bluuebunny/crossref_metadata_2025_split huggingface dataset:
BET bromodomain inhibitors synergize with ATR inhibitors in melanoma
Authors: Muralidharan Somsundar Veppil , Einarsdottir Berglind Osk , Bhadury Joydeep , Lindberg Mattias F , Wu Jin , Campeau Eric , Bagge Roger Olofsson , Stierner Ulrika , Ny Lars , Nilsson Lisa M , Nilsson Jonas A 
Published: August 2017

AbstractMetastatic malignant melanoma continues to be a challenging disease despite clinical translation of the comprehensive understanding of driver mutations and how melanoma cells evade immune attack. In Myc-driven lymphoma, efficacy of epigenetic inhibitors of the bromodomain and extra-terminal domain (BET) family of bromodomain proteins can be enhanced by combination therapy with inhibitors of the DNA damage response kinase ATR. Whether this combination is active in solid malignancies like melanoma, and how it relates to immune therapy, has not previously investigated. To test efficacy and molecular consequences of combination therapies cultured melanoma cells were used. To assess tumor responses to therapies in vivo we use patient-derived xenografts and B6 mice transplanted with B16F10 melanoma cells. Concomitant inhibition of BET proteins and ATR of cultured melanoma cells resulted in similar effects as recently shown in lymphoma, such as induction of apoptosis and p62, implicated in autophagy, senescence-associated secretory pathway and ER stress. In vivo, apoptosis and suppression of subcutaneous growth of patient-derived melanoma and B16F10 cells were observed. Our data suggest that ATRI/BETI combination therapies are effective in melanoma.
Sunitinib induces genomic instability of renal carcinoma cells through affecting the interaction of LC3-II and PARP-1
Authors: Yan Siyuan , Liu Ling , Ren Fengxia , Gao Quan , Xu Shanshan , Hou Bolin , Wang Yange , Jiang Xuejun , Che Yongsheng 
Published: August 2017

AbstractDeficiency of autophagy has been linked to increase in nuclear instability, but the role of autophagy in regulating the formation and elimination of micronuclei, a diagnostic marker for genomic instability, is limited in mammalian cells. Utilizing immunostaining and subcellular fractionation, we found that either LC3-II or the phosphorylated Ulk1 localized in nuclei, and immunoprecipitation results showed that both LC3 and Unc-51-like kinase 1 (Ulk1) interacted with γ-H2AX, a marker for the DNA double-strand breaks (DSB). Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, was found to enhance the autophagic flux concurring with increase in the frequency of micronuclei accrued upon inhibition of autophagy, and similar results were also obtained in the rasfonin-treated cells. Moreover, the punctate LC3 staining colocalized with micronuclei. Unexpectedly, deprivation of SQSTM1/p62 alone accumulated micronuclei, which was not further increased upon challenge with ST. Rad51 is a protein central to repairing DSB by homologous recombination and treatment with ST or rasfonin decreased its expression. In several cell lines, p62 appeared in the immunoprecipites of Rad51, whereas LC3, Ulk1 and p62 interacted with PARP-1, another protein involved in DNA repair and genomic stability. In addition, knockdown of either Rad51 or PARP-1 completely inhibited the ST-induced autophagic flux. Taken together, the data presented here demonstrated that both LC3-II and the phosphorylated Ulk1 localized in nuclei and interacted with the proteins essential for nuclear stability, thereby revealing a more intimate relationship between autophagy and genomic stability.
RETRACTED ARTICLE: Dioscin induces prostate cancer cell apoptosis through activation of estrogen receptor-β
Authors: Tao Xufeng , Xu Lina , Yin Lianhong , Han Xu , Qi Yan , Xu Youwei , Song Shasha , Zhao Yanyan , Peng Jinyong 
Published: August 2017

