julilili42/papers huggingface dataset:
Azathioprine favourably influences the course of malaria
2009-05-14

Abstract Background Azathioprine triggers suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and exposure of phosphatidylserine at the erythrocyte surface. Eryptosis may accelerate the clearance of Plasmodium -infected erythrocytes. The present study thus explored whether azathioprine influences eryptosis of Plasmodium -infected erythrocytes, development of parasitaemia and thus the course of malaria. Methods Human erythrocytes were infected in vitro with Plasmodium falciparum (P. falciparum) (strain BinH) in the absence and presence of azathioprine (0.001 – 10 μM), parasitaemia determined utilizing Syto16, phosphatidylserine exposure estimated from annexin V-binding and cell volume from forward scatter in FACS analysis. Mice were infected with Plasmodium berghei (P. berghei) ANKA by injecting parasitized murine erythrocytes (1 × 10 6 ) intraperitoneally. Where indicated azathioprine (5 mg/kg b.w.) was administered subcutaneously from the eighth day of infection. Results In vitro infection of human erythrocytes with P. falciparum increased annexin V-binding and initially decreased forward scatter, effects significantly augmented by azathioprine. At higher concentrations azathioprine significantly decreased intraerythrocytic DNA/RNA content (≥ 1 μM) and in vitro parasitaemia (≥ 1 μM). Administration of azathioprine significantly decreased the parasitaemia of circulating erythrocytes and increased the survival of P. berghei -infected mice (from 0% to 77% 22 days after infection). Conclusion Azathioprine inhibits intraerythrocytic growth of P. falciparum , enhances suicidal death of infected erythrocytes, decreases parasitaemia and fosters host survival during malaria.
The Immunosuppressive Properties of Mesenchymal Stem Cells
2009-05-15

Mesenchymal stem cells (MSC) are a type of multipotent progenitor cell, originally isolated from the bone marrow. In addition to multilineage differentiation and participation in the hematopoietic niche, they exert powerful immunomodulatory effects, which include inhibition of proliferation and function of T cells, B cells, and natural killer cells. These unique properties make MSC of great interest for clinical applications in tissue engineering and immunosuppression. Underlying the MSC-mediated immunomodulatory mechanisms is a nonspecific antiproliferative effect, which is the consequence of cyclin D2 inhibition. Of special interest are the molecular mechanisms, by which MSC influence their target cells. Several studies have been conducted in this field, and the current data suggest roles for indoleamine 2,3-dioxygenase, prostaglandin E2, nitric oxide, histocompatibility locus antigen-G, insulin-like growth factor-binding proteins, and tolerogenic antigen-presenting cells. Understanding these mechanisms is crucial for future use of MSC in research and clinical applications.
Ficolin 2 (FCN2) functional polymorphisms and the risk of rheumatic fever and rheumatic heart disease
2009-05-15

Summary Ficolins are pattern-recognition proteins involved in innate immunity, which upon binding to their specific pathogen-associated molecular patterns on the microbial surfaces trigger the immune response either by binding to collectin cellular receptors or by initiating the complement lectin pathway. In humans, three ficolin genes have been identified, which encode ficolin-1 (M-ficolin), ficolin-2 (L-ficolin) and ficolin-3 (H-ficolin or Hakata antigen). Ficolin-2 was shown to bind to lipoteichoic acid, a cell wall constituent in all Gram-positive bacteria such as Streptococcus pyogenes, which is the aetiological agent of rheumatic fever (RF) and its most severe sequelae, chronic rheumatic heart disease (CRHD). Here we investigated polymorphisms in the promoter region of the FCN2 gene (at positions −986/−602 and +4) in 122 patients with RF and CRHD and in 210 healthy subjects from the same geographic region and socioeconomic background. The haplotype −986/−602/−4 G/G/A, which is related to low levels of L-ficolin, was observed more frequently in the CRHD group when compared to the healthy subjects [99/162, 61·1% versus 211/420, 50·2%, odds ratio (OR) 1·6, confidence interval (CI) 95% 1·1–2·3, P = 0·021]. The haplotype −986/−602/−4 A/G/A was observed more frequently in the healthy group when compared to the affected (RF plus CRHD) subjects (31/420, 7·4% versus 6/244, 2·5%, OR 3·2, CI 95% 0·13–0·77, P = 0·008). Based on those findings, one can conclude that polymorphisms associated with low levels of L-ficolin level may predispose an individual to recurrent and/or more severe streptococcal infection.
Effects of medical training scenarios on heart rate variability and motivation in students and simulated patients
2009-05-15

