Chlorin Index: A new parameter for organic matter freshness in sediments

Total chlorins, comprising degradation products of chlorophyll, have been used recently to reconstruct paleoproductivity from marine sediment cores. Here, we report on a new index, the Chlorin Index (CI), that proves to be a helpful tool for rapidly estimating organic matter freshness in marine sediments. The CI is a ratio between the fluorescence intensity of a sediment extracted with acetone and treated with hydrochloric acid and the original sediment extract. It represents the ratio of chlorophyll and its degradation products deposited in the sediments that could still be chemically transformed and those that are inert to chemical attack. The ratio is lower in sediments that include freshly deposited phytoplankton material and higher in older, more degraded sediments. We measured this new parameter on surface sediments, and sediments from several short and a long sediment core from different oceanic settings. CI values range from 0.2 for chlorophyll a to 0.36–0.56 for fresh material deposited on the shelf off Namibia to values around 0.67 in sediments off Chile and Peru to values up to 0.97 for sediments in a deep core from the northeastern slope of the Arabian Sea. We have compared the CI to rates of bacterial sulfate reduction, as a direct measure of organic matter reactivity and to other degradation indices based on amino acid composition. We conclude that the CI is a reliable and simple tool for the characterization of organic material freshness in sediments in respect to its degradation state

Spinocerebellar ataxia types 1, 2, 3, and 6: disease severity and nonataxia symptoms.

OBJECTIVE: To identify factors that determine disease severity and clinical phenotype of the most common spinocerebellar ataxias (SCAs), we studied 526 patients with SCA1, SCA2, SCA3. or SCA6. METHODS: To measure the severity of ataxia we used the Scale for the Assessment and Rating of Ataxia (SARA). In addition, nonataxia symptoms were assessed with the Inventory of Non-Ataxia Symptoms (INAS). The INAS count denotes the number of nonataxia symptoms in each patient. RESULTS: An analysis of covariance with SARA score as dependent variable and repeat lengths of the expanded and normal allele, age at onset, and disease duration as independent variables led to multivariate models that explained 60.4% of the SARA score variance in SCA1, 45.4% in SCA2, 46.8% in SCA3, and 33.7% in SCA6. In SCA1, SCA2, and SCA3, SARA was mainly determined by repeat length of the expanded allele, age at onset, and disease duration. The only factors determining the SARA score in SCA6 were age at onset and disease duration. The INAS count was 5.0 +/- 2.3 in SCA1, 4.6 +/- 2.2 in SCA2, 5.2 +/- 2.5 in SCA3, and 2.0 +/- 1.7 in SCA6. In SCA1, SCA2, and SCA3, SARA score and disease duration were the strongest predictors of the INAS count. In SCA6, only age at onset and disease duration had an effect on the INAS count. CONCLUSIONS: Our study suggests that spinocerebellar ataxia (SCA) 1, SCA2, and SCA3 share a number of common biologic properties, whereas SCA6 is distinct in that its phenotype is more determined by age than by disease-related factors

Comparative genomics of isolates of a pseudomonas aeruginosa epidemic strain associated with chronic lung infections of cystic fibrosis patients

Pseudomonas aeruginosa is the main cause of fatal chronic lung infections among individuals suffering from cystic fibrosis (CF). During the past 15 years, particularly aggressive strains transmitted among CF patients have been identified, initially in Europe and more recently in Canada. The aim of this study was to generate high-quality genome sequences for 7 isolates of the Liverpool epidemic strain (LES) from the United Kingdom and Canada representing different virulence characteristics in order to: (1) associate comparative genomics results with virulence factor variability and (2) identify genomic and/or phenotypic divergence between the two geographical locations. We performed phenotypic characterization of pyoverdine, pyocyanin, motility, biofilm formation, and proteolytic activity. We also assessed the degree of virulence using the Dictyostelium discoideum amoeba model. Comparative genomics analysis revealed at least one large deletion (40-50 kb) in 6 out of the 7 isolates compared to the reference genome of LESB58. These deletions correspond to prophages, which are known to increase the competitiveness of LESB58 in chronic lung infection. We also identified 308 non-synonymous polymorphisms, of which 28 were associated with virulence determinants and 52 with regulatory proteins. At the phenotypic level, isolates showed extensive variability in production of pyocyanin, pyoverdine, proteases and biofilm as well as in swimming motility, while being predominantly avirulent in the amoeba model. Isolates from the two continents were phylogenetically and phenotypically undistinguishable. Most regulatory mutations were isolate-specific and 29% of them were predicted to have high functional impact. Therefore, polymorphism in regulatory genes is likely to be an important basis for phenotypic diversity among LES isolates, which in turn might contribute to this strain's adaptability to varying conditions in the CF lung

