julilili42/papers huggingface dataset:
Characterization of the ‘pristinamycin supercluster’ of Streptomyces pristinaespiralis
2010-10-15

Summary Pristinamycin, produced by Streptomyces pristinaespiralis Pr11, is a streptogramin antibiotic consisting of two chemically unrelated compounds, pristinamycin I and pristinamycin II. The semi‐synthetic derivatives of these compounds are used in human medicine as therapeutic agents against methicillin‐resistant Staphylococcus aureus strains. Only the partial sequence of the pristinamycin biosynthetic gene cluster has been previously reported. To complete the sequence, overlapping cosmids were isolated from a S. pristinaespiralis Pr11 gene library and sequenced. The boundaries of the cluster were deduced, limiting the cluster size to approximately 210 kb. In the central region of the cluster, previously unknown pristinamycin biosynthetic genes were identified. Combining the current and previously identified sequence information, we propose that all essential pristinamycin biosynthetic genes are included in the 210 kb region. A pristinamycin biosynthetic pathway was established. Furthermore, the pristinamycin gene cluster was found to be interspersed by a cryptic secondary metabolite cluster, which probably codes for a glycosylated aromatic polyketide. Gene inactivation experiments revealed that this cluster has no influence on pristinamycin production. Overall, this work provides new insights into pristinamycin biosynthesis and the unique genetic organization of the pristinamycin gene region, which is the largest antibiotic ‘supercluster’ known so far.
Insulin Sensitivity Is Reflected by Characteristic Metabolic Fingerprints - A Fourier Transform Mass Spectrometric Non-Targeted Metabolomics Approach
2010-10-15

Our results suggest that altered metabolite patterns that reflect changes in insulin sensitivity respectively the ISI(Matsuda) are dominated by lipid-related pathways. Furthermore, a metabolic transition state reflected by heterogeneous metabolite fingerprints may precede severe alterations of metabolism. Our findings offer future prospects for novel insights in the pathogenesis of the pre-diabetic phase.
Activation of Membrane Androgen Receptors in Colon Cancer Inhibits the Prosurvival Signals Akt/Bad In Vitro and In Vivo and Blocks Migration via Vinculin/Actin Signaling
2010-10-15

Recently, we reported that membrane androgen receptors (mARs) are expressed in colon tumors triggering strong apoptotic responses. In the present study, we analyzed mAR-induced downstream effectors controlling cell survival and migration of Caco2 colon cancer cells. We show that long-term activation of mAR downregulated the activity of PI-3K and Akt and induced de-phosphorylation/activation of the proapoptotic Bad (p-Bad). Moreover, treatment of APC(Min/+) mice, which spontaneously develop intestinal tumors, with mAR-activating testosterone conjugates reduced the tumor incidence by 80% and significantly decreased the expression of p-Akt and p-Bad levels in tumor tissue. Furthermore, mAR activation strongly inhibited Caco2 cell migration. In accordance with these findings, vinculin, a protein controlling cell adhesion and actin reorganization, was effectively phosphorylated upon mAR activation. Phosphorylation inhibitors genistein and PP2 inhibited actin reorganization and restored motility. Moreover, silencing vinculin by appropriate siRNA's, or blocking actin reorganization by cytochalasin B, restored the migration potential. From these results we conclude that mAR activation inhibits the prosurvival signals Akt/Bad in vitro and in vivo and blocks migration of colon cancer cells via regulation of vinculin signaling and actin reorganization, supporting the powerful tumoristatic effect of those receptors.
Novel Rodent Models for Macular Research
2010-10-15

The retinal specializations of Gerbillus perpallidus, Meriones unguiculatus and Phodopus campbelli resemble features of the primate macula. Hence, the rodents reported here may serve to study aspects of macular development and diseases like age-related macular degeneration and diabetic macular edema, and the preclinical assessment of therapeutic strategies.
Autoantibodies to muscarinic acetylcholine receptors found in patients with primary biliary cirrhosis
2010-10-16

For the first time, our data demonstrate the presence of autoantibodies to the hmAchR M3 in PBC patients. These findings might contribute to the understanding of the pathogenesis of this disease. Further studies have to focus on the functionality of hmAchR M3 autoantibodies in PBC patients.
Expression of HSP 90, PTEN and Bcl-2 in conjunctival melanoma
2010-10-17

