bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-tumor activity of BET inhibitors in androgen-receptor-expressing triple-negative breast cancer
Authors: Park In Hae , Yang Han Na , Jeon Su Yeon , Hwang Jung-Ah , Kim Min Kyeong , Kong Sun-Young , Shim Sung Hoon , Lee Keun Seok 
Published: September 2019

AbstractTriple-negative breast cancer (TNBC) is a heterogeneous disease comprising several subtypes. Androgen-receptor (AR) signaling has been targeted by several investigational agents in luminal AR subtype TNBCs. Bromodomain (BRD) and extra-terminal motif (BET) protein inhibitors have been shown to attenuate AR signaling in metastatic castration-resistant prostate cancer and to overcome enzalutamide resistance. We demonstrated potent anti-tumor effects of the BET inhibitor JQ1 against AR-positive TNBC cell lines using cell viability and cell cycle analysis. To reveal the mechanisms of JQ1 effects, multiplex gene expression analysis and immunoblotting assays were used. We examined in vivo effects of JQ1 in a xenograft model of AR expressing TNBC. JQ1 exhibited its anti-proliferative activity by inducing apoptosis and cell cycle arrest. JQ1 activity was not mediated by MYC downregulation. Instead, JQ1 blocked the interactions among the ATPase-family AAA-domain-containing 2 protein (ATAD2), BRD2, BRD4, and AR; effectively suppressing the expression of AR associated targets. In addition, JQ1 showed significant anti-tumor activity in vivo in TNBC xenograft mouse models as a monotherapy and in combination with anti-AR therapy. Taken together, our results showed that the BET inhibitor JQ1 is a promising therapeutic agent for the treatment of AR-positive TNBC.
Largest Cretaceous lizard track assemblage, new morphotypes and longest trackways comprise diverse components of an exceptional Korean Konservat-Lagerstätten ichnofauna
Authors: Kim Kyung Soo , Lim Jong Deock , Lockley Martin G. , Hee Kim Dong , Piñuela Laura , Yoo Jae Sang 
Published: September 2019

AbstractA newly discovered assemblage of lizard tracks from the Lower Cretaceous Jinju Formation (Sindong Group, Gyeongsang Basin) Korea is the largest yet reported from the Cretaceous. It consists of at least 95 tracks comprising five trackways, including a meter-long trackway (T1) with 50 footprints assigned to the new ichnotaxon Neosauroides innovatus ichnosp. nov. Two other trackways (T2 and T3) are designated N. innovatus paratypes characterized by strong heteropody, relatively wide trackways and small narrow manus tracks. These morphological characteristics distinguish Neosauroides innovatus from the previously reported lizard trackways Sauripes hadongensis from the Hasandong Formation and Neosauroides koreaensis from the Haman Formation, both also from the Gyeongsang Basin. These three lizard track assemblages from the Korean Cretaceous constitute the entire global lizard track record for this period. The Mesozoic record of lizard tracksites is more localized than the lizard body fossil record. This limited distribution suggests bias in the track record and the fossil record more generally. However, due to deposition of fine-grained substrates, suitable for high definition track registration, the Jinju Formation is increasingly well known as an ichnological window on small tetrapod activity and based on diversity, abundance and high-quality preservation, is regarded as an exceptional Konservat-Lagerstätten.
Spaceflight influences gene expression, photoreceptor integrity, and oxidative stress-related damage in the murine retina
Authors: Overbey Eliah G. , da Silveira Willian Abraham , Stanbouly Seta , Nishiyama Nina C. , Roque-Torres Gina D. , Pecaut Michael J. , Zawieja David Carl , Wang Charles , Willey Jeffrey S. , Delp Michael D. , Hardiman Gary , Mao Xiao Wen 
Published: September 2019

AbstractExtended spaceflight has been shown to adversely affect astronaut visual acuity. The purpose of this study was to determine whether spaceflight alters gene expression profiles and induces oxidative damage in the retina. Ten week old adult C57BL/6 male mice were flown aboard the ISS for 35 days and returned to Earth alive. Ground control mice were maintained on Earth under identical environmental conditions. Within 38 (+/−4) hours after splashdown, mice ocular tissues were collected for analysis. RNA sequencing detected 600 differentially expressed genes (DEGs) in murine spaceflight retinas, which were enriched for genes related to visual perception, the phototransduction pathway, and numerous retina and photoreceptor phenotype categories. Twelve DEGs were associated with retinitis pigmentosa, characterized by dystrophy of the photoreceptor layer rods and cones. Differentially expressed transcription factors indicated changes in chromatin structure, offering clues to the observed phenotypic changes. Immunofluorescence assays showed degradation of cone photoreceptors and increased retinal oxidative stress. Total retinal, retinal pigment epithelium, and choroid layer thickness were significantly lower after spaceflight. These results indicate that retinal performance may decrease over extended periods of spaceflight and cause visual impairment.
Hypoxia Activates the PTHrP –MEF2C Pathway to Attenuate Hypertrophy in Mesenchymal Stem Cell Derived Cartilage
Authors: Browe David C. , Coleman Cynthia M. , Barry Frank P. , Elliman Stephen J. 
Published: September 2019