Deep subsurface carbon cycling in the Nankai Trough (Japan)-Evidence of tectonically induced stimulation of a deep microbial biosphere

The abundance of microbial life and the sources of energy necessary for deep subsurface microbial communities remain enigmatic. Here we investigate deep microbial processes and their potential relationships to tectonic events in sediments from the Nankai Trough offshore Japan, drilled and sampled during IODP (Integrated Ocean Drilling Program) Expedition 316. Observed methane isotope profiles indicate that microbially mediated methane production occurs at Sites C0006 and C0007 in sediments below ∼450 meters below seafloor (mbsf) and ∼425 mbsf, respectively. The active carbon cycling in these deep subsurface sediments is likely related to the highly dynamic tectonic regime at Nankai Trough. We propose that transient increases in temperature have restimulated organic matter degradation at these distinct depths and explore several candidate processes for transient heating. Our favored hypothesis is frictional heating associated with earthquakes. In concert with transient heating leading to the reactivation of recalcitrant organic matter, the heterogeneous sedimentary system provides niches for microbial life. The newly available/accessible organic carbon compounds fuel the microbial community—resulting in an onset of methanogenesis several hundred meters below the seafloor. This process is captured in the methane C-isotope signal, showing the efficacy of methane C-isotopes for delineating locations of active microbial processes in deeply buried sediments. Additionally, simple model approaches applied to observed chemical pore water profiles can potentially constrain timing relationships, which can then be linked to causative tectonic events. Our results suggest the occurrence of slip-to-the-trench earthquake(s) 200–400 year ago, which could relate to historical earthquakes (1707 Hoei and/or 1605 Keicho earthquakes)

CerebNet: A fast and reliable deep-learning pipeline for detailed cerebellum sub-segmentation

Quantifying the volume of the cerebellum and its lobes is of profound interest in various neurodegenerative and acquired diseases. Especially for the most common spinocerebellar ataxias (SCA), for which the first antisense oligonculeotide-base gene silencing trial has recently started, there is an urgent need for quantitative, sensitive imaging markers at pre-symptomatic stages for stratification and treatment assessment. This work introduces CerebNet, a fully automated, extensively validated, deep learning method for the lobular segmentation of the cerebellum, including the separation of gray and white matter. For training, validation, and testing, T1-weighted images from 30 participants were manually annotated into cerebellar lobules and vermal sub-segments, as well as cerebellar white matter. CerebNet combines FastSurferCNN, a UNet-based 2.5D segmentation network, with extensive data augmentation, e.g. realistic non-linear deformations to increase the anatomical variety, eliminating additional preprocessing steps, such as spatial normalization or bias field correction. CerebNet demonstrates a high accuracy (on average 0.87 Dice and 1.742mm Robust Hausdorff Distance across all structures) outperforming state-of-the-art approaches. Furthermore, it shows high test-retest reliability (average ICC >0.97 on OASIS and Kirby) as well as high sensitivity to disease effects, including the pre-ataxic stage of spinocerebellar ataxia type 3 (SCA3). CerebNet is compatible with FreeSurfer and FastSurfer and can analyze a 3D volume within seconds on a consumer GPU in an end-to-end fashion, thus providing an efficient and validated solution for assessing cerebellum sub-structure volumes. We make CerebNet available as source-code (https://github.com/Deep-MI/FastSurfer)

Pedestrian, Crowd, and Evacuation Dynamics

This contribution describes efforts to model the behavior of individual pedestrians and their interactions in crowds, which generate certain kinds of self-organized patterns of motion. Moreover, this article focusses on the dynamics of crowds in panic or evacuation situations, methods to optimize building designs for egress, and factors potentially causing the breakdown of orderly motion.Comment: This is a review paper. For related work see http://www.soms.ethz.c

Health-related quality of life in patients with spinocerebellar ataxia: a validation study of the EQ-5D-3L