Context Research regarding the experience of stress during medical training scenarios using standardised patients (SPs) has been primarily qualitative and has focused on the SPs. The purpose of this study was to quantitatively evaluate stress and motivation in both students and SPs during these scenarios by measuring heart rate variability (HRV) and administering the German version of the Questionnaire on Current Motivation (QCM). Methods A total of 44 medical students (23 women, 21 men) participated in two medical history‐taking training scenarios. In one scenario the SP role‐played a patient with a somatic disease; in the other the SP played a patient with a psychosomatic disease, creating easy and difficult scenarios, respectively, for the student. Each student interviewed one of 11 SPs (five women, six men), using the same SP in both scenarios. Heart rate variability was measured during baseline periods and during the training scenarios in both students and SPs. Motivation was assessed before each training scenario. Results Heart rate variability was lower in both students and SPs during the scenarios compared with baseline values, but did not differ by scenario type. For students, motivation increased when the first scenario involved psychosomatic illness, but decreased when the first condition was somatic. For SPs motivation was consistent over time for scenarios involving psychosomatic disease, but decreased for somatic disease‐related scenarios. Conclusions The training scenarios induced stress in both students and SPs, as indicated by decreased HRV. Student motivation was high, indicating that SP scenarios represent a valid teaching method. Further studies in the natural setting of SP examinations are needed.
Uridine insertion/deletion RNA editing in trypanosomatid mitochondria: In search of the editosome
2009-05-15

The RNA ligase-containing or L-complex is the core complex involved in uridine insertion/deletion RNA editing in trypanosome mitochondria. Blue native gels of glycerol gradient-separated fractions of mitochondrial lysate from cells transfected with the TAP-tagged editing protein, LC-8 (TbMP44/KREPB5), show a ∼1 MDa L-complex band and, in addition, two minor higher molecular weight REL1-containing complexes: one (L*a) co-sedimenting with the L-complex and running in the gel at around 1.2 MDa; the other (L*b) showing a continuous increase in molecular weight from 1 MDa to particles sedimenting over 70S. The L*b-complexes appear to be mainly composed of L-complex components, since polypeptide profiles of L- and L*b-complex gradient fractions were similar in composition and L*b-complex bands often degraded to L-complex bands after manipulation or freeze–thaw cycles. The L*a-complex may be artifactual since this gel shift can be produced by various experimental manipulations. However, the nature of the change and any cellular role remain to be determined. The L*b-complexes from both lysate and TAP pull-down were sensitive to RNase A digestion, suggesting that RNA is involved with the stability of the L*b-complexes. The MRP1/2 RNA binding complex is localized mainly in the L*b-complexes in substoichiometric amounts and this association is RNase sensitive. We suggest that the L*b-complexes may provide a scaffold for dynamic interaction with other editing factors during the editing process to form the active holoenzyme or “editosome.”
A Key Enzyme of the Leloir Pathway Is Involved in Pathogenicity of Leptosphaeria maculans Toward Oilseed Rape
2009-05-15

Agrobacterium tumefaciens-mediated random insertional mutagenesis was used to investigate pathogenicity determinants in Leptosphaeria maculans. One tagged nonpathogenic mutant, termed m186, is analyzed in detail here. Microscopic analyses of infected plant tissues revealed that m186 is specifically blocked at the invasive growth phase after an unaffected initial penetration stage and is unable to switch to the necrotrophic lifestyle. In addition, m186 exhibits an altered cell wall and seems to be affected in its ability to produce cell-wall-degrading enzymes. The T-DNA insertion occurs in the intergenic region between two head-to-tail genes, leading to a constitutive upregulation of their expression. Complementation experiments showed that only one of these two genes, Lmepi, fully accounts for the mutant phenotype. Bioinformatics and expression analyses along with functional studies suggested that the Lmepi gene encodes for the highly conserved UDP-glucose-4-epimerase, a key enzyme of the Leloir pathway involved in galactose metabolism. For the third time, this study highlights the intimate connection between primary metabolism and pathogenicity in L. maculans. This finding, along with similar data obtained from the related species Stagonospora nodorum, indicates the importance of in planta nutrition for the success of infection of plants by fungi belonging to class Dothideomycete.
Tracer kinetics analysis of dynamic contrast‐enhanced CT and MR data in patients with squamous cell carcinoma of the upper aerodigestive tract: comparison of the results
2009-05-15

