Assembly of viral genomes from metagenomes

Viral infections remain a serious global health issue. Metagenomic approaches are increasingly used in the detection of novel viral pathogens but also to generate complete genomes of uncultivated viruses. In silico identification of complete viral genomes from sequence data would allow rapid phylogenetic characterization of these new viruses. Often, however, complete viral genomes are not recovered, but rather several distinct contigs derived from a single entity are, some of which have no sequence homology to any known proteins. De novo assembly of single viruses from a metagenome is challenging, not only because of the lack of a reference genome, but also because of intrapopulation variation and uneven or insufficient coverage. Here we explored different assembly algorithms, remote homology searches, genome-specific sequence motifs, k-mer frequency ranking, and coverage profile binning to detect and obtain viral target genomes from metagenomes. All methods were tested on 454-generated sequencing datasets containing three recently described RNA viruses with a relatively large genome which were divergent to previously known viruses from the viral families Rhabdoviridae and Coronaviridae. Depending on specific characteristics of the target virus and the metagenomic community, different assembly and in silico gap closure strategies were successful in obtaining near complete viral genomes.

The role of syllables in sign language production

The aim of the present study was to investigate the functional role of syllables in sign language and how the different phonological combinations influence sign production. Moreover, the influence of age of acquisition was evaluated. Deaf signers (native and non-native) of Catalan Signed Language (LSC) were asked in a picture-sign interference task to sign picture names while ignoring distractor-signs with which they shared two phonological parameters (out of three of the main sign parameters: Location, Movement, and Handshape). The results revealed a different impact of the three phonological combinations. While no effect was observed for the phonological combination Handshape-Location, the combination Handshape-Movement slowed down signing latencies, but only in the non-native group. A facilitatory effect was observed for both groups when pictures and distractors shared Location-Movement. Importantly, linguistic models have considered this phonological combination to be a privileged unit in the composition of signs, as syllables are in spoken languages. Thus, our results support the functional role of syllable units during phonological articulation in sign language production.

Spinal circuits can accommodate interaction torques during multijoint limb movements

The dynamic interaction of limb segments during movements that involve multiple joints creates torques in one joint due to motion about another. Evidence shows that such interaction torques are taken into account during the planning or control of movement in humans. Two alternative hypotheses could explain the compensation of these dynamic torques. One involves the use of internal models to centrally compute predicted interaction torques and their explicit compensation through anticipatory adjustment of descending motor commands. The alternative, based on the equilibrium-point hypothesis, claims that descending signals can be simple and related to the desired movement kinematics only, while spinal feedback mechanisms are responsible for the appropriate creation and coordination of dynamic muscle forces. Partial supporting evidence exists in each case. However, until now no model has explicitly shown, in the case of the second hypothesis, whether peripheral feedback is really sufficient on its own for coordinating the motion of several joints while at the same time accommodating intersegmental interaction torques. Here we propose a minimal computational model to examine this question. Using a biomechanics simulation of a two-joint arm controlled by spinal neural circuitry, we show for the first time that it is indeed possible for the neuromusculoskeletal system to transform simple descending control signals into muscle activation patterns that accommodate interaction forces depending on their direction and magnitude. This is achieved without the aid of any central predictive signal. Even though the model makes various simplifications and abstractions compared to the complexities involved in the control of human arm movements, the finding lends plausibility to the hypothesis that some multijoint movements can in principle be controlled even in the absence of internal models of intersegmental dynamics or learned compensatory motor signals.

Unveiling the factors shaping the distribution of widely distributed alpine vertebrates, using multi-scale ecological niche modelling of the bat Plecotus macrobullaris

Several alpine vertebrates share a distribution pattern that extends across the South-western Palearctic but is limited to the main mountain massifs. Although they are usually regarded as cold-adapted species, the range of many alpine vertebrates also includes relatively warm areas, suggesting that factors beyond climatic conditions may be driving their distribution. In this work we first recognize the species belonging to the mentioned biogeographic group and, based on the environmental niche analysis of Plecotus macrobullaris, we identify and characterize the environmental factors constraining their ranges. Distribution overlap analysis of 504 European vertebrates was done using the Sorensen Similarity Index, and we identified four birds and one mammal that share the distribution with P. macrobullaris. We generated 135 environmental niche models including different variable combinations and regularization values for P. macrobullaris at two different scales and resolutions. After selecting the best models, we observed that topographic variables outperformed climatic predictors, and the abruptness of the landscape showed better predictive ability than elevation. The best explanatory climatic variable was mean summer temperature, which showed that P. macrobullaris is able to cope with mean temperature ranges spanning up to 16 degrees C. The models showed that the distribution of P. macrobullaris is mainly shaped by topographic factors that provide rock-abundant and open-space habitats rather than climatic determinants, and that the species is not a cold-adapted, but rather a cold-tolerant eurithermic organism. P. macrobullaris shares its distribution pattern as well as several ecological features with five other alpine vertebrates, suggesting that the conclusions obtained from this study might be extensible to them. We concluded that rock-dwelling and open-space foraging vertebrates with broad temperature tolerance are the best candidates to show wide alpine distribution in the Western Palearctic.

