Sensitivity to Visual-Tactile Colocation on the Body Prior to Skilled Reaching in Early Infancy

Two experiments examined perceptual colocation of visual and tactile stimuli in young infants. Experiment 1 compared 4‐ (n = 15) and 6‐month‐old (n = 12) infants’ visual preferences for visual‐tactile stimulus pairs presented across the same or different feet. The 4‐ and 6‐month‐olds showed, respectively, preferences for colocated and noncolocated conditions, demonstrating sensitivity to visual‐tactile colocation on their feet. This extends previous findings of visual‐tactile perceptual colocation on the hands in older infants. Control conditions excluded the possibility that both 6‐ (Experiment 1), and 4‐month‐olds (Experiment 2, n = 12) perceived colocation on the basis of an undifferentiated supramodal coding of spatial distance between stimuli. Bimodal perception of visual‐tactile colocation is available by 4 months of age, that is, prior to the development of skilled reaching

Dynorphin is expressed primarily by GABAergic neurons that contain galanin in the rat dorsal horn

Background The opioid peptide dynorphin is expressed by certain neurons in the superficial dorsal horn of the spinal cord, but little is known about the types of cell that contain dynorphin. In this study, we have used an antibody against the dynorphin precursor preprodynorphin (PPD), to reveal the cell bodies and axons of dynorphin-expressing neurons in the rat spinal cord. The main aims were to estimate the proportion of neurons in each of laminae I-III that express dynorphin and to determine whether they are excitatory or inhibitory neurons. Results PPD-immunoreactive cells were concentrated in lamina I and the outer part of lamina II (IIo), where they constituted 17% and 8%, respectively, of all neurons. Around half of those in lamina I and 80% of those in lamina II were GABA-immunoreactive. We have previously identified four non-overlapping neurochemical populations of inhibitory interneurons in this region, defined by the presence of neuropeptide Y, galanin, parvalbumin and neuronal nitric oxide synthase. PPD co-localised extensively with galanin in both cell bodies and axons, but rarely or not at all with the other three markers. PPD was present in around 4% of GABAergic boutons (identified by the presence of the vesicular GABA transporter) in laminae I-II. Conclusions These results show that most dynorphin-expressing cells in the superficial dorsal horn are inhibitory interneurons, and that they largely correspond to the population that is defined by the presence of galanin. We estimate that dynorphin is present in ~32% of inhibitory interneurons in lamina I and 11% of those in lamina II. Since the proportion of GABAergic boutons that contain PPD in these laminae was considerably lower than this, our findings suggest that these neurons may generate relatively small axonal arborisations

Galanin-immunoreactivity identifies a distinct population of inhibitory interneurons in laminae I-III of the rat spinal cord

Background: Inhibitory interneurons constitute 30-40% of neurons in laminae I-III and have an important anti-nociceptive role. However, because of the difficulty in classifying them we know little about their organisation. Previous studies have identified 3 non-overlapping groups of inhibitory interneuron, which contain neuropeptide Y (NPY), neuronal nitric oxide synthase (nNOS) or parvalbumin, and have shown that these differ in postsynaptic targets. Some inhibitory interneurons contain galanin and the first aim of this study was to determine whether these form a different population from those containing NPY, nNOS or parvalbumin. We also estimated the proportion of neurons and GABAergic axons that contain galanin in laminae I-III. Results: Galanin cells were concentrated in laminae I-IIo, with few in laminae IIi-III. Galanin showed minimal co-localisation with NPY, nNOS or parvalbumin in laminae I-II, but most galanin-containing cells in lamina III were nNOS-positive. Galanin cells constituted similar to 7%, 3% and 2% of all neurons in laminae I, II and III, and we estimate that this corresponds to 26%, 10% and 5% of the GABAergic neurons in these laminae. However, galanin was only found in similar to 6% of GABAergic boutons in laminae I-IIo, and similar to 1% of those in laminae IIi-III. Conclusions: These results show that galanin, NPY, nNOS and parvalbumin can be used to define four distinct neurochemical populations of inhibitory interneurons. Together with results of a recent study, they suggest that the galanin and NPY populations account for around half of the inhibitory interneurons in lamina I and a quarter of those in lamina I

Precursors to social and communication difficulties in infants at-risk for autism: gaze following and attentional engagement

