Interaction of metal salts with cytoskeletal motor protein systems

Interactions of chemicals with the microtubular network of cells may lead to genotoxicity. Micronuclei (MN) might be caused by interaction of metals with tubulin and/or kinesin. The genotoxic effects of inorganic lead and mercury salts were studied using the MN assay and the CREST analysis in V79 Chinese hamster fibroblasts. Effects on the functional activity of motor protein systems were examined by measurement of tubulin assembly and kinesin-driven motility. Lead and mercury salts induced MN dose-dependently. The no-effect-concentration for MN induction was 1.1 μM PbCl2, 0.05 μM Pb(OAc)2 and 0.01 μM HgCl2. The in vitro results obtained for PbCl2 correspond to reported MN induction in workers occupationally exposed to lead, starting at 1.2 μM Hg(II) (Vaglenov et al., 2001, Environ. Health Perspect. 109, 295-298). The CREST Analysis indicate aneugenic effects of Pb(II) and aneugenic and additionally clastogenic effects of Hg(II). Lead (chloride, acetate, and nitrate) and mercury (chloride and nitrate) interfered dose-dependently with tubulin assembly in vitro. The no-effect-concentration for lead salts in this assay was 10 μM. Inhibition of tubulin assembly by mercury started at 2 μM. The gliding velocity of microtubules along immobilised kinesin molecules was affected by 25 μM Pb(NO3)2 and 0.1 μM HgCl2 in a dose-dependent manner. Our data support the hypothesis that lead and mercury genotoxicity may result, at least in part, via disturbance of chromosome segregation via interaction with cytoskeletal proteins.

Gray matter deficits, mismatch negativity, and outcomes in schizophrenia

Reduced mismatch negativity (MMN) in response to auditory change is a well-established finding in schizophrenia and has been shown to be correlated with impaired daily functioning, rather than with hallmark signs and symptoms of the disorder. In this study, we investigated (1) whether the relationship between reduced MMN and impaired daily functioning is mediated by cortical volume loss in temporal and frontal brain regions in schizophrenia and (2) whether this relationship varies with the type of auditory deviant generating MMN. MMN in response to duration, frequency, and intensity deviants was recorded from 18 schizophrenia subjects and 18 pairwise age- and gender-matched healthy subjects. Patients’ levels of global functioning were rated on the Social and Occupational Functioning Assessment Scale. High-resolution structural magnetic resonance scans were acquired to generate average cerebral cortex and temporal lobe models using cortical pattern matching. This technique allows accurate statistical comparison and averaging of cortical measures across subjects, despite wide variations in gyral patterns. MMN amplitude was reduced in schizophrenia patients and correlated with their impaired day-to-day function level. Only in patients, bilateral gray matter reduction in Heschl’s gyrus, as well as motor and executive regions of the frontal cortex, correlated with reduced MMN amplitude in response to frequency deviants, while reduced gray matter in right Heschl’s gyrus also correlated with reduced MMN to duration deviants. Our findings further support the importance of MMN reduction in schizophrenia by linking frontotemporal cerebral gray matter pathology to an automatically generated event-related potential index of daily functioning.

The driving visual field and a history of motor vehicle collision involvement in older drivers: A population-based examination

Purpose We designed a visual field test focused on the field utilized while driving to examine associations between field impairment and motor vehicle collision involvement in 2,000 drivers ≥70 years old. Methods The "driving visual field test" involved measuring light sensitivity for 20 targets in each eye, extending 15° superiorly, 30° inferiorly, 60° temporally and 30° nasally. The target locations were selected on the basis that they fell within the field region utilized when viewing through the windshield of a vehicle or viewing the dashboard while driving. Monocular fields were combined into a binocular field based on the more sensitive point from each eye. Severe impairment in the overall field or a region was defined as average sensitivity in the lowest quartile of sensitivity. At-fault collision involvement for five years prior to enrollment was obtained from state records. Poisson regression was used to calculate crude and adjusted rate ratios examining the association between field impairment and at-fault collision involvement. Results Drivers with severe binocular field impairment in the overall driving visual field had a 40% increased rate of at-fault collision involvement (RR 1.40, 95%CI 1.07-1.83). Impairment in the lower and left fields was associated with elevated collision rates (RR 1.40 95%CI 1.07-1.82 and RR 1.49, 95%CI 1.15-1.92, respectively), whereas impairment in the upper and right field regions was not. Conclusions Results suggest that older drivers with severe impairment in the lower or left region of the driving visual field are more likely to have a history of at-fault collision involvement.

