Comparison of Immunogenicity in Rhesus Macaques of Transmitted-Founder, HIV-1 Group M Consensus, and Trivalent Mosaic Envelope Vaccines Formulated as a DNA Prime, NYVAC, and Envelope Protein Boost.

An effective human immunodeficiency virus type 1 (HIV-1) vaccine must induce protective antibody responses, as well as CD4(+) and CD8(+) T cell responses, that can be effective despite extraordinary diversity of HIV-1. The consensus and mosaic immunogens are complete but artificial proteins, computationally designed to elicit immune responses with improved cross-reactive breadth, to attempt to overcome the challenge of global HIV diversity. In this study, we have compared the immunogenicity of a transmitted-founder (T/F) B clade Env (B.1059), a global group M consensus Env (Con-S), and a global trivalent mosaic Env protein in rhesus macaques. These antigens were delivered using a DNA prime-recombinant NYVAC (rNYVAC) vector and Env protein boost vaccination strategy. While Con-S Env was a single sequence, mosaic immunogens were a set of three Envs optimized to include the most common forms of potential T cell epitopes. Both Con-S and mosaic sequences retained common amino acids encompassed by both antibody and T cell epitopes and were central to globally circulating strains. Mosaics and Con-S Envs expressed as full-length proteins bound well to a number of neutralizing antibodies with discontinuous epitopes. Also, both consensus and mosaic immunogens induced significantly higher gamma interferon (IFN-γ) enzyme-linked immunosorbent spot assay (ELISpot) responses than B.1059 immunogen. Immunization with these proteins, particularly Con-S, also induced significantly higher neutralizing antibodies to viruses than B.1059 Env, primarily to tier 1 viruses. Both Con-S and mosaics stimulated more potent CD8-T cell responses against heterologous Envs than did B.1059. Both antibody and cellular data from this study strengthen the concept of using in silico-designed centralized immunogens for global HIV-1 vaccine development strategies. IMPORTANCE: There is an increasing appreciation for the importance of vaccine-induced anti-Env antibody responses for preventing HIV-1 acquisition. This nonhuman primate study demonstrates that in silico-designed global HIV-1 immunogens, designed for a human clinical trial, are capable of eliciting not only T lymphocyte responses but also potent anti-Env antibody responses.

What keeps female problematic internet users busy online?

While problematic Internet use is recognized to be predominant among male adolescents, a female trend is gradually becoming apparent. Our study aimed at investigating the characteristics of female Internet users and distinguishing between the online activities of problematic and regular Internet users' on school days. Data were retrieved from a cross-sectional survey of a representative sample of 3067 8th graders in the canton of Vaud, Switzerland, that completed an online questionnaire in 2012. Only females were included. Based on the Internet addiction test, the sample was divided into regular (RUs) (IAT < 50, n = 1339) and problematic users (PIUs) (IAT ≥ 50, n = 201). Groups were compared regarding sociodemographic variables, online activities, devices used to access the Internet, substance use, and physical activity. Significant variables were included in a backward logistic regression. At the multivariate level, PIUs were more prone to spend time online for leisure activities (odds ratio [OR] 2.38) and to access the Internet through a smartphone (OR 1.79) or tablet (OR 1.84). PIUs were less likely to be physically active (OR 0.86) and more likely to present poor emotional well-being (OR 2.67) and to smoke (OR 1.88). CONCLUSION: A sizeable percentage of female adolescents are problematic Internet users. When performing a comprehensive biopsychosocial assessment, teenagers owning numerous devices to access the Internet, presenting other health-compromising behaviors or poor emotional well-being should be specifically targeted. WHAT IS KNOWN: ? Problematic Internet use has been found to be predominant among males. ? Specific online activities have been identified as being addictive for young men and women differently. ? Problematic Internet use is known to impact in several ways the general health and daily functioning of teenagers. What is New: ? A sizeable percentage of female adolescents are problematic Internet users. ? Tobacco use, poor well-being, as well as compact devices to access the Internet are positively related to problematic Internet use. ? In addition to their special interest in online social and communicational activities, female problematic Internet users also reported more online gambling.

Dispersal is a major driver of the latitudinal diversity gradient of Carnivora

AimUnderstanding the relative contribution of diversification rates (speciation and extinction) and dispersal in the formation of the latitudinal diversity gradient - the decrease in species richness with increasing latitude - is a main goal of biogeography. The mammalian order Carnivora, which comprises 286 species, displays the traditional latitudinal diversity gradient seen in almost all mammalian orders. Yet the processes driving high species richness in the tropics may be fundamentally different in this group from that in other mammalian groups. Indeed, a recent study suggested that in Carnivora, unlike in all other major mammalian orders, net diversification rates are not higher in the tropics than in temperate regions. Our goal was thus to understand the reasons why there are more species of Carnivora in the tropics. LocationWorld-wide. MethodsWe reconstructed the biogeographical history of Carnivora using a time-calibrated phylogeny of the clade comprising all terrestrial species and dispersal-extinction-cladogenesis models. We also analysed a fossil dataset of carnivoran genera to examine how the latitudinal distribution of Carnivora varied through time. ResultsOur biogeographical analyses suggest that Carnivora originated in the East Palaearctic (i.e. Central Asia, China) in the early Palaeogene. Multiple independent lineages dispersed to low latitudes following three main paths: toward Africa, toward India/Southeast Asia and toward South America via the Bering Strait. These dispersal events were probably associated with local extinctions at high latitudes. Fossil data corroborate a high-latitude origin of the group, followed by late dispersal events toward lower latitudes in the Neogene. Main conclusionsUnlike most other mammalian orders, which originated and diversified at low latitudes and dispersed out of the tropics', Carnivora originated at high latitudes, and subsequently dispersed southward. Our study provides an example of combining phylogenetic and fossil data to understand the generation and maintenance of global-scale geographical variations in species richness.

Finska ängskötselens hinder och hjelp

Invocatio: M.G.H.

L'Univers

1870/03/30 (Numéro 1059).

Sibelius-kuva ja sen metamorfoosi meillä ja muualla : vastaus Rabbe Forsmanille, Bo Marschnerille ja Veijo Murtomäelle

Causa Tawaststjerna ja Mäkelän kielitaito ; Joitain kommentteja pesutuvasta ; Lopuksi.

Rameaun suppositioteoria

Rameaun teoriat ja niiden vaikutus ; Nelisointujen muodostaminen ; Täydelliset ja septimittömät noonisoinnut ; Kvarttipidätykset ; Urkupiste ja kaksoissuppositio ; Traité ja suppositioteorian systematiikka ; Musiikillinen konteksti.

Moniääninen musiikinhistoria

Lectio praecursoria.

"Between me and myself" : äänellisen minän muotoutuminen Björkin kappaleessa Undo

Miten lähestyä laulajan tulkintaa? ; Empaattinen ja anlyyttinen kuunteleminen ; Sanallinen minä ja äänellinen minä ; Björkin äänen semioottinen ; Yrittäminen ja irtipäästäminen ; Muutoksen vastustaminen - pysähdykset äänen virtauksessa ; Kommentointia eleillä ja ilmeillä ; Musiikillinen hengästyminen ; Äänellinen minä monistuu ; Lauluäänen merkityksistä ; Moninainen Björk.

Melartinin Aino-oopperan reseptiohistoria

Musiikin reseptiotutkimuksen piirteitä ; Lähdeaineisto ja metodiset rajaukset ; Teoksen syntyhistoria ; Ensiesitys ja sen saama vastaanotto joulukuussa 1909 ; Savonlinnan ensimmäiset oopperajuhlat ja Ainon vastaanotto 1912 ; Ensimmäinen uusintaesitys itsenäisessä Suomessa ; Kalevalan juhlavuosi 1935 ja Sortavalan laulujuhlat ; Välirauhan aikainen esitys 1941 ; Oopperaan Aino liitetyt lajimääreet ja toistuvat attribuutit ; Melartin symbolistisen taiteen vaikutuspiirissä ; Symbolistiset tunnusmerkit ja niiden yhteenkietoutuminen Ainossa ; Epilogi.