bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic re-expression of HIF-2α suppresses soft tissue sarcoma growth
Authors: Nakazawa Michael S. , Eisinger-Mathason T. S. Karin , Sadri Navid , Ochocki Joshua D. , Gade Terence P. F. , Amin Ruchi K. , Simon M. Celeste 
Published: February 2016

AbstractIn soft tissue sarcomas (STS), low intratumoural O2 (hypoxia) is a poor prognostic indicator. HIF-1α mediates key transcriptional responses to hypoxia, and promotes STS metastasis; however, the role of the related HIF-2α protein is unknown. Surprisingly, here we show that HIF-2α inhibits high-grade STS cell growth in vivo, as loss of HIF-2α promotes sarcoma proliferation and increases calcium and mTORC1 signalling in undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. We find that most human STS have lower levels of EPAS1 (the gene encoding HIF-2α) expression relative to normal tissue. Many cancers, including STS, contain altered epigenetics, and our findings define an epigenetic mechanism whereby EPAS1 is silenced during sarcoma progression. The clinically approved HDAC inhibitor Vorinostat specifically increases HIF-2α, but not HIF-1α, accumulation in multiple STS subtypes. Vorinostat inhibits STS tumour growth, an effect ameliorated by HIF-2α deletion, implicating HIF-2α as a biomarker for Vorinostat efficacy in STS.
Therapeutically engineered induced neural stem cells are tumour-homing and inhibit progression of glioblastoma
Authors: Bagó Juli R. , Alfonso-Pecchio Adolfo , Okolie Onyi , Dumitru Raluca , Rinkenbaugh Amanda , Baldwin Albert S. , Miller C. Ryan , Magness Scott T. , Hingtgen Shawn D. 
Published: February 2016

AbstractTransdifferentiation (TD) is a recent advancement in somatic cell reprogramming. The direct conversion of TD eliminates the pluripotent intermediate state to create cells that are ideal for personalized cell therapy. Here we provide evidence that TD-derived induced neural stem cells (iNSCs) are an efficacious therapeutic strategy for brain cancer. We find that iNSCs genetically engineered with optical reporters and tumouricidal gene products retain the capacity to differentiate and induced apoptosis in co-cultured human glioblastoma cells. Time-lapse imaging shows that iNSCs are tumouritropic, homing rapidly to co-cultured glioblastoma cells and migrating extensively to distant tumour foci in the murine brain. Multimodality imaging reveals that iNSC delivery of the anticancer molecule TRAIL decreases the growth of established solid and diffuse patient-derived orthotopic glioblastoma xenografts 230- and 20-fold, respectively, while significantly prolonging the median mouse survival. These findings establish a strategy for creating autologous cell-based therapies to treat patients with aggressive forms of brain cancer.
Supercurrent in van der Waals Josephson junction
Authors: Yabuki Naoto , Moriya Rai , Arai Miho , Sata Yohta , Morikawa Sei , Masubuchi Satoru , Machida Tomoki 
Published: February 2016

AbstractSupercurrent flow between two superconductors with different order parameters, a phenomenon known as the Josephson effect, can be achieved by inserting a non-superconducting material between two superconductors to decouple their wavefunctions. These Josephson junctions have been employed in fields ranging from digital to quantum electronics, yet their functionality is limited by the interface quality and use of non-superconducting material. Here we show that by exfoliating a layered dichalcogenide (NbSe2) superconductor, the van der Waals (vdW) contact between the cleaved surfaces can instead be used to construct a Josephson junction. This is made possible by recent advances in vdW heterostructure technology, with an atomically flat vdW interface free of oxidation and inter-diffusion achieved by eliminating all heat treatment during junction preparation. Here we demonstrate that this artificially created vdW interface provides sufficient decoupling of the wavefunctions of the two NbSe2 crystals, with the vdW Josephson junction exhibiting a high supercurrent transparency.
A structural and functional magnetic resonance imaging dataset of brain tumour patients
Authors: Pernet Cyril R. , Gorgolewski Krzysztof J. , Job Dominic , Rodriguez David , Whittle Ian , Wardlaw Joanna 
Published: February 2016

