Increased functional sensorimotor network efficiency relates to disability in multiple sclerosis

BACKGROUND: Network abnormalities could help explain physical disability in multiple sclerosis (MS), which remains poorly understood. OBJECTIVE: This study investigates functional network efficiency changes in the sensorimotor system. METHODS: We included 222 MS patients, divided into low disability (LD, Expanded Disability Status Scale (EDSS) ⩽3.5, n = 185) and high disability (HD, EDSS ⩾6, n = 37), and 82 healthy controls (HC). Functional connectivity was assessed between 23 sensorimotor regions. Measures of efficiency were computed and compared between groups using general linear models corrected for age and sex. Binary logistic regression models related disability status to local functional network efficiency (LE), brain volumes and demographics. Functional connectivity patterns of regions important for disability were explored. RESULTS: HD patients demonstrated significantly higher LE of the left primary somatosensory cortex (S1) and right pallidum compared to LD and HC, and left premotor cortex compared to HC only. The logistic regression model for disability (R2 = 0.38) included age, deep grey matter volume and left S1 LE. S1 functional connectivity was increased with prefrontal and secondary sensory areas in HD patients, compared to LD and HC. CONCLUSION: Clinical disability in MS associates with functional sensorimotor increases in efficiency and connectivity, centred around S1, independent of structural damage

Establishment Failure in Biological Invasions: A Case History of Littorina littorea in California, USA

The early stages of biological invasions are rarely observed, but can provide significant insight into the invasion process as well as the influence vectors have on invasion success or failure.We characterized three newly discovered populations of an introduced gastropod, Littorina littorea (Linné, 1758), in California, USA, comparing them to potential source populations in native Europe and the North American East Coast, where the snail is also introduced. Demographic surveys were used to assess spatial distribution and sizes of the snail in San Francisco and Anaheim Bays, California. Mitochondrial DNA was sequenced and compared among these nascent populations, and various populations from the North American East Coast and Europe, to characterize the California populations and ascertain their likely source. Demographic and genetic data were considered together to deduce likely vectors for the California populations. We found that the three large California L. littorea populations contained only adult snails and had unexpectedly high genetic diversity rather than showing an extreme bottleneck as typically expected in recent introductions. Haplotype diversity in Californian populations was significantly reduced compared to European populations, but not compared to East Coast populations. Genetic analyses clearly suggested the East Coast as the source region for the California introductions.The California L. littorea populations were at an early, non-established phase of invasion with no evidence of recruitment. The live seafood trade is the most likely invasion vector for these populations, as it preferentially transports large numbers of adult L. littorea, matching the demographic structure of the introduced California L. littorea populations. Our results highlight continued operation of live seafood trade vectors and the influence of vectors on the demographic and genetic structure of the resulting populations, especially early stages of the invasion process

Identification and Structural Characterization of a New Three-Finger Toxin Hemachatoxin from Hemachatus haemachatus Venom

10.1371/journal.pone.0048112PLoS ONE710

Assessing Computational Methods of Cis-Regulatory Module Prediction

Computational methods attempting to identify instances of cis-regulatory modules (CRMs) in the genome face a challenging problem of searching for potentially interacting transcription factor binding sites while knowledge of the specific interactions involved remains limited. Without a comprehensive comparison of their performance, the reliability and accuracy of these tools remains unclear. Faced with a large number of different tools that address this problem, we summarized and categorized them based on search strategy and input data requirements. Twelve representative methods were chosen and applied to predict CRMs from the Drosophila CRM database REDfly, and across the human ENCODE regions. Our results show that the optimal choice of method varies depending on species and composition of the sequences in question. When discriminating CRMs from non-coding regions, those methods considering evolutionary conservation have a stronger predictive power than methods designed to be run on a single genome. Different CRM representations and search strategies rely on different CRM properties, and different methods can complement one another. For example, some favour homotypical clusters of binding sites, while others perform best on short CRMs. Furthermore, most methods appear to be sensitive to the composition and structure of the genome to which they are applied. We analyze the principal features that distinguish the methods that performed well, identify weaknesses leading to poor performance, and provide a guide for users. We also propose key considerations for the development and evaluation of future CRM-prediction methods

Metabolism of halophilic archaea

In spite of their common hypersaline environment, halophilic archaea are surprisingly different in their nutritional demands and metabolic pathways. The metabolic diversity of halophilic archaea was investigated at the genomic level through systematic metabolic reconstruction and comparative analysis of four completely sequenced species: Halobacterium salinarum, Haloarcula marismortui, Haloquadratum walsbyi, and the haloalkaliphile Natronomonas pharaonis. The comparative study reveals different sets of enzyme genes amongst halophilic archaea, e.g. in glycerol degradation, pentose metabolism, and folate synthesis. The carefully assessed metabolic data represent a reliable resource for future system biology approaches as it also links to current experimental data on (halo)archaea from the literature

Microstructural correlates of 23Na relaxation in human brain at 7 Tesla.

23Na provides the second strongest MR-observable signal in biological tissue and exhibits bi-exponential T2∗ relaxation in micro-environments such as the brain. There is significant interest in developing 23Na biomarkers for neurological diseases that are associated with sodium channel dysfunction such as multiple sclerosis and epilepsy. We have previously reported methods for acquisition of multi-echo sodium MRI and continuous distribution modelling of sodium relaxation properties as surrogate markers of brain microstructure. This study aimed to compare 23Na T2∗ relaxation times to more established measures of tissue microstructure derived from advanced diffusion MRI at 7 T. Six healthy volunteers were scanned using a 3D multi-echo radial ultra-short TE sequence using a dual-tuned 1H/23Na birdcage coil, and a high-resolution multi-shell, high angular resolution diffusion imaging sequence using a 32-channel 1H receive coil. 23Na T2∗ relaxation parameters [mean T2∗ (T2∗mean) and fast relaxation fraction (T2∗ff)] were calculated from a voxel-wise continuous gamma distribution signal model. White matter (restricted anisotropic diffusion) and grey matter (restricted isotropic diffusion) density were calculated from multi-shell multi-tissue constrained spherical deconvolution. Sodium parameters were compared with white and grey matter diffusion properties. Sodium T2∗mean and T2∗ff showed little variation across a range of white matter axonal fibre and grey matter densities. We conclude that sodium T2∗ relaxation parameters are not greatly influenced by relative differences in intra- and extracellular partial volumes. We suggest that care be taken when interpreting sodium relaxation changes in terms of tissue microstructure in healthy tissue

An Experimental Investigation of White Matter Venous Hemodynamics: Basic Physiology and Disruption in Neuroinflammatory Disease

The white matter is highly vascularised by the cerebral venous system. In this paper, we describe a unique blood oxygen-level dependent (BOLD) signal within the white matter using functional MRI and spatial independent components analysis. The signal is characterized by a narrow peak frequency band between 0.05 and 0.1 Hz. Hypercapnia, induced transient increases in white matter venous BOLD that disrupted the oscillation indicative of a vasocontractile mechanism. Comparison of the white matter venous BOLD oscillations between 14 healthy subjects and 18 people with perivenular inflammation due to multiple sclerosis (MS), revealed loss of power in the white matter venous BOLD signal in the peak frequency band (patients = 6.70 ± 0.94 dB/Hz vs. controls = 7.64 ± 0.71 dB/Hz; p = 0.006). In MS, lower power was associated with greater levels of neuroinflammatory activity (R = -0.64, p = 0.006). Using a signal modeling technique, we assessed the anatomical distribution of white matter venous BOLD signal abnormalities and detected reduced power in the periventricular white matter, a region of known venous damage in MS. These results demonstrate a novel link between neuroinflammation and vascular physiological dysfunction in the cerebral white matter, and could indicate enduring loss of vascular compliance associated with imperfect repair of blood-brain barrier damage after resolution of acute neuroinflammation

Serial Diffusion Tensor Imaging of the Optic Radiations after Acute Optic Neuritis

Previous studies have reported diffusion tensor imaging (DTI) changes within the optic radiations of patients after optic neuritis (ON). We aimed to study optic radiation DTI changes over 12 months following acute ON and to study correlations between DTI parameters and damage to the optic nerve and primary visual cortex (V1). We measured DTI parameters [fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD)] from the optic radiations of 38 acute ON patients at presentation and 6 and 12 months after acute ON. In addition, we measured retinal nerve fibre layer thickness, visual evoked potential amplitude, optic radiation lesion load, and V1 thickness. At baseline, FA was reduced and RD and MD were increased compared to control. Over 12 months, FA reduced in patients at an average rate of -2.6% per annum (control = -0.51%; p = 0.006). Change in FA, RD, and MD correlated with V1 thinning over 12 months (FA: R = 0.450, p = 0.006; RD: R = -0.428, p = 0.009; MD: R = -0.365, p = 0.029). In patients with no optic radiation lesions, AD significantly correlated with RNFL thinning at 12 months (R = 0.489, p = 0.039). In conclusion, DTI can detect optic radiation changes over 12 months following acute ON that correlate with optic nerve and V1 damage

Visual search efficiency and functional visual cortical size in children with and without dyslexia

Dyslexia is characterised by poor reading ability. Its aetiology is probably multifactorial, with abnormal visual processing playing an important role. Among adults with normal reading ability, there is a larger representation of central visual field in the primary visual cortex (V1) in those with more efficient visuospatial attention. In this study, we tested the hypothesis that poor reading ability in school-aged children (17 children with dyslexia, 14 control children with normal reading ability) is associated with deficits in visuospatial attention using a visual search task. We corroborated the psychophysical findings with neuroimaging, by measuring the functional size of V1 in response to a central 12° visual stimulus. Consistent with other literature, visual search was impaired and less efficient in the dyslexic children, particularly with more distractor elements in the search array (p=0.04). We also found atypical interhemispheric asymmetry in functional V1 size in the dyslexia group (p=0.02). Reading impaired children showed poorer visual search efficiency (p=0.01), needing more time per unit distractor (higher ms/item). Reading ability was also correlated with V1 size asymmetry (p=0.03), such that poorer readers showed less left hemisphere bias relative to the right hemisphere. Our findings support the view that dyslexic children have abnormal visuospatial attention and interhemispheric V1 asymmetry, relative to chronological age-matched peers, and that these factors may contribute to inter-individual variation in reading performance in children