julilili42/papers huggingface dataset:
Cyclophilin A predicts clinical outcome in patients with congestive heart failure undergoing endomyocardial biopsy
2012-12-14

Aims Cyclophilin A (CyPA) represents a ubiquitous intracellular protein, which is secreted by inflammatory and by dying/necrotic cells. The aim of this study was to evaluate the prognostic relevance of CyPA expression in endomyocardial biopsies of consecutive patients with congestive heart failure. Methods and results A total of 227 unselected patients (age 53.9 ± 15 years) with congestive heart failure undergoing endomyocardial biopsy for diagnostic reasons were enrolled. Biopsies were analysed using established histopathological and immunohistological criteria together with CyPA staining. Virus genome was studied by polymerase chain reaction. CyPA was significantly enhanced in patients with inflammatory cardiomyopathy ( n = 127) as compared with patients with non‐inflammatory cardiomyopathy ( n = 100, P &lt; 0.0001). During a mean follow‐up of 16.3 months, 60 patients (26.4%) reached the primary endpoint, a composite of all‐cause death, heart transplantation, malignant arrhythmia, and heart failure‐related rehospitalization. Of all clinical (ejection fraction, New York Heart Association functional class), laboratory (brain natriuretic peptide), and immunohistological parameters (CyPA, extracellular matrix metalloproteinase inducer, CD68, CD3, major hisocompatibility complex II, and virus genome) tested, only CyPA was identified as an independent predictor for the composite endpoint [hazard ratio (HR) 2.4; 95% confidence interval (CI) 1.2–5.2; P = 0.019] as well as for all‐cause death and heart transplantation alone (HR 4.7; 95% CI 1.1–19.8; P = 0.036). Subgroup analysis revealed CyPA as a predictor in patients with non‐inflammatory cardiomyopathy for the composite endpoint (HR 3.0; 95% CI 1.3–6.6; P = 0.007) as well as all‐cause death or heart transplantation alone (HR 6.4; 95% CI 1.4–28.1; P = 0.014). Conclusions CyPA is an independent predictor of clinical outcome in patients with congestive heart failure undergoing endomyocardial biopsy.
Loss of DJ‐1 protein stability and cytoprotective function by Parkinson's disease‐associated proline‐158 deletion
2012-12-14

Abstract DJ ‐1 is a ubiquitous protein regulating cellular viability. Recessive mutations in the PARK 7/ DJ ‐1 gene are linked to Parkinson's disease ( PD ). Although the most dramatic L166P point mutation practically eliminates DJ ‐1 protein and function, the effects of other PD ‐linked mutations are subtler. Here, we investigated two recently described PD ‐associated DJ ‐1 point mutations, the A179T substitution and the P158Δ in‐frame deletion. [A179T] DJ ‐1 protein was as stable as wild‐type [wt] DJ ‐1, but the P158Δ mutant protein was less stable. In accord with the notion that dimer formation is essential for DJ ‐1 protein stability, [P158Δ] DJ ‐1 was impaired in dimer formation. Similar to our previous findings for [M26I] DJ ‐1, [P158Δ] DJ ‐1 bound aberrantly to apoptosis signal‐regulating kinase 1. Thus, the PD ‐associated P158Δ mutation destabilizes DJ ‐1 protein and function. As there is also evidence for an involvement of DJ ‐1 in multiple system atrophy, a PD ‐related α‐synucleinopathy characterized by oligodendroglial cytoplasmic inclusions, we studied an oligodendroglial cell line stably expressing α‐synuclein. α‐Synuclein aggregate dependent microtubule retraction upon co‐transfection with tubulin polymerization‐promoting protein p25α was ameliorated by [wt] DJ ‐1. In contrast, DJ ‐1 mutants including P158Δ failed to protect in this system, where we found evidence of apoptosis signal‐regulating kinase 1 ( ASK 1) involvement. In conclusion, the P158Δ point mutation may contribute to neurodegeneration by protein destabilization and hence loss of DJ ‐1 function.
Heritage – Contemporary Uses of Culture beyond the Everyday? Challenging Ethnography and Cultural Analysis
2012-12-14

