julilili42/papers huggingface dataset:
Quantitative Analysis of the Cellular Actin Cytoskeleton on Geometrically Designed Surface Topography
2012-01-03

In tissue engineering, topographical modification of implants has been used as a powerful tool for the development of biorelevant implant designs. However, there is still a lack of knowledge about the fundamental principles of the cell–material interaction and quantitative correlations between cell biological parameters and physicochemical surface characteristics. The focus of our studies on cell architecture–cell function dependencies on regular micro-scaled surface structures was to investigate and further quantify the cell phenotype obtained from images of confocal microscopy and scanning electron microscopy. We used periodically structured titanium surfaces with regular cubic pillar geometry (dimension 3x3x5 μm and 5x5x5 μm) in comparison to planar samples. Confocal microscopy revealed a considerable rearrangement of the actin cytoskeleton on the top of the pillars with a reduced filament length. The quantification of different actin filament networks of cells grown on structured surfaces was carried out with a novel software for automatic filament recognition, covering the majority of filaments and their branching in noisy data. The quantitative analysis of cell phenotype changes on surfaces with regular geometry opens new possibilities for the data correlation cell vs. material.
Faculty Opinions recommendation of Random biopsies taken during colonoscopic surveillance of patients with longstanding ulcerative colitis: low yield and absence of clinical consequences.
2012-01-03

Read the full review for this Faculty Opinions recommended article: Random biopsies taken during colonoscopic surveillance of patients with longstanding ulcerative colitis: low yield and absence of clinical consequences.
EEG-Guided Transcranial Magnetic Stimulation Reveals Rapid Shifts in Motor Cortical Excitability during the Human Sleep Slow Oscillation
2012-01-04

Evoked cortical responses do not follow a rigid input–output function but are dynamically shaped by intrinsic neural properties at the time of stimulation. Recent research has emphasized the role of oscillatory activity in determining cortical excitability. Here we employed EEG-guided transcranial magnetic stimulation (TMS) during non-rapid eye movement sleep to examine whether the spontaneous &lt;1 Hz neocortical slow oscillation (SO) is associated with corresponding fluctuations of evoked responses. Whereas the SO's alternating phases of global depolarization (up-state) and hyperpolarization (down-state) are clearly associated with fluctuations in spontaneous neuronal excitation, less is known about state-dependent shifts in neocortical excitability. In 12 human volunteers, single-pulse TMS of the primary motor cortical hand area (M1 HAND ) was triggered online by automatic detection of SO up-states and down-states in the EEG. State-dependent changes in cortical excitability were traced by simultaneously recording motor-evoked potentials (MEPs) and TMS-evoked EEG potentials (TEPs). Compared to wakefulness and regardless of SO state, sleep MEPs were smaller and delayed whereas sleep TEPs were fundamentally altered, closely resembling a spontaneous SO. However, both MEPs and TEPs were consistently larger when evoked during SO up-states than during down-states, and ampliudes within each SO state depended on the actual EEG potential at the time and site of stimulation. These results provide first-time evidence for a rapid state-dependent shift in neocortical excitability during a neuronal oscillation in the human brain. We further demonstrate that EEG-guided temporal neuronavigation is a powerful tool to investigate the phase-dependent effects of neuronal oscillations on perception, cognition, and motor control.
Species-specific response to human infant faces in the premotor cortex
2012-01-04

The human infant face represents an essential source of communicative signals on the basis of which adults modulate their interactions with infants. Behavioral studies demonstrate that infants' faces activate sensitive and attuned responses in adults through their gaze, face expression, voice, and gesture. In this study we aimed to identify brain responses that underlie adults' general propensity to respond to infant faces. We recorded fMRI during adults' (non-parents) processing of unfamiliar infant faces compared to carefully matched adult faces and infrahuman mammal infant and adult faces. Human infant faces activated several brain systems including the lateral premotor cortex, supplementary motor area, cingulate cortex, anterior insula and the thalamus. Activation of these brain circuits suggests adults' preparation for communicative behavior with infants as well as attachment and caregiving. The same brain regions preferentially responded to human infant faces when compared to animal infant faces, indicating species-specific adult brain responses. Moreover, results of support vector machine based classification analysis indicated that these regions allowed above chance-level prediction of brain state during perception of human infant faces. The complex of brain responses to human infant faces appears to include biological mechanisms that underlie responsiveness and a caring inclination toward young children which appear to transcend adult's biological relationship to the baby.
Effects of Sleep Loss and Circadian Rhythm on Executive Inhibitory Control in the Stroop and Simon Tasks
2012-01-04