Physiological modules for generating discrete and rhythmic movements: action identification by a dynamic recurrent neural network

In this study we employed a dynamic recurrent neural network (DRNN) in a novel fashion to reveal characteristics of control modules underlying the generation of muscle activations when drawing figures with the outstretched arm. We asked healthy human subjects to perform four different figure-eight movements in each of two workspaces (frontal plane and sagittal plane). We then trained a DRNN to predict the movement of the wrist from information in the EMG signals from seven different muscles. We trained different instances of the same network on a single movement direction, on all four movement directions in a single movement plane, or on all eight possible movement patterns and looked at the ability of the DRNN to generalize and predict movements for trials that were not included in the training set. Within a single movement plane, a DRNN trained on one movement direction was not able to predict movements of the hand for trials in the other three directions, but a DRNN trained simultaneously on all four movement directions could generalize across movement directions within the same plane. Similarly, the DRNN was able to reproduce the kinematics of the hand for both movement planes, but only if it was trained on examples performed in each one. As we will discuss, these results indicate that there are important dynamical constraints on the mapping of EMG to hand movement that depend on both the time sequence of the movement and on the anatomical constraints of the musculoskeletal system. In a second step, we injected EMG signals constructed from different synergies derived by the PCA in order to identify the mechanical significance of each of these components. From these results, one can surmise that discrete-rhythmic movements may be constructed from three different fundamental modules, one regulating the co-activation of all muscles over the time span of the movement and two others elliciting patterns of reciprocal activation operating in orthogonal directions.

Cerebral hemodynamics during graded Valsalva maneuvers

The Valsalva maneuver (VM) produces large and abrupt changes in mean arterial pressure (MAP) that challenge cerebral blood flow and oxygenation. We examined the effect of VM intensity on middle cerebral artery blood velocity (MCAv) and cortical oxygenation responses during (phases I-III) and following (phase IV) a VM. Healthy participants (n = 20 mean +/- SD: 27 +/- 7 years) completed 30 and 90% of their maximal VM mouth pressure for 10 s (order randomized) whilst standing. Beat-to-beat MCAv, cerebral oxygenation (NIRS) and MAP across the different phases of the VM are reported as the difference from standing baseline. There were significant interaction (phase * intensity) effects for MCAv, total oxygenation index (TOI) and MAP (all P < 0.01). MCAv decreased during phases II and III (P < 0.01), with the greatest decrease during phase III (-5 +/- 8 and -19 +/- 15 cm.s(-1) for 30 and 90% VM, respectively). This pattern was also evident in TOI (phase III: -1 +/- 1 and -5 +/- 4%, both P < 0.05). Phase IV increased MCAv (22 +/- 15 and 34 +/- 23 cm.s(-1)), MAP (15 +/- 14 and 24 +/- 17 mm Hg) and TOI (5 +/- 6 and 7 +/- 5%) relative to baseline (all P < 0.05). Cerebral autoregulation, indexed, as the % MCAv/%MAP ratio, showed a phase effect only (P < 0.001), with the least regulation during phase IV (2.4 +/- 3.0 and 3.2 +/- 2.9). These data illustrate that an intense VM profoundly affects cerebral hemodynamics, with a reactive hyperemia occurring during phase IV following modest ischemia during phases II and III.