AbstractWe collected high resolution structural (T1, T2, DWI) and several functional (BOLD T2*) MRI data in 22 patients with different types of brain tumours. Functional imaging protocols included a motor task, a verb generation task, a word repetition task and resting state. Imaging data are complemented by demographics (age, sex, handedness, and pathology), behavioural results to motor and cognitive tests and direct cortical electrical stimulation data (pictures of stimulation sites with outcomes) performed during surgery. Altogether, these data are suited to test functional imaging methods for single subject analyses, in particular methods that focus on locating eloquent cortical areas, critical functional and/or structural network hubs, and predict patient status based on imaging data (presurgical mapping).
Implication of retinoic acid receptor selective signaling in myogenic differentiation
Authors: Chen Jihong , Li Qiao 
Published: February 2016

AbstractSignaling molecules are important for committing individual cells into tissue-specific lineages during early vertebrate development. Retinoic acid (RA) is an important vertebrate morphogen, in that its concentration gradient is essential for correct patterning of the vertebrate embryo. RA signaling is mediated through the activation of retinoic acid receptors (RARs), which function as ligand-dependent transcription factors. In this study, we examined the molecular mechanisms of RAR-selective signaling in myogenic differentiation. We found that just like natural ligand RA, a RAR-selective ligand is an effective enhancer in the commitment of skeletal muscle lineage at the early stage of myogenic differentiation. Interestingly, the kinetics and molecular basis of the RAR-selective ligand in myogenic differentiation are similar to that of natural ligand RA. Also similar to natural ligand RA, the RAR-selective ligand enhances myogenic differentiation through β-catenin signaling pathway while inhibiting cardiac differentiation. Furthermore, while low concentrations of natural ligand RA or RAR-selective ligand regulate myogenic differentiation through RAR function and coactivator recruitment, high concentrations are critical to the expression of a model RA-responsive gene. Thus our data suggests that RAR-mediated gene regulation may be highly context-dependent, affected by locus-specific interaction or local chromatin environment.
Graph theoretical analysis of brain connectivity in phantom sound perception
Authors: Mohan Anusha , De Ridder Dirk , Vanneste Sven 
Published: February 2016

AbstractTinnitus is a phantom sound commonly thought of to be produced by the brain related to auditory deafferentation. The current study applies concepts from graph theory to investigate the differences in lagged phase functional connectivity using the average resting state EEG of 311 tinnitus patients and 256 healthy controls. The primary finding of the study was a significant increase in connectivity in beta and gamma oscillations and a significant reduction in connectivity in the lower frequencies for the tinnitus group. There also seems to be parallel processing of long-distance information between delta, theta, alpha1 and gamma frequency bands that is significantly stronger in the tinnitus group. While the network reorganizes into a more regular topology in the low frequency carrier oscillations, development of a more random topology is witnessed in the high frequency oscillations. In summary, tinnitus can be regarded as a maladaptive ‘disconnection’ syndrome, which tries to both stabilize into a regular topology and broadcast the presence of a deafferentation-based bottom-up prediction error as a result of a top-down prediction.
Proteolytic and non-proteolytic regulation of collective cell invasion: tuning by ECM density and organization
Authors: Kumar Sandeep , Kapoor Aastha , Desai Sejal , Inamdar Mandar M. , Sen Shamik 
Published: February 2016

AbstractCancer cells manoeuvre through extracellular matrices (ECMs) using different invasion modes, including single cell and collective cell invasion. These modes rely on MMP-driven ECM proteolysis to make space for cells to move. How cancer-associated alterations in ECM influence the mode of invasion remains unclear. Further, the sensitivity of the two invasion modes to MMP dynamics remains unexplored. In this paper, we address these open questions using a multiscale hybrid computational model combining ECM density-dependent MMP secretion, MMP diffusion, ECM degradation by MMP and active cell motility. Our results demonstrate that in randomly aligned matrices, collective cell invasion is more efficient than single cell invasion. Although increase in MMP secretion rate enhances invasiveness independent of cell–cell adhesion, sustenance of collective invasion in dense matrices requires high MMP secretion rates. However, matrix alignment can sustain both single cell and collective cell invasion even without ECM proteolysis. Similar to our in-silico observations, increase in ECM density and MMP inhibition reduced migration of MCF-7 cells embedded in sandwich gels. Together, our results indicate that apart from cell intrinsic factors (i.e., high cell–cell adhesion and MMP secretion rates), ECM density and organization represent two important extrinsic parameters that govern collective cell invasion and invasion plasticity.
Skeletal muscle alkaline Pi pool is decreased in overweight-to-obese sedentary subjects and relates to mitochondrial capacity and phosphodiester content
Authors: Valkovič Ladislav , Chmelík Marek , Ukropcová Barbara , Heckmann Thomas , Bogner Wolfgang , Frollo Ivan , Tschan Harald , Krebs Michael , Bachl Norbert , Ukropec Jozef , Trattnig Siegfried , Krššák Martin 
Published: February 2016