AbstractRecent researches have shown that estrogen receptor-β (ERβ) activator may be a potent anticancer agent for prostate cancer (PCa), and our previous study also indicated that dioscin can upregulate the expression of ERβ in MC3T3-E1 cell. In the present work, the activity and mechanism of dioscin, a natural product, against PCa were investigated. The results showed that dioscin markedly inhibited cell viability, colony formation, motility and induced apoptosis in PC3 cells. Moreover, dioscin disrupted the formation of PC3 cell-derived mammospheres and reduced aldehyde dehydrogenase (ALDH) level and the CD133+/CD44+ cells, indicating that dioscin had a potent inhibitory activity on prostate cancer stem cells (PCSCs). In vivo results also showed that dioscin significantly suppressed the tumor growth of PC3 cell xenografts in nude mice. Furthermore, mechanism investigation showed that dioscin markedly upregulated ERβ expression level, subsequently increased prolyl hydroxylase 2 level, decreased the levels of hypoxia-inducible factor-1α, vascular endothelial growth factor A and BMI-1, and thus induced cell apoptosis by regulating the expression levels of caspase-3 and Bcl-2 family proteins. In addition, transfection experiment of ERβ-siRNA further indicated that diosicn showed excellent activity against PCa in vitro and in vivo by increasing ERβ expression level. The co-immunoprecipitation (Co-IP) results further suggested that dioscin promoted the interaction of c-ABL and ERβ, but did not change c-ABL expression. Moreover, the molecular docking assay showed that dioscin processed powerful affinity toward to ERβ mainly through the strong hydrogen bonding and hydrophobic effects, and the actions of dioscin on ERβ activation and tumor cells inhibition were significantly weakened in the mutational (Phe-336, Phe-468) PC3 cells. Collectively, these findings proved that dioscin exerted efficient anti-PCa activity via activation of ERβ, which should be developed as an efficient candidate in clinical for treating this cancer in the future.
CD206+ M2-like macrophages regulate systemic glucose metabolism by inhibiting proliferation of adipocyte progenitors
Authors: Nawaz Allah , Aminuddin Aminuddin , Kado Tomonobu , Takikawa Akiko , Yamamoto Seiji , Tsuneyama Koichi , Igarashi Yoshiko , Ikutani Masashi , Nishida Yasuhiro , Nagai Yoshinori , Takatsu Kiyoshi , Imura Johji , Sasahara Masakiyo , Okazaki Yukiko , Ueki Kohjiro , Okamura Tadashi , Tokuyama Kumpei , Ando Akira , Matsumoto Michihiro , Mori Hisashi , Nakagawa Takashi , Kobayashi Norihiko , Saeki Kumiko , Usui Isao , Fujisaka Shiho , Tobe Kazuyuki 
Published: August 2017

AbstractAdipose tissue resident macrophages have important roles in the maintenance of tissue homeostasis and regulate insulin sensitivity for example by secreting pro-inflammatory or anti-inflammatory cytokines. Here, we show that M2-like macrophages in adipose tissue regulate systemic glucose homeostasis by inhibiting adipocyte progenitor proliferation via the CD206/TGFβ signaling pathway. We show that adipose tissue CD206+ cells are primarily M2-like macrophages, and ablation of CD206+ M2-like macrophages improves systemic insulin sensitivity, which was associated with an increased number of smaller adipocytes. Mice genetically engineered to have reduced numbers of CD206+ M2-like macrophages show a down-regulation of TGFβ signaling in adipose tissue, together with up-regulated proliferation and differentiation of adipocyte progenitors. Our findings indicate that CD206+ M2-like macrophages in adipose tissues create a microenvironment that inhibits growth and differentiation of adipocyte progenitors and, thereby, control adiposity and systemic insulin sensitivity.
Sequential conformational transitions and α-helical supercoiling regulate a sensor histidine kinase
Authors: Berntsson Oskar , Diensthuber Ralph P. , Panman Matthijs R. , Björling Alexander , Gustavsson Emil , Hoernke Maria , Hughes Ashley J. , Henry Léocadie , Niebling Stephan , Takala Heikki , Ihalainen Janne A. , Newby Gemma , Kerruth Silke , Heberle Joachim , Liebi Marianne , Menzel Andreas , Henning Robert , Kosheleva Irina , Möglich Andreas , Westenhoff Sebastian 
Published: August 2017

