Current whole-body MRI applications in the neurofibromatoses

ObjectivesThe Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration Whole-Body MRI (WB-MRI) Working Group reviewed the existing literature on WB-MRI, an emerging technology for assessing disease in patients with neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN), to recommend optimal image acquisition and analysis methods to enable WB-MRI as an endpoint in NF clinical trials.MethodsA systematic process was used to review all published data about WB-MRI in NF syndromes to assess diagnostic accuracy, feasibility and reproducibility, and data about specific techniques for assessment of tumor burden, characterization of neoplasms, and response to therapy.ResultsWB-MRI at 1.5T or 3.0T is feasible for image acquisition. Short tau inversion recovery (STIR) sequence is used in all investigations to date, suggesting consensus about the utility of this sequence for detection of WB tumor burden in people with NF. There are insufficient data to support a consensus statement about the optimal imaging planes (axial vs coronal) or 2D vs 3D approaches. Functional imaging, although used in some NF studies, has not been systematically applied or evaluated. There are no comparative studies between regional vs WB-MRI or evaluations of WB-MRI reproducibility.ConclusionsWB-MRI is feasible for identifying tumors using both 1.5T and 3.0T systems. The STIR sequence is a core sequence. Additional investigation is needed to define the optimal approach for volumetric analysis, the reproducibility of WB-MRI in NF, and the diagnostic performance of WB-MRI vs regional MRI

Evaluation of T1 relaxation time in prostate cancer and benign prostate tissue using a Modified Look-Locker inversion recovery sequence

Purpose of this study was to evaluate the diagnostic performance of T1 relaxation time (T1) for differentiating prostate cancer (PCa) from benign tissue as well as high- from low-grade PCa. Twenty-three patients with suspicion for PCa were included in this prospective study. 3 T MRI including a Modified Look-Locker inversion recovery sequence was acquired. Subsequent targeted and systematic prostate biopsy served as a reference standard. T1 and apparent diffusion coefficient (ADC) value in PCa and reference regions without malignancy as well as high- and low-grade PCa were compared using the Mann-Whitney U test. The performance of T1, ADC value, and a combination of both to differentiate PCa and reference regions was assessed by receiver operating characteristic (ROC) analysis. T1 and ADC value were lower in PCa compared to reference regions in the peripheral and transition zone (p < 0.001). ROC analysis revealed high AUCs for T1 (0.92; 95%-CI, 0.87-0.98) and ADC value (0.97; 95%-CI, 0.94 to 1.0) when differentiating PCa and reference regions. A combination of T1 and ADC value yielded an even higher AUC. The difference was statistically significant comparing it to the AUC for ADC value alone (p = 0.02). No significant differences were found between high- and low-grade PCa for T1 (p = 0.31) and ADC value (p = 0.8). T1 relaxation time differs significantly between PCa and benign prostate tissue with lower T1 in PCa. It could represent an imaging biomarker for PCa

Proposal of \u3cem\u3eVibrionimonas magnilacihabitans\u3c/em\u3e gen. nov., sp. nov., a Curved Gram Negative Bacterium Isolated From Lake Michigan Water

A mesophilic bacterium appearing as curved rod-shaped cells was isolated from Lake Michigan water. It exhibited highest similarities with Sediminibacterium ginsengisoli DCY13T (94.4 %); Sediminibacterium salmoneum NJ-44T (93.6 %) and Hydrotalea flava CCUG 51397 T (93.1 %) while similarities with other recognized species were sym-homospermidine was the primary polyamine. The major cellular fatty acids were iso-C15 : 1G, iso-C15 : 0, iso-C16 : 0 3-OH and iso-C17 : 0 3-OH, with moderate amounts of iso-C16 : 0. The presence of glycolipids differentiated the novel strains from related genera. The DNA mol% G+C content of the type strain MU-2T was 45.2. Results for other phenotypic and molecular analyses indicated that strain MU-2T is a representative of a novel genus and species for which the name Vibrionimonas magnilacihabitans is proposed. The type strain is MU-2T ( = NRRL B-59231 = DSM 22423)

Mesorhizobium septentrionale sp nov and Mesorhizobium temperatum sp nov., isolated from Astragalus adsurgens growing in the northern regions of China

Ninety-five rhizobial strains isolated from Astragalus adsurgens growing in the northern regions of China were classified into three main groups, candidate species 1, 11 and 111, based on a polyphasic approach. Comparative analysis of full-length 16S rRNA gene sequences of representative strains showed that candidate species I and 11 were Mesorhizobium, while candidate species 111, which consisted of non-nodulating strains, was closely related to Agrobacterium tumefaciens. The phylogenetic relationships of the three candidate species and some related strains were also confirmed by the sequencing of glnA genes, which were used as an alternative chromosomal marker. The DNA-DNA relatedness was between 11.3 and 47-1 % among representative strains of candidate species I and 11 and the type strains of defined Mesorhizobium species. Candidate III had DNA relatedness of between 4(.)3 and 25(.)2 % with type strains of Agrobacterium tumefaciens and Agrobacterium rubi. Two novel species are proposed to accommodate candidate species I and 11, Mesorhizobium septentrionale sp. nov. (type strain, SIDW014(T) =CCBAU 11014(T) = HAMBI 2582(T)) and Mesorhizobium temperatum sp. nov. (type strain, SIDW018(T) = CCBAU 11018(T) =HAMBI 2583(T)), respectively. At least two distinct nodA sequences were identified among the strains. The numerically dominant nodA sequence type was most similar to that from the Mesorhizobium tianshanense type strain and was identified in strains belonging to the two novel species as well as other, as yet, undefined genome types. Host range studies indicate that the different nodA sequences correlate with different host ranges. Further comparative studies with the defined Agrobacterium species are needed to clarify the taxonomic identity of candidate species 111

