julilili42/papers huggingface dataset:
Highly Efficient Staphylococcus carnosus Mutant Selection System Based on Suicidal Bacteriocin Activation
2011-12-17

ABSTRACT Strains from various staphylococcal species produce bacteriocin peptides, which are thought to play important roles in bacterial competition and offer interesting biotechnological avenues. Many bacteriocins are secreted as inactive prepeptides with subsequent activation by specific proteolytic cleavage. By deletion of the protease gene gdmP in Staphylococcus gallinarum Tü3928, which produces the highly active lanthionine-containing bacteriocin gallidermin (lantibiotic), a strain was created producing inactive pregallidermin. On this basis, a new suicidal mutant selection system in the food-grade bacterium Staphylococcus carnosus was developed. Whereas pregallidermin was inactive against S. carnosus , it exerted potent bactericidal activity toward GdmP-secreting S. carnosus strains. To take advantage of this effect, gdmP was cloned in plasmid vectors used for random transposon mutagenesis or targeted allelic replacement of chromosomal genes. Both mutagenesis strategies rely on rare recombination events, and it has remained difficult and laborious to identify mutants among a vast majority of bacterial clones that still contain the delivery vectors. The gdmP -expressing plasmids pGS1 and pGS2 enabled very fast, easy, and reliable identification of transposon and gene replacement mutants, respectively. Mutant selection in the presence of pregallidermin caused suicidal inactivation of all clones that had retained the plasmids and allowed growth of only plasmid-cured mutants. Efficiency of mutant identification was several magnitudes higher than standard screening for the absence of plasmid-encoded antibiotic resistance markers and reached 100% specificity. Thus, the new pregallidermin-based mutant selection system represents a substantial improvement of staphylococcal mutagenesis methodology.
ROAD - A Portal and Platform for Research on Early Humans
2011-12-18

The new research centre entitled “The Ro le of C ulture in E arly E xpansions of H umans” (ROCEEH), funded by the Heidelberg Academy of Sciences and Humanities, is projected to run for 20 years. The research centre's aim is to reconstruct the spatial and temporal patterns of the expansions of hominins between 3 million to 20000 years ago within Africa and Eurasia. The main goal of the research centre is to explain the biotic and abiotic reasons for different hominin expansions. Implicit in the current working hypothesis is the assumption that the influence of changing environmental conditions decreased as the importance of cultural and technological innovations grew. To achieve these general objectives, a geo-relational spatial database was developed and implemented, containing information about archaeology, palaeontology, and environmental circumstances. The database is called ROAD, an acronym standing for “ R OCEEH O ut of A frica D atabase”. In this paper we focus on the technical issues of this database, the functionalities, as well as the implementation in order to assess early human expansions. Moreover, we discuss the role of ROAD as an international platform and portal for researchers focussing on early human investigations.
Neuromyelitis optica spectrum disorders in patients with myasthenia gravis: ten new aquaporin-4 antibody positive cases and a review of the literature
2011-12-19

Background: Neuromyelitis optica (NMO, Devic syndrome) and myasthenia gravis (MG) are rare antibody-mediated autoimmune disorders. Concurrent incidence has been reported in only few patients, mostly non-Caucasians. Objective: To report on ten Caucasian patients with NMO spectrum disorders (NMOSD) and MG and to provide a comprehensive review of the literature. Method: Retrospective study. Results: In total, 26 patients (m:f = 1:12; Caucasian in 12) with MG (generalized in 17) and NMOSD (NMO in 21, longitudinally extensive transverse myelitis in five) were identified from the authors’ own files ( n = 10) and the previous literature ( n = 16). MG preceded NMOSD in 24/25 cases (96%). AQP4-Ab were tested in 20 patients and were positive in 17 (85%). Twenty out of 25 patients (80%) had been treated with thymectomy or thymic irradiation, which preceded NMOSD in all cases (median latency, 12 years; range, 0.3–32). At last follow-up, complete remission of MG was reported in 15/22 (68%), and MG was well controlled with pyridostigmine in three. Co-existing autoimmune disorders or autoimmune antibodies were reported in 17 patients. Conclusion: Our study demonstrates that i) AQP4-Ab-positive NMOSD are more commonly associated with MG in Caucasians than previously thought; ii) MG precedes NMOSD in most cases, often by more than a decade; iii) NMOSD almost exclusively occur in females with juvenile or early-onset MG; and iv) MG frequently takes an unusually mild course in patients with NMOSD. A history of thymectomy could be a possible risk factor for the later development of NMOSD. We recommend testing for AQP4-Ab in MG patients presenting with atypical motor or optic symptoms.
Tri- and Tetrasubstituted Pyrazole Derivates: Regioisomerism Switches Activity from p38MAP Kinase to Important Cancer Kinases
2011-12-19

