Parallel imaging: is GRAPPA a useful acquisition tool for MR imaging intended for volumetric brain analysis?

<p>Abstract</p> <p>Background</p> <p>The work presented here investigates parallel imaging applied to T1-weighted high resolution imaging for use in longitudinal volumetric clinical studies involving Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI) patients. This was in an effort to shorten acquisition times to minimise the risk of motion artefacts caused by patient discomfort and disorientation. The principle question is, "Can parallel imaging be used to acquire images at 1.5 T of sufficient quality to allow volumetric analysis of patient brains?"</p> <p>Methods</p> <p>Optimisation studies were performed on a young healthy volunteer and the selected protocol (including the use of two different parallel imaging acceleration factors) was then tested on a cohort of 15 elderly volunteers including MCI and AD patients. In addition to automatic brain segmentation, hippocampus volumes were manually outlined and measured in all patients. The 15 patients were scanned on a second occasion approximately one week later using the same protocol and evaluated in the same manner to test repeatability of measurement using images acquired with the GRAPPA parallel imaging technique applied to the MPRAGE sequence.</p> <p>Results</p> <p>Intraclass correlation tests show that almost perfect agreement between repeated measurements of both segmented brain parenchyma fraction and regional measurement of hippocampi. The protocol is suitable for both global and regional volumetric measurement dementia patients.</p> <p>Conclusion</p> <p>In summary, these results indicate that parallel imaging can be used without detrimental effect to brain tissue segmentation and volumetric measurement and should be considered for both clinical and research studies where longitudinal measurements of brain tissue volumes are of interest.</p

Influence of Culture Conditions on the Bioreduction of Organic Acids to Alcohols by Thermoanaerobacter pseudoethanolicus

Thermoanaerobacter species have recently been observed to reduce carboxylic acids to their corresponding alcohols. The present investigation shows that Thermoanaerobacter pseudoethanolicus converts C2–C6 short-chain fatty acids (SCFAs) to their corresponding alcohols in the presence of glucose. The conversion yields varied from 21% of 3-methyl-1-butyrate to 57.9% of 1-pentanoate being converted to their corresponding alcohols. Slightly acidic culture conditions (pH 6.5) was optimal for the reduction. By increasing the initial glucose concentration, an increase in the conversion of SCFAs reduced to their corresponding alcohols was observed. Inhibitory experiments on C2–C8 alcohols showed that C4 and higher alcohols are inhibitory to T. pseudoethanolicus suggesting that other culture modes may be necessary to improve the amount of fatty acids reduced to the analogous alcohol. The reduction of SCFAs to their corresponding alcohols was further demonstrated using 13C-labelled fatty acids and the conversion was followed kinetically. Finally, increased activity of alcohol dehydrogenase (ADH) and aldehyde oxidation activity was observed in cultures of T. pseudoethanolicus grown on glucose as compared to glucose supplemented with either 3-methyl-1-butyrate or pentanoate, using both NADH and NADPH as cofactors, although the presence of the latter showed higher ADH and aldehyde oxidoreductase (ALDH) activity

Locomotor adaptability in persons with unilateral transtibial amputation

Background Locomotor adaptation enables walkers to modify strategies when faced with challenging walking conditions. While a variety of neurological injuries can impair locomotor adaptability, the effect of a lower extremity amputation on adaptability is poorly understood. Objective Determine if locomotor adaptability is impaired in persons with unilateral transtibial amputation (TTA). Methods The locomotor adaptability of 10 persons with a TTA and 8 persons without an amputation was tested while walking on a split-belt treadmill with the parallel belts running at the same (tied) or different (split) speeds. In the split condition, participants walked for 15 minutes with the respective belts moving at 0.5 m/s and 1.5 m/s. Temporal spatial symmetry measures were used to evaluate reactive accommodations to the perturbation, and the adaptive/de-adaptive response. Results Persons with TTA and the reference group of persons without amputation both demonstrated highly symmetric walking at baseline. During the split adaptation and tied post-adaptation walking both groups responded with the expected reactive accommodations. Likewise, adaptive and de-adaptive responses were observed. The magnitude and rate of change in the adaptive and de-adaptive responses were similar for persons with TTA and those without an amputation. Furthermore, adaptability was no different based on belt assignment for the prosthetic limb during split adaptation walking. Conclusions Reactive changes and locomotor adaptation in response to a challenging and novel walking condition were similar in persons with TTA to those without an amputation. Results suggest persons with TTA have the capacity to modify locomotor strategies to meet the demands of most walking conditions despite challenges imposed by an amputation and use of a prosthetic limb

