bluuebunny/crossref_metadata_2025_split huggingface dataset:
miR-211 facilitates platinum chemosensitivity by blocking the DNA damage response (DDR) in ovarian cancer
Authors: Wang Tianzhen , Hao Dapeng , Yang Shucai , Ma Jianhui , Yang Weiwei , Zhu Yuanyuan , Weng Mingjiao , An Xiang , Wang Xuefei , Li Yafei , Wu Di , Tang Jing , Yang Chao , He Yan , Zhang Lei , Jin Xiaoming , Wang Guangyu , Li Zhiwei , Zheng Tongsen , Meng Hongxue , Feng Yukuan , Li Xiaobo 
Published: June 2019

AbstractThe DNA damage response (DDR) is one of the most important mechanisms of platinum resistance in ovarian cancer. Some miRNAs have been identified to be involved in the regulatory network of DDR, thus the abnormal expression of miRNAs might affect platinum chemosensitivity in ovarian cancer. In this study, by assessing miRNAs simultaneously targeting a set of DDR genes that exhibited response to platinum, we found that miR-211 inhibited most of those genes, and proposed that miR-211 might affect the sensitivity of ovarian cancer cells to platinum by targeting multiple DDR genes and thereby determine the prognosis of ovarian cancer. To verify the hypothesis, we analyzed the association between miR-211 level and clinical prognosis, assessed the effect of miR-211 on DDR and platinum chemosensitivity, and explored the possible molecular mechanism. We revealed that miR-211 enhanced platinum chemosensitivity and was positively correlated with favorable outcomes in ovarian cancer patients. Many DDR genes including TDP1 were identified as targets of miR-211. In contrast, TDP1 suppressed DNA damage and platinum chemosensitivity. Moreover, the miR-211 level in tissues was shown to be associated with the good outcome of neoadjuvant chemotherapy and negatively correlated with the expression of TDP1. Conclusively, we demonstrated that miR-211 improves the prognosis of ovarian cancer patients by enhancing the chemosensitivity of cancer cells to platinum via inhibiting DDR gene expression, which provides an essential basis to identify novel treatment targets to block DDR effectively and improve chemosensitivity in ovarian cancer.
Discovery of potent necroptosis inhibitors targeting RIPK1 kinase activity for the treatment of inflammatory disorder and cancer metastasis
Authors: Hou Jue , Ju Jie , Zhang Zili , Zhao Cong , Li Zhanhui , Zheng Jiyue , Sheng Tian , Zhang Hongjian , Hu Linkun , Yu Xiaoliang , Zhang Wei , Li Yangxin , Wu Meng , Ma Haikuo , Zhang Xiaohu , He Sudan 
Published: June 2019

AbstractNecroptosis is a form of regulated necrosis controlled by receptor-interacting kinase 1 (RIPK1 or RIP1), RIPK3 (RIP3), and pseudokinase mixed lineage kinase domain-like protein (MLKL). Increasing evidence suggests that necroptosis is closely associated with pathologies including inflammatory diseases, neurodegenerative diseases, and cancer metastasis. Herein, we discovered the small-molecule PK6 and its derivatives as a novel class of necroptosis inhibitors that directly block the kinase activity of RIPK1. Optimization of PK6 led to PK68, which has improved efficacy for the inhibition of RIPK1-dependent necroptosis, with an EC50of around 14–22 nM in human and mouse cells. PK68 efficiently blocks cellular activation of RIPK1, RIPK3, and MLKL upon necroptosis stimuli. PK68 displays reasonable selectivity for inhibition of RIPK1 kinase activity and favorable pharmacokinetic properties. Importantly, PK68 provides strong protection against TNF-α-induced systemic inflammatory response syndrome in vivo. Moreover, pre-treatment of PK68 significantly represses metastasis of both melanoma cells and lung carcinoma cells in mice. Together, our study demonstrates that PK68 is a potent and selective inhibitor of RIPK1 and also highlights its great potential for use in the treatment of inflammatory disorders and cancer metastasis.
Long non-coding RNA (lncRNA) transcriptional landscape in breast cancer identifies LINC01614 as non-favorable prognostic biomarker regulated by TGFβ and focal adhesion kinase (FAK) signaling
Authors: Vishnubalaji Radhakrishnan , Shaath Hibah , Elkord Eyad , Alajez Nehad M. 
Published: June 2019

