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1.
Inorg Chem ; 60(10): 6976-6980, 2021 May 17.
Article in English | MEDLINE | ID: mdl-33890765

ABSTRACT

An on-demand electrochemical synthesis of copper(I) triflate under both batch and continuous flow conditions has been developed. A major benefit of the electrochemical methodology is that the only byproduct of the reaction is hydrogen gas, which obviates the need for workup and purification, and water is not incorporated into the product. Upon completion of the electrochemical synthesis, solutions are directly transferred or dispensed into reaction mixtures for the catalytic oxidation of benzyl alcohol with no requirement for workup or purification.

2.
J Chem Inf Model ; 61(10): 4890-4899, 2021 10 25.
Article in English | MEDLINE | ID: mdl-34549957

ABSTRACT

Solvent-dependent reactivity is a key aspect of synthetic science, which controls reaction selectivity. The contemporary focus on new, sustainable solvents highlights a need for reactivity predictions in different solvents. Herein, we report the excellent machine learning prediction of the nucleophilicity parameter N in the four most-common solvents for nucleophiles in the Mayr's reactivity parameter database (R2 = 0.93 and 81.6% of predictions within ±2.0 of the experimental values with Extra Trees algorithm). A Causal Structure Property Relationship (CSPR) approach was utilized, with focus on the physicochemical relationships between the descriptors and the predicted parameters, and on rational improvements of the prediction models. The nucleophiles were represented with a series of electronic and steric descriptors and the solvents were represented with principal component analysis (PCA) descriptors based on the ACS Solvent Tool. The models indicated that steric factors do not contribute significantly, because of bias in the experimental database. The most important descriptors are solvent-dependent HOMO energy and Hirshfeld charge of the nucleophilic atom. Replacing DFT descriptors with Parameterization Method 6 (PM6) descriptors for the nucleophiles led to an 8.7-fold decrease in computational time, and an ∼10% decrease in the percentage of predictions within ±2.0 and ±1.0 of the experimental values.


Subject(s)
Algorithms , Principal Component Analysis , Solvents
3.
J Vis ; 21(11): 12, 2021 10 05.
Article in English | MEDLINE | ID: mdl-34668930

ABSTRACT

Adult homeostatic visual plasticity can be induced by short-term patching, heralded by a shift in ocular dominance in favor of the deprived eye after monocular occlusion. The potential to boost visual neuroplasticity with environmental enrichment such as exercise has also been explored; however, the results are inconsistent, with some studies finding no additive effect of exercise. Studies to date have only considered the effect of patching alone or in combination with exercise. Whether exercise alone affects typical outcome measures of experimental estimates of short-term visual neuroplasticity is unknown. We therefore measured binocular rivalry in 20 healthy young adults (20-34 years old) at baseline and after three 2-hour interventions: patching (of the dominant eye) only, patching with exercise, and exercise only. Consistent with previous work, the patching interventions produced a shift in ocular dominance toward the deprived (dominant) eye. Mild- to moderate-intensity exercise in the absence of patching had several effects on binocular rivalry metrics, including a reduction in the dominant eye percept. The proportion of mixed percept and the time to first switch (onset rivalry) did not change from baseline across all interventions. Thus, we demonstrate that exercise alone can impact binocular rivalry outcomes measures. We did not observe a synergistic effect between patching and exercise in our data.


Subject(s)
Dominance, Ocular , Vision, Monocular , Adult , Exercise , Humans , Neuronal Plasticity , Sensory Deprivation , Vision, Binocular , Young Adult
4.
Headache ; 60(8): 1817-1829, 2020 09.
Article in English | MEDLINE | ID: mdl-32767768

