Detection of Forces and Body Load in Standing and Walking in the American Cockroach

Sense organs in the legs that detect body weight are an important component in the regulation of posture and locomotion. This thesis seeks to gain an understanding of how body weight is detected by sense organs of the legs, and determine how this information influences muscle activities in standing and walking. The first study tested the ability of tibial campaniform sensilla (receptors that monitor forces in the cockroach leg) to encode variations in body load using magnets attached to the thorax. Recordings of sensory activities in freely standing animals showed that proximal tibial sensilla (oriented perpendicular to the leg long axis) encode the level of body load while distal receptors (oriented parallel) fired to decreasing loads. In some postures, sensillum discharges paralleled changes in activity of the trochanteral extensor muscle consistent with a known interjoint reflex. These findings demonstrate that tibial campaniform sensilla can monitor the effects of body weight upon the legs and may aid in generating support of body load. In the second study, sensory activities were compared when animals walked freely in an arena, or upon an oiled glass plate with their body weight supported. Sensilla discharges persisted but were abbreviated when body load was reduced. The results suggest that sensory discharges early in stance result from forces generated by contractions of muscles that press the leg against the substrate. Force feedback later in stance may adjust motor output to changes in loading. In the third study, muscle activities and leg movements were recorded before and after denervation of distal leg segments. Regular bursts occurred in motoneurons to leg extensor muscles following denervation, including ‘fictive’ bursting in a muscle whose tendon (apodeme) was cut in the ablation. Similar motoneuron activities were found in walking on an oiled glass surface, when effects of body weight and mechanical coupling were minimized. When distal segments were completely severed, leg use and muscle bursting were disrupted but could be restored if the stumps were pressed against the substrate. These results support the hypothesis that feedback from receptors in proximal leg segments, that indicate forces, allow for active leg use in walking

Differences in lean and obese skeletal muscle myoblasts of adult and post-natal LA/N (faf) rats: a confocal description of the skeletal muscle myoblast

Mutant strains of obese rats are currently being studied to reveal the mechanisms of increased lipid synthesis and decreased lipid oxidation in these rats. It was originally thought that much of the fat production that leads to obesity is the result of metabolic processes in the liver and adipose tissue. Studies by Kahle et al.3 showed that the liver and adipose tissue account for only 22% and 7% respectively, of total fatty acid synthesis. It was also shown that 21 % of total de novo fatty acid was localized in the postural skeletal muscle. The dry weight of the body is 40% skeletal muscle, thus it is likely that this tissue type has some role in controlling the body’s metabolism.1 Previous work has gone into characterizing differences present within the skeletal muscle of lean and obese phenotypes that may have an influence on metabolism. Electron microscopy was used to determine structural differences in skeletal muscle tissue as well as in myoblasts. It was shown that the myoblasts of the obese phenotype have a higher capacity metabolic synthesis. The work of this thesis was done in order to further investigate some of these previously studied parameters. The focus of this work was to characterize differences in metabolic potential in skeletal muscle myoblasts of the obese and lean phenotypes of the rodent model, the LA/Nfat rat. One important parameter in question is the amount of intracellular lipid deposits present within the individual myoblasts. To determine differences between the two phenotypes, confocal microcopy was used to visually observe, with a lipid specific probe nile red, both intracellular lipid concentration and lipid distribution within the cell. After digitally capturing micrographs into specifically designed computer software, it was possible to determine the amount of fluorescence present within a single cell in a culture. Post-natal (14 days of age) animals were also studied in the same manner to determine if pre-obese pups (Figure 1b) showed the same situation as their adult counterparts. The results of the experiment indicated a significant difference (p \u3c 0.50) present within the lipid content between obese and lean adult rats. The same situation was not shown in post-natal animals. The size of the cells studied however, differed significantly (p \u3c 0.05) between the two age groups studied, but not within them. This difference may be directly attributable to the increased rate of mitosis of the post-natal myoblasts. This increased rate of mitosis may also explain the similarity in lipid content of the obese and lean pups. Another parameter briefly examined was the role of the mitochondria in the metabolism of the cell. No results were attained from the mitochondrial studies. Skeletal muscle has recently been proven to be an important tool in the delivery of proteins and drugs throughout the body. It has been shown that hybrid skeletal muscle myotubes can be used to deliver such necessary proteins as dystrophin and human growth hormone.33-37 Using this type of myoblast-mediated gene therapy it may be possible with continued study to determine regulatory hormones in lipid metabolism. These hormones when delivered to the body in the correct manner may be used as an effective means to not only study the effect of certain drugs on metabolism but perhaps as an effective treatment to obesity

