julilili42/papers huggingface dataset:
Osteoblast‐secreted factors enhance the expression of dysadherin and CCL2‐dependent migration of renal carcinoma cells
2011-02-15

Abstract Renal cell carcinoma (RCC) frequently metastasizes to the bone marrow. These metastases are characterized by extensive osteolytic lesions. The mechanism, however, by which RCC cells metastasize to bone marrow remains poorly understood. To unravel the role of bone marrow cells in this context, we performed cell adhesion and migration assays using human RCC cell lines to analyze the influence of resident bone marrow cells on renal tumor cells. The strongest adhesion of RCC cells was observed to osteoblasts. Moreover, conditioned medium of osteoblasts (OB‐CM) significantly increased RCC cell migration. By gene expression analysis dysadherin was identified as a transcript whose expression could be elevated more than twofold in RCC cells when exposed to OB‐CM. Suppression of dysadherin expression in RCC cells by siRNA reduced their ability to migrate in the presence of OB‐CM. Furthermore, the RCC cells secreted high amounts of the chemokine CCL2 when tumor cells migrated under the influence of osteoblast‐secreted factors. CCL2 neutralization strongly reduced the migratory ability of the RCC cells. Silencing the expression of dysadherin in RCC cells resulted in a twofold reduction of CCL2 protein expression indicating a dysadherin‐dependent expression of the chemokine. Taken together, our data show that osteoblasts are the major cell type of the bone marrow that affect RCC cells by secreting factors that increase the expression of dysadherin and CCL2 in the tumor cells leading to enhanced cell migration. These data suggest an osteoblast‐induced autocrine mechanism for a facilitated homing of RCC cells to the bone marrow.
Acute inflammatory neuropathies: new evidence for disease classification from Japan
2011-02-15

The classification of acute inflammatory neuropathies has undergone constant modifications since the original description of the Guillain–Barre Syndrome (GBS) in 1936.1 Several types of inflammatory neuropathies have been described and it remains a matter of debate whether they represent a continuous spectrum of disorders or distinct disease entities. The diagnosis of GBS is based exclusively on clinical parameters which include ascending muscle weakness, diminished tendon reflexes, a peak of the disease within 4 weeks after symptom onset and exclusion of other causes.2 A subgroup of patients with GBS present with ataxia that cannot be attributed to paralysis or sensory loss.3 This condition has been termed ...
Structure-Based Discovery of Inhibitors of Microsomal Prostaglandin E2 Synthase−1, 5-Lipoxygenase and 5-Lipoxygenase-Activating Protein: Promising Hits for the Development of New Anti-inflammatory Agents
2011-02-16

Microsomal prostaglandin E(2) synthase (mPGES)-1 catalyzes the transformation of PGH(2) to PGE(2) that is involved in several pathologies like fever, pain, and inflammatory disorders. To identify novel mPGES-1 inhibitors, we used in silico screening to rapidly direct the synthesis, based on the copper-catalyzed 3 + 2 Huisgen's reaction (click chemistry), of potential inhibitors. We designed 26 new triazole-based compounds in accordance with the pocket binding requirements of human mPGES-1. Docking results, in agreement with ligand efficiency values, suggested the synthesis of 15 compounds that at least in theory were shown to be more efficient in inhibiting mPGES-1. Biological evaluation of these selected compounds has disclosed three new potential anti-inflammatory drugs: (I) compound 4 displaying selectivity for mPGES-1 with an IC(50) value of 3.2 μM, (II) compound 20 that dually inhibits 5-lipoxygenase and mPGES-1, and (III) compound 7 apparently acting as 5-lipoxygenase-activating protein inhibitor (IC(50) = 0.4 μM).
Cardiotoxicity testing using pluripotent stem cell‐derived human cardiomyocytes and state‐of‐the‐art bioanalytics: a review
2011-02-16