AbstractLong non-coding RNAs (lncRNAs) represent a class of epigenetic regulators implicated in a number of physiological and pathological conditions. Herein, we characterized the lncRNA expression portrait from 837 patients with invasive breast cancer and 105 normals from the cancer genome atlas (TCGA), which revealed eighteen upregulated and forty-six downregulated lncRNAs. Clustering analysis revealed distinct lncRNA profile for the triple negative breast cancer (TNBC) and normal breast tissue, while less separation was observed among the HER2+HR+, HER2+HR−, HER2−HR+ molecular subtypes. LINC01614, and LINC01235 correlated with worse disease-free survival (DFS), while the expression of lnc-LRR1–1, lnc-ODF3B-2, AC015712.5, lnc-LAMB3–1, lnc-SPP2–3, and lnc-MAP9–2 correlated with better DFS. The expression of LINC01235 correlated with worse overall survival (OS), while the expression of MIR205HG, lnc-MAP2K6–5, FGF14-AS2, lnc-SPP2–3 correlated with better OS. Highest expression of LINC01614 was observed in progesterone receptor (PR)+, Estrogen receptor (PR)+, and HER2+ tumors, while lowest expression was in TNBC. Concordantly, LINC01614 was highly expressed in the luminalB/HER2+ subtype from the SRP062132 dataset. Elevated expression of LINC01614 was subsequently validated in primary breast cancer tissue and breast cancer cell lines. Bioinformatics and pathway analyses on LINC01614high vs. LINC01614low BC tissue revealed TGFβ1 and ECM as the most activated networks in LINC01614high tumors. Concordantly, strong correlation between the expression of LINC01614 and COL10A1 (R2 = 0.6929), SPOCK1 (R2 = 0.5156), ZEB1 (R2 = 0.3372), TGFBI (R2 = 0.2978), TGFB1 (R2 = 0.1985), ACTA2 (R2 = 0.1833), and TAGLN (R2 = 0.1909) was observed. Mechanistically, exogenous TGFB1 induced LINC01614 expression in the BT474 triple positive BC model, while small-molecule inhibition of transforming growth factor β (TGFβ, SB-431542) or focal adhesion kinase (FAK, PF-573228) abrogated LINC01614 expression. Our data revealed the lncRNA transcription landscape in breast cancer and its molecular subtypes. Our data provide novel insight implicating LINC01614 as unfavorable prognostic marker in BC, its association with the HR+/HER2+ BC molecular subtype and its regulation by TGFβ and FAK signaling.
Update of the EMQN/ACGS best practice guidelines for molecular analysis of Prader-Willi and Angelman syndromes
Authors: Beygo Jasmin , Buiting Karin , Ramsden Simon C. , Ellis Rachael , Clayton-Smith Jill , Kanber Deniz 
Published: June 2019