AbstractArticular cartilage lacks an intrinsic repair capacity and due to the ability of mesenchymal stem cells (MSCs) to differentiate into chondrocytes, MSCs have been touted as a cellular source to regenerate damaged cartilage. However, a number of prevailing concerns for such a treatment remain. Generally, administration of MSCs into a cartilage defect results in poor regeneration of the damaged cartilage with the repaired cartilage consisting primarily of fibro-cartilage rather than hyaline cartilage. Methods that improve the chondrogenic potential of transplanted MSCs in vivo may be advantageous. In addition, the proclivity of MSC-derived cartilage to undergo hypertrophic differentiation or form bone in vivo also remains a clinical concern. If MSC-derived cartilage was to undergo hypertrophic differentiation in vivo, this would be deleterious in a clinical setting. This study focuses on establishing a mechanism of action by which hypoxia or low oxygen tension can be used to both enhance chondrogenesis and attenuate hypertrophic differentiation of both MSC and ATDC5 derived chondrocytes. Having elucidated a novel mechanism of action, the subsequent goals of this study were to develop an in vitro culture regime to mimic the beneficial effects of physiological low oxygen tension in a normoxic environment.
Early Life Supraphysiological Levels of Oxygen Exposure Permanently Impairs Hippocampal Mitochondrial Function
Authors: Ramani Manimaran , Miller Kiara , Brown Jamelle , Kumar Ranjit , Kadasamy Jegen , McMahon Lori , Ballinger Scott , Ambalavanan Namasivayam 
Published: September 2019

AbstractPreterm infants requiring prolonged oxygen therapy often develop cognitive dysfunction in later life. Previously, we reported that 14-week-old young adult mice exposed to hyperoxia as newborns had spatial and learning deficits and hippocampal shrinkage. We hypothesized that the underlying mechanism was the induction of hippocampal mitochondrial dysfunction by neonatal hyperoxia. C57BL/6J mouse pups were exposed to 85% oxygen or room air from P2–P14. Hippocampal proteomic analysis was performed in young adult mice (14 weeks). Mitochondrial bioenergetics were measured in neonatal (P14) and young adult mice. We found that hyperoxia exposure reduced mitochondrial ATP-linked oxygen consumption and increased state 4 respiration linked proton leak in both neonatal and young adult mice while complex I function was decreased at P14 but increased in young adult mice. Proteomic analysis revealed that hyperoxia exposure decreased complex I NDUFB8 and NDUFB11 and complex IV 7B subunits, but increased complex III subunit 9 in young adult mice. In conclusion, neonatal hyperoxia permanently impairs hippocampal mitochondrial function and alters complex I function. These hippocampal mitochondrial changes may account for cognitive deficits seen in children and adolescents born preterm and may potentially be a contributing mechanism in other oxidative stress associated brain disorders.
Fourier transforms for fast and quantitative Laser Speckle Imaging
Authors: Buijs J. , Gucht J. van der , Sprakel J. 
Published: September 2019

AbstractLaser speckle imaging is a powerful imaging technique that visualizes microscopic motion within turbid materials. At current two methods are widely used to analyze speckle data: one is fast but qualitative, the other quantitative but computationally expensive. We have developed a new processing algorithm based on the fast Fourier transform, which converts raw speckle patterns into maps of microscopic motion and is both fast and quantitative, providing a dynamnic spectrum of the material over a frequency range spanning several decades. In this article we show how to apply this algorithm and how to measure a diffusion coefficient with it. We show that this method is quantitative and several orders of magnitude faster than the existing quantitative method. Finally we harness the potential of this new approach by constructing a portable laser speckle imaging setup that performs quantitative data processing in real-time on a tablet.
A robust method for automatic identification of landmarks on surface models of the pelvis
Authors: Fischer Maximilian C. M. , Krooß Felix , Habor Juliana , Radermacher Klaus 
Published: September 2019

