Alzheimer's Disease Protein Relevance Analysis Using Human and Mouse Model Proteomics Data.

The principles governing genotype-phenotype relationships are still emerging(1-3), and detailed translational as well as transcriptomic information is required to understand complex phenotypes, such as the pathogenesis of Alzheimer's disease. For this reason, the proteomics of Alzheimer disease (AD) continues to be studied extensively. Although comparisons between data obtained from humans and mouse models have been reported, approaches that specifically address the between-species statistical comparisons are understudied.

Corrigendum: Absolute winding number differentiates mouse spatial navigation strategies with genetic risk for Alzheimer's disease.

[This corrects the article DOI: 10.3389/fnins.2022.

Infection and inflammation: New perspectives on Alzheimer's disease.

Neuroinflammation has been recognized as a component of Alzheimer's Disease (AD) pathology since the original descriptions by Alois Alzheimer and a role for infections in AD pathogenesis has long been hypothesized. More recently, this hypothesis has gained strength as human genetics and experimental data suggest key roles for inflammatory cells in AD pathogenesis. To review this topic, Duke/University of North Carolina (Duke/UNC) Alzheimer's Disease Research Center hosted a virtual symposium: "Infection and Inflammation: New Perspectives on Alzheimer's Disease (AD).

Behavioral "bycatch" from camera trap surveys yields insights on prey responses to human-mediated predation risk.

Human disturbance directly affects animal populations and communities, but indirect effects of disturbance on species behaviors are less well understood. For instance, disturbance may alter predator activity and cause knock-on effects to predator-sensitive foraging in prey. Camera traps provide an emerging opportunity to investigate such disturbance-mediated impacts to animal behaviors across multiple scales.

Absolute Winding Number Differentiates Mouse Spatial Navigation Strategies With Genetic Risk for Alzheimer's Disease.

Spatial navigation and orientation are emerging as promising markers for altered cognition in prodromal Alzheimer's disease, and even in cognitively normal individuals at risk for Alzheimer's disease. The different APOE gene alleles confer various degrees of risk. The APOE2 allele is considered protective, APOE3 is seen as control, while APOE4 carriage is the major known genetic risk for Alzheimer's disease.

Mouse Pluripotent Stem Cell Differentiation Under Physiological Oxygen Reduces Residual Teratomas.

Introduction: Residual pluripotent stem cells (PSC) within differentiated populations are problematic because of their potential to form tumors. Simple methods to reduce their occurrence are needed.

Methods: Here, we demonstrate that control of the oxygen partial pressure (pO) to physiological levels typical of the developing embryo, enabled by culture on a highly oxygen permeable substrate, reduces the fraction of PSC within and the tumorigenic potential of differentiated populations.

Metabolism-Based Gene Differences in Neurons Expressing Hyperphosphorylated AT8- Positive (AT8+) Tau in Alzheimer's Disease.

Metabolic adaptations in the brain are critical to the establishment and maintenance of normal cellular functions and to the pathological responses to disease processes. Here, we have focused on specific metabolic pathways that are involved in immune-mediated neuronal processes in brain using isolated neurons derived from human autopsy brain sections of normal individuals and individuals diagnosed as Alzheimer's disease (AD). Laser capture microscopy was used to select specific cell types in immune-stained thin brain sections followed by NanoString technology to identify and quantify differences in mRNA levels between age-matched control and AD neuronal samples.

Capillary Electrophoresis-High Resolution Mass Spectrometry for Measuring In Vivo Arginine Isotope Incorporation in Alzheimer's Disease Mouse Models.

Immune-based metabolic reprogramming of arginine utilization in the brain contributes to the neuronal pathology associated with Alzheimer's disease (AD). To enable our long-term goals of differentiation of AD mouse model genotypes, ages, and sexes based on activity of this pathway, we describe here the novel dosing (using uniformly labeled (CN) arginine) and analysis methods using capillary electrophoresis high-resolution accurate-mass mass spectrometry for isotope tracing of metabolic products of arginine. We developed a pseudoprimed infusion-dosing regimen, using repeated injections, to achieve a steady state of uniformly labeled arginine in 135-195 min post bolus dose.