This study assessed the influence of sleep loss and circadian rhythm on executive inhibitory control (i.e., the ability to inhibit conflicting response tendencies due to irrelevant information). Twelve ordinarily diurnally active, healthy young male participants performed the Stroop and the Simon task every 3 h in a 40-h constant routine protocol that comprised constant wakefulness under controlled behavioral and environmental conditions. In both tasks, overall performance showed clear circadian rhythm and sleep-loss effects. However, both Stroop and Simon interference remained unchanged across the 40 h of wakefulness, suggesting that neither cumulative sleep loss nor the circadian clock affects executive inhibitory control. The present findings challenge the widely held view that executive functions are especially vulnerable to the influence of sleep loss and circadian rhythm.
Lattice constants and thermal expansion of H2O and D2O Ice Ih between 10 and 265 K. Addendum
2012-01-06

In a previous paper we reported the lattice constants and thermal expansion of normal and deuterated ice I h [Röttger et al. (1994). Acta Cryst. B 50 , 644–648]. Synchrotron X-ray powder diffraction data were used to obtain the lattice constants and unit-cell volumes of H 2 O and D 2 O ice I h in the temperature range 15–265 K. A polynomial expression was given for the unit-cell volumes. It turns out that the coefficients quoted have an insufficient number of digits to faithfully reproduce the volume cell data. Here we provide a table with more significant digits. Moreover, we also provide the coefficients of a polynomial fit to the previously published a and c lattice constants of normal and deuterated ice I h for the same temperature range.
Personality and Relationship Quality During the Transition From High School to Early Adulthood
2012-01-06

Abstract The post–high school transition period is believed to be associated with considerable changes in social networks, yet longitudinal studies documenting these changes are scarce. To address this gap, the current research explored 3 relevant issues. First, changes in participants' relationship characteristics during the transition from high school were examined. Second, the roles of personality traits as antecedents of these changes were studied. Third, the association between change in relationship characteristics and personality during the transition was explored. A sample of over 2,000 G erman emerging adults, surveyed before leaving school and then 2 years after the transition from high school, was assessed on personality traits and a multidimensional assessment of the quality of their relationships. Findings indicated that participants experienced mostly positive changes in relationship quality during the transition from high school and that antecedent personality at school was an important predictor of the nature of this change. Finally, change in relationship quality was found to be associated with personality change during the post‐school transition. Findings indicated that personality traits may influence transition success and that change in relationships during this transition may influence personality development. The implications of the research for post‐school transition success are discussed.
Chorein‐sensitive polymerization of cortical actin and suicidal cell death in chorea‐acanthocytosis
2012-01-06

