Neuronal hypoxia in vitro: Investigation of therapeutic principles of HUCB-MNC and CD133+ stem cells

Background The therapeutic capacity of human umbilical cord blood mononuclear cells (HUCB-MNC) and stem cells derived thereof is documented in animal models of focal cerebral ischemia, while mechanisms behind the reduction of lesion size and the observed improvement of behavioral skills still remain poorly understood. Methods A human in vitro model of neuronal hypoxia was used to address the impact of total HUCB-MNC (tMNC), a stem cell enriched fraction (CD133+, 97.38% CD133-positive cells) and a stem cell depleted fraction (CD133-, 0.06% CD133-positive cells) of HUCB-MNC by either direct or indirect co-cultivation with post-hypoxic neuronal cells (differentiated SH-SY5Y). Over three days, development of apoptosis and necrosis of neuronal cells, chemotaxis of MNC and production of chemokines (CCL2, CCL3, CCL5, CXCL8, CXCL9) and growth factors (G-CSF, GM-CSF, VEGF, bFGF) were analyzed using fluorescence microscopy, FACS and cytometric bead array. Results tMNC, CD133+ and surprisingly CD133- reduced neuronal apoptosis in direct co-cultivations significantly to levels in the range of normoxic controls (7% ± 3%). Untreated post-hypoxic control cultures showed apoptosis rates of 85% ± 11%. tMNC actively migrated towards injured neuronal cells. Both co-cultivation types using tMNC or CD133- reduced apoptosis comparably. CD133- produced high concentrations of CCL3 and neuroprotective G-CSF within indirect co-cultures. Soluble factors produced by CD133+ cells were not detectable in direct co-cultures. Conclusion Our data show that heterogeneous tMNC and even CD133-depleted fractions have the capability not only to reduce apoptosis in neuronal cells but also to trigger the retaining of neuronal phenotypes

Rift Valley Fever Virus Seroprevalence in Human Rural Populations of Gabon

Rift Valley fever (RVF) is a disease transmitted by a mosquito bite (Aedes). Humans can also be infected through direct contact with blood (aerosols) or tissues (placenta, stillborn) of infected animals. Although severe clinical cases can be observed, infection with RVF virus (RVFV) in humans in most cases causes a febrile illness without serious symptoms. In small ruminants RVFV mainly causes abortion and neonatal death. RVFV distribution has been poorly investigated in Central Africa. We conducted a large scale serological survey of RVF antibodies in rural populations in Gabon, involving 4,323 individuals from 212 randomly selected villages. The results showed an overall RVFV prevalence of 3.3%, with values of 2.9% in the forested zones, 2.2% in savannas and 8.3% in the lakes region. These findings strongly suggest for the first time the wide circulation of Rift valley fever virus in Gabon and the possible existence of a sylvan cycle of RVF virus in this country. The serological higher prevalence in the lake region suggests that this region is likely to have particular ecological conditions, especially mosquito vector species, favoring the circulation of this virus. In Gabon, human cases of RVF may occur but are either misdiagnosed or not reported

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

MAGIC observations of the microquasar V404 Cygni during the 2015 outburst

The microquasar V404 Cygni underwent a series of outbursts in 2015, June 15-31, during which its flux in hard X-rays (20-40 keV) reached about 40 times the Crab nebula flux. Because of the exceptional interest of the flaring activity from this source, observations at several wavelengths were conducted. The MAGIC telescopes, triggered by the INTEGRAL alerts, followed-up the flaring source for several nights during the period June 18-27, for more than 10 h. One hour of observation was simultaneously conducted on a giant 22 GHz radio flare and a hint of signal at GeV energies seen by Fermi-LAT. The MAGIC observations did not show significant emission in any of the analysed time intervals. The derived flux upper limit, in the energy range 200-1250 GeV, is 4.8 x 10(-12) photons cm(-2) s(-1). We estimate the gamma-ray opacity during the flaring period, which along with our non-detection points to an inefficient acceleration in the V404 Cyg jets if a very high energy emitter is located further than 1 x 10(10) cm from the compact object

Observation of the black widow B1957+20 millisecond pulsar binary system with the MAGIC telescopes

