Fractionation of a three-particle mixture by Brownian sieving hydrodynamic chromatography

Particles ranging in size from a few nanometers (exosomes or viruses) to a few micrometers (bacteria or red blood cells) can be sorted using a size-based separation process. One of the simplest techniques is provided by hydrodynamic chromatography (HDC) which typically requires long channels to achieve adequate resolution. A new separation mechanism based on a Brownian sieving effect coupled with HDC has recently been proposed to overcome these limitations. An efficiency improvement of up to 2000 % has been predicted for a two-size mixture. The aim of this work is to study and optimize a modified geometry useful for obtaining the simultaneous separation of a three-size diluted suspension. The results suggest a significant performance improvement, up to 3000 %, over the standard HDC

Prefrontal cortex-driven dopamine signals in the striatum show unique spatial and pharmacological properties

Dopamine (DA) signals in the striatum are critical for a variety of vital processes, including motivation, motor learning, and reinforcement learning. Striatal DA signals can be evoked by direct activation of inputs from midbrain DA neurons (DANs) as well as cortical and thalamic inputs to the striatum. In this study, we show that in vivo optogenetic stimulation of prelimbic (PrL) and infralimbic (IL) cortical afferents to the striatum triggers an increase in extracellular DA concentration, which coincides with elevation of striatal acetylcholine (ACh) levels. This increase is blocked by a nicotinic ACh receptor (nAChR) antagonist. Using single or dual optogenetic stimulation in brain slices from male and female mice, we compared the properties of these PrL/IL-evoked DA signals with those evoked by stimulation from midbrain DAN axonal projections. PrL/IL-evoked DA signals are undistinguishable from DAN evoked DA signals in their amplitudes and electrochemical properties. However, PrL/IL-evoked DA signals are spatially restricted and preferentially recorded in the dorsomedial striatum. PrL/IL-evoked DA signals also differ in their pharmacological properties, requiring activation of glutamate and nicotinic ACh receptors. Thus, both in vivo and in vitro results indicate that cortical evoked DA signals rely on recruitment of cholinergic interneurons, which renders DA signals less able to summate during trains of stimulation and more sensitive to both cholinergic drugs and temperature. In conclusion, cortical and midbrain inputs to the striatum evoke DA signals with unique spatial and pharmacological properties that likely shape their functional roles and behavioral relevance.Fil: Adrover, Martín Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. National Institutes of Health; Estados UnidosFil: Shin, Jung Hoon. National Institutes of Health; Estados UnidosFil: Quiroz, Cesar. National Institutes of Health; Estados UnidosFil: Ferré, Sergi. National Institutes of Health; Estados UnidosFil: Lemos, Julia C.. National Institutes of Health; Estados UnidosFil: Alvarez, Veronica A.. National Institutes of Health; Estados Unido

Sic1 plays a role in timing and oscillatory behaviour of B-type cyclins

Budding yeast cell cycle oscillates between states of low and high cyclin-dependent kinase activity, driven by association of Cdk1 with B-type (Clb) cyclins. Various Cdk1-Clb complexes are activated and inactivated in a fixed, temporally regulated sequence, inducing the behaviour known as "waves of cyclins". The transition from low to high Clb activity is triggered by degradation of Sic1, the inhibitor of Cdk1-Clb complexes, at the entry to S phase. The G(1) phase is characterized by low Clb activity and high Sic1 levels. High Clb activity and Sic1 proteolysis are found from the beginning of the S phase until the end of mitosis. The mechanism regulating the appearance on schedule of Cdk1-Clb complexes is currently unknown. Here, we analyse oscillations of Clbs, focusing on the role of their inhibitor Sic1. We compare mathematical networks differing in interactions that Sic1 may establish with Cdk1-Clb complexes. Our analysis suggests that the wave-like cyclins pattern derives from the binding of Sic1 to all Clb pairs rather than from Clb degradation. These predictions are experimentally validated, showing that Sic1 indeed interacts and coexists in time with Clbs. Intriguingly, a sic1Delta strain looses cell cycle-regulated periodicity of Clbs, which is observed in the wild type, whether a SIC1-0P strain delays the formation of Clb waves. Our results highlight an additional role for Sic1 in regulating Cdk1-Clb complexes, coordinating their appearance

Revista de Vertebrados de la Estación Biológica de Doñana

Anfibios fósiles del Pleistoceno de Mallorca.Species densities of Reptiles and Amphibiansfon the Iberian PeninsulaEcología alimenticia del Petirrojo (Erithacus rubecula) durante su invernada en encinares del Sur de EspañaEl papel d. la Perdiz roja (Alectoris rufa) en la dieta de los predadores IbéricosComposición de las Comunidades de Passeriformes en dos biotopos de Sierra Morena Occidental.Sobre las Ginetas de la Isla de Ibiza (Genetta genetta isabelae n. ssp.)Peer reviewe