Based on the premise that, today, “doing culture” has to be understood as both “acting in culture” and “acting with culture”, this paper discusses new perspectives on the complex field of cultural heritage. Using examples from dialect research as well as museum and heritage studies, it points out a conscious usage of culture in everyday life and states the need for a more elaborate understanding of the concepts of culture and the way they are perceived, negotiated and used by different actors. *** Na podlagi izhodišča, da moramo danes zvezo »delati/ustvarjati kulturo« razumeti hkrati kot »delovati v kulturi« in »delovati s kulturo«, prispevek obravnava nove perspektive na kompleksnem področju kulturne dediščine. Z zgledi iz raziskav narečij, muzejev in dediščinskih študij opozarja na zavestno rabo kulture v vsakdanjem življenju in ugotavlja potrebo po bolj iztanjšanem razumevanju konceptov kulture in načina, kako kulturo dojemajo, obravnavajo in uporabljajo različni akterji.
Doing European Ethnology in a Time of Change. The Metamorphosis of a Discipline (In Germany and in Europe)
2012-12-14

Sciences change and develop, but rare are the disciplines that experience such shifts in paradigm as is the case in ethnology, Volkskunde, in German-speaking countries. This is linked to its history (and its involvement in national socialism), but it is also possible to explain with the profound changes of the research field – from a peasant society to the globalized everyday of the 21st century. We may ask ourselves, if in this regard the “special German path”, “German Sonderweg” has come to its end or if the discipline – together with its national sister discipline such as European ethnology is moving towards a common European future. This piece represents an attempt to shed light on the problems as well as possibilities of such a project. In any case Slovenian ethnology also has an important role in this endeavor. *** Znanosti se spreminjajo, pa vendar so le redke discipline doživele takšne paradigmatske spremembe kakor etnologija/narodopisje (Volkskunde) na nemškem jezikovnem območju. To je povezano z njeno zgodovino (in njeno vpletenostjo v nacionalsocializem), mogoče pa jih je pojasniti tudi s korenito spremenjenim raziskovalnim poljem – od kmečke družbe h globaliziranemu vsakdanjiku 21. stoletja. Lahko se vprašamo, ali gre pri tem »posebna nemška pot« h koncu? In, ali gre disciplina skupaj z nacionalnimi sestrskimi disciplinami kot evropska etnologija k skupni evropski prihodnosti? V prispevku gre za poskus osvetlitve težav, a tudi možnosti pri takšnem projektu. Vsekakor ima pri tem pomembno vlogo tudi slovenska etnologija.
Receptor Activator for NF-κB Ligand in Acute Myeloid Leukemia: Expression, Function, and Modulation of NK Cell Immunosurveillance
2012-12-16

Abstract The TNF family member receptor activator for NF-κB ligand (RANKL) and its receptors RANK and osteoprotegerin are key regulators of bone remodeling but also influence cellular functions of tumor and immune effector cells. In this work, we studied the involvement of RANK–RANKL interaction in NK cell–mediated immunosurveillance of acute myeloid leukemia (AML). Substantial levels of RANKL were found to be expressed on leukemia cells in 53 of 78 (68%) investigated patients. Signaling via RANKL into the leukemia cells stimulated their metabolic activity and induced the release of cytokines involved in AML pathophysiology. In addition, the immunomodulatory factors released by AML cells upon RANKL signaling impaired the anti-leukemia reactivity of NK cells and induced RANK expression, and NK cells of AML patients displayed significantly upregulated RANK expression compared with healthy controls. Treatment of AML cells with the clinically available RANKL Ab Denosumab resulted in enhanced NK cell anti-leukemia reactivity. This was due to both blockade of the release of NK-inhibitory factors by AML cells and prevention of RANK signaling into NK cells. The latter was found to directly impair NK anti-leukemia reactivity with a more pronounced effect on IFN-γ production compared with cytotoxicity. Together, our data unravel a previously unknown function of the RANK–RANKL molecule system in AML pathophysiology as well as NK cell function and suggest that neutralization of RANKL with therapeutic Abs may serve to reinforce NK cell reactivity in leukemia patients.
Tools for Label-free Peptide Quantification
2012-12-17

The increasing scale and complexity of quantitative proteomics studies complicate subsequent analysis of the acquired data. Untargeted label-free quantification, based either on feature intensities or on spectral counting, is a method that scales particularly well with respect to the number of samples. It is thus an excellent alternative to labeling techniques. In order to profit from this scalability, however, data analysis has to cope with large amounts of data, process them automatically, and do a thorough statistical analysis in order to achieve reliable results. We review the state of the art with respect to computational tools for label-free quantification in untargeted proteomics. The two fundamental approaches are feature-based quantification, relying on the summed-up mass spectrometric intensity of peptides, and spectral counting, which relies on the number of MS/MS spectra acquired for a certain protein. We review the current algorithmic approaches underlying some widely used software packages and briefly discuss the statistical strategies for analyzing the data.
Murine Guanylate Binding Protein 2 (mGBP2) controlsToxoplasma gondiireplication
2012-12-17

