Enhanced DNA binding affinity of RecA protein from Deinococcus radiodurans

© 2015 Elsevier B.V. Deinococcus radiodurans (Dr) has a significantly more robust DNA repair response than Escherichia coli (Ec), which helps it survive extremely high doses of ionizing radiation and prolonged periods of desiccation. DrRecA protein plays an essential part in this DNA repair capability. In this study we directly compare the binding of DrRecA and EcRecA to the same set of short, defined single (ss) and double stranded (ds) DNA oligomers. In the absence of cofactors (ATPγS or ADP), DrRecA binds to dsDNA oligomers more than 20 fold tighter than EcRecA, and binds ssDNA up to 9 fold tighter. Binding to dsDNA oligomers in the absence of cofactor presumably predominantly monitors DNA end binding, and thus suggests a significantly higher affinity of DrRecA for ds breaks. Upon addition of ATPγS, this species-specific affinity difference is nearly abolished, as ATPγS significantly decreases the affinity of DrRecA for DNA. Other findings include that: (1) both proteins exhibit a dependence of binding affinity on the length of the ssDNA oligomer, but not the dsDNA oligomer; (2) the salt dependence of binding is modest for both species of RecA, and (3) in the absence of DNA, DrRecA produces significantly shorter and/or fewer free-filaments in solution than does EcRecA. The results suggest intrinsic biothermodynamic properties of DrRecA contribute directly to the more robust DNA repair capabilities of D. radiodurans

Aberrant activity in conceptual networks underlies N400 deficits and unusual thoughts in schizophrenia.

BackgroundThe N400 event-related potential (ERP) is triggered by meaningful stimuli that are incongruous, or unmatched, with their semantic context. Functional magnetic resonance imaging (fMRI) studies have identified brain regions activated by semantic incongruity, but their precise links to the N400 ERP are unclear. In schizophrenia (SZ), N400 amplitude reduction is thought to reflect overly broad associations in semantic networks, but the abnormalities in brain networks underlying deficient N400 remain unknown. We utilized joint independent component analysis (JICA) to link temporal patterns in ERPs to neuroanatomical patterns from fMRI and investigate relationships between N400 amplitude and neuroanatomical activation in SZ patients and healthy controls (HC).MethodsSZ patients (n = 24) and HC participants (n = 25) performed a picture-word matching task, in which words were either matched (APPLE→apple) by preceding pictures, or were unmatched by semantically related (in-category; IC, APPLE→lemon) or unrelated (out of category; OC, APPLE→cow) pictures, in separate ERP and fMRI sessions. A JICA "data fusion" analysis was conducted to identify the fMRI brain regions specifically associated with the ERP N400 component. SZ and HC loading weights were compared and correlations with clinical symptoms were assessed.ResultsJICA identified an ERP-fMRI "fused" component that captured the N400, with loading weights that were reduced in SZ. The JICA map for the IC condition showed peaks of activation in the cingulate, precuneus, bilateral temporal poles and cerebellum, whereas the JICA map from the OC condition was linked primarily to visual cortical activation and the left temporal pole. Among SZ patients, fMRI activity from the IC condition was inversely correlated with unusual thought content.ConclusionsThe neural networks associated with the N400 ERP response to semantic violations depends on conceptual relatedness. These findings are consistent with a distributed network underlying neural responses to semantic incongruity including unimodal visual areas as well as integrative, transmodal areas. Unusual thoughts in SZ may reflect impaired processing in transmodal hub regions such as the precuneus, leading to overly broad semantic associations

A Data-Driven Investigation of Gray Matter–Function Correlations in Schizophrenia during a Working Memory Task

