Tectono-magmatic evolution of the Indian crust in western Himalayas during Paleoproterozoic: Insights from Nanga Parbat and Indus syntaxis in northern Pakistan

http://dx.doi.org/10.13039/100005156 Alexander von Humboldt-Stiftun

Alpha-synuclein misfolding as fluid biomarker for Parkinson’s disease measured with the iRS platform

Abstract Misfolding and aggregation of alpha-synuclein (αSyn) play a key role in the pathophysiology of Parkinson’s disease (PD). Despite considerable advances in diagnostics, an early and differential diagnosis of PD still represents a major challenge. We innovated the immuno-infrared sensor (iRS) platform for measuring αSyn misfolding. We analyzed cerebrospinal fluid (CSF) from two cohorts comprising PD cases, atypical Parkinsonian disorders, and disease controls. We obtained an AUC of 0.90 ( n  = 134, 95% CI 0.85–0.96) for separating PD/MSA from controls by determination of the αSyn misfolding by iRS. Using two thresholds divided individuals as unaffected/affected by misfolding with an intermediate area in between. Comparing the affected/unaffected cases, controls versus PD/MSA cases were classified with 97% sensitivity and 92% specificity. The spectral data revealed misfolding from an α-helical/random-coil αSyn in controls to β-sheet enriched αSyn in PD and MSA cases. Moreover, a first subgroup analysis implied the potential for patient stratification in clinically overlapping cases. The iRS, directly measuring all αSyn conformers, is complementary to the αSyn seed-amplification assays (SAAs), which however only amplify seeding competent conformers

Comparison of marker-less 2D image-based methods for infant pose estimation

Abstract In this study we compare the performance of available generic- and specialized infant-pose estimators for a video-based automated general movement assessment (GMA), and the choice of viewing angle for optimal recordings, i.e., conventional diagonal view used in GMA vs. top-down view. We used 4500 annotated video-frames from 75 recordings of infant spontaneous motor functions from 4 to 16 weeks. To determine which pose estimation method and camera angle yield the best pose estimation accuracy on infants in a GMA related setting, the error with respect to human annotations and the percentage of correct key-points (PCK) were computed and compared. The results show that the best performing generic model trained on adults, ViTPose, also performs best on infants. We see no improvement from using specific infant-pose estimators over the generic pose estimators on our infant dataset. However, when retraining a generic model on our data, there is a significant improvement in pose estimation accuracy. This indicates limited generalization capabilities of infant-pose estimators to other infant datasets, meaning that one should be careful when choosing infant pose estimators and using them on infant datasets which they were not trained on. The pose estimation accuracy obtained from the top-down view is significantly better than that obtained from the diagonal view (the standard view for GMA). This suggests that a top-down view should be included in recording setups for automated GMA research

Definition Zusammengefasster Krankheitsgruppen für ein Klassifikationssystem zur Messung des morbiditätsbezogenen Versorgungsbedarfs – PopGroup

Zusammenfassung Ziel In den letzten Jahren wurde verstärkt eine Morbiditätsorientierung in der Versorgungsstrukturplanung gefordert. Für die regional differenzierte Erhebung des Versorgungsbedarfs werden bevölkerungsbezogene Klassifikationssysteme benötigt, wie sie in verschiedenen Ländern bereits existieren. Das PopGroup Projekt hat zum Ziel, ein solches Klassifikationssystem (PopGrouper) für den deutschen Versorgungskontext zu entwickeln und verschiedene Anwendungen zu erproben. Der PopGrouper soll jede Person genau einer PopGroup zuordnen, die durch bestimmte klinische Eigenschaften und einen bestimmten Versorgungsbedarf charakterisiert ist. Das Ziel des ersten Schrittes der PopGrouper Entwicklung war es, als Basis für die Bildung von PopGroups, Diagnosen in medizinisch sinnvollen Gruppen zusammenzufassen – in sogenannten Zusammengefassten Krankheitsgruppen (ZKGs). Dieser Artikel befasst sich mit der Bildung und Validierung der ZKGs sowie mit der Definition eines Krankheitsschweregrads zu den entstandenen ZKGs. Methodik Die ZKGs wurden unter Einbeziehung medizinischer Expertise sowie Analysen der Routinedaten der BARMER-Krankenkasse gebildet. Dabei wurden bereits zuvor definierte Diagnosegruppen verwendet – die DxGs des morbiditätsorientierten Risikostrukturausgleichs. Zunächst wurden übergeordnete Makro-Krankheitsgruppen (MKGs) gebildet. Innerhalb der MKGs wurden die DxGs anhand definierter Kriterien zu ZKGs gruppiert. Die gebildeten ZKGs wurden durch Expert*innen wissenschaftlicher medizinischer Fachgesellschaften validiert. Abschließend wurde ein Krankheitsschweregrad anhand von drei Dimensionen (Mortalität, Kosten, Inanspruchnahme) sowie Schweregrad-Kategorien von „sehr schwer“ bis „sehr leicht“ definiert, um die ZKGs zu hierarchisieren. Ergebnisse Insgesamt wurden 32 MKGs und 433 ZKGs definiert und validiert. Jede ZKG erhielt einen Schweregrad-Score. Schlussfolgerung Die ZKGs und MKGs bilden einen wichtigen ersten Schritt der PopGrouper-Entwicklung. Auf dieser Grundlage konnten anschließend PopGroups gebildet werden, die diverse ZKGs und MKGs sowie Kombinationen berücksichtigen. Die Einteilung von Diagnosen in eine kleinere Anzahl medizinisch sinnvoller Gruppen bietet auch außerhalb des Projekts Möglichkeiten für die Versorgungsforschung, für die Analyse von Krankheiten sowie für die Identifikation von Versichertengruppen mit ähnlichen Eigenschaften

