Dopamine is one of a number of neurotransmitter candidates found in the insect CNS, It has been localised in a number of neurones, and others have been shown to respond to the application of dopamine. This study investigates the response of the common inhibitory motoneurone D3 to dopamine, and its ionic basis. The response to dopamine is distinguished pharmacologically from responses to noradrenaline, octopamlne and acetylcholine, all neurotransmitter candidates within the insect CNS, and it is concluded that a receptor specific for dopamine is present on this cell. Finally, this putative dopamine receptor is characterised pharmacologically, and its position relative to the extant classification schemes for mammalian receptors, and its similarity or otherwise to other invertebrate dopamine receptors is discussed.

<p> The development of episodic autobiographical memory (EAM) has been well documented in those with typical development (TD), yet many questions remain about the development of EAM and its operations in those with high functioning autism (HFA). In this study, youths (9 to 18 years old) with and without HFA (<i>N</i> = 48) participated in a semi-distressing event and then 3 weeks later were interviewed using one of two forensic interview protocols (10 Step or Cognitive Interview [CI]). Accuracy was assessed via cued recall narratives and responses to direct questions. Individual differences in working memory, cognitive flexibility, and pragmatic language were assessed. Results indicated that, although HFA youths&rsquo; cued recall memory for event details was diminished, memory accuracy for people, actions, and objects depended upon interview protocol and youth age. Younger HFA youths performed comparably to younger TD youths when receiving the 10 Step protocol. Yet, older HFA benefitted more from the Cognitive Interview&rsquo;s methods. Deficits in working memory, cognitive flexibility, and pragmatic language were more readily associated with performance in the CI condition and for youths with HFA. Indirect effects of age on memory performance via individual differences were observed mainly for the HFA group; maturational changes in these abilities may be occurring during adolescence, a period when youths with HFA begin to use compensatory mechanisms to perform EAM tasks. Direct question performance did not vary diagnostically, expanding the application of the task support hypothesis to a younger age. Implications for existing theories and forensic interview methods are discussed.</p><p>

AN ABSTRACT OF THE THESIS OF JACQUELINE BRIDGET GILLIAM, for the Master of Science degree in BEHAVIOR ANALYSIS AND THERAPY presented on October 26, 2014, at Southern Illinois University Carbondale. TITLE: IMPLEMENTATION OF PEAK RELATIONAL TRAINING SYSTEM FOR ADULTS WITH DEVELOPMENTAL DISABILITIES MAJOR PROFESSOR: Dr. Mark R. Dixon The first experiment sought to determine if a relationship did exist between two empirical assessment tools, the Inventory for Client and Agency Planning (ICAP) and the Promoting the Emergence of Advanced knowledge (PEAK) Relational Training System when assessing adults with developmental disabilities. The ICAP is tool that offers a service score for levels of support needed to adequately support the individual and is also used to determine rate determination for services. The tool does not offer suggestions for programming or teaching the individual skills in which they are lacking. The PEAK Relational Training System does offer an assessment and programming to train skills that an individual is unable to complete. The second experiment sought to determine if adults with developmental disabilities could learn new skills by using the PEAK Relational Training System. Assessments were conducted with 20 individuals with developmental disabilities and a relationship between the two assessment tools was found. Additionally, three individuals with disabilities were trained skills from nine programs in the PEAK Relational Training System and evidence of learning was shown in eight of the nine programs.

<p> All children with autism spectrum disorders (ASD) present with some form of impairment in social communication. Social cognitive learning theory suggests children&rsquo;s early joint attention skills provide a foundation for future language development. Preliminary research suggests social cognitive behaviors such as joint attention in the context of parent scaffolding may serve as a mechanism for language development in children with ASD. The current study utilized a parent-child free play task to explore the relations among parent and child attention and responsivity and child pragmatic language in 26 children ages 3:1 to 6:11 and their parents. Parent supported joint attention was assessed during a parent child free-play task. Pragmatic language ability was assessed by the Comprehensive Assessment of Spoken Language (CASL; Carrow-Woolfolk, 1999). Developmental status significantly predicted child&rsquo;s pragmatic language score while controlling for overall verbal ability, <i>F</i>(2, 23) = 6.37, <i>p</i> = 0.01, &Delta;R₂ = .15. Developmental status was not a significant predictor of parent supported joint attention, <i> F</i>(1, 24) = 1.09, <i>p</i> = 0.31, indicating that regardless of developmental status there was no significant difference in the percentage of time parents and children spent in parent supported joint attention. Children with autism spectrum disorders initiated joint attention with their parents (<i>M</i> = 0.28) about half as much as their typically developing peers (<i>M</i> = 0.55). Post hoc analyses indicated for children with ASD in this current study, initiation of joint attention was significantly correlated to child RJA, <i>r</i> = 0.60, <i>p</i> = 0.04, suggesting that child with ASD who initiate joint attention with their parents also spend a larger amount of time responding to their parent&rsquo;s bids for joint attention. The interaction between developmental status and child RJA was also significant, <i>F</i> = 6.16, <i>p</i> =.02, &Delta;R₂ = .13, indicating that for children with ASD, responsiveness to their parent&rsquo;s bids for joint attention of their parents plays a significant role for their pragmatic language ability in comparison to children with typically development. Collectively, the nature of these findings provides evidence for supporting social cognition in children with autism.</p><p>

