Pisgah Astronomical Research Institute

Commotio retinae (CR) resulting from retinal trauma can lead to focal photoreceptor degeneration and permanent vision loss. Currently no therapies exist for CR-induced retinal degeneration, in part because of the lack of a large-animal model that replicates human injury pathology and allows testing of therapeutics. Severe CR is clinically characterized by subretinal fluid and focal photoreceptor outer nuclear layer thinning. To develop a porcine CR model, we developed a laser-guided projectile apparatus and optimized projectile delivery procedure using porcine cadaveric eyes embedded in a 3D-printed porcine skull. Scleral and corneal impacts resulted in retinal damage consistent with patient injury, but corneal impacts also led to cornea damage and opacification, which precluded follow-up imaging. In live porcine eyes, scleral impacts of 39.5 m/s induced transient blood-retinal barrier breakdown evidenced by subretinal fluid on optical coherence tomography (OCT), leakage observed on fluorescein and indocyanine green angiography, and transient photoreceptor outer segment disruption seen by OCT and multifocal electroretinography. Impacts above 39.5 m/s induced longer-lasting photoreceptor degeneration but only transient blood-retinal barrier breakdown. This porcine model, combined with clinically relevant imaging and diagnostic modalities, will be valuable for testing the safety and efficacy of therapies to restore vision after focal photoreceptor degeneration.

Abstract BackgroundAdults with Down Syndrome (DS) are at high risk for Alzheimer's disease (AD), which is characterized by the early accumulation of amyloid‐beta (Aβ), followed by neurofibrillary tangles of tau, and subsequent pathology. There is variability in the age of AD onset in DS, which may mean that non‐genetic factors impact AD timing. Physical activity is associated with less age‐related cognitive declines and lower risk of AD in non‐DS populations. The goal of this study was to examine the association between physical activity and cognitive performance and AD biomarkers (Aβ PET, tau PET, and white matter (WM)) in non‐demented adults with DS.Methods66 adults with DS from the Alzheimer Biomarker Consortium Down Syndrome participated. Participants wore an actigraph accelerometer on their non‐dominant wrist for 7‐days. Cognitive performance was assessed via measures of memory, executive functioning, visuospatial ability, and dementia symptoms. Participants underwent MRI and PET scans to assess the standard uptake value ratio of [11C]PiB (15 mCi) in the neocortex and striatum and [18F]AV‐145 across braak regions I‐VI. WM integrity was assessed using DTI mean diffusivity and fractional anisotrophy in major association tracts.ResultsGreater sedentary activity was associated with more dementia symptoms (r = ‐0.298, p<.05). Higher moderate‐to‐vigorous activity was associated with better memory (r = 0.309, p<.01), executive functioning (r = 0.270, p<.05), visuospatial ability (r = 0.311, p<.05), and fewer dementia symptoms (r = 0.356, p<.01). Models controlled for age and level of intellectual disability. Neither sedentary nor moderate‐to‐vigorous activity were significantly related to PET Aβ or tau PET. However, both were associated with WM integrity in the superior longitudinal fasciculus (r = ‐0.445, p<.05; r = 0.393, p<.05) and sedentary was associated with inferior longitudinal fasciculus tracts (r = ‐0.362, p<.05), after controlling for age and intellectual disability.ConclusionPhysical activity might have a protective effect against age‐related cognitive declines in in DS. However, the reverse time‐order could also be true. Physical activity was not associated with PET Aβ or tau PET cross‐sectionally. In contrast, physical activity was associated with WM integrity, Longitudinal studies are needed to understand mechanisms driving associations, including the cardiovascular impairment

Theory and research on the general population suggest that parents' marital relationship quality is associated with children's emotional and behavioral functioning directly, as well as indirectly, by affecting parenting attitudes and behaviors. However, little has been done to investigate the potential connection among parent marital satisfaction, parenting styles, and outcomes for autistic children. Using longitudinal data collected from 188 couples parenting an autistic child, this study tested the time-ordered indirect effect of parent marital satisfaction (assessed at Time 1) on the internalizing and externalizing symptoms (assessed at Time 3) of autistic children (originally aged 5-12years) via parenting styles (assessed at Time 2) using actor-partner interdependence modeling extended to mediation. Results indicated that a lower level of marital satisfaction at Time 1 predicted impaired child outcomes at Time 3 via its impact on parenting style at Time 2. For both parents, lower marital satisfaction predicted more child externalizing symptoms via reports of more authoritarian parenting style. Lower marital satisfaction in mothers at Time 1 was also associated with higher levels of child internalizing symptoms at Time 3 via increased authoritarian parenting in mothers. No partner effects were found. A family-wide approach that includes support for the parent marital relationship, which may have downstream effects on parenting, is important for promoting optimal emotional and behavioral health in autistic children.

Parents of adults with serious mental illness (SMI) often are primary caregivers for their affected relative. Prior work has suggested that the toll of caregiving is associated with poorer well-being in family caregivers, particularly parents of affected adults. However, due to methodological limitations, it has not been possible to assess these family caregivers' own genetic vulnerability to mental and physical health problems, and thus the impact of caregivers' genetic risk on well-being may not have been accounted for. With the addition of genetic data to large survey samples, family caregivers' genetic vulnerability to mental and physical health problems can now be estimated. Parents from the Wisconsin Longitudinal Study who have an adult child with an SMI (n = 265) and a comparison group of parents with a child without disabilities (n = 5,036) reported their psychological well-being and mental and physical health across 4 measures. Genetic vulnerability was assessed using polygenic risk scores of neuroticism, bipolar disorder, schizophrenia, and depression. Results indicate that the effect of having a child with an SMI still had significant effects for all 4 parental health outcomes even after controlling for these measures of genetic vulnerability. This study's results affirm the negative health impact of parenting a child with SMI, above and beyond genetic vulnerability. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The original version of this Article contained an error in the spelling of the author Laurence Faivre, which was incorrectly given as Laurence Faive. This has now been corrected in both the PDF and HTML versions of the Article.

The Angrite meteorite group is comprised of a diverse set of ancient and enigmatic achondrites. Members of the group have been dated to 4563.36 0.34 Ga [1], making them almost as old as the solar system itself. Angrites fall into two distinct groups easily distinguished by textures indicating cooling regimes from shallow dike and lava flow emplacement (referred to hereafter as volcanic angrites) to deep seated plutonism (referred to hereafter as plutonic angrites) Angrite ages and textures indicate they were formed on a planetary sized body when many short lived isotopes were still present (i.e. 26 Al) and therefore provide important clues to the earliest stages of planetary melting and differentiation. Consequently, candidates for the Angrite parent body (APB) range from Mercury to large asteroids disrupted early in solar system history

There is a great need for valid outcome measures of functional improvement for impending clinical trials of targeted interventions for fragile X syndrome (FXS). Families often report conversational language improvement during clinical treatment, but no validated measures exist to quantify this outcome. This small-scale study sought to determine the feasibility, reproducibility, and clinical validity of highly structured expressive language sampling as an outcome measure reflecting language ability. Narrative and conversation tasks were administered to 36 verbal participants (25 males and 11 females) with FXS (aged 5-36 years, mean, 18 ± 7 years). Alternate versions were used with randomized task order at 2- to 3-week intervals (mean, 19.6 ± 6.4 days). Audio recordings of sessions were transcribed and analyzed. Dependent measures reflected talkativeness (total number of utterances), utterance planning (proportion of communication [C] units with mazes), articulation (proportion of unintelligible/partly unintelligible C-units), vocabulary (number of different word roots), and syntactic ability (mean length of utterance [MLU] in words). Reproducibility of measures was evaluated with intraclass correlation coefficients (ICC). All participants could complete the tasks. Coded data were highly reproducible with Pearson's correlations at p < .01 for all measures and ICC values of .911 to .966 (conversation) and .728 to .940 (narration). Some measures including MLU and different word roots were correlated with expressive language subscale scores from the Vineland Adaptive Behavior Scale. These expressive language sampling tasks appear to be feasible, reproducible, and clinically valid and should be further validated in a larger cohort, as a promising means of assessing functional expressive language outcomes during clinical trials in FXS.

Glial fibrillary acidic protein (GFAP) is the major intermediate filament protein of astrocytes in the vertebrate central nervous system. Increased levels of GFAP are the hallmark feature of gliosis, a non-specific response of astrocytes to a wide variety of injuries and disorders of the CNS, and also occur in Alexander disease where the initial insult is a mutation within the coding region of GFAP itself. In both settings, excess GFAP may cause or exacerbate astrocyte dysfunction. With the goal of finding drugs that reduce the expression of GFAP, we have devised screens to detect changes in GFAP promoter activity or protein levels in primary cultures of mouse astrocytes in a 96-well format. We have applied these screens to libraries enriched in compounds that are already approved for human use by the FDA. We report that several compounds are active at micromolar levels in suppressing the expression of GFAP. Treatment of mice for 3 weeks with one of these drugs, clomipramine, causes nearly 50% reduction in the levels of GFAP protein in brain.

For the promise of human induced pluripotent stem cells (iPSCs) to be realized, it is necessary to ask if and how efficiently they may be differentiated to functional cells of various lineages. Here, we have directly compared the neural-differentiation capacity of human iPSCs and embryonic stem cells (ESCs). We have shown that human iPSCs use the same transcriptional network to generate neuroepithelia and functionally appropriate neuronal types over the same developmental time course as hESCs in response to the same set of morphogens; however, they do it with significantly reduced efficiency and increased variability. These results were consistent across iPSC lines and independent of the set of reprogramming transgenes used to derive iPSCs as well as the presence or absence of reprogramming transgenes in iPSCs. These findings, which show a need for improving differentiation potency of iPSCs, suggest the possibility of employing human iPSCs in pathological studies, therapeutic screening, and autologous cell transplantation.

Oxidative stress has been implicated in the etiology of Parkinson's disease (PD) and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of PD. It is known that under conditions of oxidative stress, the transcription factor NF-E2-related factor (Nrf2) binds to antioxidant response element (ARE) to induce antioxidant and phase II detoxification enzymes. To investigate the role of Nrf2 in the process of MPTP-induced toxicity, mice expressing the human placental alkaline phosphatase (hPAP) gene driven by a promoter containing a core ARE sequence (ARE-hPAP) were used. ARE-hPAP mice were injected (30 mg/kg) once per day for 5 days and killed 7 days after the last MPTP injection. In response to this design, ARE-dependent gene expression was decreased in striatum whereas it was increased in substantia nigra. The same MPTP protocol was applied in Nrf2(+/+) and Nrf2(-/-) mice; Nrf2 deficiency increases MPTP sensitivity. Furthermore, we evaluated the potential for astrocytic Nrf2 overexpression to protect from MPTP toxicity. Transgenic mice with Nrf2 under control of the astrocyte-specific promoter for the glial fribillary acidic protein (GFAP-Nrf2) on both a Nrf2(+/+) and Nrf2(-/-) background were administered MPTP. In the latter case, only the astrocytes expressed Nrf2. Independent of background, MPTP-mediated toxicity was abolished in GFAP-Nrf2 mice. These striking results indicate that Nrf2 expression restricted to astrocytes is sufficient to protect against MPTP and astrocytic modulation of the Nrf2-ARE pathway is a promising target for therapeutics aimed at reducing or preventing neuronal death in PD.