julilili42/papers huggingface dataset:
Oxo-magnesio-hastingsite, NaCa2(Mg2Fe3+3 )(Al2Si6)O22O2, a new anhydrous amphibole from the Deeti volcanic cone, Gregory rift, northern Tanzania
2013-08-01

Abstract Oxo-magnesio-hastingsite, ideally NaCa 2 (Mg 2 Fe 3+ 3 )(Al 2 Si 6 )O 22 O 2 , is a new anhydrous amphibole from the Deeti volcanic cone in the Gregory rift (northern Tanzania). The mineral occurs as megacrysts up to 12 cm in size in crystal-rich tuff. Oxo-magnesio-hastingsite is brown with a vitreous lustre and has a perfect {110} cleavage. The measured density is 3.19(1) g/cm 3 . Ferri-kaersutite is biaxial (–), α = 1.706 (2), β = 1.715(2), γ = 1.720(2) (Na light, 589 nm). 2V (calc.) = 73°. Dispersion: r &gt; v, weak; orientation: Y = b ; Z ^ c = 8°; pleochroism: strong, Z: dark brown, Y: brown, X: light brown. The average chemical formula of the mineral derived from electron microprobe analyses, Mössbauer spectroscopy and direct water determination is (Na 0.67 K 0.33 ) Σ1.00 (Ca 1.87 Na 0.14 Mn 0.01 ) Σ2.02 (Mg 3.27 Fe 3+ 1.25 Ti 0.44 Al 0.08 ) Σ5.04 (Al 1.80 Si 6.20 O 22 )(O 1.40 OH 0.60 ) Σ2.00 . It has monoclinic symmetry, space group C2/ m and unit-cell parameters a = 9.8837(3), b = 18.0662(6), c = 5.3107(2) Å, b = 105.278(1)o, V = 914.77(5) Å 3 , Z = 2. The five strongest powder-diffraction lines [ d in Å, (I/Io), hkl ] are: 3.383 (62) (131), 2.708 (97) (151), 2.555 (100) ( ), 2.349 (29) ( ) and 2.162 (36) (261). The isotopic composition of H and O, as well as the concentration of trace elements in oxo-magnesio-hastingsite suggest its formation from a melt originated from a mantle source metasomatized by slab-derived fluids.
Notch receptors in human choroid plexus tumors.
2013-08-01

Notch signaling plays a role in development and formation of the normal choroid plexus (nCP), and in formation of various tumors in humans. Activation of Notch3 has been reported to promote tumor growth in invasive gliomas and to initiate formation of choroid plexus tumors (CPT) in mice. We investigated the expression of all currently known Notch receptors (Notch 1-4) in 55 samples of nCP and 88 CPT, including 61 choroid plexus papillomas (CPP), 22 atypical CPP and 5 choroid plexus carcinomas by immunohistochemistry. Notch expression was semiquantitatively evaluated separately for membranous/cytoplasmic and for nuclear staining. In addition, we examined Her2 expression (EGFR2, Her2/neu, ErbB2, CD340) because of its functional link to Notch signaling. All samples were negative for Notch3. Membranous/cytoplasmic expression of Notch1 (p<0.0001) and Notch4 (p=0.046) was significantly higher, whereas Notch2 expression was significantly lower (p<0.0001) in nCP compared to CPT. Nuclear expression of Notch1, -2 and -4 was significantly higher in CPT compared to nCP (p<0.0001 each). Expression of Notch2 and Notch4 showed a shift from a prevailing membranous/cytoplasmic expression in nCP to a predominant nuclear expression in CPT. Her2 was weakly expressed in 42/84 CPT but only in 2/53 nCP (p=0.0001) and positively correlated with nuclear expression of Notch1, -2 and 4 in CPT. In summary, a shift between membranous/cytoplasmic (non-canonical signaling pathway) and nuclear expression (canonical signaling pathway) of Notch1, -2 and -4 and upregulation of Her2 indicate neoplastic transformation in human CP and may reveal new therapeutic approaches.
cGMP-dependent kinase 2, Na+/H+ regulatory factor 2, and Na+/H+ exchanger isoform 3 assemble within lipid rafts in murine small intestinal brush border membrane
2013-08-01