B1957+20 is a millisecond pulsar located in a black-widow-type compact binary system with a low-mass stellar companion. The interaction of the pulsar wind with the companion star wind and/or the interstellar plasma is expected to create plausible conditions for acceleration of electrons to TeV energies and subsequent production of very high-energy gamma-rays in the inverse Compton process. We performed extensive observations with the Major Atmospheric Gamma Imaging Cherenkov Telescopes (MAGIC) telescopes of B1957+20. We interpret results in the framework of a few different models, namely emission from the vicinity of the millisecond pulsar, the interaction of the pulsar and stellar companion wind region or bow shock nebula. No significant steady very high-energy gamma-ray emission was found. We derived a 95 per cent confidence level upper limit of 3.0 x 10(-12) cm(-2) s(-1) on the average gamma-ray emission from the binary system above 200 GeV. The upper limits obtained with the MAGIC constrain, for the first time, different models of the high-energy emission in B1957+20. In particular, in the inner mixed wind nebula model with mono-energetic injection of electrons, the acceleration efficiency of electrons is constrained to be below similar to 2-10 per cent of the pulsar spin-down power. For the pulsar emission, the obtained upper limits for each emission peak are well above the exponential cut-off fits to the Fermi-LAT data, extrapolated to energies above 50 GeV. The MAGIC upper limits can rule out a simple power-law tail extension through the sub-TeV energy range for the main peak seen at radio frequencies

Search for very high-energy gamma-ray emission from the microquasar Cygnus X-1 with the MAGIC telescopes

The microquasar Cygnus X-1 displays the two typical soft and hard X-ray states of a black hole transient. During the latter, Cygnus X-1 shows a one-sided relativistic radio-jet. Recent detection of the system in the high energy (HE; E greater than or similar to 60 MeV) gamma-ray range with FermiLAT associates this emission with the outflow. Former MAGIC observations revealed a hint of flaring activity in the very high-energy (VHE; E greater than or similar to 100 GeV) regime during this X-ray state. We analyse similar to 97 h of Cygnus X-1 data taken with the MAGIC telescopes between July 2007 and October 2014. To shed light on the correlation between hard X-ray and VHE gamma rays as previously suggested, we study each main X-ray state separately. We perform an orbital phase-folded analysis to look for variability in the VHE band. Additionally, to place this variability behaviour in a multiwavelength context, we compare our results with Fermi-LAT, AGILE, Swift-BAT, MAXI, RXTE-ASM, AMI and RATAN-600 data. We do not detect Cygnus X-1 in the VHE regime. We establish upper limits for each X-ray state, assuming a power-law distribution with photon index Gamma = 3.2. For steady emission in the hard and soft X-ray states, we set integral upper limits at 95 per cent confidence level for energies above 200 GeV at 2.6 x 10(-12) photons cm(-2) s(-1) and 1.0 x 10(-11) photons cm(-2) s(-1), respectively. We rule out steady VHE gamma-ray emission above this energy range, at the level of theMAGIC sensitivity, originating in the interaction between the relativistic jet and the surrounding medium, while the emission above this flux level produced inside the binary still remains a valid possibility

Constraining Lorentz Invariance Violation Using the Crab Pulsar Emission Observed up to TeV Energies by MAGIC

Spontaneous breaking of Lorentz symmetry at energies on the order of the Planck energy or lower is predicted by many quantum gravity theories, implying non-trivial dispersion relations for the photon in vacuum. Consequently, gamma-rays of different energies, emitted simultaneously from astrophysical sources, could accumulate measurable differences in their time of flight until they reach the Earth. Such tests have been carried out in the past using fast variations of gamma-ray flux from pulsars, and more recently from active galactic nuclei and gamma-ray bursts. We present new constraints studying the gamma-ray emission of the galactic Crab Pulsar, recently observed up to TeV energies by the Major Atmospheric Gamma-ray Imaging Cherenkov (MAGIC) collaboration. A profile likelihood analysis of pulsar events reconstructed for energies above 400. GeV finds no significant variation in arrival time as their energy increases.. Ninety-five percent CL limits are obtained on the effective Lorentz invariance violating energy scale at the level of E-QG1 > 5.5 x 10(17) GeV (4.5 x 10(17) GeV) for a linear, and E-QG2 > 5.9 x 10(10) GeV (5.3 x 10(10) GeV) for a quadratic scenario, for the subluminal and the superluminal cases, respectively. A substantial part of this study is dedicated to calibration of the test statistic, with respect to bias and coverage properties. Moreover, the limits take into account systematic uncertainties, which are found to worsen the statistical limits by about 36%-42%. Our constraints would have been much more stringent if the intrinsic pulse shape of the pulsar between 200 GeV and 400 GeV was understood in sufficient detail and allowed inclusion of events well below 400 GeV

