Characterization of microtubule-associated protein tau isoforms and Alzheimer’s disease-like pathology in normal sheep (Ovis aries):Relevance to their potential as a model of Alzheimer’s disease

Alzheimer’s disease is a chronic neurodegenerative disease that accounts for up to 80% of all dementias. Characterised by deteriorations of memory and cognitive function, the key neuropathological features are accumulations of β-amyloid and hyperphosphorylated tau, as ‘plaques’ and ‘tangles’, respectively. Despite extensive study, however, the exact mechanism underlying aggregate formation in Alzheimer’s disease remains elusive, as does the contribution of these aggregates to disease progression. Importantly, a recent evaluation of current Alzheimer’s disease animal models suggested that rodent models are not able to fully recapitulate the pathological intricacies of the disease as it occurs in humans. Therefore, increasing attention is being paid to species that might make good alternatives to rodents for studying the molecular pathology of Alzheimer’s disease. The sheep (Ovis aries) is one such species, although to date, there have been few molecular studies relating to Alzheimer’s disease in sheep. Here, we investigated the Alzheimer’s disease relevant histopathological characteristics of 22 sheep, using anti-β-amyloid (Abcam 12267 and mOC64) and phosphorylation specific anti-tau (AT8 and S396) antibodies. We identified numerous intraneuronal aggregates of both β-amyloid and tau that are consistent with early Alzheimer’s disease-like pathology. We confirmed the expression of two 3-repeat (1N3R, 2N3R) and two 4-repeat (1N4R, 2N4R) tau isoforms in the ovine brain, which result from the alternative splicing of two tau exons. Finally, we investigated the phosphorylation status of the serine396 residue in 30 sheep, and report that the phosphorylation of this residue begins in sheep aged as young as 2 years. Together, these data show that sheep exhibit naturally occurring β-amyloid and tau pathologies, that reflect those that occur in the early stages of Alzheimer’s disease. This is an important step towards the validation of the sheep as a feasible large animal species in which to model Alzheimer’s disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-022-04572-z

Manipulations of List Type in the DRM Paradigm: A Review of How Structural and Conceptual Similarity Affect False Memory

The use of list-learning paradigms to explore false memory has revealed several critical findings about the contributions of similarity and relatedness in memory phenomena more broadly. Characterizing the nature of “similarity and relatedness” can inform researchers about factors contributing to memory distortions and about the underlying associative and semantic networks that support veridical memory. Similarity can be defined in terms of semantic properties (e.g., shared conceptual and taxonomic features), lexical/associative properties (e.g., shared connections in associative networks), or structural properties (e.g., shared orthographic or phonological features). By manipulating the type of list and its relationship to a non-studied critical item, we review the effects of these types of similarity on veridical and false memory. All forms of similarity reviewed here result in reliable error rates and the effects on veridical memory are variable. The results across a variety of paradigms and tests provide partial support for a number of theoretical explanations of false memory phenomena, but none of the theories readily account for all results

Reducing in-stent restenosis therapeutic manipulation of miRNA in vascular remodeling and inflammation

Background: Drug-eluting stents reduce the incidence of in-stent restenosis, but they result in delayed arterial healing and are associated with a chronic inflammatory response and hypersensitivity reactions. Identifying novel interventions to enhance wound healing and reduce the inflammatory response may improve long-term clinical outcomes. Micro–ribonucleic acids (miRNAs) are noncoding small ribonucleic acids that play a prominent role in the initiation and resolution of inflammation after vascular injury.<p></p> Objectives: This study sought to identify miRNA regulation and function after implantation of bare-metal and drug-eluting stents.<p></p> Methods: Pig, mouse, and in vitro models were used to investigate the role of miRNA in in-stent restenosis.<p></p> Results: We documented a subset of inflammatory miRNAs activated after stenting in pigs, including the miR-21 stem loop miRNAs. Genetic ablation of the miR-21 stem loop attenuated neointimal formation in mice post-stenting. This occurred via enhanced levels of anti-inflammatory M2 macrophages coupled with an impaired sensitivity of smooth muscle cells to respond to vascular activation.<p></p> Conclusions: MiR-21 plays a prominent role in promoting vascular inflammation and remodeling after stent injury. MiRNA-mediated modulation of the inflammatory response post-stenting may have therapeutic potential to accelerate wound healing and enhance the clinical efficacy of stenting