Neural mechanisms for emotional contagion and spontaneous mimicry of live facial expressions

Viewing a live facial expression typically elicits a similar expression by the observer (facial mimicry) that is associated with a concordant emotional experience (emotional contagion). The model of embodied emotion proposes that emotional contagion and facial mimicry are functionally linked although the neural underpinnings are not known. To address this knowledge gap, we employed a live two-person paradigm (n = 20 dyads) using functional near-infrared spectroscopy during live emotive face-processing while also measuring eye-tracking, facial classifications and ratings of emotion. One dyadic partner, ‘Movie Watcher’, was instructed to emote natural facial expressions while viewing evocative short movie clips. The other dyadic partner, ‘Face Watcher’, viewed the Movie Watcher's face. Task and rest blocks were implemented by timed epochs of clear and opaque glass that separated partners. Dyadic roles were alternated during the experiment. Mean cross-partner correlations of facial expressions (r = 0.36 ± 0.11 s.e.m.) and mean cross-partner affect ratings (r = 0.67 ± 0.04) were consistent with facial mimicry and emotional contagion, respectively. Neural correlates of emotional contagion based on covariates of partner affect ratings included angular and supramarginal gyri, whereas neural correlates of the live facial action units included motor cortex and ventral face-processing areas. Findings suggest distinct neural components for facial mimicry and emotional contagion. This article is part of a discussion meeting issue ‘Face2face: advancing the science of social interaction’

Emergency supply of prescription-only medicines to patients by community pharmacists: a mixed methods evaluation incorporating patient, pharmacist and GP perspectives

Objective To evaluate and inform emergency supply of prescription-only medicines by community pharmacists (CPs), including how the service could form an integral component of established healthcare provision to maximise adherence. Design Mixed methods. 4 phases: prospective audit of emergency supply requests for prescribed medicines (October–November 2012 and April 2013); interviews with CPs (February–April 2013); follow-up interviews with patients (April–May 2013); interactive feedback sessions with general practice teams (October–November 2013). Setting 22 community pharmacies and 6 general practices in Northwest England. Participants 27 CPs with experience of dealing with requests for emergency supplies; 25 patients who received an emergency supply of a prescribed medicine; 58 staff at 6 general practices. Results Clinical audit in 22 pharmacies over two 4-week periods reported that 526 medicines were requested by 450 patients. Requests peaked over a bank holiday and around weekends. A significant number of supplies were made during practice opening hours. Most requests were for older patients and for medicines used in long-term conditions. Difficulty in renewing repeat medication (forgetting to order, or prescription delays) was the major reason for requests. The majority of medicines were ‘loaned’ in advance of a National Health Service (NHS) prescription. Interviews with CPs and patients indicated that continuous supply had a positive impact on medicines adherence, removing the need to access urgent care. General practice staff were surprised and concerned by the extent of emergency supply episodes. Conclusions CPs regularly provide emergency supplies to patients who run out of their repeat medication, including during practice opening hours. This may aid adherence. There is currently no feedback loop, however, to general practice. Patient care and interprofessional communication may be better served by the introduction of a formally structured and funded NHS emergency supply service from community pharmacies, with ongoing optimisation of repeat prescribing

Activation in Right Dorsolateral Prefrontal Cortex Underlies Stuttering Anticipation

People who stutter learn to anticipate many of their overt stuttering events. Despite the critical role of anticipation, particularly how responses to anticipation shape stuttering behaviors, the neural bases associated with anticipation are unknown. We used a novel approach to identify anticipated and unanticipated words in 22 adult stutterers, which were produced in a delayed-response task while hemodynamic activity was measured using functional near infrared spectroscopy (fNIRS). Twenty-two control participants were included such that each individualized set of anticipated/unanticipated words was produced by one stutterer and one control. We conducted an analysis on the right dorsolateral prefrontal cortex (R-DLPFC) based on converging lines of evidence from the stuttering and cognitive control literatures. We also assessed connectivity between the R-DLPFC and right supramarginal gyrus (R-SMG), two key nodes of the frontoparietal network (FPN), to assess the role of cognitive control, particularly error-likelihood monitoring, in stuttering anticipation. All analyses focused on the five-second anticipation phase preceding the go signal to produce speech. Results indicate that anticipated words are associated with elevated activation in the R-DLPFC, and that compared to non-stutterers, stutterers exhibit greater activity in the R-DLPFC, irrespective of anticipation. Further, anticipated words are associated with reduced connectivity between the R-DLPFC and R-SMG. These findings highlight the potential roles of the R-DLPFC and the greater FPN as a neural substrate of stuttering anticipation. The results also support previous accounts of error-likelihood monitoring and action-stopping in stuttering anticipation. Overall, this work offers numerous directions for future research with clinical implications for targeted neuromodulation

