julilili42/papers huggingface dataset:
Tet3-Mediated Hydroxymethylation of Epigenetically Silenced Genes Contributes to Bone Morphogenic Protein 7-Induced Reversal of Kidney Fibrosis
2014-01-31

Methylation of CpG island promoters is an epigenetic event that can effectively silence transcription over multiple cell generations. Hypermethylation of the Rasal1 promoter contributes to activation of fibroblasts and progression of kidney fibrosis. Here, we explored whether such causative hypermethylation could be reversed through endogenous mechanisms and whether such reversal of hypermethylation is a constituent of the antifibrotic activity of bone morphogenic protein 7 (BMP7). We show that successful inhibition of experimental kidney fibrosis through administration of BMP7 associates with normalization of Rasal1 promoter hypermethylation. Furthermore, this reversal of pathologic hypermethylation was achieved specifically through Tet3-mediated hydroxymethylation. Collectively, our findings reveal a new mechanism that may be exploited to facilitate therapeutic DNA demethylation to reverse kidney fibrosis.
Spatial Filtering Based on Canonical Correlation Analysis for Classification of Evoked or Event-Related Potentials in EEG Data
2014-01-31

Classification of evoked or event-related potentials is an important prerequisite for many types of brain-computer interfaces (BCIs). To increase classification accuracy, spatial filters are used to improve the signal-to-noise ratio of the brain signals and thereby facilitate the detection and classification of evoked or event-related potentials. While canonical correlation analysis (CCA) has previously been used to construct spatial filters that increase classification accuracy for BCIs based on visual evoked potentials, we show in this paper, how CCA can also be used for spatial filtering of event-related potentials like P300. We also evaluate the use of CCA for spatial filtering on other data with evoked and event-related potentials and show that CCA performs consistently better than other standard spatial filtering methods.
Resistant Against De-depression: LTD-Like Plasticity in the Human Motor Cortex Induced by Spaced cTBS
2014-01-31

The long-term depression (LTD)-like changes in human primary motor cortex (M1) excitability induced by continuous theta burst stimulation (cTBS) are subject to reversal (i.e., de-depression) following behavioral engagement of M1, limiting its therapeutic potential under behaviorally relevant conditions. Experiments in animals suggest that the repeated, spaced application of stimulation trains may consolidate synaptic plasticity, making it resistant to reversal by physiological activity. Although there is evidence that repeated cTBS prolongs LTD-like M1 neuroplasticity in humans, whether these effects are resistant to de-depression has not been tested. We investigated whether the neuroplastic effects of paired cTBS trains were resistant to de-depression by a sustained, submaximal voluntary contraction of the hand muscles. In the absence of cTBS, voluntary contraction had no effect on motor evoked potentials (MEPs) recorded from the right first dorsal interosseous muscle. While the LTD-like MEP depression induced by a single cTBS was abolished by subsequent voluntary contraction, paired cTBS induced MEP depression that was resistant to reversal. This MEP depression was also resistant to reversal when an experimental de-depression protocol was used instead of a voluntary contraction. Our findings suggest that repeated cTBS applications consolidate LTD-like M1 neuroplasticity, which may have important implications for the clinical application of cTBS.
Interferon‐γ induces leucine‐rich repeat kinase LRRK2 via extracellular signal‐regulated kinase ERK5 in macrophages
2014-01-31