AbstractThis article is an update of the best practice guidelines for the molecular analysis of Prader-Willi and Angelman syndromes published in 2010 in BMC Medical Genetics [1]. The update takes into account developments in terms of techniques, differential diagnoses and (especially) reporting standards. It highlights the advantages and disadvantages of each method and moreover, is meant to facilitate the interpretation of the obtained results - leading to improved standardised reports.
Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data
Authors: Shungin Dmitry , Haworth Simon , Divaris Kimon , Agler Cary S. , Kamatani Yoichiro , Keun Lee Myoung , Grinde Kelsey , Hindy George , Alaraudanjoki Viivi , Pesonen Paula , Teumer Alexander , Holtfreter Birte , Sakaue Saori , Hirata Jun , Yu Yau-Hua , Ridker Paul M. , Giulianini Franco , Chasman Daniel I. , Magnusson Patrik K. E. , Sudo Takeaki , Okada Yukinori , Völker Uwe , Kocher Thomas , Anttonen Vuokko , Laitala Marja-Liisa , Orho-Melander Marju , Sofer Tamar , Shaffer John R. , Vieira Alexandre , Marazita Mary L. , Kubo Michiaki , Furuichi Yasushi , North Kari E. , Offenbacher Steve , Ingelsson Erik , Franks Paul W. , Timpson Nicholas J. , Johansson Ingegerd 
Published: June 2019

AbstractDental caries and periodontitis account for a vast burden of morbidity and healthcare spending, yet their genetic basis remains largely uncharacterized. Here, we identify self-reported dental disease proxies which have similar underlying genetic contributions to clinical disease measures and then combine these in a genome-wide association study meta-analysis, identifying 47 novel and conditionally-independent risk loci for dental caries. We show that the heritability of dental caries is enriched for conserved genomic regions and partially overlapping with a range of complex traits including smoking, education, personality traits and metabolic measures. Using cardio-metabolic traits as an example in Mendelian randomization analysis, we estimate causal relationships and provide evidence suggesting that the processes contributing to dental caries may have undesirable downstream effects on health.
High sensitivity variable-temperature infrared nanoscopy of conducting oxide interfaces
Authors: Luo Weiwei , Boselli Margherita , Poumirol Jean-Marie , Ardizzone Ivan , Teyssier Jérémie , van der Marel Dirk , Gariglio Stefano , Triscone Jean-Marc , Kuzmenko Alexey B. 
Published: June 2019

AbstractProbing the local transport properties of two-dimensional electron systems (2DES) confined at buried interfaces requires a non-invasive technique with a high spatial resolution operating in a broad temperature range. In this paper, we investigate the scattering-type scanning near field optical microscopy as a tool for studying the conducting LaAlO3/SrTiO3 interface from room temperature down to 6 K. We show that the near-field optical signal, in particular its phase component, is highly sensitive to the transport properties of the electron system present at the interface. Our modeling reveals that such sensitivity originates from the interaction of the AFM tip with coupled plasmon–phonon modes with a small penetration depth. The model allows us to quantitatively correlate changes in the optical signal with the variation of the 2DES transport properties induced by cooling and by electrostatic gating. To probe the spatial resolution of the technique, we image conducting nano-channels written in insulating heterostructures with a voltage-biased tip of an atomic force microscope.
Integrative analysis of genomic and transcriptomic characteristics associated with progression of aggressive thyroid cancer
Authors: Yoo Seong-Keun , Song Young Shin , Lee Eun Kyung , Hwang Jinha , Kim Hwan Hee , Jung Gyeongseo , Kim Young A , Kim Su-jin , Cho Sun Wook , Won Jae-Kyung , Chung Eun-Jae , Shin Jong-Yeon , Lee Kyu Eun , Kim Jong-Il , Park Young Joo , Seo Jeong-Sun 
Published: June 2019

AbstractAnaplastic thyroid cancer (ATC) and advanced differentiated thyroid cancers (DTCs) show fatal outcomes, unlike DTCs. Here, we demonstrate mutational landscape of 27 ATCs and 86 advanced DTCs by massively-parallel DNA sequencing, and transcriptome of 13 ATCs and 12 advanced DTCs were profiled by RNA sequencing.TERT,AKT1,PIK3CA, andEIF1AXwere frequently co-mutated with driver genes (BRAFV600EandRAS) in advanced DTCs as well as ATC, but tumor suppressors (e.g.,TP53andCDKN2A) were predominantly altered in ATC.CDKN2Aloss was significantly associated with poor disease-specific survival in patients with ATC or advanced DTCs, and up-regulation ofCD274(PD-L1) andPDCD1LG2(PD-L2). Transcriptome analysis revealed a fourth molecular subtype of thyroid cancer (TC), ATC-like, which hardly reflects the molecular signatures in DTC. Furthermore, the activation of JAK-STAT signaling pathway could be a potential druggable target inRAS-positive ATC. Our findings provide insights for precision medicine in patients with advanced TCs.
A bed nucleus of stria terminalis microcircuit regulating inflammation-associated modulation of feeding
Authors: Wang Yong , Kim JungMin , Schmit Matthew B. , Cho Tiffany S. , Fang Caohui , Cai Haijiang 
Published: June 2019

