bluuebunny/crossref_metadata_2025_split huggingface dataset:
Price Expectations and Supply Response in the Thoroughbred Yearling Market
Authors: Neibergs J. Shannon , Thalheimer Richard 
Published: February 2016

AbstractLimited information is available concerning price determination in the thoroughbred yearling market. A recursive model incorporating price expectations and biological constraints is used to estimate supply and demand functions for thoroughbred horses. Empirical results characterize a market with inelastic supply and elastic demand that converges to equilibrium under static conditions. Purses were identified as the most influential variable impacting price. Comparative statics illustrate the effectiveness of purses as a policy instrument for the thoroughbred industry. Federal tax policy also was found to have a significant impact on the decisions to breed or invest in thoroughbred yearlings.
Atomic Force Microscopy Study of Atherosclerosis Progression in Arterial Walls
Authors: Timashev Peter S. , Kotova Svetlana L. , Belkova Galina V. , Gubar’kova Ekaterina V. , Timofeeva Lidia B. , Gladkova Natalia D. , Solovieva Anna B. 
Published: February 2016

AbstractCardiovascular disease remains the leading cause of mortality worldwide. Here we suggest a novel approach for tracking atherosclerosis progression based on the use of atomic force microscopy (AFM). Using AFM, we studied cross-sections of coronary arteries with the following types of lesions: Type II—thickened intima; Type III—thickened intima with a lipid streak; Type IV—fibrotic layer over a lipid core; Type Va—unstable fibrotic layer over a lipid core; Type Vc—very thick fibrotic layer. AFM imaging revealed that the fibrotic layer of an atherosclerotic plaque is represented by a basket-weave network of collagen fibers and a subscale network of fibrils that become looser with atherosclerosis progression. In an unstable plaque (Type Va), packing of the collagen fibers and fibrils becomes even less uniform than that at the previous stages, while a stable fibrotic plaque (Vc) has significantly tighter packing. Such alterations of the collagen network morphology apparently, led to deterioration of the Type Va plaque mechanical properties, that, in turn, resulted in its instability and propensity to rupture. Thus, AFM may serve as a useful tool for tracking atherosclerosis progression in the arterial wall tissue.
c-Met and CREB1 are involved in miR-433-mediated inhibition of the epithelial–mesenchymal transition in bladder cancer by regulating Akt/GSK-3β/Snail signaling
Authors: Xu X , Zhu Y , Liang Z , Li S , Xu X , Wang X , Wu J , Hu Z , Meng S , liu B , Qin J , Xie L , Zheng X 
Published: February 2016

AbstractEmerging evidence has suggested that microRNAs (miRNAs) have an important role in tumor development and progression by regulating diverse cellular pathways. Here we describe the function and regulation network of miR-433 in bladder cancer (BCa). miR-433 is frequently downregulated in BCa tissues compared with adjacent non-cancerous tissues. Epigenetic mechanisms may be involved in the regulation of miR-433 expression. Enforced expression of miR-433 significantly inhibits proliferation, colony formation, migration, and invasion in BCa cells. In addition, miR-433 inhibits the epithelial–mesenchymal transition (EMT) in BCa cells by regulating c-Met/Akt/GSK-3β/Snail signaling pathway. Both c-Met and CREB1 are downstream target genes of miR-433. CREB1 can also indirectly regulate c-Met/Akt/GSK-3β/Snail signaling via MITF. Furthermore, CREB1 expression is an independent prognostic factor for overall survival in patients with BCa. Finally, there appears to exist a reciprocal regulation between c-Met and miR-433/miR-409-3p. Taken together, this study reveals that miR-433-c-MET/CREB1-Akt/GSK-3β/Snail signaling is critical to EMT in BCa. Targeting the pathway described here may open up new prospects to restrict metastatic progression of BCa.
FGF1 C-terminal domain and phosphorylation regulate intracrine FGF1 signaling for its neurotrophic and anti-apoptotic activities
Authors: Delmas E , Jah N , Pirou C , Bouleau S , Le Floch N , Vayssière J-L , Mignotte B , Renaud F 
Published: February 2016

