A photoelectron imaging and quantum chemistry study of the deprotonated indole anion

Indole is an important molecular motif in many biological molecules and exists in its deprotonated anionic form in the cyan fluorescent protein, an analogue of green fluorescent protein. However, the electronic structure of the deprotonated indole anion has been relatively unexplored. Here, we use a combination of anion photoelectron velocity-map imaging measurements and quantum chemistry calculations to probe the electronic structure of the deprotonated indole anion. We report vertical detachment energies (VDEs) of 2.45 ± 0.05 eV and 3.20 ± 0.05 eV, respectively. The value for D₀ is in agreement with recent high-resolution measurements whereas the value for D₁ is a new measurement. We find that the first electronically excited singlet state of the anion, S₁(ππ*), lies above the VDE and has shape resonance character with respect to the D₀ detachment continuum and Feshbach resonance character with respect to the D₁ continuum

Controlling electron emission from the photoactive yellow protein chromophore by substitution at the coumaric acid group

Understanding how the interactions between a chromophore and its surrounding protein control the function of a photoactive protein remains a challenge. Here, we present the results of photoelectron spectroscopy measurements and quantum chemistry calculations aimed at investigating how substitution at the coumaryl tail of the photoactive yellow protein chromophore controls competing relaxation pathways following photoexcitation of isolated chromophores in the gas phase with ultraviolet light in the range 350-315 nm. The photoelectron spectra are dominated by electrons resulting from direct detachment and fast detachment from the 2(1)ππ* state but also have a low electron kinetic energy component arising from autodetachment from lower lying electronically excited states or thermionic emission from the electronic ground state. We find that substituting the hydrogen atom of the carboxylic acid group with a methyl group lowers the threshold for electron detachment but has very little effect on the competition between the different relaxation pathways, whereas substituting with a thioester group raises the threshold for electron detachment and appears to 'turn off' the competing electron emission processes from lower lying electronically excited states. This has potential implications in terms of tuning the light-induced electron donor properties of photoactive yellow protein

Differentiation state-specific mitochondrial dynamic regulatory networks are revealed by global transcriptional analysis of the developing chicken lens.

The mature eye lens contains a surface layer of epithelial cells called the lens epithelium that requires a functional mitochondrial population to maintain the homeostasis and transparency of the entire lens. The lens epithelium overlies a core of terminally differentiated fiber cells that must degrade their mitochondria to achieve lens transparency. These distinct mitochondrial populations make the lens a useful model system to identify those genes that regulate the balance between mitochondrial homeostasis and elimination. Here we used an RNA sequencing and bioinformatics approach to identify the transcript levels of all genes expressed by distinct regions of the lens epithelium and maturing fiber cells of the embryonic Gallus gallus (chicken) lens. Our analysis detected more than 15,000 unique transcripts expressed by the embryonic chicken lens. Of these, more than 3000 transcripts exhibited significant differences in expression between lens epithelial cells and fiber cells. Multiple transcripts coding for separate mitochondrial homeostatic and degradation mechanisms were identified to exhibit preferred patterns of expression in lens epithelial cells that require mitochondria relative to lens fiber cells that require mitochondrial elimination. These included differences in the expression levels of metabolic (DUT, PDK1, SNPH), autophagy (ATG3, ATG4B, BECN1, FYCO1, WIPI1), and mitophagy (BNIP3L/NIX, BNIP3, PARK2, p62/SQSTM1) transcripts between lens epithelial cells and lens fiber cells. These data provide a comprehensive window into all genes transcribed by the lens and those mitochondrial regulatory and degradation pathways that function to maintain mitochondrial populations in the lens epithelium and to eliminate mitochondria in maturing lens fiber cells