AbstractLoss of appetite or anorexia associated with inflammation impairs quality of life and increases morbidity in many diseases. However, the exact neural mechanism that mediates inflammation-associated anorexia is still poorly understood. Here we identified a population of neurons, marked by the expression of protein kinase C-delta, in the oval region of the bed nucleus of the stria terminalis (BNST), which are activated by various inflammatory signals. Silencing of these neurons attenuates the anorexia caused by these inflammatory signals. Our results demonstrate that these neurons mediate bidirectional control of general feeding behaviors. These neurons inhibit the lateral hypothalamus-projecting neurons in the ventrolateral part of BNST to regulate feeding, receive inputs from the canonical feeding regions of arcuate nucleus and parabrachial nucleus. Our data therefore define a BNST microcircuit that might coordinate canonical feeding centers to regulate food intake, which could offer therapeutic targets for feeding-related diseases such as anorexia and obesity.
Change in Spatial Distribution Patterns and Regeneration of Populus euphratica under Different Surface Soil Salinity Conditions
Authors: Zhang Pei , Deng Xiaoya , Long Aihua , Xu Hailiang , Ye Mao , Li Junfeng 
Published: June 2019

AbstractEcological conservation and restoration have increasingly captured attention worldwide due to the degradation of ecosystems. As one of the most ecologically fragile areas, the Tarim River Basin, of Xinjiang, China, encountered serious decline of desert riparian forests. The Chinese government has implemented the “Ecological Water Conveyance Project” (EWCP) since 2000, protecting and restoring the dominant natural species of the desert riparian forests, i.e., Populus euphratica Oliv. The regenerative effect after the water conveyance was noteworthy. For the purpose of clarifying the mechanism of P. euphratica forest regeneration to find a better prescription for the ecological restoration works in the Tarim River Basin, we investigated the relationship between the distribution of P. euphratica and soil salinity. Experimentally evaluated the effects of surface soil salinity on P. euphratica seed germination and the influence of river flooding on the salinity of surface soils. The results showed that (1) P. euphratica trees mainly spread along the river channel within 2 km; with increasing vertical distance to the channel, the number of trees declined significantly; (2) where the salinity of the surface soil is high, there are less living P. euphratica trees; (3) the germination of P. euphratica seeds decreases with increased soil conductivity; when the soil conductivity was higher than 7 ms/cm, the germination of P. euphratica seeds was severely curtailed. (4) Flooding regimes were a pre-condition of P. euphratica restoration; they had profound effects on improving the germination of the seeds via ameliorating water conditions and reducing salinity. Our results point out that the most efficient ecological prescription for restoring and protecting desert riparian forests is to induce flooding twice yearly during June to August with 10- to 15-day durations each time. Such a plan (especially in the Tarim River Basin) should prioritize the protection of seedlings.
Identifying pre-disease signals before metabolic syndrome in mice by dynamical network biomarkers
Authors: Koizumi Keiichi , Oku Makito , Hayashi Shusaku , Inujima Akiko , Shibahara Naotoshi , Chen Luonan , Igarashi Yoshiko , Tobe Kazuyuki , Saito Shigeru , Kadowaki Makoto , Aihara Kazuyuki 
Published: June 2019