Opportunities for topical antimicrobial therapy: permeation of canine skin by fusidic acid

BACKGROUND: Staphylococcal infection of the canine epidermis and hair follicle is amongst the commonest reasons for antimicrobial prescribing in small animal veterinary practice. Topical therapy with fusidic acid (FA) is an attractive alternative to systemic therapy based on low minimum inhibitory concentrations (MICs, commonly <0.03 mg/l) documented in canine pathogenic staphylococci, including strains of MRSA and MRSP (methicillin-resistant Staphylococcus aureus and S. pseudintermedius). However, permeation of canine skin by FA has not been evaluated in detail. This study aimed to define the degree and extent of FA permeation in canine skin in vitro from two sites with different hair follicle density following application of a licensed ophthalmic formulation that shares the same vehicle as an FA-betamethasone combination product approved for dermal application in dogs. Topical FA application was modelled using skin held in Franz-type diffusion cells. Concentrations of FA in surface swabs, receptor fluid, and transverse skin sections of defined anatomical depth were determined using high-performance liquid chromatography and ultraviolet (HPLC-UV) analysis. RESULTS: The majority of FA was recovered by surface swabs after 24 h, as expected (mean ± SEM: 76.0 ± 17.0%). FA was detected within 424/470 (90%) groups of serial sections of transversely cryotomed skin containing follicular infundibula, but never in 48/48 (100%) groups of sections containing only deeper follicular structures, nor in receptor fluid, suggesting that FA does not permeate beyond the infundibulum. The FA concentration (mean ± SEM) in the most superficial 240 μm of skin was 2000 ± 815 μg/g. CONCLUSIONS: Topically applied FA can greatly exceed MICs for canine pathogenic staphylococci at the most common sites of infection. Topical FA therapy should now be evaluated using available formulations in vivo as an alternative to systemic therapy for canine superficial bacterial folliculitis.Peer reviewedFinal Published versio

A novel locus for Meckel-Gruber syndrome, MKS3, maps to chromosome 8q24

Meckel-Gruber syndrome (MKS), the most common monogenic cause of neural tube defects, is an autosomal recessive disorder characterised by a combination of renal cysts and variably associated features, including developmental anomalies of the central nervous system (typically encephalcoele), hepatic ductal dysplasia and cysts, and polydactyly. Locus heterogeneity has been demonstrated by the mapping of the MKS1 locus to 17q21-24 in Finnish kindreds, and of MKS2 to 11q13 in North African-Middle Eastern cohorts. In the present study, we have investigated the genetic basis of MKS in eight consanguineous kindreds, originating from the Indian sub-continent, that do not show linkage to either MKS1 or MKS2. We report the localisation of a third MKS locus (MKS3) to chromosome 8q24 in this cohort by a genome-wide linkage search using autozygosity mapping. We identified a 26-cM region of autozygosity between D8S586 and D8S1108 with a maximum cumulative two-point LOD score at D8S1179 (Z(max)=3.04 at theta=0.06). A heterogeneity test provided evidence of one unlinked family. Exclusion of this family from multipoint analysis maximised the cumulative multipoint LOD score at locus D8S1128 (Z(max)=5.65). Furthermore, a heterozygous SNP in DDEF1, a putative candidate gene, suggested that MKS3 mapped within a 15-cM interval. Comparison of the clinical features of MKS3-linked cases with reports of MKS1- and MKS2-linked kindreds suggests that polydactyly (and possibly encephalocele) appear less common in MKS3-linked families

Multimodal influences on learning walks in desert ants (Cataglyphis fortis)

Ants are excellent navigators using multimodal information for navigation. To accurately localise the nest at the end of a foraging journey, visual cues, wind direction and also olfactory cues need to be learnt. Learning walks are performed at the start of an ant’s foraging career or when the appearance of the nest surrounding has changed. We investigated here whether the structure of such learning walks in the desert ant Cataglyphis fortis takes into account wind direction in conjunction with the learning of new visual information. Ants learnt to travel back and forth between their nest and a feeder, and we then introduced a black cylinder near their nest to induce learning walks in regular foragers. By doing this across days with different wind directions, we were able to probe how ants balance different sensory modalities. We found that (1) the ants’ outwards headings are influenced by the wind direction with their routes deflected such that they will arrive downwind of their target, (2) a novel object along the route induces learning walks in experienced ants and (3) the structure of learning walks is shaped by the wind direction rather than the position of the visual cue

Generation and quality control of lipidomics data for the alzheimers disease neuroimaging initiative cohort.