In the course of searching for new p38α MAP kinase inhibitors, we found that the regioisomeric switch from 3-(4-fluorophenyl)-4-(pyridin-4-yl)-1-(aryl)-1H-pyrazol-5-amine to 4-(4-fluorophenyl)-3-(pyridin-4-yl)-1-(aryl)-1H-pyrazol-5-amine led to an almost complete loss of p38α inhibition, but they showed activity against important cancer kinases. Among the tested derivatives, 4-(4-fluorophenyl)-3-(pyridin-4-yl)-1-(2,4,6-trichlorophenyl)-1H-pyrazol-5-amine (6a) exhibited the best activity, with IC(50) in the nanomolar range against Src, B-Raf wt, B-Raf V600E, EGFRs, and VEGFR-2, making it a good lead for novel anticancer programs.
Thermodynamics of 5D black holes on asymptotically locally flat gravitational instantons
2011-12-19

We investigate the thermodynamical properties of solutions to the 5D Einstein\\nand Einstein-Maxwell-dilaton equations describing static black holes on ALF\\ngravitational instantons. Some general expressions regarding the nut charge and\\npotential are derived, as well as Smarr-like relations. The thermodynamics of\\ntwo particular solutions representing a static black hole on Taub-Nut and\\nTaub-Bolt instantons are examined in detail. Two dierent approaches for\\ncomputation of the mass and the tension - the Komar and counterterm method, are\\napplied and compared. A new charged black hole on Taub-Bolt instanton is\\nconstructed and investigated.\\n
Utilizing echo‐shifts in k‐space for generation of positive contrast in areas with marked susceptibility alterations
2011-12-19

Abstract A technique for generation of positive contrast near susceptibility alterations utilizing echo‐shifts in k‐space is introduced, based on altered Larmor‐frequencies and resulting phase‐shifts accumulating during the echo‐time at the site of local magnetic field gradients. 3D gradient‐echo raw‐data is acquired and weighted with an inverse Hanning filter. The filter partly suppresses central raw‐data points, while maintaining outer areas. Reconstruction of the filtered raw‐data results in images where pixels with apparent magnetic field gradients are highlighted against homogeneous pixels. Further processing steps are introduced to remove remaining intensities in the homogeneous parts of the filtered image. Feasibility is shown by an agar phantom containing magnetically labeled cells, with concentrations of 25, 50, 100, and 250 cells/μL, and by images of the human head. The technique allows detection of echo‐shifted pixels with automatic suppression of magnetically homogeneous parts while keeping post‐processing time short. Fewer than four labeled cells per pixel were clearly displayed with positive contrast. Application to the human head shows bright veins and complete suppression of homogeneous regions. The presented technique has high potential for specific detection of low concentrations of labeled cells or susceptibility altered regions in vivo with positive contrast, whereas areas with low spin density are not highlighted. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.
Changes in Antigen-specific IgG1 Fc N-glycosylation Upon Influenza and Tetanus Vaccination
2011-12-20

Antibody effector functions have been shown to be influenced by the structure of the Fc N-glycans. Here we studied the changes in plasma or serum IgG Fc N-glycosylation upon vaccination of 10 Caucasian adults and 10 African children. Serum/plasma IgG was purified by affinity chromatography prior to and at two time points after vaccination. Fc N-glycosylation profiles of individual IgG subclasses were determined for both total IgG and affinity-purified anti-vaccine IgG using a recently developed fast nanoliquid chromatography-electrospray ionization MS (LC-ESI-MS) method. While vaccination had no effect on the glycosylation of total IgG, anti-vaccine IgG showed increased levels of galactosylation and sialylation upon active immunization. Interestingly, the number of sialic acids per galactose increased during the vaccination time course, suggesting a distinct regulation of galactosylation and sialylation. In addition we observed a decrease in the level of IgG1 bisecting N-acetylglucosamine whereas no significant changes were observed for the level of fucosylation. Our data indicate that dependent on the vaccination time point the infectious agent will encounter IgGs with different glycosylation profiles, which are expected to influence the antibody effector functions relevant in immunity.
Variants of the FTO Gene in Obese Children and their Impact on Body Composition and Metabolism before and after Lifestyle Intervention
2011-12-20