Although health-related quality of life (HRQoL) has developed into a crucial outcome parameter in clinical research, evidence of the EQ-5D-3L validation performance is lacking in patients with spinocerebellar ataxia (SCA) types 1, 2, 3, and 6. The objective of this study is to assess the acceptability, validity, reliability, and responsiveness of the EQ-5D-3L. For n = 842 predominantly European SCA patients of two longitudinal cohort studies, the EQ-5D-3L, PHQ-9 (Patient Health Questionnaire), and ataxia-specific clinical assessments (SARA: Scale for Assessment and Rating of Ataxia; ADL: activities of daily living as part of Friedreich's Ataxia Rating Scale; INAS: Inventory of Non-Ataxia Signs) were assessed at baseline and multiple annual follow-ups. The EQ-5D-3L was evaluated regarding acceptability, distribution properties, convergent and known-groups validity, test-retest reliability, and effect size measures to analyze health changes. The non-item response was low (EQ-5D-3L index: 0.8%; EQ-VAS: 3.4%). Ceiling effects occurred in 9.9% (EQ-5D-3L) and 3.0% (EQ-VAS) with a mean EQ-5D-3L index of 0.65 ± 0.21. In total, convergent validity showed moderate to strong Spearman's rho (r(s) > 0.3) coefficients comparing EQ-5D-3L and EQ-VAS with PHQ-9, SARA, ADL, and INAS. EQ-5D-3L could discriminate between groups of age, SARA, ADL, and INAS. Intra-class correlation coefficients (EQ-5D-3L(ICC): 0.95/EQ-VAS(ICC): 0.88) and Kappa statistics (range 0.44 to 0.93 for EQ-5D-3L items) indicated tolerable reliability. EQ-5D-3L shows small (effect size < 0.3) to moderate (effect size 0.3-0.59) health changes regarding ataxia severity. The analysis confirms an acceptable, reliable, valid, and responsive recommended EQ-5D-3L in SCA patients, measuring the HRQoL adequately, besides well-established clinical instruments

Characterization of Lifestyle in Spinocerebellar Ataxia Type 3 and Association with Disease Severity

BACKGROUND: Lifestyle could influence the course of hereditary ataxias, but representative data are missing. OBJECTIVE: The objective of this study was to characterize lifestyle in spinocerebellar ataxia type 3 (SCA3) and investigate possible associations with disease parameters. METHODS: In a prospective cohort study, data on smoking, alcohol consumption, physical activity, physiotherapy, and body mass index (BMI) were collected from 243 patients with SCA3 and 119 controls and tested for associations with age of onset, disease severity, and progression. RESULTS: Compared with controls, patients with SCA3 were less active and consumed less alcohol. Less physical activity and alcohol abstinence were associated with more severe disease, but not with progression rates or age of onset. Smoking, BMI, or physiotherapy did not correlate with disease parameters. CONCLUSION: Differences in lifestyle factors of patients with SCA3 and controls as well as associations of lifestyle factors with disease severity are likely driven by the influence of symptoms on behavior. No association between lifestyle and disease progression was detected. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Mutation Detection with Next-Generation Resequencing through a Mediator Genome

The affordability of next generation sequencing (NGS) is transforming the field of mutation analysis in bacteria. The genetic basis for phenotype alteration can be identified directly by sequencing the entire genome of the mutant and comparing it to the wild-type (WT) genome, thus identifying acquired mutations. A major limitation for this approach is the need for an a-priori sequenced reference genome for the WT organism, as the short reads of most current NGS approaches usually prohibit de-novo genome assembly. To overcome this limitation we propose a general framework that utilizes the genome of relative organisms as mediators for comparing WT and mutant bacteria. Under this framework, both mutant and WT genomes are sequenced with NGS, and the short sequencing reads are mapped to the mediator genome. Variations between the mutant and the mediator that recur in the WT are ignored, thus pinpointing the differences between the mutant and the WT. To validate this approach we sequenced the genome of Bdellovibrio bacteriovorus 109J, an obligatory bacterial predator, and its prey-independent mutant, and compared both to the mediator species Bdellovibrio bacteriovorus HD100. Although the mutant and the mediator sequences differed in more than 28,000 nucleotide positions, our approach enabled pinpointing the single causative mutation. Experimental validation in 53 additional mutants further established the implicated gene. Our approach extends the applicability of NGS-based mutant analyses beyond the domain of available reference genomes