Neural correlates of eye contact and social function in autism spectrum disorder

Reluctance to make eye contact during natural interactions is a central diagnostic criterion for autism spectrum disorder (ASD). However, the underlying neural correlates for eye contacts in ASD are unknown, and diagnostic biomarkers are active areas of investigation. Here, neuroimaging, eye-tracking, and pupillometry data were acquired simultaneously using two-person functional near-infrared spectroscopy (fNIRS) during live "in-person" eye-to-eye contact and eye-gaze at a video face for typically-developed (TD) and participants with ASD to identify the neural correlates of live eye-to-eye contact in both groups. Comparisons between ASD and TD showed decreased right dorsal-parietal activity and increased right ventral temporal-parietal activity for ASD during live eye-to-eye contact (p≤0.05, FDR-corrected) and reduced cross-brain coherence consistent with atypical neural systems for live eye contact. Hypoactivity of right dorsal-parietal regions during eye contact in ASD was further associated with gold standard measures of social performance by the correlation of neural responses and individual measures of: ADOS-2, Autism Diagnostic Observation Schedule, 2nd Edition (r = -0.76, -0.92 and -0.77); and SRS-2, Social Responsiveness Scale, Second Edition (r = -0.58). The findings indicate that as categorized social ability decreases, neural responses to real eye-contact in the right dorsal parietal region also decrease consistent with a neural correlate for social characteristics in ASD

Investigation of functional near-infrared spectroscopy signal quality and development of the hemodynamic phase correlation signal

SIGNIFICANCE: There is a longstanding recommendation within the field of fNIRS to use oxygenated ( HbO 2 ) and deoxygenated (HHb) hemoglobin when analyzing and interpreting results. Despite this, many fNIRS studies do focus on HbO 2 only. Previous work has shown that HbO 2 on its own is susceptible to systemic interference and results may mostly reflect that rather than functional activation. Studies using both HbO 2 and HHb to draw their conclusions do so with varying methods and can lead to discrepancies between studies. The combination of HbO 2 and HHb has been recommended as a method to utilize both signals in analysis. AIM: We present the development of the hemodynamic phase correlation (HPC) signal to combine HbO 2 and HHb as recommended to utilize both signals in the analysis. We use synthetic and experimental data to evaluate how the HPC and current signals used for fNIRS analysis compare. APPROACH: About 18 synthetic datasets were formed using resting-state fNIRS data acquired from 16 channels over the frontal lobe. To simulate fNIRS data for a block-design task, we superimposed a synthetic task-related hemodynamic response to the resting state data. This data was used to develop an HPC-general linear model (GLM) framework. Experiments were conducted to investigate the performance of each signal at different SNR and to investigate the effect of false positives on the data. Performance was based on each signal's mean T -value across channels. Experimental data recorded from 128 participants across 134 channels during a finger-tapping task were used to investigate the performance of multiple signals [ HbO 2 , HHb, HbT, HbD, correlation-based signal improvement (CBSI), and HPC] on real data. Signal performance was evaluated on its ability to localize activation to a specific region of interest. RESULTS: Results from varying the SNR show that the HPC signal has the highest performance for high SNRs. The CBSI performed the best for medium-low SNR. The next analysis evaluated how false positives affect the signals. The analyses evaluating the effect of false positives showed that the HPC and CBSI signals reflect the effect of false positives on HbO 2 and HHb. The analysis of real experimental data revealed that the HPC and HHb signals provide localization to the primary motor cortex with the highest accuracy. CONCLUSION: We developed a new hemodynamic signal (HPC) with the potential to overcome the current limitations of using HbO 2 and HHb separately. Our results suggest that the HPC signal provides comparable accuracy to HHb to localize functional activation while at the same time being more robust against false positives

Dialogue Act Modeling for Automatic Tagging and Recognition of Conversational Speech