The body social: an enactive approach to the self

This paper takes a new look at an old question: what is the human self? It offers a proposal for theorizing the self from an enactive perspective as an autonomous system that is constituted through interpersonal relations. It addresses a prevalent issue in the philosophy of cognitive science: the body-social problem. Embodied and social approaches to cognitive identity are in mutual tension. On the one hand, embodied cognitive science risks a new form of methodological individualism, implying a dichotomy not between the outside world of objects and the brain-bound individual but rather between body-bound individuals and the outside social world. On the other hand, approaches that emphasize the constitutive relevance of social interaction processes for cognitive identity run the risk of losing the individual in the interaction dynamics and of downplaying the role of embodiment. This paper adopts a middle way and outlines an enactive approach to individuation that is neither individualistic nor disembodied but integrates both approaches. Elaborating on Jonas' notion of needful freedom it outlines an enactive proposal to understanding the self as co-generated in interactions and relations with others. I argue that the human self is a social existence that is organized in terms of a back and forth between social distinction and participation processes. On this view, the body, rather than being identical with the social self, becomes its mediator

Never-resting microglia: physiological roles in the healthy brain and pathological implications

Microglia are largely known as the major orchestrators of the brain inflammatory response. As such, they have been traditionally studied in various contexts of disease, where their activation has been assumed to induce a wide range of detrimental effects. In the last few years, a series of discoveries have challenged the current view of microglia, showing their active and positive contribution to normal brain function. This Research Topic will review the novel physiological roles of microglia in the developing, mature and aging brain, under non-pathological conditions. In particular, this Research Topic will discuss the cellular and molecular mechanisms by which microglia contribute to the formation, pruning and plasticity of synapses; the maintenance of the blood brain barrier; the regulation of adult neurogenesis and hippocampal learning; and neuronal survival, among other important roles. Because these novel findings defy our understanding of microglial function in health as much as in disease, this Research Topic will also summarize the current view of microglial nomenclature, phenotypes, origin and differentiation, sex differences, and contribution to various brain pathologies. Additionally, novel imaging approaches and molecular tools to study microglia in their non-activated state will be discussed. In conclusion, this Research Topic seeks to emphasize how the current research in neuroscience is challenged by never-resting microglia.

Modeling habits as self-sustaining patterns of sensorimotor behavior

In the recent history of psychology and cognitive neuroscience, the notion of habit has been reduced to a stimulus-triggered response probability correlation. In this paper we use a computational model to present an alternative theoretical view (with some philosophical implications), where habits are seen as self-maintaining patterns of behavior that share properties in common with self-maintaining biological processes, and that inhabit a complex ecological context, including the presence and influence of other habits. Far from mechanical automatisms, this organismic and self-organizing concept of habit can overcome the dominating atomistic and statistical conceptions, and the high temporal resolution effects of situatedness, embodiment and sensorimotor loops emerge as playing a more central, subtle and complex role in the organization of behavior. The model is based on a novel "iterant deformable sensorimotor medium (IDSM)," designed such that trajectories taken through sensorimotor-space increase the likelihood that in the future, similar trajectories will be taken. We couple the IDSM to sensors and motors of a simulated robot, and show that under certain conditions, the IDSM conditions, the IDSM forms self-maintaining patterns of activity that operate across the IDSM, the robot's body, and the environment. We present various environments and the resulting habits that form in them. The model acts as an abstraction of habits at a much needed sensorimotor "meso-scale" between microscopic neuron-based models and macroscopic descriptions of behavior. Finally, we discuss how this model and extensions of it can help us understand aspects of behavioral self-organization, historicity and autonomy that remain out of the scope of contemporary representationalist frameworks.

We can work it out: an enactive look at cooperation

The past years have seen an increasing debate on cooperation and its unique human character. Philosophers and psychologists have proposed that cooperative activities are characterized by shared goals to which participants are committed through the ability to understand each other’s intentions. Despite its popularity, some serious issues arise with this approach to cooperation. First, one may challenge the assumption that high-level mental processes are necessary for engaging in acting cooperatively. If they are, then how do agents that do not possess such ability (preverbal children, or children with autism who are often claimed to be mind-blind) engage in cooperative exchanges, as the evidence suggests? Secondly, to define cooperation as the result of two de-contextualized minds reading each other’s intentions may fail to fully acknowledge the complexity of situated, interactional dynamics and the interplay of variables such as the participants’ relational and personal history and experience. In this paper we challenge such accounts of cooperation, calling for an embodied approach that sees cooperation not only as an individual attitude toward the other, but also as a property of interaction processes. Taking an enactive perspective, we argue that cooperation is an intrinsic part of any interaction, and that there can be cooperative interaction before complex communicative abilities are achieved. The issue then is not whether one is able or not to read the other’s intentions, but what it takes to participate in joint action. From this basic account, it should be possible to build up more complex forms of cooperation as needed. Addressing the study of cooperation in these terms may enhance our understanding of human social development, and foster our knowledge of different ways of engaging with others, as in the case of autism.

