julilili42/papers huggingface dataset:
A regulon conserved in monocot and dicot plants defines a functional module in antifungal plant immunity
2010-11-22

At least two components that modulate plant resistance against the fungal powdery mildew disease are ancient and have been conserved since the time of the monocot–dicot split (≈200 Mya). These components are the seven transmembrane domain containing MLO/MLO2 protein and the syntaxin ROR2/PEN1, which act antagonistically and have been identified in the monocot barley ( Hordeum vulgare ) and the dicot Arabidopsis thaliana , respectively. Additionally, syntaxin-interacting N -ethylmaleimide sensitive factor adaptor protein receptor proteins (VAMP721/722 and SNAP33/34) as well as a myrosinase (PEN2) and an ABC transporter (PEN3) contribute to antifungal resistance in both barley and/or Arabidopsis. Here, we show that these genetically defined defense components share a similar set of coexpressed genes in the two plant species, comprising a statistically significant overrepresentation of gene products involved in regulation of transcription, posttranslational modification, and signaling. Most of the coexpressed Arabidopsis genes possess a common cis -regulatory element that may dictate their coordinated expression. We exploited gene coexpression to uncover numerous components in Arabidopsis involved in antifungal defense. Together, our data provide evidence for an evolutionarily conserved regulon composed of core components and clade/species-specific innovations that functions as a module in plant innate immunity.
Investigation of Myostatin Serum Levels Before and After a 6-Month Lifestyle Intervention Program in Obese Children
2010-11-22

Both muscle mass and serum myostatin increased concordantly. Patients with the greatest rise of myostatin had a significantly lower increase of muscle mass suggesting a negative feedback loop between myostatin and muscle tissue. In our study, the change of myostatin serum levels was not associated with the amount of fat mass or HOMA insulin sensitivity index.
PARP1 Gene Knock-Out Increases Resistance to Retinal Degeneration without Affecting Retinal Function
2010-11-23

Retinitis pigmentosa (RP) is a group of inherited neurodegenerative diseases affecting photoreceptors and causing blindness in humans. Previously, excessive activation of enzymes belonging to the poly-ADP-ribose polymerase (PARP) group was shown to be involved in photoreceptor degeneration in the human homologous rd1 mouse model for RP. Since there are at least 16 different PARP isoforms, we investigated the exact relevance of the predominant isoform - PARP1 - for photoreceptor cell death using PARP1 knock-out (KO) mice. In vivo and ex vivo morphological analysis using optic coherence tomography (OCT) and conventional histology revealed no major alterations of retinal phenotype when compared to wild-type (wt). Likewise, retinal function as assessed by electroretinography (ERG) was normal in PARP1 KO animals. We then used retinal explant cultures derived from wt, rd1, and PARP1 KO animals to test their susceptibility to chemically induced photoreceptor degeneration. Since photoreceptor degeneration in the rd1 retina is triggered by a loss-of-function in phosphodiesterase-6 (PDE6), we used selective PDE6 inhibition to emulate the rd1 situation on non-rd1 genotypes. While wt retina subjected to PDE6 inhibition showed massive photoreceptor degeneration comparable to rd1 retina, in the PARP1 KO situation, cell death was robustly reduced. Together, these findings demonstrate that PARP1 activity is in principle dispensable for normal retinal function, but is of major importance for photoreceptor degeneration under pathological conditions. Moreover, our results suggest that PARP dependent cell death or PARthanatos may play a major role in retinal degeneration and highlight the possibility to use specific PARP inhibitors for the treatment of RP.
Netrin-1 Signaling Dampens Inflammatory Peritonitis
2010-11-23

Abstract Previous studies implicated the anti-inflammatory potential of the adenosine 2B receptor (A2BAR). A2BAR activation is achieved through adenosine, but this is limited by its very short t1/2. To further define alternative adenosine signaling, we examined the role of netrin-1 during acute inflammatory peritonitis. In this article, we report that animals with endogenous repression of netrin-1 (Ntn1+/−) demonstrated increased cell count, increased peritoneal cytokine concentration, and pronounced histological changes compared with controls in a model of zymosan A peritonitis. Exogenous netrin-1 significantly decreased i.p. inflammatory changes. This effect was not present in animals with deletion of A2BAR (A2BAR−/−). A2BAR−/− animals demonstrated no change in cell count, i.p. cytokine concentration, or histology in response to netrin-1 injection. These data strengthen the role of netrin-1 as an immunomodulatory protein exerting its function in dependence of the A2BAR and further define alternative adenosine receptor signaling.
Dual antitumour effect of 5-azacytidine by inducing a breakdown of resistance-mediating factors and epigenetic modulation
2010-11-23

