Neurofilament light chain as a biomarker in multiple sclerosis

Due to the unpredictable course and heterogenous treatment response in multiple sclerosis (MS), there is a clear need for biomarkers that reflect disease activity in the clinical follow-up of these patients. Neurofilaments are neuron-specific components of the cytoskeleton that can be assayed in different body compartments. They have been explored as potential biomarkers for many years. Neurofilament light chain (NF-L) appears the most promising biomarker in MS patients, and there is now little doubt that NF-L should have a role in the follow-up of MS patients. Newer assays and techniques for NF-L detection available in serum samples confirms the usefulness of NF-L as a biomarker. Nevertheless, there is still a need for prospective studies, and studies to determine clinical useful cut-off values. This review evaluates the strengths and weaknesses of NF-L as a biomarker in patients with MS.publishedVersio

Relationship between Polycyclic Aromatic Hydrocarbons in Sediments and Invertebrates of Natural and Artificial Stormwater Retention Ponds

Sediments and invertebrates were sampled from 9 stormwater retention ponds (SWRPs) and 11 natural, shallow lakes in Denmark. Samples were analyzed for 13 polycyclic aromatic hydrocarbons (PAHs). The SWRPs received urban and highway runoff from various types of drainage areas and the lakes were located in areas of various land uses. Comparing PAHs in the sediments of the SWRPs and the lakes, it was found that levels of total PAH were similar in the two aquatic systems, with median values of 0.94 and 0.63 mg·(kg·DM)−1 in sediments of SWRPs and lakes, respectively. However, the SWRP sediments tended to have higher concentrations of high-molecular-weight PAHs than the lakes. A similar pattern was seen for PAHs accumulated in invertebrates where the median of total PAH was 2.8 and 2.1 mg·(kg·DM)−1 for SWRPs and lakes, respectively. Principal component analysis on the PAH distribution in the sediments and invertebrates showed that ponds receiving highway runoff clustered with lakes in forests and farmland. The same was the case for some of the ponds receiving runoff from residential areas. Overall, results showed that sediment PAH levels in all SWRPs receiving runoff from highways were similar to the levels found in some of the investigated natural, shallow lakes, as were the sediment PAH levels from some of the residential SWRPs. Furthermore, there was no systematic trend that one type of water body exceeded environmental quality standards (EQS) values more often than others. Together this indicates that at least some SWRPs can sustain an invertebrate ecosystem without the organisms experiencing higher bioaccumulation of PAHs then what is the case in shallow lakes of the same region

USER fusion: a rapid and efficient method for simultaneous fusion and cloning of multiple PCR products

We present a method that allows simultaneous fusion and cloning of multiple PCR products in a rapid and efficient manner. The procedure is based on the use of PCR primers that contain a single deoxyuridine residue near their 5′ end. Treatment of the PCR products with a commercial deoxyuridine-excision reagent generates long 3′ overhangs designed to specifically complement each other. The combination of this principle with the improved USER cloning technique provides a simple, fast and very efficient method to simultaneously fuse and clone multiple PCR fragments into a vector of interest. Around 90% positive clones were obtained when three different PCR products were fused and cloned into a USER-compatible vector in a simple procedure that, apart from the single PCR amplification step and the bacterial transformation, took approximately one hour. We expect this method to replace overlapping PCR and the use of type IIS restriction enzymes in many of their applications

Scalable Group Level Probabilistic Sparse Factor Analysis

Many data-driven approaches exist to extract neural representations of functional magnetic resonance imaging (fMRI) data, but most of them lack a proper probabilistic formulation. We propose a group level scalable probabilistic sparse factor analysis (psFA) allowing spatially sparse maps, component pruning using automatic relevance determination (ARD) and subject specific heteroscedastic spatial noise modeling. For task-based and resting state fMRI, we show that the sparsity constraint gives rise to components similar to those obtained by group independent component analysis. The noise modeling shows that noise is reduced in areas typically associated with activation by the experimental design. The psFA model identifies sparse components and the probabilistic setting provides a natural way to handle parameter uncertainties. The variational Bayesian framework easily extends to more complex noise models than the presently considered.Comment: 10 pages plus 5 pages appendix, Submitted to ICASSP 1

Distribution, Size, and Shape of Abdominal Aortic Calcified Deposits and Their Relationship to Mortality in Postmenopausal Women

Abdominal aortic calcifications (AACs) correlate strongly with coronary artery calcifications and can be predictors of cardiovascular mortality. We investigated whether size, shape, and distribution of AACs are related to mortality and how such prognostic markers perform compared to the state-of-the-art AC24 marker introduced by Kauppila. Methods. For 308 postmenopausal women, we quantified the number of AAC and the percentage of the abdominal aorta that the lesions occupied in terms of their area, simulated plaque area, thickness, wall coverage, and length. We analysed inter-/intraobserver reproducibility and predictive ability of mortality after 8-9 years via Cox regression leading to hazard ratios (HRs). Results. The coefficient of variation was below 25% for all markers. The strongest individual predictors were the number of calcifications (HR = 2.4) and the simulated area percentage (HR = 2.96) of a calcified plaque, and, unlike AC24 (HR = 1.66), they allowed mortality prediction also after adjusting for traditional risk factors. In a combined Cox regression model, the strongest complementary predictors were the number of calcifications (HR = 2.76) and the area percentage (HR = −3.84). Conclusion. Morphometric markers of AAC quantified from radiographs may be a useful tool for screening and monitoring risk of CVD mortality

