julilili42/papers huggingface dataset:
IκBζ is a key driver in the development of psoriasis
2015-10-12

Significance Psoriasis is an inflammatory skin disease affecting 2–3% of the population. IL-17A plays a key role in psoriasis pathogenesis, and antibodies targeting IL-17A have recently been approved for psoriasis treatment. Here we demonstrate that IκBζ is a key protein for IL-17A–driven effects in psoriasis. IκBζ was demonstrated essential for both TNFα/IL-17A– and IL-17A–induced expression of a panel of psoriasis-associated proteins. Moreover, IκBζ expression was increased in psoriatic skin, and in two different psoriasis mouse models we showed that psoriasis development was completely absent in IκBζ-deficient mice, but inducible in IL-17A– and TNFα-deficient mice. Finally, local abrogation of IκBζ function in mouse skin abolished psoriasis development. These findings uncover a novel crucial regulatory mechanism involved in psoriasis development.
Replacement of brain-resident myeloid cells does not alter cerebral amyloid-β deposition in mouse models of Alzheimer’s disease
2015-10-12

Immune cells of myeloid lineage are encountered in the Alzheimer’s disease (AD) brain, where they cluster around amyloid-β plaques. However, assigning functional roles to myeloid cell subtypes has been problematic, and the potential for peripheral myeloid cells to alleviate AD pathology remains unclear. Therefore, we asked whether replacement of brain-resident myeloid cells with peripheral monocytes alters amyloid deposition in two mouse models of cerebral β-amyloidosis (APP23 and APPPS1). Interestingly, early after repopulation, infiltrating monocytes neither clustered around plaques nor showed Trem2 expression. However, with increasing time in the brain, infiltrating monocytes became plaque associated and also Trem2 positive. Strikingly, however, monocyte repopulation for up to 6 mo did not modify amyloid load in either model, independent of the stage of pathology at the time of repopulation. Our results argue against a long-term role of peripheral monocytes that is sufficiently distinct from microglial function to modify cerebral β-amyloidosis. Therefore, myeloid replacement by itself is not likely to be effective as a therapeutic approach for AD.
On the maximum accretion luminosity of magnetized neutron stars: connecting X-ray pulsars and ultraluminous X-ray sources
2015-10-13

We study properties of luminous X-ray pulsars using a simplified model of the accretion column. The maximal possible luminosity is calculated as a function of the neutron star (NS) magnetic field and spin period. It is shown that the luminosity can reach values of the order of 1040 erg s−1 for the magnetar-like magnetic field (&lt;it&gt;B&lt;/it&gt; &amp;gsim; 1014 G) and long spin periods (&lt;it&gt;P&lt;/it&gt; &amp;gsim; 1.5 s). The relative narrowness of an area of feasible NS parameters which are able to provide higher luminosities leads to the conclusion that &lt;it&gt;L&lt;/it&gt; &amp;sime; 1040 erg s−1 is a good estimate for the limiting accretion luminosity of an NS. Because this luminosity coincides with the cut-off observed in the high-mass X-ray binaries luminosity function which otherwise does not show any features at lower luminosities, we can conclude that a substantial part of ultraluminous X-ray sources are accreting neutron stars in binary systems.
The population of X-ray supernova remnants in the Large Magellanic Cloud
2015-10-13