Development and testing of a practicum matching program for baccalaureate nursing education, a local public health unit

This article describes a novel approach to nursing education, designed to improve the experience of both students in public health nursing, and the local public health unit where they affiliate. Students, faculty, and public health department staff developed a method for matching programs and needs of the local public health unit to the skills and learning needs of nursing students. We describe our experience articulating student competencies, program‐specific functions, and an approach to matching student interests and learning opportunities to agency needs. Students, faculty, and staff rated the program moderately to very high in feasibility, satisfaction, and acceptability. Data suggest the novel program served to improve the quality of the practicum affiliation, to the satisfaction of both the school and agency, while contributing to a robust public health learning experience for emerging professional nurses.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162738/2/phn12767.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162738/1/phn12767_am.pd

Self-efficacy for managing pain, symptoms, and function in patients with lung cancer and their informal caregivers: Associations with symptoms and distress

This study examined self-efficacy for managing pain, symptoms, and function in patients with lung cancer and their caregivers, and associations between self-efficacy and patient and caregiver adjustment. 152 patients with early stage lung cancer completed measures of self-efficacy, pain, fatigue, quality of life, depression, and anxiety. Their caregivers completed a measure assessing their self-efficacy for helping the patient manage symptoms and measures of psychological distress and caregiver strain. Analyses indicated that, overall, patients and caregivers were relatively low in self-efficacy for managing pain, symptoms, and function, and that there were significant associations between self-efficacy and adjustment. Patients low in self-efficacy reported significantly higher levels of pain, fatigue, lung cancer symptoms, depression, and anxiety, and significantly worse physical and functional well being, as did patients whose caregivers were low in self-efficacy. When patients and caregivers both had low self-efficacy, patients reported higher levels of anxiety and poorer quality of life than when both were high in self-efficacy. There were also significant associations between patient and caregiver self-efficacy and caregiver adjustment, with lower levels of self-efficacy associated with higher levels of caregiver strain and psychological distress. These preliminary findings raise the possibility that patient and caregiver self-efficacy for managing pain, symptoms, and function may be important factors affecting adjustment, and that interventions targeted at increasing self-efficacy may be useful in this population

Galaxy morphology and star formation in the Illustris Simulation at

We study how optical galaxy morphology depends on mass and star formation rate (SFR) in the Illustris Simulation. To do so, we measure automated galaxy structures in 10 808 simulated galaxies at z = 0 with stellar masses 10[superscript 9.7] < M*/Mȯ < 10[superscript12.3]. We add observational realism to idealized synthetic images and measure non-parametric statistics in rest-frame optical and near-IR images from four directions. We find that Illustris creates a morphologically diverse galaxy population, occupying the observed bulge strength locus and reproducing median morphology trends versus stellar mass, SFR, and compactness. Morphology correlates realistically with rotation, following classification schemes put forth by kinematic surveys. Type fractions as a function of environment agree roughly with data. These results imply that connections among mass, star formation, and galaxy structure arise naturally from models matching global star formation and halo occupation functions when simulated with accurate methods. This raises a question of how to construct experiments on galaxy surveys to better distinguish between models. We predict that at fixed halo mass near 10[superscript 12] Mȯ, disc-dominated galaxies have higher stellar mass than bulge-dominated ones, a possible consequence of the Illustris feedback model. While Illustris galaxies at M* ∼ 10[superscript 11] Mȯ have a reasonable size distribution, those at M* ∼ 10[superscript 10] Mȯ have half-light radii larger than observed by a factor of 2. Furthermore, at M* ∼ 10[superscript 10.5]–10[superscript 11] Mȯ, a relevant fraction of Illustris galaxies have distinct ‘ring-like’ features, such that the bright pixels have an unusually wide spatial extent