Interpreting moderated multiple regression: A comment on Van Iddekinge, Aguinis, Mackey, and DeOrtentiis (2018).

When data contradict theory, data usually win. Yet, the conclusion of Van Iddekinge, Aguinis, Mackey, and DeOrtentiis (2018) that performance is an additive rather than multiplicative function of ability and motivation may not be valid, despite applying a meta-analytic lens to the issue. We argue that the conclusion was likely reached because of a common error in the interpretation of moderated multiple-regression results.

Miller Edwin Preston (1879-1928); pioneer of fracture biomechanics-a biographical vignette.

Miller Edwin Preston (1879-1928) is cited in the literature in connection with the first angled implant for the fixation of fractures of the femoral neck. Further research has shown that this surgeon emphasised the principles of internal fixation and is the author of several extraordinary and still-valid concepts: "There is no branch of surgery in which nature is more exacting than bone work. To be successful in this field, the cases must be carefully selected, the most rigid asepsis should be observed, the surgeon must possess a good working knowledge of anatomy and fully appreciate the laws of stress, strain and leverage.

CVN-AD Alzheimer's mice show premature reduction in neurovascular coupling in response to spreading depression and anoxia compared to aged controls.

We compared the efficacy of neurovascular coupling and substrate supply in cerebral cortex during severe metabolic challenges in transgenic Alzheimer's [CVN-AD] and control [C57Bl/6] mice, to evaluate the hypothesis that metabolic insufficiency is a critical component of degeneration leading to dementia. We analyzed cerebral blood flow and metabolic responses to spreading depression (induced by K applied to the cortex) and anoxia across aging in CVN-AD + C57Bl/6 genotypes. In the CVN-AD genotype progression to histological and cognitive hallmarks of dementia is a stereotyped function of age.

Likelihood ratio statistics for gene set enrichment in Alzheimer's disease pathways.

Introduction: The study of Alzheimer's disease (AD) has revealed biological pathways with implications for disease neuropathology and pathophysiology. These pathway-level effects may also be mediated by individual characteristics or covariates such as age or sex. Evaluation of AD biological pathways in the context of interactions with these covariates is critical to the understanding of AD as well as the development of model systems used to study the disease.

Neurovascular and immune mechanisms that regulate postoperative delirium superimposed on dementia.

Objective: The present work evaluates the relationship between postoperative immune and neurovascular changes and the pathogenesis of surgery-induced delirium superimposed on dementia.

Background And Rationale: Postoperative delirium is a common complication in many older adults and in patients with dementia including Alzheimer's disease (AD). The course of delirium can be particularly debilitating, while its pathophysiology remains poorly defined.

Vascular Cellular Adhesion Molecule-1 (VCAM-1) and Memory Impairment in African-Americans after Small Vessel-Type Stroke.

Background: African-Americans (AA) are 3 times more likely to have small-vessel-type ischemic strokes (SVS) than Whites. Small vessel strokes are associated with cognitive impairment, a relationship incompletely explained by white matter hyperintensity (WMH) burden. We examined whether inflammatory/endothelial dysfunction biomarkers are associated with cognition after SVS in AAs.

Skyline for Small Molecules: A Unifying Software Package for Quantitative Metabolomics.

Vendor-independent software tools for quantification of small molecules and metabolites are lacking, especially for targeted analysis workflows. Skyline is a freely available, open-source software tool for targeted quantitative mass spectrometry method development and data processing with a 10 year history supporting six major instrument vendors. Designed initially for proteomics analysis, we describe the expansion of Skyline to data for small molecule analysis, including selected reaction monitoring, high-resolution mass spectrometry, and calibrated quantification.

Identifying Vulnerable Brain Networks in Mouse Models of Genetic Risk Factors for Late Onset Alzheimer's Disease.