Abstract To investigate the impact of variants of the FTO gene (rs1421085, rs17817449, rs9939609) in obese children before and after lifestyle intervention. Design: Longitudinal, clinical intervention study with an increase in physical activity, and nutritional recommendations based on the Optimized Mixed Diet for German Children and Adolescents’ (Research Institute of Child Nutrition, Germany). Study population: 75 overweight children (40 male, mean BMI 30.4±5.5 kg/m2, mean age 12.6±2.6 years). Measurements: Genotyping by means of a TaqMan SNP genotyping assay. Lean and fat mass were determined by means of DXA. For the whole study population, the 6-month lifestyle intervention resulted in a significant improvement (before intervention minus time point 6 months; mean±SD) in BMI-SDS (0.10±0.17, p&lt;0.001), HOMA (1.41±3.19, p&lt;0.001) and relative fat-mass-SDS (0.09±0.23, p=0.005). Before and after lifestyle intervention, there was no significant difference between heterozygote (n=52) and homozygote (n=21) carriers of the FTO gene in terms of BMI, body composition, and the metabolic profile (Insulin, HOMA, lipids, liver function tests). Variants in the FTO gene are common in obese children but have no impact on body composition and metabolism before and after lifestyle intervention.
Characterization and adaptive optical correction of aberrations during in vivo imaging in the mouse cortex
2011-12-21

The signal and resolution during in vivo imaging of the mouse brain is limited by sample-induced optical aberrations. We find that, although the optical aberrations can vary across the sample and increase in magnitude with depth, they remain stable for hours. As a result, two-photon adaptive optics can recover diffraction-limited performance to depths of 450 μm and improve imaging quality over fields of view of hundreds of microns. Adaptive optical correction yielded fivefold signal enhancement for small neuronal structures and a threefold increase in axial resolution. The corrections allowed us to detect smaller neuronal structures at greater contrast and also improve the signal-to-noise ratio during functional Ca 2+ imaging in single neurons.
Green Rust Formation during Fe(II) Oxidation by the Nitrate-Reducing Acidovorax sp. Strain BoFeN1
2011-12-22

Green rust (GR) as highly reactive iron mineral potentially plays a key role for the fate of (in)organic contaminants, such as chromium or arsenic, and nitroaromatic compounds functioning both as sorbent and reductant. GR forms as corrosion product of steel but is also naturally present in hydromorphic soils and sediments forming as metastable intermediate during microbial Fe(III) reduction. Although already suggested to form during microbial Fe(II) oxidation, clear evidence for GR formation during microbial Fe(II) oxidation was lacking. In the present study, powder XRD, synchrotron-based XAS, Mössbauer spectroscopy, and TEM demonstrated unambiguously the formation of GR as an intermediate product during Fe(II) oxidation by the nitrate-reducing Fe(II)-oxidizer Acidovorax sp. strain BoFeN1. The spatial distribution and Fe redox-state of the precipitates associated with the cells were visualized by STXM. It showed the presence of extracellular Fe(III), which can be explained by Fe(III) export from the cells or extracellular Fe(II) oxidation by an oxidant diffusing from the cells. Moreover, GR can be oxidized by nitrate/nitrite and is known as a catalyst for oxidation of dissolved Fe(II) by nitrite/nitrate and may thus contribute to the production of extracellular Fe(III). As a result, strain BoFeN1 may contribute to Fe(II) oxidation and nitrate reduction both by an direct enzymatic pathway and an indirect GR-mediated process.
Volatiles of two growth‐inhibiting rhizobacteria commonly engage AtWRKY18 function
2011-12-22

Summary Interactions with the (a)biotic environment play key roles in a plant’s fitness and vitality. In addition to direct surface‐to‐surface contact, volatile chemicals can also affect the physiology of organism. Volatiles of Serratia plymuthica and Stenotrophomonas maltophilia significantly inhibited growth and induced H 2 O 2 production in Arabidopsis in dual culture. Within 1 day, transcriptional changes were observed by promoter–GUS assays using a stress‐inducible W‐box‐containing 4x GST1 construct. Expression studies performed at 6, 12 and 24 h revealed altered transcript levels for 889 genes and 655 genes in response to Se. plymuthica or St. maltophilia volatiles, respectively. Expression of 162 genes was altered in both treatments. Meta‐analysis revealed that specifically volatile‐responsive genes were significantly overlapping with those affected by abiotic stress. We use the term mVAMP (microbial volatile‐associated molecular pattern) to describe these volatile‐specific responses. Genes responsive to both treatments were enriched for W‐box motifs in their promoters, and were significantly enriched for transcription factors ( ERF2 , ZAT10 , MYB73 and WRKY18 ). The susceptibility of wrky18 mutant lines to volatiles was significantly delayed, suggesting an indispensable role for WRKY18 in bacterial volatile responses.
LACHESIS-dependent egg-cell signaling regulates the development of female gametophytic cells
2011-12-22