Abstract The gene encoding leucine‐rich repeat kinase 2 ( LRRK 2) comprises a major risk factor for Parkinson's disease. Recently, it has emerged that LRRK 2 plays important roles in the immune system. LRRK 2 is induced by interferon‐γ ( IFN ‐γ) in monocytes, but the signaling pathway is not known. Here, we show that IFN ‐γ‐mediated induction of LRRK 2 was suppressed by pharmacological inhibition and RNA interference of the extracellular signal‐regulated kinase 5 ( ERK 5). This was confirmed by LRRK 2 immunostaining, which also revealed that the morphological responses to IFN ‐γ were suppressed by ERK 5 inhibitor treatment. Both human acute monocytic leukemia THP ‐1 cells and human peripheral blood monocytes stimulated the ERK 5‐ LRRK 2 pathway after differentiation into macrophages. Thus, LRRK 2 is induced via a novel, ERK 5‐dependent IFN ‐γ signal transduction pathway, pointing to new functions of ERK 5 and LRRK 2 in human macrophages. image Leucine‐rich repeat kinase 2 (LRRK2) is a major risk factor for the development of Parkinson's disease (PD). However, the role of LRRK2 in the affected neurons remains enigmatic. Recently, LRRK2 has been reported to be strongly expressed in the immune system. Here, we demonstrate that LRRK2 is induced by Interferon gamma via extracellular signal‐regulated kinase 5 (ERK5) in macrophages, thus providing new insights in LRRK2 and ERK5 biology.
Distribution of Young's Modulus in Porcine Corneas after Riboflavin/UVA-Induced Collagen Cross-Linking as Measured by Atomic Force Microscopy
2014-01-31

Riboflavin/UVA-induced corneal collagen cross-linking has become an effective clinical application to treat keratoconus and other ectatic disorders of the cornea. Its beneficial effects are attributed to a marked stiffening of the unphysiologically weak stroma. Previous studies located the stiffening effect predominantly within the anterior cornea. In this study, we present an atomic force microscopy-derived analysis of the depth-dependent distribution of the Young's modulus with a depth resolution of 5 μm in 8 cross-linked porcine corneas and 8 contralateral controls. Sagittal cryosections were fabricated from every specimen and subjected to force mapping. The mean stromal depth of the zone with effective cross-linking was found to be 219 ± 67 μm. Within this cross-linked zone, the mean Young's modulus declined from 49 ± 18 kPa at the corneal surface to 46 ± 17 kPa, 33 ± 11 kPa, 17 ± 5 kPa, 10 ± 4 kPa and 10 ± 4 kPa at stromal depth intervals of 0-50 μm, 50-100 μm, 100-150 μm, 150-200 μm and 200-250 μm, respectively. This corresponded to a stiffening by a factor of 8.1 (corneal surface), 7.6 (0-50 μm), 5.4 (50-100 μm), 3.0 (100-150 μm), 1.6 (150-200 μm), and 1.5 (200-250 μm), when compared to the Young's modulus of the posterior 100 μm. The mean Young's modulus within the cross-linked zone was 20 ± 8 kPa (2.9-fold stiffening), while it was 11 ± 4 kPa (1.7-fold stiffening) for the entire stroma. Both values were significantly distinct from the mean Young's modulus obtained from the posterior 100 μm of the cross-linked corneas and from the contralateral controls. In conclusion, we were able to specify the depth-dependent distribution of the stiffening effect elicited by standard collagen cross-linking in porcine corneas. Apart from determining the depth of the zone with effective corneal cross-linking, we also developed a method that allows for atomic force microscopy-based measurements of gradients of Young's modulus in soft tissues in general.
XMM-Newtonobservation of the Galactic supernova remnant W51C (G49.1–0.1)
2014-01-31

The supernova remnant (SNR) W51C is a Galactic object located in a strongly\\ninhomogeneous interstellar medium with signs of an interaction of the SNR blast\\nwave with dense molecular gas. Diffuse X-ray emission from the interior of the\\nSNR can reveal element abundances in the different emission regions and shed\\nlight on the type of supernova (SN) explosion and its progenitor. The hard\\nX-ray emission helps to identify possible candidates for a pulsar formed in the\\nSN explosion and for its pulsar wind nebula (PWN). We have analysed X-ray data\\nobtained with XMM-Newton. Spectral analyses in selected regions were performed.\\nEjecta emission in the bright western part of the SNR, located next to a\\ncomplex of dense molecular gas, was confirmed. The Ne and Mg abundances suggest\\na massive progenitor with a mass of &gt; 20 M_sun. Two extended regions emitting\\nhard X-rays were identified (corresponding to the known sources [KLS2002] HX3\\nwest and CXO J192318.5+140305 discovered with ASCA and Chandra, respectively),\\neach of which has an additional point source inside and shows a power-law\\nspectrum with Gamma ~ 1.8. Based on their X-ray emission, both sources can be\\nclassified as PWN candidates.\\n
Synthesis of Sterically Congested Triarylamines by Palladium‐Catalyzed Amination
2014-01-31