We present a comprehensive X-ray study of the population of supernova\\nremnants (SNRs) in the LMC. Using primarily XMM-Newton, we conduct a systematic\\nspectral analysis of LMC SNRs to gain new insights on their evolution and the\\ninterplay with their host galaxy. We combined all the archival XMM observations\\nof the LMC with those of our Very Large Programme survey. We produced X-ray\\nimages and spectra of 51 SNRs, out of a list of 59. Using a careful modelling\\nof the background, we consistently analysed all the X-ray spectra and measure\\ntemperatures, luminosities, and chemical compositions. We investigated the\\nspatial distribution of SNRs in the LMC and the connection with their\\nenvironment, characterised by various SFHs. We tentatively typed all LMC SNRs\\nto constrain the ratio of core-collapse to type Ia SN rates in the LMC. We\\ncompared the X-ray-derived column densities to HI maps to probe the\\nthree-dimensional structure of the LMC. This work provides the first\\nhomogeneous catalogue of X-ray spectral properties of LMC SNRs. It offers a\\ncomplete census of LMC SNRs exhibiting Fe K lines (13% of the sample), or\\nrevealing contribution from hot SN ejecta (39%). Abundances in the LMC ISM are\\nfound to be 0.2-0.5 solar, with a lower [ /Fe] than in the Milky Way.\\nThe ratio of CC/type Ia SN in the LMC is , lower than in local SN surveys and galaxy clusters.\\nComparison of X-ray luminosity functions of SNRs in Local Group galaxies\\nreveals an intriguing excess of bright objects in the LMC. We confirm that 30\\nDoradus and the LMC Bar are offset from the main disc of the LMC, to the far\\nand near sides, respectively. (abridged)\\n
Positive correlation between the cyclotron line energy and luminosity in sub-critical X-ray pulsars: Doppler effect in the accretion channel
2015-10-13

Cyclotron resonance scattering features observed in the spectra of some X-ray pulsars show significant changes of the line centroid energy with the pulsar luminosity. Whereas for bright sources above the so-called critical luminosity, these variations are established to be connected with the appearance of the high-accretion column above the neutron star surface, at low, sub-critical luminosities the nature of the variations (but with the opposite sign) has not been discussed widely. We argue here that the cyclotron line is formed when the radiation from a hotspot propagates through the plasma falling with a mildly relativistic velocity on to the neutron star surface. The position of the cyclotron resonance is determined by the Doppler effect. The change of the cyclotron line position in the spectrum with luminosity is caused by variations of the velocity profile in the line-forming region affected by the radiation pressure force. The presented model has several characteristic features: (i) the line centroid energy is positively correlated with the luminosity; (ii) the line width is positively correlated with the luminosity as well; (iii) the position and the width of the cyclotron absorption line are variable over the pulse phase; (iv) the line has a more complicated shape than widely used Lorentzian or Gaussian profiles; (v) the phase-resolved cyclotron line centroid energy and the width are negatively and positively correlated with the pulse intensity, respectively. The predictions of the proposed theory are compared with the variations of the cyclotron line parameters in the X-ray pulsar GX 304−1 over a wide range of sub-critical luminosities as seen by the &lt;it&gt;INTEGRAL&lt;/it&gt; observatory.
Triggered fragmentation in self-gravitating discs: forming fragments at small radii
2015-10-13

We carry out three dimensional radiation hydrodynamical simulations of gravitationally unstable discs to explore the movement of mass in a disc following its initial fragmentation. We find that the radial velocity of the gas in some parts of the disc increases by up to a factor of &amp;ap;10 after the disc fragments, compared to before. While the movement of mass occurs in both the inward and outward directions, the inwards movement can cause the inner spirals of a self-gravitating disc to become sufficiently dense such that they can potentially fragment. This suggests that the dynamical behaviour of fragmented discs may cause subsequent fragmentation to occur at smaller radii than initially expected, but only &lt;it&gt;after&lt;/it&gt; an initial fragment has formed in the outer disc.
Analysing neutron star in HESS J1731–347 from thermal emission and cooling theory
2015-10-13

The central compact object in the supernova remnant HESS J1731–347 appears to be the hottest observed isolated cooling neutron star. The cooling theory of neutron stars enables one to explain observations of this star by assuming the presence of strong proton superfluidity in the stellar core and the existence of the surface heat blanketing envelope which almost fully consists of carbon. The cooling model of this star is elaborated to take proper account of the neutrino emission due to neutron–neutron collisions which is not suppressed by proton superfluidity. Using the results of spectral fits of observed thermal spectra for the distance of 3.2 kpc and the cooling theory for the neutron star of age 27 kyr, new constraints on the stellar mass and radius are obtained which are more stringent than those derived from the spectral fits alone.
Triggering of Suicidal Erythrocyte Death by the Antibiotic Ionophore Nigericin
2015-10-13