Greater aortic inflammation and calcification in abdominal aortic aneurysmal disease than atherosclerosis: a prospective matched cohort study

Funder: British Heart Foundation; FundRef: http://dx.doi.org/10.13039/501100000274Objective: Using combined positron emission tomography and CT (PET-CT), we measured aortic inflammation and calcification in patients with abdominal aortic aneurysms (AAA), and compared them with matched controls with atherosclerosis. Methods: We prospectively recruited 63 patients (mean age 76.1±6.8 years) with asymptomatic aneurysm disease (mean size 4.33±0.73 cm) and 19 age-and-sex-matched patients with confirmed atherosclerosis but no aneurysm. Inflammation and calcification were assessed using combined 18F-FDG PET-CT and quantified using tissue-to-background ratios (TBRs) and Agatston scores. Results: In patients with AAA, 18F-FDG uptake was higher within the aneurysm than in other regions of the aorta (mean TBRmax2.23±0.46 vs 2.12±0.46, p=0.02). Compared with atherosclerotic control subjects, both aneurysmal and non-aneurysmal aortae showed higher 18F-FDG accumulation (total aorta mean TBRmax2.16±0.51 vs 1.70±0.22, p=0.001; AAA mean TBRmax2.23±0.45 vs 1.68±0.21, p<0.0001). Aneurysms containing intraluminal thrombus demonstrated lower 18F-FDG uptake within their walls than those without (mean TBRmax2.14±0.43 vs 2.43±0.45, p=0.018), with thrombus itself showing low tracer uptake (mean TBRmax thrombus 1.30±0.48 vs aneurysm wall 2.23±0.46, p<0.0001). Calcification in the aneurysmal segment was higher than both non-aneurysmal segments in patients with aneurysm (Agatston 4918 (2901–8008) vs 1017 (139–2226), p<0.0001) and equivalent regions in control patients (442 (304-920) vs 166 (80-374) Agatston units per cm, p=0.0042). Conclusions: The entire aorta is more inflamed in patients with aneurysm than in those with atherosclerosis, perhaps suggesting a generalised inflammatory aortopathy in patients with aneurysm. Calcification was prominent within the aneurysmal sac, with the remainder of the aorta being relatively spared. The presence of intraluminal thrombus, itself metabolically relatively inert, was associated with lower levels of inflammation in the adjacent aneurysmal wall

Caregiver-Assisted Coping Skills Training for Lung Cancer: Results of a Randomized Clinical Trial

Lung cancer is one of the most common cancers in the U.S. and is associated with high levels of symptoms including pain, fatigue, shortness of breath, and psychological distress. Caregivers as well as patients are adversely affected. However, previous studies of coping skills training (CST) interventions have not been tested in patients with lung cancer nor systematically included caregivers

Brief Report: Sensorimotor Gating in Idiopathic Autism and Autism Associated with Fragile X Syndrome

Prepulse inhibition (PPI) may useful for exploring the proposed shared neurobiology between idiopathic autism and autism caused by FXS. We compared PPI in four groups: typically developing controls (n = 18), FXS and autism (FXS+A; n = 15), FXS without autism spectrum disorder (FXS−A; n = 17), and idiopathic autism (IA; n = 15). Relative to controls, the FXS+A (p < 0.002) and FXS−A (p < 0.003) groups had impaired PPI. The FXS+A (p < 0.01) and FXS−A (p < 0.03) groups had lower PPI than the IA group. Prolonged startle latency was seen in the IA group. The differing PPI profiles seen in the FXS+A and IA indicates these groups may not share a common neurobiological abnormality of sensorimotor gating

The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III

The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Ly alpha forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap, bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameters pipeline, which has better determination of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from submitted version