ABSTRACT

BACKGROUND: Migraine is underdiagnosed and undertreated. Optometrists are primary eye care providers, who regularly encounter people with migraine as an incidental finding during routine eye examinations, or when patients present to rule out whether visual or ocular problems are contributing to headache symptoms. Knowledge and use of a migraine screening tool in optometric practice is, therefore, important to be able to identify and refer people with migraine for appropriate management. OBJECTIVE: We sought to investigate optometrists' current behaviors regarding screening for migraine, and to assess the effectiveness of an educational resource in promoting the use of a 3-item validated migraine screening questionnaire, the ID-Migraine. METHODS: We first conducted a cross-sectional study using a survey to assess optometrists' current knowledge and behaviors about migraine screening and willingness to participate in a pilot implementation program. Participants who provided their contact details were invited to watch an online educational resource about a validated migraine screening tool. After 6 weeks, these participants were invited to participate in a follow-up cohort study involving a survey to assess the effectiveness of the educational resource. RESULTS: Ninety-eight optometrists completed the initial survey as part of the cross-sectional study. We found that most optometrists actively asked patients about migraine (79/98 respondents, 81%) as part of routine eye examinations and self-rated themselves as confident in identifying migraine (71/98 respondents, 72%). However, the majority (90/98 respondents, 92%) were not aware of any validated migraine screening tools. Seventy-eight respondents provided their contact details to receive information about the subsequent cohort study. In response to the follow-up study survey (31/78 participants, 40%), 45% (14/31 respondents) of participants self-reported using the ID-Migraine tool after watching our educational video, and most of these participants (12/14 respondents, 86%) were likely or extremely likely to continue to use the tool in their practice. CONCLUSIONS: From our initial cross-sectional survey, we conclude that optometrists do not currently use validated screening tools for migraine and as such, there is an opportunity for continuing professional development in this area. Our follow-up cohort study demonstrates that educating optometrists on the importance and utility of a validated migraine screening tool is achievable with a relatively simple, low-time investment intervention (an online educational video). Such education may result in improved identification of migraine, which may lead to improved management.


Subject(s)
Education, Continuing , Health Knowledge, Attitudes, Practice , Health Personnel/education , Migraine Disorders/diagnosis , Optometry , Primary Health Care , Adult , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Male , Self Report
5.
Ophthalmic Physiol Opt ; 40(2): 117-127, 2020 03.
Article in English | MEDLINE | ID: mdl-32080894

ABSTRACT

PURPOSE: It is more difficult to perceive the direction of motion of larger, high contrast patterns than smaller, low contrast patterns due to spatial suppression. Spatial suppression of motion is considered important to the segmentation of moving objects in the visual environment. Previous studies have shown that such spatial suppression of motion is reduced in older adults in central vision, to the extent that older adults can have better sensitivity than younger adults for foveally presented stimuli. Our study was designed to explore whether spatial suppression of motion is similarly reduced for older adults in parafoveal regions and whether divided attention impacts on suppression strength because attention is known to impact on spatial interactions. METHODS: Twenty younger (19-34 years) and 18 older (61-77 years) adults completed a single task, where observers identified the direction of a drifting Gabor patch of variable size (σ of the Gaussian envelope = 0.5, 1, 2, 3, 4°) presented at 10 degrees of visual angle while observing a central fixation marker, and a dual task, where observers were required to divide their attention across two stimuli, the peripheral drifting Gabor patch and a central rapid serial visual presentation (RSVP) stream. RESULTS: Older adults showed increased spatial suppression of motion relative to younger adults for both tasks (main effect of group: p < 0.001). Dividing attention elevated thresholds for both age groups to a similar extent (main effect of attention: p = 0.002), but did not specifically alter spatial interactions (group x attention interaction: p = 0.13). CONCLUSIONS: Older adults require significantly longer than younger adults to correctly identify stimulus motion, and demonstrate increased spatial suppression of motion, in peripheral vision. When considered alongside previous evidence for reduced suppression for central fixation, our study provides evidence for substantial differences between foveal and parafoveal mechanisms of spatial suppression.