AbstractSensor histidine kinases are central to sensing in bacteria and in plants. They usually contain sensor, linker, and kinase modules and the structure of many of these components is known. However, it is unclear how the kinase module is structurally regulated. Here, we use nano- to millisecond time-resolved X-ray scattering to visualize the solution structural changes that occur when the light-sensitive model histidine kinase YF1 is activated by blue light. We find that the coiled coil linker and the attached histidine kinase domains undergo a left handed rotation within microseconds. In a much slower second step, the kinase domains rearrange internally. This structural mechanism presents a template for signal transduction in sensor histidine kinases.
Atg4 proteolytic activity can be inhibited by Atg1 phosphorylation
Authors: Sánchez-Wandelmer Jana , Kriegenburg Franziska , Rohringer Sabrina , Schuschnig Martina , Gómez-Sánchez Rubén , Zens Bettina , Abreu Susana , Hardenberg Ralph , Hollenstein David , Gao Jieqiong , Ungermann Christian , Martens Sascha , Kraft Claudine , Reggiori Fulvio 
Published: August 2017

AbstractThe biogenesis of autophagosomes depends on the conjugation of Atg8-like proteins with phosphatidylethanolamine. Atg8 processing by the cysteine protease Atg4 is required for its covalent linkage to phosphatidylethanolamine, but it is also necessary for Atg8 deconjugation from this lipid to release it from membranes. How these two cleavage steps are coordinated is unknown. Here we show that phosphorylation by Atg1 inhibits Atg4 function, an event that appears to exclusively occur at the site of autophagosome biogenesis. These results are consistent with a model where the Atg8-phosphatidylethanolamine pool essential for autophagosome formation is protected at least in part by Atg4 phosphorylation by Atg1 while newly synthesized cytoplasmic Atg8 remains susceptible to constitutive Atg4 processing.
The non-coding RNA BC1 regulates experience-dependent structural plasticity and learning
Authors: Briz Victor , Restivo Leonardo , Pasciuto Emanuela , Juczewski Konrad , Mercaldo Valentina , Lo Adrian C. , Baatsen Pieter , Gounko Natalia V. , Borreca Antonella , Girardi Tiziana , Luca Rossella , Nys Julie , Poorthuis Rogier B. , Mansvelder Huibert D. , Fisone Gilberto , Ammassari-Teule Martine , Arckens Lutgarde , Krieger Patrik , Meredith Rhiannon , Bagni Claudia 
Published: August 2017

AbstractThe brain cytoplasmic (BC1) RNA is a non-coding RNA (ncRNA) involved in neuronal translational control. Absence of BC1 is associated with altered glutamatergic transmission and maladaptive behavior. Here, we show that pyramidal neurons in the barrel cortex of BC1 knock out (KO) mice display larger excitatory postsynaptic currents and increased spontaneous activity in vivo. Furthermore, BC1 KO mice have enlarged spine heads and postsynaptic densities and increased synaptic levels of glutamate receptors and PSD-95. Of note, BC1 KO mice show aberrant structural plasticity in response to whisker deprivation, impaired texture novel object recognition and altered social behavior. Thus, our study highlights a role for BC1 RNA in experience-dependent plasticity and learning in the mammalian adult neocortex, and provides insight into the function of brain ncRNAs regulating synaptic transmission, plasticity and behavior, with potential relevance in the context of intellectual disabilities and psychiatric disorders.
Acoustically actuated ultra-compact NEMS magnetoelectric antennas
Authors: Nan Tianxiang , Lin Hwaider , Gao Yuan , Matyushov Alexei , Yu Guoliang , Chen Huaihao , Sun Neville , Wei Shengjun , Wang Zhiguang , Li Menghui , Wang Xinjun , Belkessam Amine , Guo Rongdi , Chen Brian , Zhou James , Qian Zhenyun , Hui Yu , Rinaldi Matteo , McConney Michael E. , Howe Brandon M. , Hu Zhongqiang , Jones John G. , Brown Gail J. , Sun Nian Xiang 
Published: August 2017

