bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sall2 is required for proapoptotic Noxa expression and genotoxic stress-induced apoptosis by doxorubicin
Authors: Escobar D , Hepp M I , Farkas C , Campos T , Sodir N M , Morales M , Álvarez C I , Swigart L , Evan G I , Gutiérrez J L , Nishinakamura R , Castro A F , Pincheira R 
Published: July 2015

AbstractThe Sall2 transcription factor is deregulated in several cancers; however, little is known about its cellular functions, including its target genes. Recently, we demonstrated that p53 directly regulates Sall2 expression under genotoxic stress. Here, we investigated the role of Sall2 in the context of cellular response to genotoxic stress. In addition, we further examined the Sall2-p53 relationship during genotoxic stress in primary mouse embryo fibroblasts (MEFs), which are derived fromSall2knockout mice separately, or in combination with thep53ERTAMknock-in mice. We found that the levels of Sall2 mRNA and protein are dynamically modulated in response to doxorubicin. At early times of stress, Sall2 is downregulated, but increases under extension of the stress in a p53-independent manner. Based on caspase-3/7 activities, expression of cleaved poly (ADP-ribose) polymerase, expression of cleaved caspase-3 and induction of proapoptotic proteins, Sall2 expression was correlated with cellular apoptosis. Consequently,Sall2−/−MEFs have decreased apoptosis, which relates with increased cell viability in response to doxorubicin. Importantly, Sall2 was required for apoptosis even in the presence of fully activated p53. Searching for putative Sall2 targets that could mediate its role in apoptosis, we identified proapoptoticNOXA/PMAIP1(phorbol-12-myristate-13-acetate-induced protein 1). We demonstrated that Sall2 positively regulatesNoxapromoter activity. Conserved putative Sall2-binding sites at theNOXApromoter were validatedin vitroby electrophoretic mobility shift assay andin vivoby ChIP experiments, identifyingNOXAas a novel Sall2 target. In agreement, induction of Noxa protein and mRNA in response to doxorubicin was significantly decreased inSall2−/−MEFs. In addition, studies in leukemia Jurkat T cells support the existence of the Sall2/Noxa axis, and the significance of this axis on the apoptotic response to doxorubicin in cancer cells. Our study highlights the relevance of Sall2 in the apoptotic response to extended genotoxic stress, which is important for understanding its role in normal physiology and disease.
Targeting Mdmx to treat breast cancers with wild-type p53
Authors: Haupt S , Buckley D , Pang J-MB , Panimaya J , Paul P J , Gamell C , Takano E A , Ying Lee Y , Hiddingh S , Rogers T-M , Teunisse A F A S , Herold M J , Marine J-C , Fox S B , Jochemsen A , Haupt Y 
Published: July 2015

AbstractThe function of the tumor suppressor p53 is universally compromised in cancers. It is the most frequently mutated gene in human cancers (reviewed). In cases where p53 is not mutated, alternative regulatory pathways inactivate its tumor suppressive functions. This is primarily achieved through elevation in the expression of the key inhibitors of p53: Mdm2 or Mdmx (also called Mdm4) (reviewed). In breast cancer (BrCa), the frequency of p53 mutations varies markedly between the different subtypes, with basal-like BrCas bearing a high frequency of p53 mutations, whereas luminal BrCas generally express wild-type (wt) p53. Here we show that Mdmx is unexpectedly highly expressed in normal breast epithelial cells and its expression is further elevated in most luminal BrCas, whereas p53 expression is generally low, consistent with wt p53 status. Inducible knockdown (KD) of Mdmx in luminal BrCa MCF-7 cells impedes the growth of these cells in culture, in a p53-dependent manner. Importantly, KD of Mdmx in orthotopic xenograft transplants resulted in growth inhibition associated with prolonged survival, both in a preventative model and also in a treatment model. Growth impediment in response to Mdmx KD was associated with cellular senescence. The growth inhibitory capacity of Mdmx KD was recapitulated in an additional luminal BrCa cell line MPE600, which expresses wt p53. Further, the growth inhibitory capacity of Mdmx KD was also demonstrated in the wt p53 basal-like cell line SKBR7 line. These results identify Mdmx growth dependency in wt p53 expressing BrCas, across a range of subtypes. Based on our findings, we propose that Mdmx targeting is an attractive strategy for treating BrCas harboring wt p53.
AIP1-mediated actin disassembly is required for postnatal germ cell migration and spermatogonial stem cell niche establishment
Authors: Xu J , Wan P , Wang M , Zhang J , Gao X , Hu B , Han J , Chen L , Sun K , Wu J , Wu X , Huang X , Chen J 
Published: July 2015

