bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultra-high field MRI reveals mood-related circuit disturbances in depression: a comparison between 3-Tesla and 7-Tesla
Authors: Morris Laurel S. , Kundu Prantik , Costi Sara , Collins Abigail , Schneider Molly , Verma Gaurav , Balchandani Priti , Murrough James W. 
Published: February 2019

AbstractUltra-high field 7-Tesla (7 T) MRI has the potential to advance our understanding of neuropsychiatric disorders, including major depressive disorder (MDD). To date, few studies have quantified the advantage of resting state functional MRI (fMRI) at 7 T compared to 3-Tesla (3 T). We conducted a series of experiments that demonstrate the improvement in temporal signal-to-noise ratio (TSNR) of a multi-echo multi-band fMRI protocol with ultra-high field 7 T MRI, compared to a similar protocol using 3 T MRI in healthy controls (HC). We also directly tested the enhancement in ultra-high field 7 T fMRI signal power by examining the ventral tegmental area (VTA), a small midbrain structure that is critical to the expected neuropathology of MDD but difficult to discern with standard 3 T MRI. We demonstrate up to 300% improvement in TSNR and resting state functional connectivity coefficients provided by ultra-high field 7 T fMRI compared to 3 T, indicating enhanced power for detection of functional neural architecture. A multi-echo based acquisition protocol and signal denoising pipeline afforded greater gain in signal power compared to classic acquisition and denoising pipelines. Furthermore, ultra-high field fMRI revealed mood-related neurocircuit disturbances in patients with MDD compared to HC, which were not detectable with 3 T fMRI. Ultra-high field 7 T fMRI may provide an effective tool for studying functional neural architecture relevant to MDD and other neuropsychiatric disorders.
P53-induced miR-1249 inhibits tumor growth, metastasis, and angiogenesis by targeting VEGFA and HMGA2
Authors: Chen Xiaoxiang , Zeng Kaixuan , Xu Mu , Liu Xiangxiang , Hu Xiuxiu , Xu Tao , He Bangshun , Pan Yuqin , Sun Huiling , Wang Shukui 
Published: February 2019

AbstractMicroRNAs (miRNAs) are important class of functional regulators involved in human cancers development, including colorectal cancer (CRC). Exploring aberrantly expressed miRNAs may provide us with new insights into the initiation and development of CRC by functioning as oncogenes or tumor suppressors. The aim of our study is to discover the expression pattern of miR-1249 in CRC and investigate its clinical significance as well as biological role in CRC progression. In our study, we found that miR-1249 was markedly downregulated in CRC tissues and cell lines, and negatively related to pN stage, pM stage, TNM stage, and overall survival (OS). Moreover, we demonstrated that miR-1249 was a direct transcriptional target of P53 and revealed that P53-induced miR-1249 inhibited tumor growth, metastasis and angiogenesis in vitro and vivo. Additionally, we verified that miR-1249 suppressed CRC proliferation and angiogenesis by targeting VEGFA as well as inhibited CRC metastasis by targeting both VEGFA and HMGA2. Further studying showed that miR-1249 suppressed CRC cell proliferation, migration, invasion, and angiogenesis via VEGFA-mediated Akt/mTOR pathway as well as inhibited EMT process of CRC cells by targeting both VEGFA and HMGA2. Our study indicated that P53-induced miR-1249 may suppress CRC growth, metastasis and angiogenesis by targeting VEGFA and HMGA2, as well as regulate Akt/mTOR pathway and EMT process in the initiation and development of CRC. miR-1249 might be a novel the therapeutic candidate target in CRC treatment.
Oocyte-derived E-cadherin acts as a multiple functional factor maintaining the primordial follicle pool in mice
Authors: Yan Hao , Wen Jia , Zhang Tuo , Zheng Wenying , He Meina , Huang Kun , Guo Qirui , Chen Qian , Yang Yi , Deng Guangcun , Xu Jinrui , Wei Zhiqing , Zhang Hua , Xia Guoliang , Wang Chao 
Published: February 2019

