Selective neuronal staining in tardigrades and onychophorans provides insights into the evolution of segmental ganglia in panarthropods

Background: Although molecular analyses have contributed to a better resolution of the animal tree of life, the phylogenetic position of tardigrades (water bears) is still controversial, as they have been united alternatively with nematodes, arthropods, onychophorans (velvet worms), or onychophorans plus arthropods. Depending on the hypothesis favoured, segmental ganglia in tardigrades and arthropods might either have evolved independently, or they might well be homologous, suggesting that they were either lost in onychophorans or are a synapomorphy of tardigrades and arthropods. To evaluate these alternatives, we analysed the organisation of the nervous system in three tardigrade species using antisera directed against tyrosinated and acetylated tubulin, the amine transmitter serotonin, and the invertebrate neuropeptides FMRFamide, allatostatin and perisulfakinin. In addition, we performed retrograde staining of nerves in the onychophoran Euperipatoides rowelli in order to compare the serial locations of motor neurons within the nervous system relative to the appendages they serve in arthropods, tardigrades and onychophorans. Results: Contrary to a previous report from a Macrobiotus species, our immunocytochemical and electron microscopic data revealed contralateral fibres and bundles of neurites in each trunk ganglion of three tardigrade species, including Macrobiotus cf. harmsworthi, Paramacrobiotus richtersi and Hypsibius dujardini. Moreover, we identified additional, extra-ganglionic commissures in the interpedal regions bridging the paired longitudinal connectives. Within the ganglia we found serially repeated sets of serotonin- and RFamid-like immunoreactive neurons. Furthermore, our data show that the trunk ganglia of tardigrades, which include the somata of motor neurons, are shifted anteriorly with respect to each corresponding leg pair, whereas no such shift is evident in the arrangement of motor neurons in the onychophoran nerve cords. Conclusions: Taken together, these data reveal three major correspondences between the segmental ganglia of tardigrades and arthropods, including (i) contralateral projections and commissures in each ganglion, (ii) segmentally repeated sets of immunoreactive neurons, and (iii) an anteriorly shifted (parasegmental) position of ganglia. These correspondences support the homology of segmental ganglia in tardigrades and arthropods, suggesting that these structures were either lost in Onychophora or, alternatively, evolved in the tardigrade/arthropod lineage

A robust coregistration method for in vivo studies using a first generation simultaneous PET/MR scanner

Purpose: Hybrid positron emission tomography (PET)/magnetic resonance (MR) imaging systems have recently been built that allow functional and anatomical information obtained from PET and MR to be acquired simultaneously. The authors have developed a robust coregistration scheme for a first generation small animal PET/MR imaging system and illustrated the potential of this system to study intratumoral heterogeneity in a mouse model. Methods: An alignment strategy to fuse simultaneously acquired PET and MR data, using the MR imaging gradient coordinate system as the reference basis, was developed. The fidelity of the alignment was evaluated over multiple study sessions. In order to explore its robustness in vivo, the alignment strategy was applied to explore the heterogeneity of glucose metabolism in a xenograft tumor model, using ^(18)F-FDG-PET to guide the acquisition of localized ^1H MR spectra within a single imaging session. Results: The alignment method consistently fused the PET/MR data sets with subvoxel accuracy (registration error mean=0.55 voxels, <0.28 mm); this was independent of location within the field of view. When the system was used to study intratumoral heterogeneity within xenograft tumors, a correlation of high ^(18)F-FDG-PET signal with high choline/creatine ratio was observed. Conclusions: The authors present an implementation of an efficient and robust coregistration scheme for multimodal noninvasive imaging using PET and MR. This setup allows time-sensitive, multimodal studies of physiology to be conducted in an efficient manner

Microglial phagolysosome dysfunction and altered neural communication amplify phenotypic severity in Prader-Willi Syndrome with larger deletion