Different binding motifs of the celiac disease-associated HLA molecules DQ2.5, DQ2.2, and DQ7.5 revealed by relative quantitative proteomics of endogenous peptide repertoires

Celiac disease is caused by intolerance to cereal gluten proteins, and HLA-DQ molecules are involved in the disease pathogenesis by presentation of gluten peptides to CD4+ T cells. The α- or β-chain sharing HLA molecules DQ2.5, DQ2.2, and DQ7.5 display different risks for the disease. It was recently demonstrated that T cells of DQ2.5 and DQ2.2 patients recognize distinct sets of gluten epitopes, suggesting that these two DQ2 variants select different peptides for display. To explore whether this is the case, we performed a comprehensive comparison of the endogenous self-peptides bound to HLA-DQ molecules of B-lymphoblastoid cell lines. Peptides were eluted from affinity-purified HLA molecules of nine cell lines and subjected to quadrupole orbitrap mass spectrometry and MaxQuant software analysis. Altogether, 12,712 endogenous peptides were identified at very different relative abundances. Hierarchical clustering of normalized quantitative data demonstrated significant differences in repertoires of peptides between the three DQ variant molecules. The neural network-based method, NNAlign, was used to identify peptide-binding motifs. The binding motifs of DQ2.5 and DQ7.5 concurred with previously established binding motifs. The binding motif of DQ2.2 was strikingly different from that of DQ2.5 with position P3 being a major anchor having a preference for threonine and serine. This is notable as three recently identified epitopes of gluten recognized by T cells of DQ2.2 celiac patients harbor serine at position P3. This study demonstrates that relative quantitative comparison of endogenous peptides sampled from our protein metabolism by HLA molecules provides clues to understand HLA association with disease.Fil: Bergseng, Elin. University of Oslo; NoruegaFil: Dørum, Siri. University of Oslo; NoruegaFil: Arntzen, Magnus Ø.. University of Oslo; NoruegaFil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Nygård, Ståle. University of Oslo; NoruegaFil: Buus, Søren. Universidad de Copenhagen; DinamarcaFil: de Souza, Gustavo A.. University of Oslo; NoruegaFil: Sollid, Ludvig M.. University of Oslo; Norueg

Reevaluation of the Phylogenetic Diversity and Global Distribution of the Genus "Candidatus Accumulibacter"

“Candidatus Accumulibacter” was the first microorganism identified as a polyphosphate-accumulating organism (PAO) important for phosphorus removal from wastewater. Members of this genus are diverse, and the current phylogeny and taxonomic framework appear complicated, with most publicly available genomes classified as “Candidatus Accumulibacter phosphatis,” despite notable phylogenetic divergence. The ppk1 marker gene allows for a finer-scale differentiation into different “types” and “clades”; nevertheless, taxonomic assignments remain inconsistent across studies. Therefore, a comprehensive reevaluation is needed to establish a common understanding of this genus, in terms of both naming and basic conserved physiological traits. Here, we provide this reassessment using a comparison of genome, ppk1, and 16S rRNA gene-based approaches from comprehensive data sets. We identified 15 novel species, along with “Candidatus Accumulibacter phosphatis,” “Candidatus Accumulibacter delftensis,” and “Candidatus Accumulibacter aalborgensis.” To compare the species in situ, we designed new species-specific fluorescence in situ hybridization (FISH) probes and revealed their morphology and arrangement in activated sludge. Based on the MiDAS global survey, “Ca. Accumulibacter” species were widespread in wastewater treatment plants (WWTPs) with phosphorus removal, indicating process design as a major driver for their abundance. Genome mining for PAO-related pathways and FISH-Raman microspectroscopy confirmed the potential for PAO metabolism in all “Ca. Accumulibacter” species, with detection in situ of the typical PAO storage polymers. Genome annotation further revealed differences in the nitrate/nitrite reduction pathways. This provides insights into the niche differentiation of these lineages, potentially explaining their coexistence in the same ecosystem while contributing to overall phosphorus and nitrogen removal. IMPORTANCE “Candidatus Accumulibacter” is the most studied PAO, with a primary role in biological nutrient removal. However, the species-level taxonomy of this lineage is convoluted due to the use of different phylogenetic markers or genome sequencing approaches. Here, we redefined the phylogeny of these organisms, proposing a comprehensive approach which could be used to address the classification of other diverse and uncultivated lineages. Using genome-resolved phylogeny, compared to phylogeny based on the 16S rRNA gene and other phylogenetic markers, we obtained a higher-resolution taxonomy and established a common understanding of this genus. Furthermore, genome mining of genes and pathways of interest, validated in situ by application of a new set of FISH probes and Raman microspectroscopy, provided additional high-resolution metabolic insights into these organisms