2,352 research outputs found

    Lack of evidence for sprouting of Aβ afferents into the superficial laminas of the spinal cord dorsal horn after nerve section

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    The central arborizations of large myelinated cutaneous afferents normally extend as far dorsally as the ventral part of lamina II in rat spinal cord. Woolf et al. (1992) reported that after nerve injury some of these afferents sprouted into lamina I and the dorsal part of lamina II, and it has been suggested that this could contribute to allodynia associated with neuropathic pain. Part of the evidence for sprouting was on the basis of the use of cholera toxin B subunit as a selective tracer for A-fibers, and the validity of this approach has recently been questioned; however, sprouting was also reported in experiments involving intra-axonal labeling of chronically axotomized afferents. We have used intra-axonal labeling in the rat to examine central terminals of 58 intact sciatic afferents of presumed cutaneous origin and 38 such afferents axotomized 7-10 weeks previously. Both normal and axotomized populations included axons with hair follicle afferent-like morphology and arbors that entered the ventral half of lamina II; however, none of these extended farther dorsally. We also performed bulk labeling of myelinated afferents by injecting biotinylated dextran into the lumbar dorsal columns bilaterally 8-11 weeks after unilateral sciatic nerve section. We observed that both ipsilateral and contralateral to the sectioned nerve, arbors of axons with hair follicle afferent-like morphology in the sciatic territory extended only as far as the ventral half of lamina II. Therefore these results do not support the hypothesis that Aβ afferents sprout into the superficial laminas after nerve section

    EEG–fMRI mapping of asymmetrical delta activity in a patient with refractory epilepsy is concordant with the epileptogenic region determined by intracranial EEG

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    We studied a patient with refractory focal epilepsy using continuous EEG-correlated fMRI. Seizures were characterized by head turning to the left and clonic jerking of the left arm, suggesting a right frontal epileptogenic region. Interictal EEG showed occasional runs of independent nonlateralized slow activity in the delta band with right frontocentral dominance and had no lateralizing value. Ictal scalp EEG had no lateralizing value. Ictal scalp EEG suggested right-sided central slow activity preceding some seizures. Structural 3-T MRI showed no abnormality. There was no clear epileptiform abnormality during simultaneous EEG–fMRI. We therefore modeled asymmetrical EEG delta activity at 1–3 Hz near frontocentral electrode positions. Significant blood oxygen level-dependent (BOLD) signal changes in the right superior frontal gyrus correlated with right frontal oscillations at 1–3 Hz but not at 4–7 Hz and with neither of the two frequency bands when derived from contralateral or posterior electrode positions, which served as controls. Motor fMRI activations with a finger-tapping paradigm were asymmetrical: they were more anterior for the left hand compared with the right and were near the aforementioned EEG-correlated signal changes. A right frontocentral perirolandic seizure onset was identified with a subdural grid recording, and electric stimulation of the adjacent contact produced motor responses in the left arm and after discharges. The fMRI localization of the left hand motor and the detected BOLD activation associated with modeled slow activity suggest a role for localization of the epileptogenic region with EEG–fMRI even in the absence of clear interictal discharges

    Experimental Control and Characterization of Autophagy in Drosophila

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    Insects such as the fruit fly Drosophila melanogaster, which fundamentally reorganize their body plan during metamorphosis, make extensive use of autophagy for their normal development and physiology. In the fruit fly, the hepatic/adipose organ known as the fat body accumulates nutrient stores during the larval feeding stage. Upon entering metamorphosis, as well as in response to starvation, these nutrients are mobilized through a massive induction of autophagy, providing support to other tissues and organs during periods of nutrient deprivation. High levels of autophagy are also observed in larval tissues destined for elimination, such as the salivary glands and larval gut. Drosophila is emerging as an important system for studying the functions and regulation of autophagy in an in vivo setting. In this chapter we describe reagents and methods for monitoring autophagy in Drosophila, focusing on the larval fat body. We also describe methods for experimentally activating and inhibiting autophagy in this system and discuss the potential for genetic analysis in Drosophila to identify novel genes involved in autophagy