AbstractIn mammals, female fecundity is determined by the size of the primordial follicle (PF) pool, which is established during the perinatal period. As a non-renewable resource, the preservation of dormant PFs is crucial for sustaining female reproduction throughout life. Although studies have revealed that several oocyte-derived functional genes and pathways, such as newborn ovary homeobox (NOBOX) and 3-phosphoinositide-dependent protein kinase-1, participate in maintaining the PF pool, our understanding of the underlying molecular mechanisms is still incomplete. Here, we demonstrate that E-cadherin (E-cad) plays a crucial role in the maintenance of PFs in mice. E-cad is specifically localized to the cytomembrane of oocytes in PFs. Knockdown of E-cad in neonatal ovaries resulted in significant PF loss owing to oocyte apoptosis. In addition, the expression pattern of NOBOX is similar to that of E-cad. Knockdown of E-cad resulted in a decreased NOBOX level, whereas overexpression of Nobox partially rescued the follicle loss induced by silencing E-cad. Furthermore, E-cad governed NOBOX expression by regulating the shuttle protein, β-catenin, which acts as a transcriptional co-activator. Notably, E-cad, which is a transmembrane protein expressed in the oocytes, was also responsible for maintaining the PF structure by facilitating cell–cell adhesive contacts with surrounding pregranulosa cells. In conclusion, E-cad in oocytes of PFs plays an indispensable role in the maintenance of the PF pool by facilitating follicular structural stability and regulating NOBOX expression. These findings shed light on the physiology of sustaining female reproduction.
Autoantibody against β1-adrenoceptor promotes the differentiation of natural regulatory T cells from activated CD4+ T cells by up-regulating AMPK-mediated fatty acid oxidation
Authors: Xu Wenli , Wu Ye , Wang Li , Bai Yan , Du Yunhui , Li Yang , Cao Ning , Zhao Yuhui , Zhang Youyi , Liu Huirong 
Published: February 2019

AbstractTherapeutic adoptive transfer of natural regulatory T cells (nTreg, CD4+ CD25+ Foxp3+ T cells) or in vivo selective expansion of nTreg cells has been demonstrated to improve the cardiac function in various cardiovascular disease models. The differentiation of nTreg cells is mediated by catecholamines via β1-adrenergic receptor (β1-AR) activation. Autoantibody against β1-adrenoceptor (β1-AA) as a β1-AR agonist is closely associated with the occurrence and deterioration of cardiac dysfunction. However, whether β1-AA has any impact on nTreg cells has not been reported. The aim of the present study was intended to assess the potential impact of β1-AA on nTreg cell differentiation and explore the underlying mechanism. It was found that the expression of multiple proteins involved in nTreg cell differentiation, immunosuppressive function, and migration was up-regulated in mice after β1-AA administration, suggesting that β1-AA may promote nTreg cell activation. In vitro, β1-AA promoted nTreg cell differentiation by up-regulating mitochondrial fatty acid oxidation (FAO) in activated CD4+ T cells via AMP-activated protein kinase (AMPK) activation and mitochondrial membrane potential reduction. In addition, the AMPK agonist facilitated β1-AA-mediated FAO and nTreg cell differentiation. To further confirm the role of AMPK in β1-AA-mediated nTreg cell differentiation, β1-AA was acted on the CD4+ T cells isolated from AMPK-deficient (AMPK−/−) mice. The result showed that the effect of β1-AA on nTreg cell differentiation was attenuated markedly after AMPK knockout. In conclusion, AMPK-mediated metabolic regulation targeting for nTreg cell restoration may be a promising therapeutic target for β1-AA-positive patients with cardiac dysfunction.
MiR-30a regulates cancer cell response to chemotherapy through SNAI1/IRS1/AKT pathway
Authors: Wang Tingting , Chen Gang , Ma Xuemei , Yang Yao , Chen Yali , Peng Yihan , Bai Zhigang , Zhang Zhongtao , Pei Huadong , Guo Wei 
Published: February 2019

AbstractDespite gemcitabine being the leading chemotherapeutic drug for pancreatic cancer, many patients still relapse due to the drug resistance. We previously reported the molecular link between FKBP51 mediated AKT inhibition and gemcitabine response in pancreatic cancers. However, the upstream regulator of this pathway, especially the involvement of non-coding RNAs in gemcitabine response is still not clear. Here we delineated the miRNA expression profile and key signaling pathways associated with gemcitabine response. Furthermore, we confirmed that miR-30a, one node of this network, regulated cellular response to gemcitabine through SNAI1-IRS1-AKT pathway. MiR-30a directly targeted SNAI1, which activates AKT and ERK through regulating IRS1 in vitro and in vivo. Clinically, miR-30a is downregulated in pancreatic cancer tissue and associated with overall patient survival. We also identified miR-30a as an AKT-FOXO3a-regulated gene that forms a feedback loop. Together, these results demonstrate that miR-30a is an upstream regulator of the Akt pathway with a critical role in cancer etiology and chemoresistance.
Long noncoding RNA EGFR-AS1 promotes cell growth and metastasis via affecting HuR mediated mRNA stability of EGFR in renal cancer
Authors: Wang Anbang , Bao Yi , Wu Zhenjie , Zhao Tangliang , Wang Dong , Shi Jiazi , Liu Bing , Sun Shuhan , Yang Fu , Wang Linhui , Qu Le 
Published: February 2019

