscopy
Authors: Izquierdo Manuel , Karolak Michael , Prabhakaran Dharmalingam , Boothroyd Andrew T. , Scherz Andreas O. , Lichtenstein Alexander , Molodtsov Serguei L. 
Published: January 2019

AbstractThe study of ultrafast dynamics is a new tool to understand and control the properties of correlated oxides. By enhancing some properties and realizing new dynamically excited phrases, this tool has opened new routes for technological applications. LaCoO3 is one paradigmatic example where the strong electron, spin, and lattice coupling induced by electronic correlations results in a low-temperature spin transition and a high-temperature semiconductor-to-metal transition that is still not completely understood. Here, we monitor ultrafast metallization in LaCoO3 using time-resolved soft x-ray reflectivity experiments. While the process is entangled at the Co L3 edge, the time information of the different channels is decrypted at different resonant energies of the O K edge. Metallization is shown to occur via transient electronic, spin, and lattice separation. Our results agree with the thermodynamical model and demonstrate the potential of femtosecond soft x-ray experiments at the O K edge to understand correlated oxides.
The transmembrane autophagy cargo receptors ATI1 and ATI2 interact with ATG8 through intrinsically disordered regions with distinct biophysical properties
Authors: Sjøgaard Ida Marie Zobbe , Bressendorff Simon , Prestel Andreas , Kausika Swathi , Oksbjerg Emilie , Kragelund Birthe B. , Brodersen Peter 
Published: January 2019

Abstract
Selective autophagy has emerged as an important mechanism by which eukaryotic cells control the abundance of specific proteins. This mechanism relies on cargo recruitment to autophagosomes by receptors that bind to both the ubiquitin-like AUTOPHAGY8 (ATG8) protein through ATG8-interacting motifs (AIMs) and to the cargo to be degraded. In plants, two autophagy cargo receptors, ATG8-interacting protein 1 (ATI1) and 2 (ATI2), were identified early on, but their molecular properties remain poorly understood. Here, we show that ATI1 and ATI2 are transmembrane proteins with long N-terminal intrinsically disordered regions (IDRs). The N-terminal IDRs contain the functional AIMs, and we use nuclear magnetic resonance spectroscopy to directly observe the disorder-order transition of the AIM upon ATG8 binding. Our analyses also show that the IDRs of ATI1 and ATI2 are not equivalent, because ATI2 has properties of a fully disordered polypeptide, while ATI1 has properties more consistent with a collapsed pre-molten globule-like conformation, possibly as a consequence of a higher content of π-orbital-containing amino acid residues. Finally, we show that a sizable fraction of ATI2, but not ATI1, is phosphorylated in planta.
The essential role of tumor suppressor gene ING4 in various human cancers and non-neoplastic disorders
Authors: Du Yang , Cheng Yan , Su Guanfang 
Published: January 2019

Abstract
Inhibitor of growth 4 (ING4), a member of the ING family discovered in 2003, has been shown to act as a tumor suppressor and is frequently down-regulated in various human cancers. Numerous published in vivo and in vitro studies have shown that ING4 is responsible for important cancer hallmarks such as pathologic cell cycle arrest, apoptosis, autophagy, contact inhibition, and hypoxic adaptation, and also affects tumor angiogenesis, invasion, and metastasis. These characteristics are typically associated with regulation through chromatin acetylation by binding histone H3 trimethylated at lysine 4 (H3K4me3) and through transcriptional activity of transcription factor P53 and NF-κB. In addition, emerging evidence has indicated that abnormalities in ING4 expression and function play key roles in non-neoplastic disorders. Here, we provide an overview of ING4-modulated chromosome remodeling and transcriptional function, as well as the functional consequences of different genetic variants. We also present the current understanding concerning the role of ING4 in the development of neoplastic and non-neoplastic diseases. These studies offer inspiration for pursuing novel therapeutics for various cancers.
LncRNA TP73-AS1 sponges miR-141-3p to promote the migration and invasion of pancreatic cancer cells through the up-regulation of BDH2
Authors: Cui Xian-Ping , Wang Chuan-Xi , Wang Zhi-Yi , Li Jian , Tan Ya-Wen , Gu Song-Tao , Qin Cheng-Kun 
Published: January 2019

Abstract
LncRNA TP73 antisense RNA 1T (TP73-AS1) plays an important role in human malignancies. However, the levels of TP73-AS1 and its functional mechanisms in pancreatic cancer metastasis remain unknown, and the clinical significance of TP73-AS1 in human pancreatic cancer is also unclear. In the present study, the levels of TP73-AS1 and its candidate target miR-141 in pancreatic cancer and adjacent normal tissue were detected using qRT-PCR. The association between TP73-AS1 levels and the clinicopathologic characteristics of pancreatic cancer patients were analyzed. The relationship between TP73-AS1 and miR-141, and miR-141 and its candidate target 3-hydroxybutyrate dehydrogenase type 2 (BDH2) was confirmed using dual-luciferase reporter assays. TP73-AS1 and/or miR-141 were knocked down using siRNA or an inhibitor in pancreatic cancer cells and cell migration and invasion then examined. The results showed that TP73-AS1 was up-regulated in pancreatic cancer tissue and cell lines. High levels of TP73-AS1 were correlated with poor clinicopathological characteristics and shorter overall survival. MiR-141 was a direct target for TP73-AS1, while BDH2 was a direct target for miR-141. The knockdown of TP73-AS1 significantly inhibited the migration and invasion of pancreatic cancer cells, while the miR-141 inhibitor significantly restored the migration and invasion. Therefore, TP73-AS1 positively regulated BDH2 expression by sponging miR-141. These findings suggest that TP73-AS1 serves as an oncogene and promotes the metastasis of pancreatic cancer. Moreover, TP73-AS1 could serve as a predictor and a potential drug biotarget for pancreatic cancer.