AbstractThe establishment of new therapeutic strategies for metabolic syndrome is urgently needed because metabolic syndrome, which is characterized by several disorders, such as hypertension, increases the risk of lifestyle-related diseases. One approach is to focus on the pre-disease state, a state with high susceptibility before the disease onset, which is considered as the best period for preventive treatment. In order to detect the pre-disease state, we recently proposed mathematical theory called the dynamical network biomarker (DNB) theory based on the critical transition paradigm. Here, we investigated time-course gene expression profiles of a mouse model of metabolic syndrome using 64 whole-genome microarrays based on the DNB theory, and showed the detection of a pre-disease state before metabolic syndrome defined by characteristic behavior of 147 DNB genes. The results of our study demonstrating the existence of a notable pre-disease state before metabolic syndrome may help to design novel and effective therapeutic strategies for preventing metabolic syndrome, enabling just-in-time preemptive interventions.
gH625-liposomes as tool for pituitary adenylate cyclase-activating polypeptide brain delivery
Authors: Iachetta Giuseppina , Falanga Annarita , Molino Yves , Masse Maxime , Jabès Francoise , Mechioukhi Yasmine , Laforgia Vincenza , Khrestchatisky Michel , Galdiero Stefania , Valiante Salvatore 
Published: June 2019

AbstractThe blood-brain barrier (BBB) regulates the traffic of molecules into the central nervous system (CNS) and also limits the drug delivery. Due to their flexible properties, liposomes are an attractive tool to deliver drugs across the BBB. We previously characterized gH625, a peptide derived from Herpes simplex virus 1. The present study investigates the efficiency of liposomes functionalized on their surface with gH625 to promote the brain uptake of neuroprotective peptide PACAP (pituitary adenylate cyclase-activating polypeptide). Using a rat in vitro BBB model, we showed that the liposomes preparations were non-toxic for the endothelial cells, as assessed by analysis of tight junction protein ZO1 organization and barrier integrity. Next, we found that gH625 improves the transfer of liposomes across endothelial cell monolayers, resulting in both low cellular uptake and increased transport of PACAP. Finally, in vivo results demonstrated that gH625 ameliorates the efficiency of liposomes to deliver PACAP to the mouse brain after intravenous administration. gH625-liposomes improve both PACAP reaching and crossing the BBB, as showed by the higher number of brain cells labelled with PACAP. gH625-liposomes represent a promising strategy to deliver therapeutic agents to CNS and to provide an effective imaging and diagnostic tool for the brain.
Optical logic operation via plasmon-exciton interconversion in 2D semiconductors
Authors: Kim Jung Ho , Lee Jubok , Kim Hyun , Yun Seok Joon , Kim Jeongyong , Lee Hyun Seok , Lee Young Hee 
Published: June 2019

AbstractNanophotonic devices manipulating light for high-speed computing are a counterpart of speed-limited electronic circuits. Although plasmonic circuits are a promising platform for subwavelength miniaturization, the logic-operation principle is still limited to mimicking those of photonic waveguides using phase shifts, polarization, interference, and resonance. Meanwhile, reconfigurable interconversion between exciton and plasmon engender emerging applications like exciton transistors and multiplexers, exciton amplifiers, chiral valleytronics, and nonlinear excitonics. Here, we propose optical logic principles realized by exciton-plasmon interconversion in Ag-nanowires (NW) overlapped on transition metal dichalcogenides (TMDs) monolayers. Excitons generated from TMDs couple to the Ag-NW plasmons, eventually collected as output signals at the Ag-NW end. Using two lasers, we demonstrate AND gate by modulating single excitons in Ag-NW on MoS2 and a half-adder by modulating dual excitons in lateral WSe2 and WS2. Moreover, a 4-to-2 binary encoder is realized in partially overlapped MoSe2 and MoS2 using four-terminal laser inputs. Our results represent great advances in communication processing for optical photonics integrable with subwavelength architectures.
A comparison of a novel endoscopic “Su-Wang technique” with the open “Jaboulay’s procedure” for the surgical treatment of adult primary vaginal hydrocele
Authors: Lei Junhao , Luo Chunhua , Zhang Yangyang , Guo Yuming , Su Xinjun , Wang Xinghuan 
Published: June 2019

