julilili42/papers huggingface dataset:
Faculty Opinions recommendation of IFN-lambda determines the intestinal epithelial antiviral host defense.
2012-10-05

Type I and type III IFNs bind to different cell-surface receptors but induce identical signal transduction pathways, leading to the expression of antiviral host effector molecules. Despite the fact that type III IFN (IFN-λ) has been shown to predominantly act on mucosal organs, in vivo infection studies have failed to attribute a specific, nonredundant function. Instead, a predominant role of type I IFN was observed, which was explained by the ubiquitous expression of the type I IFN receptor. Here we comparatively analyzed the role of functional IFN-λ and type I IFN receptor signaling in the innate immune response to intestinal rotavirus infection in vivo, and determined viral replication and antiviral gene expression on the cellular level. We observed that both suckling and adult mice lacking functional receptors for IFN-λ were impaired in the control of oral rotavirus infection, whereas animals lacking functional receptors for type I IFN were similar to wild-type mice. Using Mx1 protein accumulation as marker for IFN responsiveness of individual cells, we demonstrate that intestinal epithelial cells, which are the prime target cells of rotavirus, strongly responded to IFN-λ but only marginally to type I IFN in vivo. Systemic treatment of suckling mice with IFN-λ repressed rotavirus replication in the gut, whereas treatment with type I IFN was not effective. These results are unique in identifying a critical role of IFN-λ in the epithelial antiviral host defense. PMID: 21518880
Identification of Serum Metabolites Associated With Risk of Type 2 Diabetes Using a Targeted Metabolomic Approach
2012-10-06

Metabolomic discovery of biomarkers of type 2 diabetes (T2D) risk may reveal etiological pathways and help to identify individuals at risk for disease. We prospectively investigated the association between serum metabolites measured by targeted metabolomics and risk of T2D in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam (27,548 adults) among all incident cases of T2D (n = 800, mean follow-up 7 years) and a randomly drawn subcohort (n = 2,282). Flow injection analysis tandem mass spectrometry was used to quantify 163 metabolites, including acylcarnitines, amino acids, hexose, and phospholipids, in baseline serum samples. Serum hexose; phenylalanine; and diacyl-phosphatidylcholines C32:1, C36:1, C38:3, and C40:5 were independently associated with increased risk of T2D and serum glycine; sphingomyelin C16:1; acyl-alkyl-phosphatidylcholines C34:3, C40:6, C42:5, C44:4, and C44:5; and lysophosphatidylcholine C18:2 with decreased risk. Variance of the metabolites was largely explained by two metabolite factors with opposing risk associations (factor 1 relative risk in extreme quintiles 0.31 [95% CI 0.21–0.44], factor 2 3.82 [2.64–5.52]). The metabolites significantly improved T2D prediction compared with established risk factors. They were further linked to insulin sensitivity and secretion in the Tübingen Family study and were partly replicated in the independent KORA (Cooperative Health Research in the Region of Augsburg) cohort. The data indicate that metabolic alterations, including sugar metabolites, amino acids, and choline-containing phospholipids, are associated early on with a higher risk of T2D.
Genome Sequence of the Bacterium Streptomyces davawensis JCM 4913 and Heterologous Production of the Unique Antibiotic Roseoflavin
2012-10-06

ABSTRACT Streptomyces davawensis JCM 4913 synthesizes the antibiotic roseoflavin, a structural riboflavin (vitamin B 2 ) analog. Here, we report the 9,466,619-bp linear chromosome of S. davawensis JCM 4913 and a 89,331-bp linear plasmid. The sequence has an average G+C content of 70.58% and contains six rRNA operons (16S-23S-5S) and 69 tRNA genes. The 8,616 predicted protein-coding sequences include 32 clusters coding for secondary metabolites, several of which are unique to S. davawensis . The chromosome contains long terminal inverted repeats of 33,255 bp each and atypical telomeres. Sequence analysis with regard to riboflavin biosynthesis revealed three different patterns of gene organization in Streptomyces species. Heterologous expression of a set of genes present on a subgenomic fragment of S. davawensis resulted in the production of roseoflavin by the host Streptomyces coelicolor M1152. Phylogenetic analysis revealed that S. davawensis is a close relative of Streptomyces cinnabarinus , and much to our surprise, we found that the latter bacterium is a roseoflavin producer as well.
miHA-match
2012-10-07