AbstractIn mammals, spermatogonial stem cells (SSCs) arise from early germ cells called gonocytes, which are derived from primordial germ cells during embryogenesis and remain quiescent until birth. After birth, these germ cells migrate from the center of testicular cord, through Sertoli cells, and toward the basement membrane to form the SSC pool and establish the SSC niche architecture. However, molecular mechanisms underlying germ cell migration and niche establishment are largely unknown. Here, we show that the actin disassembly factor actin interacting protein 1 (AIP1) is required in both germ cells and Sertoli cells to regulate this process. Germ cell-specific or Sertoli cell-specific deletion of Aip1 gene each led to significant defects in germ cell migration after postnatal day 4 or 5, accompanied by elevated levels of actin filaments (F-actin) in the affected cells. Furthermore, our data demonstrated that interaction between germ cells and Sertoli cells, likely through E-cadherin-mediated cell adhesion, is critical for germ cells’ migration toward the basement membrane. At last, Aip1 deletion in Sertoli cells decreased SSC self-renewal, increased spermatogonial differentiation, but did not affect the expression and secretion levels of growth factors, suggesting that the disruption of SSC function results from architectural changes in the postnatal niche.
miR-205-5p-mediated downregulation of ErbB/HER receptors in breast cancer stem cells results in targeted therapy resistance
Authors: De Cola A , Volpe S , Budani M C , Ferracin M , Lattanzio R , Turdo A , D'Agostino D , Capone E , Stassi G , Todaro M , Di Ilio C , Sala G , Piantelli M , Negrini M , Veronese A , De Laurenzi V 
Published: July 2015

AbstractThe ErbB tyrosine kinase receptor family has been shown to have an important role in tumorigenesis, and the expression of its receptor members is frequently deregulated in many types of solid tumors. Various drugs targeting these receptors have been approved for cancer treatment. Particularly, in breast cancer, anti-Her2/EGFR molecules represent the standard therapy for Her2-positive malignancies. However, in a number of cases, the tumor relapses or progresses thus suggesting that not all cancer cells have been targeted. One possibility is that a subset of cells capable of regenerating the tumor, such as cancer stem cells (CSCs), may not respond to these therapeutic agents. Accumulating evidences indicate that miR-205-5p is significantly downregulated in breast tumors compared with normal breast tissue and acts as a tumor suppressor directly targeting oncogenes such as Zeb1 and ErbB3. In this study, we report that miR-205-5p is highly expressed in BCSCs and represses directly ERBB2 and indirectly EGFR leading to resistance to targeted therapy. Furthermore, we show that miR-205-5p directly regulates the expression of p63 which is in turn involved in the EGFR expression suggesting a miR-205/p63/EGFR regulation.
Highly indistinguishable photons from deterministic quantum-dot microlenses utilizing three-dimensional in situ electron-beam lithography
Authors: Gschrey M. , Thoma A. , Schnauber P. , Seifried M. , Schmidt R. , Wohlfeil B. , Krüger L. , Schulze J. -H. , Heindel T. , Burger S. , Schmidt F. , Strittmatter A. , Rodt S. , Reitzenstein S. 
Published: July 2015

AbstractThe success of advanced quantum communication relies crucially on non-classical light sources emitting single indistinguishable photons at high flux rates and purity. We report on deterministically fabricated microlenses with single quantum dots inside which fulfil these requirements in a flexible and robust quantum device approach. In our concept we combine cathodoluminescence spectroscopy with advanced in situ three-dimensional electron-beam lithography at cryogenic temperatures to pattern monolithic microlenses precisely aligned to pre-selected single quantum dots above a distributed Bragg reflector. We demonstrate that the resulting deterministic quantum-dot microlenses enhance the photon-extraction efficiency to (23±3)%. Furthermore we prove that such microlenses assure close to pure emission of triggered single photons with a high degree of photon indistinguishability up to (80±7)% at saturation. As a unique feature, both single-photon purity and photon indistinguishability are preserved at high excitation power and pulsed excitation, even above saturation of the quantum emitter.
High-quality EuO thin films the easy way via topotactic transformation
Authors: Mairoser Thomas , Mundy Julia A. , Melville Alexander , Hodash Daniel , Cueva Paul , Held Rainer , Glavic Artur , Schubert Jürgen , Muller David A. , Schlom Darrell G. , Schmehl Andreas 
Published: July 2015