Trafficking, brush border membrane (BBM) retention, and signal-specific regulation of the Na+/H+ exchanger NHE3 is regulated by Na+/H+ Exchanger Regulatory Factor (NHERF) family of PDZ-adapter proteins, which enable the formation of multiprotein complexes. It is unclear, however, what determines signal specificity of the very homologous NHERFs. We studied the association of NHE3, as well as NHERF1 (EBP50), NHERF2 (E3KARP) and NHERF3 (PDZK1) with lipid rafts in murine small intestinal BBM and their possible association with signaling molecules. NHE3 was found to partially associate with glycosphingolipid-enriched microdomains in the native BBM, and NHE3 raft association had an impact on NHE3 transport activity as well as on second-messenger-dependent regulation in vivo. NHERF1, 2 and 3 were differentially distributed to rafts and non-rafts, with NHERF2 being most raft-associated and NHERF3 entirely non-raft associated. A search for other signalling molecules that are implicated in regulating NHE3 through a NHERF interaction, cGMP-dependent kinase II, which together with NHERF2 is essential for guanylin/heat stable enterotoxin of E.coli (STa)-mediated NHE3 inhibition in the intestine, was found exclusively lipid-raft associated. In conclusion, the differential association of the NHERFs, as well as kinases, with the raft-associated and the non-raft fraction of NHE3 in the brush border membrane is likely one component of the differential and signal-specific NHE3 regulation by the different NHERFs.
Monoclonal Antibodies to Discriminate the EF Hand Containing Calcium Binding Adaptor Proteins EFhd1 and EFhd2
2013-08-01

Small Ca(2+) binding adaptor proteins of the EF hand family play important roles in neuronal and immune cell Ca(2+) signaling. Swiprosin-1/EFhd2 (EFhd2) and Swiprosin-2/EFhd1 (EFhd1) are conserved and very homologous Ca(2+) binding adaptor proteins of the EF hand family, with possibly redundant functions. In particular, EFhd2 has been proposed to be involved in B cell signaling and neuropathological disorders. Little is known thus far about the expression of EFhd2 on the single cell level in tissue sections or blood cells. Here we describe the generation of four specific anti-EFhd2 monoclonal antibodies. These recognize murine and human EFhd2, but not murine EFhd1, and their binding site maps to a region in the N-terminal part of EFhd2, where EFhd2 and EFhd1 differ most. Moreover, to detect EFhd1 specifically, we also generated anti-EFhd1 polyclonal antibodies, making use of a singular peptide of the N-terminal part of the protein. Using anti-EFhd2 MAb, we reveal two EFhd2 pools in B cells, one at the membrane and one cytoplasmic pool. Staining of human peripheral blood mononuclear cells shows EFhd2 expression in B cells but a ∼5 fold higher expression in monocytes. Taken together, EFhd2 monoclonal antibodies will be valuable to assess the real subcellular localization and expression level of EFhd2 in healthy and diseased primary cells and tissues.
Edge superconductivity in Nb thin film microbridges revealed by electric transport measurements and visualized by scanning laser microscopy
2013-08-01

The resistance R versus perpendicular external magnetic field H was measured for superconducting Nb thin film microbridges with and without microholes (antidots, ADs). Well below the transition temperature, integral R(H) measurements of the resistive transition to the normal state on the plain bridge show two distinct regions, which can be identified as bulk and edge superconductivity, respectively. The latter case appears when bulk superconductivity becomes suppressed at the upper critical field Hc2 and below the critical field of edge superconductivity Hc3 ≈ 1.7 Hc2. The presence of additional edges in the AD bridge leads to a different shape of the R(H) curves. We used low-temperature scanning laser microscopy (LTSLM) to visualize the current distribution in the plain and AD bridges upon sweeping H. While the plain bridge shows a dominant LTSLM signal at its edges for H > Hc2 the AD bridge also gives a signal from the inner parts of the bridge due to the additional edge states around the ADs. LTSLM reveals an asymmetry in the current distribution between the left and right edges, which confirms theoretical predictions. Furthermore, the experimental results are in good agreement with our numerical simulations (based on the time-dependent Ginzburg–Landau model), yielding the spatial distribution of the order parameter and current density for different bias currents and H values.
Replacement of Osmotic Minipumps to Extend the Intracerebral Infusion time of Compounds into the Mouse Brain
2013-08-01