AbstractThe recognition of bony landmarks of the pelvis is a required operation in patient-specific orthopedics, subject-specific biomechanics or morphometrics. A fully automatic detection is preferable to a subjective and time-consuming manual identification. In this paper, a new approach, called the iterative tangential plane (ITP) method, for fully automatic identification of landmarks on surface models of the pelvis is introduced. The method includes the landmarks to construct the two most established anatomical reference frames of the pelvis: the anterior pelvic plane (APP) coordinate system and superior inferior spine plane (SISP) coordinate system. The ITP method proved to be robust against the initial alignment of the pelvis in space. A comparison to a manual identification was performed that showed minor but significant (p < 0.05) median differences below 3 mm for the position of the landmarks and below 1° for the orientation of the APP coordinate system. Whether these differences are acceptable, has to be evaluated for each specific use case. There were no significant differences for the orientation of the SISP coordinate system recommended by the International Society of Biomechanics.
Oceanic mantle reflections in deep seismic profiles offshore Sumatra are faults or fakes
Authors: Sibuet Jean-Claude , He Enyuan , Zhao Minghui , Pang Xinming , Klingelhoefer Frauke 
Published: September 2019

AbstractIn the late 90’s, some faults identified within oceanic crust were demonstrated to be artifacts arising from out-of-plane scattering along linear sediment-buried fault scarps. Symmetrical mantle reflections observed southwest northern Sumatra on seismic reflection profiles have been identified as faults cutting through the upper mantle down to unprecedented depths reaching ~45 km. Seawater being conveyed along sub-vertical re-activated fracture zones (FZs) to the upper mantle, the mantle portions of FZs are serpentinized and act as mirrors for seismic rays. We suggest that the mantle features are not faults but artifacts resulting from out-of-plane reflections on these mirrors. Two perpendicular seismic profiles crossing the same FZ display two dipping features down to 30 km, which cannot be explained as faults from recent tectonic and structural constraints but merely as out-of-plane reflections on this FZ. This result confirms that most of mantle reflections observed southwest northern Sumatra are fakes rather than faults.
CXCL16 positively correlated with M2-macrophage infiltration, enhanced angiogenesis, and poor prognosis in thyroid cancer
Authors: Kim Min Joo , Sun Hyun Jin , Song Young Shin , Yoo Seong-Keun , Kim Young A , Seo Jeong-Sun , Park Young Joo , Cho Sun Wook 
Published: September 2019

AbstractAlthough various chemokines have pro-tumorigenic actions in cancers, the effects of CXCL16 remain controversial. The aim of this study was to investigate the molecular characteristics of CXCL16-expressing papillary thyroid cancers (PTCs). CXCL16 expressions were significantly higher in PTCs than benign or normal thyroid tissues. In the TCGA dataset for PTCs, a higher CXCL16 expression was associated with M2 macrophage- and angiogenesis-related genes and poor prognostic factors including a higher TNM staging and the BRAFV600E mutation. PTCs with a higher expression of 3-gene panel including CXCL16, AHNAK2, and THBS2 showed poor recurrence-free survivals than that of the lower expression group. Next, shCXCL16 was introduced into BHP10-3SCp cells to deplete the endogenous CXCL16, and then, the cells were subcutaneously injected to athymic mice. Tumors from the BHP10-3SCpshCXCL16 exhibited a delayed tumor growth with decreased numbers of ERG+ endothelial cells and F4/80+ macrophages than those from the BHP10-3SCpcontrol. CXCL16-related genes including AHNAK2 and THBS2 were downregulated in the tumors from the BHP10-3SCpshCXCL16 compared with that from the BHP10-3SCpcontrol. In conclusion, a higher CXCL16 expression was associated with macrophage- and angiogenesis-related genes and aggressive phenotypes in PTC. Targeting CXCL16 may be a good therapeutic strategy for advanced thyroid cancer.
CED-4 CARD domain residues can modulate non-apoptotic neuronal regeneration functions independently from apoptosis
Authors: Wang Guoqiang , Sun Lin , Reina Christopher P. , Song Isaac , Gabel Christopher V. , Driscoll Monica 
Published: September 2019