    Effect of age and gender on serum periostin: Relationship to cortical measures, bone turnover and hormones

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    Periostin is an extracellular matrix protein, and in bone is expressed most highly in the periosteum. It increases bone formation through osteoblast differentiation, cell adhesion, Wnt signalling and collagen cross-linking. We hypothesised that serum periostin would be high at times of life when cortical modeling is active, in early adulthood and in older age, and that it would correlate with cortical bone measures, bone turnover and hormones that regulate cortical modeling. We conducted a cross-sectional observational study of 166 healthy men and women at three skeletal stages; the end of longitudinal growth (16–18 years), peak bone mass (30–32 years) and older age (over 70 years). We measured serum periostin with a new ELISA optimised for human serum and plasma which recognises all known splice variants (Biomedica). We measured the distal radius and distal tibia with HR-pQCT, and measured serum PINP, CTX, sclerostin, PTH, IGF-1, estradiol and testosterone. Periostin was higher at age 16–18 than age 30–32 (1253 vs 842 pmol/l, p < 0.001), but not different between age 30–32 and over age 70. Periostin was inversely correlated with tibia cortical thickness and density (R − 0.229, − 0.233, both p = 0.003). It was positively correlated with PINP (R 0.529, p < 0.001), CTX (R 0.427, p < 0.001) and IGF-1 (R 0.440, p < 0.001). When assessed within each age group these correlations were only significant at age 16–18, except for PINP which was also significant over age 70. We conclude that periostin may have a role in IGF-1 driven cortical modeling and consolidation in young adults, but it may not be an important mediator in older adults

    Psychometric evaluation of the Dutch translation of the Overall Assessment of the Speaker’s Experience of Stuttering for adults (OASES-A-D)

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    Abstract: The Overall Assessment of the Speaker’s Experience of Stuttering for adults (OASES-A; Yaruss & Quesal, 2006, 2010) is a patient-reported outcome measure that was designed to provide a comprehensive assessment of “the experience of the stuttering disorder from the perspective of individuals who stutter” (Yaruss & Quesal, 2006, p.90). This paper reports on the translation process and evaluates the psychometric performance of a Dutch version of the OASES-A. Translation of the OASES-A into Dutch followed a standard forward and backward translation process. The Dutch OASES-A (OASES-A-D) was then administered to 138 adults who stutter. A subset of 91 respondents also evaluated their speech on a 10-point Likert scale. For another subset of 45 respondents, a clinician-based stuttering severity rating on a 5-point Likert scale was available. Thirty-two of the respondents also completed the Dutch S-24 scale (Brutten & Vanryckeghem, 2003). The OASES-A-D showed acceptable item properties. No ceiling effects were observed. For 30 out of 100 items, most of which were in Section IV (Quality of Life), floor effects were observed. Cronbach’s alpha coefficients for all sections and subsections surpassed the 0.70 criterion of good internal consistency and reliability. Concurrent validity was moderate to high. Construct validity was confirmed by distinct scores on the OASES-A-D for groups with different levels of stuttering severity as rated by the speakers themselves or by clinicians. These results suggest that the OASES-A-D is a reliable and valid measure that can be used to assess the impact of stuttering on Dutch adults who stutter

    A difference expansion technique to analyse the advection/dispersion/sorption equation for phosphorous

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    A finite difference technique for numerical analysis of the partial differential equation for advection and dispersion with sorption is presented in detail. The sorption term is non-linear and it is difficult to simulate the breakthrough curves when the rate of change of concentration is large. A general technique is used which expands the derivatives in terms of increasing orders of finite differences. This has become possible with the advent of symbolic manipulation. It is possible to expand to any order and, importantly, separate out the terms for each order. Details are presented, together with methods for exploring the convergence and stability as well as adjusting the time and spatial differencing to lower or minimise· the error