For certain hematologic malignancies, allogenenic hematopoietic stem cell transplantation (alloHCT) is a well-established therapy [1]. Initially alloHCT was used to strengthen the hematopoiesis after chemo-/radiotherapy, but nowadays the beneficial effects of graft-versus-leukemia (GvL) or graft-versus-tumor (GvT) is the main aim [2]. The beneficial effects are mediated by donor T cells recognizing patient-specific HLA-binding peptides. These peptides are called minor histocompatibility antigens (miHAs) and are typically caused by single nucleotide polymorphisms. Tissue-specific miHAs have successfully been used in anti-tumor therapy without causing unspecific graft-versus-host reactions. However, only a small number of miHAs have been identified to date, limiting the clinical use. There is thus a substantial need for fast and accurate identification of novel miHAs to enable immunotherapy for a large number of patients.
A demographic approach to study effects of climate change in desert plants
2012-10-08

Desert species respond strongly to infrequent, intense pulses of precipitation. Consequently, indigenous flora has developed a rich repertoire of life-history strategies to deal with fluctuations in resource availability. Examinations of how future climate change will affect the biota often forecast negative impacts, but these—usually correlative—approaches overlook precipitation variation because they are based on averages . Here, we provide an overview of how variable precipitation affects perennial and annual desert plants, and then implement an innovative, mechanistic approach to examine the effects of precipitation on populations of two desert plant species. This approach couples robust climatic projections, including variable precipitation, with stochastic, stage-structured models constructed from long-term demographic datasets of the short-lived Cryptantha flava in the Colorado Plateau Desert (USA) and the annual Carrichtera annua in the Negev Desert (Israel). Our results highlight these populations' potential to buffer future stochastic precipitation. Population growth rates in both species increased under future conditions: wetter, longer growing seasons for Cryptantha and drier years for Carrichtera . We determined that such changes are primarily due to survival and size changes for Cryptantha and the role of seed bank for Carrichtera . Our work suggests that desert plants, and thus the resources they provide, might be more resilient to climate change than previously thought.
Antioxidant and Anti-Protease Activities of Diazepinomicin from the Sponge-Associated Micromonospora Strain RV115
2012-10-08

Diazepinomicin is a dibenzodiazepine alkaloid with an unusual structure among the known microbial metabolites discovered so far. Diazepinomicin was isolated from the marine sponge-associated strain Micromonospora sp. RV115 and was identified by spectroscopic analysis and by comparison to literature data. In addition to its interesting preclinical broad-spectrum antitumor potential, we report here new antioxidant and anti-protease activities for this compound. Using the ferric reducing antioxidant power (FRAP) assay, a strong antioxidant potential of diazepinomicin was demonstrated. Moreover, diazepinomicin showed a significant antioxidant and protective capacity from genomic damage induced by the reactive oxygen species hydrogen peroxide in human kidney (HK-2) and human promyelocytic (HL-60) cell lines. Additionally, diazepinomicin inhibited the proteases rhodesain and cathepsin L at an IC50 of 70–90 μM. It also showed antiparasitic activity against trypomastigote forms of Trypanosoma brucei with an IC50 of 13.5 μM. These results showed unprecedented antioxidant and anti-protease activities of diazepinomicin, thus further highlighting its potential as a future drug candidate.
Light baryons and their electromagnetic interactions in the covariant constituent quark model
2012-10-08

We extend the confined covariant constituent quark model that was previously\\ndeveloped by us for mesons to the baryon sector. In our numerical calculation\\nwe use the same values for the constituent quark masses and the infrared cutoff\\nas have been previously used in the meson sector. In a first application we\\ndescribe the static properties of the proton and neutron, and the\\n -hyperon (magnetic moments and charge radii) and the behavior of the\\nnucleon form factors at low momentum transfers. We discuss in some detail the\\nconservation of gauge invariance of the electromagnetic transition matrix\\nelements in the presence of a nonlocal coupling of the baryons to the three\\nconstituent quark fields.\\n
Discovery of Novel Orally Active Anti-Inflammatory N-Phenylpyrazolyl-N-Glycinyl-Hydrazone Derivatives That Inhibit TNF-α Production
2012-10-08