Longitudinal Assessment of Antisaccades in Patients with Multiple Sclerosis

We have previously demonstrated that assessment of antisaccades (AS) provides not only measures of motor function in multiple sclerosis (MS), but measures of cognitive control processes in particular, attention and working memory. This study sought to demonstrate the potential for AS measures to sensitively reflect change in functional status in MS. Twenty-four patients with relapsing-remitting MS and 12 age-matched controls were evaluated longitudinally using an AS saccade task. Compared to control subjects, a number of saccade parameters changed significantly over a two year period for MS patients. These included saccade error rates, latencies, and accuracy measures. Further, for MS patients, correlations were retained between OM measures and scores on the PASAT, which is considered the reference task for the cognitive evaluation of MS patients. Notably, EDSS scores for these patients did not change significantly over this period. These results demonstrate that OM measures may reflect disease evolution in MS, in the absence of clinically evident changes as measured using conventional techniques. With replication, these markers could ultimately be developed into a cost-effective, non-invasive, and well tolerated assessment tool to assist in confirming progression early in the disease process, and in measuring and predicting response to therapy

Workplace health promotion: assessing the cardiopulmonary risks of the construction workforce in Hong Kong

Objective Health needs of different employee subgroups within an industry can differ. We report the results of a workplace cardiopulmonary risk assessment targeting workers and support staff in the construction industry. Methods A free worksite-based cardiopulmonary risk assessment for 1,903 workers on infrastructural contracts across Hong Kong was initiated in May 2014. Cardiopulmonary risk screening was performed in 60-minute blocks for approximately 30 workers/block with individualized feedback and lifestyle counseling. Risk profiles stratified by occupational roles are differentiated using the χ2-test for categorical and Student’s t-test for continuous variables. Results Most construction workers and clerks/professionals were male (83.2% and 71.2%, respectively) and Chinese (78.7% and 90.9%, respectively). Construction workers were older (mean: 44.9 years, SD 11.5) and less well-educated (6.1% received tertiary education) than clerks/professionals (35.0 years, 10.7; 72.6% received tertiary education), but more likely to be hypertensive (22.6% vs. 15.4%, p<0.001), overweight/obese (71.7% vs. 56.6%, p<0.001), centrally obese (53.1% vs. 35.5%, p<0.001), and have undesirable levels of high-density lipoprotein (41.6% vs. 35.8%, p<0.05) and diabetic levels of non-fasting blood glucose (4.3% vs. 1.6%, p<0.05). Up to 12.6% of construction workers and 9.7% of office clerks/professions had three or more metabolic syndrome risk factors. While construction workers were more likely than clerks/professionals to be daily smokers, they reported better work-related physical activity and diet. Conclusions Simple worksite health risk screening can identify potentially high-cardiopulmonary-risk construction industry employee subgroups for onward confirmatory referral. Separate cardiopulmonary health promotion strategies that account for the varying lifestyle profiles of the two employee subgroups in the industry appear justified.published_or_final_versio

Hong Kong Chinese community leaders' perspectives on family health, happiness and harmony: A qualitative study

This paper examines the views of Hong Kong community leaders on the underlying issues that affect family health, happiness and harmony (3Hs) in Hong Kong. Using a community reconnaissance method, a series of individual in-depth interviews with 26 leaders that represent neighbourhoods of diverse socio-economic status (SES) from June to August 2008 were conducted. Participants considered that changing family structure, economic situation and strong work ethic are the most salient factors that affect family 3Hs. The deprived comprehensive social security assistance recipients, single-parent families and migrant women were considered to be the most vulnerable groups to breakdown in family 3Hs and particularly, they lack family resources. Families from different SES have to overcome different challenges in order to achieve and sustain family 3Hs. Leaders from low SES neighbourhood were concerned more about providing tangible help such as child care facilities to improve family resources, whereas leaders from high SES neighbourhood focused more on preventive interventions such as education on relationship skills to achieve better family well-being. The findings offer insights in designing effective social marketing education campaigns and family-friendly workplace policy to promote social harmony through the maintenance of 3Hs families. © The Author 2011. Published by Oxford University Press. All rights reserved.postprin

Homozygosity Mapping and Genetic Analysis of Autosomal Recessive Retinal Dystrophies in 144 Consanguineous Pakistani Families.