<p> The goal of the present study was to examine the development of semantic and episodic memory in middle childhood. Specifically, we sought to understand the relation between episodic and semantic memory by examining how an aspect of semantic memory&mdash;spatial semantic knowledge&mdash;may influence children&rsquo;s episodic memory for events and their spatial locations. Children ages 5, 6, and 7 participated in events in 6 exhibits representing locations in a model town in a local children&rsquo;s museum. Events were manipulated by the extent to which the event and the spatial location match. Event conditions included spatially congruent, incongruent, and independent. After a short delay, children were tested for their recognition of the events and the location in which the event occurred. In addition, a novel semantic interview task directly assessed knowledge of the locations represented in the museum exhibits. Most notably, we found older children to exhibit greater semantic knowledge of locations (as measured through the semantic interview task) and, in the experimental manipulation, we found children&rsquo;s semantic memory to influence their memory for the locations of events. Results implicate the nature of the relations of children&rsquo;s semantic and episodic memory as well as the utility of research conducted in naturalistic settings.</p><p>

Cardiac development is a tightly controlled, step-wise process, as the heart is one of the first functional organs to develop. The major cell type of the heart is the cardiomyocyte and is known to be the work horse of the heart. Cardiac myocytes are very different than any other cell type, as they contain an infrastructure that allows for the involuntary contraction of the heart. Beginning at the anchoring of proteins at the z-disk, the sarcomere structure is gradually patterned. By adult, most cardiomyocytes are bi-nucleated, rod-shaped, and terminally differentiated. Although the microtubule network is a key organelle in the differentiation of every cell type, the role of microtubules in the heart, specifically in cardiac myocytes, has not been thoroughly explored. Genetic alteration of the microtubule network by Centromere Protein F (CENP-F) results in several structural and functional abnormalities in both humans and mice. Without CENP-F, mice hearts are dilated and undergo cardiac arrythmias. In isolated cardiomyocytes, calcium influx is disrupted, myocyte stiffness is greatly reduced, and major contractile components are significantly altered. As we observe changes in how CENP-F loss of function differs from cell to cell, our studies underlie the importance of understanding the role of CENP-F in the specific cell types of the organ of interest. Ultimately, these findings are novel as they lay the foundation for further studies on microtubules in cardiac development and health and, provide evidence for the potential impact of microtubule targeted chemotherapy treatments on heart disease.

Temporal, kinematic and kinetic patterns of independent walking (IW) in toddlers have been characterized in various studies with postural control identified as a critical component influencing the coordination between gait mechanisms to maintain a dynamic equilibrium. Variations in parameters across development indicate that toddlers possess more adult-like integration capabilities in locomotor control after 4 to 5 months of independent walking (Bril & Breniere, 1989, 1990, 1991, 1992). However, whether this integration would be influenced in a subtle complex locomotor task, obstacle crossing remains unknown. This study examined locomotor modulation during obstacle crossing in eight healthy toddlers (six males and two females; mean height = 80.6 cm) with 1 to 8 months IW experience. At least five trials of unobstructed walking (UW) and obstacle crossing (OC) were recorded using a Vicon motion analysis system (Oxford Metric Ltd, Oxford, UK). Lower extremity trajectories during unobstructed walking and while crossing a visible fixed obstacle were analyzed (Visual3D Motion Analysis System, C-motion Inc., Rockville, Maryland. US). As months of walking increased, segmental trajectories over the obstacle appeared to be more consistent. With 4- to 5-month IW toddlers displaying more adult-like OC patterns. This tendency was reflected by less variability of leading and trailing toe-to-obstacle distance (TD) and crossing stride length (SL). As IW experience increased, safety and stability were improved as the leading and trailing toe clearance distance over the obstacle (TC), knee flexion, crossing step length (SL), and heel distance (HD) increased accordingly. The most dramatic changes of these variables occurred after 4 to 5 months IW. In addition, success rate increased as months of walking suggested that better integrated postural control was achieved.