AbstractState-of-the-art compact antennas rely on electromagnetic wave resonance, which leads to antenna sizes that are comparable to the electromagnetic wavelength. As a result, antennas typically have a size greater than one-tenth of the wavelength, and further miniaturization of antennas has been an open challenge for decades. Here we report on acoustically actuated nanomechanical magnetoelectric (ME) antennas with a suspended ferromagnetic/piezoelectric thin-film heterostructure. These ME antennas receive and transmit electromagnetic waves through the ME effect at their acoustic resonance frequencies. The bulk acoustic waves in ME antennas stimulate magnetization oscillations of the ferromagnetic thin film, which results in the radiation of electromagnetic waves. Vice versa, these antennas sense the magnetic fields of electromagnetic waves, giving a piezoelectric voltage output. The ME antennas (with sizes as small as one-thousandth of a wavelength) demonstrates 1–2 orders of magnitude miniaturization over state-of-the-art compact antennas without performance degradation. These ME antennas have potential implications for portable wireless communication systems.
Differential oxidation of protein-tyrosine phosphatases during zebrafish caudal fin regeneration
Authors: Wu Wei , Hale Alexander James , Lemeer Simone , den Hertog Jeroen 
Published: August 2017

AbstractZebrafish have the capacity to regenerate lost tissues and organs. Amputation of the caudal fin results in a rapid, transient increase in H2O2 levels emanating from the wound margin, which is essential for regeneration, because quenching of reactive oxygen species blocks regeneration. Protein-tyrosine phosphatases (PTPs) have a central role in cell signalling and are susceptible to oxidation, which results in transient inactivation of their catalytic activity. We hypothesized that PTPs may become oxidized in response to amputation of the caudal fin. Using the oxidized PTP-specific (ox-PTP) antibody and liquid chromatography-mass spectrometry, we identified 33 PTPs in adult zebrafish fin clips of the total of 44 PTPs that can theoretically be detected based on sequence conservation. Of these 33 PTPs, 8 were significantly more oxidized 40 min after caudal fin amputation. Surprisingly, Shp2, one of the PTPs that were oxidized in response to caudal fin amputation, was required for caudal fin regeneration. In contrast, Rptpα, which was not oxidized upon amputation, was dispensable for caudal fin regeneration. Our results demonstrate that PTPs are differentially oxidized in response to caudal fin amputation and that there is a differential requirement for PTPs in regeneration.
Baicalein prevents 6-OHDA/ascorbic acid-induced calcium-dependent dopaminergic neuronal cell death
Authors: Wang Sheng-Fang , Liu Liang-Feng , Wu Ming-Yue , Cai Cui-Zan , Su Huanxing , Tan Jieqiong , Lu Jia-Hong , Li Min 
Published: August 2017

