Novel leaf morphology and variation in foliage similar to Rhacopteris from the Early Carboniferous Price Formation, southwestern Virginia, USA

The plant fossil foliage genus Rhacopteris existed approximately 350 million years ago in the Lower Carboniferous and conforms to seed fern organization and affinity. A collection of foliage similar to Rhacopteris has been found in one of several outcrops of the Price Formation near Pulaski, Virginia, North Carolina, USA. While superficially resembling previously described Rhacopteris species, about 30 individuals of the collection (labeled PGR) exhibit a distinctive bilobed leaflet morphology that is unlike those described for any existing Rhacopteris species. This project aims to determine whether the specimens of the PGR collection represent a single taxon or more than one related taxa, and if they are most appropriately assigned to the genus Rhacopteris as an existing or new species? In order to determine the affinity of these specimens, quantitative and qualitative morphological measurements of both published Rhacopteris specimens and the PGR specimens exhibiting the distinct bilobed leaflet morphology from the Price Formation were obtained and analyzed. Methods include dégagement (a process of uncovering any leaf parts obscured by the rock matrix), measuring leaflet length, leaflet perimeter, leaflet surface area, rachis internode length, and depth of lobing with ImageJ, leaf transverse sectioning, and illustrating specimens and simulating taphonomic distortion with Adobe Illustrator. The distinct bilobed leaflet shape and venation pattern of the PGR specimens were found to be notably distinct from all previously described species of Rhacopteris, thus supporting that the collection under study represents a single new species. This work will contribute to a better understanding and classification of the floral composition of a region considered to have a wet-dry climate, and to our overall knowledge regarding the plant distribution of early seed plants in the Lower Carboniferous.Bachelor of Art

Implementation of a Novel Social-Emotional Learning Program to Advance Integration of Wellness in Education Practice

Social-emotional learning (SEL) programs aim to enhance emotional intelligence by teaching problem solving, self-awareness, self-management, social awareness, and relationship building skills. SEL interventions have been shown to improve quality of life and wellbeing, increasingly important outcomes in the wake of the staggering effects of the COVID-19 crisis on mental health. HappiGenius is a novel SEL program with the addition of mindful attention and self-compassion. We hypothesized HappiGenius would improve positive emotions, self-compassion, attention, mindful self-awareness, and social skills in a group of students. This observational cohort study took place at a diverse elementary school in a midsize midwestern city and included 48 students across four 3rd grade classrooms. HappiGenius included 12 lessons, approximately 45 minutes each, delivered twice a week for 6 weeks. The results demonstrated increased frequency of positive emotions (Positive Affect Scale for Children, median increase from 3.57 to 4.04, p=0.04) and improved self-compassion (Self-Compassion Scale for Children, 3.04 to 3.25, p=0.0094). Changes in student reported mindful self-awareness (Mindful Attentive Awareness Scale for Children, 3.27 to 3.47, p=0.56) and teacher ratings of hyperactivity/ inattention (Strengths and Difficulties Questionnaire, 3.0 to 2.5, p=0.26) were not statistically significant. Strong positive changes were observed in other teacher-reported behavioral outcomes on the Strengths and Difficulties Questionnaire, including total difficulties (6.0 to 3.5, p=0.0004) and prosocial skills (9.0 to 10.0,

Physiology-based simulation of the retinal vasculature enables annotation-free segmentation of OCT angiographs

Optical coherence tomography angiography (OCTA) can non-invasively image the eye's circulatory system. In order to reliably characterize the retinal vasculature, there is a need to automatically extract quantitative metrics from these images. The calculation of such biomarkers requires a precise semantic segmentation of the blood vessels. However, deep-learning-based methods for segmentation mostly rely on supervised training with voxel-level annotations, which are costly to obtain. In this work, we present a pipeline to synthesize large amounts of realistic OCTA images with intrinsically matching ground truth labels; thereby obviating the need for manual annotation of training data. Our proposed method is based on two novel components: 1) a physiology-based simulation that models the various retinal vascular plexuses and 2) a suite of physics-based image augmentations that emulate the OCTA image acquisition process including typical artifacts. In extensive benchmarking experiments, we demonstrate the utility of our synthetic data by successfully training retinal vessel segmentation algorithms. Encouraged by our method's competitive quantitative and superior qualitative performance, we believe that it constitutes a versatile tool to advance the quantitative analysis of OCTA images.Comment: Accepted at MICCAI 202

Retinal inner nuclear layer volume reflects inflammatory disease activity in multiple sclerosis: a longitudinal OCT study

