Antagonistic paralogs control a switch between growth and pathogen resistance in C. elegans

Immune genes are under intense, pathogen-induced pressure, which causes these genes to diversify over evolutionary time and become species-specific. Through a forward genetic screen we recently described a C. elegans-specific gene called pals-22 to be a repressor of “Intracellular Pathogen Response” or IPR genes. Here we describe pals-25, which, like pals-22, is a species-specific gene of unknown biochemical function. We identified pals-25 in a screen for suppression of pals-22 mutant phenotypes and found that mutations in pals-25 suppress all known phenotypes caused by mutations in pals-22. These phenotypes include increased IPR gene expression, thermotolerance, and immunity against natural pathogens, including Nematocida parisii microsporidia and the Orsay virus. Mutations in pals-25 also reverse the reduced lifespan and slowed growth of pals-22 mutants. Transcriptome analysis indicates that pals-22 and pals-25 control expression of genes induced not only by natural pathogens of the intestine, but also by natural pathogens of the epidermis. Indeed, in an independent forward genetic screen we identified pals-22 as a repressor and pals-25 as an activator of epidermal defense gene expression. In summary, the species-specific pals-22 and pals-25 genes act as a switch to regulate a program of gene expression, growth, and defense against diverse natural pathogens in C. elegans

Integrating personality research and animal contest theory: aggressiveness in the green swordtail <i>Xiphophorus helleri</i>

&lt;p&gt;Aggression occurs when individuals compete over limiting resources. While theoretical studies have long placed a strong emphasis on context-specificity of aggression, there is increasing recognition that consistent behavioural differences exist among individuals, and that aggressiveness may be an important component of individual personality. Though empirical studies tend to focus on one aspect or the other, we suggest there is merit in modelling both within-and among-individual variation in agonistic behaviour simultaneously. Here, we demonstrate how this can be achieved using multivariate linear mixed effect models. Using data from repeated mirror trials and dyadic interactions of male green swordtails, &lt;i&gt;Xiphophorus helleri&lt;/i&gt;, we show repeatable components of (co)variation in a suite of agonistic behaviour that is broadly consistent with a major axis of variation in aggressiveness. We also show that observed focal behaviour is dependent on opponent effects, which can themselves be repeatable but were more generally found to be context specific. In particular, our models show that within-individual variation in agonistic behaviour is explained, at least in part, by the relative size of a live opponent as predicted by contest theory. Finally, we suggest several additional applications of the multivariate models demonstrated here. These include testing the recently queried functional equivalence of alternative experimental approaches, (e. g., mirror trials, dyadic interaction tests) for assaying individual aggressiveness.&lt;/p&gt

Physical activity to improve cognition in older adults: can physical activity programs enriched with cognitive challenges enhance the effects? A systematic review and meta-analysis

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A flexible coupling approach to multi-agent planning under incomplete information

The final publication is available at Springer via http://dx.doi.org/10.1007/s10115-012-0569-7Multi-agent planning (MAP) approaches are typically oriented at solving loosely coupled problems, being ineffective to deal with more complex, strongly related problems. In most cases, agents work under complete information, building complete knowledge bases. The present article introduces a general-purpose MAP framework designed to tackle problems of any coupling levels under incomplete information. Agents in our MAP model are partially unaware of the information managed by the rest of agents and share only the critical information that affects other agents, thus maintaining a distributed vision of the task. Agents solve MAP tasks through the adoption of an iterative refinement planning procedure that uses single-agent planning technology. In particular, agents will devise refinements through the partial-order planning paradigm, a flexible framework to build refinement plans leaving unsolved details that will be gradually completed by means of new refinements. Our proposal is supported with the implementation of a fully operative MAP system and we show various experiments when running our system over different types of MAP problems, from the most strongly related to the most loosely coupled.This work has been partly supported by the Spanish MICINN under projects Consolider Ingenio 2010 CSD2007-00022 and TIN2011-27652-C03-01, and the Valencian Prometeo project 2008/051.Torreño Lerma, A.; Onaindia De La Rivaherrera, E.; Sapena Vercher, O. (2014). A flexible coupling approach to multi-agent planning under incomplete information. 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Speech and Non-Speech Audio-Visual Illusions: A Developmental Study

It is well known that simultaneous presentation of incongruent audio and visual stimuli can lead to illusory percepts. Recent data suggest that distinct processes underlie non-specific intersensory speech as opposed to non-speech perception. However, the development of both speech and non-speech intersensory perception across childhood and adolescence remains poorly defined. Thirty-eight observers aged 5 to 19 were tested on the McGurk effect (an audio-visual illusion involving speech), the Illusory Flash effect and the Fusion effect (two audio-visual illusions not involving speech) to investigate the development of audio-visual interactions and contrast speech vs. non-speech developmental patterns. Whereas the strength of audio-visual speech illusions varied as a direct function of maturational level, performance on non-speech illusory tasks appeared to be homogeneous across all ages. These data support the existence of independent maturational processes underlying speech and non-speech audio-visual illusory effects

Cerebral small vessel disease: capillary pathways to stroke and cognitive decline

