Stimulus-evoked high frequency oscillations are present in neuronal networks on microelectrode arrays

Pathological high frequency oscillations (250–600 Hz) are present in the brains of epileptic animals and humans. The etiology of these oscillations and how they contribute to the diseased state remains unclear. This work identifies the presence of microstimulation-evoked high frequency oscillations (250–400 Hz) in dissociated neuronal networks cultured on microelectrode arrays (MEAs). Oscillations are more apparent with higher stimulus voltages. As with in vivo studies, activity is isolated to a single electrode, however, the MEA provides improved spatial resolution with no spread of the oscillation to adjacent electrodes 200 μm away. Oscillations develop across four weeks in vitro. Oscillations still occur in the presence of tetrodotoxin and synaptic blockers, and they cause no apparent disruption in the ability of oscillation-presenting electrodes to elicit directly evoked action potentials (dAPs) or promote the spread of synaptic activity throughout the culture. Chelating calcium with ethylene glycol tetraacetic acid (EGTA) causes a temporal prolongation of the oscillation. Finally, carbenoxolone significantly reduces or eliminates the high frequency oscillations. Gap junctions may play a significant role in maintaining the oscillation given the inhibitory effect of carbenoxolone, the propagating effect of reduced calcium conditions and the isolated nature of the activity as demonstrated in previous studies. This is the first demonstration of stimulus-evoked high frequency oscillations in dissociated cultures. Unlike current models that rely on complex in vivo recording conditions, this work presents a simple controllable model in neuronal cultures on MEAs to further investigate how the oscillations occur at the molecular level and how they may contribute to the pathophysiology of disease

ALMA observations of Elias 2–24: a protoplanetary disk with multiple gaps in the Ophiuchus molecular cloud

We present ALMA 1.3 mm continuum observations at 0. 2 (25 au) resolution of Elias 2–24, one of the largest and brightest protoplanetary disks in the Ophiuchus Molecular Cloud, and we report the presence of three partially resolved concentric gaps located at ∼20, 52, and 87 au from the star. We perform radiative transfer modeling of the disk to constrain its surface density and temperature radial profile and place the disk structure in the context of mechanisms capable of forming narrow gaps such as condensation fronts and dynamical clearing by actively forming planets. In particular, we estimate the disk temperature at the locations of the gaps to be 23, 15, and 12 K (at 20, 52, and 87 au, respectively), very close to the expected snowlines of CO (23–28 K) and N2 (12–15 K). Similarly, by assuming that the widths of the gaps correspond to 4–8× the Hill radii of forming planets (as suggested by numerical simulations), we estimate planet masses in the range of 0.2 1.5 – MJup, 1.0 8.0 – MJup, and 0.02 0.15 – MJup for the inner, middle, and outer gap, respectively. Given the surface density profile of the disk, the amount of “missing mass” at the location of each one of these gaps (between 4 and 20 MJup) is more than sufficient to account for the formation of such planets.Fil: Cieza, Lucas A.. Universidad Diego Portales; ChileFil: Casassus, Simon. Universidad de Chile; ChileFil: Pérez, Sebastian. Universidad de Chile; ChileFil: Hales, Antonio. Alma Observatory; ChileFil: Cárcamo, Miguel. Universidad de Chile; ChileFil: Ansdell, Megan. University of California at Berkeley; Estados UnidosFil: Avenhaus, Henning. Universitat Zurich; SuizaFil: Bayo, Amelia. Universidad de Valparaiso; ChileFil: Bertrang, Gesa H.-M.. Universidad Diego Portales; ChileFil: Cánovas, Hector. Agencia Espacial Europea; EspañaFil: Christiaens, Valentin. Universidad de Chile; ChileFil: Dent, William. Alma Observatory; ChileFil: Ferrero, Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Gamen, Roberto Claudio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Olofsson, Johan. Universidad de Valparaiso; ChileFil: Orcajo, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Astrofísica La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Astronómicas y Geofísicas. Instituto de Astrofísica La Plata; ArgentinaFil: Osses, Axel. Universidad de Chile; ChileFil: Peña Ramirez, Karla. Universidad de Antofagasta; ChileFil: Principe, David. Massachusetts Institute of Technology; Estados UnidosFil: Ruíz Rodríguez, Dary. Rochester Institute Of Technology; Estados UnidosFil: Schreiber, Matthias R.. Universidad de Valparaiso; ChileFil: Plas, Gerrit van der. Univ. Grenoble Alpes; SuizaFil: Williams, Jonathan P.. Institute For Astronomy, University Of Hawaii; Estados UnidosFil: Zurlo, Alice. Universidad Diego Portales; Chil

Confirming the Primarily Smooth Structure of the Vega Debris Disk at Millimeter Wavelengths