Abstract An efficient protocol for the palladium‐catalyzed synthesis of sterically congested triarylamines from commercially available 1‐chloro‐ or 1‐bromonaphthalenes and diarylamines is described. The application of alkyllithium reagents as strong bases and a combination of Pd(OAc) 2 and SPhos (2‐dicyclohexylphosphino‐2′,6′‐dimethoxybiphenyl) plays a crucial role in the success of this otherwise difficult to achieve C–N coupling reaction. A variety of secondary aromatic amines with versatile steric and electronic properties can be successfully used in this transformation to give the desired triarylamines in up to 99 % yield. The obtained products are important structural motifs in hole‐transport materials for organic light‐emitting diode applications.
“SCHWINGER-THEOREM”: ASCENDING PHOTONS IN EQUIVALENCE PRINCIPLE IMPLY GLOBALLY CONSTANT c IN GENERAL RELATIVITY
2014-01-31

Nobel laureate Julian Schwinger in his 1986 book “Einstein’s Legacy” cast a new light on the Einstein equivalence principle and, by implication, on general relativity. He demonstrated that the gravitationally redshifted photons arriving upstairs in gravity possess their lower frequency and energy on emission already, without this fact being locally manifest downstairs. Thus unlike a stone thrown, photons do not lose their kinetic energy on the way up. The consequences of this counterintuitive finding are far-reaching. In particular, the long-abandoned global constancy of the speed of light c gets resurrected. This fact rules out all globally expanding solutions to the Einstein equation. The same far-reaching cosmological finding is already implicit in the recently discovered fundamental field of cryodynamics, sister discipline to thermodynamics.
A Facility for Soft Proton Irradiation and Instrument Testing for Future Space Missions
2014-01-31

Orbital soft protons (from tens of keV to a few MeV) can seriously degrade the performance of astronomical X-ray detectors. An irradiation setup for large detectors as well as passive satellite components has been constructed at the accelerator facility of the University of Tübingen. The experimental setup and recent applications are briefly described. Simulations and measurements of an improved aperture design are presented in detail. Modifications of the irradiation setup to enable measurements of the small angle scattering efficiency of Wolter-type X-ray mirror shells are underway. Details of the implementation and the current status are given.
Comparative analysis of capitalism from a regulationist perspective extended by neo-Gramscian IPE
2014-02-01

Over time, the comparative analysis of capitalism has moved beyond the strict confines of the narrow varieties of capitalism (VoC) framework. In this sense, it is possible to observe an emergent post-VoC discussion that goes beyond the static design and methodological nationalism that can be found in a strictly comparative and institutionalist account of capitalism. So far, however, the post-VoC discussion has been barely able to address important politico-economic and societal themes and issues. For the most part, assertions about time-diagnostic characterisations of the current state of capitalism, the causes and processes of specific crisis dynamics inherent to this current form of capitalism, and the asymmetrical forms of international networks or formative transnational power relations, remain weak or chaotic. In order to overcome these existing deficiencies, this paper argues from an analytical perspective that situates itself in regulation theory and allows itself to be characterised as an extended neo-Gramscian international political economy (IPE) approach.
Embryotoxic and proteotoxic effects of water and sediment from the Neckar River (Southern Germany) to zebrafish (Danio rerio) embryos
2014-02-01

The Neckar River (Southern Germany) represents an aquatic system strongly affected by numerous anthropogenic activities. Thus, it is an excellent model for ecotoxicological investigations. The present study aims to assess time and spatial variations of embryo- and proteotoxic effects in surface water and sediment. For this end, embryos of zebrafish (Danio rerio) were exposed to Neckar River samples collected in the Tübingen region in different seasons over 2 years. Additionally, quantification of the heat shock (stress) protein Hsp70 was carried out in newly hatched larvae; furthermore, physico-chemical water parameters were measured in order to gain baseline information about the limnologic conditions. Nearly all of the investigated Neckar River sites caused elevated mortality, developmental retardation and failures, modified heart rate and reduced hatching success in zebrafish embryos and larvae. Additionally, exposure to Neckar River water and sediment led to changes in larval Hsp70 level. During the 2 years of investigation, seasonal differences of embryo- and proteotoxic effects occurred. Along these lines, physico-chemical measurements delivered basic information for the interpretation of in vivo test data. Our study suggests a changing toxic burden in the whole investigated study area. Consequently, for ecotoxicological field studies, time and spatial variations on small scale must be dealt with. The lethal and sublethal endpoints of the fish embryo test combined with Hsp70 level measurements proved to be effective tools for toxicity assessment of environmental samples.
DOP044 Patient education in a 14 month randomized trial fails to improve adherence in ulcerative colitis: Influence of demographic and clinical parameters on non-adherence
2014-02-01

