Immunoinformatics: Predicting Peptide–MHC Binding

Immunoinformatics is a discipline that applies methods of computer science to study and model the immune system. A fundamental question addressed by immunoinformatics is how to understand the rules of antigen presentation by MHC molecules to T cells, a process that is central to adaptive immune responses to infections and cancer. In the modern era of personalized medicine, the ability to model and predict which antigens can be presented by MHC is key to manipulating the immune system and designing strategies for therapeutic intervention. Since the MHC is both polygenic and extremely polymorphic, each individual possesses a personalized set of MHC molecules with different peptide-binding specificities, and collectively they present a unique individualized peptide imprint of the ongoing protein metabolism. Mapping all MHC allotypes is an enormous undertaking that cannot be achieved without a strong bioinformatics component. Computational tools for the prediction of peptide?MHC binding have thus become essential in most pipelines for T cell epitope discovery and an inescapable component of vaccine and cancer research. Here, we describe the development of several such tools, from pioneering efforts to the current state-of-the-art methods, that have allowed for accurate predictions of peptide binding of all MHC molecules, even including those that have not yet been characterized experimentally.Fil: Nielsen, Morten. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina. Technical University of Denmark; DinamarcaFil: Andreatta, Massimo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Peters, Bjoern. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Buus, Søren. Universidad de Copenhagen; Dinamarc

Lymphatic Filariasis Control in Tanzania: Effect of Six Rounds of Mass Drug Administration with Ivermectin and Albendazole on Infection and Transmission.

Control of lymphatic filariasis (LF) in most countries of sub-Saharan Africa is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. We present findings from a detailed study on the effect of six rounds of MDA with this drug combination as implemented by the National Lymphatic Filariasis Elimination Programme (NLFEP) in a highly endemic rural area of north-eastern Tanzania.\ud The effect of treatment on transmission and human infection was monitored in a community- and a school-based study during an 8-year period (one pre-intervention and 7 post-intervention years) from 2003 to 2011. Before intervention, 24.5% of the community population had microfilariae (mf) in the blood, 53.3% had circulating filarial antigens (CFA) and 78.9% had specific antibodies to the recombinant filarial antigen Bm14. One year after the sixth MDA, these values had decreased considerably to 2.7%, 19.6% and 27.5%, respectively. During the same period, the CFA prevalence among new intakes of Standard 1 pupils in 10 primary schools decreased from 25.2% to 5.6%. In line with this, transmission by the three vectors (Anopheles gambiae, An. funestus and Culex quinquefasciatus) as determined by dissection declined sharply (overall vector infectivity rate by 99.3% and mean monthly transmission potential by 99.2% between pre-intervention and fifth post-intervention period). A major shift in vector species composition, from predominantly anopheline to almost exclusively culicine was observed over the years. This may be largely unrelated to the MDAs but may have important implications for the epidemiology of LF in the area. Six MDAs caused considerable decrease in all the measured indices for transmission and human infection. In spite of this, indices were still relatively high in the late period of the study, and it may take a long time to reach the recommended cut-off levels for interruption of transmission unless extra efforts are made. These should include increased engagement of the target population in the control activities, to ensure higher treatment coverage. It is expected that the recent initiative to distribute insecticide impregnated bed nets to every household in the area will also contribute towards reaching the goal of successful LF elimination

CHROMOSPHERICALLY ACTIVE STARS in the RAVE SURVEY. II. YOUNG DWARFS in the SOLAR NEIGHBORHOOD

© 2017. The American Astronomical Society. All rights reserved. A large sample of over 38,000 chromospherically active candidate solar-like stars and cooler dwarfs from the RAVE survey is addressed in this paper. An improved activity identification with respect to the previous study was introduced to build a catalog of field stars in the solar neighborhood with an excess emission flux in the calcium infrared triplet wavelength region. The central result of this work is the calibration of the age-activity relation for main-sequence dwarfs in a range from a few 10 Myr up to a few Gyr. It enabled an order of magnitude age estimation of the entire active sample. Almost 15,000 stars are shown to be younger than 1 Gyr and ∼2000 younger than 100 Myr. The young age of the most active stars is confirmed by their position off the main sequence in the J - K versus N UV - V diagram showing strong ultraviolet excess, mid-infrared excess in the J - K versus W 1 - W 2 diagram, and very cool temperatures (J - K < 0.7). They overlap with the reference pre-main-sequence RAVE stars often displaying X-ray emission. The activity level increasing with the color reveals their different nature from the solar-like stars and probably represents an underlying dynamo-generating magnetic fields in cool stars. Of the RAVE objects from DR5, 50% are found in the TGAS catalog and supplemented with accurate parallaxes and proper motions by Gaia. This makes the database of a large number of young stars in a combination with RAVE's radial velocities directly useful as a tracer of the very recent large-scale star formation history in the solar neighborhood. The data are available online in the Vizier database

Galactic kinematics from RAVE to Gaia-RVS Data

RAVE data has provided new results on Galactic kinematics like the kinematical decomposition of the Galactic disk. This decomposition permits to identify the different components of the disk and to characterize them in terms of scale height and scale length. With the data provided by Gaia and in particular the RVS, we will have a completly renewed view of the Galaxy. The precision of the RVS will permit to undertake a precise analysis of the kinematics of the Galactic disks. This knowledge will provide significant clues to constrain the scenarios of the Galactic disk formation

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

A hypothetico-deductive approach to assessing the social function of chemical signalling in a non-territorial solitary carnivore

The function of chemical signalling in non-territorial solitary carnivores is still relatively unclear. Studies on territorial solitary and social carnivores have highlighted odour capability and utility, however the social function of chemical signalling in wild carnivore populations operating dominance hierarchy social systems has received little attention. We monitored scent marking and investigatory behaviour of wild brown bears Ursus arctos, to test multiple hypotheses relating to the social function of chemical signalling. Camera traps were stationed facing bear ‘marking trees’ to document behaviour by different age sex classes in different seasons. We found evidence to support the hypothesis that adult males utilise chemical signalling to communicate dominance to other males throughout the non-denning period. Adult females did not appear to utilise marking trees to advertise oestrous state during the breeding season. The function of marking by subadult bears is somewhat unclear, but may be related to the behaviour of adult males. Subadults investigated trees more often than they scent marked during the breeding season, which could be a result of an increased risk from adult males. Females with young showed an increase in marking and investigation of trees outside of the breeding season. We propose the hypothesis that females engage their dependent young with marking trees from a young age, at a relatively ‘safe’ time of year. Memory, experience, and learning at a young age, may all contribute towards odour capabilities in adult bears

Chromospherically Active Stars in the RAVE Survey. II. Young dwarfs in the Solar neighborhood

A large sample of over 38,000 chromospherically active candidate solar-like stars and cooler dwarfs from the RAVE survey is addressed in this paper. An improved activity identification with respect to the previous study was introduced to build a catalog of field stars in the Solar neighborhood with an excess emission flux in the calcium infrared triplet wavelength region. The central result of this work is the calibration of the age--activity relation for the main sequence dwarfs in a range from a few $10 \; \mathrm{Myr}$ up to a few Gyr. It enabled an order of magnitude age estimation of the entire active sample. Almost 15,000 stars are shown to be younger than $1\;\mathrm{Gyr}$ and $\sim$2000 younger than $100\;\mathrm{Myr}$. The young age of the most active stars is confirmed by their position off the main sequence in the $J-K$ versus $N_{UV}-V$ diagram showing strong ultraviolet excess, mid-infrared excess in the $J-K$ versus $W_1-W_2$ diagram and very cool temperatures ($J-K>0.7$). They overlap with the reference pre-main sequence RAVE stars often displaying X-ray emission. The activity level increasing with the color reveals their different nature from the solar-like stars and probably represents an underlying dynamo generating magnetic fields in cool stars. 50\% of the RAVE objects from DR5 are found in the TGAS catalog and supplemented with accurate parallaxes and proper motions by Gaia. This makes the database of a large number of young stars in a combination with RAVE's radial velocities directly useful as a tracer of the very recent large-scale star formation history in the Solar neighborhood. The data are available online in the Vizier database