ABSTRACT In this article, recent progress in cardiotoxicity testing based on the use of immortalized cell lines or human embryonic stem cell (hESC) derived cardiomyocytes in combination with state‐of‐the‐art bioanalytical methods and sensors is reviewed. The focus is on hESC‐derived cells and their refinement into competent testing cells, but the access and utility of other relevant cell types are also discussed. Recent developments in sensor techniques and bioanalytical approaches for measuring critical cardiotoxicity parameters are highlighted, together with aspects of data evaluation and validation. Finally, recommendations for further research are given. Copyright © 2011 John Wiley &amp; Sons, Ltd.
Low-Dose Interferon Type I Treatment Is Effective Against H5N1 and Swine-Origin H1N1 Influenza A VirusesIn VitroandIn Vivo
2011-02-16

The recent emergence of pandemic swine-origin influenza virus (H1N1) and the severe outbreaks of highly pathogenic avian influenza virus of the H5N1 subtype leading to death in humans is a reminder that influenza remains a frightening foe throughout the world. Besides vaccination, there is an urgent need for new antiviral strategies to protect against influenza. The innate immune response to influenza viruses involves production of interferon alpha and beta (IFN-α/β), which plays a crucial role in virus clearance during the initial stage of infection. We examined the effect of IFN-α on the replication of H5N1 and H1N1 in vitro and in vivo. A single pretreatment with low-dose IFN-α reduced lung virus titers up to 1.4 log(10) pfu. The antiviral effect increased after multiple pretreatments. Low-dose IFN-α protected mice against lethal H5N1 viral infection. Further, IFN-α was also effective against H1N1 in vitro and in the mouse model. These results indicate that low-dose IFN-α treatment leads to the induction of antiviral cytokines that are involved in the reduction of influenza virus titers in the lung. Moreover, it might be possible that a medical application during pandemic outbreak could help contain fulminant infections.
FDG-PET/CT-guided biopsy of bone metastases sets a new course in patient management after extensive imaging and multiple futile biopsies
2011-02-16

A 73-year-old man with a history of prostate and bladder carcinoma and persistent back pain was diagnosed by MRI with multiple vertebral metastases including a compression fracture of T7. He received radiotherapy for pain relief and for vertebral instability with incipient spinal stenosis, but additional targeted systemic therapy was intended. Therefore, multiple attempts at minimally invasive and open biopsies for histological characterisation of the bone metastases were performed, but failed to provide a conclusive specimen, although CT, MRI and bone scintigraphy were used for biopsy planning. Only histopathological analysis of an (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT-guided additional biopsy at a site with high metabolic activity yielded the final diagnosis of bone metastases of a neuroendocrine small cell cancer of unknown origin; hence, the patient had a third malignancy requiring a different therapy regimen and diagnostic work-up.
Effectiveness of Carboplatin and Paclitaxel as First- and Second-Line Treatment in 61 Patients with Metastatic Melanoma
2011-02-16

Among patients with metastatic melanoma a subgroup achieved disease control under CP therapy which may be associated with a survival benefit. This potential advantage has to be weighed against considerable toxicity. Since response rates and survival were not improved in previously untreated patients compared to pretreated patients, CP should thus not be applied as first-line treatment.
XMM-Newtonobservations of the superbubble in N 158 in the LMC
2011-02-16

Aims: We study the diffuse X-ray emission observed in the field of view of\\nthe pulsar B 0540-69 in the Large Magellanic Cloud (LMC) by XMM-Newton. We want\\nto understand the nature of this soft diffuse emission, which coincides with\\nthe superbubble in the HII region N 158, and improve our understanding of the\\nevolution of superbubbles. Methods: We analyse the XMM-Newton spectra of the\\ndiffuse emission. Using the parameters obtained from the spectral fit, we\\nperform calculations of the evolution of the superbubble. The mass loss and\\nenergy input rates are based on the initial mass function (IMF) of the observed\\nOB association inside the superbubble. Results: The analysis of the spectra\\nshows that the soft X-ray emission arises from hot shocked gas surrounded by a\\nthin shell of cooler, ionised gas. We show that the stellar winds alone cannot\\naccount for the energy inside the superbubble, but the energy release of 2 - 3\\nsupernova explosions in the past ~1 Myr provides a possible explanation.\\nConclusions: The combination of high sensitivity X-ray data, allowing spectral\\nanalysis, and analytical models for superbubbles bears the potential to reveal\\nthe evolutionary state of interstellar bubbles, if the stellar content is\\nknown.\\n
Seropositivity to Cytomegalovirus, Inflammation, All-Cause and Cardiovascular Disease-Related Mortality in the United States
2011-02-17