Background: The cytokine tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown promising anticancer activity in early clinical settings by selectively inducing apoptosis in different tumour types. However, some tumour entities such as hepatocellular carcinoma (HCC) display an inherent resistance to TRAIL. A huge effort has been made to unravel strategies for a clinically applicable sensitisation of resistant cancer cells to TRAIL. Reversible epigenetic alterations such as DNA methylation play a major role in development, maintenance and resistance phenomena of tumour cells. Currently, several clinical trials are exploiting the potential of epigenetic drugs, such as 5-azacytidine (5-aza-CR) or 5-aza-2′-deoxycytidine (5-aza-dC) to break primary or secondary resistance phenomena of cancer cells. Therefore, 5-aza-CR and 5-aza-dC were investigated in the context of TRAIL resistance. Methods: Alterations in proliferation, apoptosis, regulatory proteins and toxicity were investigated in TRAIL-resistant hepatoma, and also in renal, colon and pancreatic cancer cells as well as non-transformed human-derived primary hepatocytes, tissue slices isolated from human liver and non-malignant colon cells, all of which had been exposed to demethylating drugs and/or TRAIL. Results: Within hours, 5-aza-CR but not 5-aza-dC sensitised in vitro cultured tumour cells to TRAIL, first by activating caspases, followed by a subsequent induction of apoptosis. This surprisingly rapid sensitisation was confirmed in vivo employing a chorioallantoic membrane assay. As a major mechanism, a 5-aza-CR-induced inhibition of cellular protein synthesis was found which led to a breakdown of tumour-protecting factors such as the antiapoptotic factor FLICE inhibitory protein (FLIP). Importantly, TRAIL and 5-aza-CR did not induce relevant toxicity or apoptosis in primary hepatocytes, liver slices from different human donors and in normal colon cells. Conclusions: Molecular evidence is provided for a novel 5-aza-CR-based translational approach enabling a twofold treatment of apoptosis-resistant tumour entities, not only by an epigenetic reversion of the malignancy-associated phenotype but also by an efficient resensitisation to apoptosis-inducing substances such as TRAIL.
The Mechanism of the ortho‐Methylation of Nitrobenzenes by Dimethylsulfonium Methylide
2010-11-23

Abstract Nitrobenzenes carrying an ortho substituent are selectively methylated at the free ortho position by reaction with dimethylsulfonium methylide. The importance of the ortho substituent is demonstrated by the failure of the methylation of nitrobenzene and 3‐ and 4‐nitroanisole. This is explained by the out‐of‐plane geometry of the nitro group in the ortho ‐substituted derivative, which enables a specific interaction between the ylide and the nitro group favourable for attack of the methylide C atom at the neighbouring free ortho position. As shown by appropriate deuterium‐labelling studies, the addition is followed by an E1‐like β‐elimination with displacement of dimethyl sulfide and subsequent protonation of the elimination product.
Harmonic morphisms on conformally flat 3-spheres
2010-11-23

We show that under some non-degeneracy assumptions the only submersive harmonic morphism on a conformally flat 3-sphere to a surface is the Hopf fibration. The proof involves an appropriate use of the Chern–Simons functional.
The Absence of Eye Muscle Fatigue Indicates That the Nervous System Compensates for Non-Motor Disturbances of Oculomotor Function
2010-11-24