Summary Purpose: (i) To evaluate the feasibility of tracer kinetics analysis of dynamic contrast‐enhanced (DCE) CT and T2‐weighted MR data of squamous cell carcinoma (SCCA) of the upper aerodigestive tract. (ii) To compare functional parameters derived by both modalities and examine the interchangeability of them as well as the intra‐ and inter‐rater agreement. Materials and methods: Dynamic contrast‐enhanced‐CT and MR images of 23 patients with SCCA were postprocessed using a distributed‐parameter (DP) tracer kinetic model. The evaluated parameters included blood flow ( F ), intravascular blood volume ( v 1 ), extravascular extracellular blood volume ( v 2 ), intravascular mean transit time ( t 1 ), lag time ( t 0 ), permeability surface area product (PS) and extraction ratio ( E ). Mean perfusion values, based on region‐of‐interest analysis, of the tumors and the healthy muscle tissue were compared and correlated. Inter‐rater and intra‐rater variability were assessed. Interchangeability of the tumor functional parameters was tested using Pearson’s correlation coeficients and Bland–Altman plots. Results: The mean values in tumor and healthy muscle tissues were significantly different for each modality (0·0001≤ P ≤0·03). The mean values of all tumor perfusion parameters apart from v 2 and E were significantly different (0·001≤ P ≤0·009) between the two modalities. The intra‐rater variability was good to very good for all parameters. The inter‐rater variability was moderate to good. Bland–Altman plots of F , t 1 , t 0 , and v 2 showed moderate interchangeability. There was a proportionality error in v 1 and PS graphs. Conclusion: The estimation of functional parameters in SCCA is feasible using DCE‐CT and ‐MR with a DP model. The parameters are mostly significantly different and the interchangeability of them is limited.
The Use of Different Transduction Principles for Qualitative and Quantitative Chiral Gas Analysis
2009-05-15

Different chiral cyclodextrin derivatives, dissolved in a polysiloxane matrix, have been used as enantioselective sensitive coatings on a three-transducer microsystem including a calorimetric, a mass-sensitive and a capacitive chemical sensor. Upon exposure to chiral analytes, such as methyl lactate and methyl-2-chloropropionate, all three transducers showed a distinct chiral discrimination of these analytes. It was shown that the absorption and desorption kinetics of the two enantiomers of, e.g., methyl-2-chloropropionate are sufficiently different to produce sensor signal features that enable an accurate determination of the enantiomeric purity and of the enantiomeric composition of the chiral analyte or mixture under investigation.
Intestinal Anion Exchanger Down-regulated in Adenoma (DRA) Is Inhibited by Intracellular Calcium
2009-05-16

The Na/H exchanger 3 (NHE3) and the Cl/HCO(3) exchanger down-regulated in adenoma (DRA) together facilitate intestinal electroneutral NaCl absorption. Elevated Ca(2+)(i) inhibits NHE3 through mechanisms involving the PDZ domain proteins NHE3 kinase A regulatory protein (E3KARP) or PDZ kidney 1 (PDZK1). DRA also possesses a PDZ-binding motif, but the roles of interactions with E3KARP or PDZK1 and Ca(2+)(i) in DRA regulation are unknown. Wild type DRA and a mutant lacking the PDZ interaction motif (DRA-ETKFminus) were expressed constitutively in human embryonic kidney (HEK) and inducibly in Caco-2/BBE cells. DRA-mediated Cl/HCO(3) exchange was measured as intracellular pH changes. Ca(2+)(i) was assessed fluorometrically. DRA was induced 8-16-fold and was delivered to the apical surface of polarized Caco-2 cells. Putative anion transporter 1 and cystic fibrosis transmembrane regulator did not contribute to Cl/HCO(3) exchange in transfected Caco-2 cells. The calcium ionophore 4Br-A23187 inhibited DRA and DRA-ETKFminus in HEK cells, but only full-length DRA was inhibited in Caco-2 cells. In contrast, 100 microm UTP, which increased Ca(2+)(i), inhibited full-length DRA but not DRA-ETKFminus in Caco-2 and HEK cells. In HEK cells, which express little PDZK1, additional transfection of PDZK1 was required for UTP to inhibit DRA. As HEK cells do not express cystic fibrosis transmembrane regulator or NHE3, the data indicate that Ca(2+)(i)-dependent DRA inhibition is not because of modulation of other transport activities. In polarized epithelium, this inhibition requires interaction of DRA with PDZK1. Together with data from PDZK1(-/-) mice, these data underscore the prominent role of PDZK1 in Ca(2+)(i)-mediated inhibition of colonic NaCl absorption.
Coupling of the biosynthesis and export of the DNA gyrase inhibitor simocyclinone in Streptomyces antibioticus
2009-05-18