Osmotic minipumps represent a convenient and established method for targeted delivery of agents into the brain of small rodents. Agents unable to cross the blood brain barrier can be directly infused into the brain parenchyma or lateral ventricle through implanted cannulas. The small volume of the minipump reservoir typically limits the infusion time to 4-6 weeks. Pump changes with reattachment of a new pump reservoir to the cannula might lead to brain tissue irritation or increased intracranial pressure associated with hydrocephalus. Here, we describe a pump reservoir exchange technique using a Y-shaped connection piece (Y-con) between the infusion cannula and the pump reservoir. This allows repeated replacement of a subcutaneously installed pump reservoir for brain delivery of agents in mice. Experimental evaluation of Y-con pump replacement revealed no signs of tissue irritation or hydrocephalus and allowed extended controlled delivery of infusion agents in the brain.
Functions are data too
2013-08-01

We demonstrate a full-fledged implementation of first-class functions for the widely used PL/SQL database programming language. Functions are treated as regular data items that may be (1) constructed at query runtime, (2) stored in and retrieved from tables, (3) assigned to variables, and (4) passed to and from other (higher-order) functions. The resulting PL/SQL dialect concisely and elegantly expresses a wide range of new query idioms which would be cumbersome to formulate if functions remained second-class citizens. We include a diverse set of application scenarios that make these advantages tangible. First-class PL/SQL functions require featherweight syntactic extensions only and come with a non-invasive implementation-- the defunctionalization transformation--that can entirely be built on top of existing relational DBMS infrastructure. An interactive demonstrator helps users to experiment with the "function as data" paradigm and to earn a solid intuition of its inner workings.
Dual actions of ANP on endothelial permeability
2013-08-01

Atrial natriuretic peptide (ANP), via its cGMP-forming guanylyl cyclase-A (GC-A) receptor, is critically involved in the regulation of arterial blood pressure and intravascular volume. To elucidate the role of the endothelial effects of ANP, we generated mice with conditional, endothelium (EC)-restricted ablation of the GC-A gene. Our observations in these and control mice demonstrated that ANP, via GC-A, mildly stimulates systemic transendothelial albumin transport in the microvasculature of skeletal muscle and skin. These and other studies indicate that concerted renal diuretic/natriuretic and mild endothelial hyperpermeability actions of ANP are essential to adjust intravascular fluid volume. However, this notion apparently contradicts published in vitro and in vivo studies showing that ANP can strenghen the pulmonary barrier under inflammatory conditions, suggesting that the hormone either acts differently on pulmonary vs systemic endothelium, or it exerts opposite effects on quiescent endothelia (enhanced permeability) and an inflammation-activated endothelium (barrier stabilization). Endothelial hyperpermeability is characteristic of many systemic diseases, such as allergic responses, edema, and sepsis. In particular, histamine markedly and acutely enhances endothelial permeability. Activation of endothelial Gq-coupled H1 receptors activates phospholipase C and elevates intracellular [Ca2+], ultimately leading to actin-myosin contraction and paracellular leakiness. Here we combined studies in microvascular endothelial cells and intravital microscopy of vascular permeability in the m. cremaster microcirculation to study whether ANP counteracts not only pulmonary but also systemic inflammation, i.e. histamine-induced hyperpermeability. Our observations reveal that transient receptor potential canonical (TRPC) 6 channels mediate the inflammatory effects of histamine. Most importantly, they characterize a regulatory pathway by which histamine-induced activation of TRPC6 channels and subsequent calcium-dependent acute endothelial hyperpermeability are prevented by ANP/GC-A-induced, cGMP-dependent protein kinase I (cGKI) - mediated inhibitory phosphorylation of these channels.
Michaelis-Menten kinetics, the operator-repressor system, and least squares approaches
2013-08-01

The Michaelis-Menten (MM) function is a fractional linear function depending on two positive parameters. These can be estimated by nonlinear or linear least squares methods. The non-linear methods, based directly on the defect of the MM function, can fail and not produce any minimizer. The linear methods always produce a unique minimizer which, however, may not be positive. Here we give sufficient conditions on the data such that the nonlinear problem has at least one positive minimizer and also conditions for the minimizer of the linear problem to be positive. We discuss in detail the models and equilibrium relations of a classical operator-repressor system, and we extend our approach to the MM problem with leakage and to reversible MM kinetics. The arrangement of the sufficient conditions exhibits the important role of data that have a concavity property (chemically feasible data).
Macro and microglial retinal cells in rat organotypic cultures
2013-08-01