Comparison of ocular modulation transfer function determined by a ray-tracing aberrometer and a double-pass system in early cataract patients

BACKGROUND: The evaluation of retinal image quality in cataract eyes has gained importance and the clinical modulation transfer functions (MTF) can obtained by aberrometer and double pass (DP) system. This study aimed to compare MTF derived from a ray tracing aberrometer and a DP system in early cataractous and normal eyes. METHODS: There were 128 subjects with 61 control eyes and 67 eyes with early cataract defined according to the Lens Opacities Classification System III. A laser ray-tracing wavefront aberrometer (iTrace) and a double pass (DP) system (OQAS) assessed ocular MTF for 6.0 mm pupil diameters following dilation. Areas under the MTF (AUMTF) and their correlations were analyzed. Stepwise multiple regression analysis assessed factors affecting the differences between iTrace- and OQAS-derived AUMTF for the early cataract group. RESULTS: For both early cataract and control groups, iTrace-derived MTFs were higher than OQAS-derived MTFs across a range of spatial frequencies (P < 0.01). No significant difference between the two groups occurred for iTrace-derived AUMTF, but the early cataract group had significantly smaller OQAS-derived AUMTF than did the control group (P < 0.01). AUMTF determined from both the techniques demonstrated significant correlations with nuclear opacities, higher-order aberrations (HOAs), visual acuity, and contrast sensitivity functions, while the OQAS-derived AUMTF also demonstrated significant correlations with age and cortical opacity grade. The factors significantly affecting the difference between iTrace and OQAS AUMTF were root-mean-squared HOAs (standardized beta coefficient = -0.63, P < 0.01) and age (standardized beta coefficient = 0.26, P < 0.01). CONCLUSIONS: MTFs determined from a iTrace and a DP system (OQAS) differ significantly in early cataractous and normal subjects. Correlations with visual performance were higher for the DP system. OQAS-derived MTF may be useful as an indicator of visual performance in early cataract eyes.

A description of neck motor performance, neck pain, fatigue, and mental effort while driving in a sample with chronic whiplash-associated disorders

Objective: Individuals with chronic whiplash-associated disorders (WADs) often note driving as a difficult task. This study’s aims were to (1) compare, while driving, neck motor performance, mental effort, and fatigue in individuals with chronic WAD against healthy controls and (2) investigate the relationships of these variables and neck pain to self-reported driving difficulty in the WAD group. Design: This study involved 14 participants in each group (WAD and control). Measures included self-reported driving difficulty and measures of neck pain intensity, overall fatigue, mental effort, and neck motor performance (head rotation and upper trapezius activity) while driving a simulator. Results: The WAD group had greater absolute path of head rotation in a simulated city area and used greater mental effort (P = 0.04), but there were no differences in other measures while driving compared with the controls (all P Q 0.05). Self-reported driving difficulty correlated moderately with neck pain intensity, fatigue level, and maximum velocity of head rotation while driving in the WAD group (all P G 0.05). Conclusions: Individuals with chronic WAD do not seem to have impaired neck motor performance while driving yet use greater mental effort. Neck pain, fatigue, and maximum head rotation velocity could be potential contributors to self-reported driving difficulty in this group.

Conformational Spread in the Flagellar Motor Switch: A Model Study

The reliable response to weak biological signals requires that they be amplified with fidelity. In E. coli, the flagellar motors that control swimming can switch direction in response to very small changes in the concentration of the signaling protein CheY-P, but how this works is not well understood. A recently proposed allosteric model based on cooperative conformational spread in a ring of identical protomers seems promising as it is able to qualitatively reproduce switching, locked state behavior and Hill coefficient values measured for the rotary motor. In this paper we undertook a comprehensive simulation study to analyze the behavior of this model in detail and made predictions on three experimentally observable quantities: switch time distribution, locked state interval distribution, Hill coefficient of the switch response. We parameterized the model using experimental measurements, finding excellent agreement with published data on motor behavior. Analysis of the simulated switching dynamics revealed a mechanism for chemotactic ultrasensitivity, in which cooperativity is indispensable for realizing both coherent switching and effective amplification. These results showed how cells can combine elements of analog and digital control to produce switches that are simultaneously sensitive and reliable. © 2012 Ma et al.

A deformable Brodmann area atlas

Functional MRI studies commonly refer to activation patterns as being localized in specific Brodmann areas, referring to Brodmann’s divisions of the human cortex based on cytoarchitectonic boundaries [3]. Typically, Brodmann areas that match regions in the group averaged functional maps are estimated by eye, leading to inaccurate parcellations and significant error. To avoid this limitation, we developed a method using high-dimensional nonlinear registration to project the Brodmann areas onto individual 3D co-registered structural and functional MRI datasets, using an elastic deformation vector field in the cortical parameter space. Based on a sulcal pattern matching approach [11], an N=27 scan single subject atlas (the Colin Holmes atlas [15]) with associated Brodmann areas labeled on its surface, was deformed to match 3D cortical surface models generated from individual subjects’ structural MRIs (sMRIs). The deformed Brodmann areas were used to quantify and localize functional MRI (fMRI) BOLD activation during the performance of the Tower of London task [7].

