Arabidopsis thaliana is the most widely studied model plant. Functional genomics is intensively underway in many laboratories worldwide. Beyond the basic annotation of the primary sequence data, the annotated genetic elements of Arabidopsis must be linked to diverse biological data and higher order information such as metabolic or regulatory pathways. The MIPS Arabidopsis thaliana database MAtDB aims to provide a comprehensive resource for Arabidopsis as a genome model that serves as a primary reference for research in plants and is suitable for transfer of knowledge to other plants, especially crops. The genome sequence as a common backbone serves as a scaffold for the integration of data, while, in a complementary effort, these data are enhanced through the application of state-of-the-art bioinformatics tools. This information is visualized on a genome-wide and a gene-by-gene basis with access both for web users and applications. This report updates the information given in a previous report and provides an outlook on further developments. The MAtDB web interface can be accessed at http://mips.gsf.de/proj/thal/db.

The prognostic role of cerebrospinal fluid molecular biomarkers determined in early pathogenic stages of multiple sclerosis has yet to be defined. In the present study, we aimed to investigate the prognostic value of chitinase 3 like 1 (CHI3L1), neurofilament light chain, and oligoclonal bands for conversion to clinically isolated syndrome and to multiple sclerosis in 75 patients with radiologically isolated syndrome. Cerebrospinal fluid levels of CHI3L1 and neurofilament light chain were measured by enzyme-linked immunosorbent assay. Uni- and multivariable Cox regression models including as covariates age at diagnosis of radiologically isolated syndrome, number of brain lesions, sex and treatment were used to investigate associations between cerebrospinal fluid CHI3L1 and neurofilament light chain levels and time to conversion to clinically isolated syndrome and multiple sclerosis. Neurofilament light chain levels and oligoclonal bands were independent risk factors for the development of clinically isolated syndrome (hazard ratio = 1.02, P = 0.019, and hazard ratio = 14.7, P = 0.012, respectively) and multiple sclerosis (hazard ratio = 1.03, P = 0.003, and hazard ratio = 8.9, P = 0.046, respectively). The best cut-off to classify cerebrospinal fluid neurofilament light chain levels into high and low was 619 ng/l, and high neurofilament light chain levels were associated with a trend to shorter time to clinically isolated syndrome (P = 0.079) and significant shorter time to multiple sclerosis (P = 0.017). Similarly, patients with radiologically isolated syndrome presenting positive oligoclonal bands converted faster to clinically isolated syndrome and multiple sclerosis (P = 0.005 and P = 0.008, respectively). The effects of high neurofilament light chain levels shortening time to clinically isolated syndrome and multiple sclerosis were more pronounced in radiologically isolated syndrome patients with ≥37 years compared to younger patients. Cerebrospinal fluid CHI3L1 levels did not influence conversion to clinically isolated syndrome and multiple sclerosis in radiologically isolated syndrome patients. Overall, these findings suggest that cerebrospinal neurofilament light chain levels and oligoclonal bands are independent predictors of clinical conversion in patients with radiologically isolated syndrome. The association with a faster development of multiple sclerosis reinforces the importance of cerebrospinal fluid analysis in patients with radiologically isolated syndrome.

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Leptomeningeal contrast enhancement (LMCE) on magnetic resonance imaging (MRI) is a newly recognized possible biomarker in multiple sclerosis (MS), associated with MS progression and cortical atrophy. In this study, we aimed to assess the prevalence of LMCE foci and their impact on neurodegeneration and disability. Materials. 54 patients with MS were included in the study. LMCE were detected with a 3 Tesla scanner on postcontrast fluid-attenuated inversion-recovery (FLAIR) sequence. Expanded Disability Status Scale (EDSS) score, number of relapses during 5 years from MS onset, and number of contrast-enhancing lesions on T1 weighted MRI were counted. Results. LMCE was detected in 41% (22/54) of patients. LMCE-positive patients had longer disease duration (p = 0,0098) and higher EDSS score (p = 0,039), but not a higher relapse rate (p = 0,091). No association of LMCE with higher frequency of contrast-enhancing lesions on T1-weighted images was detected (p = 0,3842). Analysis of covariates, adjusted for age, sex, and disease duration, revealed a significant effect of LMCE on the cortex volume (p = 0.043, F = 2.529), the total grey matter volume (p = 0.043, F = 2.54), and total ventricular volume (p = 0.039, F = 2.605). Conclusions. LMCE was shown to be an independent and significant biomarker of grey matter atrophy and disability in MS.

Background and objectiveIn this study, we evaluated the diagnostic and prognostic significance of cerebrospinal fluid free light chains (CSF FLC) at the time of clinically isolated syndrome (CIS).MethodsWe compared FLC-parameters at the moment of CIS in patients with conversion to multiple sclerosis (MS) after 2 years (CIS-MS), patients who remained stable both clinically and radiologically after 2 years (CIS-nonMS), patients with non-inflammatory neurologic diseases (NIND) as a comparison group and patients with other inflammatory neurologic diseases (IND) with intrathecal oligoclonal bands (OCB) synthesis. ROC-analysis was conducted to define FLC-assay characteristics and cut-off values. We also compared FLC-concentrations in CIS patients to determine their OCB-status. A correlation analysis was performed between FLC-concentrations and the expanded disability scale score (EDSS), annualized relapse rate (ARR) and MRI-activity (i.e., number of new and gadolinium-enhancing (Gd+) lesions) in patients.ResultsThe levels of kappa-FLC (k-FLCCSF) and lambda-FLC (λ-FLCCSF) as well as kappa- and lambda-quotients (Q-k and Q-λ) were elevated in CIS-MS compared to the CIS-nonMS and NIND groups. These levels did not differ significantly when compared with the IND group. We identified several patients with high k-FLCCSF and λ-FLCCSF in OCB-negative CIS and IND groups. The level of k-FLCCSF production was significantly higher in OCB-positive patients in the CIS-MS group compared to the CIS-nonMS group. The concentrations of k-FLCCSF and Q-k in the CIS-MS group showed significant correlation with the level of EDSS after 2 years (k-FLC: r = 0.4477,p = 0.0016; Q-k: r = 0.4621, p = 0.0016). λ-FLCCSF and Q-λ inversely correlated with the number of Gd+ lesions (CSF λ-FLC: r = -0.3698, p = 0.0223; Q-λ: r = -0.4527, p = 0.0056).ConclusionThe concentration of CSF FLC predicts conversion to MS within 2 years following CIS. OCB-positive patients with an early conversion have a higher concentration of CSF-FLC. We have also shown a prognostic significance of k-FLCCSF for future EDSS-progression.