In contrast to animals, plant germ cells are formed along with accessory cells in specialized haploid generations, termed gametophytes. The female gametophyte of flowering plants consists of four different cell types, which exert distinct functions in the reproductive process. For successful fertilization, the development of the four cell types has to be tightly coordinated; however, the underlying mechanisms are not yet understood. We have previously isolated the lachesis (lis) mutant, which forms supernumerary gametes at the expense of adjacent accessory cells. LIS codes for the Arabidopsis homolog of the pre-mRNA splicing factor PRP4 and shows a dynamic expression pattern in the maturing female gametophyte. Here, we used LIS as a molecular tool to study cell-cell communication in the female gametophyte. We show that reducing LIS transcript amounts specifically in the egg cell, affects the development of all female gametophytic cells, indicating that cell differentiation in the female gametophyte is orchestrated by the egg cell. Among the defects observed is the failure of homotypic nuclei fusion in the central cell and, as a consequence, a block in endosperm formation. LIS-mediated egg cell signaling, thus, provides a safeguard mechanism that prevents the formation of nurturing tissue in the absence of a functional egg cell.
The hinge region of the scaffolding protein of cell contacts, zonula occludens protein 1, regulates interacting with various signaling proteins
2011-12-22

Abstract Zonula occludens protein 1 (ZO‐1) is a ubiquitous scaffolding protein, but it is unknown why it functions in very different cellular contacts. We hypothesized that a specific segment, the unique hinge region, can be bound by very different regulatory proteins. Using surface plasmon resonance spectroscopy and binding assays to peptide libraries, we show, for the first time, that the hinge region directly interacts with disparate signal elements such as G‐proteins alpha 12 and alpha i2, the regulator of G‐protein signaling 5, multifunctional signaling protein ahnak1, and L‐type Ca 2+ ‐channel beta‐2‐subunit. The novel binding proteins specifically bound to a coiled coil‐helix predicted in the hinge region of ZO‐1. The interactions were modulated by phosphorylation in the hinge helix. Activation of the G‐proteins influenced their association to ZO‐1. In colon cells, G alpha i2 and ZO‐1 were associated, as shown by coimmunoprecipitation. After cotransfection in kidney cells, G alpha i2 barely colocalized with ZO‐1; the colocalization coefficient was significantly increased when epinephrine activated G‐protein signaling. In conclusion, proteins with different regulatory potential adhere to and influence cellular functions of ZO‐proteins, and the interactions can be modulated via its hinge region and/or the binding proteins. J. Cell. Biochem. 113: 934–945, 2012. © 2011 Wiley Periodicals, Inc.
Kinetic Tracking of Therapy-Induced Senescence Using the Real-Time Cell Analyzer Single Plate System
2011-12-22

In recent years, terminal growth arrest, that is, senescence, especially therapy-induced senescence (TIS), has become a major subject in cancer research and several fields of life sciences. Senescence is characterized by a specific set of morphological and biochemical changes. However, methods that evidence senescence induction are still very limited and show large variation between individual examiners. Most notably, these assays are classical endpoint assays, and, therefore, screening for senescence is time consuming and expensive. Here, we describe an efficient, simple, and objective method to screen for TIS over time by modifying the Real-Time Cell Analyzer SP system, thus enabling to pin point the induction of senescence. This method continuously detects the cell's impedance in each well of a 96-microwell plate that allows to observe increment of cell size, a hallmark feature of cellular senescence. This technique is suitable for high-throughput TIS screening by measuring several compounds, small molecules, and/or cell lines simultaneously.
The locomotory system of pearlfish Carapus acus: What morphological features are characteristic for highly flexible fishes?
2011-12-22