Subject(s)
Aging/physiology , Attention/physiology , Motion Perception/physiology , Space Perception/physiology , Adult , Aged , Discrimination, Psychological , Female , Humans , Male , Middle Aged , Photic Stimulation , Sensory Thresholds/physiology , Young Adult
6.
Ophthalmic Physiol Opt ; 38(4): 363-375, 2018 07.
Article in English | MEDLINE | ID: mdl-29774576

ABSTRACT

PURPOSE: The number of older adults is rapidly increasing internationally, leading to a significant increase in research on how healthy ageing impacts vision. Most clinical assessments of spatial vision involve simple detection (letter acuity, grating contrast sensitivity, perimetry). However, most natural visual environments are more spatially complicated, requiring contrast discrimination, and the delineation of object boundaries and contours, which are typically present on non-uniform backgrounds. In this review we discuss recent research that reports on the effects of normal ageing on these more complex visual functions, specifically in the context of recent neurophysiological studies. RECENT FINDINGS: Recent research has concentrated on understanding the effects of healthy ageing on neural responses within the visual pathway in animal models. Such neurophysiological research has led to numerous, subsequently tested, hypotheses regarding the likely impact of healthy human ageing on specific aspects of spatial vision. SUMMARY: Healthy normal ageing impacts significantly on spatial visual information processing from the retina through to visual cortex. Some human data validates that obtained from studies of animal physiology, however some findings indicate that rethinking of presumed neural substrates is required. Notably, not all spatial visual processes are altered by age. Healthy normal ageing impacts significantly on some spatial visual processes (in particular centre-surround tasks), but leaves contrast discrimination, contrast adaptation, and orientation discrimination relatively intact. The study of older adult vision contributes to knowledge of the brain mechanisms altered by the ageing process, can provide practical information regarding visual environments that older adults may find challenging, and may lead to new methods of assessing visual performance in clinical environments.


Subject(s)
Aging , Discrimination, Psychological/physiology , Form Perception/physiology , Visual Acuity/physiology , Visual Cortex/physiology , Visual Pathways/physiology , Aged , Humans
7.
Nucleic Acids Res ; 43(14): 7152-61, 2015 Aug 18.
Article in English | MEDLINE | ID: mdl-26138488

ABSTRACT

Effector-triggered immunity (ETI) is activated when plant disease resistance (R) proteins recognize the presence of pathogen effector proteins delivered into host cells. The ETI response generally encompasses a defensive 'hypersensitive response' (HR) that involves programmed cell death at the site of pathogen recognition. While many R protein and effector protein pairs are known to trigger HR, other components of the ETI signaling pathway remain elusive. Effector genes regulated by inducible promoters cause background HR due to leaky protein expression, preventing the generation of relevant transgenic plant lines. By employing the HyP5SM suicide exon, we have developed a strategy to tightly regulate effector proteins such that HR is chemically inducible and non-leaky. This alternative splicing-based gene regulation system was shown to successfully control Bs2/AvrBs2-dependent and RPP1/ATR1Δ51-dependent HR in Nicotiana benthamiana and Nicotiana tabacum, respectively. It was also used to generate viable and healthy transgenic Arabidopsis thaliana plants that inducibly initiate HR. Beyond enabling studies on the ETI pathway, our regulatory strategy is generally applicable to reduce or eliminate undesired background expression of transgenes.


Subject(s)
Disease Resistance/genetics , Exons , Gene Expression Regulation, Plant , Promoter Regions, Genetic , Transcription, Genetic , Alternative Splicing , Arabidopsis/genetics , Bacterial Proteins/genetics , Dexamethasone/pharmacology , Oomycetes/genetics , Phenotype , Plants, Genetically Modified/genetics , Nicotiana/genetics , Transcription, Genetic/drug effects
8.
J Vis ; 17(1): 16, 2017 01 01.
Article in English | MEDLINE | ID: mdl-28114491

ABSTRACT

Numerous previous studies have shown that healthy aging results in increased foveal center surround contrast suppression when the center and surround patterns are presented to both eyes. The mechanistic cause of this observation is not well established. Neurophysiological and psychophysical studies have shown that different mechanisms of parafoveal center surround suppression can be tapped by manipulating viewing conditions to present the center and surround to the same eye (intraocular viewing) or to different eyes (interocular viewing), or by manipulating stimulus parameters such as duration. Here, we tested intraocular and interocular foveal center surround contrast suppression for stimuli of 40 ms and 200 ms duration in 18 younger and 18 older adults. For both groups, foveal intraocular center surround contrast suppression decreased with longer stimulus duration whereas interocular surround suppression did not, confirming contributions from separate mechanisms to these forms of suppression. Intraocular center surround contrast suppression was increased in older adults compared to younger adults; however, interocular suppression was similar in both groups. Our results indicate that aging differentially affects distinct forms of suppression arising at various levels of the visual pathway.