Conjunctival melanocytes differentially express Bcl-2, HSP-90 and PTEN, depending on their entity. HSP-90- and PTEN expression may add relevant information for the differentiation between conjunctival melanoma and nevi.
Suicide bombers in Western literature: demythologizing a mythic discourse
2010-10-17

In facing the challenge of suicide terrorism today on a global scale, it is tempting to attribute the phenomenon to cultural or religious behavior patterns observed solely in non‐Western countries. Yet recent scholarly research on its possible cultural or religious origins has led less to convincing and satisfactory results than to an unresolved aporia between arbitrariness and contingency. By the same token, little notice is taken of the fact that, in Western history and literature, actions and figures can be found whose development and strategies conspicuously resemble those of today's suicide bombers. A series of such analogous examples in Western literature from antiquity to the present is explored in order to provide deeper insights into situational and systemic factors at work beyond cultural and religious determinants. To more effectively counter suicide terrorism, alternative policies are proposed with the vision of a peaceful coexistence of diverse cultures and religions.
The head-fixed behaving rat—Procedures and pitfalls
2010-10-18

This paper describes experimental techniques with head-fixed, operantly conditioned rodents that allow the control of stimulus presentation and tracking of motor output at hitherto unprecedented levels of spatio-temporal precision. Experimental procedures for the surgery and behavioral training are presented. We place particular emphasis on potential pitfalls using these procedures in order to assist investigators who intend to engage in this type of experiment. We argue that head-fixed rodent models, by allowing the combination of methodologies from molecular manipulations, intracellular electrophysiology, and imaging to behavioral measurements, will be instrumental in combining insights into the functional neuronal organization at different levels of observation. Provided viable behavioral methods are implemented, model systems based on rodents will be complementary to current primate models--the latter providing highest comparability with the human brain, while the former offer hugely advanced methodologies on the lower levels of organization, for example, genetic alterations, intracellular electrophysiology, and imaging.
The aesthetics of water and land: a promising concept for managing scarce water resources under climate change
2010-10-18

The eastern Mediterranean faces a severe water crisis: water supply decreases due to climate change, while demand increases due to rapid population growth. The GLOWA Jordan River project generates science-based management strategies for maximizing water productivity under global climate change. We use a novel definition of water productivity as the full range of services provided by landscapes per unit blue (surface) and green (in plants and soil) water. Our combined results from climatological, ecological, economic and hydrological studies suggest that, in Israel, certain landscapes provide high returns as ecosystem services for little input of additional blue water. Specifically, cultural services such as recreation may by far exceed that of food production. Interestingly, some highly valued landscapes (e.g. rangeland) appear resistant to climate change, making them an ideal candidate for adaptive land management. Vice versa, expanding irrigated agriculture is unlikely to be sustainable under global climate change. We advocate the inclusion of a large range of ecosystem services into integrated land and water resources management. The focus on cultural services and integration of irrigation demand will lead to entirely different but productive water and land allocation schemes that may be suitable for withstanding the problems caused by climate change.
Histopathological and molecular features of late relapses in non‐seminomas
2010-10-18

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Late relapses from germ cell tumors respond poorly to systemic chemotherapy. This feature has been partly attributed to their presumed derivation from mature teratomas giving rise to secondary non‐germ cell histologies that have lost the original germ cell‐like behaviour. Our series demonstrates the occurrence of non‐germ cell malignancies in the absence of mature teratoma and points towards microsatellite instability and BRAF‐mutations as the biologic basis for chemotherapy resistance in about half of the cases. OBJECTIVE • To describe the histopathological types of late relapses of germ cell tumours and to search for molecular markers associated with chemotherapy resistance. PATIENTS AND METHODS • Samples from 14 patients with late relapse from a non‐seminoma were analysed. • Archival tumour tissue was gathered at intial diagnosis ( n = 9) and at relapse ( n = 9), mostly after previous treatment with chemotherapy. • In addition to routine histopathology, tumours were analysed for microsatellite instability and screened for mutations in the KRAS and BRAF genes. RESULTS • Relapse occurred after 76.5 months (median, range: 24–209 months). • The histology in relapse was pure yolk sac tumour in four of the nine patients analysed. • Three had a non‐germ cell malignancy, one was a mixed non‐seminoma and one was a pure mature teratoma. • One sample with non‐germ cell malignancy originated from a yolk sac tumour without any evidence of teratoma. • In four of 12 evaluable patients, high‐level microsatellite instability was observed. • All patients were KRAS wild‐type but four showed a BRAF mutation at V600E. CONCLUSIONS • Many late relapses of germ cell tumours show pure yolk sac histology. • Non‐germ cell malignancies do not necessarily develop from teratoma but can also arise from yolk sac histology. • The biology underlying chemotherapy resistance in late relapse could be related to a high incidence of microsatellite instability and BRAF mutation V600E, which were found in half of the patients.
Bidirectional relations of religious orientation and depressive symptoms in adolescents: A short-term longitudinal study.
2010-10-18