Prader-Willi Syndrome (PWS) is a rare neurodevelopmental disorder of genetic etiology, characterized by paternal deletion of genes located at chromosome 15 in 70% of cases. Two distinct genetic subtypes of PWS deletions are characterized, where type I (PWS T1) carries four extra haploinsufficient genes compared to type II (PWS T2). PWS T1 individuals display more pronounced physiological and cognitive abnormalities than PWS T2, yet the exact neuropathological mechanisms behind these differences remain unclear. Our study employed postmortem hypothalamic tissues from PWS T1 and T2 individuals, conducting transcriptomic analyses and cell-specific protein profiling in white matter, neurons, and glial cells to unravel the cellular and molecular basis of phenotypic severity in PWS sub-genotypes. In PWS T1, key pathways for cell structure, integrity, and neuronal communication are notably diminished, while glymphatic system activity is heightened compared to PWS T2. The microglial defect in PWS T1 appears to stem from gene haploinsufficiency, as global and myeloid-specific Cyfip1 haploinsufficiency in murine models demonstrated. Our findings emphasize microglial phagolysosome dysfunction and altered neural communication as crucial contributors to the severity of PWS T1’s phenotype

Resilience and stress in later life: a network analysis approach depicting complex interactions of resilience resources and stress-related risk factors in older adults

Background: Emerging systemic approaches on resilience propose that a person's or group's adaptability to significant stress relies on a network of interdependent resources. However, little knowledge exists on systemic resilience in older survivors of early-life adversity (ELA) and how ELA affects their resource network in later life. Objective: This study investigated how ELA may be linked to the interplay of resources and stress-related risk factors in later life. Research Design and Methods: Data from N = 235 older adults (M age = 70.43 years; 46.40% female) were assessed. Half the participants were affected by ELA through compulsory social measures and placements in childhood, and/or adolescence ("risk group"). The other half were age-matched, non-affected participants ("control group"). Using psychometric instruments, a set of resilience-supporting resources in later life and current stress indices were assessed. Regularized partial correlation networks examined the interplay of resources in both groups, whilst also considering the impact of stress. Results: Both groups demonstrated only positive resource interrelations. Although the control group showed more possible resource connections, the groups did not significantly differ in the overall strength of connections. While group-specific resource interrelations were identified, self-esteem was observed to be the most important resource for the network interconnectedness of both groups. The risk group network showed a higher vulnerability to current stress. Discussion and Implications: Network analysis is a useful approach in the examination of the complex interrelationships between resilience resources and stress-related risk factors in older adulthood

Is the Femoro-Epiphyseal Acetabular Roof (FEAR) index on MRI a relevant predictive factor of instability in a borderline dysplastic hip?

Aims A borderline dysplastic hip can behave as either stable or unstable and this makes surgical decision making challenging. While an unstable hip may be best treated by acetabular reorientation, stable hips can be treated arthroscopically. Several imaging parameters can help to identify the appropriate treatment, including the Femoro-Epiphyseal Acetabular Roof (FEAR) index, measured on plain radiographs. The aim of this study was to assess the reliability and the sensitivity of FEAR index on MRI compared with its radiological measurement. Patients and Methods The technique of measuring the FEAR index on MRI was defined and its reliability validated. A retrospective study assessed three groups of 20 patients: an unstable group of 'borderline dysplastic hips' with lateral centre edge angle (LCEA) less than 25° treated successfully by periacetabular osteotomy; a stable group of 'borderline dysplastic hips' with LCEA less than 25° treated successfully by impingement surgery; and an asymptomatic control group with LCEA between 25° and 35°. The following measurements were performed on both standardized radiographs and on MRI: LCEA, acetabular index, femoral anteversion, and FEAR index. Results The FEAR index showed excellent intraobserver and interobserver reliability on both MRI and radiographs. The FEAR index was more reliable on radiographs than on MRI. The FEAR index on MRI was lower in the stable borderline group (mean -4.2° (sd 9.1°)) compared with the unstable borderline group (mean 7.9° (sd 6.8°)). With a FEAR index cut-off value of 2°, 90% of patients were correctly identified as stable or unstable using the radiological FEAR index, compared with 82.5% using the FEAR index on MRI. The FEAR index was a better predictor of instability on plain radiographs than on MRI. Conclusion The FEAR index measured on MRI is less reliable and less sensitive than the FEAR index measured on radiographs. The cut-off value of 2° for radiological FEAR index predicted hip stability with 90% probability. Cite this article: Bone Joint J 2019;101-B:1578-158