Abstract Purpose Organotypic retinal cultures constitute a useful tool to perform preclinical drug testing. The aim of the present study was characterize the morphologic changes in macro‐ and microglial cells in this culture system. Methods Retinas were isolated from 7‐day‐old Crl:CD(SD) rats with the retinal pigment epithelium attached. Retinal explants were cultured for 4, 10, and 14 days (DIV4, DIV10, and DIV14). Cryosections and whole‐mounts of age‐matched control and cultured retinas were used to analyze macro‐ and microglial cells by immunostaining using antibodies against GFAP, vimentin and CD11‐b. Results In comparison with in vivo, in DIV4 and DIV10 cultures, GFAP‐positive astrocytes were more robust, the astrocytic network being thicker in some retinal areas while in other regions astrocytes were sparsely distributed. Few thin GFAP‐positive astrocytes were observed at DIV14. Müller cells in the cultures exhibited GFAP up‐regulation in comparison with in vivo retinas. CD11‐b+ microglial cells at DIV4 and DIV10 showed more robust somas and thicker and more retracted processes than in vivo. Overall, at DIV14 CD11‐b+, microglial cells exhibited a rounded morphology. Conclusion In rat organotypic culture both macro‐ and microglial cells showed progressive changes: i) reactive macrogliosis, ii) rearranged astrocytic distribution, iii) GFAP up‐regulation in Müller cells, and iv) microglial activation. Given that this glial response is a hallmark of several retinal diseases, organotypic retinal culture is a valuable resource for future investigations in retinal degenerative processes and therapy.
Cyclic GMP-mediated intercellular communication in mammalian ovarian follicles
2013-08-01

Background In mammalian ovarian follicles, granulosa cells keep fully grown oocytes arrested in meiotic prophase. A key inhibitory signal is cGMP, which diffuses into the oocyte from the granulosa cells, where it is synthesized by guanylyl cyclase B/ natriuretic peptide receptor 2 (NPR2) in response to the agonist C-type natriuretic peptide (CNP) [1]. Then in response to luteinizing hormone (LH), cGMP in the granulosa cells and oocyte decreases, promoting resumption of meiosis [2]. The primary mechanism by which LH signaling reduces cGMP in the granulosa cells is by reducing the activity of NPR2; this occurs by a rapid modification of the NPR2 protein, followed by a decrease in CNP in the ovary [3].
About the role and underlying mechanisms of cofactors in anaphylaxis
2013-08-02

Abstract Anaphylaxis is the systemic and most severe presentation of type I allergy. A number of conditions were identified that modulate the onset of anaphylaxis such as co‐ or augmentation factors, which significantly lower the allergen dose necessary for triggering anaphylaxis. Next to physical exercise or alcohol consumption, co‐administration of nonsteroidal anti‐inflammatory drugs ( NSAID ) or concomitant infectious diseases are well‐documented cofactors of anaphylaxis. Registries for anaphylaxis document a role for cofactors in about 30% of anaphylactic reactions. Some disease entities such as ‘wheat‐dependent exercise‐induced anaphylaxis’ ( WDEIA ) are explicitly characterized by elicitation of anaphylaxis only in the presence of at least one such cofactor. Using WDEIA as a model disease, studies demonstrated that exercise increases skin prick test reactivity to and bioavailability of the allergen. Additional data indicate that alcohol consumption and NSAID administration display similar effects. Modulation of the cellular activation threshold is another mechanism underlying cofactor‐induced anaphylaxis, most likely also functional when infectious diseases orchestrate elicitation of anaphylaxis. Cofactors are increasingly accepted to play a fundamental role in eliciting anaphylaxis. Consequently, to improve patient management modalities, a better understanding of the underlying mechanisms is warranted. This review aims to update clinicians and clinical scientists on recent developments.
Population‐specific frequencies for LRRK2 susceptibility variants in the genetic epidemiology of Parkinson's disease (GEO‐PD) consortium
2013-08-02