Religious orientation can be divided into intrinsic and extrinsic: intrinsically oriented individuals âlive their religion,â whereas extrinsically oriented individuals practice religion mainly to gain external benefits. In adults, depression has been found to correlate negatively with intrinsic religious orientation and positively with extrinsic orientation. Studies of the relation between religiosity and depression typically have not been longitudinal, conducted with adolescents, controlled for the influence of other factors associated with depression (i.e., negative cognitions), or examined the reverse relation of depression predicting religious orientation. Our four-month longitudinal study of 273 ninth-grade students addressed these issues. Results showed that higher intrinsic religious orientation measured at baseline significantly predicted lower self-reported depressive symptoms four months later, controlling for initial level of depressive symptoms and cognitive style; in contrast, extrinsic orientation and the interaction between religious orientation and life events did not significantly predict later depressive symptoms. Self-reported depressive symptoms, however, did not predict either intrinsic or extrinsic religious orientation four months later. Factors contributing to different findings for adolescents versus adults in the relation between extrinsic religious orientation and depression are suggested.
Seedling dynamics at elevation limits: Complex interactions beyond seed and microsite limitations
2010-10-18

• Premise of the study: Limited availability of seeds and microsites are important constraints for seedling emergence and survival. However, little is known about population‐level feedbacks between seed and microsite limitation and how these relationships vary in contrasting conditions. Focusing on Armeria caespitosa , a high‐mountain endemic, we asked whether seedling establishment was simultaneously limited by seed and microsite availability, whether the balance between seed and microsite limitations varied with contrasting environments, and whether seed and microsite limitations interacted with each other. • Methods: We studied seedling emergence and survival at the edges of the elevation range of A. caespitosa in central Spain over 4 years. We used mixed linear models and structural equation modeling. • Key results: Our results showed that A. caespitosa recruits similar numbers of new seedlings per plot in contrasting environments. Seedling emergence and survival in A. caespitosa were both limited by seed and microsite availability. Habitat suitability (the surrogate of microsite limitation) varied between populations and indirectly affected fertility (the surrogate of seed limitation). • Conclusions: Seedling emergence and survival are both seed and microsite limited, there are interactions between seed and microsite limitations, and both factors, which control seedling establishment, and their interconnections, vary among local populations.
Fine specificity of anti-MSP119 antibodies and multiplicity of Plasmodium falciparum Merozoite Surface Protein 1 types in individuals in Nigeria with sub-microscopic infection
2010-10-18