IFN-γ orchestrates the host response against intracellular pathogens. Members of the guanylate binding proteins (GBP) comprise the most abundant IFN-γ–induced transcriptional response. mGBPs are GTPases that are specifically up-regulated by IFN-γ, other proinflammatory cytokines, toll-like receptor agonists, as well as in response to Listeria monocytogenes and Toxoplasma gondii infection. mGBP2 localizes at the parasitophorous vacuole (PV) of T. gondii ; however, the molecular function of mGBP2 and its domains in T. gondii infection is not known. Here, we show that mGBP2 is highly expressed in several cell types, including T and B cells after stimulation. We provide evidence that the C-terminal domain is sufficient and essential for recruitment to the T. gondii PV. Functionally, mGBP2 reduces T. gondii proliferation because mGBP2-deficient cells display defects in the replication control of T. gondii . Ultimately, mGBP2-deficient mice reveal a marked immune susceptibility to T. gondii . Taken together, mGBP2 is an essential immune effector molecule mediating antiparasitic resistance.
Influence of viscosity and the adiabatic index on planetary migration
2012-12-17

\\n Context. The strength and direction of migration of low mass embedded planets depends on the disk’s thermodynamic state. It has been shown that in active disks, where the internal dissipation is balanced by radiative transport, migration can be directed outwards, a process which extends the lifetime of growing embryos. Very important parameters determining the structure of disks, and hence the direction of migration, are the viscosity and the adiabatic index. \\n Aims. In this paper we investigate the influence of different viscosity prescriptions (α-type and constant) and adiabatic indices on disk structures. We then determine how this affects the migration rate of planets embedded in such disks. \\n Methods. We perform three-dimensional numerical simulations of accretion disks with embedded planets. We use the explicit/implicit hydrodynamical code NIRVANA that includes full tensor viscosity and radiation transport in the flux-limited diffusion approximation, as well as a proper equation of state for molecular hydrogen. The migration of embedded 20 MEarth planets is studied. \\n Results. Low-viscosity disks have cooler temperatures and the migration rates of embedded planets tend toward the isothermal limit. Hence, in these disks, planets migrate inwards even in the fully radiative case. The effect of outward migration can only be sustained if the viscosity in the disk is large. Overall, the differences between the treatments for the equation of state seem to play a more important role in disks with higher viscosity. A change in the adiabatic index and in the viscosity changes the zero-torque radius that separates inward from outward migration.\\n Conclusions. For larger viscosities, temperatures in the disk become higher and the zero-torque radius moves to larger radii, allowing outward migration of a 20-MEarth planet to persist over an extended radial range. In combination with large disk masses, this may allow for an extended period of the outward migration of growing protoplanetary cores. \\n
N terminus of ASPP2 binds to Ras and enhances Ras/Raf/MEK/ERK activation to promote oncogene-induced senescence
2012-12-17

The ASPP2 (also known as 53BP2L) tumor suppressor is a proapoptotic member of a family of p53 binding proteins that functions in part by enhancing p53-dependent apoptosis via its C-terminal p53-binding domain. Mounting evidence also suggests that ASPP2 harbors important nonapoptotic p53-independent functions. Structural studies identify a small G protein Ras-association domain in the ASPP2 N terminus. Because Ras-induced senescence is a barrier to tumor formation in normal cells, we investigated whether ASPP2 could bind Ras and stimulate the protein kinase Raf/MEK/ERK signaling cascade. We now show that ASPP2 binds to Ras–GTP at the plasma membrane and stimulates Ras-induced signaling and pERK1/2 levels via promoting Ras–GTP loading, B-Raf/C-Raf dimerization, and C-Raf phosphorylation. These functions require the ASPP2 N terminus because BBP (also known as 53BP2S), an alternatively spliced ASPP2 isoform lacking the N terminus, was defective in binding Ras–GTP and stimulating Raf/MEK/ERK signaling. Decreased ASPP2 levels attenuated H-RasV12–induced senescence in normal human fibroblasts and neonatal human epidermal keratinocytes. Together, our results reveal a mechanism for ASPP2 tumor suppressor function via direct interaction with Ras–GTP to stimulate Ras-induced senescence in nontransformed human cells.
Thomson scattering and collisional ionization in the X-ray grating spectra of the recurrent nova U Scorpii
2012-12-17