Molecular biology techniques as a tool for detection and characterisation of Mycobacterium avium subsp. paratuberculosis

Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) is the causative agent of paratuberculosis, also known as Johne’s disease, a chronic intestinal infection in cattle and other ruminants. Paratuberculosis is characterised by diarrhea and weight loss that occurs after a period of a few months up to several years without any clinical signs. The considerable economic losses to dairy and beef cattle producers are caused by reduced milk production and poor reproduction performance in subclinically infected animals. Early diagnosis of infected cattle is essential to prevent the spread of the disease. Efforts have been made to eradicate paratuberculosis by using a detection and cull strategy, but eradication is hampered by the lack of suitable and sensitive diagnostic methods. This thesis, based on five scientific investigations, describes the development of different DNA amplification strategies for detection and characterisation of M. paratuberculosis. Various ways to pre-treat bacterial cultures, tissue specimens and fecal samples prior to PCR analysis were investigated. Internal positive PCR control molecules were developed and used in PCR analyses to improve the reliability and to facilitate the interpretation of the results. The sensitivity of the ultimate methods was found to be approximate that of culture and allowed detection of low numbers of M. paratuberculosis expected to be found in subclinically infected animals. Genomic DNA of a Swedish mycobacterial isolate, incorrectly identified by PCR as M. paratuberculosis was characterised. The isolate was closely related to M. cookii and harboured one copy of a DNA segment with 94% similarity to IS900, the target sequence used in diagnostic PCR for detection of M. paratuberculosis. This finding highlighted the urgency of developing or evaluating PCR systems based on genes other than IS900. A PCR-based fingerprinting method using primers targeting the enterobacterial intergenic consensus sequence (ERIC) and the IS900 sequence was developed and successfully used to distinguish M. paratuberculosis from closely related mycobacteria, including the above mentioned mycobacterial isolate. In conclusion, the molecular biology techniques developed in these studies have proved useful for accelerating the diagnostic detection and characterisation of M. paratuberculosis

Randomized benchmarking with gate-dependent noise

We analyze randomized benchmarking for arbitrary gate-dependent noise and prove that the exact impact of gate-dependent noise can be described by a single perturbation term that decays exponentially with the sequence length. That is, the exact behavior of randomized benchmarking under general gate-dependent noise converges exponentially to a true exponential decay of exactly the same form as that predicted by previous analysis for gate-independent noise. Moreover, we show that the operational meaning of the decay parameter for gate-dependent noise is essentially unchanged, that is, we show that it quantifies the average fidelity of the noise between ideal gates. We numerically demonstrate that our analysis is valid for strongly gate-dependent noise models. We also show why alternative analyses do not provide a rigorous justification for the empirical success of randomized benchmarking with gate-dependent noise.Comment: It measures what you expect. Comments welcome. v2: removed an inconsistent assumption from theorem 3 and clarified discussion of prior work. Results unchanged. v3: further clarified discussion of prior work, numerics now available at https://github.com/jjwallman/numerics. v4: licence change as required by Quantu

Computational identification of transcription factor binding sites by functional analysis of sets of genes sharing overrepresented upstream motifs

BACKGROUND: Transcriptional regulation is a key mechanism in the functioning of the cell, and is mostly effected through transcription factors binding to specific recognition motifs located upstream of the coding region of the regulated gene. The computational identification of such motifs is made easier by the fact that they often appear several times in the upstream region of the regulated genes, so that the number of occurrences of relevant motifs is often significantly larger than expected by pure chance. RESULTS: To exploit this fact, we construct sets of genes characterized by the statistical overrepresentation of a certain motif in their upstream regions. Then we study the functional characterization of these sets by analyzing their annotation to Gene Ontology terms. For the sets showing a statistically significant specific functional characterization, we conjecture that the upstream motif characterizing the set is a binding site for a transcription factor involved in the regulation of the genes in the set. CONCLUSIONS: The method we propose is able to identify many known binding sites in S. cerevisiae and new candidate targets of regulation by known transcription factors. Its application to less well studied organisms is likely to be valuable in the exploration of their regulatory interaction network.Comment: 19 pages, 1 figure. Published version with several improvements. Supplementary material available from the author

Capturing the ‘ome’ : the expanding molecular toolbox for RNA and DNA library construction

All sequencing experiments and most functional genomics screens rely on the generation of libraries to comprehensively capture pools of targeted sequences. In the past decade especially, driven by the progress in the field of massively parallel sequencing, numerous studies have comprehensively assessed the impact of particular manipulations on library complexity and quality, and characterized the activities and specificities of several key enzymes used in library construction. Fortunately, careful protocol design and reagent choice can substantially mitigate many of these biases, and enable reliable representation of sequences in libraries. This review aims to guide the reader through the vast expanse of literature on the subject to promote informed library generation, independent of the application