The brain is a vastly interconnected organ and methods are needed to investigate its long range structure(S)–function(F) associations to better understand disorders such as schizophrenia that are hypothesized to be due to distributed disconnected brain regions. In previous work we introduced a methodology to reduce the whole brain S–F correlations to a histogram and here we reduce the correlations to brain clusters. The application of our approach to sMRI [gray matter (GM) concentration maps] and functional magnetic resonance imaging data (general linear model activation maps during Encode and Probe epochs of a working memory task) from patients with schizophrenia (SZ, n = 100) and healthy controls (HC, n = 100) presented the following results. In HC the whole brain correlation histograms for GM–Encode and GM–Probe overlap for Low and Medium loads and at High the histograms separate, but in SZ the histograms do not overlap for any of the load levels and Medium load shows the maximum difference. We computed GM–F differential correlation clusters using activation for Probe Medium, and they included regions in the left and right superior temporal gyri, anterior cingulate, cuneus, middle temporal gyrus, and the cerebellum. Inter-cluster GM–Probe correlations for Medium load were positive in HC but negative in SZ. Within group inter-cluster GM–Encode and GM–Probe correlation comparisons show no differences in HC but in SZ differences are evident in the same clusters where HC vs. SZ differences occurred for Probe Medium, indicating that the S–F integrity during Probe is aberrant in SZ. Through a data-driven whole brain analysis approach we find novel brain clusters and show how the S–F differential correlation changes during Probe and Encode at three memory load levels. Structural and functional anomalies have been extensively reported in schizophrenia and here we provide evidences to suggest that evaluating S–F associations can provide important additional information

Multilevel Mapping of Sexual Dimorphism in Intrinsic Functional Brain Networks

Differences in cognitive performance between males and females are well-described, most commonly in certain spatial and language tasks. Sex-related differences in cognition are relevant to the study of the neurotypical brain and to neuropsychiatric disorders, which exhibit prominent disparities in the incidence, prevalence and severity of symptoms between men and women. While structural dimorphism in the human brain is well-described, controversy exists regarding the existence and degree of sex-related differences in brain function. We analyzed resting-state functional MRI from 650 neurotypical young adults matched for age and sex to determine the degree of sexual dimorphism present in intrinsic functional networks. Multilevel modeling was pursued to create 8-, 24-, and 51-network models of whole-brain data to quantify sex-related effects in network activity with increasing resolution. We determined that sexual dimorphism is present in the majority of intrinsic brain networks and affects ∼0.5–2% of brain locations surveyed in the three whole-brain network models. It is particularly common in task-positive control networks and is pervasive among default mode networks. The size of sex-related effects varied by network but can be moderate or even large in size. Female > male effects were on average larger, but male > female effects spread across greater network territory. Using a novel methodology, we mapped dimorphic locations to meta-analytic association test maps derived from task fMRI, demonstrating that the neurocognitive footprint of intrinsic neural correlates is much larger in males. All results were replicated in a motion-matched sub-sample. Our findings argue that sex is an important biological variable in human brain function and suggest that observed differences in neurocognitive performance have identifiable intrinsic neural correlates

ICA of Functional MRI Data: An Overview

Independent component analysis (ICA) has found a fruitful application in the analysis of functional magnetic resonance imaging (fMRI) data. A principal advantage of this approach is its applicability to cognitive paradigms for which detailed a priori models of brain activity are not available. ICA has been successfully utilized in a number of exciting fMRI applications including the identification of various signal-types (e.g. task and transiently task-related, and physiology-related signals) in the spatial or temporal domain, the analysis of multi-subject fMRI data, the incorporation of a priori information, and for the analysis of complex-valued fMRI data (which has proved challenging for standard approaches). In this paper, we 1) introduce fMRI data and its properties, 2) review the basic motivation for using ICA on fMRI data, and 3) review the current work on ICA of fMRI with some specific examples from our own work. The purpose of this paper is to motivate ICA research to focus upon this exciting application

The influence of different length between match microcycles on neuromuscular, hormonal and perceptual responses in professional rugby league players