AbstractFibroblast growth factor 1 (FGF1) is a prototypic member of the FGFs family overexpressed in various tumors. Contrarily to most FGFs, FGF1 lacks a secretion peptide signal and acts mainly in an intracellular and nuclear manner. Intracellular FGF1 induces cell proliferation, differentiation and survival. We previously showed that intracellular FGF1 induces neuronal differentiation and inhibits both p53- and serum-free-medium-induced apoptosis in PC12 cells. FGF1 nuclear localization is required for these intracellular activities, suggesting that FGF1 regulates p53-dependent apoptosis and neuronal differentiation by new nuclear pathways. To better characterize intracellular FGF1 pathways, we studied the effect of three mutations localized in the C-terminal domain of FGF1 (i.e., FGF1K132E, FGF1S130A and FGF1S130D) on FGF1 neurotrophic and anti-apoptotic activities in PC12 cells. The change of the serine 130 to alanine precludes FGF1 phosphorylation, while its mutation to aspartic acid mimics phosphorylation. These FGF1 mutants kept both a nuclear and cytosolic localization in PC12 cells. Our study highlights for the first time the role of FGF1 phosphorylation and the implication of FGF1 C-terminal domain on its intracellular activities. Indeed, we show that the K132E mutation inhibits both the neurotrophic and anti-apoptotic activities of FGF1, suggesting a regulatory activity for FGF1 C terminus. Furthermore, we observed that both FGF1S130A and FGF1S130D mutant forms induced PC12 cells neuronal differentiation. Therefore, FGF1 phosphorylation does not regulate FGF1-induced differentiation of PC12 cells. Then, we showed that only FGF1S130A protects PC12 cells against p53-dependent apoptosis, thus phosphorylation appears to inhibit FGF1 anti-apoptotic activity in PC12 cells. Altogether, our results show that phosphorylation does not regulate FGF1 neurotrophic activity but inhibits its anti-apoptotic activity after p53-dependent apoptosis induction, giving new insight into the poorly described FGF1 intracrine/nuclear pathway. The study of nuclear pathways could be crucial to identify key regulators involved in neuronal differentiation, tumor progression and resistances to radio- and chemo-therapy.
ANP32B deficiency impairs proliferation and suppresses tumor progression by regulating AKT phosphorylation
Authors: Yang S , Zhou L , Reilly P T , Shen S-M , He P , Zhu X-N , Li C-X , Wang L-S , Mak T W , Chen G-Q , Yu Y 
Published: February 2016

AbstractThe acidic leucine-rich nuclear phosphoprotein 32B (ANP32B) is reported to impact normal development, with Anp32b-knockout mice exhibiting smaller size and premature aging. However, its cellular and molecular mechanisms, especially its potential roles in tumorigenesis, remain largely unclear. Here, we utilize 'knockout' models, RNAi silencing and clinical cohorts to more closely investigate the role of this enigmatic factor in cell proliferation and cancer phenotypes. We report that, compared with Anp32b wild-type (Anp32b+/+) littermates, a broad panel of tissues in Anp32b-deficient (Anp32b−/−) mice are demonstrated hypoplasia. Anp32b−/− mouse embryo fibroblast cell has a slower proliferation, even after oncogenic immortalization. ANP32B knockdown also significantly inhibits in vitro and in vivo growth of cancer cells by inducing G1 arrest. In line with this, ANP32B protein has higher expression in malignant tissues than adjacent normal tissues from a cohort of breast cancer patients, and its expression level positively correlates with their histopathological grades. Moreover, ANP32B deficiency downregulates AKT phosphorylation, which involves its regulating effect on cell growth. Collectively, our findings suggest that ANP32B is an oncogene and a potential therapeutic target for breast cancer treatment.
Origin of the spin Seebeck effect in compensated ferrimagnets
Authors: Geprägs Stephan , Kehlberger Andreas , Coletta Francesco Della , Qiu Zhiyong , Guo Er-Jia , Schulz Tomek , Mix Christian , Meyer Sibylle , Kamra Akashdeep , Althammer Matthias , Huebl Hans , Jakob Gerhard , Ohnuma Yuichi , Adachi Hiroto , Barker Joseph , Maekawa Sadamichi , Bauer Gerrit E. W. , Saitoh Eiji , Gross Rudolf , Goennenwein Sebastian T. B. , Kläui Mathias 
Published: February 2016

AbstractMagnons are the elementary excitations of a magnetically ordered system. In ferromagnets, only a single band of low-energy magnons needs to be considered, but in ferrimagnets the situation is more complex owing to different magnetic sublattices involved. In this case, low lying optical modes exist that can affect the dynamical response. Here we show that the spin Seebeck effect (SSE) is sensitive to the complexities of the magnon spectrum. The SSE is caused by thermally excited spin dynamics that are converted to a voltage by the inverse spin Hall effect at the interface to a heavy metal contact. By investigating the temperature dependence of the SSE in the ferrimagnet gadolinium iron garnet, with a magnetic compensation point near room temperature, we demonstrate that higher-energy exchange magnons play a key role in the SSE.
Transplanted neurons integrate into adult retinas and respond to light
Authors: Venugopalan Praseeda , Wang Yan , Nguyen Tu , Huang Abigail , Muller Kenneth J. , Goldberg Jeffrey L. 
Published: February 2016