Cerebral small vessel disease (SVD) gives rise to one in five strokes worldwide and constitutes a major source of cognitive decline in the elderly. SVD is known to occur in relation to hypertension, diabetes, smoking, radiation therapy and in a range of inherited and genetic disorders, autoimmune disorders, connective tissue disorders, and infections. Until recently, changes in capillary patency and blood viscosity have received little attention in the aetiopathogenesis of SVD and the high risk of subsequent stroke and cognitive decline. Capillary flow patterns were, however, recently shown to limit the extraction efficacy of oxygen in tissue and capillary dysfunction therefore proposed as a source of stroke-like symptoms and neurodegeneration, even in the absence of physical flow-limiting vascular pathology. In this review, we examine whether capillary flow disturbances may be a shared feature of conditions that represent risk factors for SVD. We then discuss aspects of capillary dysfunction that could be prevented or alleviated and therefore might be of general benefit to patients at risk of SVD, stroke or cognitive decline

Deep RNA Sequencing Reveals Novel Cardiac Transcriptomic Signatures for Physiological and Pathological Hypertrophy

Although both physiological hypertrophy (PHH) and pathological hypertrophy (PAH) of the heart have similar morphological appearances, only PAH leads to fatal heart failure. In the present study, we used RNA sequencing (RNA-Seq) to determine the transcriptomic signatures for both PHH and PAH. Approximately 13–20 million reads were obtained for both models, among which PAH showed more differentially expressed genes (DEGs) (2,041) than PHH (245). The expression of 417 genes was barely detectable in the normal heart but was suddenly activated in PAH. Among them, Foxm1 and Plk1 are of particular interest, since Ingenuity Pathway Analysis (IPA) using DEGs and upstream motif analysis showed that they are essential hub proteins that regulate the expression of downstream proteins associated with PAH. Meanwhile, 52 genes related to collagen, chemokines, and actin showed opposite expression patterns between PHH and PAH. MAZ-binding motifs were enriched in the upstream region of the participating genes. Alternative splicing (AS) of exon variants was also examined using RNA-Seq data for PAH and PHH. We found 317 and 196 exon inclusions and exon exclusions, respectively, for PAH, and 242 and 172 exon inclusions and exclusions, respectively for PHH. The AS pattern was mostly related to gains or losses of domains, changes in activity, and localization of the encoded proteins. The splicing variants of 8 genes (i.e., Fhl1, Rcan1, Ndrg2, Synpo, Ttll1, Cxxc5, Egfl7, and Tmpo) were experimentally confirmed. Multilateral pathway analysis showed that the patterns of quantitative (DEG) and qualitative (AS) changes differ depending on the type of pathway in PAH and PHH. One of the most significant changes in PHH is the severe downregulation of autoimmune pathways accompanied by significant AS. These findings revealed the unique transcriptomic signatures of PAH and PHH and also provided a more comprehensive understanding at both the quantitative and qualitative levels

Comparative Genomic Analysis of Human Fungal Pathogens Causing Paracoccidioidomycosis

Paracoccidioides is a fungal pathogen and the cause of paracoccidioidomycosis, a health-threatening human systemic mycosis endemic to Latin America. Infection by Paracoccidioides, a dimorphic fungus in the order Onygenales, is coupled with a thermally regulated transition from a soil-dwelling filamentous form to a yeast-like pathogenic form. To better understand the genetic basis of growth and pathogenicity in Paracoccidioides, we sequenced the genomes of two strains of Paracoccidioides brasiliensis (Pb03 and Pb18) and one strain of Paracoccidioides lutzii (Pb01). These genomes range in size from 29.1 Mb to 32.9 Mb and encode 7,610 to 8,130 genes. To enable genetic studies, we mapped 94% of the P. brasiliensis Pb18 assembly onto five chromosomes. We characterized gene family content across Onygenales and related fungi, and within Paracoccidioides we found expansions of the fungal-specific kinase family FunK1. Additionally, the Onygenales have lost many genes involved in carbohydrate metabolism and fewer genes involved in protein metabolism, resulting in a higher ratio of proteases to carbohydrate active enzymes in the Onygenales than their relatives. To determine if gene content correlated with growth on different substrates, we screened the non-pathogenic onygenale Uncinocarpus reesii, which has orthologs for 91% of Paracoccidioides metabolic genes, for growth on 190 carbon sources. U. reesii showed growth on a limited range of carbohydrates, primarily basic plant sugars and cell wall components; this suggests that Onygenales, including dimorphic fungi, can degrade cellulosic plant material in the soil. In addition, U. reesii grew on gelatin and a wide range of dipeptides and amino acids, indicating a preference for proteinaceous growth substrates over carbohydrates, which may enable these fungi to also degrade animal biomass. These capabilities for degrading plant and animal substrates suggest a duality in lifestyle that could enable pathogenic species of Onygenales to transfer from soil to animal hosts.National Institute of Allergy and Infectious Diseases (U.S.)National Institutes of Health. Department of Health and Human Services (contract HHSN266200400001C)National Institutes of Health. Department of Health and Human Services(contract HHSN2722009000018C)Brazil. National Council for Scientific and Technological Developmen