AbstractLong noncoding RNAs (lncRNAs) are implicated in renal cell carcinoma (RCC), but remain largely unclear. Using publicly available transcriptome sequencing data from renal cancer (n = 703) and integrating bioinformatics analyses, we screened and identified a valuable lncRNA, EGFR-AS1. In our validation cohort (n = 204), EGFR-AS1 was significantly upregulated in RCC tissues (P < 0.001). Gain-of-function and loss-of-function studies showed that EGFR-AS1 promoted cell proliferation and invasion in vitro and in vivo. Based on previous studies and sequence complementarity of EGFR with EGFR-AS1, we demonstrated that EGFR-AS1 directly bound to EGFR mRNA and inhibited its degradation. Furthermore, RNA pull-down and mass spectrometry analyses showed that EGFR-AS1 interacted with HuR, which was responsible for the mRNA stability of EGFR. Multivariate analysis suggested that higher EGFR-AS1 expression predicted a poor prognosis in RCC patients (high vs low: P = 0.018, HR = 2.204, 95% CI: 1.145–4.241). In conclusion, EGFR-AS1 enhances the malignant phenotype of RCC cells by enhancing HuR-mediated mRNA stability of EGFR. Our data also provide biological rationales for EGFR-AS1 as a prognostic biomarker and a potential therapeutic target for RCC.
Long non-coding RNA ZNFX1-AS1 promotes the tumor progression and metastasis of colorectal cancer by acting as a competing endogenous RNA of miR-144 to regulate EZH2 expression
Authors: Shi Liangliang , Hong Xiaohua , Ba Li , He Xiaoxiao , Xiong Yin , Ding Qian , Yang Shengli , Peng Gang 
Published: February 2019

AbstractMounting evidences indicated that long non-coding RNA is dysregulated and involved in the pathology of tumors. However, the role of lncRNAs in colorectal cancer (CRC) progression is not fully determined. Differentially expressed lncRNA profile in CRC was conducted by lncRNA microarray in 15 pairs of CRC tissues and adjacent normal tissues, and validated by real-time PCR analysis in another 106 pairs of tissues. The biological effect of lncRNA ZNFX1-AS1 was evaluated by in vitro and in vivo assays. The regulation between lncRNA ZNFX1-AS1 and miR-144 was evaluated by a series of experiments. We found that lncRNA ZNFX1-AS1 expression was significantly upregulated in CRC tissues and cell lines, and the expression of lncRNA ZNFX1-AS1 was associated with aggressive tumor phenotype and poor prognosis in CRC. Functionally, knockdown of lncRNA ZNFX1-AS1 inhibited cell proliferation, invasion, in vitro and tumorigenesis and metastasis in vivo. Further investigation demonstrated that lncRNA ZNFX1-AS1 functioned as a competing endogenous RNA (ceRNA) for miR-144, thereby leading to the depression of its endogenous target gene Polycomb group protein enhancer of zeste homolog 2 (EZH2). We found that lncRNA ZNFX1-AS1 is significantly upregulated in CRC, and the newly identified lncRNA ZNFX1-AS1-miR-144-EZH2 axis is involved in the regulation of CRC progression, which might be used as potential therapeutic targets for CRC patients.
LncRNA H19 promotes the committed differentiation of stem cells from apical papilla via miR-141/SPAG9 pathway
Authors: Li Zehan , Yan Ming , Yu Yan , Wang Yanqiu , Lei Gang , Pan Yin , Li Na , Gobin Romila , Yu Jinhua 
Published: February 2019

AbstractLong noncoding RNAs (lncRNAs) exert significant roles at transcriptional and post-transcriptional levels. Stem cells from apical papilla (SCAPs) differentiate into dentin/bone-like tissues under certain conditions. So far, whether lncRNA-H19 can affect the proliferative behaviors and osteo/odontogenesis of SCAPs, as well as its specific mechanism remain to be elucidated. Here, SCAPs were isolated and transfected with the lentiviruses or packaging vectors. Our results showed that lncRNA-H19 had no significant effect on the proliferative behaviors of SCAPs, as presented by CCK-8 assay, EdU assay and flow cytometry (FCM). Furthermore, alkaline phosphatase (ALP) activity, alizarin red staining, Western blot assay (WB), quantitative real-time polymerase chain reaction (qRT-PCR) and in vivo bone formation assay were conducted to verify the biological influences of H19 on SCAPs. Overexpression of H19 led to the enhanced osteo/odontogenesis of SCAPs, whereas knockdown of H19 inhibited these effects. Mechanistically, H19 competitively bound to miR-141 and prevented SPAG9 from miRNA-mediated degradation, thus significantly elevating phosphorylated levels of p38 and JNK and facilitating the committed differentiation of SCAPs. Taken together, the osteo/odontogenesis of SCAPs was upregulated by overexpression of H19 via miR-141/SPAG9 pathway.
RETRACTED ARTICLE: Long noncoding RNA LINC01234 promotes serine hydroxymethyltransferase 2 expression and proliferation by competitively binding miR-642a-5p in colon cancer
Authors: Lin Changwei , Zhang Yi , Chen Yifei , Bai Yang , Zhang Yi 
Published: February 2019

AbstractLong noncoding RNAs (lncRNAs) have been indicated as important regulators in various human cancers. However, the overall biological roles and clinical significance of most lncRNAs in colon carcinogenesis are not fully understood. Hence, we investigated the clinical significance, biological function and mechanism of LINC01234 in colon cancer. First, we analyzed LINC01234 alterations in colon cancer tissues and corresponding paracancerous tissues through the analysis of sequencing data obtained from The Cancer Genome Atlas and colon cancer patients. Next, we evaluated the effect of LINC01234 on colon cancer cell proliferation and its regulatory mechanism of serine hydroxymethyltransferase 2 (SHMT2) by acting as a competing endogenous RNA (ceRNA). We found that LINC01234 expression was significantly upregulated in colon cancer tissues and was associated with a shorter survival time. Furthermore, the knockdown of LINC01234 induced proliferation arrest via suppressing serine/glycine metabolism. Mechanistic investigations have indicated that LINC01234 functions as a ceRNA for miR-642a-5p, thereby leading to the derepression of its endogenous target serine hydroxymethyltransferase 2 (SHMT2). LINC01234 is significantly overexpressed in colon cancer, and the LINC01234–miR642a-5p–SHMT2 axis plays a critical role in colon cancer proliferation. Our findings may provide a potential new target for colon cancer diagnosis and therapy.
A genetically encoded single-wavelength sensor for imaging cytosolic and cell surface ATP
Authors: Lobas Mark A. , Tao Rongkun , Nagai Jun , Kronschläger Mira T. , Borden Philip M. , Marvin Jonathan S. , Looger Loren L. , Khakh Baljit S. 
Published: February 2019

AbstractAdenosine 5′ triphosphate (ATP) is a universal intracellular energy source and an evolutionarily ancient, ubiquitous extracellular signal in diverse species. Here, we report the generation and characterization of single-wavelength genetically encoded fluorescent sensors (iATPSnFRs) for imaging extracellular and cytosolic ATP from insertion of circularly permuted superfolder GFP into the epsilon subunit of F0F1-ATPase from Bacillus PS3. On the cell surface and within the cytosol, iATPSnFR1.0 responds to relevant ATP concentrations (30 μM to 3 mM) with fast increases in fluorescence. iATPSnFRs can be genetically targeted to specific cell types and sub-cellular compartments, imaged with standard light microscopes, do not respond to other nucleotides and nucleosides, and when fused with a red fluorescent protein function as ratiometric indicators. After careful consideration of their modest pH sensitivity, iATPSnFRs represent promising reagents for imaging ATP in the extracellular space and within cells during a variety of settings, and for further application-specific refinements.
MapB, the Brucella suis TamB homologue, is involved in cell envelope biogenesis, cell division and virulence
Authors: Bialer Magalí Graciela , Ruiz-Ranwez Verónica , Sycz Gabriela , Estein Silvia Marcela , Russo Daniela Marta , Altabe Silvia , Sieira Rodrigo , Zorreguieta Angeles 
Published: February 2019