The major genetic risk for late onset Alzheimer's disease has been associated with the presence of APOE4 alleles. However, the impact of different APOE alleles on the brain aging trajectory, and how they interact with the brain local environment in a sex specific manner is not entirely clear. We sought to identify vulnerable brain circuits in novel mouse models with homozygous targeted replacement of the mouse ApoE gene with either human APOE3 or APOE4 gene alleles.

Multivariate MR biomarkers better predict cognitive dysfunction in mouse models of Alzheimer's disease.

To understand multifactorial conditions such as Alzheimer's disease (AD) we need brain signatures that predict the impact of multiple pathologies and their interactions. To help uncover the relationships between pathology affected brain circuits and cognitive markers we have used mouse models that represent, at least in part, the complex interactions altered in AD, while being raised in uniform environments and with known genotype alterations. In particular, we aimed to understand the relationship between vulnerable brain circuits and memory deficits measured in the Morris water maze, and we tested several predictive modeling approaches.

Long-term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply.

Transplantation of encapsulated islets can cure diabetes without immunosuppression, but oxygen supply limitations can cause failure. We investigated a retrievable macroencapsulation device wherein islets are encapsulated in a planar alginate slab and supplied with exogenous oxygen from a replenishable gas chamber. Translation to clinically-useful devices entails reduction of device size by increasing islet surface density, which requires increased gas chamber pO Here we show that islet surface density can be substantially increased safely by increasing gas chamber pO to a supraphysiological level that maintains all islets viable and functional.

Two Aviation Accident Investigation Questionnaires for Passenger and Crew Survival Factors and Injuries.

Background: Review of injuries resulting from aircraft accidents and analysis of their mechanisms have proved helpful in generating and implementing survival-related improvements. Ideally, such information should be correlated with seat belt type and use, as well as any brace position adopted. This information should be recorded and made publicly available to future researchers.

T Induces Both Markers of Maturation and Aging in Pancreatic β-Cells.

Previously, we showed that thyroid hormone (TH) triiodothyronine (T) enhanced β-cell functional maturation through induction of High levels of T have been linked to decreased life span in mammals and low levels to lengthened life span, suggesting a relationship between TH and aging. Here, we show that T increased (a β-cell senescence marker and effector) mRNA in rodent and human β-cells. The kinetics of and induction suggested both genes as targets of TH via TH receptors (THRs) binding to specific response elements.

Favorable outcome of experimental islet xenotransplantation without immunosuppression in a nonhuman primate model of diabetes.

Transplantation of pancreatic islets for treating type 1 diabetes is restricted to patients with critical metabolic lability resulting from the need for immunosuppression and the shortage of donor organs. To overcome these barriers, we developed a strategy to macroencapsulate islets from different sources that allow their survival and function without immunosuppression. Here we report successful and safe transplantation of porcine islets with a bioartificial pancreas device in diabetic primates without any immune suppression.

Speaking out about gender imbalance in invited speakers improves diversity.

Omissions of qualified women scientists from major meeting programs continue to occur despite a surge in articles indicating persistent gender-discriminatory practices in hiring and promotion, and calls for gender balance in conference organizing committees.

The fornix provides multiple biomarkers to characterize circuit disruption in a mouse model of Alzheimer's disease.

Multivariate biomarkers are needed for detecting Alzheimer's disease (AD), understanding its etiology, and quantifying the effect of therapies. Mouse models provide opportunities to study characteristics of AD in well-controlled environments that can help facilitate development of early interventions. The CVN-AD mouse model replicates multiple AD hallmark pathologies, and we identified multivariate biomarkers characterizing a brain circuit disruption predictive of cognitive decline.

Chronic Systemic Immune Dysfunction in African-Americans with Small Vessel-Type Ischemic Stroke.

The incidence of small vessel-type (lacunar) ischemic strokes is greater in African-Americans compared to whites. The chronic inflammatory changes that result from lacunar stroke are poorly understood. To elucidate these changes, we measured serum inflammatory and thrombotic biomarkers in African-Americans at least 6 weeks post-stroke compared to control individuals.