Biology subjects

Fischer, S. M.

Publications and source records attributed to Fischer, S. M..

3 recordsLinked to original sources

bioRxiv2022

The Use and Misuse of Composite Environmental Indices

Composite indices have been widely used to rank the environmental performance of nations. Such environmental indices can be useful in communicating complex information as a single value and have the potential to generate political and media awareness of environmental issues. However, indices that are poorly constructed can hinder efforts to identify environmental failings. Here, we provide a critical review of the theoretical and methodological foundations of environmental indices to enhance our understanding of the accuracy and applicability of such indices. In the present study we classify existing indices according to ranking goal, measurement components, and weighting methods. Using New Zealand and Niger as case studies, we examine correlations between ranks in ten national level indices to outline how measurement components and the goal of ranking itself may provide a more, or less, optimistic view of the state of a countrys environment. Our results suggest that environmental indices that include human health, socioeconomic, and policy indicators (such as human access to sanitation and clean drinking water) are positively correlated with each other, and that those excluding human health, socioeconomic, and policy indicators are also positively correlated with each other, while these two types of environmental indices are negatively correlated to each other. Our results demonstrate that the inclusion of indicators that do not relate to the actual state of natural environments can confound results. When choosing an existing environmental index - or developing a new one - it is important to assess whether the ranking goal and the included indicators are appropriate. This is important because the inclusion of confounding indicators in environmental indices may misrepresent the actual state of natural environments.

scientific communication and education↗

bioRxiv2019

Accelerated trans-sulfuration metabolically defines a discrete subclass of ALS patients

Amyotrophic lateral sclerosis (ALS) is a disease characterized by progressive paralysis and death. Most ALS cases are sporadic (sALS) and patient heterogeneity poses a formidable challenge for the development of viable biomarkers and effective therapies. Applying untargeted metabolite profiling on 77 sALS patient-derived primary dermal fibroblast lines and 45 sex/age matched controls, we found that [~]25% of cell lines (termed sALS-1) are characterized by upregulated trans-sulfuration, where methionine-derived homocysteine is channeled into cysteine and glutathione synthesis. sALS-1 fibroblasts exhibit a growth defect when grown under oxidative conditions, that can be fully-rescued by N-acetylcysteine. [U-13C]-glucose tracing shows that activation of the trans-sulfuration pathway is associated with accelerated glucose flux into the TCA cycle. Based on four metabolites, we developed a support vector machine model capable of distinguishing sALS-1 with 97.5% accuracy. Importantly, plasma metabolite profiling identifies a systemic perturbation of cysteine metabolism as a hallmark of sALS-1. These results indicate that sALS patients can be stratified into distinct metabotypes, differently sensitive to metabolic stress, and provides new insights into metabolic biomarkers for personalized sALS therapy.

neuroscience↗

bioRxiv2018

Identification of a Distinct Metabolomic Subtype of Sporadic ALS Patients

Sporadic amyotrophic lateral sclerosis (sALS) is a progressive motor neuron disease resulting in paralysis and death. Genes responsible for familial ALS have been identified, however the molecular basis for sALS is unknown. To discover metabotypic biomarkers that inform on disease etiology, untargeted metabolite profiling was performed on 77 patient-derived dermal fibroblast lines and 45 age/sex-matched controls. Surprisingly, 25% of sALS lines showed upregulated methionine-derived homocysteine, channeled to cysteine and glutathione (GSH). Stable isotope tracing of [U-13C]-glucose showed activation of the trans-sulfuration pathway, associated with accelerated glucose flux into the TCA cycle, glutamate, GSH, alanine, aspartate, acylcarnitines and nucleotide phosphates. A four-molecule support vector machine model distinguished the sALS subtype from controls with 97.5% accuracy. Plasma metabolite profiling identified increased taurine as a hallmark metabolite for this sALS subset, suggesting systemic perturbation of cysteine metabolism. Furthermore, integrated multiomics (mRNAs/microRNAs/metabolites) identified the super-trans-sulfuration pathway as a top hit for the sALS subtype. We conclude that sALS can be stratified into distinct metabotypes, providing for future development of personalized therapies that offer new hope to sufferers.

neuroscience↗