Subject(s)
Aging/physiology , Contrast Sensitivity/physiology , Fovea Centralis/physiology , Visual Cortex/physiology , Visual Pathways/physiology , Visual Perception/physiology , Adult , Aged , Female , Humans , Male , Middle Aged , Photic Stimulation , Psychophysics , Time Factors , Young Adult
9.
Cephalalgia ; 36(1): 5-14, 2016 Jan.
Article in English | MEDLINE | ID: mdl-25787685

ABSTRACT

BACKGROUND: People with migraine show increased surround suppression of perceived contrast, a perceptual analogue of centre-surround antagonistic interactions in visual cortex. A proposed mechanism is that cortical 'hyperexcitability' or 'hyperresponsivity', a prominent theory in the migraine literature, drives abnormal excitatory-inhibitory balance to give increased local inhibition. The purpose of this cross-sectional study was to determine whether cortical hyperresponsivity and excitatory-inhibitory imbalance manifests in the visual cortical response of migraine sufferers. METHODS: Interictal steady-state visual evoked potentials (VEPs) in response to 0 to 97% contrast were recorded in 30 migraine participants (15 without aura, 15 with aura) and 21 non-headache controls. Monotonicity indices were calculated to determine response saturation or supersaturation. Contrast gain was modelled with a modified saturating hyperbolic function to allow for variation in excitation and inhibition. RESULTS: A greater proportion of migraine participants (43%) than controls (14%) exhibited significant VEP supersaturation at high contrast, based on monotonicity index (chi-square, p = 0.028). Supersaturation was also evident by the trend for greater suppressive exponent values in migraine compared to control individuals (Mann-Whitney rank sum, p = 0.075). CONCLUSIONS: Supersaturation in migraine is consistent with excess excitation (hyperresponsivity) driving increased network inhibition and provides support for excitatory-inhibitory imbalance as a pathophysiological disturbance in migraine.


Subject(s)
Evoked Potentials, Visual/physiology , Migraine with Aura/physiopathology , Migraine without Aura/physiopathology , Visual Cortex/physiology , Adolescent , Adult , Child , Excitatory Postsynaptic Potentials/physiology , Female , Humans , Inhibitory Postsynaptic Potentials/physiology , Male , Migraine with Aura/diagnosis , Migraine without Aura/diagnosis , Young Adult
10.
J Vis ; 16(3): 10, 2016.
Article in English | MEDLINE | ID: mdl-26868888

ABSTRACT

Visual contextual effects enable inference regarding neural mechanisms of cortical function, principally because of similarities between the stimulus properties influencing human perception and those modifying primate visual cortical neural responses. Most neurophysiology assesses nonfoveal cellular function and circuitry, while most human studies are foveal. Here we use parafoveal stimuli to measure center-surround perception of contrast in older and younger adults. We measure the influence of both near and far surround because neurophysiology demonstrates different circuitry for these areas. Contrast suppression from the near surround was reduced in older observers, while that from the far surround was intact. Our results are consistent with reduced intracortical inhibition with age and normal extrastriate feedback. Interestingly, in the same older observers, foveal surround suppression of contrast was strengthened relative to younger adults, demonstrating a clear distinction between foveal and parafoveal center-surround behavior. We assume that underlying alterations in cortical neurotransmitter levels with age should not differ substantially between the areas of visual cortex representing foveal and near foveal regions. Consequently, our results suggest regional differences in center-surround circuitry. That older adults have varied contextual effects of visual contrast as a function of retinal eccentricity suggests complex effects of aging on scene and object perception.