Non-adherence is frequent in a population with quiescent/mildly active UC. Although more than 25% of the population was not in remission at the various time points, no relationship between disease activity and adherence was seen over the 14-month observation period. Physicians should maximise their efforts to motivate high-risk patients for adherence. Future trials should use objective exposure assessments to examine the impact of continuous education and consultations on the background of individual risks to develop non-adherence.
Glycosylated Metal Phthalocyanines
2014-02-01

Methods for the synthesis of mono-, di-, and tetra-glycosylated phthalonitriles are described, which are key building blocks for the preparation of the corresponding glycosylated metal (mostly zinc) phthalocyanines. Than the preparation of symmetrically and unsymmetrically tetra- and octa-glycosylated zinc phthalocyanines in which the carbohydrate is attached either anomerically or via another one of its OH-groups to the phthalocyanine macrocycle is assessed.
RACK1 and the microRNA pathway
2014-02-01

MicroRNAs (miRNAs) control many aspects of development and adaption in plants and in animals by post-transcriptional control of mRNA stability and translatability. Over the last years numerous proteins have been identified in the miRNA pathway. The versatile scaffold protein RACK1 has been associated with efficient miRNA production and function in plants and metazoans. Here, we briefly summarize the differences of RACK1 function in the plant and animal miRNA pathways and discuss putative mechanisms and functional roles of RACK1 in miRNA biogenesis and action.
ALK-Positive Cancer: Still a Growing Entity
2014-02-01

Since the discovery of ALK-positive anaplastic large-cell lymphoma in 1994 many other types of tumors showing ALK expression were disclosed. They form a heterogeneous group, including lung, renal and soft tissue tumors. The biological function of ALK, its role in carcinogenesis and impact exerted on the clinical outcome have been studied by many research groups. New drugs specifically dedicated for ALK inhibition, for example, crizotinib, have been synthesized and have become a viable treatment option for ALK-positive lung adenocarcinoma, and potentially for other ALK-positive cancers. This review summarizes the current state of knowledge concerning ALK-positive neoplasms, focusing on the clinical aspects of the subject.
Rediscovery of Living Land Snails on Trindade Island, Brazil
2014-02-01

For four decades it has been suspected that the endemic land snails of Trindade Island, Brazil, were extinct. Here we report finding live Succinea lopesi Lanzieri, 1966 and a species of Happia Bourguignat, 1889 on top of the island's highest peaks. Happia is a new record for the island and possibly also a new endemic species. As Trindade's environment has suffered much degradation due to introduced feral goats, such remote places might have acted as refuges for the snails. With the ongoing recovery of the native flora after the eradication of the goats, the snails' populations might re-establish themselves.
Abstract T P225: cGMP-Dependent Protein Kinase I in Smooth Muscle Cells Protects Against Stroke Injury in Mice
2014-02-01