Abstract Background The absence of antibodies specific for the 19 kDa C-terminal domain of merozoite surface protein 1 (MSP1 19 ) has been associated with high-density malaria parasitaemia in African populations. The hypothesis that a high prevalence and/or level of anti-MSP1 19 antibodies that may inhibit erythrocyte invasion would be present in apparently healthy individuals who harbour a sub-microscopic malaria infection was tested in this study. Methods Plasma samples were collected from residents in a region in Nigeria hyperendemic for malaria, who had no detectable parasitaemia by microscopy. Using a competition-based enzyme-linked-immunosorbent assay with two invasion-inhibitory monoclonal antibodies (mAbs) 12.10 and 12.8, the levels and prevalence of specific antibodies were measured. The minimum multiplicity of infection was determined using PCR. The prevalence of anaemia was also measured. Results Plasma samples from 85% of individuals contained antibodies that bound to MSP1 19 . The inhibition of mAb 12.10 binding was strongly correlated with the prevalence (Spearman correlation test, p &lt; 0.0001) and mean titre of anti-MSP1 19 antibodies (Spearman correlation test, p &lt; 0.001) in the samples. Comparing samples from individuals with multiple infection (group M) and single infection (Group S), group M contained a higher (p = 0.04) prevalence of anti-MSP1 19 antibodies that competed with mAb 12.10. Using a logistic regression model, it was found that the presence of antibodies competitive with mAb 12.10 was affected negatively by anaemia (p = 0.0016) and positively by the carriage of multiple parasite genotypes (p = 0.04). Conclusions In the search for correlates of protection against malaria, which will be essential to evaluate clinical trials of malaria vaccines based on MSP1, this study examines some potential assays and the factors that need to taken into account during their evaluation, using samples from individuals naturally exposed to malaria infection.
Life at the end of the Holocene moist phase in south‐east Arabia — the Late Neolithic site of Jebel Thanais 1 (JTH1)
2010-10-18

The surface site of Jebel Thanais 1 is located in the Emirate of Sharjah (U.A.E.) at the western flank of the Jebel Faya/Jebel Buhais anticline structure. A dense scatter of lithic artefacts and fireplaces indicates Stone Age settlement activities in this area. Radiocarbon dates obtained from fireplaces date the occupation of the site to both the beginning and the very end of the fifth millennium cal. BC. During the second half of the fifth millennium the deterioration of climatic conditions in south‐east Arabia had a noticeable impact on settlement patterns and subsistence strategies. While coastal habitation sites from this time are well known along the shores of the Oman peninsula, only a few poorly dated sites allow insights into habitation and raw material procurement strategies and lithic technology in the interior. Investigations into the spatial structure of the site and an analysis of lithic finds will contribute to a better understanding of this period.
Cyanobacterial Heterocysts
2010-10-18

Abstract Cyanobacteria are phototrophic bacteria carrying out oxygen‐producing photosynthesis. Indeed, cyanobacteria were the inventors of oxygenic photosynthesis carried out by eukaryotic algae and plants. Besides showing the capability of building their cellular carbon from carbon dioxide, available in the atmosphere, several strains of cyanobacteria have also acquired the ability to fix molecular dinitrogen (N 2 ). As the enzyme responsible for nitrogen fixation ( nitrogenase ) is highly sensitive towards oxygen, nitrogen fixation and oxygenic photosynthesis cannot take place simultaneously in cyanobacterial cells. To solve this problem, some filamentous strains are able to restrict N 2 fixation to a special cell type, the heterocyst. Heterocysts are specialised, morphologically distinct, terminally differentiated cells that develop, in the absence of alternative sources of combined nitrogen, mostly in a semiregular pattern along the filament. Thus, a filament containing heterocysts provides division of labour between photosynthetic carbon dioxide fixation (in vegetative cells) and anaerobic N 2 fixation (in heterocysts). These cyanobacteria represent true multicellular organisms with profound morphological cell differentiation and sophisticated intercellular communication systems. Key Concepts: Although bacteria, some filamentous cyanobacteria are true multicellular organisms, showing different cell types for specialised tasks. When starved for a source of combined nitrogen these cyanobacteria start a programme of cell differentiation resulting in a pattern of semiregularly spaced heterocysts along the filament. Heterocysts develop from vegetative cells, the sites for oxygenic photosynthesis, and provide a microoxic environment for the oxygen‐labile nitrogenase. Nitrogenase is the enzyme responsible for N 2 fixation and allows the organism to live from sunlight, air (carbon dioxide and N 2 ) and some minerals. Under nitrogen fixing conditions the two cell types rely on each other and exchange metabolites and signalling molecules, presumably via protein‐complex‐mediated cell‐to‐cell contact or the continuous periplasmic space that surrounds all cells of the multicellular filament. Global nitrogen control factor NtcA controls activation of many genes involved in heterocyst differentiation and function. HetR, the activator of heterocyst differentiation, is regulated by NtcA, known inhibitors of heterocyst differentiation PatS and HetN, as well as by proteins HetF and PatA controlling HetR turnover. The pattern of spaced heterocysts is regulated by inhibitor gradients that promote the decay of HetR, confirming mathematical models of two‐dimensional pattern formation in heterocystous cyanobacteria.
[Grading the level of suspicion in criminal proceedings, restrictions of the proportionality principle and veto options in forensic autopsies].
2010-10-18