Subject(s)
Aging/physiology , Contrast Sensitivity/physiology , Fovea Centralis/physiology , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult
11.
J Am Chem Soc ; 137(12): 4151-7, 2015 Apr 01.
Article in English | MEDLINE | ID: mdl-25768298

ABSTRACT

A highly robust immobilized [Cp*IrCl2]2 precatalyst on Wang resin for transfer hydrogenation, which can be recycled up to 30 times, was studied using a novel combination of X-ray absorption spectroscopy (XAS) at Ir L3-edge, Cl K-edge, and K K-edge. These culminate in in situ XAS experiments that link structural changes of the Ir complex with its catalytic activity and its deactivation. Mercury poisoning and "hot filtration" experiments ruled out leached Ir as the active catalyst. Spectroscopic evidence indicates the exchange of one chloride ligand with an alkoxide to generate the active precatalyst. The exchange of the second chloride ligand, however, leads to a potassium alkoxide-iridate species as the deactivated form of this immobilized catalyst. These findings could be widely applicable to the many homogeneous transfer hydrogenation catalysts with Cp*IrCl substructure.


Subject(s)
Chlorides/chemistry , Iridium/chemistry , Potassium/chemistry , Catalysis , Hydrogenation , Ligands , X-Ray Absorption Spectroscopy
12.
J Synchrotron Radiat ; 22(6): 1426-39, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26524308

ABSTRACT

The 2-4 keV energy range provides a rich window into many facets of materials science and chemistry. Within this window, P, S, Cl, K and Ca K-edges may be found along with the L-edges of industrially important elements from Y through to Sn. Yet, compared with those that cater for energies above ca. 4-5 keV, there are relatively few resources available for X-ray spectroscopy below these energies. In addition, in situ or operando studies become to varying degrees more challenging than at higher X-ray energies due to restrictions imposed by the lower energies of the X-rays upon the design and construction of appropriate sample environments. The XMaS beamline at the ESRF has recently made efforts to extend its operational energy range to include this softer end of the X-ray spectrum. In this report the resulting performance of this resource for X-ray spectroscopy is detailed with specific attention drawn to: understanding electrostatic and charge transfer effects at the S K-edge in ionic liquids; quantification of dilution limits at the Cl K- and Rh L3-edges and structural equilibria in solution; in vacuum deposition and reduction of [Rh(I)(CO)2Cl]2 to γ-Al2O3; contamination of γ-Al2O3 by Cl and its potential role in determining the chemical character of supported Rh catalysts; and the development of chlorinated Pd catalysts in `green' solvent systems. Sample environments thus far developed are also presented, characterized and their overall performance evaluated.

13.
Eukaryot Cell ; 13(6): 785-95, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24728195

ABSTRACT

Conditional gene silencing by RNA interference in Trypanosoma brucei can be inconclusive if knockdowns are inefficient or have off-target effects. To enable efficient, specific silencing of single-copy genes in mammalian-infective, bloodstream form trypanosomes, we developed a system that targets the heterologous and functional Trypanosoma cruzi U2AF35 3' untranslated region (UTR) (Tc3) or, alternatively, the sequence of the PTP tag, which can be fused to any mRNA of interest. Two cell lines were created, single-marker Tc3 (smTc3) and smPTP, which conditionally express Tc3 and PTP double-stranded RNA (dsRNA), respectively. The system depends on manipulating both alleles of the gene of interest so that cells exclusively express the target mRNA as a fusion to one of these heterologous sequences. We generated allele integration vectors in which the C-terminal part of a gene's coding sequence can be fused to either heterologous sequence in a single cloning step. We first tested this system with CITFA7, which encodes a well-characterized subunit of the class I transcription factor A (CITFA), an essential factor for transcription initiation by RNA polymerase I. Targeting either Tc3 or PTP fused to the CITFA7 mRNA resulted in gene knockdowns that were as efficient and specific as targeting the endogenous CITFA7 mRNA. Moreover, application of this system to CITFA1, which could not be silenced by established methods, demonstrated that the gene encodes an essential CITFA subunit that mediates binding of the transcription factor complex to RNA polymerase I promoters.