AbstractThis paper was aimed to introduce and compare outcomes of a novel “Su-Wang (S-W) technique” for endoscopic treatment of adult hydrocele with conventional open hydrocelectomy with “Jaboulay’s (JA) procedure” regarding adverse events (AEs) and patient satisfaction. In the randomized controlled trial, adult males with primary hydroceles were prospectively assigned into S-W or JA group. We recorded perioperative data and postoperative AEs (incision length, recurrence, hematoma, wound infection and edema vanished time). Finally, a total of 42 adult patients underwent the S-W (n = 22) or JA (n = 20) procedure. Procedures were successfully completed for all 42 patients. No significant differences were found between the two groups regarding age, symptom duration, body mass index, and size of the hydrocele. The incision length was significantly shorter in the S-W group (1.00 ± 0.24 cm) than in the JA group (6.10 ± 1.46 cm). After 6 months’ follow-up, complete data of 90.5% (38/42) were obtained. Severe AEs did not occur in any patient. Recurrence, hematoma, wound infection, edema vanished time values, and satisfaction in the S-W group were superior to those in the JA group. All patients in the S-W group were satisfied with this novel procedure, particularly due to the minimally invasive incision. In conclusion, the novel “S-W technique” for hydrocelectomy provided satisfactory cosmetic results with a 1-cm scrotal incision only. With the near-complete excision of the parietal TV, it resulted in no recurrence, fewer AEs, and rapid postoperative rehabilitation in comparison to the traditional “JA procedure.” The endoscopic “S-W technique” may be a viable alternative for the surgical treatment of adult primary vaginal hydrocele.
Functional Roles of Metabolic Intermediates in Regulating the Human Mitochondrial NAD(P)+-Dependent Malic Enzyme
Authors: Hsieh Ju-Yi , Shih Wan-Ting , Kuo Yu-Hsuan , Liu Guang-Yaw , Hung Hui-Chih 
Published: June 2019

AbstractHuman mitochondrial NAD(P)+-dependent malic enzyme (m-NAD(P)-ME) has a dimer of dimers quaternary structure with two independent allosteric sites in each monomer. Here, we reveal the different effects of nucleotide ligands on the quaternary structure regulation and functional role of the human m-NAD(P)-ME exosite. In this study, size distribution analysis was utilized to investigate the monomer-dimer-tetramer equilibrium of m-NAD(P)-ME in the presence of different ligands, and the monomer-dimer (Kd,12) and dimer-tetramer (Kd,24) dissociation constants were determined with these ligands. With NAD+, the enzyme formed more tetramers, and its Kd,24 (0.06 µM) was 6-fold lower than the apoenzyme Kd,24 (0.34 µM). When ATP was present, the enzyme displayed more dimers, and its Kd,24 (2.74 µM) was 8-fold higher than the apoenzyme. Similar to the apoenzyme, the ADP-bound enzyme was present as a tetramer with a small amount of dimers and monomers. These results indicate that NAD+ promotes association of the dimeric enzyme into tetramers, whereas ATP stimulates dissociation of the tetrameric enzyme into dimers, and ADP has little effect on the tetrameric stability of the enzyme. A series of exosite mutants were created using site-directed mutagenesis. Size distribution analysis and kinetic studies of these mutants with NAD+ or ATP indicated that Arg197, Asn482 and Arg556 are essential for the ATP binding and ATP-induced dissociation of human m-NAD(P)-ME. In summary, the present results demonstrate that nucleotides perform discrete functions regulating the quaternary structure and catalysis of m-NAD(P)-ME. Such regulation by the binding of different nucleotides may be critically associated with the physiological concentrations of these ligands.