AbstractRetinal ganglion cells (RGCs) degenerate in diseases like glaucoma and are not replaced in adult mammals. Here we investigate whether transplanted RGCs can integrate into the mature retina. We have transplanted GFP-labelled RGCs into uninjured rat retinas in vivo by intravitreal injection. Transplanted RGCs acquire the general morphology of endogenous RGCs, with axons orienting towards the optic nerve head of the host retina and dendrites growing into the inner plexiform layer. Preliminary data show in some cases GFP+ axons extending within the host optic nerves and optic tract, reaching usual synaptic targets in the brain, including the lateral geniculate nucleus and superior colliculus. Electrophysiological recordings from transplanted RGCs demonstrate the cells’ electrical excitability and light responses similar to host ON, ON–OFF and OFF RGCs, although less rapid and with greater adaptation. These data present a promising approach to develop cell replacement strategies in diseased retinas with degenerating RGCs.
Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer
Authors: Dubeykovskaya Zina , Si Yiling , Chen Xiaowei , Worthley Daniel L. , Renz Bernhard W. , Urbanska Aleksandra M. , Hayakawa Yoku , Xu Ting , Westphalen C. Benedikt , Dubeykovskiy Alexander , Chen Duan , Friedman Richard A. , Asfaha Samuel , Nagar Karan , Tailor Yagnesh , Muthupalani Sureshkumar , Fox James G. , Kitajewski Jan , Wang Timothy C. 
Published: February 2016

AbstractCD11b+Gr-1+myeloid-derived suppressor cells (MDSCs) expand in the spleen during cancer and promote progression through suppression of cytotoxic T cells. An anti-inflammatory reflex arc involving the vagus nerve and memory T cells is necessary for resolution of acute inflammation. Failure of this neural circuit could promote procarcinogenic inflammation and altered tumour immunity. Here we show that splenic TFF2, a secreted anti-inflammatory peptide, is released by vagally modulated memory T cells to suppress the expansion of MDSCs through CXCR4. Splenic denervation interrupts the anti-inflammatory neural arc, resulting in the expansion of MDSCs and colorectal cancer. Deletion ofTff2recapitulates splenic denervation to promote carcinogenesis. Colorectal carcinogenesis could be suppressed through transgenic overexpression of TFF2, adenoviral transfer of TFF2 or transplantation of TFF2-expressing bone marrow. TFF2 is important to the anti-inflammatory reflex arc and plays an essential role in arresting MDSC proliferation. TFF2 offers a potential approach to prevent and to treat cancer.
MeCP2 SUMOylation rescues Mecp2-mutant-induced behavioural deficits in a mouse model of Rett syndrome
Authors: Tai Derek J. C. , Liu Yen C. , Hsu Wei L. , Ma Yun L. , Cheng Sin J. , Liu Shau Y. , Lee Eminy H. Y. 
Published: February 2016

AbstractThe methyl-CpG-binding protein 2 (MeCP2) gene, MECP2, is an X-linked gene encoding the MeCP2 protein, and mutations of MECP2 cause Rett syndrome (RTT). However, the molecular mechanism of MECP2-mutation-caused RTT is less known. Here we find that MeCP2 could be SUMO-modified by the E3 ligase PIAS1 at Lys-412. MeCP2 phosphorylation (at Ser-421 and Thr-308) facilitates MeCP2 SUMOylation, and MeCP2 SUMOylation is induced by NMDA, IGF-1 and CRF in the rat brain. MeCP2 SUMOylation releases CREB from the repressor complex and enhances Bdnf mRNA expression. Several MECP2 mutations identified in RTT patients show decreased MeCP2 SUMOylation. Re-expression of wild-type MeCP2 or SUMO-modified MeCP2 in Mecp2-null neurons rescues the deficits of social interaction, fear memory and LTP observed in Mecp2 conditional knockout (cKO) mice. These results together reveal an important role of MeCP2 SUMOylation in social interaction, memory and synaptic plasticity, and that abnormal MeCP2 SUMOylation is implicated in RTT.
GABAergic interneurons form transient layer-specific circuits in early postnatal neocortex
Authors: Anastasiades Paul G. , Marques-Smith Andre , Lyngholm Daniel , Lickiss Tom , Raffiq Sayda , Kätzel Dennis , Miesenböck Gero , Butt Simon J. B. 
Published: February 2016