AGILE Observations of the Gravitational Wave Event GW150914

We report the results of an extensive search in the AGILE data for a gamma-ray counterpart of the LIGO gravitational wave event GW150914. Currently in spinning mode, AGILE has the potential of covering with its gamma-ray instrument 80 % of the sky more than 100 times a day. It turns out that AGILE came within a minute from the event time of observing the accessible GW150914 localization region. Interestingly, the gamma-ray detector exposed about 65 % of this region during the 100 s time intervals centered at -100 s and +300 s from the event time. We determine a 2-sigma flux upper limit in the band 50 MeV - 10 GeV, $UL = 1.9 \times 10^{-8} \rm \, erg \, cm^{-2} \, s^{-1}$ obtained about 300 s after the event. The timing of this measurement is the fastest ever obtained for GW150914, and significantly constrains the electromagnetic emission of a possible high-energy counterpart. We also carried out a search for a gamma-ray precursor and delayed emission over timescales ranging from minutes to days: in particular, we obtained an optimal exposure during the interval -150 / -30 s. In all these observations, we do not detect a significant signal associated with GW150914. We do not reveal the weak transient source reported by Fermi-GBM 0.4 s after the event time. However, even though a gamma-ray counterpart of the GW150914 event was not detected, the prospects for future AGILE observations of gravitational wave sources are decidedly promising.Comment: 20 pages, 6 figures. Submitted to the Astrophysical Journal Letters on April 1, 201

Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior

Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions. We found that while motor coordination and reward learning were largely unchanged, these animals showed prominent deficits in effort-related behavioral tasks. These results provide genetic evidence that glutamatergic transmission onto dopaminergic neurons underlies incentive motivation, a willingness to exert high levels of effort to obtain reinforcers, and have important implications for understanding the normal function of the midbrain dopamine system.Fil: Hutchison, M. A.. National Institutes of Health; Estados UnidosFil: Gu, X.. National Institutes of Health; Estados UnidosFil: Adrover, Martín Federico. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Lee, M. R.. National Institutes of Health; Estados UnidosFil: Hnasko, T. S.. University of California at San Diego; Estados UnidosFil: Alvarez, V. A.. National Institutes of Health; Estados UnidosFil: Lu, W.. National Institutes of Health; Estados Unido

Multiwavelength variability and correlation studies of Mrk 421 during historically low X-ray and γ-ray activity in 2015-2016

Acciari, V. A., et al. (MAGIC Collaboration)We report a characterization of the multiband flux variability and correlations of the nearby (z = 0.031) blazar Markarian 421 (Mrk 421) using data from Metsähovi, Swift, Fermi-LAT, MAGIC, FACT, and other collaborations and instruments from 2014 November till 2016 June. Mrk 421 did not show any prominent flaring activity, but exhibited periods of historically low activity above 1 TeV (F>1 TeV 0.1 TeV) γ-rays, which, despite the low activity, show a significant positive correlation with no time lag. The HRkeV and HRTeV show the harder-when-brighter trend observed in many blazars, but the trend flattens at the highest fluxes, which suggests a change in the processes dominating the blazar variability. Enlarging our data set with data from years 2007 to 2014, we measured a positive correlation between the optical and the GeV emission over a range of about 60 d centred at time lag zero, and a positive correlation between the optical/GeV and the radio emission over a range of about 60 d centred at a time lag of 43+9-6 d. This observation is consistent with the radio-bright zone being located about 0.2 parsec downstream from the optical/GeV emission regions of the jet. The flux distributions are better described with a lognormal function in most of the energy bands probed, indicating that the variability in Mrk 421 is likely produced by a multiplicative process.The financial support of the German BMBF and MPG; the Italian INFN and INAF; the Swiss National Fund SNF; the ERDF under the Spanish MINECO (FPA2017-87859-P, FPA2017-85668-P, FPA2017-82729-C6-2-R, FPA2017-82729-C6-6-R, FPA2017-82729-C6-5-R, AYA2015-71042-P, AYA2016-76012-C3-1-P, ESP2017-87055-C2-2-P, FPA2017-90566-REDC); the Indian Department of Atomic Energy; the Japanese ICRR, the University of Tokyo, JSPS, and MEXT; the Bulgarian Ministry of Education and Science, National RI Roadmap Project DO1-268/16.12.2019 and the Academy of Finland grant nr. 320045 is gratefully acknowledged. This work was also supported by the Spanish Centro de Excelencia ‘Severo Ochoa’ SEV-2016-0588 and SEV-2015-0548, the Unidad de Excelencia ‘María de Maeztu’ MDM-2014-0369 and the ‘la Caixa’ Foundation (fellowship LCF/BQ/PI18/11630012), by the Croatian Science Foundation (HrZZ) Project IP-2016-06-9782 and the University of Rijeka Project 13.12.1.3.02, by the DFG Collaborative Research Centers SFB823/C4 and SFB876/C3, the Polish National Research Centre grant UMO-2016/22/M/ST9/00382 and by the Brazilian MCTIC, CNPq, and FAPERJ

From START to FINISH : the influence of osmotic stress on the cell cycle

Peer reviewedPublisher PD