ABSTRACT Background Variants within the leucine‐rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine‐rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late‐onset sporadic disorders like Parkinson's disease. Methods The Genetic Epidemiology of Parkinson's Disease Consortium recently performed the largest genetic association study for variants in the leucine‐rich repeat kinase 2 gene across 23 different sites in 15 countries. Results Herein, we detail the allele frequencies for the novel risk factors (p.A419V and p.M1646T) and the protective haplotype (p.N551K‐R1398H‐K1423K) nominated in the original publication. Simple population allele frequencies not only can provide insight into the clinical relevance of specific variants but also can help genetically define patient groups. Conclusions Establishing individual patient‐based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies. © 2013 International Parkinson and Movement Disorder Society
Stable and metastable hard-sphere crystals in fundamental measure theory
2013-08-02

Using fully minimized fundamental measure functionals, we investigate free energies, vacancy concentrations, and density distributions for bcc, fcc, and hcp hard-sphere crystals. Results are complemented by an approach due to Stillinger, which is based on expanding the crystal partition function in terms of the number n of free particles while the remaining particles are frozen at their ideal lattice positions. The free energies of fcc and hcp and one branch of bcc agree well with Stillinger's approach truncated at n=2. A second branch of bcc solutions features rather spread-out density distributions around lattice sites and large equilibrium vacancy concentrations and is presumably linked to the shear instability of the bcc phase. Within fundamental measure theory and the Stillinger approach (n=2), hcp is more stable than fcc by a free energy per particle of about 0.001k(B)T. In previous simulation work, the reverse situation has been found, which can be rationalized in terms of effects due to a correlated motion of at least five particles in the Stillinger picture.
Heme oxygenase-1 mediates ROS production and ongoing injury in CVB3 myocarditis
2013-08-02

Purpose: In different inflammatory processes heme oxygenase-1 (HO-1), the heat shock/stress cognate of the heat shock protein 32 (HSP32) family of proteins, has been shown to play a role in defending the organism against oxidative stress-mediated injury during. HO-1 can be induced by different molecules including nitric oxide (NO). Based on our findings that in contrast to resistant C57BL/6 mice coxsackievirus B3 (CVB3)-infected SWR/J mice, which are susceptible for chronic myocarditis, show enhanced NO production and cardiac damage at later stages of the disease, we aimed to investigate the molecular interplay between HO-1, oxidative stress and apoptosis in chronic viral myocarditis. Methods and results: In hearts of SWR/J mice revealing ongoing inflammatory processes we found that CVB3-activated macrophages are characterized by increased oxidative activities as visualized by superoxide production. In the myocardium, the enhanced oxidative activities are correlated with the upregulation of the HO-1 mRNA and protein in macrophages and myocytes as shown by qRT-PCR, in situ hybridization and immunohistochemistry. Cell culture experiments confirmed these results by demonstrating an increase of HO-1 mRNA in CVB3-stimulated RAW 264.7 macrophages. In CVB3-infected SWR/J mice but not in C57BL/6 mice, nitric-oxide synthase (iNOS) mRNA was found to be highly expressed in cardiac macrophages in correlation with enhanced activation of HO-1. Cell culture experiments revealed that inhibition of NO production with L-NAME can decrease HO-1 protein expression. Blockage of HO-1 with tin mesoporphyrin resulted in a decrease of ROS production, suggesting that HO-1 might enhance oxidative stress in CVB3-infected hearts and increase cardiac damage. In the myocardium HO-1 expression was not only detected in macrophages but also in myocytes upon CVB3 infection as shown by in situ hybridization and immunohistochemistry. Interestingly, cardiomyocytes of CVB3-infected SWR/J mice revealed a much stronger expression of HO-1 than those of C57BL/6 mice which was correlated which apoptosis at later stages of the disease. Knockdown experiments in CVB3-infected HeLa cells, a well known model for CVB3-induced myocarditis, by siRNA directed against HO-1 were found to be associated with the downregulation of caspase-3, and thus apoptosis. Conclusions: In ongoing enteroviral myocarditis HO-1, which is mainly described as a cytoprotective antioxidant molecule, induces a paracrine signalling via ROS production in virus-activated macrophages and mediates apoptosis of cardiomyocytes, thus contributing to chronic cardiac injury.