Proper cell division to yield two daughter cells with identical complements of genomic material requires coordination between mitosis and cytokinesis. In the event of a mitotic error, checkpoint mechanisms must inhibit both mitotic exit and cytokinesis to ensure accurate segregation of chromosomes. In response to mitotic spindle errors, the spindle checkpoint delays cytokinesis by inhibiting the septation initiation network (SIN), a GTPase-driven signaling cascade. Specifically, Hhp1 and Hhp2 phosphorylate the SIN scaffold protein, Sid4, recruiting dimeric the E3 ligase Dma1. Dma1 ubiquitinates Sid4, antagonizing the localization of the Polo-like kinase Plo1, and preventing phosphorylation of its downstream target Byr4. Consequently, the SIN kinase cascade and cytokinesis are delayed. Upon resolution of the mitotic spindle error, the Dma1 checkpoint signal must be withdrawn to allow continuation of the cell division cycle. However, the mechanism by which Dma1 ubiquitination of Sid4 is stopped is not known. Furthermore, whether Dma1 itself is regulated by the checkpoint remains unclear. In this work, I show that Dma1 is post-translationally modified by auto-ubiquitination and phosphorylation. Dma1 exhibits previously unreported localization dynamics that are dependent on its catalytic activity. In addition to ubiquitinating Sid4, Dma1 demonstrates promiscuous Dma1 auto-ubiquitination in vivo, and evidence indicates that its localization dynamics are impaired in the absence of auto-ubiquitination. I also determined that Dma1 is phosphorylated in vivo throughout the cell cycle and that this phosphorylation occurs on seven sites. Furthermore, I demonstrated that Cdk1 and Plo1 can phosphorylate Dma1 in vitro. The Cdk1/Plo1 phospho-mimetic inhibits Dma1 auto-ubiquitination while maintaining checkpoint activity. Overall, the current data point to a model wherein Dma1 auto-ubiquitination decreases its SPB binding and therefore access to its checkpoint substrate. Dma1 phosphorylation at Cdk1 and Plo1 sites prevents auto-ubiquitination, enabling increased SPB localization and maintenance of the checkpoint.

<p> Visual information is relayed from retina to the brain at first order synapses within the lateral geniculate nucleus (dLGN). During development, activity-dependent synaptic competition drives the segregation of retinal ganglion cell terminals into eye-specific zones. It has been assumed that the gain of synaptic transmission within these eye-specific zones is equivalent, providing uniform information transfer from the periphery to the CNS. Here, we revise this understanding. First, we demonstrate that anatomical segregation of retinal axons triggers a profound (200&ndash;300%) potentiation of neurotransmitter release selectively within the projection zone of the ipsilateral eye. Second, optogenetic recruitment of genetically defined axons within the ipsilateral projection zone provides evidence that functional synaptic connectivity is sub-stratified within the ipsilateral dLGN. Thus, we define a new functional organization within the dLGN and propose that synaptic competition acts as a developmental timer that triggers respecification of set point synaptic gain within the ipsilateral dLGN.</p><p>

The intestinal brush border serves as the sole site of nutrient absorption within the body, and also acts as an important barrier against luminal pathogens. The brush border is comprised of membrane protrusions called microvilli that are found on the apical surface of enterocytes. These protrusions are supported by a core bundle of 20 to 30 parallel actin filaments with the plus ends oriented towards the lumen. Our laboratory showed that protocadherin-24 and mucin-like protocadherin play a key role in the assembly and organization of the brush border. These protocadherins interact to form a trans-heterophilic adhesion complex that physically connects the distal tips of microvilli and regulates the tight packing. How these complexes are targeted to microvillar tips remains unknown. Microvillar protocadherins interact with several cytoplasmic binding partners, including the actin based motor, myosin-7b (Myo7b). Given the role of other myosin motors in building actin-based protrusions, this work focuses on elucidating the function of Myo7b in brush border assembly. We show that Myo7b is highly enriched at the tips of microvilli in both kidney and intestinal brush borders. Loss of Myo7b results in the mislocalization of the intermicrovillar adhesion links along the microvillar axis, disrupting brush border assembly. We also found that Myo7b motor domains are capable of supporting tip-directed transport. However, motor activity is supplemented by other passive targeting mechanisms, which together drive highly efficient accumulation of the adhesion complex at the tips. Additionally, we have established an in-cell reconstitution assay using filopodial protrusions that can be used to study protein interactions within the adhesion complex. Using this assay, we have begun to characterize the morphological effects of tip-enriched adhesion on actin-based protrusions. Initial experiments suggest adhesion at the distal tips regulates the stability and length of these protrusions. This work provides evidence that the actin-based motor Myo7b promotes the accumulation of adhesion complexes at microvillar tips, which may alter the morphology and dynamics of actin-based protrusions. These findings hold important implications for understanding apical morphogenesis in transporting and sensory epithelial tissues.