Chronic stress and impaired glutamate function elicit a depressive-like phenotype and common changes in gene expression in the mouse frontal cortex

Major depression might originate from both environmental and genetic risk factors. The environmental chronic mild stress (CMS) model mimics some environmental factors contributing to human depression and induces anhedonia and helplessness. Mice heterozygous for the synaptic vesicle protein (SVP) vesicular glutamate transporter 1 (VGLUT1) have been proposed as a genetic model of deficient glutamate function linked to depressive-like behaviour. Here, we aimed to identify, in these two experimental models, gene expression changes in the frontal cortex, common to stress and impaired glutamate function. Both VGLUT1+/- and CMS mice showed helpless and anhedonic-like behavior. Microarray studies in VGLUT1+/- mice revealed regulation of genes involved in apoptosis, neurogenesis, synaptic transmission, protein metabolic process or learning and memory. In addition, RT-PCR studies confirmed gene expression changes in several glutamate, GABA, dopamine and serotonin neurotransmitter receptors. On the other hand, CMS affected the regulation of 147 transcripts, some of them involved in response to stress and oxidoreductase activity. Interestingly, 52 genes were similarly regulated in both models. Specifically, a dowregulation in genes that promote cell proliferation (Anapc7), cell growth (CsnK1g1), cell survival (Hdac3), inhibition of apoptosis (Dido1) was observed. Genes linked to cytoskeleton (Hspg2, Invs), psychiatric disorders (Grin1, MapK12) or an antioxidant enzyme (Gpx2) were also downregulated. Moreover, genes that inhibit the MAPK pathways (Dusp14), stimulate oxidative metabolism (Eif4a2) and enhance glutamate transmission (Rab8b) were upregulated. We suggest that these genes could form part of the altered “molecular context” underlying depressive-like behaviour in animal models. The clinical relevance of these findings is discussed

The afterglow and kilonova of the short GRB 160821B

GRB 160821B is a short duration gamma-ray burst (GRB) detected and localized by the Neil Gehrels Swift Observatory in the outskirts of a spiral galaxy at z=0.1613, at a projected physical offset of 16 kpc from the galaxy's center. We present X-ray, optical/nIR and radio observations of its counterpart and model them with two distinct components of emission: a standard afterglow, arising from the interaction of the relativistic jet with the surrounding medium, and a kilonova, powered by the radioactive decay of the sub-relativistic ejecta. Broadband modeling of the afterglow data reveals a weak reverse shock propagating backward into the jet, and a likely jet-break at 3.5 d. This is consistent with a structured jet seen slightly off-axis while expanding into a low-density medium. Analysis of the kilonova properties suggests a rapid evolution toward red colors, similar to AT2017gfo, and a low nIR luminosity, possibly due to the presence of a long-lived neutron star. The global properties of the environment, the inferred low mass (M_ej < 0.006 Msun) and velocities (v > 0.05 c) of lanthanide-rich ejecta are consistent with a binary neutron star merger progenitor.Comment: 14 pages, 6 figures, MNRAS, in press. Moderate revision, added Figure 5 and X-ray data to Table

Identification of circulating miRNA profiles that distinguish malignant pleural mesothelioma from lung adenocarcinoma

Accurate diagnosis of malignant pleura mesothelioma (MPM) is challenging. Differential diagnosis of MPM versus lung adenocarcinoma (AD) is particularly difficult, yet clinically important since the two neoplasias call for different treatment approaches. Circulating miRNA-profiling to identify miRNAs that can be used to distinguish MPM from AD has not been reported. We conducted a wide screening study of miRNA profiles in serum pools of MPM patients (N = 11), AD patients (N = 36), and healthy subjects (N = 45) to identify non-invasive biomarkers for differential diagnosis of MPM and AD, using deep sequencing. Sequencing detected up to 300 known miRNAs and up to 25 novel miRNAs species in the serum samples. Among known miRNAs, 7 were upregulated in MPM and 12 were upregulated in AD compared to healthy controls. Of these, eight were distinctive for AD and three were unique for MPM. Direct comparison of the miRNA profiles for MPM and AD revealed differences in miRNA levels that could be useful for differential diagnosis. No differentially expressed novel miRNAs were found. Further bioinformatics analysis indicated that three upregulated miRNAs in MPM are associated with the p38 pathway. There are unique alterations in serum miRNAs in MPM and AD compared to healthy controls, as well as differences between MPM and AD profiles. Differing miRNA levels between MPM and AD may be useful for differential diagnosis. A potential association to p38 pathway of three upregulated miRNAs in MPM was revealed

Transition from Fireball to Poynting-flux-dominated Outflow in Three-Episode GRB 160625B