Herein, we describe the synthesis and pharmacological evaluation of novel N-phenylpyrazolyl-N-glycinyl-hydrazone derivatives that were designed as novel prototypes of p38 mitogen-activated protein kinase (MAPK) inhibitors. All of the novel synthesized compounds described in this study were evaluated for their in vitro capacity to inhibit tumor necrosis factor α (TNF-α production in cultured macrophages) and in vitro MAPK p38α inhibition. The two most active anti-TNF-α derivatives, (E)-2-(3-tert-butyl-1-phenyl-1H-pyrazol-5-ylamino)-N'-((4-(2-morpholinoethoxy)naphthalen-1-yl)methylene)acetohydrazide (4a) and (E)-2-(3-tert-butyl-1-phenyl-1H-pyrazol-5-ylamino)-N'-(4-chlorobenzylidene)acetohydrazide (4f), were evaluated to determine their in vivo anti-hyperalgesic profiles in carrageenan-induced thermal hypernociception model in rats. Both compounds showed anti-inflammatory and antinociceptive properties comparable to SB-203580 used as a standard drug, by oral route at a dose of 100 μmol/kg. This bioprofile is correlated with the ability of NAH derivatives (4a) and (4f) suppressing TNF-α levels in vivo by 57.3 and 55.8%, respectively.
Coulomb gauge Yang-Mills theory at finite temperatures: Glueballs versus quasi-gluons
2012-10-08

We consider a variational approach to the finite temperature Yang-Mills theory in the Coulomb gauge. The partition function is computed in the ensemble of glueballs and quasi-gluons which emerge as eigenstates of the Coulomb gauge Hamiltonian. We compute the energy density and pressure and compare with results of lattice computations for both SU(2) and SU(3). The emergence of a phase transition is discussed.
Tissue-specific opposing functions of the inflammasome adaptor ASC in the regulation of epithelial skin carcinogenesis
2012-10-09

A chronic inflammatory microenvironment favors tumor progression through molecular mechanisms that are still incompletely defined. In inflammation-induced skin cancers, IL-1 receptor- or caspase-1–deficient mice, or mice specifically deficient for the inflammasome adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD) in myeloid cells, had reduced tumor incidence, pointing to a role for IL-1 signaling and inflammasome activation in tumor development. However, mice fully deficient for ASC were not protected, and mice specifically deficient for ASC in keratinocytes developed more tumors than controls, suggesting that, in contrast to its proinflammatory role in myeloid cells, ASC acts as a tumor-suppressor in keratinocytes. Accordingly, ASC protein expression was lost in human cutaneous squamous cell carcinoma, but not in psoriatic skin lesions. Stimulation of primary mouse keratinocytes or the human keratinocyte cell line HaCaT with UVB induced an ASC-dependent phosphorylation of p53 and expression of p53 target genes. In HaCaT cells, ASC interacted with p53 at the endogenous level upon UVB irradiation. Thus, ASC in different tissues may influence tumor growth in opposite directions: it has a proinflammatory role in infiltrating cells that favors tumor development, but it also limits keratinocyte proliferation in response to noxious stimuli, possibly through p53 activation, which helps suppressing tumors.
Intimin and Invasin Export Their C-Terminus to the Bacterial Cell Surface Using an Inverse Mechanism Compared to Classical Autotransport
2012-10-09

Invasin and intimin are major virulence factors of enteropathogenic Yersiniae and Escherichia coli, mediating invasion into and intimate adherence to host cells, respectively. Several studies have hinted that extracellular portion of these homologous proteins might be exported via an autotransport mechanism, but rigorous experimental proof has been lacking. Here, we present a topology model for invasin and intimin, consistent with the hypothesis that the N-terminal β-barrel domain acts as a translocation pore to secrete the C-terminal passenger domain. We confirmed this topology model by inserting epitope tags into the loops of the β-barrel. We further show that obstructing the pore of β-barrel hinders the export of the passenger domain. As for classical autotransport, the biogenesis of invasin and intimin is dependent on the Bam complex and the periplasmic chaperone SurA, whereas the chaperone/protease DegP is involved in quality control. However, compared to classical autotransporters (Type Va secretion), the domain structure of intimin and invasin is inverted. We conclude that proteins of the intimin and invasin family constitute a novel group of autotransported proteins, and propose that this class of autotransporters be termed Type Ve secretion.
Vascular endothelial growth factor signals through platelet-derived growth factor receptor β in meningiomas in vitro
2012-10-09