Subject(s)
Gene Knockdown Techniques/methods , Protozoan Proteins/genetics , RNA Interference , RNA, Small Interfering/genetics , Transcription Factors/genetics , Trypanosoma brucei brucei/genetics , Protozoan Proteins/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Transcription Factors/metabolism , Trypanosoma brucei brucei/metabolism
14.
Cephalalgia ; 34(1): 42-57, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23969723

ABSTRACT

PURPOSE: In between migraine attacks, some people show visual field defects that are worse when measured closer to the end of a migraine event. In this cohort study, we consider whether electrophysiological responses correlate with visual field performance at different times post-migraine, and explore evidence for cortical versus retinal origin. METHODS: Twenty-six non-headache controls and 17 people with migraine performed three types of perimetry (static, flicker and blue-on-yellow) to assess different aspects of visual function at two visits conducted at different durations post-migraine. On the same days, the pattern electroretinogram (PERG) and visual evoked response (PVER) were recorded. RESULTS: Migraine participants showed persistent, interictal, localised visual field loss, with greater deficits at the visit nearer to migraine offset. Spatial patterns of visual field defect consistent with retinal and cortical dysfunction were identified. The PERG was normal, whereas the PVER abnormality found did not change with time post-migraine and did not correlate with abnormal visual field performance. CONCLUSIONS: Dysfunction on clinical tests of vision is common in between migraine attacks; however, the nature of the defect varies between individuals and can change with time. People with migraine show markers of both retinal and/or cortical dysfunction. Abnormal visual field sensitivity does not predict abnormality on electrophysiological testing.


Subject(s)
Evoked Potentials, Visual , Migraine Disorders/diagnosis , Migraine Disorders/physiopathology , Vision Disorders/diagnosis , Vision Disorders/physiopathology , Visual Fields , Adolescent , Child , Child, Preschool , Electroretinography , Female , Humans , Male , Migraine Disorders/complications , Time Factors , Vision Disorders/etiology , Visual Field Tests
15.
Clin Exp Optom ; 107(1): 83-92, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37078177

ABSTRACT

CLINICAL RELEVANCE: Interpersonal skills are crucial for successful clinician-patient interactions. To prepare future optometrists for clinical practice, pedagogical evaluation is important to support the implementation of new strategies for teaching and evaluating interpersonal skills. BACKGROUND: Optometry students largely develop their interpersonal skills through in-person patient interactions. Telehealth is increasing, yet strategies to develop the interpersonal skills of students for teleconsulting have not been explored. This study aimed to assess the feasibility, effectiveness and perceived usefulness of an online, multisource (patients, clinicians and students) evaluation and feedback program for developing interpersonal skills. METHODS: Via an online teleconferencing platform, optometry students (n = 40) interacted with a volunteer patient, observed by a teaching clinician. Patients and clinicians evaluated the interpersonal skills of the student in two ways: (1) qualitative written feedback, and (2) quantitative rating (Doctors' Interpersonal Skills Questionnaire). All students received written patient and clinician feedback after the session, but not their quantitative ratings. A subset of students (n = 19) completed two sessions, self-ratings, and were provided with their written feedback and an audiovisual recording from their first interaction before completing the second session. All participants were invited to complete an anonymous survey at program completion. RESULTS: Patient and clinician overall interpersonal skills ratings were positively correlated (Spearman's r = 0.35, p = 0.03) and showed moderate agreement (Lin's concordance coefficient = 0.34). Student self-ratings did not match patient ratings (r = 0.01, p = 0.98), whereas there was moderate agreement between clinician and student ratings (Lin's concordance coefficient = 0.30). Ratings improved at the second visit (p = 0.01). Patient ratings were higher than clinicians (p = 0.01) and students (p = 0.03). All participants agreed that the program was feasible, useful and effective at fostering good interpersonal skills. CONCLUSION: Multisource feedback about interpersonal skills contributes to improvement in student performance. Patients and clinicians can evaluate and provide useful feedback to optometry students about their interpersonal skills using online methods.