First multi-wavelength campaign on the gamma-ray-loud active galaxy IC 310

Context. The extragalactic very-high-energy gamma-ray sky is rich in blazars. These are jetted active galactic nuclei that are viewed at a small angle to the line-of-sight. Only a handful of objects viewed at a larger angle are so far known to emit above 100 GeV. Multi-wavelength studies of such objects up to the highest energies provide new insights into the particle and radiation processes of active galactic nuclei.Aims. We aim to report the results from the first multi-wavelength campaign observing the TeV detected nucleus of the active galaxy IC 310, whose jet is observed at a moderate viewing angle of 10 degrees-20 degrees.Methods. The multi-instrument campaign was conducted between 2012 November and 2013 January, and involved observations with MAGIC, Fermi, INTEGRAL, Swift, OVRO, MOJAVE and EVN. These observations were complemented with archival data from the AllWISE and 2MASS catalogs. A one-zone synchrotron self-Compton model was applied to describe the broadband spectral energy distribution.Results. IC 310 showed an extraordinary TeV flare at the beginning of the campaign, followed by a low, but still detectable TeV flux. Compared to previous measurements in this energy range, the spectral shape was found to be steeper during the low emission state. Simultaneous observations in the soft X-ray band showed an enhanced energy flux state and a harder-when-brighter spectral shape behavior. No strong correlated flux variability was found in other frequency regimes. The broadband spectral energy distribution obtained from these observations supports the hypothesis of a double-hump structure.Conclusions. The harder-when-brighter trend in the X-ray and VHE emission, observed for the first time during this campaign, is consistent with the behavior expected from a synchrotron self-Compton scenario. The contemporaneous broadband spectral energy distribution is well described with a one-zone synchrotron self-Compton model using parameters that are comparable to those found for other gamma-ray-emitting misaligned blazars

Observations of Sagittarius A* during the pericenter passage of the G2 object with MAGIC

Context. We present the results of a multi-year monitoring campaign of the Galactic center (GC) with the MAGIC telescopes. These observations were primarily motivated by reports that a putative gas cloud (G2) would be passing in close proximity to the super-massive black hole (SMBH), associated with Sagittarius A*, located at the center of our galaxy. This event was expected to give astronomers a unique chance to study the effect of in-falling matter on the broad-band emission of a SMBH.Aims. We search for potential flaring emission of very-high-energy (VHE; >= 100 GeV) gamma rays from the direction of the SMBH at the GC due to the passage of the G2 object. Using these data we also study the morphology of this complex region.Methods. We observed the GC region with the MAGIC Imaging Atmospheric Cherenkov Telescopes during the period 2012-2015, collecting 67 h of good-quality data. In addition to a search for variability in the flux and spectral shape of the GC gamma-ray source, we use a point-source subtraction technique to remove the known gamma-ray emitters located around the GC in order to reveal the TeV morphology of the extended emission inside that region.Results. No effect of the G2 object on the VHE gamma-ray emission from the GC was detected during the 4 yr observation campaign. We confirm previous measurements of the VHE spectrum of Sagittarius A*, and do not detect any significant variability of the emission from the source. Furthermore, the known VHE gamma-ray emitter at the location of the supernova remnant G0.9+0.1 was detected, as well as the recently discovered VHE source close to the GG radio arc

Investigating the peculiar emission from the new VHE gamma-ray source H1722+119

The Major Atmospheric Gamma-ray Imaging Cherenkov (MAGIC) telescopes observed the BL Lac object H1722+119 (redshift unknown) for six consecutive nights between 2013 May 17 and 22, for a total of 12.5 h. The observations were triggered by high activity in the optical band measured by the KVA (Kungliga Vetenskapsakademien) telescope. The source was for the first time detected in the very high energy (VHE, E > 100 GeV) gamma-ray band with a statistical significance of 5.9s. The integral flux above 150 GeV is estimated to be (2.0 +/- 0.5) per cent of the Crab nebula flux. We used contemporaneous high energy (HE, 100 MeV < E < 100 GeV) gamma-ray observations from Fermi-Large Area Telescope to estimate the redshift of the source. Within the framework of the current extragalactic background light models, we estimate the redshift to be z = 0.34 +/- 0.15. Additionally, we used contemporaneous X-ray to radio data collected by the instruments on board the Swift satellite, the KVA, and the Owens Valley Radio Observatory telescope to study multifrequency characteristics of the source. We found no significant temporal variability of the flux in the HE and VHE bands. The flux in the optical and radio wavebands, on the other hand, did vary with different patterns. The spectral energy distribution of H1722+119 shows surprising behaviour in the similar to 3 x 10(14)-10(18) Hz frequency range. It can be modelled using an inhomogeneous helical jet synchrotron self-Compton model