Clumpy structure in the debris disk around Vega has been previously reported at millimeter wavelengths and attributed to concentrations of dust grains trapped in resonances with an unseen planet. However, recent imaging at similar wavelengths with higher sensitivity has disputed the observed structure. We present three new millimeter wavelength observations that help to resolve the puzzling and contradictory observations. We have observed the Vega system with the Submillimeter Array (SMA) at a wavelength of 880 μm and an angular resolution of 5"; with the Combined Array for Research in Millimeter-wave Astronomy (CARMA) at a wavelength of 1.3 mm and an angular resolution of 5"; and with the Green Bank Telescope (GBT) at a wavelength of 3.3 mm and angular resolution of 10". Despite high sensitivity and short baselines, we do not detect the Vega debris disk in either of the interferometric data sets (SMA and CARMA), which should be sensitive at high significance to clumpy structure based on previously reported observations. We obtain a marginal (3σ) detection of disk emission in the GBT data; the spatial distribution of the emission is not well constrained.We analyze the observations in the context of several different models, demonstrating that the observations are consistent with a smooth, broad, axisymmetric disk with inner radius 20–100 AU and width ≾50 AU. The interferometric data require that at least half of the 860 μm emission detected by previous single-dish observations with the James Clerk Maxwell Telescope be distributed axisymmetrically, ruling out strong contributions from flux concentrations on spatial scales of ≾100 AU. These observations support recent results from the Plateau de Bure Interferometer indicating that previous detections of clumpy structure in the Vega debris disk were spurious

First-Borns Carry a Higher Metabolic Risk in Early Adulthood: Evidence from a Prospective Cohort Study

Birth order has been associated with early growth variability and subsequent increased adiposity, but the consequent effects of increased fat mass on metabolic risk during adulthood have not been assessed. We aimed to quantify the metabolic risk in young adulthood of being first-born relative to those born second or subsequently.Body composition and metabolic risk were assessed in 2,249 men, aged 17-19 years, from a birth cohort in southern Brazil. Metabolic risk was assessed using a composite z-score integrating standardized measurements of blood pressure, total cholesterol, high density lipoprotein, triglycerides and fat mass. First-borns had lower birth weight z-score (Δ = -0.25, 95%CI -0.35, -0.15,p<0.001) but showed greater weight gain during infancy (change in weight z-score from birth to 20 months: Δ = 0.39, 95%CI 0.28-0.50, p<0.0001) and had greater mean height (Δ = 1.2 cm, 95%CI: 0.7-1.6, p<0.0001) and weight (Δ = 0.34 kg, 95%CI: 0.13-0.55, p<0.002) at 43 months. This greater weight and height tracked into early adulthood, with first-borns being significantly taller, heavier and with significantly higher fat mass than later-borns. The metabolic risk z-score was significantly higher in first-borns.First-born status is associated with significantly elevated adiposity and metabolic risk in young adult men in Brazil. Our results, linking cardiovascular risk with life history variables, suggest that metabolic risk may be associated with the worldwide trend to smaller family size and it may interact with changes in behavioural or environmental risk factors

Empathy among undergraduate medical students: A multi-centre cross-sectional comparison of students beginning and approaching the end of their course

BACKGROUND: Although a core element in patient care the trajectory of empathy during undergraduate medical education remains unclear. Empathy is generally regarded as comprising an affective capacity: the ability to be sensitive to and concerned for, another and a cognitive capacity: the ability to understand and appreciate the other person's perspective. The authors investigated whether final year undergraduate students recorded lower levels of empathy than their first year counterparts, and whether male and female students differed in this respect. METHODS: Between September 2013 and June 2014 an online questionnaire survey was administered to 15 UK, and 2 international medical schools. Participating schools provided both 5-6 year standard courses and 4 year accelerated graduate entry courses. The survey incorporated the Jefferson Scale of Empathy-Student Version (JSE-S) and Davis's Interpersonal Reactivity Index (IRI), both widely used to measure medical student empathy. Participation was voluntary. Chi squared tests were used to test for differences in biographical characteristics of student groups. Multiple linear regression analyses, in which predictor variables were year of course (first/final); sex; type of course and broad socio-economic group were used to compare empathy scores. RESULTS: Five medical schools (4 in the UK, 1 in New Zealand) achieved average response rates of 55 % (n = 652) among students starting their course and 48 % (n = 487) among final year students. These schools formed the High Response Rate Group. The remaining 12 medical schools recorded lower response rates of 24.0 % and 15.2 % among first and final year students respectively. These schools formed the Lower Response Rate Group. For both male and female students in both groups of schools no significant differences in any empathy scores were found between students starting and approaching the end of their course. Gender was found to significantly predict empathy scores, with females scoring higher than males. CONCLUSIONS: Participant male and female medical students approaching the end of their undergraduate education, did not record lower levels of empathy, compared to those at the beginning of their course. Questions remain concerning the trajectory of empathy after qualification and how best to support it through the pressures of starting out in medical practice