Mindfulness training for reducing anger, anxiety, and depression in fibromyalgia patients

Fibromyalgia is a disabling syndrome. Results obtained with different therapies are very limited to date.The goal of this study was to verify whether the application of a mindfulnessbased training program was effective in modifying anger, anxiety, and depression levels in a group of women diagnosed with fibromyalgia. This study is an experimental trial that employed a waiting list control group. Measures were taken at three different times: pretest, posttest, and follow-up. The statistical analyses revealed a significant reduction of anger (trait) levels, internal expression of anger, state anxiety, and depression in the experimental group as compared to the control group, as well as a significant increase in internal control of anger. It can be concluded that the mindfulness-based treatment was effective after 7 weeks. These results were maintained 3 months after the end of the intervention.

Bipolar disorder comorbid with alcohol use disorder: Focus on neurocognitive correlates

Bipolar disorder (BD) and alcohol use disorders (AUDs) are usually comorbid, and both have been associated with significant neurocognitive impairment. Patients with the BD-AUD comorbidity (dual diagnosis) may have more severe neurocognitive deficits than those with a single diagnosis, but there is paucity of research in this area. To explore this hypothesis more thoroughly, we carried out a systematic literature review through January 2015. Eight studies have examined the effect of AUDs on the neurocognitive functioning of BD patients. Most studies found that BD patients with current or past history of comorbid AUDs show more severe impairments, especially in verbal memory and executive cognition, than their non-dual counterparts. Greater neurocognitive dysfunction is another facet of this severe comorbid presentation. Implications for clinical practice and research are discussed. Specifically, the application of holistic approaches, such as clinical staging and systems biology, may open new avenues of discoveries related to the BD-AUD comorbidity.

Mass spectrometry coupled to imaging techniques: The better the view the greater the challenge

These are definitively exciting times for membrane lipid researchers. Once considered just as the cell membrane building blocks, the important role these lipids play is steadily being acknowledged. The improvement occurred in mass spectrometry techniques (MS) allows the establishment of the precise lipid composition of biological extracts. However, to fully understand the biological function of each individual lipid species, we need to know its spatial distribution and dynamics. In the past 10 years, the field has experienced a profound revolution thanks to the development of MS-based techniques allowing lipid imaging (MSI). Images reveal and verify what many lipid researchers had already shown by different means, but none as convincing as an image: each cell type presents a specific lipid composition, which is highly sensitive to its physiological and pathological state. While these techniques will help to place membrane lipids in the position they deserve, they also open the black box containing all the unknown regulatory mechanisms accounting for such tailored lipid composition. Thus, these results urges to different disciplines to redefine their paradigm of study by including the complexity revealed by the MSI techniques.

Physiological modules for generating discrete and rhythmic movements: Component analysis of EMG signals

A central question in Neuroscience is that of how the nervous system generates the spatiotemporal commands needed to realize complex gestures, such as handwriting. A key postulate is that the central nervous system (CNS) builds up complex movements from a set of simpler motor primitives or control modules. In this study we examined the control modules underlying the generation of muscle activations when performing different types of movement: discrete, point-to-point movements in eight different directions and continuous figure-eight movements in both the normal, upright orientation and rotated 90 degrees. To test for the effects of biomechanical constraints, movements were performed in the frontal-parallel or sagittal planes, corresponding to two different nominal flexion/abduction postures of the shoulder. In all cases we measured limb kinematics and surface electromyographic activity (EMB) signals for seven different muscles acting around the shoulder. We first performed principal component analysis (PCA) of the EMG signals on a movement-by-movement basis. We found a surprisingly consistent pattern of muscle groupings across movement types and movement planes, although we could detect systematic differences between the PCs derived from movements performed in each sholder posture and between the principal components associated with the different orientations of the figure. Unexpectedly we found no systematic differences between the figute eights and the point-to-point movements. The first three principal components could be associated with a general co-contraction of all seven muscles plus two patterns of reciprocal activatoin. From these results, we surmise that both "discrete-rhythmic movements" such as the figure eight, and discrete point-to-point movement may be constructed from three different fundamental modules, one regulating the impedance of the limb over the time span of the movement and two others operating to generate movement, one aligned with the vertical and the other aligned with the horizontal.