AbstractEpitaxy is widely employed to create highly oriented crystalline films. A less appreciated, but nonetheless powerful means of creating such films is via topotactic transformation, in which a chemical reaction transforms a single crystal of one phase into a single crystal of a different phase, which inherits its orientation from the original crystal. Topotactic reactions may be applied to epitactic films to substitute, add or remove ions to yield epitactic films of different phases. Here we exploit a topotactic reduction reaction to provide a non-ultra-high vacuum (UHV) means of growing highly oriented single crystalline thin films of the easily over-oxidized half-metallic semiconductor europium monoxide (EuO) with a perfection rivalling that of the best films of the same material grown by molecular-beam epitaxy or UHV pulsed-laser deposition. As the technique only requires high-vacuum deposition equipment, it has the potential to drastically improve the accessibility of high-quality single crystalline films of EuO as well as other difficult-to-synthesize compounds.
A spectrally tunable all-graphene-based flexible field-effect light-emitting device
Authors: Wang Xiaomu , Tian He , Mohammad Mohammad Ali , Li Cheng , Wu Can , Yang Yi , Ren Tian-Ling 
Published: July 2015

AbstractThe continuous tuning of the emission spectrum of a single light-emitting diode (LED) by an external electrical bias is of great technological significance as a crucial property in high-quality displays, yet this capability has not been demonstrated in existing LEDs. Graphene, a tunable optical platform, is a promising medium to achieve this goal. Here we demonstrate a bright spectrally tunable electroluminescence from blue (∼450 nm) to red (∼750 nm) at the graphene oxide/reduced-graphene oxide interface. We explain the electroluminescence results from the recombination of Poole–Frenkel emission ionized electrons at the localized energy levels arising from semi-reduced graphene oxide, and holes from the top of the π band. Tuning of the emission wavelength is achieved by gate modulation of the participating localized energy levels. Our demonstration of current-driven tunable LEDs not only represents a method for emission wavelength tuning but also may find applications in high-quality displays.
Locking GTPases covalently in their functional states
Authors: Wiegandt David , Vieweg Sophie , Hofmann Frank , Koch Daniel , Li Fu , Wu Yao-Wen , Itzen Aymelt , Müller Matthias P. , Goody Roger S. 
Published: July 2015

AbstractGTPases act as key regulators of many cellular processes by switching between active (GTP-bound) and inactive (GDP-bound) states. In many cases, understanding their mode of action has been aided by artificially stabilizing one of these states either by designing mutant proteins or by complexation with non-hydrolysable GTP analogues. Because of inherent disadvantages in these approaches, we have developed acryl-bearing GTP and GDP derivatives that can be covalently linked with strategically placed cysteines within the GTPase of interest. Binding studies with GTPase-interacting proteins and X-ray crystallography analysis demonstrate that the molecular properties of the covalent GTPase–acryl–nucleotide adducts are a faithful reflection of those of the corresponding native states and are advantageously permanently locked in a defined nucleotide (that is active or inactive) state. In a first application, in vivo experiments using covalently locked Rab5 variants provide new insights into the mechanism of correct intracellular localization of Rab proteins.
Oral administration of the Aureobasidium pullulans-derived β-glucan effectively prevents the development of high fat diet-induced fatty liver in mice
Authors: Aoki Shiho , Iwai Atsushi , Kawata Koji , Muramatsu Daisuke , Uchiyama Hirofumi , Okabe Mitsuyasu , Ikesue Masahiro , Maeda Naoyoshi , Uede Toshimitsu 
Published: July 2015