Wide-band spectral power fluctuations characterize the response of simulated cortical networks to increasing stimulus intensity

The hippocampus is an anatomically distinct region of the medial temporal lobe that plays a critical role in the formation of declarative memories. Here we show that a computer simulation of simple compartmental cells organized with basic hippocampal connectivity is capable of producing stimulus intensity sensitive wide-band fluctuations of spectral power similar to that seen in real EEG. While previous computational models have been designed to assess the viability of the putative mechanisms of memory storage and retrieval, they have generally been too abstract to allow comparison with empirical data. Furthermore, while the anatomical connectivity and organization of the hippocampus is well defined, many questions regarding the mechanisms that mediate large-scale synaptic integration remain unanswered. For this reason we focus less on the specifics of changing synaptic weights and more on the population dynamics. Spectral power in four distinct frequency bands were derived from simulated field potentials of the computational model and found to depend on the intensity of a random input. The majority of power occurred in the lowest frequency band (3-6 Hz) and was greatest to the lowest intensity stimulus condition (1% maximal stimulus). In contrast, higher frequency bands ranging from 7-45 Hz show an increase in power directly related with an increase in stimulus intensity. This trend continues up to a stimulus level of 15% to 20% of the maximal input, above which power falls dramatically. These results suggest that the relative power of intrinsic network oscillations are dependent upon the level of activation and that above threshold levels all frequencies are damped, perhaps due to over activation of inhibitory interneurons.

Copycat firesetting : bridging two research areas

Deliberate firesetting costs our community in destruction to property and lives. Public concern heightens when similar fires occur in a series, raising the specter of copycat firesetting. Difficulties associated with researching copycat crimes in general mean that not a lot is known about copycat firesetting. As an initial step toward filling this research gap, we explore connections between research on copycat crime and research into deliberate firesetting. The intention is to extract salient features from what is known about the phenomena of deliberate firesetting and copycat crime, map them together, and point out shared and unique characteristics. It is argued that a “copycat firesetter” is likely to exist as a distinct subgroup and potentially requiring targeted interventions.

An improved robust field weakening algorithm for direct torque controlled synchronous reluctance motor drives

This paper presents an improved field weakening algorithm for synchronous reluctance motor (RSMs) drives. The proposed algorithm is robust to the variations in the machine d- and q-axes inductances. The transition between the maximum torque per ampere (MTPA), current and voltage limits as well as the maximum torque per flux (MTPF) trajectories is smooth. The proposed technique is combined with the direct torque control method to attain a high performance drive in the field weakening region. Simulation and experimental results are supplemented to verify the effectiveness of the proposed approach.

Planning and governance approaches for protecting World Heritage Areas: A comparison of the Great Barrier Reef and the Florida Everglades

The focus of this paper is on two World Heritage Areas: the Great Barrier Reef in Queensland, Australia and the Everglades in Florida. While both are World Heritage listed by the UNESCO, the Everglades is on the "World Heritage in Danger" list and the Great Barrier Reef could be on this list within the next year if present pressures continue. This paper examines the planning approaches and governance structures used in these two areas (Queensland and Florida) to manage the growth and development pressures. To make the analysis manageable, given the scale of these World Heritage areas, case studies at the local government level will be used: the Cairns Regional Council in Queensland and Monroe County in Florida. The case study analysis will involve three steps: (1) examination of the various plans at the federal, state, local levels that impact upon environmental quality in the Great Barrier Reef and Everglades; (2) assessing the degree to which these plans have been implemented; and (3) determine if (and how) the plans have improved environmental quality. In addition to the planning analysis we will also examine the governance structures (Lebel et al. 2006) within which planning operates. In any comparative analysis context is important (Hantrais 2009). Contextual differences between Queensland and Florida have previously been examined by Sipe, et al. (2007) and will be used as the starting point for this analysis. Our operating hypothesis and preliminary analysis suggests that the planning approaches and governance structures used in Florida and Queensland are considerably different, but the environmental outcomes may be similar. This is based, in part, on Vella (2004) who did a comparative analysis of environmental practices in the sugar industry in Florida and Queensland. This research re-examines this hypothesis and broadens the focus beyond the sugar industry to growth and development more broadly.