Subject(s)
Optometry , Students, Medical , Humans , Feedback , Social Skills , Clinical Competence
16.
J Parkinsons Dis ; 14(1): 167-180, 2024.
Article in English | MEDLINE | ID: mdl-38189711

ABSTRACT

BACKGROUND: Visual biomarkers of Parkinson's disease (PD) are attractive as the retina is an outpouching of the brain. Although inner retinal neurodegeneration in PD is well-established this has overlap with other neurodegenerative diseases and thus outer retinal (photoreceptor) measures warrant further investigation. OBJECTIVE: To examine in a cross-sectional study whether clinically implementable measures targeting outer retinal function and structure can differentiate PD from healthy ageing and whether these are sensitive to intraday levodopa (L-DOPA) dosing. METHODS: Centre-surround perceptual contrast suppression, macular visual field sensitivity, colour discrimination, light-adapted electroretinography and optical coherence tomography (OCT) were tested in PD participants (n = 16) and controls (n = 21). Electroretinography and OCT were conducted before and after midday L-DOPA in PD participants, or repeated after ∼2 hours in controls. RESULTS: PD participants had decreased center-surround contrast suppression (p < 0.01), reduced macular visual field sensitivity (p < 0.05), color vision impairment (p < 0.01) photoreceptor dysfunction (a-wave, p < 0.01) and photoreceptor neurodegeneration (outer nuclear layer thinning, p < 0.05), relative to controls. Effect size comparison between inner and outer retinal parameters showed that photoreceptor metrics were similarly robust in differentiating the PD group from age-matched controls as inner retinal changes. Electroretinography and OCT were unaffected by L-DOPA treatment or time. CONCLUSIONS: We show that outer retinal outcomes of photoreceptoral dysfunction (decreased cone function and impaired color vision) and degeneration (i.e., outer nuclear layer thinning) were equivalent to inner retinal metrics at differentiating PD from healthy age-matched adults. These findings suggest outer retinal metrics may serve as useful biomarkers for PD.


Subject(s)
Parkinson Disease , Adult , Humans , Parkinson Disease/complications , Parkinson Disease/diagnostic imaging , Parkinson Disease/drug therapy , Levodopa/pharmacology , Levodopa/therapeutic use , Cross-Sectional Studies , Retina/diagnostic imaging , Tomography, Optical Coherence/methods , Visual Perception , Biomarkers , Electrophysiology
17.
Chem Sci ; 15(15): 5764-5774, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38638222

ABSTRACT

A principal component surfactant_map was developed for 91 commonly accessible surfactants for use in surfactant-enabled organic reactions in water, an important approach for sustainable chemical processes. This map was built using 22 experimental and theoretical descriptors relevant to the physicochemical nature of these surfactant-enabled reactions, and advanced principal component analysis algorithms. It is comprised of all classes of surfactants, i.e. cationic, anionic, zwitterionic and neutral surfactants, including designer surfactants. The value of this surfactant_map was demonstrated in activating simple inorganic fluoride salts as effective nucleophiles in water, with the right surfactant. This led to the rapid development (screening 13-15 surfactants) of two fluorination reactions for ß-bromosulfides and sulfonyl chlorides in water. The latter was demonstrated in generating a sulfonyl fluoride with sufficient purity for direct use in labelling of chymotrypsin, under physiological conditions.

18.
Eukaryot Cell ; 11(12): 1573-81, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23104567

ABSTRACT

Trypanosoma brucei is the only organism known to have evolved a multifunctional RNA polymerase I (pol I) system that is used to express the parasite's ribosomal RNAs, as well as its major cell surface antigens, namely, the variant surface glycoprotein (VSG) and procyclin, which are vital for establishing successful infections in the mammalian host and the tsetse vector, respectively. Thus far, biochemical analyses of the T. brucei RNA pol I transcription machinery have elucidated the subunit structure of the enzyme and identified the class I transcription factor A (CITFA). CITFA binds to RNA pol I promoters, and its CITFA-2 subunit was shown to be absolutely essential for RNA pol I transcription in the parasite. Tandem affinity purification (TAP) of CITFA revealed the subunits CITFA-1 to -6, which are conserved only among kinetoplastid organisms, plus the dynein light chain DYNLL1. Here, by tagging CITFA-6 instead of CITFA-2, a complex was purified that contained all known CITFA subunits, as well as a novel proline-rich protein. Functional studies carried out in vivo and in vitro, as well as a colocalization study, unequivocally demonstrated that this protein is a bona fide CITFA subunit, essential for parasite viability and indispensable for RNA pol I transcription of ribosomal gene units and the active VSG expression site in the mammalian-infective life cycle stage of the parasite. Interestingly, CITFA-7 function appears to be species specific, because expression of an RNA interference (RNAi)-resistant CITFA-7 transgene from Trypanosoma cruzi could not rescue the lethal phenotype of silencing endogenous CITFA-7.