AbstractAureobasidium pullulans-derived β-glucan (AP-PG) consisting of a β-(1,3)-linked glucose main chain and β-(1,6)-linked glucose branches is taken as a supplement to improve health. This study demonstrates that oral administration of AP-PG is effective to prevent the development of high-fat diet (HFD)-induced fatty liver in mice. Here, C57BL/6N mice were fed with a normal diet or HFD and AP-PG diluted in drinking water was administered orally. After 16 weeks, the serological analysis showed that HFD-induced high blood cholesterol and triglyceride levels were reduced by the oral administration of AP-PG. Further, HFD induced-fatty liver was significantly reduced by the oral administration of AP-PG. The triglyceride accumulation in the liver was also significantly reduced in mice administered AP-PG. Liver injury as indicated by an increase in serum alanine aminotransferase (ALT) in the HFD-fed mice was significantly reduced in the mice administered AP-PG orally and the gene expression of cholesterol 7 alpha-hydroxylase (CYP7A1) which is known to be involved in cholesterol degradation in the liver was significantly increased in the AP-PG administered mice. These results suggest the possibility that the oral administration of AP-PG is effective to prevent the development of non-alcoholic fatty liver disease (NAFLD).
Thyroid function modifies the association between ratio of triglyceride to high-density lipoprotein cholesterol and renal function: a multicenter cross-sectional study
Authors: Yuan Zhongshang , Zhao Meng , Zhang Bingchang , Zhang Haiqing , Zhang Xu , Guan Qingbo , Ning Guang , Gao Ling , Xue Fuzhong , Zhao Jiajun 
Published: July 2015

AbstractHypothyroidism was confirmed to be associated with both dyslipidemia and renal dysfunction. However, the impact of thyroid function on the relationship between serum lipid levels and renal function has never been given sufficient attention. In this large-scale multicenter cross-sectional study, the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL) and the prevalence of hypothyroidism in CKD subjects were significantly higher than those in non-CKD ones (P < 0.001). After adjustment for potential confounding factors, TG/HDL was shown to be significantly associated with serum Cr levels (β = 0.551; 95%CI, 0.394–0.708) and eGFR (β = −0.481; 95%CI, −0.731–−0.230). The risk for CKD was significantly increased as TG/HDL ratio was elevated (adjusted odds ratio = 1.20; 95%CI, 1.11–1.27). These significant associations were found among subjects with euthyroidism and hypothyroidism rather than hyperthyroidism. Furthermore, the associations between TG/HDL and Cr or CKD status were significantly greater in hypothyroidism than those in euthyroidism (P < 0.05). These results suggested that elevated TG/HDL ratio was associated with renal dysfunction; it exhibited a significantly stronger association with Cr and CKD in hypothyroidism than in euthyroidism. Therefore, more attention should be paid on lipid profile to prevent or delay the occurrence and progression of renal dysfunction, especially for those with hypothyroidism.
Efficient search for a face by chimpanzees (Pan troglodytes)
Authors: Tomonaga Masaki , Imura Tomoko 
Published: July 2015

AbstractThe face is quite an important stimulus category for human and nonhuman primates in their social lives. Recent advances in comparative-cognitive research clearly indicate that chimpanzees and humans process faces in a special manner; that is, using holistic or configural processing. Both species exhibit the face-inversion effect in which the inverted presentation of a face deteriorates their perception and recognition. Furthermore, recent studies have shown that humans detect human faces among non-facial objects rapidly. We report that chimpanzees detected chimpanzee faces among non-facial objects quite efficiently. This efficient search was not limited to own-species faces. They also found human adult and baby faces-but not monkey faces-efficiently. Additional testing showed that a front-view face was more readily detected than a profile, suggesting the important role of eye-to-eye contact. Chimpanzees also detected a photograph of a banana as efficiently as a face, but a further examination clearly indicated that the banana was detected mainly due to a low-level feature (i.e., color). Efficient face detection was hampered by an inverted presentation, suggesting that configural processing of faces is a critical element of efficient face detection in both species. This conclusion was supported by a simple simulation experiment using the saliency model.
Visual measurement of the evaporation process of a sessile droplet by dual-channel simultaneous phase-shifting interferometry
Authors: Sun Peng , Zhong Liyun , Luo Chunshu , Niu Wenhu , Lu Xiaoxu 
Published: July 2015

AbstractTo perform the visual measurement of the evaporation process of a sessile droplet, a dual-channel simultaneous phase-shifting interferometry (DCSPSI) method is proposed. Based on polarization components to simultaneously generate a pair of orthogonal interferograms with the phase shifts of π/2, the real-time phase of a dynamic process can be retrieved with two-step phase-shifting algorithm. Using this proposed DCSPSI system, the transient mass (TM) of the evaporation process of a sessile droplet with different initial mass were presented through measuring the real-time 3D shape of a droplet. Moreover, the mass flux density (MFD) of the evaporating droplet and its regional distribution were also calculated and analyzed. The experimental results show that the proposed DCSPSI will supply a visual, accurate, noncontact, nondestructive, global tool for the real-time multi-parameter measurement of the droplet evaporation.
Geometric diffusion of quantum trajectories
Authors: Yang Fan , Liu Ren-Bao 
Published: July 2015