PurposeThe Pakistan Punjab population has been a rich source for identifying genes causing or contributing to autosomal recessive retinal degenerations (arRD). This study was carried out to delineate the genetic architecture of arRD in the Pakistani population.MethodsThe genetic origin of arRD in a total of 144 families selected only for having consanguineous marriages and multiple members affected with arRD was examined. Of these, causative mutations had been identified in 62 families while only the locus had been identified for an additional 15. The remaining 67 families were subjected to homozygosity exclusion mapping by screening of closely flanking microsatellite markers at 180 known candidate genes/loci followed by sequencing of the candidate gene for pathogenic changes.ResultsOf these 67 families subjected to homozygosity mapping, 38 showed homozygosity for at least one of the 180 regions, and sequencing of the corresponding genes showed homozygous cosegregating mutations in 27 families. Overall, mutations were detected in approximately 61.8 % (89/144) of arRD families tested, with another 10.4% (15/144) being mapped to a locus but without a gene identified.ConclusionsThese results suggest the involvement of unmapped novel genes in the remaining 27.8% (40/144) of families. In addition, this study demonstrates that homozygosity mapping remains a powerful tool for identifying the genetic defect underlying genetically heterogeneous arRD disorders in consanguineous marriages for both research and clinical applications

Mechanism of resonant electron emission from the deprotonated GFP chromophore and its biomimetics

The Green Fluorescent Protein (GFP), which is widely used in bioimaging, is known to undergo light-induced redox transformations. Electron transfer is thought to occur resonantly through excited states of its chromophore; however, a detailed understanding of the electron gateway states of the chromophore is still missing. Here, we use photoelectron spectroscopy and high-level quantum chemistry calculations to show that following UV excitation, the ultrafast electron dynamics in the chromophore anion proceeds via an excited shape resonance strongly coupled to the open continuum. The impact of this state is found across the entire 355–315 nm excitation range, from above the first bound–bound transition to below the opening of higher-lying continua. By disentangling the electron dynamics in the photodetachment channels, we provide an important reference for the adiabatic position of the electron gateway state, which is located at 348 nm, and discover the source of the curiously large widths of the photoelectron spectra that have been reported in the literature. By introducing chemical modifications to the GFP chromophore, we show that the detachment threshold and the position of the gateway state, and hence the underlying excited-state dynamics, can be changed systematically. This enables a fine tuning of the intrinsic electron emission properties of the GFP chromophore and has significant implications for its function, suggesting that the biomimetic GFP chromophores are more stable to photooxidation

Non-radiative relaxation dynamics of pyrrole following excitation in the range 249.5-200nm

The non-radiative relaxation dynamics of pyrrole have been investigated using time-resolved photoelectron spectroscopy and quantum dynamics simulations. Following excitation of the A2(11πσ*) state, we observe population flow out of the Franck-Condon region on a ≲50 fs timescale. Following excitation of the B2(21ππ*) state, we observe population being transferred to the A2(11πσ*) state on a <50. fs timescale and subsequently out of the Franck-Condon region, also on a <50. fs timescale. Quantum dynamics calculations suggest that population is transferred from the B2(21ππ*) state through the A2(1π3pz) state to the B1(21πσ*) state before being transferred to the A2(11πσ*) state

Applying the Coulomb Failure Function with an optimally oriented plane to the 2008 Mw 7.9 Wenchuan earthquake triggering

The Coulomb failure function (CFF) quantitatively describes static stress changes in secondary faults near the source fault of an earthquake. CFF can be employed to monitor how static stress transfers and then shed some light on the probability of successive events occurring around a source fault. In this paper we focus on the CFF and particularly on optimally oriented planes. We present a unified model to determine an optimally oriented plane and its corresponding Coulomb stress, then apply the model to the 2003 Mw 6.6 Bam (Iran) earthquake and the 2008 Mw 7.9 Wenchuan (China) earthquake, thereby checking its effectiveness. Our results show that spatial correlation between positive Coulomb stress changes and aftershocks are, for the 2003 Bam earthquake, 47.06% when elastic Coulomb stress changes are resolved on uniform planes and 87.53% when these are resolved on optimally oriented planes at depth; for the 2008 Wenchuan earthquake the correlations are 45.68% and 58.20%, respectively. It is recommended that account be taken of optimally oriented planes when drawing a Coulomb stress map for analyzing earthquake triggering effects