Alzheimers disease (AD) is a major public health priority with a large socioeconomic burden and complex etiology. The Alzheimer Disease Metabolomics Consortium (ADMC) and the Alzheimer Disease Neuroimaging Initiative (ADNI) aim to gain new biological insights in the disease etiology. We report here an untargeted lipidomics of serum specimens of 806 subjects within the ADNI1 cohort (188 AD, 392 mild cognitive impairment and 226 cognitively normal subjects) along with 83 quality control samples. Lipids were detected and measured using an ultra-high-performance liquid chromatography quadruple/time-of-flight mass spectrometry (UHPLC-QTOF MS) instrument operated in both negative and positive electrospray ionization modes. The dataset includes a total 513 unique lipid species out of which 341 are known lipids. For over 95% of the detected lipids, a relative standard deviation of better than 20% was achieved in the quality control samples, indicating high technical reproducibility. Association modeling of this dataset and available clinical, metabolomics and drug-use data will provide novel insights into the AD etiology. These datasets are available at the ADNI repository at http://adni.loni.usc.edu/

Identifying metabolites by integrating metabolome databases with mass spectrometry cheminformatics.

Novel metabolites distinct from canonical pathways can be identified through the integration of three cheminformatics tools: BinVestigate, which queries the BinBase gas chromatography-mass spectrometry (GC-MS) metabolome database to match unknowns with biological metadata across over 110,000 samples; MS-DIAL 2.0, a software tool for chromatographic deconvolution of high-resolution GC-MS or liquid chromatography-mass spectrometry (LC-MS); and MS-FINDER 2.0, a structure-elucidation program that uses a combination of 14 metabolome databases in addition to an enzyme promiscuity library. We showcase our workflow by annotating N-methyl-uridine monophosphate (UMP), lysomonogalactosyl-monopalmitin, N-methylalanine, and two propofol derivatives

The impact of ageing reveals distinct roles for human dentate gyrus and CA3 in pattern separation and object recognition memory

© 2017 The Author(s). Both recognition of familiar objects and pattern separation, a process that orthogonalises overlapping events, are critical for effective memory. Evidence is emerging that human pattern separation requires dentate gyrus. Dentate gyrus is intimately connected to CA3 where, in animals, an autoassociative network enables recall of complete memories to underpin object/event recognition. Despite huge motivation to treat age-related human memory disorders, interaction between human CA3 and dentate subfields is difficult to investigate due to small size and proximity. We tested the hypothesis that human dentate gyrus is critical for pattern separation, whereas, CA3 underpins identical object recognition. Using 3 T MR hippocampal subfield volumetry combined with a behavioural pattern separation task, we demonstrate that dentate gyrus volume predicts accuracy and response time during behavioural pattern separation whereas CA3 predicts performance in object recognition memory. Critically, human dentate gyrus volume decreases with age whereas CA3 volume is age-independent. Further, decreased dentate gyrus volume, and no other subfield volume, mediates adverse effects of aging on memory. Thus, we demonstrate distinct roles for CA3 and dentate gyrus in human memory and uncover the variegated effects of human ageing across hippocampal regions. Accurate pinpointing of focal memory-related deficits will allow future targeted treatment for memory loss

Directed -in vitro- evolution of Precambrian and extant Rubiscos

Rubisco is an ancient, catalytically conserved yet slow enzyme, which plays a central role in the biosphere’s carbon cycle. The design of Rubiscos to increase agricultural productivity has hitherto relied on the use of in vivo selection systems, precluding the exploration of biochemical traits that are not wired to cell survival. We present a directed -in vitro- evolution platform that extracts the enzyme from its biological context to provide a new avenue for Rubisco engineering. Precambrian and extant form II Rubiscos were subjected to an ensemble of directed evolution strategies aimed at improving thermostability. The most recent ancestor of proteobacteria -dating back 2.4 billion years- was uniquely tolerant to mutagenic loading. Adaptive evolution, focused evolution and genetic drift revealed a panel of thermostable mutants, some deviating from the characteristic trade-offs in CO2-fixing speed and specificity. Our findings provide a novel approach for identifying Rubisco variants with improved catalytic evolution potential.This work was supported by the REPSOL Research contracts Rubolution (RC020401120018), Rubolution 2.0 (RC 020401140042), the CSIC project PIE-201780E043 and the Australian Research Council grant CE140100015