Inner nuclear layer; Multiple sclerosis; Optical coherence tomographyCapa nuclear interna; Esclerosis múltiple; Tomografía de coherencia ópticaCapa nuclear interior; Esclerosi múltiple; Tomografia de coherència òpticaBackground: The association of peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness with neurodegeneration in multiple sclerosis (MS) is well established. The relationship of the adjoining inner nuclear layer (INL) with inflammatory disease activity is less well understood. Objective: The objective of this paper is to investigate the relationship of INL volume changes with inflammatory disease activity in MS. Methods In this longitudinal, multi-centre study, optical coherence tomography (OCT) and clinical data (disability status, relapses and MS optic neuritis (MSON)) were collected in 785 patients with MS (68.3% female) and 92 healthy controls (63.4% female) from 11 MS centres between 2010 and 2017 and pooled retrospectively. Data on pRNFL, GCIPL and INL were obtained at each centre. Results: There was a significant increase in INL volume in eyes with new MSON during the study (N=61/1562, β=0.01mm3, p<.001). Clinical relapses (other than MSON) were significantly associated with increased INL volume (β=0.005, p=.025). INL volume was independent of disease progression (β=0.002mm3, p=.474). Conclusion: Our data demonstrate that an increase in INL volume is associated with MSON and the occurrence of clinical relapses. Therefore, INL volume changes may be useful as an outcome marker for inflammatory disease activity in MSON and MS treatment trials

Optical coherence tomography angiography indicates subclinical retinal disease in neuromyelitis optica spectrum disorders

Background: Neuromyelitis optica spectrum disorders (NMOSD) are neuroinflammatory diseases of the central nervous system. Patients suffer from recurring relapses and it is unclear whether relapse-independent disease activity occurs and whether this is of clinical relevance. Objective: To detect disease-specific alterations of the retinal vasculature that reflect disease activity during NMOSD. Methods: Cross-sectional analysis of 16 patients with NMOSD, 21 patients with relapsing-remitting multiple sclerosis, and 21 healthy controls using retinal optical coherence tomography (OCT), optical coherence tomography angiography (OCT-A), measurement of glial fibrillary acidic protein (GFAP) serum levels, and assessment of visual acuity. Results: Patients with NMOSD but not multiple sclerosis revealed lower foveal thickness (FT) (p = 0.02) measures and an increase of the foveal avascular zone (FAZ) (p = 0.02) compared to healthy controls independent to optic neuritis. Reduced FT (p = 0.01), enlarged FAZ areas (p = 0.0001), and vessel loss of the superficial vascular complex (p = 0.01) were linked to higher serum GFAP levels and superficial vessel loss was associated with worse visual performance in patients with NMOSD irrespective of optic neuritis. Conclusion: Subclinical parafoveal retinal vessel loss might occur during NMOSD and might be linked to astrocyte damage and poor visual performance. OCT-A may be a tool to study subclinical disease activity during NMOSD

Formation and immunomodulatory function of meningeal B cell aggregates in progressive CNS autoimmunity

Meningeal B lymphocyte aggregates have been described in autopsy material of patients with chronic multiple sclerosis. The presence of meningeal B cell aggregates has been correlated with worse disease. However, the functional role of these meningeal B cell aggregates is not understood. Here, we use a mouse model of multiple sclerosis, the spontaneous opticospinal encephalomyelitis model, which is built on the double transgenic expression of myelin oligodendrocyte glycoprotein-specific T-cell and B-cell receptors, to show that the formation of meningeal B cell aggregates is dependent on the expression of alpha 4 integrins by antigen-specific T cells. T cell-conditional genetic ablation of alpha 4 integrins in opticospinal encephalomyelitis mice impaired the formation of meningeal B cell aggregates, and surprisingly, led to a higher disease incidence as compared to opticospinal encephalomyelitis mice with alpha 4 integrin-sufficient T cells. B cell-conditional ablation of alpha 4 integrins in opticospinal encephalomyelitis mice resulted in the entire abrogation of the formation of meningeal B cell aggregates, and opticospinal encephalomyelitis mice with alpha 4 integrin-deficient B cells suffered from a higher disease burden than regular opticospinal encephalomyelitis mice. While anti-CD20 antibody-mediated systemic depletion of B cells in opticospinal encephalomyelitis mice after onset of disease failed to efficiently decrease meningeal B cell aggregates without significantly modulating disease progression, treatment with anti-CD19 chimeric antigen receptor-T cells eliminated meningeal B cell aggregates and exacerbated clinical disease in opticospinal encephalomyelitis mice. Since about 20% of B cells in organized meningeal B cell aggregates produced either IL-10 or IL-35, we propose that meningeal B cell aggregates might also have an immunoregulatory function as to the immunopathology in adjacent spinal cord white matter. The immunoregulatory function of meningeal B cell aggregates needs to be considered when designing highly efficient therapies directed against meningeal B cell aggregates for clinical application in multiple sclerosis

