Biology subjects

Scheel, M.

Publications and source records attributed to Scheel, M..

4 recordsLinked to original sources

bioRxiv2023

Macromolecule modelling for improved metabolite quantification using short echo time brain 1H-MRS at 3 T and 7 T: The PRaMM Model

PurposeTo improve reliability of metabolite quantification at both, 3 T and 7 T, we propose a novel parametrized macromolecules quantification model (PRaMM) for brain 1H MRS, in which the ratios of macromolecule peak intensities are used as soft constraints. MethodsFull- and metabolite-nulled spectra were acquired in three different brain regions with different ratios of grey and white matter from six healthy volunteers, at both 3 T and 7 T. Metabolite-nulled spectra were used to identify highly correlated macromolecular signal contributions and estimate the ratios of their intensities. These ratios were then used as soft constraints in the proposed PRaMM model for quantification of full spectra. The PRaMM model was validated by comparison with a single component macromolecule model and a macromolecule subtraction technique. Moreover, the influence of the PRaMM model on the repeatability and reproducibility compared to those other methods was investigated. ResultsThe developed PRaMM model performed better than the two other approaches in all three investigated brain regions. Several estimates of metabolite concentration and their Cramer-Rao lower bounds were affected by the PRaMM model reproducibility, and repeatability of the achieved concentrations were tested by evaluating the method on a second repeated acquisitions dataset. While the observed effects on both metrics were not significant, the fit quality metrics were improved for the PRaMM method (p[≤]0.0001). Minimally detectable changes are in the range 0.5 - 1.9 mM and percent coefficients of variations are lower than 10% for almost all the clinically relevant metabolites. Furthermore, potential overparameterization was ruled out. ConclusionHere, the PRaMM model, a method for an improved quantification of metabolites was developed, and a method to investigate the role of the MM background and its individual components from a clinical perspective is proposed.

neuroscience↗

bioRxiv2023

Multiscale networks in multiple sclerosis

Complex diseases such as Multiple Sclerosis (MS) cover a wide range of biological scales, from genes and proteins to cells and tissues, up to the full organism. We conducted a multilayer network analysis and deep phenotyping with multi-omics data (genomics, phosphoproteomics and cytomics), brain and retinal imaging, and clinical data, obtained from a multicenter prospective cohort of 328 patients and 90 healthy controls. Multilayer networks were constructed using mutual information, and Boolean simulations identified paths within and among all layers. The path more commonly found from the boolean simulations connects MP2K, with Th17 cells, the retinal nerve fiber layer (RNFL) thickness and the age related MS severity score (ARMSS). Combinations of several proteins (HSPB1, MP2K1, SR6, KS6B1, SRC, MK03, LCK and STAT6)) and immune cells (Th17, Th1 non-classic, CD8, CD8 Treg, CD56 neg, and B memory) were part of the paths explaining the clinical phenotype. Specific paths identified were subsequently analyzed by flow cytometry at the single-cell level. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=94 SRC="FIGDIR/small/530153v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@7dd26org.highwire.dtl.DTLVardef@482239org.highwire.dtl.DTLVardef@1bef03borg.highwire.dtl.DTLVardef@8dc6e6_HPS_FORMAT_FIGEXP M_FIG C_FIG Author SummaryComplex diseases such as Multiple Sclerosis (MS) involve the contribution of a wide range of biological processes. We conducted a systems biology study of MS based on network analysis and deep phenotyping in a prospective cohort of patients with clinical, imaging, genetics, and omics assessments. The gene, proteins and cell paths explained variation in central nervous system damage, and in metrics of disease severity. Such multilayer paths explain the different phenotypes of the disease and can be developed as biomarkers of MS.

systems biology↗

bioRxiv2022

Abrupt permafrost thaw triggers microbial bloom and increased activity of microbial predators

Permafrost soils store a substantial part of the global soil carbon and nitrogen. However global warming causes abrupt erosion and gradual thaw, which make these stocks vulnerable to microbial decomposition into greenhouse gases. Here, we investigated the microbial response to abrupt in situ permafrost thaw. We sequenced the total RNA of a 1 m deep soil core consisting of up to 26500-year-old permafrost material from an active abrupt erosion site. We analysed the microbial community in the active layer soil, the recently thawed, and the intact permafrost and found maximum RNA:DNA ratios indicating a microbial bloom in recently thawed permafrost. Several fast-growing prokaryotic taxa dominated thawed permafrost, including Sphingobacteriales, Burkholderiales, and Nitrosomonadales. Overall, the thaw state and soil moisture consistently explained changes in community composition, with especially the permafrost community being significantly distinct from thawed soils. Predation correlated with changes in prokaryotic composition. Bacterial grazers were dominated by Myxococcales and abundant in the active layer. In contrast, protozoa, especially Cercozoa and Ciliophora, doubled in relative abundance in thawed layers. Our findings highlight the ecological importance of a rapid development of microbial blooms as well as the successive predation as biological control mechanism in abruptly thawing permafrost. One sentence summaryUsing total RNA from an up to 26500-year-old abruptly eroding permafrost site in Greenland, we described a microbial bloom and its controls, including bacterial and microeukaryotic predators. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=146 SRC="FIGDIR/small/499897v2_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@10ab79eorg.highwire.dtl.DTLVardef@9d0146org.highwire.dtl.DTLVardef@1bec509org.highwire.dtl.DTLVardef@179f397_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2019

Modulating the human functional connectome using deep brain stimulation

Neuroimaging has seen a paradigm shift from a formal description of local activity patterns toward studying distributed brain networks. The recently defined framework of the human connectome allows to globally analyse parts of the brain and their interconnections. Deep brain stimulation (DBS) is an invasive therapy for patients with severe movement disorders aiming to retune abnormal brain network activity by local high frequency stimulation of the basal ganglia. Beyond clinical utility, DBS represents a powerful research platform to study functional connectomics and the modulation of distributed brain networks in the human brain. We acquired resting-state functional MRI in twenty Parkinsons disease (PD) patients with subthalamic DBS switched ON and OFF. An age-matched control cohort of fifteen subjects was acquired from an open data repository. DBS lead placement in the subthalamic nucleus (STN) was localized using a state-of-the art pipeline that involved brain shift correction, multispectral image registration and use of a precise subcortical atlas. Based on a realistic 3D model of the electrode and surrounding anatomy, the amount of local impact of DBS was estimated using a finite element method approach. On a global level, average connectivity increases and decreases throughout the brain were estimated by contrasting ON and OFF DBS scans on a voxel-wise graph comprising eight thousand nodes. Local impact of DBS on the sensorimotor STN explained half the variance in global connectivity increases within the sensorimotor network (R = 0.711, p < 0.001). Moreover, local impact of DBS on the motor STN could explain the degree of how much voxel-wise average brain connectivity normalized toward healthy controls (R = 0.713, p < 0.001). Finally, a network based statistics analysis revealed that DBS attenuated specific couplings that are known to be pathological in PD. Namely, coupling between motor thalamus and sensorimotor cortex was increased and striatal coupling with cerebellum, external pallidum and STN was decreased by DBS. Our results show that rs-fMRI may be acquired in DBS ON and OFF conditions on clinical MRI hardware and that data is useful to gain additional insight into how DBS modulates the functional connectome of the human brain. We demonstrate that effective DBS increases overall connectivity in the motor network, normalizes the network profile toward healthy controls and specifically strengthens thalamo-cortical connectivity while reducing striatal control over basal ganglia and cerebellar structures.

neuroscience↗