Abstract The body curvature displayed by fishes differs remarkably between species. Some nonmuscular features (e.g., number of vertebrae) are known to influence axial flexibility, but we have poor knowledge of the influence of the musculotendinous system (myosepta and muscles). Whereas this system has been described in stiff‐bodied fishes, we have little data on flexible fishes. In this study, we present new data on the musculotendinous system of a highly flexible fish and compare them to existing data on rigid fishes. We use microdissections with polarized light microscopy to study the three‐dimensional anatomy of myoseptal tendons, histology and immunohistology to study the insertion of muscle fiber types into tendons, and μ‐CT scans to study skeletal anatomy. Results are compared with published data from stiff‐bodied fishes. We identify four important morphological differences between stiff‐bodied fishes and Carapus acus : (1) Carapus bears short tendons in the horizontal septum, whereas rigid fishes have elongated tendons. (2) Carapus bears short lateral tendons in its myosepta, whereas stiff‐bodied fishes bear elongated tendons. Because of its short myoseptal tendons, Carapus retains high axial flexibility. In contrast, elongated tendons restrict axial flexibility in rigid fishes but are able to transmit anteriorly generated muscle forces through long tendons down to the tail. (3) Carapus bears distinct epineural and epipleural tendons in its myosepta, whereas these tendons are weak or absent in rigid fishes. As these tendons firmly connect vertebral axis and skin in Carapus , we consider them to constrain lateral displacement of the vertebral axis during extreme body flexures. (4) Ossifications of myoseptal tendons are only present in C. acus and other more flexible fishes but are absent in rigid fishes. The functional reasons for this remain unexplained. J. Morphol., 2012. © 2011 Wiley Periodicals, Inc.
Effect of Oligomer Procyanidins on Reperfusion Arrhythmias and Lactate Dehydrogenase Release in the Isolated Rat Heart
2011-12-22

The antiarrhythmic effect of an oral 3-week-pretreatment with oligomer procyanidins derived from Vitis vinifera was investigated on the isolated perfused heart after global no-flow ischemia (procyanidin-treated group: n = 9, control group: n = 13). Hearts were perfused with a modified Krebs-Henseleit solution in which the K+ content was reduced to 3.0 mmol/l in order to lower the fibrillation threshold. Monophasic action potentials in addition to ECG were recorded. The durations of ischemia and reperfusion were 20 and 30 min, respectively. Arrhythmias including ventricular fibrillation (VF), ventricular tachycardia (VT), flutter (Fl) and bradycardia were evaluated. During the reperfusion, irreversible VF occurred in most of control hearts. The incidence of VF (percentage of the hearts in which VF occurred) was lowered by oligomer procyanidins from 84.6 to 55.6 %, and the duration of the episodes of VF (expressed as percentage relative to the total duration) was significantly shortened from 76.1 +/- 27.9 % to 36.6 +/- 40.6 % (p = 0.036). Simultaneously, the percentage of duration of normal sinus rhythm (NSR) increased from 19.5 +/- 30.3 % to 46.2 +/- 35.9 % (n.s.). VF occuring in the procyanidin-treated hearts could be reversed in two hearts within few minutes to a stage of "reversible arrhythmias" consisting of short episodes (1 to 60 s) of either Fl or VT or bradycardia or NSR alternating with each other. LDH (lactate dehydrogenase) release in the first drops appearing from the reperfused heart was significantly reduced in the procyanidin-treated rats (66.7 +/- 36.2 mU/min, n = 8) in comparison to controls (159.7 +/- 79.0 mU/min, n = 10; p = 0.010). These results demonstrate an antiarrhythmic and cytoprotective effect of oral pretreatment with oligomer procyanidins under the given experimental conditions.
Synthesis and Biological Evaluation of Isomeric Derivatives of Naturally Occurring Spatozoate
2011-12-22

An isomer of the natural phthalate ester spatozoate (1), n-butyl 2-benzoyloxymethylbenzoate (2a) and a series of its new derivatives 2b-2s were synthesized and exposed to selected biological screening, as phthalates were reported to possess different biological activities. Compound 2g was found to be the most potent cytotoxic agent with a LD50 = 8.98 microg/ml. In a bactericidal assay the compounds showed a broad spectrum of activities. Compound 2a has a very promising fungicidal activity against Microsporum canis.
Stress-dependent dilated cardiomyopathy in mice with cardiomyocyte-restricted inactivation of cyclic GMP-dependent protein kinase I
2011-12-23

These results indicate that the loss of cGKI in cardiac myocytes compromises the hypertrophic program to pathological stimulation, rendering the heart more susceptible to dysfunction. In particular, cGKI mediates stimulatory effects of CNP on myocyte Ca(2+)i handling and contractility.