CMV was associated with a significant increased risk for all-cause mortality and CMV seropositive subjects who also had high CRP levels were at substantially higher risk for both for all-cause and CVD-related mortality than subjects with low CRP levels. Future work should target the mechanisms by which CMV infection and low-level inflammation interact to yield significant impact on mortality.
BRAF mutations in cutaneous melanoma are independently associated with age, anatomic site of the primary tumor, and the degree of solar elastosis at the primary tumor site
2011-02-17

Summary Oncogenic BRAF mutations are more frequent in cutaneous melanoma occurring at sites with little or moderate sun‐induced damage than at sites with severe cumulative solar ultraviolet (UV) damage. We studied cutaneous melanomas from geographic regions with different levels of ambient UV radiation to delineate the relative effects of cumulative UV damage, age, and anatomic site on the frequency of BRAF mutations. We show that BRAF ‐mutated melanomas occur in a younger age group on skin without marked solar elastosis and less frequently affect the head and neck area, compared to melanomas without BRAF mutations. The findings indicate that BRAF ‐mutated melanomas arise early in life at low cumulative UV doses, whereas melanomas without BRAF mutations require accumulation of high UV doses over time. The effect of anatomic site on the mutation spectrum further suggests regional differences among cutaneous melanocytes.
Stability of general-relativistic accretion disks
2011-02-18

Self-gravitating relativistic disks around black holes can form as transient\\nstructures in a number of astrophysical scenarios such as binary neutron star\\nand black hole-neutron star coalescences, as well as the core-collapse of\\nmassive stars. We explore the stability of such disks against runaway and\\nnon-axisymmetric instabilities using three-dimensional hydrodynamics\\nsimulations in full general relativity using the THOR code. We model the disk\\nmatter using the ideal fluid approximation with a -law equation of\\nstate with . We explore three disk models around non-rotating black\\nholes with disk-to-black hole mass ratios of 0.24, 0.17 and 0.11. Due to metric\\nblending in our initial data, all of our initial models contain an initial\\naxisymmetric perturbation which induces radial disk oscillations. Despite these\\noscillations, our models do not develop the runaway instability during the\\nfirst several orbital periods. Instead, all of the models develop unstable\\nnon-axisymmetric modes on a dynamical timescale. We observe two distinct types\\nof instabilities: the Papaloizou-Pringle and the so-called intermediate type\\ninstabilities. The development of the non-axisymmetric mode with azimuthal\\nnumber m = 1 is accompanied by an outspiraling motion of the black hole, which\\nsignificantly amplifies the growth rate of the m = 1 mode in some cases.\\nOverall, our simulations show that the properties of the unstable\\nnon-axisymmetric modes in our disk models are qualitatively similar to those in\\nNewtonian theory.\\n
Slowly-Developing Facial Nerve Paralysis
2011-02-18

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Autophagy differentially controls plant basal immunity to biotrophic and necrotrophic pathogens
2011-02-19