Exploring anterior thalamus functional connectivity with cortical regions in prospective memory with ultra-high-field functional MRI

Abstract Prospective memory, or memory for future intentions, engages particular cortical regions. Lesion studies also implicate the thalamus, with prospective memory deterioration following thalamic stroke. Neuroimaging, anatomical and lesion studies suggest the anterior nuclei of the thalamus (ANT), in particular, are involved in episodic memory, with electrophysiological studies suggesting an active role in selecting neural assemblies underlying particular memory traces. Here, we hypothesized that the ANT are engaged in realizing prospectively-encoded intentions, detectable using ultra-high-field strength functional MRI. Using a within-subject design, participants (N = 14; age 20–35 years) performed an ongoing n-back working memory task with two cognitive loads, each with and without a prospective memory component, during 7-Tesla functional MRI. Seed-to-voxel whole brain functional connectivity analyses were performed to establish whether including a prospective memory component in an ongoing task results in greater connectivity between ANT and cortical regions engaged in prospective memory. Repeated measures ANOVAs were applied to behavioral and connectivity measures, with the factors Task Type (with prospective memory or not) and N-Back (2-back or 3-back). Response accuracy was greater and reaction times faster without the prospective memory component, and accuracy was higher in the 2- than 3-back condition. Task Type had a main effect on connectivity with an ANT seed, with greater ANT–DLPFC and ANT–STG connectivity when including a prospective memory component. Post hoc testing based on a significant interaction showed greater ANT–DLPFC connectivity (p-FWE = 0.007) when prospective memory was included with the low cognitive load and ANT–STG connectivity (p-FWE = 0.019) with the high cognitive load ongoing task. Direct comparison showed greater functional connectivity between these areas and the ANT than dorsomedial nucleus of the thalamus (DMNT) during prospective remembering. Enhanced ANT–DLPFC connectivity, a brain region with an established role in strategic monitoring for prospective memory cues, arose with a low cognitive load ongoing task that enabled monitoring. This connectivity was significantly less on direct comparison with increasing the cognitive load of the ongoing task without prospective memory, suggesting specificity for prospective memory. Greater ANT–STG connectivity on prospective memory inclusion in the higher cognitive load ongoing task fits with reported STG activation on prospective memory through spontaneous retrieval. Lower connectivity on direct comparison with a DMNT seed suggests ANT specificity. The findings fit with a coordinating role for the ANT in prospective remembering. Given the small sample, these findings should be considered preliminary, with replication required

Herbariomic approach solved identity crisis of the putatively extinct Armeria arcuata Welw. ex Boiss. & Reut. (Plumbaginaceae)

Abstract Background and Aims Herbaria are powerful sources of data and material nowadays that can be used for analyses other than taxonomic purposes. Improved techniques of DNA extraction from old herbarium specimens combined with modern and relatively cheap genomic tools, allow the reassessment of the identity of important specimens with potential consequences on species conservation status. In this study, we used a genomic approach applied to type herbarium specimens from the mid-19th century to elucidate the taxonomic identity of Armeria arcuata and correctly identify a living plant (code: 1984BL00463) cultivated at the Utrecht University Botanic Gardens, which was suggested to represent the last individual of the Portuguese endemic A. arcuata. Methods DNA was extracted from historical herbarium specimens of A. arcuata, the living specimen at Utrecht Botanic Gardens, and selected specimens of seven other Armeria species. Genomic sequencing was conducted on chloroplast and nuclear ribosomal DNA regions, using Illumina and Nanopore technologies. Phylogenetic analyses were then performed to compare the sequences extracted. Key Results While the chloroplast genome highlights similarities of 1984BL00463 with the Armeria maritima group including the South American A. curvifolia, the nrDNA suggests a relationship of 1984BL00463 with A. caespitosa. Our results suggest that 1984BL00463 differs substantially from the type specimens of A. arcuata and may have a hybrid origin. Therefore, A. arcuata is declared extinct. Our results support that A. arcuata was a hybrid, one of whose progenitors was a sand-dune coastal species, A. pungens, but are inconclusive as to whether it was an established or an ephemeral hybrid. Conclusions Armeria arcuata is confirmed as extinct, while the Utrecht specimen represents a distinct lineage, potentially of hybrid origin too. This study highlights the importance of genomic tools in re-evaluating the status of rare or extinct species, demonstrating how herbarium and living botanical collections can complement conservation efforts and resolve taxonomic ambiguities. The approach presented here can inform similar studies on other putatively extinct taxa, guiding conservation priorities and strategies for biodiversity preservation