AbstractDefects in skeletal muscle energy metabolism are indicative of systemic disorders such as obesity or type 2 diabetes. Phosphorus magnetic resonance spectroscopy (31P-MRS), in particularly dynamic31P-MRS, provides a powerful tool for the non-invasive investigation of muscular oxidative metabolism. The increase in spectral and temporal resolution of31P-MRS at ultra high fields (i.e., 7T) uncovers new potential for previously implemented techniques, e.g., saturation transfer (ST) or highly resolved static spectra. In this study, we aimed to investigate the differences in muscle metabolism between overweight-to-obese sedentary (Ob/Sed) and lean active (L/Ac) individuals through dynamic, static and ST31P-MRS at 7T. In addition, as the dynamic31P-MRS requires a complex setup and patient exercise, our aim was to identify an alternative technique that might provide a biomarker of oxidative metabolism. The Ob/Sed group exhibited lower mitochondrial capacity, and, in addition, static31P-MRS also revealed differences in the Pi-to-ATP exchange flux, the alkaline Pi-pool and glycero-phosphocholine concentrations between the groups. In addition to these differences, we have identified correlations between dynamically measured oxidative flux and static concentrations of the alkaline Pi-pool and glycero-phosphocholine, suggesting the possibility of using high spectral resolution31P-MRS data, acquired at rest, as a marker of oxidative metabolism.
Distinctive origin of artemisinin-resistant Plasmodium falciparum on the China-Myanmar border
Authors: Ye Run , Hu Dongwei , Zhang Yilong , Huang Yufu , Sun Xiaodong , Wang Jian , Chen Xuedi , Zhou Hongning , Zhang Dongmei , Mungthin Mathirut , Pan Weiqing 
Published: February 2016

AbstractThe artemisinin (ART), discovered in China, has been widely used against malaria in China over the last 30 years. Understanding the emergence and origin of ART resistance in China is therefore of great interest. We analyzed 111 culture-adapted isolates of P. falciparum from China-Myanmar (CM) border for their susceptibility to dihydroartemisinin using the ring stage survival assay (RSA0−3h) and genotyped their K13 genes. Of the isolates, 59 had a wild type of the K13 marker and a median ring survival rate of 0.26% (P95 = 1.005%). Among the remaining isolates harboring single mutations in the K13 marker, 26 survived at >P95(median survival rate = 2.95%). Further, we genotyped the K13 gene of 693 isolates collected from different regions in China and China-Myanmar/Thai-Cambodia/Thai-Myanmar (CM/TC/TM) borders, 308 (44.4%) had K13 mutations and marked differences in the patterns of K13 mutations were observed between the CM and the TC/TM borders. A network diagram showed that majority of the K13 mutant alleles from the CM border clustered together including those harboring the high resistant-associated R539T mutations. The resistant parasites carrying distinct halplotypes suggested the multiple indigenous origins of the resistant alleles, which highlight the importance of surveillance of resistance in all malaria endemic areas where ART has been introduced.
A physiological role of cyclic electron transport around photosystem I in sustaining photosynthesis under fluctuating light in rice
Authors: Yamori Wataru , Makino Amane , Shikanai Toshiharu 
Published: February 2016

AbstractPlants experience a highly variable light environment over the course of the day. To reveal the molecular mechanisms of their photosynthetic response to fluctuating light, we examined the role of two cyclic electron flows around photosystem I (CEF-PSI)—one depending on PROTON GRADIENT REGULATION 5 (PGR5) and one on NADH dehydrogenase-like complex (NDH)—in photosynthetic regulation under fluctuating light in rice (Oryza sativaL.). The impairment of PGR5-dependent CEF-PSI suppressed the photosynthetic response immediately after sudden irradiation, whereas the impairment of NDH-dependent CEF-PSI did not. However, the impairment of either PGR5-dependent or NDH-dependent CEF-PSl reduced the photosynthetic rate under fluctuating light, leading to photoinhibition at PSI and consequently a reduction in plant biomass. The results highlight that (1) PGR5-dependent CEF-PSI is a key regulator of rapid photosynthetic responses to high light intensity under fluctuating light conditions after constant high light; and (2) both PGR5-dependent and NDH-dependent CEF-PSI have physiological roles in sustaining photosynthesis and plant growth in rice under repeated light fluctuations. The highly responsive regulatory system managed by CEF-PSI appears able to optimize photosynthesis and plant growth under naturally fluctuating light conditions.
The Citrus transcription factor, CitERF13, regulates citric acid accumulation via a protein-protein interaction with the vacuolar proton pump, CitVHA-c4
Authors: Li Shao-jia , Yin Xue-ren , Xie Xiu-lan , Allan Andrew C. , Ge Hang , Shen Shu-ling , Chen Kun-song 
Published: February 2016