The physical properties of our bodies are subject to change (due to fatigue, heavy equipment, injury or aging) as we move around in the surrounding environment. The traditional definition of motor adaptation dictates that a mechanism in our brain needs to compensate for such alterations by appropriately modifying neural motor commands, if the vitally important accuracy of executed movements is to be preserved. In this article we describe how a repetitive eye movement task brings about changes in eye saccade kinematics that compromise accurate motor performance in the absence of a proper compensatory response. Surgical lesions in animals and human patient studies have previously demonstrated that an intact cerebellum is necessary for the compensation to arise and prevent the occurrence of hypometric movements. Here we identified the dynamic properties of the eye plant by recording from abducens motoneurons responsible for the required movement and measured the muscle response to microstimulation of the abducens nucleus in rhesus monkeys. The ensuing results demonstrate that the muscular periphery remains intact during the fatiguing eye movement task, while internal sources of noise (drowsiness, attentional modulation, neuronal fatigue etc.) must be responsible for a diminished oculomotor performance. This finding leads to the important realization that while supervising the accuracy of our movements, the nervous system takes additionally into account and adapts to any disruptive processes within the brain itself, clearly unrelated to the dynamical behavior of muscles or the environment. The existence of this supplementary mechanism forces a reassessment of traditional views of cerebellum-dependent motor adaptation.
Immune surveillance of the normal human CNS takes place in dependence of the locoregional blood-brain barrier configuration and is mainly performed by CD3+/CD8+ lymphocytes
2010-11-24

Despite the blood-brain barrier (BBB) the human CNS is continuously screened by blood-derived immunological cells. In certain brain areas the local BBB configuration grants passage of large molecules, whereas others are better shielded. We investigated whether these regional BBB compositions are paralleled by differences in the degree of cellular immunosurveillance by investigating tissue from 23 normal human brains for several CD markers, FoxP3, granzyme B, and perforin. Our results provide evidence that immunosurveillance is associated with locoregional BBB configuration and is mainly performed by CD3(+)/CD8(+)/granzyme B(-)/perforin(-) lymphocytes.
Biological Evaluation and Structural Determinants of p38α Mitogen‐Activated‐Protein Kinase and c‐Jun‐N‐Terminal Kinase 3 Inhibition by Flavonoids
2010-11-24

Abstract A series of 42 naturally occurring flavonoids and one flavonoid glucuronide were tested for their ability to inhibit p38α mitogen‐activated protein kinase (p38α) and c‐Jun‐N‐terminal kinase 3 (JNK3). Potent inhibitors with IC 50 values in the low micromolar range were identified. Structure–activity relationships were evaluated and the most promising compounds were docked into the ATP binding site of these kinases. Among the different classes of flavonoids, the flavonol group showed better inhibition of p38α. Of this class, kaempferol‐7,4′‐dimethylether was a potent p38α inhibitor, displaying 13‐fold selectivity for p38α over JNK3. The flavone compounds without a 6‐methoxy group preferentially inhibited JNK3. The flavone glycoside, luteolin‐7‐ O ‐glycoside, was identified as a potent inhibitor with the greatest selectivity toward JNK3. In contrast, the flavanol compounds displayed similar inhibitory activities toward both kinases.
Immune Evasion by Yersinia enterocolitica: Differential Targeting of Dendritic Cell Subpopulations In Vivo
2010-11-24

CD4(+) T cells are essential for the control of Yersinia enterocolitica (Ye) infection in mice. Ye can inhibit dendritic cell (DC) antigen uptake and degradation, maturation and subsequently T-cell activation in vitro. Here we investigated the effects of Ye infection on splenic DCs and T-cell proliferation in an experimental mouse infection model. We found that OVA-specific CD4(+) T cells had a reduced potential to proliferate when stimulated with OVA after infection with Ye compared to control mice. Additionally, proliferation of OVA-specific CD4(+) T cells was markedly reduced when cultured with splenic CD8α(+) DCs from Ye infected mice in the presence of OVA. In contrast, T-cell proliferation was not impaired in cultures with CD4(+) or CD4(-)CD8α(-) DCs isolated from Ye infected mice. However, OVA uptake and degradation as well as cytokine production were impaired in CD8α(+) DCs, but not in CD4(+) and CD4(-)CD8α(-) DCs after Ye infection. Pathogenicity factors (Yops) from Ye were most frequently injected into CD8α(+) DCs, resulting in less MHC class II and CD86 expression than on non-injected CD8α(+) DCs. Three days post infection with Ye the number of splenic CD8α(+) and CD4(+) DCs was reduced by 50% and 90%, respectively. The decreased number of DC subsets, which was dependent on TLR4 and TRIF signaling, was the result of a faster proliferation and suppressed de novo DC generation. Together, we show that Ye infection negatively regulates the stimulatory capacity of some but not all splenic DC subpopulations in vivo. This leads to differential antigen uptake and degradation, cytokine production, cell loss, and cell death rates in various DC subpopulations. The data suggest that these effects might be caused directly by injection of Yops into DCs and indirectly by affecting the homeostasis of CD4(+) and CD8α(+) DCs. These events may contribute to reduced T-cell proliferation and immune evasion of Ye.
Intra‐individual variation in stable carbon (δ13C) and nitrogen (δ15N) isotopes in mandibles of modern caribou of Qamanirjuaq (Rangifer tarandus groenlandicus) and Banks Island (Rangifer tarandus pearyi): Implications for tracing seasonal and temporal changes in diet
2010-11-24