Chorea‐acanthocytosis is an inevitably lethal genetic disease characterized by a progressive hyperkinetic movement disorder and cognitive and behavioral abnormalities as well as acanthocytosis. The disease is caused by loss‐of‐function mutations of the gene encoding vacuolar protein sorting‐associated protein 13A ( VPS13A ) or chorein, a protein with unknown function expressed in various cell types. How chorein deficiency leads to the pathophysiology of chorea‐acanthocytosis remains enigmatic. Here we show decreased phosphoinositide‐3‐kinase (PI3K)‐p85‐subunit phosphorylation, ras‐related C3 botunlinum toxin substrate 1 (Rac1) activity, and p21 protein‐activated kinase 1 (PAK1) phosphorylation as well as depolymerized cortical actin in erythrocytes from patients with chorea‐acanthocytosis and in K562‐erythrocytic cells following chorein silencing. Pharmacological inhibition of PI3K, Rac1, or PAK1 similarly triggered actin depolymerization. Moreover, in K562 cells, both chorein silencing and PAK1 inhibition with IPA‐3 decreased phosphorylation of Bad, a Bcl2‐associated protein, promoting apoptosis by forming mitochondrial pores, followed by mitochondrial depolarization, DNA fragmentation, and phosphatidylserine exposure at the cell surface, all hallmarks of apoptosis. Our observations reveal chorein as a novel powerful regulator of cytoskeletal architecture and cell survival, thus explaining erythrocyte misshape and possibly neurodegeneration in chorea‐acanthocytosis.—Föller, M., Hermann, A., Gu, S., Alesutan, I., Qadri, S. M., Borst, O., Schmidt, E.‐M., Schiele, F., Müller vom Hagen, J., Saft, C., Schöls, L., Lerche, H., Stournaras, C., Storch, A., Lang, F. Chorein‐sensitive polymerization of cortical actin and suicidal cell death in chorea‐acanthocytosis. FASEB J. 26, 1526–1534 (2012). www.fasebj.org
The Bispecific SDF1-GPVI Fusion Protein Preserves Myocardial Function After Transient Ischemia in Mice
2012-01-06

Background CXCR4-positive bone marrow cells (BMCs) are critically involved in cardiac repair mechanisms contributing to preserved cardiac function. Stromal cell–derived factor-1 (SDF-1) is the most prominent BMC homing factor known to augment BMC engraftment, which is a limiting step of stem cell–based therapy. After myocardial infarction, SDF-1 expression is rapidly upregulated and promotes myocardial repair. Methods and Results We have established a bifunctional protein consisting of an SDF-1 domain and a glycoprotein VI (GPVI) domain with high binding affinity to the SDF-1 receptor CXCR4 and extracellular matrix proteins that become exposed after tissue injury. SDF1-GPVI triggers chemotaxis of CXCR4-positive cells, preserves cell survival, enhances endothelial differentiation of BMCs in vitro, and reveals proangiogenic effects in ovo. In a mouse model of myocardial infarction, administration of the bifunctional protein leads to enhanced recruitment of BMCs, increases capillary density, reduces infarct size, and preserves cardiac function. Conclusions These results indicate that administration of SDF1-GPVI may be a promising strategy to treat myocardial infarction to promote myocardial repair and to preserve cardiac function.
Cognitive neuroenhancement: false assumptions in the ethical debate
2012-01-06

The present work critically examines two assumptions frequently stated by supporters of cognitive neuroenhancement. The first, explicitly methodological, assumption is the supposition of effective and side effect-free neuroenhancers. However, there is an evidence-based concern that the most promising drugs currently used for cognitive enhancement can be addictive. Furthermore, this work describes why the neuronal correlates of key cognitive concepts, such as learning and memory, are so deeply connected with mechanisms implicated in the development and maintenance of addictive behaviour so that modification of these systems may inevitably run the risk of addiction to the enhancing drugs. Such a potential risk of addiction could only be falsified by in-depth empirical research. The second, implicit, assumption is that research on neuroenhancement does not pose a serious moral problem. However, the potential for addiction, along with arguments related to research ethics and the potential social impact of neuroenhancement, could invalidate this assumption. It is suggested that ethical evaluation needs to consider the empirical data as well as the question of whether and how such empirical knowledge can be obtained.
Simultaneous Quantification of Eleven Thiopurine Nucleotides by Liquid Chromatography-Tandem Mass Spectrometry
2012-01-06