Abstract6-OHDA plus ascorbic acid (AA) has long been used to induce Parkinson’s disease in rodents, while only 6-OHDA is commonly used to induce cell damage in cellular PD models. AA was believed to act as an anti-oxidant to prevent the degradation of 6-OHDA; however, some studies suggested that AA dramatically enhanced the selectivity and toxicity of 6-OHDA. To understand the mechanisms by which 6-OHDA/AA induces cell death, we established a 6-OHDA/AA cell toxicity model in human dopaminergic neuroblastoma SH-SY5Y cells. We confirmed that the toxicity of 6-OHDA was dramatically increased in the presence of AA, and the toxicity can be prevented by a flavonoid, baicalein. Mechanistically, our research reveals that 6-OHDA/AA induces cell death mainly through the interruption of intracellular calcium homeostasis, which leads to calpain activation and mitochondrial damage. Baicalein prevents 6-OHDA/AA-induced intracellular calcium elevation as well as consequent mitochondria damage. Taken together, our study confirms that 6-OHDA/AA is a more sensitive model for inducing neuronal lesion in vitro and reveals the central role of intracellular calcium in 6-OHDA/AA-induced cell death. Our studies further show that baicalein prevents 6-OHDA/AA-induced cell death by inhibiting intracellular calcium elevation.
Juxtacrine Activity of Estrogen Receptor α in Uterine Stromal Cells is Necessary for Estrogen-Induced Epithelial Cell Proliferation
Authors: Winuthayanon Wipawee , Lierz Sydney L. , Delarosa Karena C. , Sampels Skylar R. , Donoghue Lauren J. , Hewitt Sylvia C. , Korach Kenneth S. 
Published: August 2017

AbstractAberrant regulation of uterine cell growth can lead to endometrial cancer and infertility. To understand the molecular mechanisms of estrogen-induced uterine cell growth, we removed the estrogen receptor α (Esr1) from mouse uterine stromal cells, where the embryo is implanted during pregnancy. Without ESR1 in neighboring stroma cells, epithelial cells that line the inside of the uterus are unable to grow due to a lack of growth factors secreted from adjacent stromal cells. Moreover, loss of stromal ESR1 caused mice to deliver fewer pups due in part due to inability of some embryos to implant in the uterus, indicating that stromal ESR1 is crucial for uterine cell growth and pregnancy.
Characterization of a novel class A carbapenemase PAD-1 from Paramesorhizobium desertii A-3-ET, a strain highly resistant to β-lactam antibiotics
Authors: Lv Ruichen , Guo Jingyu , Yan YanFeng , Chen Rong , Xiao Lisheng , Wang Min , Fang Nan , Fang Chengxiang , Cui Yujun , Yang Ruifu , Song Yajun 
Published: August 2017

AbstractAlthough clinical antibiotic-resistant bacteria have attracted tremendous attention in the microbiology community, the resistant bacteria that persist in natural environments have been overlooked for a longtime. We previously proposed a new species Paramesorhizobium desertii, isolated from the soil of the Taklimakan Desert in China that is highly resistant to most β-lactam antibiotics. To identify potential β-lactamase(s) in this bacteria, we first confirmed the carbapenemase activity in the freeze–thawed supernatant of a P. desertii A-3-ET culture using the modified Hodge assay. We then identified a novel chromosome-encoded carbapenemase (PAD-1) in strain A-3-ET, using a shotgun proteomic analysis of the supernatant and genomic information. The bioinformatics analysis indicated that PAD-1 is a class A carbapenemase. Subsequent enzyme kinetic assays with purified PAD-1 confirmed its carbapenemase activity, which is similar to that of clinically significant class A carbapenemases, including BKC-1 and KPC-2. Because the location in which A-3-ET was isolated is not affected by human activity, PAD-1 is unlikely to be associated with the selection pressures exerted by modern antibiotics. This study confirmed the diversity of antibiotic-resistant determinants in the environmental resistome.
Prevalence of smoking in patients with bipolar disorder, major depressive disorder and schizophrenia and their relationships with quality of life
Authors: Li Xiao-Hong , An Feng-Rong , Ungvari Gabor S. , Ng Chee H. , Chiu Helen F. K. , Wu Ping-Ping , Jin Xin , Xiang Yu-Tao 
Published: August 2017