Summary Because most antibiotics are potentially lethal to the producing organism, there must be mechanisms to ensure that the machinery responsible for export of the mature antibiotic is in place at the time of biosynthesis. Simocyclinone D8 is a potent DNA gyrase inhibitor produced by Streptomyces antibioticus Tü 6040. Within the simocyclinone biosynthetic cluster are two divergently transcribed genes, simR and simX , encoding proteins that resemble the TetR/TetA repressor–efflux pump pair that cause widespread resistance to clinically important tetracyclines. Engineered expression of simX from a strong, heterologous promoter conferred high level simocyclinone D8 resistance on Streptomyces lividans , showing that simX encodes a simocyclinone efflux pump. Transcription of simX is controlled by SimR, which directly represses the simX and simR promoters by binding to two operator sites in the simX–simR intergenic region. Simocyclinone D8 abolishes DNA binding by SimR, providing a mechanism that couples the biosynthesis of simocyclinone to its export. In addition, an intermediate in the biosynthetic pathway, simocyclinone C4, which is essentially inactive as a DNA gyrase inhibitor, also induces simX expression in vivo and relieves simX repression by SimR in vitro .
Endovascular repair of infrarenal abdominal aortic aneurysm associated with a horseshoe kidney and graft thrombosis in early follow-up
2009-05-18

Endovascular aneurysm repair (EVAR) is a well-established alternative to open surgery. The presented case underwent endovascular therapy of an abdominal aortic aneurysm (AAA) with the anatomical prerequisite of a horseshoe kidney. We describe the technique used, including the embolization of aortic side branches, to avoid endoleaks, and the management of thrombotic complications during follow-up.
MRI Findings in Inflammatory Muscle Diseases and Their Noninflammatory Mimics
2009-05-19

MRI is a highly sensitive tool for the diagnosis of muscle diseases. Although it has low specificity, awareness of the potential imaging findings in the various, sometimes rare, muscular disorders is helpful for accurate diagnosis.
Lipoproteins in Staphylococcus aureus Mediate Inflammation by TLR2 and Iron-Dependent Growth In Vivo
2009-05-19

Abstract Lipoproteins (Lpp) are ligands of TLR2 and signal by the adaptor MyD88. As part of the bacterial cell envelope, Lpp are mainly involved in nutrient acquisition for Staphylococcus aureus. The impact of Lpp on TLR2-MyD88 activation for S. aureus in systemic infection is unknown. S. aureus strain SA113 deficient in the enzyme encoded by the prolipoprotein diacylglyceryl transferase gene (Δlgt), which attaches the lipid anchor to pro-Lpp, was used to study benefits and costs of Lpp maturation. Lpp in S. aureus induced early and strong cytokines by TLR2-MyD88 signaling in murine peritoneal macrophages. Lpp contributed via TLR2 to pathogenesis of sepsis in C57BL/6 mice with IL-1β, chemokine-mediated inflammation, and high bacterial numbers. In the absence of MyD88-mediated inflammation, Lpp allowed bacterial clearing from liver devoid of infiltrating cells, but still conferred a strong growth advantage in mice, which was shown to rely on iron uptake and storage in vitro and in vivo. With iron-restricted bacteria, the Lpp-related growth advantage was evident in infection of MyD88−/−, but not of C57BL/6, mice. On the other hand, iron overload of the host restored the growth deficit of Δlgt in MyD88−/−, but not in immunocompetent C57BL/6 mice. These results indicate that iron acquisition is improved by Lpp of S. aureus but is counteracted by inflammation. Thus, lipid anchoring is an evolutionary advantage for S. aureus to retain essential proteins for better survival in infection.
Mitochondria and Energetic Depression in Cell Pathophysiology
2009-05-19