AbstractBrucella species are Gram-negative, facultative intracellular pathogens responsible for a worldwide zoonosis. The envelope of Brucella exhibits unique characteristics that make these bacteria furtive pathogens and resistant to several host defence compounds. We have identified a Brucella suis gene (mapB) that appeared to be crucial for cell envelope integrity. Indeed, the typical resistance of Brucella to both lysozyme and the cationic lipopeptide polymyxin B was markedly reduced in a ∆mapB mutant. MapB turned out to represent a TamB orthologue. This last protein, together with TamA, a protein belonging to the Omp85 family, form a complex that has been proposed to participate in the translocation of autotransporter proteins across the outer membrane (OM). Accordingly, we observed that MapB is required for proper assembly of an autotransporter adhesin in the OM, as most of the autotransporter accumulated in the mutant cell periplasm. Both assessment of the relative amounts of other specific outer membrane proteins (OMPs) and a proteome approach indicated that the absence of MapB did not lead to an extensive alteration in OMP abundance, but to a reduction in the relative amounts of a protein subset, including proteins from the Omp25/31 family. Electron microscopy revealed that ∆mapB cells exhibit multiple anomalies in cell morphology, indicating that the absence of the TamB homologue in B. suis severely affects cell division. Finally, ∆mapB cells were impaired in macrophage infection and showed an attenuated virulence phenotype in the mouse model. Collectively, our results indicate that the role of B. suis TamB homologue is not restricted to participating in the translocation of autotransporters across the OM but that it is essential for OM stability and protein composition and that it is involved in cell envelope biogenesis, a process that is inherently coordinated with cell division.
A method for combining multiple-units readout of optogenetic control with natural stimulation-evoked eyeblink conditioning in freely-moving mice
Authors: Zhang Jie , Zhang Kai-Yuan , Zhang Li-Bin , Zhang Wei-Wei , Feng Hua , Yao Zhong-Xiang , Hu Bo , Chen Hao 
Published: February 2019

AbstractA growing pool of transgenic mice expressing Cre-recombinases, together with Cre-dependent opsin viruses, provide good tools to manipulate specific neural circuits related to eyeblink conditioning (EBC). However, currently available methods do not enable to get fast and precise readout of optogenetic control when the freely-moving mice are receiving EBC training. In the current study, we describe a laser diode (LD)-optical fiber (OF)-Tetrode assembly that allows for simultaneous multiple units recording and optical stimulation. Since the numbers of various cables that require to be connected are minimized, the LD-OF-Tetrode assembly can be combined with CS-US delivery apparatus for revealing the effects of optical stimulation on EBC in freely- moving mice. Moreover, this combination of techniques can be utilized to optogenetically intervene in hippocampal neuronal activities during the post-conditioning sleep in a closed-loop manner. This novel device thus enhances our ability to explore how specific neuronal assembly contributes to associative motor memory in vivo.
Facile Fabrication of Size-Tunable Core/Shell Ferroelectric/Polymeric Nanoparticles with Tailorable Dielectric Properties via Organocatalyzed Atom Transfer Radical Polymerization Driven by Visible Light
Authors: You Ning , Zhang Chenxi , Liang Yachao , Zhang Qi , Fu Peng , Liu Minying , Zhao Qingxiang , Cui Zhe , Pang Xinchang 
Published: February 2019

AbstractAn unconventional but facile approach to prepare size-tunable core/shell ferroelectric/polymeric nanoparticles with uniform distribution is achieved by metal-free atom transfer radical polymerization (ATRP) driven by visible light under ambient temperature based on novel hyperbranched aromatic polyamides (HBPA) as a functional matrix. Cubic BaTiO3/HBPA nanocomposites can be prepared by in-situ polycondensation process with precursors (barium hydroxide (Ba(OH)2) and titanium(IV) tetraisopropoxide (TTIP)) of ferroelectric BaTiO3 nanocrystals, because precursors can be selectively loaded into the domain containing the benzimidazole rings. At 1200 °C, the aromatic polyamide coating of cubic BaTiO3 nanoparticles are carbonized to form carbon layer in the inert environment, which prevents regular nanoparticles from gathering. In addition, cubic BaTiO3 nanoparticles are simultaneously transformed into tetragonal BaTiO3 nanocrystals after high temperature calcination (1200 °C). The outer carbon shell of tetragonal BaTiO3 nanoparticles is removed via 500 °C calcination in air. Bi-functional ligand can modify the surface of tetragonal BaTiO3 nanoparticles. PMMA polymeric chains are growing from the initiating sites of ferroelectric BaTiO3 nanocrystal surface via the metal-free ATRP technique to obtain core/shell ferroelectric BaTiO3/PMMA hybrid nanoparticles. Changing the molar ratio between benzimidazole ring units and precursors can tune the size of ferroelectric BaTiO3 nanoparticles in the process of polycondensation, and the thickness of polymeric shell can be tailored by changing the white LED irradiation time in the organocatalyzed ATRP process. The dielectric properties of core/shell BaTiO3/PMMA hybrid nanoparticles can be also tuned by adjusting the dimension of BaTiO3 core and the molecular weight of PMMA shell.