The signaling pathways by which NO protects against stroke injury are mediated by cyclic guanosine monophosphate (cGMP) formation. However, the mechanisms of downstream signaling from cGMP to smooth muscle cells (SMC) remain incompletely understood. The cGMP-dependent protein kinase I (cGKI) is a key mediator of cGMP signaling. The goal of this study is to test the hypothesis that cGKI in SMC protects against stroke injury. Animals: We used the novel mouse line for highly efficient tamoxifen-inducible SMC-specific gene knockout, SMA-CreERT2, which expresses the CreERT2 recombinase under the control of the smooth muscle alpha-actin promoter (cGKI KO mice). The litter mate wild-type (WT) mice (no Cre gene) receiving the same tamoxifen treatment were used as control (cGKI WT) mice. Methods and Results: Mean blood pressure measured acutely from the common carotid artery under anesthesia (30% oxygen, 70% nitrous oxide and 1.5% isoflurane) was higher in cGKI KO mice (107±8 mmHg, Mean±SD) than in cGKI WT mice (95±1 mmHg, n=4/group, P&lt;0.05). One hour of middle cerebral artery (MCA) occlusion by filament with 23 hours of reperfusion produced increased cerebral infarct volume (TTC staining, indirect calculation) in cGKI KO mice (123±39 mm3) as compared with cGKI WT (85±17 mm3, n=5/group, p&lt; 0.05). Neurological deficit by 5 point scale was worse in cGKI KO mice (4.0 points) as compared with cGKI WT (2.4 points). Cerebral blood flow monitored by laser Doppler flowmetry above the core of the MCA territory indicated that reperfusion was less in cGKI KO mice than in cGKI WT mice, suggesting that cGKI mediates cerebrovascular SMC relaxation and protects against ischemic stroke. Vascular relaxation of mesenteric resistance arteries to acetylcholine, and the NO donor, NONOate after preconstriction with phenylephrine was dramatically impaired in cGKI KO mice. It suggests the importance of cGKI in the vascular SMC for NO-induced relaxation. In conclusion, stroke injury was more pronounced in cGKI SMC specific inducible conditional knockout mice than in cGKI WT mice, suggesting a protective role for cGKI in SMC against cerebral reperfusion injury. These studies identify the cGKI in cerebral vasculature as a potential target for therapies aimed at reducing stroke injury.
Solvation of a sponge-like geometry
2014-02-01

Abstract Periodic entanglements of filaments and networks, which resemble sponge-like materials, are often found as self-assembled materials. The interaction between the geometry of the assembly and a solvent in its interstices can dictate the geometric configuration of the structure as well as influence macroscopic properties such as swelling and mechanics. In this paper, we show the calculation of the solvation free energy as a function of the solute–solvent interaction from hydrophilic to hydrophobic, for a candidate entanglement of filaments. We do this using the morphometric approach to solvation free energy, a method that disentangles geometric properties from thermodynamic coefficients, which we compute via density functional theory.
Impact of altered Wnt1/ß-catenin expression on clinicopathology and prognosis in renal cell carcinoma.
2014-02-01

465 Background: Members of the Wnt/ß-catenin signaling pathway are abnormally expressed in renal cell carcinoma (RCC). This study analyzed the role of Wnt1/ß-catenin alterations in clear cell RCC (ccRCC) with regard to clinicopathology, overall survival (OS) and cancer specific survival (CSS) to prove the options of a Wnt targeted therapy. Methods: Corresponding ccRCCs and benign renal tissue were analyzed in 278 patients for Wnt1 and ß-catenin by immunohistochemistry in tissue microarrays. Expression scores including intensity and percentage of stained cells were compared between normal kidney and ccRCCs. Data was categorized according to the mean expressions core and correlated to tumor and patients’ characteristics and analyzed for OS and CSS according to the Kaplan-Meier and log-rank test. To identify prognostics value of wnt1 and ß-catenin, univariable and multivariable Cox proportional hazard regression models were used. Results: High Wnt1 tumor expression was associated with increased tumor diameter (p=0.01), stage (p=0.004) and vascular invasion (p=0.02). Positive membranous ß-catenin was associated with advanced stage (p=0.003), vascular invasion (p=0.01) and tumor necrosis (p=0.004). Increased tumor diameter (p=0.01), stage (p=0.003), node involvement (0.04), grade (p=0.001), vascular invasion (p=0.002), and sarcomatoid differentiation (p=0.01) were found in patients with high cytoplasmic ß-catenin. Furthermore, this patient subgroup showed reduced OS (p=0.03) and CSS (p=0.009). Conclusions: Significant clinicopathological associations underline the oncogenic potential of Wnt1/ß-catenin pathway parameters. Whereas, cytoplasmic ß-catenin was identified as the most valuable parameter with regard to clinico-prognostic implications for future targeted therapies.