The prodrugs azathioprine and 6-mercaptopurine, which are well-established anticancer and immunosuppressive agents, are extensively metabolized by activating and inactivating enzymes. Whereas the 6-thioguanine nucleotides (TGN) are currently being considered as major active metabolites, methylthioinosine nucleotides seem to contribute to the cytotoxic effect as well. Thiopurine-related adverse drug reactions and thiopurine failure are frequent. Thus, therapeutic monitoring of TGN and methylthioinosine derivatives has been suggested to improve thiopurine therapy, however with limited success. To elucidate systematically underlying molecular mechanisms as potential explanation for interindividual variability of thiopurine response, we developed a novel highly specific and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous quantitation of eleven mono-, di-, and triphosphates of thioguanosine, methylthioinosine, methylthioguanosine, and thioinosine. Using stable isotope-labeled analogues as internal standards obtained by chemical synthesis, an intra- and interassay variability below 8% and an accuracy of 92% to 107% were achieved in spiked quality control samples with known standards. All eleven metabolites could be determined in red blood cells from patients with inflammatory bowel diseases and long-term azathioprine therapy. Thus, our novel method opens a new avenue for the understanding of the thiopurine metabolism by quantitation of all important thiopurine nucleotide metabolites in one run.
Discovery of hard-spectrumγ-ray emission from the BL Lacertae object 1ES 0414+009
2012-01-06

Context. 1ES 0414 + 009 (z = 0.287) is a distant high-frequency-peaked BL Lac object, and has long been considered a likely emitter of very-high-energy (VHE, E &gt; 100 GeV) γ-rays due to its high X-ray and radio flux.&#13;\\n&#13;\\nAims. Observations in the VHE γ-ray band and across the electromagnetic spectrum can provide insights into the origin of highly energetic particles present in the source and the radiation processes at work. Because of the distance of the source, the γ-ray spectrum might provide further limits on the level of the extragalactic background light (EBL).&#13;\\n&#13;\\nMethods. We report observations made between October 2005 and December 2009 with H.E.S.S., an array of four imaging atmospheric Cherenkov telescopes. Observations at high energies (HE, 100 MeV–100 GeV) with the Fermi-LAT instrument in the first 20 months of its operation are also reported. To complete the multi-wavelength picture, archival UV and X-ray observations with the Swift satellite and optical observations with the ATOM telescope are also used.&#13;\\n&#13;\\nResults. Based on the observations with H.E.S.S., 1ES 0414 + 009 is detected for the first time in the VHE band. An excess of 224 events is measured, corresponding to a significance of 7.8σ. The photon spectrum of the source is well described by a power law, with photon index of ΓVHE = 3.45 ± 0.25stat ± 0.20syst. The integral flux above 200 GeV is (1.88 ± 0.20stat ± 0.38syst) × 10-12 cm-2 s-1. Observations with the Fermi-LAT in the first 20 months of operation show a flux between 200 MeV and 100 GeV of (2.3 ± 0.2stat) × 10-9 erg cm-2 s-1, and a spectrum well described by a power-law function with a photon index ΓHE = 1.85 ± 0.18. Swift/XRT observations show an X-ray flux between 2 and 10 keV of (0.8−1) × 10-11 erg cm-2 s-1, and a steep spectrum ΓX = (2.2−2.3). Combining X-ray with optical-UV data, a fit with a log-parabolic function locates the synchrotron peak around 0.1 keV.&#13;\\n&#13;\\nConclusions. Although the GeV–TeV observations do not provide better constraints on the EBL than previously obtained, they confirm a low density of the EBL, close to the lower limits from galaxy counts. The absorption-corrected HE and VHE γ-ray spectra are both hard and have similar spectral indices (≈1.86), indicating no significant change of slope between the HE and VHE γ-ray bands, and locating the γ-ray peak in the SED above 1–2 TeV. As for other TeV BL Lac objects with the γ-ray peak at such high energies and a large separation between the two SED humps, this average broad-band SED represents a challenge for simple one-zone synchrotron self-Compton models, requiring a high Doppler factor and very low B-field.
XMMU J0541.8-6659, a new supernova remnant in the Large Magellanic Cloud
2012-01-06