AbstractA quantum object can acquire a geometric phase (such as Berry phases and Aharonov–Bohm phases) when evolving along a path in a parameter space with non-trivial gauge structures. Inherent to quantum evolutions of wavepackets, quantum diffusion occurs along quantum trajectories. Here we show that quantum diffusion can also be geometric as characterized by the imaginary part of a geometric phase. The geometric quantum diffusion results from interference between different instantaneous eigenstate pathways which have different geometric phases during the adiabatic evolution. As a specific example, we study the quantum trajectories of optically excited electron-hole pairs in time-reversal symmetric insulators, driven by an elliptically polarized terahertz field. The imaginary geometric phase manifests itself as elliptical polarization in the terahertz sideband generation. The geometric quantum diffusion adds a new dimension to geometric phases and may have applications in many fields of physics, e.g., transport in topological insulators and novel electro-optical effects.
Zbtb16 (PLZF) is stably suppressed and not inducible in non-innate T cells via T cell receptor-mediated signaling
Authors: Zhang Sai , Laouar Amale , Denzin Lisa K. , Sant’Angelo Derek B. 
Published: July 2015

AbstractThe transcription factor PLZF (promyelocytic leukemia zinc finger; zbtb16) is essential for nearly all of the unique characteristics of NKT cells including their rapid and potent response to antigen. In the immune system, zbtb16 expression is only found in innate cells. Conventional T cells that ectopically express PLZF spontaneously acquire an activated, effector phenotype. Activation induced expression of lineage defining transcription factors such as T-bet, FoxP3, RORγt, GATA3 and others is essential for naïve T cell differentiation into effector T cells. In this study, we used sensitive genetic-based approaches to assess the induction of PLZF expression in non-innate T cells by T cell receptor (TCR)-mediated activation. Surprisingly, we found that PLZF was stably repressed in non-innate T cells and that TCR-mediated signaling was not sufficient to induce PLZF in conventional T cells. The inactivated state of PLZF was stably maintained in mature T cells, even under inflammatory conditions imposed by bacterial infection. Collectively, our data show that, in contrast to multiple recent reports, PLZF expression is highly specific to innate T cells and cannot be induced in conventional T cells via TCR-mediated activation or inflammatory challenge.
Regioselective Halogenation of 1,4-Benzodiazepinones via CH Activation
Authors: Abdelkafi Hajer , Cintrat Jean-Christophe 
Published: July 2015

AbstractThis article reports an efficient CH activation process for regioselective halogenation of 1,4-benzodiazepinones. Direct halogenation with NXS (X = Br, I) affords halogenated benzodiazepinones on the central aromatic ring whereas catalyst (Pd(OAc)2) controlled CH activation furnishes regioselectively ortho halogenated benzodiazepinones on the phenyl side chain.
Uric Acid Produces an Inflammatory Response through Activation of NF-κB in the Hypothalamus: Implications for the Pathogenesis of Metabolic Disorders
Authors: Lu Wenjie , Xu Youzhi , Shao Xiaoni , Gao Fabao , Li Yan , Hu Jing , Zuo Zeping , Shao Xue , Zhou Liangxue , Zhao Yinglan , Cen Xiaobo 
Published: July 2015

AbstractEpidemiological studies have shown that an elevated uric acid (UA) level predicts the development of metabolic syndrome and diabetes; however, there is no direct evidence of this and the underlying mechanism remains unclear. Here, we showed that a high-UA diet triggered the expression of pro-inflammatory cytokines, activated the NF-κB pathway and increased gliosis in the hypothalamus. Intracerebroventricular injection of UA induced hypothalamic inflammation and reactive gliosis, whereas these effects were markedly ameliorated by the inhibition of NF-κB. Moreover, magnetic resonance imaging confirmed that hyperuricemia in rodents and humans was associated with gliosis in the mediobasal hypothalamus. Importantly, the rats administered UA exhibited dyslipidemia and glucose intolerance, which were probably mediated by hypothalamic inflammation and hypothalamic neuroendocrine alterations. These results suggest that UA can cause hypothalamic inflammation via NF-κB signaling. Our findings provide a potential therapeutic strategy for UA-induced metabolic disorders.