Summary In plants, autophagy has been assigned ‘pro‐death’ and ‘pro‐survival’ roles in controlling programmed cell death associated with microbial effector‐triggered immunity. The role of autophagy in basal immunity to virulent pathogens has not been addressed systematically, however. Using several autophagy‐deficient ( atg ) genotypes, we determined the function of autophagy in basal plant immunity. Arabidopsis mutants lacking ATG5 , ATG10 and ATG18a develop spreading necrosis upon infection with the necrotrophic fungal pathogen, Alternaria brassicicola , which is accompanied by the production of reactive oxygen intermediates and by enhanced hyphal growth. Likewise, treatment with the fungal toxin fumonisin B1 causes spreading lesion formation in atg mutant genotypes. We suggest that autophagy constitutes a ‘pro‐survival’ mechanism that controls the containment of host tissue‐destructive microbial infections. In contrast, atg plants do not show spreading necrosis, but exhibit marked resistance against the virulent biotrophic phytopathogen, Pseudomonas syringae pv. tomato . Inducible defenses associated with basal plant immunity, such as callose production or mitogen‐activated protein kinase activation, were unaltered in atg genotypes. However, phytohormone analysis revealed that salicylic acid (SA) levels in non‐infected and bacteria‐infected atg plants were slightly higher than those in Col‐0 plants, and were accompanied by elevated SA‐dependent gene expression and camalexin production. This suggests that previously undetected moderate infection‐induced rises in SA result in measurably enhanced bacterial resistance, and that autophagy negatively controls SA‐dependent defenses and basal immunity to bacterial infection. We infer that the way in which autophagy contributes to plant immunity to different pathogens is mechanistically diverse, and thus resembles the complex role of this process in animal innate immunity.
Heat tolerance and recovery in Mediterranean land snails after pre-exposure in the field
2011-02-20

Mediterranean land snails such as Xeropicta derbentina (Hygromiidae) and Theba pisana (Helicidae) are known for their remarkable tolerance to elevated temperatures and desiccation, yet the biochemical and cellular mechanisms underlying this tolerance are relatively unknown. We investigated the effects of increased temperatures and the ability of these snail species to recover from heat stress, examining the condition and amount of different types of hepatopancreatic cells (histopathology) and heat-shock protein 70 (stress protein) levels. Snails were exposed to defined control and increased temperatures and allowed a postheat phase for possible recovery. Results indicate the ability of X. derbentina to recover from natural and experimental temperature stress to some extent within the set time, whereas no such ability was found in T. pisana. Xeropicta derbentina is more heat-tolerant in general and less affected by heat stress than T. pisana. This is probably due to its greater ability to increase size and number of hepatopancreatic calcium cells that are essential for osmoregulation. The hypertrophy and hyperplasia of calcium cells can be regarded as a general response of molluscs to osmotic stressors, e.g. heat, as long as the organism is not overwhelmed by the stressor. Additionally, it can be assumed that the robust stress-protein system of X. derbentina plays a crucial role in this species' high thermotolerance.
The Structure and Behavior of Platinum in SnO2‐Based Sensors under Working Conditions
2011-02-21

Sensor at work: The structure of platinum in a 50 micrometer thin SnO2 layer is monitored by the combination of a specially designed experimental sensor setup with high-energy-resolution fluorescence-detected X-ray absorption spectroscopy and "range-extended" EXAFS to gain new insights into the local structure of the platinum dopant. Detailed facts of importance to specialist readers are published as "Supporting Information". Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The Sphene-Centered Ocellar Texture: An Effect of Grain-Supported Flow and Melt Migration in a Hyperdense Magma Mush
2011-02-21

The sphene-centered ocellar texture consists of leucocratic ocelli with sphene (titanite) crystals at the center, enclosed in a biotite-rich matrix. This texture has been recognized worldwide in hybrid intermediate rocks. On the basis of structural, petrological, and geochronological data from selected outcrops of the Variscan Ribadelago pluton (NW Iberian Massif), we propose that the ocelli were formed by migration and accumulation of a residual melt through a plagioclase- and biotite-dominated crystalline framework. At the late stage of crystallization, the magma acted as a hyperdense suspension and reacted to the pressure gradient caused by the regional stress field, entering the domain of grain-supported flow. Microstructures reveal that aligned crystal domains arose in the crystal framework from the shearing and compaction of the crystal mush and behaved as magmatic microshears. Relative displacement of adjacent crystal clusters along these microshears corresponded to the onset of Reynolds dilatancy that generated an expansion of the crystal mush, involving melt migration and pore aperture. The mineralogy of the ocelli, dominated by andesine and sphene, represents the composition of the migrating melt. The chemistry of this late, Ti-rich melt stems from the incongruent melting of biotite. Magmatic sphene from the ocelli yields a U-Pb age of 317 +/- 1 Ma, which represents the final crystallization of the hybridized magmatic system. Moreover, this texture offers an opportunity to better understand the rheological behavior of highly crystallized magmas.
Reduced TRPC Channel Expression in Psoriatic Keratinocytes Is Associated with Impaired Differentiation and Enhanced Proliferation
2011-02-22