Mitochondrial dysfunction is a hallmark of almost all diseases. Acquired or inherited mutations of the mitochondrial genome DNA may give rise to mitochondrial diseases. Another class of disorders, in which mitochondrial impairments are initiated by extramitochondrial factors, includes neurodegenerative diseases and syndromes resulting from typical pathological processes, such as hypoxia/ischemia, inflammation, intoxications, and carcinogenesis. Both classes of diseases lead to cellular energetic depression (CED), which is characterized by decreased cytosolic phosphorylation potential that suppresses the cell’s ability to do work and control the intracellular Ca2+ homeostasis and its redox state. If progressing, CED leads to cell death, whose type is linked to the functional status of the mitochondria. In the case of limited deterioration, when some amounts of ATP can still be generated due to oxidative phosphorylation (OXPHOS), mitochondria launch the apoptotic cell death program by release of cytochrome c. Following pronounced CED, cytoplasmic ATP levels fall below the thresholds required for processing the ATP-dependent apoptotic cascade and the cell dies from necrosis. Both types of death can be grouped together as a mitochondrial cell death (MCD). However, there exist multiple adaptive reactions aimed at protecting cells against CED. In this context, a metabolic shift characterized by suppression of OXPHOS combined with activation of aerobic glycolysis as the main pathway for ATP synthesis (Warburg effect) is of central importance. Whereas this type of adaptation is sufficiently effective to avoid CED and to control the cellular redox state, thereby ensuring the cell survival, it also favors the avoidance of apoptotic cell death. This scenario may underlie uncontrolled cellular proliferation and growth, eventually resulting in carcinogenesis.
The effect of 40 h constant wakefulness on task‐switching efficiency
2009-05-19

Summary This study investigated efficiency of switching between different tasks in 12 male participants (19–30 years) during 40 h of constant wakefulness. As index of task‐switching efficiency, switch costs in reaction time were assessed every 3 h under controlled behavioural and environmental conditions. Overall reaction times and switch costs showed a temporal pattern consistent with the assumption of a combined influence of a sleep homeostatic and a circadian process. An additional analysis indicated that the variation in switch costs could not be attributed to interference of the current task with persisting activation from preceding tasks. We therefore conclude that sleep loss and the circadian system affect the ability to prepare the current task rather than automatic processing of irrelevant stimulus information.
A new species ofAdenomera(Amphibia: Anura: Leptodactylidae) from the Atlantic rain forest in Santa Catarina, southern Brazil
2009-05-19

As part of the remarkable biodiversity of anurans in the southern range of the Brazilian Mata Atlântica, Adenomera engelsi sp. nov. is described here as a new taxon occurring on the island of Santa Catarina and adjacent coastal mainland. This litter-inhabiting frog is restricted to the Atlantic rain forest biome, living in primary and secondary woods and semi-open areas from sea level to about 900 m a.s.l., partly in sympatry with its congener A. araucaria. Both species are also referred to the Leptodactylus marmoratus group. Adenomera engelsi sp. nov. is a medium-sized member of the genus (snout–vent length 20.9–22.7 mm in males), characterized by a brown dorsal coloration with a maculated pattern of variable dark spots and blotches and a unique advertisement call, consisting of single, unpulsed notes with duration of 95–160 ms, dominant frequency between 3500 and 4300 Hz, and note repetition rates of 10–24 notes/min. Está descrita, como parte da enorme biodiversidade de anuros na região sul da Mata Atlântica brasileira, Adenomera engelsi sp. nov. que ocorre na Ilha de Santa Catarina e no litoral adjacente. A espécie está restrita ao bioma da Mata Atlântica, onde vive no folhiço em mata primária, secundária e áreas semi-abertas, desde o nível do mar até 900 m, parcialmente em simpatria com A. araucaria. Ambas as espécies também são atribuidas ao grupo Leptodactylus marmoratus. Adenomera engelsi sp. nov., de tamanho medio dentro do gênero (SVL 20.9–22.7 mm em machos), é caraterizada pela coloração dorsal marrom, com manchas escuras de tamanho e forma variável e um canto de anúncio distinto, que consiste de notas únicas e sem pulsos de 95–160 ms com frequência dominante entre 3500–4300 Hz e taxa de repetição de 10–24 notas por minuto.