We present a Chandra observation of the recurrent nova U Scorpii, done with the High Resolution camera-S (HRC-S) detector and the Low Energy Transmission Grating (LETG) on day 18 after the observed visual maximum of 2010, and compare it with XMM-Newton observations obtained on days 23 and 35 after maximum. The total absorbed flux was in the range 2.2-2.6 × 10-11 erg cm-2 s-1, corresponding to unabsorbed luminosity 7-8.5 × 1036 ×(d/12 kpc)2 for N(H) = 2-2.7 × 1021 cm-2. On day 18, 70 per cent of the soft X-tray flux was in a continuum typical of a very hot white dwarf (WD) atmosphere, which accounted for about 80 per cent of the flux on days 23 and 35. In addition, all spectra display very broad emission lines, due to higher ionization stages at later times. With Chandra we observed apparent P Cygni profiles. We find that these peculiar profiles are not due to blueshifted absorption and redshifted emission in photoionized ejecta, like the optical P Cyg of novae, but they are rather a superposition of WD atmospheric absorption features reflected by the already discovered Thomson scattering corona, and emission lines due to collisional ionization in condensations in the ejecta. On days 23 and 35, the absorption components were no longer measurable, having lost the initial large blueshift that displaced them from the core of the broad emission lines. We interpret this as an indication that mass-loss ceased between day 18 and day 23. On day 35, the emission line spectrum became very complex, with several different components. Model atmospheres indicate that theWD atmospheric temperature was about 730 000 K on day 18 and reached 900 000-1000 000 K on day 35. This peak temperature is consistent with a WD mass of at least 1.3 M⊙. © 2012 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society.
Dip of the granular shear stress
2012-12-17

Recent experiments reveal an unexpected dip of the shear stress as the shear rate increases, from the rate-independent regime to Bagnold flow. Employing granular solid hydrodynamics, it is shown that in uniform systems, such dips occur for given pressure or normal stress, but not for given density. If the shear rate is strongly nonuniform, enforcing a constant volume does not prevent the local density to vary, and a stress dip may still occur.
Transient receptor potential vanilloid 1 (TRPV1), TRPV4, and the kidney
2012-12-18

Abstract Recent preclinical data indicate that activators of transient receptor potential channels of the vanilloid receptor subtype 1 ( TRPV 1) may improve the outcome of ischaemic acute kidney injury ( AKI ). The underlying mechanisms are unclear, but may involve TRPV 1 channels in dorsal root ganglion neurones that innervate the kidney. Recent data identified TRPV 4, together with TRPV 1, to serve as major calcium influx channels in endothelial cells. In these cells, gating of individual TRPV 4 channels within a four‐channel cluster provides elementary calcium influx (calcium sparklets) to open calcium‐activated potassium channels and promote vasodilation. The TRPV receptors can also form heteromers that exhibit unique conductance and gating properties, further increasing their spatio‐functional diversity. This review summarizes data on electrophysiological properties of TRPV 1/4 and their modulation by endogenous channel agonists such as 20‐HETE, phospholipase C and phosphatidylinositide 3‐kinase ( PI 3 kinase). We review important roles of TRPV 1 and TRPV 4 in kidney physiology and renal ischaemia reperfusion injury; further studies are warranted to address renoprotective mechanism of vanilloid receptors in ischaemic AKI including the role of the capsaicin receptor TRPV 1 in primary sensory nerves and/or endothelium. Particular attention should be paid to understand the kidneys' ability to respond to ischaemic stimuli after catheter‐based renal denervation therapy in man, whereas the discovery of novel pharmacological TRPV modulators may be a successful strategy for better treatment of acute or chronic kidney failure.
Optimized Demineralization Technique for the Measurement of Stable Isotope Ratios of Nonexchangeable H in Soil Organic Matter
2012-12-18

To make use of the isotope ratio of nonexchangeable hydrogen (δ(2)H(n (nonexchangeable))) of bulk soil organic matter (SOM), the mineral matrix (containing structural water of clay minerals) must be separated from SOM and samples need to be analyzed after H isotope equilibration. We present a novel technique for demineralization of soil samples with HF and dilute HCl and recovery of the SOM fraction solubilized in the HF demineralization solution via solid-phase extraction. Compared with existing techniques, organic C (C(org)) and organic N (N(org)) recovery of demineralized SOM concentrates was significantly increased (C(org) recovery using existing techniques vs new demineralization method: 58% vs 78%; N(org) recovery: 60% vs 78%). Chemicals used for the demineralization treatment did not affect δ(2)H(n) values as revealed by spiking with deuterated water. The new demineralization method minimized organic matter losses and thus artificial H isotope fractionation, opening up the opportunity to use δ(2)H(n) analyses of SOM as a new tool in paleoclimatology or geospatial forensics.
Selective Protection of Human Liver Tissue in TNF-Targeting of Cancers of the Liver by Transient Depletion of Adenosine Triphosphate
2012-12-18