Abstract The K + ,H + ionophore and antibiotic nigericin has been shown to trigger apoptosis and is thus considered for the treatment of malignancy. Cellular mechanisms involved include induction of oxidative stress, which is known to activate erythrocytic Ca 2+ ‐permeable unselective cation channels leading to Ca 2+ entry, increase in cytosolic Ca 2+ activity ([Ca 2+ ] i ) and subsequent stimulation of eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. This study explored whether and how nigericin induces eryptosis. Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, [Ca 2+ ] i from Fluo3 fluorescence, pH i from BCECF fluorescence, ceramide abundance utilizing antibodies and reactive oxygen species ( ROS ) formation from DCFDA ‐dependent fluorescence. A 48‐hr exposure of human erythrocytes to nigericin significantly increased the percentage of annexin‐V‐binding cells (0.1–10 nM), significantly decreased forward scatter (0.1–1 nM), significantly decreased cytosolic pH (0.1–1 nM) and significantly increased Fluo3 fluorescence (0.1–10 nM). Nigericin (1 nM) slightly, but significantly, increased ROS , but did not significantly modify ceramide abundance. The effect of nigericin on annexin V binding was significantly blunted, but not abolished by removal of extracellular Ca 2+ . The nigericin‐induced increase in [Ca 2+ ] i and annexin V binding was again significantly blunted but not abolished by the Na + /H + exchanger inhibitor cariporide (10 μM). Nigericin triggers eryptosis, an effect paralleled by ROS formation, in part dependent on stimulation of Ca 2+ entry, and involving the cariporide‐sensitive Na + /H + exchanger.
Lack of Gαi2leads to dilative cardiomyopathy and increased mortality in β1-adrenoceptor overexpressing mice
2015-10-13

Gαi2 deficiency combined with cardiac β1-adrenoceptor overexpression strongly impaired survival and cardiac function. At 300 days of age, β1-adrenoceptor overexpression alone had not induced cardiac hypertrophy or dysfunction while there was overt cardiomyopathy in mice additionally lacking Gαi2. We propose an enhanced effect of increased β1-adrenergic drive by the lack of protection via Gαi2. Gαi3 up-regulation was not sufficient to compensate for Gαi2 deficiency, suggesting an isoform-specific or a concentration-dependent mechanism.
Role of Autocleavage in the Function of a Type III Secretion Specificity Switch Protein in Salmonella enterica Serovar Typhimurium
2015-10-14

ABSTRACT Type III secretion systems (T3SSs) are multiprotein machines employed by many Gram-negative bacteria to inject bacterial effector proteins into eukaryotic host cells to promote bacterial survival and colonization. The core unit of T3SSs is the needle complex, a supramolecular structure that mediates the passage of the secreted proteins through the bacterial envelope. A distinct feature of the T3SS is that protein export occurs in a strictly hierarchical manner in which proteins destined to form the needle complex filament and associated structures are secreted first, followed by the secretion of effectors and the proteins that will facilitate their translocation through the target host cell membrane. The secretion hierarchy is established by complex mechanisms that involve several T3SS-associated components, including the “switch protein,” a highly conserved, inner membrane protease that undergoes autocatalytic cleavage. It has been proposed that the autocleavage of the switch protein is the trigger for substrate switching. We show here that autocleavage of the Salmonella enterica serovar Typhimurium switch protein SpaS is an unregulated process that occurs after its folding and before its incorporation into the needle complex. Needle complexes assembled with a precleaved form of SpaS function in a manner indistinguishable from that of the wild-type form. Furthermore, an engineered mutant of SpaS that is processed by an external protease also displays wild-type function. These results demonstrate that the cleavage event per se does not provide a signal for substrate switching but support the hypothesis that cleavage allows the proper conformation of SpaS to render it competent for its switching function. IMPORTANCE Bacterial interaction with eukaryotic hosts often involves complex molecular machines for targeted delivery of bacterial effector proteins. One such machine, the type III secretion system of some Gram-negative bacteria, serves to inject a multitude of structurally diverse bacterial proteins into the host cell. Critical to the function of these systems is their ability to secrete proteins in a strict hierarchical order, but it is unclear how the mechanism of switching works. Central to the switching mechanism is a highly conserved inner membrane protease that undergoes autocatalytic cleavage. Although it has been suggested previously that the autocleavage event is the trigger for substrate switching, we show here that this is not the case. Rather, our results show that cleavage allows the proper conformation of the protein to render it competent for its switching function. These findings may help develop inhibitors of type III secretion machines that offer novel therapeutic avenues to treat various infectious diseases.
Gestational Diabetes Impairs Human Fetal Postprandial Brain Activity
2015-10-14