The ejecta composition is an open question in gamma-ray bursts (GRB) physics. Some GRBs possess a quasi-thermal spectral component in the time-resolved spectral analysis, suggesting a hot fireball origin. Others show a featureless non-thermal spectrum known as the "Band" function, consistent with a synchrotron radiation origin and suggesting that the jet is Poynting-flux-dominated at the central engine and likely in the emission region as well. There are also bursts showing a sub-dominant thermal component and a dominant synchrotron component suggesting a likely hybrid jet composition. Here we report an extraordinarily bright GRB 160625B, simultaneously observed in gamma-rays and optical wavelengths, whose prompt emission consists of three isolated episodes separated by long quiescent intervals, with the durations of each "sub-burst" being $\sim$ 0.8 s, 35 s, and 212 s, respectively. Its high brightness (with isotropic peak luminosity L$_{\rm p, iso}\sim 4\times 10^{53}$ erg/s) allows us to conduct detailed time-resolved spectral analysis in each episode, from precursor to main burst and to extended emission. The spectral properties of the first two sub-bursts are distinctly different, allowing us to observe the transition from thermal to non-thermal radiation between well-separated emission episodes within a single GRB. Such a transition is a clear indication of the change of jet composition from a fireball to a Poynting-flux-dominated jet.Comment: Revised version reflecting the referees' comments. 27 pages, 11 figures, 5 tables. The final edited version will appear in Nature Astronom

Estimation of the charge carrier localization length from Gaussian fluctuations in the magneto-thermopower of La_{0.6}Y_{0.1}Ca_{0.3}MnO_3

The magneto-thermoelectric power (TEP) $\Delta S(T,H)$ of perovskite type manganise oxide $La_{0.6}Y_{0.1}Ca_{0.3}MnO_3$ is found to exhibit a sharp peak at some temperature $T^{*}=170K$. By approximating the true shape of the measured magneto-TEP in the vicinity of $T^{*}$ by a linear triangle of the form $\Delta S(T,H)\simeq S_p(H)\pm B^{\pm}(H)(T^{*}-T)$, we observe that $B ^{-}(H)\simeq 2B ^{+}(H)$. We adopt the electron localization scenario and introduce a Ginzburg-Landau (GL) type theory which incorporates the two concurrent phase transitions, viz., the paramagnetic-ferromagnetic transition at the Curie point $T_C$ and the "metal-insulator" (M-I) transition at $T_{MI}$. The latter is characterized by the divergence of the field-dependent charge carrier localization length $\xi (T,H)$ at some characteristic field $H_0$. Calculating the average and fluctuation contributions to the total magnetization and the transport entropy related magneto-TEP $\Delta S(T,H)$ within the GL theory, we obtain a simple relationship between $T^{*}$ and the above two critical temperatures ($T_{C}$ and $T_{MI}$). The observed slope ratio $B ^{-}(H)/B ^{+}(H)$ is found to be governed by the competition between the electron-spin exchange $JS$ and the induced magnetic energy $M_sH_0$. The comparison of our data with the model predictions produce $T_{C}=195K$, $JS=40meV$, $M_0=0.4M_s$, $\xi_0=10\AA$, and $n_e/n_i=2/3$ for the estimates of the Curie temperature, the exchange coupling constant, the critical magnetization, the localization length, and the free-to-localized carrier number density ratio, respectively.Comment: 6 pages (REVTEX), 2 PS figures (epsf.sty); submitted to Phys.Rev.

ALMA Long Baseline Observations of the Strongly Lensed Submillimeter Galaxy HATLAS J090311.6+003906 at z=3.042

We present initial results of very high resolution Atacama Large Millimeter/submillimeter Array (ALMA) observations of the $z$=3.042 gravitationally lensed galaxy HATLAS J090311.6+003906 (SDP.81). These observations were carried out using a very extended configuration as part of Science Verification for the 2014 ALMA Long Baseline Campaign, with baselines of up to 15 km. We present continuum imaging at 151, 236 and 290 GHz, at unprecedented angular resolutions as fine as 23 milliarcseconds (mas), corresponding to an un-magnified spatial scale of ~180 pc at z=3.042. The ALMA images clearly show two main gravitational arc components of an Einstein ring, with emission tracing a radius of ~1.5". We also present imaging of CO(10-9), CO(8-7), CO(5-4) and H2O line emission. The CO emission, at an angular resolution of ~170 mas, is found to broadly trace the gravitational arc structures but with differing morphologies between the CO transitions and compared to the dust continuum. Our detection of H2O line emission, using only the shortest baselines, provides the most resolved detection to date of thermal H2O emission in an extragalactic source. The ALMA continuum and spectral line fluxes are consistent with previous Plateau de Bure Interferometer and Submillimeter Array observations despite the impressive increase in angular resolution. Finally, we detect weak unresolved continuum emission from a position that is spatially coincident with the center of the lens, with a spectral index that is consistent with emission from the core of the foreground lensing galaxy.Comment: 9 pages, 5 figures and 3 tables, accepted for publication in the Astrophysical Journal Letter

First Results from High Angular Resolution ALMA Observations Toward the HL Tau Region