Optimal recovery between matches is critically important in team sports. Indeed, altered neuromuscular performance, hormone levels and increased fatigue can manifest in under recovered team sport athletes. However, the recovery patterns in these variables in the days following professional rugby league matches is unknown. The purpose of this study was to examine the influence of different between-match training periods on neuromuscular, hormonal and perceptual measures in professional rugby league players. Following familiarization, 12 professional rugby league players from the same team were assessed for changes in countermovement jump (CMJ) (force, power, flight time), perceptual responses (fatigue, well being and muscle soreness) and salivary hormone (testosterone (T) and cortisol (C)) levels during 5, 7 and 9 day periods between matches. Measures were taken 4h prior to the initial match, and then 1, 2, 4, 6*, 7*, 8* and 9* days following (*depending on group). All training was prescribed by the coaches and monitored using the session-RPE method. Lower daily training load was completed on the 5-day compared with the 7 and 9-day conditions (p\u3c0.05). Some CMJ variables (flight time and flight time:contraction time), perception of fatigue, well-being and muscle soreness were reduced in the 2 days following the match in each condition (p\u3c0.05). All CMJ variables returned to near baseline values following 4 days in each condition. Both CMJ maximum and relative power were lower in the 7 day condition when compared with the 9 day condition (p\u3c0.05). Fatigue levels were reduced at 48 h in the 7 and 9-day groups (p\u3c0.05) but had returned to baseline in the 5-day group. All perceptual measures returned to baseline levels prior to the following match in each condition and followed changes in training load. Salivary T and C did not change in response to the match. These results show that neuromuscular performance and perception of fatigue are reduced for at least 48 h following a rugby league match but these can be fully recovered within 4 days. CMJ variables involving flight time appear to be best for assessing acute fatigue caused by a match, and variables involving power may be useful in assessing accumulated fatigue. The perceptual measures were sensitive to both acute fatigue and accumulated fatigue. The salivary hormone analyses were of limited value for assessing recovery. These findings show that with correct training, it is possible to recover neuromuscular, perceptual and endocrine measures within 4 days after a rugby league match

Metabolic Profiling of Heathland Plants in the Diet of Sheep

Little is known about how plant biochemistry influences the grazing behaviour of animals grazing heterogeneous vegetation communities. Furthermore, most biochemical profiles of grassland species are restricted to major nutritional characteristics. Recent developments in analytical techniques have made possible the detailed analysis of minor components, which can potentially affect animal feeding preferences, performance and health. Gas chromatography/time of flight mass spectroscopy (GC/TOF-MS) coupled with automated library annotation is ideally suited to the acquisition of detailed metabolite profiles of plant extracts (Wagner et al., 2003) and can be applied to other matrices such as blood and faeces. In this study GC/TOF-MS was used to identify metabolites within heathland plants, and to investigate which of these metabolites were present and absent within plasma and faeces from sheep consuming mixtures of these plants

Reduced executive and default network functional connectivity in cigarette smokers

Altered functional connectivity has been associated with acute and chronic nicotine use. Connectivity alterations, specifically in the right and left executive control networks (RECN/LECN) and the default mode network (DMN), may contribute to the addiction cycle. The objective of this study was to determine if executive control network (ECN) and DMN connectivity is different between non‐smokers and smokers and whether reductions in connectivity are related to chronic cigarette use. The RECN, LECN, and DMN were identified in resting state functional magnetic resonance imaging data in 650 subjects. Analyses tested for group differences in network connectivity strength, controlling for age and alcohol use. There was a significant group effect on LECN and DMN connectivity strength with smokers (n = 452) having lower network strengths than non‐smokers (n = 198). Smokers had lower connectivity than non‐smokers associated with key network hubs: the dorsolateral prefrontal cortex, and parietal nodes within ECNs. Further, ECN connectivity strength was negatively associated with pack years of cigarette use. Our data suggest that chronic nicotine use negatively impacts functional connectivity within control networks that may contribute to the difficulty smokers have in quitting. Hum Brain Mapp 36:872–882, 2015. © 2014 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110754/1/hbm22672.pd

Dynamics of a hyperbolic system that applies at the onset of the oscillatory instability

A real hyperbolic system is considered that applies near the onset of the oscillatory instability in large spatial domains. The validity of that system requires that some intermediate scales (large compared with the basic wavelength of the unstable modes but small compared with the size of the system) remain inhibited; that condition is analysed in some detail. The dynamics associated with the hyperbolic system is fully analysed to conclude that it is very simple if the coefficient of the cross-nonlinearity is such that , while the system exhibits increasing complexity (including period-doubling sequences, quasiperiodic transitions, crises) as the bifurcation parameter grows if ; if then the system behaves subcritically. Our results are seen to compare well, both qualitatively and quantitatively, with the experimentally obtained ones for the oscillatory instability of straight rolls in pure Rayleigh - Bénard convection