Fetal postprandial brain responses were slower in the offspring of women with GDM. This might indicate that gestational diabetes directly affects fetal brain development and may lead to central nervous insulin resistance in the fetus.
The Interaction of CCDC104/BARTL1 with Arl3 and Implications for Ciliary Function
2015-10-14

Cilia are small antenna-like cellular protrusions critical for many developmental signaling pathways. The ciliary protein Arl3 has been shown to act as a specific release factor for myristoylated and farnesylated ciliary cargo molecules by binding to the effectors Unc119 and PDE6δ. Here we describe a newly identified Arl3 binding partner, CCDC104/CFAP36. Biochemical and structural analyses reveal that the protein contains a BART-like domain and is called BARTL1. It recognizes an LLxILxxL motif at the N-terminal amphipathic helix of Arl3, which is crucial for the interaction with the BART-like domain but also for the ciliary localization of Arl3 itself. These results seem to suggest a ciliary role of BARTL1, and possibly link it to the Arl3 transport network. We thus speculate on a regulatory mechanism whereby BARTL1 aids the presentation of active Arl3 to its GTPase-activating protein RP2 or hinders Arl3 membrane binding in the area of the transition zone.
“Same, Same—but Different!” On Consumers’ Use of Corporate PR Media in Sports
2015-10-14

Organizations around the globe have numerous avenues to share information with their target groups and communicate directly without any intermediaries such as journalists. Particularly, sports organizations like professional sports teams make frequent use of e-mail newsletters, (online) club TV channels, stadium magazines, and Internet platforms. In addition, they frequently share information using social networks like Twitter and Facebook. Surprisingly, however, very little is known about the factors influencing consumers’ use of these different communication channels. This paper is the first to analyze simultaneously the factors associated with consumers’ use of different public relations (PR) media by using representative data from club members of one of the biggest professional soccer clubs in Germany and employing a multivariate ordered probit model. Results suggest that decisions on the use of different PR media are closely related, though sociodemographic and membership characteristics have a media-specific impact on the frequency of use.
Immobilization of Heteroleptic Bis(oxazoline) Zinc Catalysts on SBA-15 for Asymmetric Hydrosilylation
2015-10-14

The C2-symmetric bis(oxazoline)s (4S,4S)-R1-BOX, with R1 = tBu and Ph, react with ZnEt2 straightforwardly to the four-coordinate complexes ((4S,4S)-R1-BOX)ZnEt2 in high yield. Their immobilization on highly dehydroxylated (700 °C) mesoporous silica SBA-15 with enlarged pore diameters (dp = 15.3 nm) led to the well-defined surface species [(≡SiO)Zn(Et)((4S,4S)-R1-BOX)]. These ethyl zinc-terminated materials react readily with one equivalent of anhydrous methanol and acetic acid to give predominantly and selectively the corresponding surface ligand-exchanged species [(≡SiO)(Zn(R)((4S,4S)-R1-BOX)] (R = OMe, OAc). All hybrid materials were characterized via N2 physisorption, elemental analysis, DRIFT, 1H/13C MAS NMR, and EXAFS spectroscopies. The SBA-15 supported heteroleptic bis(oxazoline) zinc ethyl, methoxide, and acetate surface species were scrutinized as catalysts for the asymmetric hydrosilylation of acetophenone.
Can we distinguish an “I” and “ME” during listening?—an event-related EEG study on the processing of first and second person personal and possessive pronouns
2015-10-14