We present Atacama Large Millimeter/submillimeter Array (ALMA) observations from the 2014 Long Baseline Campaign in dust continuum and spectral line emission from the HL Tau region. The continuum images at wavelengths of 2.9, 1.3, and 0.87 mm have unprecedented angular resolutions of 0.075 arcseconds (10 AU) to 0.025 arcseconds (3.5 AU), revealing an astonishing level of detail in the circumstellar disk surrounding the young solar analogue HL Tau, with a pattern of bright and dark rings observed at all wavelengths. By fitting ellipses to the most distinct rings, we measure precise values for the disk inclination (46.72pm0.05 degrees) and position angle (+138.02pm0.07 degrees). We obtain a high-fidelity image of the 1.0 mm spectral index ($\alpha$), which ranges from $\alpha\sim2.0$ in the optically-thick central peak and two brightest rings, increasing to 2.3-3.0 in the dark rings. The dark rings are not devoid of emission, we estimate a grain emissivity index of 0.8 for the innermost dark ring and lower for subsequent dark rings, consistent with some degree of grain growth and evolution. Additional clues that the rings arise from planet formation include an increase in their central offsets with radius and the presence of numerous orbital resonances. At a resolution of 35 AU, we resolve the molecular component of the disk in HCO+ (1-0) which exhibits a pattern over LSR velocities from 2-12 km/s consistent with Keplerian motion around a ~1.3 solar mass star, although complicated by absorption at low blue-shifted velocities. We also serendipitously detect and resolve the nearby protostars XZ Tau (A/B) and LkHa358 at 2.9 mm.Comment: 11 pages, 5 figures, 2 tables, accepted for publication in the Astrophysical Journal Letter

ALMA Observations of Asteroid 3 Juno at 60 Kilometer Resolution

We present Atacama Large Millimeter/submillimeter Array (ALMA) 1.3 mm continuum images of the asteroid 3 Juno obtained with an angular resolution of 0.042 arcseconds (60 km at 1.97 AU). The data were obtained over a single 4.4 hr interval, which covers 60% of the 7.2 hr rotation period, approximately centered on local transit. A sequence of ten consecutive images reveals continuous changes in the asteroid's profile and apparent shape, in good agreement with the sky projection of the three-dimensional model of the Database of Asteroid Models from Inversion Techniques. We measure a geometric mean diameter of 259pm4 km, in good agreement with past estimates from a variety of techniques and wavelengths. Due to the viewing angle and inclination of the rotational pole, the southern hemisphere dominates all of the images. The median peak brightness temperature is 215pm13 K, while the median over the whole surface is 197pm15 K. With the unprecedented resolution of ALMA, we find that the brightness temperature varies across the surface with higher values correlated to the subsolar point and afternoon areas, and lower values beyond the evening terminator. The dominance of the subsolar point is accentuated in the final four images, suggesting a reduction in the thermal inertia of the regolith at the corresponding longitudes, which are possibly correlated to the location of the putative large impact crater. These results demonstrate ALMA's potential to resolve thermal emission from the surface of main belt asteroids, and to measure accurately their position, geometric shape, rotational period, and soil characteristics.Comment: 8 pages, 3 figures, 2 tables, accepted for publication in the Astrophysical Journal Letter

Oscillatory Exchange Coupling and Positive Magnetoresistance in Epitaxial Oxide Heterostructures

Oscillations in the exchange coupling between ferromagnetic $La_{2/3}Ba_{1/3}MnO_3$ layers with paramagnetic $LaNiO_3$ spacer layer thickness has been observed in epitaxial heterostructures of the two oxides. This behavior is explained within the RKKY model employing an {\it ab initio} calculated band structure of $LaNiO_3$, taking into account strong electron scattering in the spacer. Antiferromagnetically coupled superlattices exhibit a positive current-in-plane magnetoresistance.Comment: 4 pages (RevTeX), 5 figures (EPS

Development of a nursing intervention to facilitate optimal antiretroviral-treatment taking among people living with HIV

<p>Abstract</p> <p>Background</p> <p>Failure by a large portion of PLHIV to take optimally ARV treatment can have serious repercussions on their health. The absence of a systematic treatment-taking promotion program in Quebec prompted stakeholders to develop jointly a theory- and evidence-based nursing intervention to this end. This article describes the results of a collective effort by researchers, clinicians and PLHIV to share their knowledge and create an appropriate intervention.</p> <p>Methods</p> <p>Intervention mapping was used as the framework for developing the intervention. First, the target population and environmental conditions were analyzed and a literature review conducted to identify predictors of optimal treatment taking. The predictors to emerge were self-efficacy and attitudes. Performance objectives were subsequently defined and crossed-referenced with the predictors to develop a matrix of change objectives. Then, theories of self-efficacy and persuasion (the predictors to emerge from step 1), together with practical strategies derived from these theories, were used to design the intervention. Finally, the sequence and content of the intervention activities were defined and organized, and the documentary material designed.</p> <p>Results</p> <p>The intervention involves an intensive, personalized follow-up over four direct-contact sessions, each lasting 45–75 minutes. Individuals are engaged in a learning process that leads to the development of skills to motivate themselves to follow the therapeutic plan properly, to overcome situations that make taking the antiretroviral medication difficult, to cope with side-effects, to relate to people in their social circle, and to deal with health professionals.</p> <p>Conclusion</p> <p>The intervention was validated by various health professionals and pre-tested with four PLHIV. Preliminary results support the suitability and viability of the intervention. A randomized trial is currently underway to verify the effectiveness of the intervention in promoting optimal antiretroviral treatment taking.</p