Whilst joint attention (JA) impairments in autism have been widely studied, little is known about the early development of gaze following, a precursor to establishing JA. We employed eye-tracking to record gaze following longitudinally in infants with and without a family history of autism spectrum disorder (ASD) at 7 and 13 months. No group difference was found between at-risk and low-risk infants in gaze following behaviour at either age. However, despite following gaze successfully at 13 months, at-risk infants with later emerging socio-communication difficulties (both those with ASD and atypical development at 36 months of age) allocated less attention to the congruent object compared to typically developing at-risk siblings and low-risk controls. The findings suggest that the subtle emergence of difficulties in JA in infancy may be related to ASD and other atypical outcomes

Profiles of Global Gene Expression in Ionizing-Radiation–Damaged Human Diploid Fibroblasts Reveal Synchronization behind the G(1) Checkpoint in a G(0)-like State of Quiescence

Cell cycle arrest and stereotypic transcriptional responses to DNA damage induced by ionizing radiation (IR) were quantified in telomerase-expressing human diploid fibroblasts. Analysis of cytotoxicity demonstrated that 1.5 Gy IR inactivated colony formation by 40–45% in three fibroblast lines; this dose was used in all subsequent analyses. Fibroblasts exhibited > 90% arrest of progression from G(2) to M at 2 hr post-IR and a similarly severe arrest of progression from G(1) to S at 6 and 12 hr post-IR. Normal rates of DNA synthesis and mitosis 6 and 12 hr post-IR caused the S and M compartments to empty by > 70% at 24 hr. Global gene expression was analyzed in IR-treated cells. A microarray analysis algorithm, EPIG, identified nine IR-responsive patterns of gene expression that were common to the three fibroblast lines, including a dominant p53-dependent G(1) checkpoint response. Many p53 target genes, such as CDKN1A, GADD45, BTG2, and PLK3, were significantly up-regulated at 2 hr post-IR. Many genes whose expression is regulated by E2F family transcription factors, including CDK2, CCNE1, CDC6, CDC2, MCM2, were significantly down-regulated at 24 hr post-IR. Numerous genes that participate in DNA metabolism were also markedly repressed in arrested fibroblasts apparently as a result of cell synchronization behind the G(1) checkpoint. However, cluster and principal component analyses of gene expression revealed a profile 24 hr post-IR with similarity to that of G(0) growth quiescence. The results reveal a highly stereotypic pattern of response to IR in human diploid fibroblasts that reflects primarily synchronization behind the G(1) checkpoint but with prominent induction of additional markers of G(0) quiescence such as GAS1

Circuit dissection of the role of somatostatin in itch and pain

Stimuli that elicit itch are detected by sensory neurons that innervate the skin. This information is processed by the spinal cord; however, the way in which this occurs is still poorly understood. Here we investigated the neuronal pathways for itch neurotransmission, particularly the contribution of the neuropeptide somatostatin. We find that in the periphery, somatostatin is exclusively expressed in Nppb+ neurons, and we demonstrate that Nppb+somatostatin+ cells function as pruriceptors. Employing chemogenetics, pharmacology and cell-specific ablation methods, we demonstrate that somatostatin potentiates itch by inhibiting inhibitory dynorphin neurons, which results in disinhibition of GRPR+ neurons. Furthermore, elimination of somatostatin from primary afferents and/or from spinal interneurons demonstrates differential involvement of the peptide released from these sources in itch and pain. Our results define the neural circuit underlying somatostatin-induced itch and characterize a contrasting antinociceptive role for the peptide

Evolutionary approaches to signal decomposition in an application service management system

The increased demand for autonomous control in enterprise information systems has generated interest on efficient global search methods for multivariate datasets in order to search for original elements in time-series patterns, and build causal models of systems interactions, utilization dependencies, and performance characteristics. In this context, activity signals deconvolution is a necessary step to achieve effective adaptive control in Application Service Management. The paper investigates the potential of population-based metaheuristic algorithms, particularly variants of particle swarm, genetic algorithms and differential evolution methods, for activity signals deconvolution when the application performance model is unknown a priori. In our approach, the Application Service Management System is treated as a black- or grey-box, and the activity signals deconvolution is formulated as a search problem, decomposing time-series that outline relations between action signals and utilization-execution time of resources. Experiments are conducted using a queue-based computing system model as a test-bed under different load conditions and search configurations. Special attention was put on high-dimensional scenarios, testing effectiveness for large-scale multivariate data analyses that can obtain a near-optimal signal decomposition solution in a short time. The experimental results reveal benefits, qualities and drawbacks of the various metaheuristic strategies selected for a given signal deconvolution problem, and confirm the potential of evolutionary-type search to effectively explore the search space even in high-dimensional cases. The approach and the algorithms investigated can be useful in support of human administrators, or in enhancing the effectiveness of feature extraction schemes that feed decision blocks of autonomous controllers

Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions

During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4Eme1. Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastroph