Nf1 mutation disrupts activity-dependent oligodendroglial plasticity and motor learning in mice.

Neurogenetic disorders, such as neurofibromatosis type 1 (NF1), can cause cognitive and motor impairments, traditionally attributed to intrinsic neuronal defects such as disruption of synaptic function. Activity-regulated oligodendroglial plasticity also contributes to cognitive and motor functions by tuning neural circuit dynamics. However, the relevance of oligodendroglial plasticity to neurological dysfunction in NF1 is unclear. Here we explore the contribution of oligodendrocyte progenitor cells (OPCs) to pathological features of the NF1 syndrome in mice. Both male and female littermates (4-24 weeks of age) were used equally in this study. We demonstrate that mice with global or OPC-specific Nf1 heterozygosity exhibit defects in activity-dependent oligodendrogenesis and harbor focal OPC hyperdensities with disrupted homeostatic OPC territorial boundaries. These OPC hyperdensities develop in a cell-intrinsic Nf1 mutation-specific manner due to differential PI3K/AKT activation. OPC-specific Nf1 loss impairs oligodendroglial differentiation and abrogates the normal oligodendroglial response to neuronal activity, leading to impaired motor learning performance. Collectively, these findings show that Nf1 mutation delays oligodendroglial development and disrupts activity-dependent OPC function essential for normal motor learning in mice.

Tumor microenvironmental determinants of high-risk DCIS progression.

Ductal carcinoma in situ (DCIS) constitutes an array of morphologically recognized intraductal neoplasms in the mammary ductal tree defined by an increased risk for subsequent invasive carcinomas at or near the site of biopsy detection. However, only 15-45% of untreated DCIS cases progress to invasive cancer, so understanding mechanisms that prevent progression is key to avoid overtreatment and provides a basis for alternative therapies and prevention. This study was designed to characterize the tumor microenvironment and molecular profile of high-risk DCIS that grew to a large size but remained as DCIS. All patients had DCIS lesions >5cm in size with at least one additional high-risk feature: young age (<45 years), high nuclear grade, hormone receptor negativity, HER2 positivity, the presence of comedonecrosis, or a palpable mass. The tumor immune microenvironment was characterized using multiplex immunofluorescence to identify immune cells and their spatial relationships within the ducts and stroma. Gene copy number analysis and whole exome DNA sequencing identified the mutational burden and driver mutations, and quantitative whole-transcriptome/gene expression analyses were performed. There was no association between the percent of the DCIS genome characterized by copy number variants (CNAs) and recurrence events (DCIS or invasive). Mutations, especially missense mutations, in the breast cancer driver genes PIK3CA and TP53 were common in this high-risk DCIS cohort (47% of evaluated lesions). Tumor infiltrating lymphocyte (TIL) density was higher in DCIS lesions with TP53 mutations (p=0.0079) compared to wildtype lesions, but not in lesions with PIK3CA mutations (p=0.44). Immune infiltrates were negatively associated with hormone receptor status and positively associated with HER2 expression. High levels of CD3+CD8- T cells were associated with good outcomes with respect to any subsequent recurrence (DCIS or invasive cancer), whereas high levels of CD3+Foxp3+ Treg cells were associated with poor outcomes. Spatial proximity analyses of immune cells and tumor cells demonstrated that close proximity of T cells with tumor cells was associated with good outcomes with respect to any recurrence as well as invasive recurrences. Interestingly, we found that myoepithelial continuity (distance between myoepithelial cells surrounding the involved ducts) was significantly lower in DCIS lesions compared to normal tissue (p=0.0002) or to atypical ductal hyperplasia (p=0.011). Gene set enrichment analysis identified several immune pathways associated with low myoepithelial continuity and a low myoepithelial continuity score was associated with better outcomes, suggesting that gaps in the myoepithelial layer may allow access/interactions between immune infiltrates and tumor cells. Our study demonstrates the immune microenvironment of DCIS, in particular the spatial proximity of tumor cells and T cells, and myoepithelial continuity are important determinants for progression of disease.

Temporal variation of mycorrhization rates in a tree diversity experiment.

While mycorrhization rates have been studied in different contexts, not much is known about their temporal patterns across seasons. Here, we asked how mycorrhization rates of 10 deciduous trees assessed by microscopy changed from winter to spring to early summer. We made use of a tree diversity experiment on nutrient-rich soil (former farmland) in Central Germany. In the experiment, saplings of host species with a preference for either arbuscular mycorrhiza (AM) or ectomycorrhiza (EM) were planted in monocultures, two-species, and four-species mixtures. In addition, mixtures were composed of tree species of only one mycorrhizal type or by AM/EM trees. For almost all species, with the exception of Aesculus hippocastanum and Acer pseudoplatanus (only AM), dual mycorrhization with both types (AM and EM) was found at every sampling time (December, March, and May), although the expected preferences for certain mycorrhizal types were confirmed. The sampling date had a significant influence on mycorrhization rates of both EM and AM tree species. Frequencies of EM and AM were lowest in May, but there were no differences between December and March. The causes of this seasonal variation may be associated with climate-induced differences in carbon allocation to mycorrhizal tree roots in the temperate climate. Within individual trees, mycorrhization rates by AM and EM fungi were not correlated over time, pointing to asynchronous variation between both types and to independent drivers for AM and EM mycorrhization. At the community level, mycorrhiza frequency of either of the two types became more asynchronous from two-species to four-species mixtures. Thus, increased community asynchrony in mycorrhization could be another important mechanism in biodiversity-ecosystem functioning relationships.

Gender differences in motor and non-motor symptoms in individuals with mild-moderate Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) affects both men and women with documented gender differences across functional domains, with findings varying among reports. Knowledge regarding gender differences in PD for different geographic locations is important for further understanding of the disease and for developing personalized gender-specific PD assessment tools and therapies. OBJECTIVE: This study aimed to examine gender differences in PD-related motor, motor-cognitive, cognitive, and psychosocial function in people with PD from the southern United States (US). METHODS: 199 (127 men and 72 women; M age: 69.08±8.94) individuals with mild-moderate idiopathic PD (Hoehn &Yahr (H&Y) Median = 2, stages I-III) from a large metro area in the southeastern US were included in this retrospective, cross-sectional study. Motor, motor-cognitive, cognitive, and psychosocial data were obtained using standardized and validated clinical tests. Univariate analyses were performed, adjusting for age and housing type. RESULTS: After adjustment for age, housing, PD duration and fall rate, men exhibited statistically significantly greater motor (Movement Disorders Society (MDS)-Unified Parkinson Disease Rating Scale (UPDRS)-II) and non-motor (MDS-UPDRS-I) impact of PD, and more severe motor signs (MDS-UPDRS-III). Men exhibited worse PD-specific health-related quality of life related to mobility, activities of daily living, emotional well-being, cognitive impairment, communication, and more depressive symptoms. Men performed worse on a subtraction working memory task. Women had slower fast gait speed. CONCLUSIONS: In the southeastern United States, men may experience worse PD-related quality of life and more depression than women. Many non-motor and motor variables that are not PD specific show no differences between genders in this cohort. These findings can contribute to the development of gender-sensitive assessment and rehabilitation policies and protocols for people with PD.

Remote and in-person research education for people with Parkinson's disease and their care partners.

OBJECTIVE: TeleDREAMS, a distance learning version of the Developing a Research Participation Enhancement and Advocacy Training Program for Diverse Seniors (DREAMS) program, provides remote clinical research process and advocacy education to older adults with Parkinson's disease (PD) and their care partners. METHOD: Participants engaged in remote learning, reading eight weekly clinical research process and advocacy education modules. They also had weekly half hour phone discussions with staff about each module. Participants (PD: n = 28, care partner: n = 15) were tested on health literacy, quality of life, depression, research involvement, and advocacy measures. RESULTS: People with PD improved on health literacy postintervention. PD participants who participated with care partners improved more on health literacy than those without care partners. PD participants' attrition rates were lower for PD participants in TeleDREAMS than those of the similar, in-person program DREAMS program studied before TeleDREAMS. Most participants reported research involvement and patient advocacy for older adults with PD 6 to 9 months postprogram. CONCLUSIONS: TeleDREAMS may improve health literacy in participants with Parkinson's and their care partners. If increased advocacy and health and research literacy translates to increased research involvement, then TeleDREAMS could be an important strategy for researchers interested in increasing participation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Relationship between parental history of dementia, motor-cognitive and executive function performance in African American women.

People with parental history (PH) of Alzheimer's Disease (AD) and Alzheimer's Disease and related dementias (ADRD) are themselves at risk of developing dementia. ADRD are more prevalent in African Americans and women. A decline in executive function and motor-cognitive integration can cause an impaired performance of functional skills. The monitoring of cognitive and psychosocial function in individuals with a PH of ADRD is important for implementing interventions to delay or prevent ADRD diagnosis. This study compared 58 African American women (M age = 63.2 ± 7.2 years) with PH of ADRD (n = 34) versus without PH (NPH; n = 24) on the performance of motor-cognitive and executive function tasks, and mental and physical quality of life (QOL) using point biserial correlations and linear regression. Linear regression revealed no difference between participants with and without PH on motor-cognitive tests. However, compared to participants with NPH, participants with PH of ADRD performed significantly worse on the DKEFS (Delis Kaplan Executive Function System) Tower Test (PH: M = 9.9 ± 2.0; NPH: M = 11.5 ± 4.3; p = 0.046), had poorer mental QOL (PH: M = 46.8 ± 10.7; NPH: M = 52.8 ± 7.8 l; p = 0.007); and physical QOL (PH: M = 40.9 ± 9.3; NPH: M = 44.7 ± 8.6; p = 0.023). African American women at risk for ADRD may exhibit deficiencies in executive function and physical and mental quality of life before memory deficits meet the criterion for ADRD diagnosis. Motor-Cognitive tasks may be preserved. Executive function and mental and physical health-related QOL may be important targets for identifying individuals at increased risk for ADRD and developing appropriate rehabilitative interventions.

Mixing tree species associated with arbuscular or ectotrophic mycorrhizae reveals dual mycorrhization and interactive effects on the fungal partners.

Recent studies found that the majority of shrub and tree species are associated with both arbuscular mycorrhizal (AM) and ectomycorrhizal (EM) fungi. However, our knowledge on how different mycorrhizal types interact with each other is still limited. We asked whether the combination of hosts with a preferred association with either AM or EM fungi increases the host tree roots' mycorrhization rate and affects AM and EM fungal richness and community composition.We established a tree diversity experiment, where five tree species of each of the two mycorrhiza types were planted in monocultures, two-species and four-species mixtures. We applied morphological assessment to estimate mycorrhization rates and next-generation molecular sequencing to quantify mycobiont richness.Both the morphological and molecular assessment revealed dual-mycorrhizal colonization in 79% and 100% of the samples, respectively. OTU community composition strongly differed between AM and EM trees. While host tree species richness did not affect mycorrhization rates, we observed significant effects of mixing AM- and EM-associated hosts in AM mycorrhization rate. Glomeromycota richness was larger in monotypic AM tree combinations than in AM-EM mixtures, pointing to a dilution or suppression effect of AM by EM trees. We found a strong match between morphological quantification of AM mycorrhization rate and Glomeromycota richness. Synthesis. We provide evidence that the combination of hosts differing in their preferred mycorrhiza association affects the host's fungal community composition, thus revealing important biotic interactions among trees and their associated fungi.

Microporous Polymer Networks Made by Cyclotrimerization of Commercial, Aromatic Diisocyanates.

The cyclotrimerization of commercial, aromatic diisocyanates allows for the formation of monolithic, microporous polymer networks with SBET surface areas up to 1300-1500 m2/g. The process has been up-scaled for production of 100 g batches. The monolithic materials show a promising potential for the removal of lipophilic components from aqueous mixtures.