Subject(s)
Protein Subunits/metabolism , Protozoan Proteins/metabolism , RNA Polymerase I/metabolism , Transcription Factors/metabolism , Transcription, Genetic , Trypanosoma brucei brucei/metabolism , Amino Acid Sequence , Dyneins/metabolism , Molecular Sequence Data , Protein Subunits/isolation & purification , Protozoan Proteins/isolation & purification , Transcription Factors/isolation & purification , Trypanosoma brucei brucei/enzymology , Trypanosoma brucei brucei/genetics
19.
IBRO Neurosci Rep ; 14: 419-427, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37388492

ABSTRACT

In healthy adults with normal vision, temporary deprivation of one eye's visual experience produces transient yet robust homeostatic plasticity effects, where the deprived eye becomes more dominant. This shift in ocular dominance is short-lived and compensatory. Previous work shows that monocular deprivation decreases resting state gamma aminobutyric acid (GABA; inhibitory neurotransmitter) levels in visual cortex, and that those with the greatest reduction in GABA have stronger shifts due to monocular deprivation. Components of the GABAergic system in visual cortex vary with age (early childhood, early teen years, ageing); hence if GABA is critical to homeostatic plasticity within the visual system, adolescence may be a key developmental period where differences in plasticity manifest. Here we measured short-term visual deprivation effects on binocular rivalry in 24 adolescents (aged 10-15 years) and 23 young adults (aged 20-25 years). Despite differences in baseline features of binocular rivalry (adolescents showed more mixed percept p < 0.001 and a tendency for faster switching p = 0.06 compared to adults), deprived eye dominance increased (p = 0.01) similarly for adolescents and adults after two hours of patching. Other aspects of binocular rivalry - time to first switch (heralding the onset of rivalry) and mixed percept - were unaltered by patching. These findings suggest that binocular rivalry after patching can be used as a behavioral proxy for experience-dependent visual cortical plasticity in adolescents in the same way as adults, and that homeostatic plasticity to compensate for temporarily reduced visual input is established and effective by adolescence.

20.
Clin Exp Optom ; 106(7): 711-725, 2023 09.
Article in English | MEDLINE | ID: mdl-36375138

ABSTRACT

Dementia comprises a group of brain disorders characterised by loss of cognitive function. Sensory loss, predominantly vision (the focus of this review) and hearing, is a significant problem for people living with dementia. Eyecare practitioners such as optometrists therefore play an important role in identifying and addressing vision-related care needs. To support provision of high quality "dementia-friendly" eyecare, this scoping review summarises recent primary research findings and available clinical practice guidelines, to identify research gaps relating to vision and dementia, and make recommendations for future research and clinical practice. The review set a priori guidelines for the population, concept and context based on the review questions. Primary research papers (2016-2021) were included via 3-step search strategy: preliminary search to index terms, full search, search reference lists of included articles for further inclusions. Additionally, websites of eyecare professional bodies in English-speaking countries were searched to identify current clinical eyecare practice guidelines relating to dementia. Study characteristics (e.g. country, study design) were reported descriptively. Patterns within findings/recommendations from included sources were identified using thematic analysis and reported as themes. 1651 titles/abstracts and 161 full-text articles were screened for eligibility. Three clinical practice guidelines were also identified. The final review included 21 sources: 18 primary research papers and 3 clinical practice guidelines. The thematic analysis reported five key themes: Diagnosis/Screening, dementia progression, findings on clinical visual testing, tailored approach to care, improving care. This scoping review demonstrated limited information about current practices of optometrists working with people living with dementia. Recent evidence reinforces the continuing need for improved eyecare for people living with dementia, taking into account their specific needs with an individualised approach. Up-to-date practical recommendations are synthesised for eyecare providers before, during and after a consultation with a person living with dementia, to better support their care.


Subject(s)
Dementia , Referral and Consultation , Humans , Dementia/diagnosis
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