ABSTRACT Intra‐individual variations in carbon (δ 13 C) and nitrogen (δ 15 N) isotope measurements of dentine collagen in ungulate teeth can be related to diet and environmental changes at different periods during the life of the animal. A protocol of serial sampling of first, second and third molar roots was applied to modern caribou (17–27 months old) of the Qamanirjuaq herd ( Rangifer tarandus groenlandicus ), Canada. Based on a previous study, we predicted that M2 would reflect winter, M3 summer and M1 a complete year in terms of the isotopic record. Relatively high δ 15 N values ( ca . 6 to 8‰), previously attributed to winter stress, were found in different molars of different specimens, reflecting a period of growth between April 1966 to April 1967. Previous results on other teeth from the same population confirmed that a high δ 15 N coll value signal corresponded to the winter of 1966/67. This temporary increase in δ 15 N value was probably linked to diet and/or environmental change. Collagen from M1 reflects the first winter whereas M2 and M3 reflect the second winter of life of young caribou. A longer time record including summer is represented by the bone collagen of the mandible. Results obtained on molar roots and mandible bone of the modern caribou of Banks Island herd ( Rangifer tarandus pearyi ) confirmed this seasonal record. Such collagen isotopic analysis on M1, M2 and M3 roots and jawbone can be applied to reindeer found in archaeological sites. Mandibles retaining deciduous premolars are preferable to avoid the possible loss of the winter tooth signal observed in animals older than 2 years. Copyright © 2010 John Wiley &amp; Sons, Ltd.
The transporter associated with antigen processing (TAP) is active in a post-ER compartment
2010-11-24

The translocation of cytosolic peptides into the lumen of the endoplasmic reticulum (ER) is a crucial step in the presentation of intracellular antigen to T cells by major histocompatibility complex (MHC) class I molecules. It is mediated by the transporter associated with antigen processing (TAP) protein, which binds to peptide-receptive MHC class I molecules to form the MHC class I peptide-loading complex (PLC). We investigated whether TAP is present and active in compartments downstream of the ER. By fluorescence microscopy, we found that TAP is localized to the ERGIC (ER-Golgi intermediate compartment) and the Golgi of both fibroblasts and lymphocytes. Using an in vitro vesicle formation assay, we show that COPII vesicles, which carry secretory cargo out of the ER, contain functional TAP that is associated with MHC class I molecules. Together with our previous work on post-ER localization of peptide-receptive class I molecules, our results suggest that loading of peptides onto class I molecules in the context of the peptide-loading complex can occur outside the ER.
IDO1 and IDO2 gene expression analysis by quantitative polymerase chain reaction
2010-11-24

Immunomodulatory properties of IDO1 relate to tryptophan catabolism. The degradation of tryptophan by IDO1 leads to suppression of T cell responses. Recently, another enzyme with IDO‐like activity, indoleamine 2,3‐dioxygenase‐like‐protein 1 (INDOL1, IDO2), has been described in both mice and humans. In order to study the gene expression of IDO1 and IDO2 , we have developed a quantitative PCR (qPCR) assay. In an exploratory application to the study of the differential expression of IDO1 and IDO2 by professional antigen‐presenting cells and MSCs (mesenchymal stromal cells) under the influence of interferon‐γ (IFN‐γ) and T‐lymphocyte conditioned media (TCM), substantial differences were observed. IDO expression measured by qPCR was valid and reliable in the cell types investigated. Further studies are needed to delineate factors driving IDO expression in MSCs.
Accelerated aging phenotype in mice with conditional deficiency for mitochondrial superoxide dismutase in the connective tissue
2010-11-25