Imaging the water snow-line during a protostellar outburst

A snow-line is the region of a protoplanetary disk at which a major volatile, such as water or carbon monoxide, reaches its condensation temperature. Snow-lines play a crucial role in disk evolution by promoting the rapid growth of ice-covered grains^1, 2, 3, 4, 5, 6. Signatures of the carbon monoxide snow-line (at temperatures of around 20 kelvin) have recently been imaged in the disks surrounding the pre-main-sequence stars TW Hydra^7, 8, 9 and HD163296 (refs 3, 10), at distances of about 30 astronomical units (au) from the star. But the water snow-line of a protoplanetary disk (at temperatures of more than 100 kelvin) has not hitherto been seen, as it generally lies very close to the star (less than 5 au away for solar-type stars^11). Water-ice is important because it regulates the efficiency of dust and planetesimal coagulation5, and the formation of comets, ice giants and the cores of gas giants^12. Here we report images at 0.03-arcsec resolution (12 au) of the protoplanetary disk around V883 Ori, a protostar of 1.3 solar masses that is undergoing an outburst in luminosity arising from a temporary increase in the accretion rate^13. We find an intensity break corresponding to an abrupt change in the optical depth at about 42 au, where the elevated disk temperature approaches the condensation point of water, from which we conclude that the outburst has moved the water snow-line. The spectral behaviour across the snow-line confirms recent model predictions^14: dust fragmentation and the inhibition of grain growth at higher temperatures results in soaring grain number densities and optical depths. As most planetary systems are expected to experience outbursts caused by accretion during their formation^15, 16, our results imply that highly dynamical water snow-lines must be considered when developing models of disk evolution and planet formation

Is Overweight in Stunted Preschool Children in Cameroon Related to Reductions in Fat Oxidation, Resting Energy Expenditure and Physical Activity?

Recent studies suggest that early modifications in metabolic pathways and behaviour, leading to energy conservation and reduced linear growth, could represent adaptations to nutritional constraints during foetal life and infancy. Impaired fat oxidation, low resting energy expenditure and reduced physical activity, resulting from these adaptations, could facilitate fat storage and development of overweight in growth-retarded children that consume more energy-dense food. This study aims at assessing whether: (1) dual-burden preschool children (simultaneously stunted and overweight) of Yaounde (Cameroon) have low birth-weight (indicator of foetal undernutrition) and reductions in fat oxidation, resting energy expenditure (REE) and physical activity, (2) fat oxidation, REE and physical activity are associated with foetal growth.162 children (24-72 months) were considered: 22 stunted-overweight (SO), 40 stunted (S), 41 overweight (O), and 59 non stunted-non overweight (NSNO). Nutritional status and body composition were assessed using anthropometry and multifrequency bioimpedance analysis. Fasting respiratory quotient (RQ) and REE were measured by indirect calorimetry. Physical activity was determined using accelerometers, food questionnaires were used for diet assessment and birth-weight was noted. Mean RQs and REE (weight adjusted) did not differ between stunted children (SO and S) and non-stunted children (O and NSNO). SO and S children spent more time in sedentary activities than O children (p = 0.01 and p = 0.02, respectively) and less time in moderate-to-vigorous activities than NSNO children (p = 0.05 and p = 0.04, respectively). SO children's diet was less diverse (p = 0.01) with less animal products (p = 0.006). Multiple linear regressions model revealed that birth-weight is predictive of RQ (β = 0.237, p<0.01, R(2) = 0.08).This study showed that growth retardation in stunted-overweight children could be associated with postnatal nutritional deficiencies. Overweight in stunted children could be associated with reduced physical activity in the context of nutrition transition. High birth-weight was a predictor of reduced lipid oxidation, a risk factor of fat deposition

Detection of a Fourth Orbivirus Non-Structural Protein

The genus Orbivirus includes both insect and tick-borne viruses. The orbivirus genome, composed of 10 segments of dsRNA, encodes 7 structural proteins (VP1–VP7) and 3 non-structural proteins (NS1–NS3). An open reading frame (ORF) that spans almost the entire length of genome segment-9 (Seg-9) encodes VP6 (the viral helicase). However, bioinformatic analysis recently identified an overlapping ORF (ORFX) in Seg-9. We show that ORFX encodes a new non-structural protein, identified here as NS4. Western blotting and confocal fluorescence microscopy, using antibodies raised against recombinant NS4 from Bluetongue virus (BTV, which is insect-borne), or Great Island virus (GIV, which is tick-borne), demonstrate that these proteins are synthesised in BTV or GIV infected mammalian cells, respectively. BTV NS4 is also expressed in Culicoides insect cells. NS4 forms aggregates throughout the cytoplasm as well as in the nucleus, consistent with identification of nuclear localisation signals within the NS4 sequence. Bioinformatic analyses indicate that NS4 contains coiled-coils, is related to proteins that bind nucleic acids, or are associated with membranes and shows similarities to nucleolar protein UTP20 (a processome subunit). Recombinant NS4 of GIV protects dsRNA from degradation by endoribonucleases of the RNAse III family, indicating that it interacts with dsRNA. However, BTV NS4, which is only half the putative size of the GIV NS4, did not protect dsRNA from RNAse III cleavage. NS4 of both GIV and BTV protect DNA from degradation by DNAse. NS4 was found to associate with lipid droplets in cells infected with BTV or GIV or transfected with a plasmid expressing NS4