Asymmetric neurotransmitter release enables rapid odor lateralization in Drosophila

In Drosophila, most individual olfactory receptor neurons (ORNs) project bilaterally to both sides of the brain1,2. Having bilateral rather than unilateral projections may represent a useful redundancy. However, bilateral ORN projections to the brain should also compromise the ability to lateralize odors. Nevertheless, walking or flying Drosophila reportedly turn toward their more strongly stimulated antenna3-5. Here we show that each ORN spike releases ~40% more neurotransmitter from the axon branch ipsilateral to the soma, as compared to the contralateral branch. As a result, when an odor activates the antennae asymmetrically, ipsilateral central neurons begin to spike a few milliseconds before contralateral neurons, and ipsilateral central neurons also fire at a 30-50% higher rate. We show that a walking fly can detect a 5% asymmetry in total ORN input to its left and right antennal lobes, and can turn toward the odor in less time than it requires the fly to complete a stride. These results demonstrate that neurotransmitter release properties can be tuned independently at output synapses formed by a single axon onto two target cells with identical functions and morphologies. Our data also show that small differences in spike timing and spike rate can produce reliable differences in olfactory behavior

Identification of interleukin-27 (IL-27)/IL-27 receptor subunit alpha as a critical immune axis for in vivo hiv control

Intact and broad immune cell effector functions and specific individual cytokines have been linked to HIV disease outcome, but their relative contribution to HIV control remains unclear. We asked whether the proteome of secreted cytokines and signaling factors in peripheral blood can be used to discover specific pathways critical for host viral control. A custom glass-based microarray, able to measure >600 plasma proteins involved in cell-to-cell communication, was used to measure plasma protein profiles in 96 HIV-infected, treatment-naive individuals with high (> 50,000) or low (<10,000 HIV RNA copies/ml) viral loads. Univariate and regression model analysis demonstrate that plasma levels of soluble interleukin-27 (IL-27) are significantly elevated in individuals with high plasma viremia (P < 0.0001) and are positively correlated with proviral HIV-DNA copy numbers in peripheral blood mononuclear cells (PBMC) (Rho = 0.4011; P = 0.0027). Moreover, soluble IL-27 plasma levels are negatively associated with the breadth and magnitude of the total virus-specific T-cell responses and directly with plasma levels of molecules involved in Wnt/beta-catenin signaling. In addition to IL-27, gene expression levels of the specific IL-27 receptor (IL27RA) in PBMC correlated directly with both plasma viral load (Rho = 0.3531; P = 0.0218) and the proviral copy number in the peripheral blood as an indirect measure of partial viral reservoir (Rho = 0.4580; P = 0.0030). These results were validated in unrelated cohorts of early infected subjects as well as subjects before and after initiation of antiretroviral treatment, and they identify IL-27 and its specific receptor as a critical immune axis for the antiviral immune response and as robust correlates of viral load and proviral reservoir size in PBMC. IMPORTANCE The detailed knowledge of immune mechanisms that contribute to HIV control is a prerequisite for the design of effective treatment strategies to achieve HIV cure. Cells communicate with each other by secreting signaling proteins, and the blood is a key conduit for transporting such factors. Investigating the communication factors promoting effective immune responses and having potentially antiviral functions against HIV using a novel focused omics approach (Peer ReviewedPostprint (published version

Youth political participation in Russia: influence of voluntary associations

The purpose of this research is to determine the relationship, in Russia, between participation in voluntary associations during education and political participation during adulthoo

Structural Disorder Provides Increased Adaptability for Vesicle Trafficking Pathways

Vesicle trafficking systems play essential roles in the communication between the organelles of eukaryotic cells and also between cells and their environment. Endocytosis and the late secretory route are mediated by clathrin-coated vesicles, while the COat Protein I and II (COPI and COPII) routes stand for the bidirectional traffic between the ER and the Golgi apparatus. Despite similar fundamental organizations, the molecular machinery, functions, and evolutionary characteristics of the three systems are very different. In this work, we compiled the basic functional protein groups of the three main routes for human and yeast and analyzed them from the structural disorder perspective. We found similar overall disorder content in yeast and human proteins, confirming the well-conserved nature of these systems. Most functional groups contain highly disordered proteins, supporting the general importance of structural disorder in these routes, although some of them seem to heavily rely on disorder, while others do not. Interestingly, the clathrin system is significantly more disordered (,23%) than the other two, COPI (,9%) and COPII (,8%). We show that this structural phenomenon enhances the inherent plasticity and increased evolutionary adaptability of the clathrin system, which distinguishes it from the other two routes. Since multi-functionality (moonlighting) is indicative of both plasticity and adaptability, we studied its prevalence in vesicle trafficking proteins and correlated it with structural disorder. Clathrin adaptors have the highest capability for moonlighting while also comprising the most highly disordered members. The ability to acquire tissue specific functions was also used to approach adaptability: clathrin route genes have the most tissue specific exons encoding for protein segments enriched in structural disorder and interaction sites. Overall, our results confirm the general importance of structural disorder in vesicle trafficking and suggest major roles for this structural property in shaping the differences of evolutionary adaptability in the three routes

Lyme Disease and YouTube™: A Cross-Sectional Study of Video Contents

Objectives: Lyme disease is the most common tick-borne disease. People seek health information on Lyme disease from YouTubeTM videos. In this study, we investigated if the contents of Lyme disease-related YouTubeTM videos varied by their sources. Methods: Most viewed English YouTubeTM videos (n = 100) were identified and manually coded for contents and sources. Results: Within the sample, 40 videos were consumer-generated, 31 were internet-based news, 16 were professional, and 13 were TV news. Compared with consumer-generated videos, TV news videos were more likely to mention celebrities (odds ratio [OR], 10.57; 95% confidence interval [CI], 2.13–52.58), prevention of Lyme disease through wearing protective clothing (OR, 5.63; 95% CI, 1.23–25.76), and spraying insecticides (OR, 7.71; 95% CI, 1.52–39.05). Conclusion: A majority of the most popular Lyme disease-related YouTubeTM videos were not created by public health professionals. Responsible reporting and creative video-making facilitate Lyme disease education. Partnership with YouTubeTM celebrities to co-develop educational videos may be a future direction

Identification of Interleukin-27 (IL-27)/IL-27 Receptor Subunit Alpha as a Critical Immune Axis for In Vivo HIV Control

Intact and broad immune cell effector functions and specific individual cytokines have been linked to HIV disease outcome, but their relative contribution to HIV control remains unclear. We asked whether the proteome of secreted cytokines and signaling factors in peripheral blood can be used to discover specific pathways critical for host viral control. A custom glass-based microarray, able to measure >600 plasma proteins involved in cell-to-cell communication, was used to measure plasma protein profiles in 96 HIV-infected, treatment-naive individuals with high (>50,000) or low (600 soluble proteins, our data highlight the importance of Th17 cells and Wnt/β-catenin signaling in HIV control and especially identify the IL-27/IL-27 receptor subunit alpha (IL-27RA) axis as a predictor of plasma viral load and proviral copy number in the peripheral blood. These data may provide important guidance to therapeutic approaches in the HIV cure agenda

Identification of Interleukin-27 (IL-27)/IL-27 Receptor Subunit Alpha as a Critical Immune Axis for In Vivo HIV Control

Intact and broad immune cell effector functions and specific individual cytokines have been linked to HIV disease outcome, but their relative contribution to HIV control remains unclear. We asked whether the proteome of secreted cytokines and signaling factors in peripheral blood can be used to discover specific pathways critical for host viral control. A custom glass-based microarray, able to measure >600 plasma proteins involved in cell-to-cell communication, was used to measure plasma protein profiles in 96 HIV-infected, treatment-naive individuals with high (>50,000) or low (600 soluble proteins, our data highlight the importance of Th17 cells and Wnt/β-catenin signaling in HIV control and especially identify the IL-27/IL-27 receptor subunit alpha (IL-27RA) axis as a predictor of plasma viral load and proviral copy number in the peripheral blood. These data may provide important guidance to therapeutic approaches in the HIV cure agenda

Parents and their Student Children in the Urals Foreshorten Material and Mone-Tary Relationship

The tendency of turning the educational system in Russian Feder-ation onto commercial basis for parental families from the authors‘ perspective creates and develops harmful for economics (and not only for it) immediate association of the quality of education and basicly socialization (professional firstly) with the level of material wellbeing of different groups of people. It is underlined in the article that material and monetary relationship of ―Fathers and Sons‖ are not limited by money-focused offsets. Material bounds usually are tightly interlaced with the spiritual ones building the system of interfamily interinfluence during which the compulsory component of social progressive development – generation succession – is carried out. Authors‘interrogations results held in some Urals‘ universities show that the majority of Urals students lacking money are not actually striving (―not bursting for more action‖) to ―fix financial matters‖ by means of their own labor efforts – extra-curricular work. Consumer‘s position formed during school years to solve the vital problems by means of ―parental purse‖ does not actually change while studying in college.Тенденция перевода системы образования в РФ на платную для роди-тедьских семей основу, по мнению авторов статьи, создает и воспроизводит в РФ опасную для экономики (и не только для нее) непосредственную зависимость качества процесса образования и, в конечном итоге, социализации (в первую очередь, профессиоональной) от уровня материальной обеспеченности различных групп населения. В статье подчеркивается, что материально-денежные отношения «отцов и детей» не ограничиваются лишь их «меркантильными взаиморасчетами». Материальные скрепы, как правило, тесно «переплетаются» с «духовными», выстраивая систему внутрисемейного взаимовлияния, в процессе которого реализуется обязательная компонента пргрессивного развития социума - преемственность поколений. Результаты опросов авторов, проведенных в ряде уральских ВУЗов, показывают, что большинство уральских студентов, испытывая дефицит денежных средств» особо не стремятся («не рвутся») «поправить свои финансовые дела» за счет собственных трудовых усилий - внеучебной трудозанятости. Устоявшаяся за предыдущие школьные годы потребительская позиция решать свои насущные потребности за счет «родительского кошелька» не претерпевает особых изменнений и за период учебы в ВУЗе

Van Gogh and Frizzled Act Redundantly in the Drosophila Sensory Organ Precursor Cell to Orient Its Asymmetric Division

Drosophila sensory organ precursor cells (SOPs) divide asymmetrically along the anterior-posterior (a-p) body axis to generate two different daughter cells. Planar Cell Polarity (PCP) regulates the a-p orientation of the SOP division. The localization of the PCP proteins Van Gogh (Vang) and Frizzled (Fz) define anterior and posterior apical membrane domains prior to SOP division. Here, we investigate the relative contributions of Vang, Fz and Dishevelled (Dsh), a membrane-associated protein acting downstream of Fz, in orienting SOP polarity. Genetic and live imaging analyses suggest that Dsh restricts the localization of a centrosome-attracting activity to the anterior cortex and that Vang is a target of Dsh in this process. Using a clone border assay, we provide evidence that the Vang and fz genes act redundantly in SOPs to orient its polarity axis in response to extrinsic local PCP cues. Additionally, we find that the activity of Vang is dispensable for the non-autonomous polarizing activity of fz. These observations indicate that both Vang and Fz act as cues for downstream effectors orienting the planar polarity axis of dividing SOPs