Summary The free radical theory of aging postulates that the production of mitochondrial reactive oxygen species is the major determinant of aging and lifespan. Its role in aging of the connective tissue has not yet been established, even though the incidence of aging‐related disorders in connective tissue‐rich organs is high, causing major disability in the elderly. We have now addressed this question experimentally by creating mice with conditional deficiency of the mitochondrial manganese superoxide dismutase in fibroblasts and other mesenchyme‐derived cells of connective tissues in all organs. Here, we have shown for the first time that the connective tissue‐specific lack of superoxide anion detoxification in the mitochondria results in reduced lifespan and premature onset of aging‐related phenotypes such as weight loss, skin atrophy, kyphosis (curvature of the spine), osteoporosis and muscle degeneration in mutant mice. Increase in p16 INK4a , a robust in vivo marker for fibroblast aging, may contribute to the observed phenotype. This novel model is particularly suited to decipher the underlying mechanisms and to develop hopefully novel connective tissue‐specific anti‐aging strategies.
Erratum to: Production of $ \\Lambda$ and $ \\Sigma^{0}_{}$ hyperons in proton-proton collisions
2010-11-25

This paper reports results on simultaneous measurements of the reaction\\nchannels pp -&gt; pK+\\\\Lambda and pp -&gt; pK+\\\\Sigma^0 at excess energies of 204, 239,\\nand 284 MeV (\\\\Lambda) and 127, 162, and 207 MeV (\\\\Sigma^0). Total and\\ndifferential cross sections are given for both reactions. It is concluded from\\nthe measured total cross sections that the high energy limit of the cross\\nsection ratio is almost reached at an excess energy of only about 200 MeV. From\\nthe differential distributions observed in the overall CMS as well as in the\\nJackson and helicity frames, a significant contribution of interfering nucleon\\nresonances to the \\\\Lambda production mechanism is concluded while resonant\\n\\\\Sigma^0-production seems to be of lesser importance and takes place only\\nthrough specific partial waves of the entrance channel. The data also indicate\\nthat kaon exchange plays a minor role in the case of \\\\Lambda- but an important\\nrole for \\\\Sigma^0-production. Thus the peculiar energy dependence of the\\n\\\\Lambda-to-\\\\Sigma^0 cross section ratio appears in a new light as its\\nexplanation requires more than mere differences between the p\\\\Lambda and the\\np\\\\Sigma^0 final state interaction. The data provide a benchmark for theoretical\\nmodels already available or yet to come.\\n
A new law on advance directives in Germany
2010-11-26

This article presents the new German law on advance directives from 1 September 2009. The history of the parliamentary process of this law is described, the present regulations are explained, their relevance for medical practice discussed and shortcomings are identified. Finally, the new law is compared with other regulations in the international context. Previously established legal practice in Germany has now become largely confirmed by the new law: An advanced directive must be respected in any decision concerning medical treatment, regardless of the stage of the illness. It can be informally revoked at any time, even with limited decision-making capacity. Nobody may be obliged to issue a directive in any way. Advance directives do not need notarisation or routine updating after certain time intervals. Provided that the patient, who is no longer mentally competent, has issued a lasting power of attorney (Bevollmächtiger), or provided that the patient has been appointed a healthcare proxy by the courts (Betreuer), this authorised surrogate must assert the patient's will. The role of the guardianship court is clarified: it only needs to be involved in cases of disagreement as to the patient's will. The new German law thus combines more legal certainty with a liberal emphasis on patient autonomy and flexible, adaptable regulations.
N-(4-Chloropyridin-2-yl)-N-methoxymethyl-4-methylbenzenesulfonamide
2010-11-26

In the crystal structure of the title compound, C(14)H(15)ClN(2)O(3)S, each mol-ecule is connected via inter-molecular C-H⋯O hydrogen bonds to three further mol-ecules, generating a three-dimensional network. The 4-methyl-phenyl-sulfonyl ring forms a dihedral angle of 40.7 (2)° with the 4-chloro-pyridine ring.
N-(4-Chloropyridin-2-yl)-N-(4-methylphenylsulfonyl)acetamide
2010-11-26

The crystal structure of the title compound, C(14)H(13)ClN(2)O(3)S, features a three-dimensional network stabilized by inter-molecular C-H⋯O hydrogen bonds between the mol-ecules. The 4-methyl-phenyl-sulfonyl ring forms a dihedral angle of 30.6 (1)° with the 4-chloro-pyridine ring.