AbstractGABAergic interneurons play key roles in cortical circuits, yet little is known about their early connectivity. Here we use glutamate uncaging and a novel optogenetic strategy to track changes in the afferent and efferent synaptic connections of developing neocortical interneuron subtypes. We find that Nkx2-1-derived interneurons possess functional synaptic connections before emerging pyramidal cell networks. Subsequent interneuron circuit maturation is both subtype and layer dependent. Glutamatergic input onto fast spiking (FS), but not somatostatin-positive, non-FS interneurons increases over development. Interneurons of both subtype located in layers (L) 4 and 5b engage in transient circuits that disappear after the somatosensory critical period. These include a pathway mediated by L5b somatostatin-positive interneurons that specifically targets L4 during the first postnatal week. The innervation patterns of immature cortical interneuron circuits are thus neither static nor progressively strengthened but follow a layer-specific choreography of transient connections that differ from those of the adult brain.
The RNA helicase DHX34 functions as a scaffold for SMG1-mediated UPF1 phosphorylation
Authors: Melero Roberto , Hug Nele , López-Perrote Andrés , Yamashita Akio , Cáceres Javier F. , Llorca Oscar 
Published: February 2016

AbstractNonsense-mediated decay (NMD) is a messenger RNA quality-control pathway triggered by SMG1-mediated phosphorylation of the NMD factor UPF1. In recent times, the RNA helicase DHX34 was found to promote mRNP remodelling, leading to activation of NMD. Here we demonstrate the mechanism by which DHX34 functions in concert with SMG1. DHX34 comprises two distinct structural units, a core that binds UPF1 and a protruding carboxy-terminal domain (CTD) that binds the SMG1 kinase, as shown using truncated forms of DHX34 and electron microscopy of the SMG1–DHX34 complex. Truncation of the DHX34 CTD does not affect binding to UPF1; however, it compromises DHX34 binding to SMG1 to affect UPF1 phosphorylation and hence abrogate NMD. Altogether, these data suggest the existence of a complex comprising SMG1, UPF1 and DHX34, with DHX34 functioning as a scaffold for UPF1 and SMG1. This complex promotes UPF1 phosphorylation leading to functional NMD.
Structural basis of complement membrane attack complex formation
Authors: Serna Marina , Giles Joanna L. , Morgan B. Paul , Bubeck Doryen 
Published: February 2016

AbstractIn response to complement activation, the membrane attack complex (MAC) assembles from fluid-phase proteins to form pores in lipid bilayers. MAC directly lyses pathogens by a ‘multi-hit’ mechanism; however, sublytic MAC pores on host cells activate signalling pathways. Previous studies have described the structures of individual MAC components and subcomplexes; however, the molecular details of its assembly and mechanism of action remain unresolved. Here we report the electron cryo-microscopy structure of human MAC at subnanometre resolution. Structural analyses define the stoichiometry of the complete pore and identify a network of interaction interfaces that determine its assembly mechanism. MAC adopts a ‘split-washer’ configuration, in contrast to the predicted closed ring observed for perforin and cholesterol-dependent cytolysins. Assembly precursors partially penetrate the lipid bilayer, resulting in an irregular β-barrel pore. Our results demonstrate how differences in symmetric and asymmetric components of the MAC underpin a molecular basis for pore formation and suggest a mechanism of action that extends beyond membrane penetration.
Cancer-associated SF3B1 mutations affect alternative splicing by promoting alternative branchpoint usage
Authors: Alsafadi Samar , Houy Alexandre , Battistella Aude , Popova Tatiana , Wassef Michel , Henry Emilie , Tirode Franck , Constantinou Angelos , Piperno-Neumann Sophie , Roman-Roman Sergio , Dutertre Martin , Stern Marc-Henri 
Published: February 2016

AbstractHotspot mutations in the spliceosome gene SF3B1 are reported in ∼20% of uveal melanomas. SF3B1 is involved in 3′-splice site (3′ss) recognition during RNA splicing; however, the molecular mechanisms of its mutation have remained unclear. Here we show, using RNA-Seq analyses of uveal melanoma, that the SF3B1R625/K666 mutation results in deregulated splicing at a subset of junctions, mostly by the use of alternative 3′ss. Modelling the differential junctions in SF3B1WT and SF3B1R625/K666 cell lines demonstrates that the deregulated splice pattern strictly depends on SF3B1 status and on the 3’ss-sequence context. SF3B1WT knockdown or overexpression do not reproduce the SF3B1R625/K666 splice pattern, qualifying SF3B1R625/K666 as change-of-function mutants. Mutagenesis of predicted branchpoints reveals that the SF3B1R625/K666-promoted splice pattern is a direct result of alternative branchpoint usage. Altogether, this study provides a better understanding of the mechanisms underlying splicing alterations induced by mutant SF3B1 in cancer, and reveals a role for alternative branchpoints in disease.
Cellular delivery and photochemical release of a caged inositol-pyrophosphate induces PH-domain translocation in cellulo
Authors: Pavlovic Igor , Thakor Divyeshsinh T. , Vargas Jessica R. , McKinlay Colin J. , Hauke Sebastian , Anstaett Philipp , Camuña Rafael C. , Bigler Laurent , Gasser Gilles , Schultz Carsten , Wender Paul A. , Jessen Henning J. 
Published: February 2016