We describe a statistical approach for modeling dialogue acts in conversational speech, i.e., speech-act-like units such as Statement, Question, Backchannel, Agreement, Disagreement, and Apology. Our model detects and predicts dialogue acts based on lexical, collocational, and prosodic cues, as well as on the discourse coherence of the dialogue act sequence. The dialogue model is based on treating the discourse structure of a conversation as a hidden Markov model and the individual dialogue acts as observations emanating from the model states. Constraints on the likely sequence of dialogue acts are modeled via a dialogue act n-gram. The statistical dialogue grammar is combined with word n-grams, decision trees, and neural networks modeling the idiosyncratic lexical and prosodic manifestations of each dialogue act. We develop a probabilistic integration of speech recognition with dialogue modeling, to improve both speech recognition and dialogue act classification accuracy. Models are trained and evaluated using a large hand-labeled database of 1,155 conversations from the Switchboard corpus of spontaneous human-to-human telephone speech. We achieved good dialogue act labeling accuracy (65% based on errorful, automatically recognized words and prosody, and 71% based on word transcripts, compared to a chance baseline accuracy of 35% and human accuracy of 84%) and a small reduction in word recognition error.Comment: 35 pages, 5 figures. Changes in copy editing (note title spelling changed

Lightly Fluorinated Graphene as a Protective Layer for n-Type Si(111) Photoanodes in Aqueous Electrolytes

The behavior of n-Si(111) photoanodes covered by monolayer sheets of fluorinated graphene (F–Gr) was investigated under a range of chemical and electrochemical conditions. The electrochemical behavior of n-Si/F–Gr and np^+-Si/F–Gr photoanodes was compared to hydride-terminated n-Si (n-Si−H) and np+-Si−H electrodes in contact with aqueous Fe(CN)_6^(3-/4-) and Br_2/HBr electrolytes as well as in contact with a series of outer-sphere, one-electron redox couples in nonaqueous electrolytes. Illuminated n-Si/F–Gr and np^+-Si/F–Gr electrodes in contact with an aqueous K_3(Fe(CN)_6/K4(Fe(CN)_6 solutions exhibited stable short-circuit photocurrent densities of ∼10 mA cm^(–2) for 100,000 s (>24 h), in comparison to bare Si electrodes, which yielded nearly a complete photocurrent decay over ∼100 s. X-ray photoelectron spectra collected before and after exposure to aqueous anodic conditions showed that oxide formation at the Si surface was significantly inhibited for Si electrodes coated with F–Gr relative to bare Si electrodes exposed to the same conditions. The variation of the open-circuit potential for n-Si/F–Gr in contact with a series of nonaqueous electrolytes of varying reduction potential indicated that the n-Si/F–Gr did not form a buried junction with respect to the solution contact. Further, illuminated n-Si/F−Gr electrodes in contact with Br_2/HBr(aq) were significantly more electrochemically stable than n-Si−H electrodes, and n-Si/F−Gr electrodes coupled to a Pt catalyst exhibited ideal regenerative cell efficiencies of up to 5% for the oxidation of Br^– to Br_2

Characterizing RNA stability genome-wide through combined analysis of PRO-seq and RNA-seq data.

BACKGROUND: The concentrations of distinct types of RNA in cells result from a dynamic equilibrium between RNA synthesis and decay. Despite the critical importance of RNA decay rates, current approaches for measuring them are generally labor-intensive, limited in sensitivity, and/or disruptive to normal cellular processes. Here, we introduce a simple method for estimating relative RNA half-lives that is based on two standard and widely available high-throughput assays: Precision Run-On sequencing (PRO-seq) and RNA sequencing (RNA-seq). RESULTS: Our method treats PRO-seq as a measure of transcription rate and RNA-seq as a measure of RNA concentration, and estimates the rate of RNA decay required for a steady-state equilibrium. We show that this approach can be used to assay relative RNA half-lives genome-wide, with good accuracy and sensitivity for both coding and noncoding transcription units. Using a structural equation model (SEM), we test several features of transcription units, nearby DNA sequences, and nearby epigenomic marks for associations with RNA stability after controlling for their effects on transcription. We find that RNA splicing-related features are positively correlated with RNA stability, whereas features related to miRNA binding and DNA methylation are negatively correlated with RNA stability. Furthermore, we find that a measure based on U1 binding and polyadenylation sites distinguishes between unstable noncoding and stable coding transcripts but is not predictive of relative stability within the mRNA or lincRNA classes. We also identify several histone modifications that are associated with RNA stability. CONCLUSION: We introduce an approach for estimating the relative half-lives of individual RNAs. Together, our estimation method and systematic analysis shed light on the pervasive impacts of RNA stability on cellular RNA concentrations