AbstractOrganic acids are essential to fruit flavor. The vacuolar H+ transporting adenosine triphosphatase (V-ATPase) plays an important role in organic acid transport and accumulation. However, less is known of V-ATPase interacting proteins and their relationship with organic acid accumulation. The relationship between V-ATPase and citric acid was investigated, using the citrus tangerine varieties ‘Ordinary Ponkan (OPK)’ and an early maturing mutant ‘Zaoshu Ponkan (ZPK)’. Five V-ATPase genes (CitVHA) were predicted as important to citric acid accumulation. Among the genes, CitVHA-c4 was observed, using a yeast two-hybrid screen, to interact at the protein level with an ethylene response factor, CitERF13. This was verified using bimolecular fluorescence complementation assays. A similar interaction was also observed between Arabidopsis AtERF017 (a CitERF13 homolog) and AtVHA-c4 (a CitVHA-c4 homolog). A synergistic effect on citric acid levels was observed between V-ATPase proteins and interacting ERFs when analyzed using transient over-expression in tobacco and Arabidopsis mutants. Furthermore, the transcript abundance of CitERF13 was concomitant with CitVHA-c4. CitERF13 or AtERF017 over-expression leads to significant citric acid accumulation. This accumulation was abolished in an AtVHA-c4 mutant background. ERF-VHA interactions appear to be involved in citric acid accumulation, which was observed in both citrus and Arabidopsis.
The promoter methylomes of monochorionic twin placentas reveal intrauterine growth restriction-specific variations in the methylation patterns
Authors: He Zhiming , Lu Hanlin , Luo Huijuan , Gao Fei , Wang Tong , Gao Yu , Fang Qun , Wang Junwen 
Published: February 2016

AbstractIntrauterine growth restriction (IUGR) affects the foetus and has a number of pathological consequences throughout life. Recent work has indicated that variations in DNA methylation might cause placental dysfunction, which may be associated with adverse pregnancy complications. Here, we investigated the promoter methylomes of placental shares from seven monochorionic (MC) twins with selective intrauterine growth restriction (sIUGR) using the healthy twin as an ideal control. Our work demonstrated that the IUGR placental shares harboured a distinct DNA hypomethylation pattern and that the methylation variations preferentially occurred in CpG island shores or non-CpG island promoters. The differentially methylated promoters could significantly separate the IUGR placental shares from the healthy ones. Ultra‐performance liquid chromatography/tandem mass spectrometry (UPLC‐MS/MS) further confirmed the genome‐wide DNA hypomethylation and the lower level of hydroxymethylation statuses in the IUGR placental shares. The methylation variations of theLRATandSLC19A1promoters, which are involved in vitamin A metabolism and folate transportation, respectively and theEFSpromoter were further validated in an additional 12 pairs of MC twins with sIUGR. Although the expressions ofLRAT,SLC19A1andEFSwere not affected, we still speculated that DNA methylation and hydroxymethylation might serve a functional role duringin uterofoetal development.
Severe impairment of male reproductive organ development in a low SMN expressing mouse model of spinal muscular atrophy
Authors: Ottesen Eric W. , Howell Matthew D. , Singh Natalia N. , Seo Joonbae , Whitley Elizabeth M. , Singh Ravindra N. 
Published: February 2016

AbstractSpinal muscular atrophy (SMA) is caused by low levels of survival motor neuron (SMN), a multifunctional protein essential for higher eukaryotes. While SMN is one of the most scrutinized proteins associated with neurodegeneration, its gender-specific role in vertebrates remains unknown. We utilized a mild SMA model (C/C model) to examine the impact of low SMN on growth and development of mammalian sex organs. We show impaired testis development, degenerated seminiferous tubules, reduced sperm count and low fertility in C/C males, but no overt sex organ phenotype in C/C females. Underscoring an increased requirement for SMN expression, wild type testis showed extremely high levels of SMN protein compared to other tissues. Our results revealed severe perturbations in pathways critical to C/C male reproductive organ development and function, including steroid biosynthesis, apoptosis and spermatogenesis. Consistent with enhanced apoptosis in seminiferous tubules of C/C testes, we recorded a drastic increase in cells with DNA fragmentation. SMN was expressed at high levels in adult C/C testis due to an adult-specific splicing switch, but could not compensate for low levels during early testicular development. Our findings uncover novel hallmarks of SMA disease progression and link SMN to general male infertility.
Callous traits in children with and without conduct problems predict reduced connectivity when viewing harm to others
Authors: Yoder Keith J. , Lahey Benjamin B. , Decety Jean 
Published: February 2016

AbstractThe presence of elevated callous unemotional (CU) traits seems to designate a distinct group of children and adolescents with serious conduct problems. However, the extent to which CU traits impact the aversive reaction to harm is still a contentious issue. Here, we examined the effective connectivity seeded in the anterior insula and anterior cingulate cortex in a large number of children (N = 123, age 9–11, 60 females) with various levels of conduct disorder (CD) symptoms in response to visual stimuli depicting other people being physically injured. Perceiving others being harmed was associated with increased hemodynamic activity in the left amygdala and right temporoparietal junction (rTPJ). Children with higher callous traits showed less functional connectivity seeded in anterior cingulate with left amygdala and anterior insula. Conversely, CD symptoms were positively related to connectivity of insula with rTPJ. Overall, these results suggest that callousness is marked by the disruption of widespread cortical networks responsible for detecting and appropriately responding to important environmental cues, such as the distress of others.
Integration or separation in the processing of facial properties - a computational view
Authors: Dahl Christoph D. , Rasch Malte J. , Bülthoff Isabelle , Chen Chien-Chung 
Published: February 2016

AbstractA face recognition system ought to read out information about the identity, facial expression and invariant properties of faces, such as sex and race. A current debate is whether separate neural units in the brain deal with these face properties individually or whether a single neural unit processes in parallel all aspects of faces. While the focus of studies has been directed toward the processing of identity and facial expression, little research exists on the processing of invariant aspects of faces. In a theoretical framework we tested whether a system can deal with identity in combination with sex, race or facial expression using the same underlying mechanism. We used dimension reduction to describe how the representational face space organizes face properties when trained on different aspects of faces. When trained to learn identities, the system not only successfully recognized identities, but also was immediately able to classify sex and race, suggesting that no additional system for the processing of invariant properties is needed. However, training on identity was insufficient for the recognition of facial expressions and vice versa. We provide a theoretical approach on the interconnection of invariant facial properties and the separation of variant and invariant facial properties.
Nifuroxazide exerts potent anti-tumor and anti-metastasis activity in melanoma
Authors: Zhu Yongxia , Ye Tinghong , Yu Xi , Lei Qian , Yang Fangfang , Xia Yong , Song Xuejiao , Liu Li , Deng Hongxia , Gao Tiantao , Peng Cuiting , Zuo Weiqiong , Xiong Ying , Zhang Lidan , Wang Ningyu , Zhao Lifeng , Xie Yongmei , Yu Luoting , Wei Yuquan 
Published: February 2016

AbstractMelanoma is a highly malignant neoplasm of melanocytes with considerable metastatic potential and drug resistance, explaining the need for new candidates that inhibit tumor growth and metastasis. The signal transducer and activator of the transcription 3 (Stat3) signaling pathway plays an important role in melanoma and has been validated as promising anticancer target for melanoma therapy. In this study, nifuroxazide, an antidiarrheal agent identified as an inhibitor of Stat3, was evaluated for its anti-melanoma activity in vitro and in vivo. It had potent anti-proliferative activity against various melanoma cell lines and could induce G2/M phase arrest and cell apoptosis. Moreover, nifuroxazide markedly impaired melanoma cell migration and invasion by down-regulating phosphorylated-Src, phosphorylated-FAK and expression of matrix metalloproteinase (MMP) -2, MMP-9 and vimentin. It also significantly inhibited tumor growth without obvious side effects in the A375-bearing mice model by inducing apoptosis and reducing cell proliferation and metastasis. Notably, nifuroxazide significantly inhibited pulmonary metastases, which might be associated with the decrease of myeloid-derived suppressor cells (MDSCs). These findings suggested that nifuroxazide might be a potential agent for inhibiting the growth and metastasis of melanoma.