Collectively, our data suggest that VEGFA primarily regulates VEGF-mediated migration through PDGFRβ in meningiomas. The inhibitory effect of gambogic acid and tandutinib against meningioma growth in vitro suggests that selective PDGFRβ inhibitors, in combination with VEGF inhibitors, should be evaluated further as potential therapies for recurrent and malignant meningiomas.
Characterization and Therapeutic Potential of Induced Pluripotent Stem Cell-Derived Cardiovascular Progenitor Cells
2012-10-09

The cell surface marker combination of Flt1 and Flt4 specifically identify and enrich for an endogenous and iPSC-derived Isl1(+)/Nkx2.5(+) CPC with trilineage cardiovascular potential in vitro and robust ability for engraftment and differentiation into morphologically and electrophysiologically mature adult CMs in vivo post transplantation into adult hearts.
Lack of the Sodium-Driven Chloride Bicarbonate Exchanger NCBE Impairs Visual Function in the Mouse Retina
2012-10-09

Regulation of ion and pH homeostasis is essential for normal neuronal function. The sodium-driven chloride bicarbonate exchanger NCBE (Slc4a10), a member of the SLC4 family of bicarbonate transporters, uses the transmembrane gradient of sodium to drive cellular net uptake of bicarbonate and to extrude chloride, thereby modulating both intracellular pH (pH(i)) and chloride concentration ([Cl(-)](i)) in neurons. Here we show that NCBE is strongly expressed in the retina. As GABA(A) receptors conduct both chloride and bicarbonate, we hypothesized that NCBE may be relevant for GABAergic transmission in the retina. Importantly, we found a differential expression of NCBE in bipolar cells: whereas NCBE was expressed on ON and OFF bipolar cell axon terminals, it only localized to dendrites of OFF bipolar cells. On these compartments, NCBE colocalized with the main neuronal chloride extruder KCC2, which renders GABA hyperpolarizing. NCBE was also expressed in starburst amacrine cells, but was absent from neurons known to depolarize in response to GABA, like horizontal cells. Mice lacking NCBE showed decreased visual acuity and contrast sensitivity in behavioral experiments and smaller b-wave amplitudes and longer latencies in electroretinograms. Ganglion cells from NCBE-deficient mice also showed altered temporal response properties. In summary, our data suggest that NCBE may serve to maintain intracellular chloride and bicarbonate concentration in retinal neurons. Consequently, lack of NCBE in the retina may result in changes in pH(i) regulation and chloride-dependent inhibition, leading to altered signal transmission and impaired visual function.
Mixing-Induced Anisotropic Correlations in Molecular Crystalline Systems
2012-10-09

We investigate the structure of mixed thin films composed of pentacene and diindenoperylene using x-ray reflectivity and grazing incidence x-ray diffraction. For equimolar mixtures we observe vanishing in-plane order coexisting with an excellent out-of-plane order, a yet unreported disordering behavior in binary mixtures of organic semiconductors, which are crystalline in their pure form. One approach to rationalize our findings is to introduce an anisotropic interaction parameter in the framework of a mean field model. By comparing the structural properties with those of other mixed systems, we discuss the effects of sterical compatibility and chemical composition on the mixing behavior, which adds to the general understanding of interactions in molecular mixtures.
Pathway-based visualization of cross-platform microarray datasets
2012-10-09

Abstract Motivation: Traditionally, microarrays were almost exclusively used for the genome-wide analysis of differential gene expression. But nowadays, their scope of application has been extended to various genomic features, such as microRNAs (miRNAs), proteins and DNA methylation (DNAm). Most available methods for the visualization of these datasets are focused on individual platforms and are not capable of integratively visualizing multiple microarray datasets from cross-platform studies. Above all, there is a demand for methods that can visualize genomic features that are not directly linked to protein-coding genes, such as regulatory RNAs (e.g. miRNAs) and epigenetic alterations (e.g. DNAm), in a pathway-centred manner. Results: We present a novel pathway-based visualization method that is especially suitable for the visualization of high-throughput datasets from multiple different microarray platforms that were used for the analysis of diverse genomic features in the same set of biological samples. The proposed methodology includes concepts for linking DNAm and miRNA expression datasets to canonical signalling and metabolic pathways. We further point out strategies for displaying data from multiple proteins and protein modifications corresponding to the same gene. Ultimately, we show how data from four distinct platform types (messenger RNA, miRNA, protein and DNAm arrays) can be integratively visualized in the context of canonical pathways. Availability: The described method is implemented as part of the InCroMAP application that is freely available at www.cogsys.cs.uni-tuebingen.de/software/InCroMAP. Contact: clemens.wrzodek@uni-tuebingen.de or andreas.zell@uni-tuebingen.de
Phosphene Thresholds Elicited by Transcorneal Electrical Stimulation in Healthy Subjects and Patients with Retinal Diseases
2012-10-10