AbstractFew studies have compared the prevalence of smoking between patients with bipolar disorder, major depressive disorder (MDD) and schizophrenia. This study examined the prevalence of smoking and its relationships with demographic and clinical characteristics, and quality of life (QOL) in patients with these psychiatric disorders. A total of 1,102 inpatients were consecutively screened. Psychopathology and QOL were measured with standardized instruments. The prevalence of current smoking in the whole sample was 16.7%; 17.5% in bipolar disorder, 10.6% in MDD and 18.5% in schizophrenia. The rates of smoking in bipolar disorder (p = 0.004, OR = 2.5, 95%CI: 1.3–4.7) and schizophrenia (p = 0.03, OR = 2.0, 95%CI: 1.06–3.8) were significantly higher than in MDD, while no difference was found between bipolar disorder and schizophrenia. Smokers had a higher mental QOL than non-smokers (p = 0.007) in MDD, but no difference was found in the other two groups. Male gender, living alone, higher personal income, older age of onset, health insurance coverage, and first episode was significantly associated with smoking in one or more diagnostic groups. Smoking appears more common in bipolar disorder and schizophrenia than in MDD in China. The figures in all disorders were lower than that reported in most of other countries.
Neuroprosthetic-enabled control of graded arm muscle contraction in a paralyzed human
Authors: Friedenberg David A. , Schwemmer Michael A. , Landgraf Andrew J. , Annetta Nicholas V. , Bockbrader Marcia A. , Bouton Chad E. , Zhang Mingming , Rezai Ali R. , Mysiw W. Jerry , Bresler Herbert S. , Sharma Gaurav 
Published: August 2017

AbstractNeuroprosthetics that combine a brain computer interface (BCI) with functional electrical stimulation (FES) can restore voluntary control of a patients’ own paralyzed limbs. To date, human studies have demonstrated an “all-or-none” type of control for a fixed number of pre-determined states, like hand-open and hand-closed. To be practical for everyday use, a BCI-FES system should enable smooth control of limb movements through a continuum of states and generate situationally appropriate, graded muscle contractions. Crucially, this functionality will allow users of BCI-FES neuroprosthetics to manipulate objects of different sizes and weights without dropping or crushing them. In this study, we present the first evidence that using a BCI-FES system, a human with tetraplegia can regain volitional, graded control of muscle contraction in his paralyzed limb. In addition, we show the critical ability of the system to generalize beyond training states and accurately generate wrist flexion states that are intermediate to training levels. These innovations provide the groundwork for enabling enhanced and more natural fine motor control of paralyzed limbs by BCI-FES neuroprosthetics.
Association between LRP1 C766T polymorphism and Alzheimer’s disease susceptibility: a meta-analysis
Authors: Wang Yun , Liu Shengyuan , Wang Jingjing , Zhang Jie , Hua Yaqiong , Li Hua , Tan Huibiao , Kuai Bin , Wang Biao , Sheng Sitong 
Published: August 2017

AbstractLow density lipoprotein receptor-related protein 1 (LRP1) C766T polymorphism (rs1799986) has been extensively investigated for Alzheimer’s disease (AD) susceptibility. However, results in different studies have been contradictory. Therefore, we conducted a meta-analysis containing 6455 AD cases and 6304 controls from 26 independent case–control studies to determine whether there was an association between the LRP1 C766T polymorphism and AD susceptibility. The combined analysis showed that there was no significant association between LRP1 C766T polymorphism and AD susceptibility (TT + CT versus CC: OR = 0.920, 95% CI = 0.817–1.037,P = 0.172). In subgroup analysis, significant decreased AD susceptibility was found among Asian population in allele model (T versus C: OR = 0.786, 95% CI = 0.635–0.974,P = 0.028) and dominant model (TT + CT versus CC: OR = 0.800, 95% CI = 0.647–0.990,P = 0.040). Moreover, T allele of LRP1 C766T was statistically associated with late onset of AD (LOAD) (T versus C: OR = 0.858, 95% CI = 0.748–0.985,P = 0.029; TT + CT versus CC: OR = 0.871, 95% CI = 0.763–0.994,P = 0.040). In conclusion, our meta-analysis suggested that LRP1 C766T polymorphism was associated with lower risk of AD in Asian, and could reduce LOAD risk especially. Considering some limitations of our meta-analysis, further large-scale studies should be done to reach a more comprehensive understanding.