AbstractA major challenge in regenerative medicine is the repair of injured neurons. Regeneration of laser-cut C. elegans neurons requires early action of core apoptosis activator CED-4/Apaf1 and CED-3/caspase. While testing models for CED-4 as a candidate calcium-sensitive activator of repair, we unexpectedly discovered that amino acid substitutions affecting alpha-helix-6 within the CED-4 caspase recruitment domain (CARD) confer a CED-4 gain-of-function (gf) activity that increases axonal regrowth without disrupting CED-4 apoptosis activity. The in vivo caspase reporter CA-GFP reveals a rapid localized increase in caspase activity upon axotomy, which is absent in ced-4 and ced-3 loss-of-function mutants but present in the ced-4(gf) mutant. The ced-3 loss-of-function mutation can significantly suppress the axonal regrowth of the ced-4(gf) mutant, indicating that CED-4(gf) regeneration depends on CED-3 caspase. Thus, we identified a subdomain within the CED-4 CARD that regulates the dynamic and controlled caspase activity required for efficient regeneration.
Wakeful rest compared to vigilance reduces intrusive but not deliberate memory for traumatic videos
Authors: Hørlyck Lone D. , Bisby James A. , King John A. , Burgess Neil 
Published: September 2019

AbstractIntrusive memories are prominent features of post-traumatic stress disorder, but the mechanisms supporting their development, and their relationship to deliberate memories, are subject to competing theories. Are they strengthened examples of a unitary memory system, or fragmented representations lacking aspects of healthy memories? Given the importance of post-encoding processing in memory consolidation, we investigated the effects of a brief wakeful rest compared to a vigilance task immediately after the encoding of traumatic material on subsequent intrusive and deliberate memory. Across two experiments, participants watched emotionally negative film clips immediately followed by a brief wakeful rest or a simple vigilance (0-back) task. Brief wakeful rest had distinct effects on memory compared to the 0-back task, reducing intrusive memory frequency but not changing deliberate memory performance. These differential effects suggest that intrusive memory and deliberate memory reflect dissociable systems, arguing against unitary accounts. Our findings highlight the importance of post-encoding processing in the consolidation of traumatic material and the development of intrusive memories and provide a new perspective for interpreting mechanisms of therapeutic intervention.
Platelet P-selectin triggers rapid surface exposure of tissue factor in monocytes
Authors: Ivanov Ivelin I. , Apta Bonita H. R. , Bonna Arkadiusz M. , Harper Matthew T. 
Published: September 2019

AbstractTissue factor (TF) plays a central role in haemostasis and thrombosis. Following vascular damage, vessel wall TF initiates the extrinsic coagulation cascade. TF can also be exposed by monocytes. Inflammatory or infectious stimuli trigger synthesis of new TF protein by monocytes over the course of hours. It has also been suggested that monocytes can expose TF within minutes when stimulated by activated platelets. Here, we have confirmed that monocytes rapidly expose TF in whole blood and further demonstrate that platelet P-selectin exposure is necessary and sufficient. Monocyte TF exposure increased within five minutes in response to platelet activation by PAR1-AP, PAR4-AP or CRP-XL. PAR1-AP did not trigger TF exposure on isolated monocytes unless platelets were also present. In whole blood, PAR1-AP-triggered TF exposure required P-selectin and PGSL-1. In isolated monocytes, although soluble recombinant P-selectin had no effect, P-selectin coupled to 2 µm beads triggered TF exposure. Cycloheximide did not affect rapid TF exposure, indicating that de novo protein synthesis was not required. These data show that P-selectin on activated platelets rapidly triggers TF exposure on monocytes. This may represent a mechanism by which platelets and monocytes rapidly contribute to intravascular coagulation.
Regulation of VEGFR2 trafficking and signaling by Rab GTPase-activating proteins
Authors: Xie Ye , Mansouri Maysam , Rizk Aurélien , Berger Philipp 
Published: September 2019