Microstructural visual system changes in AQP4-antibody-seropositive NMOSD

OBJECTIVE: To trace microstructural changes in patients with aquaporin-4 antibody (AQP4-ab)-seropositive neuromyelitis optica spectrum disorders (NMOSDs) by investigating the afferent visual system in patients without clinically overt visual symptoms or visual pathway lesions. METHODS: Of 51 screened patients with NMOSD from a longitudinal observational cohort study, we compared 6 AQP4-ab-seropositive NMOSD patients with longitudinally extensive transverse myelitis (LETM) but no history of optic neuritis (ON) or other bout (NMOSD-LETM) to 19 AQP4-ab-seropositive NMOSD patients with previous ON (NMOSD-ON) and 26 healthy controls (HCs). Foveal thickness (FT), peripapillary retinal nerve fiber layer (pRNFL) thickness, and ganglion cell and inner plexiform layer (GCIPL) thickness were measured with optical coherence tomography (OCT). Microstructural changes in the optic radiation (OR) were investigated using diffusion tensor imaging (DTI). Visual function was determined by high-contrast visual acuity (VA). OCT results were confirmed in a second independent cohort. RESULTS: FT was reduced in both patients with NMOSD-LETM (p = 3.52e(-14)) and NMOSD-ON (p = 1.24e(-16)) in comparison with HC. Probabilistic tractography showed fractional anisotropy reduction in the OR in patients with NMOSD-LETM (p = 0.046) and NMOSD-ON (p = 1.50e(-5)) compared with HC. Only patients with NMOSD-ON but not NMOSD-LETM showed neuroaxonal damage in the form of pRNFL and GCIPL thinning. VA was normal in patients with NMOSD-LETM and was not associated with OCT or DTI parameters. CONCLUSIONS: Patients with AQP4-ab-seropositive NMOSD without a history of ON have microstructural changes in the afferent visual system. The localization of retinal changes around the Mueller-cell rich fovea supports a retinal astrocytopathy

Fatigue in multiple sclerosis: Associations with clinical, MRI and CSF parameters

Background: Damage of different brain structures has been related to fatigue. Alternatively, functional alterations of central nervous system (CNS) cells by the inflammatory milieu within the CNS may be responsible for the development of fatigue. Aim: To investigate the effect of structural brain damage and inflammatory cerebrospinal fluid (CSF) changes on fatigue in multiple sclerosis (MS). Methods: We determined the association of different clinical, CSF and magnetic resonance imaging (MRI) parameters with prevalence and severity of fatigue, as measured by the Fatigue Scale for Motor and Cognitive Functions in 68 early MS patients (discovery cohort). We validated our findings in two MS cohorts: the MRI validation cohort (N=233) for the clinical and MRI parameters, and the CSF validation cohort (N=81) for the clinical and CSF parameters. Results: Fatigue was associated with clinical disability. Fatigue did not correlate with any CSF parameter but correlated negatively with total and cortical grey matter volume. However, when controlling for Expanded Disability Status Scale (EDSS) in a multivariate model, these associations lost significance. Conclusion: Disability and disease duration best explain fatigue severity but none of the tested MRI or CSF parameter was reliably associated with fatigue

A computational study of the influence of methyl substituents on competitive ring closure to α- and β-lactones

Ring-closure of substituted 2-chlorosuccinates to α- or β-lactones has been studied by means of MP2/6-311+G(d,p)//MP2/6-31+G(d) calculations in water treated as a polarised continuum (PCM) and in vacuum. Optimised geometries have been obtained for 2-chlorosuccinate and its 2-methyl, 3,3-dimethyl, and 2,3,3-trimethyl derivatives, along with the transition structures and products for intramolecular nucleophilic displacement leading to the 3- or 4-membered rings. Relative enthalpies and Gibbs free energies of activation and reaction are presented, along with key geometrical parameters, and changes in electrostatic-potential-derived atomic charges. The difference in free-energy barriers for α- and β-lactone formation from the 2-methyl substrate at 298 K is less than 1 kJ mol−1. Primary 14C kinetic isotope effects calculated for substitution at C2 are significantly smaller for α-lactone formation than for β, suggesting a possible way to distinguish between the competing pathways of reaction. The B3LYP method without dispersion corrections predicts the wrong relative stability order for methyl-substituted succinate dianions in PCM water