Theoretically, stimuli can be related to the self as subject ("I") or object ("ME") of experience. This event-related brain potential (ERP) study investigated whether listening to personal and possessive pronouns elicits different modes of self-processing regarding time-course and neural sources. Going beyond previous research, first (1PP) and second person (2PP) pronouns were included to determine the specificity of self-processing. Participants listened passively to German pronouns while the electroencephalogram was recorded. Modulation of ERPs revealed a processing advantage for the 2PP personal pronoun "du" ("you") already in early time windows. Regarding possessive pronouns, N1 amplitudes indicated increased attention orientation to the 1PP pronoun "mein" ("my"), whereas during later time windows, processing of 1PP and 2PP possessive pronouns did not differ but differed from the third person pronoun "sein" ("his"). ERP source imaging suggests that primary sensory brain regions (auditory cortex), the insula and cortical midline structures are differentially involved into these two processing modes. The results support the idea of distinct self-processing modes ("I" and "ME") and confirm their dynamic nature. Moreover, they demonstrate that on a neural level neither "I" or "ME" are invariantly tied to the first person, in line with the hypothesis that self-processing is relational and context-dependent.
The Central Biobank and Virtual Biobank of BIOMARKAPD: A Resource for Studies on Neurodegenerative Diseases
2015-10-15

Biobanks are important resources for biomarker discovery and assay development. Biomarkers for Alzheimer's and Parkinson's disease (BIOMARKAPD) is a European multicenter study, funded by the EU Joint Programme-Neurodegenerative Disease Research, which aims to improve the clinical use of body fluid markers for the diagnosis and prognosis of Alzheimer's disease (AD) and Parkinson's disease (PD). The objective was to standardize the assessment of existing assays and to validate novel fluid biomarkers for AD and PD. To support the validation of novel biomarkers and assays, a central and a virtual biobank for body fluids and associated data from subjects with neurodegenerative diseases have been established. In the central biobank, cerebrospinal fluid (CSF) and blood samples were collected according to the BIOMARKAPD standardized pre-analytical procedures and stored at Integrated BioBank of Luxembourg. The virtual biobank provides an overview of available CSF, plasma, serum, and DNA samples at each site. Currently, at the central biobank of BIOMARKAPD samples are available from over 400 subjects with normal cognition, mild cognitive impairment (MCI), AD, frontotemporal dementia (FTD), vascular dementia, multiple system atrophy, progressive supranuclear palsy, PD, PD with dementia, and dementia with Lewy bodies. The virtual biobank contains information on over 8,600 subjects with varying diagnoses from 21 local biobanks. A website has been launched to enable sample requests from the central biobank and virtual biobank.
Support for the slip hypothesis from whisker-related tactile perception of rats in a noisy environment
2015-10-15

Rodents use active whisker movements to explore their environment. The "slip hypothesis" of whisker-related tactile perception entails that short-lived kinematic events (abrupt whisker movements, called "slips", due to bioelastic whisker properties that occur during active touch of textures) carry the decisive texture information. Supporting this hypothesis, previous studies have shown that slip amplitude and frequency occur in a texture-dependent way. Further, experiments employing passive pulsatile whisker deflections revealed that perceptual performance based on pulse kinematics (i.e., signatures that resemble slips) is far superior to the one based on time-integrated variables like frequency and intensity. So far, pulsatile stimuli were employed in a noise free environment. However, the realistic scenario involves background noise (e.g., evoked by rubbing across the texture). Therefore, if slips are used for tactile perception, the tactile neuronal system would need to differentiate slip-evoked spikes from those evoked by noise. To test the animals under these more realistic conditions, we presented passive whisker-deflections to head-fixed trained rats, consisting of "slip-like" events (waveforms mimicking slips occurring with touch of real textures) embedded into background noise. Varying the (i) shapes (ramp or pulse); (ii) kinematics (amplitude, velocity, etc.); and (iii) the probabilities of occurrence of slip-like events, we observed that rats could readily detect slip-like events of different shapes against noisy background. Psychophysical curves revealed that the difference of slip event and noise amplitude determined perception, while increased probability of occurrence (frequency) had barely any effect. These results strongly support the notion that encoding of kinematics dominantly determines whisker-related tactile perception while the computation of frequency or intensity plays a minor role.