Psoriasis is a characteristic inflammatory and scaly skin condition with typical histopathological features including increased proliferation and hampered differentiation of keratinocytes. The activation of innate and adaptive inflammatory cellular immune responses is considered to be the main trigger factor of the epidermal changes in psoriatic skin. However, the molecular players that are involved in enhanced proliferation and impaired differentiation of psoriatic keratinocytes are only partly understood. One important factor that regulates differentiation on the cellular level is Ca(2+). In normal epidermis, a Ca(2+) gradient exists that is disturbed in psoriatic plaques, favoring impaired keratinocyte proliferation. Several TRPC channels such as TRPC1, TRPC4, or TRPC6 are key proteins in the regulation of high [Ca(2+)](ex) induced differentiation. Here, we investigated if TRPC channel function is impaired in psoriasis using calcium imaging, RT-PCR, western blot analysis and immunohistochemical staining of skin biopsies. We demonstrated substantial defects in Ca(2+) influx in psoriatic keratinocytes in response to high extracellular Ca(2+) levels, associated with a downregulation of all TRPC channels investigated, including TRPC6 channels. As TRPC6 channel activation can partially overcome this Ca(2+) entry defect, specific TRPC channel activators may be potential new drug candidates for the topical treatment of psoriasis.
Conjugated Linoleic Acids Mediate Insulin Release through Islet G Protein-coupled Receptor FFA1/GPR40
2011-02-22

Among dietary components, conjugated linoleic acids (CLAs) have attracted considerable attention as weight loss supplements in the Western world because they reduce fat stores and increase muscle mass. However, a number of adverse effects are also ascribed to the intake of CLAs such as aggravation of insulin resistance and the risk of developing diabetes. However, the mechanisms accounting for the effects of CLAs on glucose homeostasis are incompletely understood. Herein we provide evidence that CLAs specifically activate the cell surface receptor FFA1, an emerging therapeutic target to treat type 2 diabetes. Using different recombinant cellular systems engineered to stably express FFA1 and a set of diverse functional assays including the novel, label-free non-invasive dynamic mass redistribution technology (Corning® Epic® biosensor), both CLA isomers cis-9, trans-11-CLA and trans-10, cis-12-CLA were found to activate FFA1 in vitro at concentrations sufficient to also account for FFA1 activation in vivo. Each CLA isomer markedly increased glucose-stimulated insulin secretion in insulin-producing INS-1E cells that endogenously express FFA1 and in primary pancreatic β-cells of wild type but not FFA1-/- knock-out mice. Our findings establish a clear mechanistic link between CLAs and insulin production and identify the cell surface receptor FFA1 as a molecular target for CLAs, explaining their acute stimulatory effects on insulin secretion in vivo. CLAs are also revealed as insulinotropic components in widely used nutraceuticals, a finding with significant implication for development of FFA1 modulators to treat type 2 diabetes.
Pretreatment Evaluation of Peripheral Vascular Malformations Using Low-Dose Contrast-Enhanced Time-Resolved 3D MR Angiography: Initial Results in 22 Patients
2011-02-22

Time-resolved MRA provided the temporal information needed for the appropriate classification of vascular malformations, enabling visualization of both the arterial feeders and draining veins. Furthermore, time-resolved MRA has the potential to be used as an initial and screening diagnostic tool obviating conventional MRA to categorize these lesions and determine their extent to correctly guide treatment.