    On educating the whole person, or learning to be a knower

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    This paper addresses the question whether liberal arts education and the humanities can currently be used to build university reputations. Laudatory in its connotations, the phrase, “Educating the Whole Person,” is widely used in heterogeneous liberal education programs to describe the purpose or function of these programs. Would the history of liberal education be useful to sort out the current meanings of the phrase, and can the phrase be used to raise the stature of educational institutions? The paper finds that in undergraduate education, learning to be a knower across disciplines is closely identified with an education of the whole person through the liberal arts. Yet, developed parallel to the historical inquiry of the phrase’s meaning is a steady erosion of the liberal arts structuring education, as disciplines subordinate or replace those arts with their own specialized concerns. Ultimately, this subordination has meant that the humanities have turned inward, away from public, cultural involvement that historically characterized the liberal arts. Instead, the humanities might re-focus upon the liberal arts, which have historically addressed both the arts and sciences, as a public expression of what it is to be a knower and, thus, help to build university reputations through educating the whole person

    Evidence for Suzuki–Miyaura cross-couplings catalyzed by ligated Pd3-clusters: from cradle to grave

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    Pdn clusters offer unique selectivity and exploitable reactivity in catalysis. Understanding the behavior of Pdn clusters is thus critical for catalysis, applied synthetic organic chemistry and greener outcomes for precious Pd. The Pd3 cluster, [Pd3(μ-Cl)(μ-PPh2)2(PPh3)3][Cl] (denoted as Pd3Cl2), which exhibits distinctive reactivity, was synthesized and immobilized on a phosphine-functionalized polystyrene resin (denoted as immob-Pd3Cl2). The resultant material served as a tool to study closely the role of Pd3 clusters in a prototypical Suzuki–Miyaura cross-coupling of 4-fluoro-1-bromobenzene and 4-methoxyphenyl boronic acid at varying low Pd ppm concentrations (24, 45, and 68 ppm). Advanced heterogeneity tests such as Hg poisoning and the three-phase test showed that leached mononuclear or nanoparticulate Pd are unlikely to be the major active catalyst species under the reaction conditions tested. EXAFS/XANES analysis from (pre)catalyst and filtered catalysts during and after catalysis has shown the intactness of the triangular structure of the Pd3X2 cluster, with exchange of chloride (X) by bromide during catalytic turnover of bromoarene substrate. This finding is further corroborated by treatment of immob-Pd3Cl2 after catalyzing the Suzuki–Miyaura reaction with excess PPh3, which releases the cluster from the polymer support and so permits direct observation of [Pd3(μ-Br)(μ-PPh2)2(PPh3)3]+ ions by ESI-MS. No evidence is seen for a proposed intermediate in which the bridging halogen on the Pd3 motif is replaced by an aryl group from the organoboronic acid, i.e. formed by a transmetallation-first process. Our findings taken together indicate that the ‘Pd3X2’ motif is an active catalyst species, which is stabilized by being immobilized, providing a more robust Pd3 cluster catalyst system. Non-immobilized Pd3Cl2 is less stable, as is followed by stepwise XAFS of the non-immobilized Pd3Cl2, which gradually changes to a species consistent with ‘Pdx(PPh3)y’ type material. Our findings have far-reaching future implications for Pd3 cluster involvement in catalysis, showing that immobilization of Pd3 cluster species offers advantages for rigorous mechanistic examination and applied chemistries

    Methodology for energy and economic modeling of net zero energy communities

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    Net zero energy (NZE) communities are becoming pivotal to the energy vision of developers. Communities that produce as much energy as they consume provide many benefits, such as reducing life-cycle costs and better resilience to grid outages. If deployed using smart-grid technology, NZE communities can act as a grid node and aid in balancing electrical demand. However, identifying cost-effective pathways to NZE requires detailed energy and economic models. Information required to build such models is not typically available at the early master-planning stages, where the largest energy and economic saving opportunities exist. Methodologies that expedite and streamline energy and economic modeling could facilitate early decision making. This paper describes a reproducible methodology that aids modelers in identifying energy and economic savings opportunities in the early community design stages. As additional information becomes available, models can quickly be recreated and evaluated. The proposed methodology is applied to the first-phase design of a NZE community under development in Southwestern Ontario
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