The high sensitivity of the XMM-Newton instrumentation offers the opportunity to study faint and extended sources in the Milky Way and nearby galaxies such as the Large Magellanic Cloud (LMC) in detail. The ROSAT PSPC survey of the LMC has revealed more than 700 X-ray sources, among which there are 46 supernova remnants (SNRs) and candidates. We have observed the field around one of the most promising SNR candidates in the ROSAT PSPC catalogue, labelled [HP99] 456 with XMM-Newton, to determine its nature. We investigated the XMM-Newton data along with new radio-continuum, near infrared and optical data. In particular, spectral and morphological studies of the X-ray and radio data were performed. The X-ray images obtained in different energy bands reveal two different structures. Below 1.0 keV the X-ray emission shows the shell-like morphology of an SNR with a diameter of ~73 pc, one of the largest known in the LMC. For its thermal spectrum we estimate an electron temperature of (0.49 +/- 0.12)keV assuming non-equilibrium ionisation. The X-ray images above 1.0 keV reveal a less extended source within the SNR emission, located ~1' west of the centre of the SNR and coincident with bright point sources detected in radio-continuum. This hard component has an extent of 0.9' (i.e. ~13 pc at a distance of ~50 kpc) and a non-thermal spectrum. The hard source coincides in position with the ROSAT source [HP99] 456 and shows an indication for substructure. We firmly identify a new SNR in the LMC with a shell-like morphology and a thermal spectrum. Assuming the SNR to be in the Sedov phase yields an age of ~23 kyr. We explore possible associations of the hard non-thermal emitting component with a pulsar wind nebula (PWN) or background active galactic nuclei (AGN).
Interplay of &#946;-Catenin with Xenobiotic-Sensing Receptors and its Role in Glutathione S-Transferase Expression
2012-01-06

The Wnt/β-catenin pathway plays an important role in liver homeostasis, as well as during prenatal liver development, liver regeneration, and hepatocarcinogenesis. The connection of hepatic β-catenin activation and expression of drug-metabolizing enzymes has been established in the past few years: on the whole, a generally positive-regulatory effect of β-catenin on the expression and inducibility of many enzymes involved in phase I and phase II of drug metabolism has been described by different groups. The mechanisms underlying these processes are still not fully understood. However, there is accumulating evidence for a complex interaction of β-catenin with different xenobiotic-sensing receptors, which act as transcription factors after ligand activation, for example the aryl hydrocarbon receptor or the constitutive androstane receptor. Among others, these crosstalk mechanisms might explain the manifold effects of β-catenin on hepatic drug metabolism. In this review, the current knowledge regarding the role of Wnt/β-catenin signaling in the regulation of hepatic expression of glutathione S-transferases is presented. In addition, the crosstalk of β-catenin signaling with nuclear receptors involved in the regulation of glutathione S-transferases will be discussed.
Hyperspectral stray light imaging of chromosomes: a novel concept for label-free karyotyping
2012-01-06

We describe the design and performance of a Hyperspectral Imaging System (HSI) for label-free characterization of human metaphase chromosomes. Chromosomes consist of a DNA-protein complex that is organized in sub-structures and can be described by an array of "particles" with different size and refractive indices. This locally resolved stray light pattern can be used to visualize and characterize unstained chromosomes. The paper describes an imaging system where stray light spectra of chromosomes are detected using a Pushbroom Imaging device attached to a standard microscope in combination with multivariate data analysis. To proof the concept, single particle spectra as well as particle array spectra are analyzed and explained by means of Mie scattering theory and the results are confirmed with FDTD (Finite Difference Time Domain) simulations. This label free signature is due to the superposition of the interference pattern of the different layer thicknesses, the spectral interference of the band pattern, changes in refractive indices along the chromosome axis as well as the absorption of chromophores in different spectral regions of the chromatin condensation. This complex spectral signature can be analyzed by means of a principal component analysis (PCA) and classified in a multidimensional PCA space.
Connecting and Encapsulation Technology for Active Middle Ear Implants
2012-01-06

Article Connecting and Encapsulation Technology for Active Middle Ear Implants was published on September 6, 2012 in the journal Biomedical Engineering / Biomedizinische Technik (volume 57, issue SI-1-Track-S).