AbstractVascular endothelial growth factor receptor-2 (VEGFR2) and its ligands (VEGFs) are crucial players in vasculogenesis and angiogenesis. General blocking of this signaling system with antibodies or small molecule inhibitors is an established strategy to treat cancer and age-related macular degeneration. Nevertheless, the activated receptor can signal to discrete downstream signaling pathways and the equilibrium between these pathways is modulated by coreceptors and distinct isoforms of VEGF. Here we investigated the influence of Rab GTPase activating proteins (RabGAPs) on VEGFR2 signaling, tube formation, and migration of endothelial cells. We demonstrate that members of the TBC1D10 subfamily of RabGAPs have opposite effects. Whereas TBC1D10A leads to increased Erk1/2 signaling, TBC1D10B lowered Erk1/2 and p38 signaling and reduced tube formation in vitro. TBC1D10A is a RabGAP acting on RAB13 that was shown before to play a role in angiogenesis and we could indeed show colocalization of these two proteins with VEGFR2 in activated cells. In addition, we observed that cells expressing TBC1D10B show lower expression of VEGFR2 and NRP1 on filopodia of activated cells. Taken together, our systematic analysis of influence of RabGAPs on VEGFR2 signaling identifies the TBC1D10 subfamily members as modulators of angiogenesis.
Adipocytes promote ovarian cancer chemoresistance
Authors: Yang Jiang , Zaman Munir M. , Vlasakov Iliyan , Roy Roopali , Huang Lan , Martin Camilia R. , Freedman Steven D. , Serhan Charles N. , Moses Marsha A. 
Published: September 2019

AbstractOvarian cancer (OvCa), while accounting for only 3% of all women’s cancer, is the fifth leading cause of cancer death among women. One of the most significant obstacles to successful OvCa treatment is chemoresistance. The current lack of understanding of the driving mechanisms underlying chemoresistance hinders the development of effective therapeutics against this obstacle. Adipocytes are key components of the OvCa microenvironment and have been shown to be involved in OvCa cell proliferation, however, little is known about their impact on OvCa chemoresistance. In the current study, we found that adipocytes, of both subcutaneous and visceral origin, secrete factors that enhance the resistance of OvCa cells against chemotherapeutic drugs by activating the Akt pathway. Importantly, we have demonstrated that secreted lipids mediate adipocyte-induced chemoresistance. Through a comprehensive lipidomic analysis, we have identified this chemo-protective lipid mediator as arachidonic acid (AA). AA acts on OvCa cells directly, not through its downstream derivatives such as prostaglandins, to activate Akt and inhibit cisplatin-induced apoptosis. Taken together, our study has identified adipocytes and their secreted AA as important mediators of OvCa chemoresistance. Strategies that block the production of AA from adipocytes or block its anti-apoptotic function may potentially inhibit chemoresistance in OvCa patients.
Realization of efficient quantum gates with a superconducting qubit-qutrit circuit
Authors: Bækkegaard T. , Kristensen L. B. , Loft N. J. S. , Andersen C. K. , Petrosyan D. , Zinner N. T. 
Published: September 2019

AbstractBuilding a quantum computer is a daunting challenge since it requires good control but also good isolation from the environment to minimize decoherence. It is therefore important to realize quantum gates efficiently, using as few operations as possible, to reduce the amount of required control and operation time and thus improve the quantum state coherence. Here we propose a superconducting circuit for implementing a tunable system consisting of a qutrit coupled to two qubits. This system can efficiently accomplish various quantum information tasks, including generation of entanglement of the two qubits and conditional three-qubit quantum gates, such as the Toffoli and Fredkin gates. Furthermore, the system realizes a conditional geometric gate which may be used for holonomic (non-adiabatic) quantum computing. The efficiency, robustness and universality of the presented circuit makes it a promising candidate to serve as a building block for larger networks capable of performing involved quantum computational tasks.
Comprehensive proteomic profiling of plasma-derived Extracellular Vesicles from dementia with Lewy Bodies patients
Authors: Gámez-Valero Ana , Campdelacreu Jaume , Reñé Ramón , Beyer Katrin , Borràs Francesc E. 
Published: September 2019

AbstractProteins and nucleic acids contained in extracellular vesicles (EVs) are considered a feasible source of putative biomarkers for physiological and pathological conditions. Within the nervous system, not only neurons but also other brain cells are able to produce EVs, which have been involved in their physiological processes and also in the development and course of several neurodegenerative diseases. Among these, dementia with Lewy bodies (DLB) is the second cause of dementia worldwide, though most cases are missed or misdiagnosed as Alzheimer’s disease (AD) due to the important clinical and pathological overlap between both diseases. In an attempt to find reliable biomarkers for DLB diagnosis, our group characterized the proteome of plasma-derived EVs from DLB patients compared to aged-matched healthy controls (HCs) using two different proteomic LC-MS/MS approaches. Remarkably, we found that gelsolin and butyrylcholinesterase were differentially identified between DLB and HCs. Further validation of these results using conventional ELISA techniques, and including an additional group of AD patients, pointed to decreased levels of gelsolin in plasma-EVs from DLB compared to HCs and to AD samples. Thus, gelsolin may be considered a possible biomarker for the differentiation between DLB and AD.