Normal human liver tissues can be protected transiently against TNF-induced cell death by systemic pretreatment with fructose used in non-toxic/physiologic concentrations. Selective TNF-targeting of primary and secondary tumors of the liver by transient and specific depletion of hepatocytic ATP opens up a new clinical avenue for the TNF-based treatment of liver cancers.
Isolation, Structure Elucidation and Total Synthesis of Lajollamide A from the Marine Fungus Asteromyces cruciatus
2012-12-19

The marine-derived filamentous fungus Asteromyces cruciatus 763, obtained off the coast of La Jolla, San Diego, USA, yielded the new pentapeptide lajollamide A (1), along with the known compounds regiolone (2), hyalodendrin (3), gliovictin (4), 1N-norgliovicitin (5), and bis-N-norgliovictin (6). The planar structure of lajollamide A (1) was determined by Nuclear Magnetic Resonance (NMR) spectroscopy in combination with mass spectrometry. The absolute configuration of lajollamide A (1) was unambiguously solved by total synthesis which provided three additional diastereomers of 1 and also revealed that an unexpected acid-mediated partial racemization (2:1) of the l-leucine and l-N-Me-leucine residues occurred during the chemical degradation process. The biological activities of the isolated metabolites, in particular their antimicrobial properties, were investigated in a series of assay systems.
Low-Noise Nano Superconducting Quantum Interference Device Operating in Tesla Magnetic Fields
2012-12-19

Superconductivity in the cuprate YBa(2)Cu(3)O(7) (YBCO) persists up to huge magnetic fields (B) up to several tens of Teslas, and sensitive direct current (dc) superconducting quantum interference devices (SQUIDs) can be realized in epitaxially grown YBCO films by using grain boundary Josephson junctions (GBJs). Here we present the realization of high-quality YBCO nanoSQUIDs, patterned by focused ion beam milling. We demonstrate low-noise performance of such a SQUID up to B = 1 T applied parallel to the plane of the SQUID loop at the temperature T = 4.2 K. The GBJs are shunted by a thin Au layer to provide nonhysteretic current voltage characteristics, and the SQUID incorporates a 90 nm wide constriction which is used for on-chip modulation of the magnetic flux through the SQUID loop. The white flux noise of the device increases only slightly from 1.3 μΦ(0)/(Hz)(1/2) at B = 0 to 2.3 μΦ(0)/(Hz))(1/2) at 1 T. Assuming that a point-like magnetic particle with magnetization in the plane of the SQUID loop is placed directly on top of the constriction and taking into account the geometry of the SQUID, we calculate a spin sensitivity S(μ)(1/2) = 62 μ(B)/(Hz))(1/2) at B = 0 and 110 μ(B)/(Hz))(1/2) at 1 T. The demonstration of low noise of such a SQUID in Tesla fields is a decisive step toward utilizing the full potential of ultrasensitive nanoSQUIDs for direct measurements of magnetic hysteresis curves of magnetic nanoparticles and molecular magnets.
Biopsy-Controlled Liver Fibrosis Staging Using the Enhanced Liver Fibrosis (ELF) Score Compared to Transient Elastography
2012-12-19

Both the ELF score as well as transient elastography allowed for high quality fibrosis staging. However, the ELF score was less discriminative in low and moderate fibrosis stages and appeared more strongly influenced by inflammatory liver injury. This should be considered when making clinical interpretations on the basis of ELF score values.
Staphylococcal Disease in Africa: Another Neglected ‘Tropical‘ Disease
2012-12-19

The term 'neglected tropical diseases' predominantly refers to single-entity, mostly parasitic diseases. However, a considerable morbidity and mortality burden is carried by patients infected with Gram-positive cocci and Gram-negative bacilli that are prevalent all over the world, yet have impact in tropical and developing countries, particularly in children, with much higher incidence rates than those reported from developed countries. Staphylococcus aureus is among these pathogens. The African-German StaphNet consortium uses microbiological characterization of African S. aureus isolates, including identification of virulence factors, alongside the gathering of epidemiological and clinical data in an innovative research network between a European country (Germany) and several African partners. By creating an accessible strain repository and by implementing personnel training and capacity building, this network aims to put staphylococcal disease on the international agenda as a truly neglected condition with a major global impact on public health.