AbstractInositol pyrophosphates, such as diphospho-myo-inositol pentakisphosphates (InsP7), are an important family of signalling molecules, implicated in many cellular processes and therapeutic indications including insulin secretion, glucose homeostasis and weight gain. To understand their cellular functions, chemical tools such as photocaged analogues for their real-time modulation in cells are required. Here we describe a concise, modular synthesis of InsP7 and caged InsP7. The caged molecule is stable and releases InsP7 only on irradiation. While photocaged InsP7 does not enter cells, its cellular uptake is achieved using nanoparticles formed by association with a guanidinium-rich molecular transporter. This novel synthesis and unprecedented polyphosphate delivery strategy enable the first studies required to understand InsP7 signalling in cells with controlled spatiotemporal resolution. It is shown herein that cytoplasmic photouncaging of InsP7 leads to translocation of the PH-domain of Akt, an important signalling-node kinase involved in glucose homeostasis, from the membrane into the cytoplasm.
PAF-Wnt signaling-induced cell plasticity is required for maintenance of breast cancer cell stemness
Authors: Wang Xin , Jung Youn-Sang , Jun Sohee , Lee Sunhye , Wang Wenqi , Schneider Andrea , Sun Oh Young , Lin Steven H. , Park Bum-Joon , Chen Junjie , Keyomarsi Khandan , Park Jae-Il 
Published: February 2016

AbstractCancer stem cells (CSCs) contribute to tumour heterogeneity, therapy resistance and metastasis. However, the regulatory mechanisms of cancer cell stemness remain elusive. Here we identify PCNA-associated factor (PAF) as a key molecule that controls cancer cell stemness. PAF is highly expressed in breast cancer cells but not in mammary epithelial cells (MECs). In MECs, ectopic expression of PAF induces anchorage-independent cell growth and breast CSC marker expression. In mouse models, conditional PAF expression induces mammary ductal hyperplasia. Moreover, PAF expression endows MECs with a self-renewing capacity and cell heterogeneity generation via Wnt signalling. Conversely, ablation of endogenous PAF induces the loss of breast cancer cell stemness. Further cancer drug repurposing approaches reveal that NVP-AUY922 downregulates PAF and decreases breast cancer cell stemness. Our results unveil an unsuspected role of the PAF-Wnt signalling axis in modulating cell plasticity, which is required for the maintenance of breast cancer cell stemness.
Nucleotide-dependent assembly of the peroxisomal receptor export complex
Authors: Grimm Immanuel , Saffian Delia , Girzalsky Wolfgang , Erdmann Ralf 
Published: February 2016

AbstractPex1p and Pex6p are two AAA-ATPases required for biogenesis of peroxisomes. Both proteins form a hetero-hexameric complex in an ATP-dependent manner, which has a dual localization in the cytosol and at the peroxisomal membrane. At the peroxisomal membrane, the complex is responsible for the release of the import receptor Pex5p at the end of the matrix protein import cycle. In this study, we analyzed the recruitment of the AAA-complex to its anchor protein Pex15p at the peroxisomal membrane. We show that the AAA-complex is properly assembled even under ADP-conditions and is able to bind efficiently to Pex15p in vivo. We reconstituted binding of the Pex1/6p-complex to Pex15p in vitro and show that Pex6p mediates binding to the cytosolic part of Pex15p via a direct interaction. Analysis of the isolated complex revealed a stoichiometry of Pex1p/Pex6p/Pex15p of 3:3:3, indicating that each Pex6p molecule of the AAA-complex binds Pex15p. Binding of the AAA-complex to Pex15p in particular and to the import machinery in general is stabilized when ATP is bound to the second AAA-domain of Pex6p and its hydrolysis is prevented. The data indicate that receptor release in peroxisomal protein import is associated with a nucleotide-depending Pex1/6p-cycle of Pex15p-binding and release.