The article deals with two topics: determination of the necessary level of suspicion for an internal post-mortem examination pursuant to Section 87 (German) Code of Criminal Procedure and options of the family to object to the forensic autopsy. The level of suspicion required in this case is to be regarded as very low, even below that of the initial suspicion, because a detailed opinion as to any third-party fault can only be given after completion of the autopsy. The individual concerned does not have a right to oppose a forensic autopsy while still alive. The same applies to the family. Other than in clinical autopsies, the interest in prosecution is to be considered the higher good to be protected, because at the time of deciding a homicide cannot be ruled out and only an internal examination can furnish the necessary evidence. Consequently, it is appropriate. Contrary to the opinion often expressed in the literature, one cannot infer from the provisions of Sections 87 subs. 4, 33 subs. 3 Code of Criminal Procedure and Section 103 subs. 3 Basic Law that the family of the deceased has a right to be informed or heard. This can only be changed by the legislator in an amendment to the autopsy law.
Late Cambrian–Ordovician northeastern Gondwanan terranes in the basement of the Apuseni Mountains, Romania
2010-10-19

Abstract: The pre-Alpine basement of the Apuseni Mountains (Romanian Carpathians) comprises three terranes: Someş, Baia de Arieş and Biharia. Metaigneous rocks within these terranes record Late Cambrian–Ordovician U–Pb zircon crystallization ages. Two samples from an orthogneiss layer in the Someş terrane yielded an age of 459.8 ± 2.7 Ma. In the Baia de Arieş terrane, an augen gneiss yielded an age of 470.8 ± 3.8 Ma, a porphyroid yielded an age of 467.8 ± 3.8 Ma and two metagranites yielded ages of 467.8 ± 4.7 Ma and 467.1 ± 3.9 Ma, respectively. Three samples from a metagranitoid outcrop located in the lower part of the Biharia terrane yielded an age of 495.0 ± 2.1 Ma. Three other samples from a metabasite layer situated lithostratigraphically several hundred metres above the metagranitoid yielded an age of 477.8 ± 3.2 Ma. Detrital U/Pb zircon ages from a paragneiss interlayered within the Baia de Arieş terrane scatter between 548 and 3518 Ma. Detrital zircon ages together with the inherited ages recorded by magmatic zircon populations suggest a northeastern Gondwanan provenance for the Someş, Baia de Arieş and Biharia terranes, adjacent to the Arabian–Nubian Shield. Lead loss in some zircons is interpreted to have taken place during the Variscan orogeny. Supplementary material: Coordinates for samples from the Apuseni Mountains, Palaeozoic palaeogeographical models of Gondwana, Laurentia and Baltica to the formation of Pangaea, sample preparation and analytical procedures, sample description, and age measurements of zircon grains are available at http://www.geolsoc.org.uk/SUP18425 .
In Vivo Characterization of a Smart MRI Agent That Displays an Inverse Response to Calcium Concentration
2010-10-20

Contrast agents for magnetic resonance imaging (MRI) that exhibit sensitivity toward specific ions or molecules represent a challenging but attractive direction of research. Here a Gd(3+) complex linked to an aminobis(methylenephosphonate) group for chelating Ca(2+) was synthesized and investigated. The longitudinal relaxivity (r(1)) of this complex decreases during the relaxometric titration with Ca(2+) from 5.76 to 3.57 mM(-1) s(-1) upon saturation. The r(1) is modulated by changes in the hydration number, which was confirmed by determination of the luminescence emission lifetimes of the analogous Eu(3+) complex. The initial in vivo characterization of this responsive contrast agent was performed by means of electrophysiology and MRI experiments. The investigated complex is fully biocompatible, having no observable effect on neuronal function after administration into the brain ventricles or parenchyma. Distribution studies demonstrated that the diffusivity of this agent is significantly lower compared with that of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA).