Structural basis for terminal loop recognition and stimulation of pri-miRNA-18a processing by hnRNP A1

International audiencePost-transcriptional mechanisms play a predominant role in the control of microRNA (miRNA) production. Recognition of the terminal loop of precursor miRNAs by RNA-binding proteins (RBPs) influences their processing; however, the mechanistic basis for how levels of individual or subsets of miRNAs are regulated is mostly unexplored. We previously showed that hnRNP A1, an RBP implicated in many aspects of RNA processing, acts as an auxiliary factor that promotes the Microprocessor-mediated processing of pri-mir-18a. Here, by using an integrative structural biology approach, we show that hnRNP A1 forms a 1:1 complex with pri-mir-18a where both RNA recognition motifs (RRMs) bind to cognate RNA sequence motifs in the terminal loop of pri-mir-18a. Terminal loop binding induces an allosteric destabilization of base-pairing in the pri-mir-18a stem that promotes its downstream processing. Our results highlight terminal loop RNA recognition by RBPs as a potential general principle of miRNA biogenesis and regulation

Evaluating the Psychometric Quality of Social Skills Measures: A Systematic Review

Introduction - Impairments in social functioning are associated with an array of adverse outcomes. Social skills measures are commonly used by health professionals to assess and plan the treatment of social skills difficulties. There is a need to comprehensively evaluate the quality of psychometric properties reported across these measures to guide assessment and treatment planning. Objective - To conduct a systematic review of the literature on the psychometric properties of social skills and behaviours measures for both children and adults. Methods - A systematic search was performed using four electronic databases: CINAHL, PsycINFO, Embase and Pubmed; the Health and Psychosocial Instruments database; and grey literature using PsycExtra and Google Scholar. The psychometric properties of the social skills measures were evaluated against the COSMIN taxonomy of measurement properties using pre-set psychometric criteria. Results - Thirty-Six studies and nine manuals were included to assess the psychometric properties of thirteen social skills measures that met the inclusion criteria. Most measures obtained excellent overall methodological quality scores for internal consistency and reliability. However, eight measures did not report measurement error, nine measures did not report cross-cultural validity and eleven measures did not report criterion validity. Conclusions - The overall quality of the psychometric properties of most measures was satisfactory. The SSBS-2, HCSBS and PKBS-2 were the three measures with the most robust evidence of sound psychometric quality in at least seven of the eight psychometric properties that were appraised. A universal working definition of social functioning as an overarching construct is recommended. There is a need for ongoing research in the area of the psychometric properties of social skills and behaviours instruments

Interplant Communication of Tomato Plants through Underground Common Mycorrhizal Networks

Plants can defend themselves to pathogen and herbivore attack by responding to chemical signals that are emitted by attacked plants. It is well established that such signals can be transferred through the air. In theory, plants can also communicate with each other through underground common mycorrhizal networks (CMNs) that interconnect roots of multiple plants. However, until now research focused on plant-to-plant carbon nutrient movement and there is no evidence that defense signals can be exchanged through such mycorrhizal hyphal networks. Here, we show that CMNs mediate plant-plant communication between healthy plants and pathogen-infected tomato plants (Lycopersicon esculentum Mill.). After establishment of CMNs with the arbuscular mycorrhizal fungus Glomus mosseae between tomato plants, inoculation of ‘donor’ plants with the pathogen Alternaria solani led to increases in disease resistance and activities of the putative defensive enzymes, peroxidase, polyphenol oxidase, chitinase, β-1,3-glucanase, phenylalanine ammonia-lyase and lipoxygenase in healthy neighbouring ‘receiver’ plants. The uninfected ‘receiver’ plants also activated six defence-related genes when CMNs connected ‘donor’ plants challenged with A. solani. This finding indicates that CMNs may function as a plant-plant underground communication conduit whereby disease resistance and induced defence signals can be transferred between the healthy and pathogen-infected neighbouring plants, suggesting that plants can ‘eavesdrop’ on defence signals from the pathogen-challenged neighbours through CMNs to activate defences before being attacked themselves

Specific Humoral Immunity versus Polyclonal B Cell Activation in Trypanosoma cruzi Infection of Susceptible and Resistant Mice

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, affects 10–12 million people in Latin America. Patent parasitemia develops during acute disease. During this phase, polyclonal B cell activation has been reported to generate high levels of serum antibody with low parasite specificity, and delayed protective humoral immunity, which is necessary to prevent the host from succumbing to infection. In this manuscript, data show that relatively resistant mice have improved parasite-specific humoral immunity and decreased polyclonal B cell activation compared to susceptible mice. Parasite-specific humoral immunity was associated with differential expansion of B cell subsets and T cells in the spleen, as well as with increased Th1 and decreased Th2 cytokine production. These data suggest that host susceptibility/genetic biases impact the development of humoral responses to infection. Th2 cytokines are generally associated with improved antibody responses. In the context of T. cruzi infection of susceptible mice, Th2 cytokines were associated with increased total antibody production concomitant with delayed pathogen-specific humoral immunity. This study highlights the need to consider the effect of host biases when investigating humoral immunity to any pathogen that has reported polyclonal B cell activation during infection

History of clinical transplantation

The emergence of transplantation has seen the development of increasingly potent immunosuppressive agents, progressively better methods of tissue and organ preservation, refinements in histocompatibility matching, and numerous innovations is surgical techniques. Such efforts in combination ultimately made it possible to successfully engraft all of the organs and bone marrow cells in humans. At a more fundamental level, however, the transplantation enterprise hinged on two seminal turning points. The first was the recognition by Billingham, Brent, and Medawar in 1953 that it was possible to induce chimerism-associated neonatal tolerance deliberately. This discovery escalated over the next 15 years to the first successful bone marrow transplantations in humans in 1968. The second turning point was the demonstration during the early 1960s that canine and human organ allografts could self-induce tolerance with the aid of immunosuppression. By the end of 1962, however, it had been incorrectly concluded that turning points one and two involved different immune mechanisms. The error was not corrected until well into the 1990s. In this historical account, the vast literature that sprang up during the intervening 30 years has been summarized. Although admirably documenting empiric progress in clinical transplantation, its failure to explain organ allograft acceptance predestined organ recipients to lifetime immunosuppression and precluded fundamental changes in the treatment policies. After it was discovered in 1992 that long-surviving organ transplant recipient had persistent microchimerism, it was possible to see the mechanistic commonality of organ and bone marrow transplantation. A clarifying central principle of immunology could then be synthesized with which to guide efforts to induce tolerance systematically to human tissues and perhaps ultimately to xenografts

All-sky search for gravitational-wave bursts in the second joint LIGO-Virgo run

We present results from a search for gravitational-wave bursts in the data collected by the LIGO and Virgo detectors between July 7, 2009 and October 20, 2010: data are analyzed when at least two of the three LIGO-Virgo detectors are in coincident operation, with a total observation time of 207 days. The analysis searches for transients of duration < 1 s over the frequency band 64-5000 Hz, without other assumptions on the signal waveform, polarization, direction or occurrence time. All identified events are consistent with the expected accidental background. We set frequentist upper limits on the rate of gravitational-wave bursts by combining this search with the previous LIGO-Virgo search on the data collected between November 2005 and October 2007. The upper limit on the rate of strong gravitational-wave bursts at the Earth is 1.3 events per year at 90% confidence. We also present upper limits on source rate density per year and Mpc^3 for sample populations of standard-candle sources. As in the previous joint run, typical sensitivities of the search in terms of the root-sum-squared strain amplitude for these waveforms lie in the range 5 10^-22 Hz^-1/2 to 1 10^-20 Hz^-1/2. The combination of the two joint runs entails the most sensitive all-sky search for generic gravitational-wave bursts and synthesizes the results achieved by the initial generation of interferometric detectors.Comment: 15 pages, 7 figures: data for plots and archived public version at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=70814&version=19, see also the public announcement at http://www.ligo.org/science/Publication-S6BurstAllSky