Considering the fast, safe, and reliable practicability of EPT testing, this test might be used more often under clinical circumstances. Determination of EPTs could be potentially useful in elucidation of the progress of ophthalmologic diseases, either in addition to standard clinical assessment or under conditions in which these standard tests cannot be used meaningfully. (ClinicalTrials.gov number, NCT00804102.).
Evidence for Functional Diversification Within a Fungal NEP1-Like Protein Family
2012-10-11

In this study, we functionally analyzed the gene family encoding necrosis- and ethylene-inducing-like proteins (NLP) of the vascular wilt pathogen Verticillium dahliae. We show that the composition of the NLP gene family varies little among V. dahliae isolates. The cytotoxic activity of NLP family members of a tomato-pathogenic V. dahliae strain was determined, demonstrating that only two of the seven NLP induced plant cell death. The genes encoding these cytotoxic NLP were found to be induced in V. dahliae upon colonization of tomato. Interestingly, targeted deletion of either of the two genes in V. dahliae significantly compromised virulence on tomato as well as on Arabidopsis plants, whereas deletion of only one of the two genes affected virulence on Nicotiana benthamiana. This could be attributed to differential induction of the two NLP genes in V. dahliae upon N. benthamiana colonization, revealing that the in planta induction of NLP genes varies between plant hosts. Intriguingly, one of the NLP genes appears to also affect vegetative growth and conidiospore production, because the corresponding deletion strain produced significantly fewer conidiospores and developed extensive aerial mycelium. In conclusion, we demonstrate that the expanded V. dahliae NLP family shows functional diversification, revealing not only differential cytotoxicity between family members but also that the cytotoxic NLP play a role in vegetative growth and asexual reproduction in addition to their contribution to virulence.
The orbits of subdwarf B + main-sequence binaries
2012-10-11

The predicted orbital period histogram of an sdB population is bimodal with a\\npeak at short (&lt; 10 days) and long (&gt; 250 days) periods. Observationally, there\\nare many short-period sdB systems known, but only very few long-period sdB\\nbinaries are identified. As these predictions are based on poorly understood\\nbinary interaction processes, it is of prime importance to confront the\\npredictions to observational data. In this contribution we aim to determine the\\nabsolute dimensions of the long-period sdB+MS binary system PG1104+243.\\nHigh-resolution spectroscopy time-series were obtained with HERMES at the\\nMercator telescope at La Palma, and analyzed to obtain radial velocities of\\nboth components. Photometry from the literature was used to construct the\\nspectral energy distribution (SED) of the binary. Atmosphere models were used\\nto fit this SED and determine the surface gravity and temperature of both\\ncomponents. The gravitational redshift provided an independent confirmation of\\nthe surface gravity of the sdB component. An orbital period of 753 +- 3 d and a\\nmass ratio of q = 0.637 +- 0.015 were found from the RV-curves. The sdB\\ncomponent has an effective temperature of Teff = 33500 +- 1200 K and a surface\\ngravity of logg = 5.84 +- 0.08 dex, while the cool companion is found to be a\\nG-type star with Teff = 5930 +- 160 K and logg = 4.29 +- 0.05 dex. Assuming a\\ncanonical mass of Msdb = 0.47 Msun, the MS component has a mass of 0.74 +- 0.07\\nMsun, and its Teff corresponds to what is expected for a terminal age\\nmain-sequence star with sub-solar metalicity. PG1104+243 is the first\\nlong-period sdB binary in which accurate physical parameters of both components\\ncould be determined, and the first sdB binary in which the gravitational\\nredshift is measured. Furthermore, PG1104+243 is the first sdB+MS system that\\nshows consistent evidence for being formed through stable Roche-lobe overflow.\\n