EFhd2 co-aggregates with monomeric and filamentous tau .

Tauopathies are characterized by the abnormal buildup of tau protein, with early oligomeric forms associated with neurodegeneration and the later neurofibrillary tangles possibly conferring neuroprotection. The molecular mechanisms governing the formation of these tau species are unclear. Lately, there has been an increased focus on examining the interactions between tau and other proteins, along with their influence on the aggregation of tau.

Engaging diverse populations in aging research during the COVID-19 pandemic: Lessons learned from four National Institutes of Health funded-Centers.

Background: The COVID-19 pandemic's impact on our personal and professional lives required a rapid adaptation to the evolving health crisis and accumulating social stresses. Established measures to reduce the spread of infection and potential death had a direct effect on ongoing research that involved older adults and underrepresented racial/ethnic groups. Although important to preserve public health, these measures risk further isolation of vulnerable research participant populations and threatened established community partnerships.

Liquid-Liquid Phase Separation to Study the Association of Proteins in Solution.

Liquid-liquid phase separation (LLPS) is a reversible biological process that contributes to the formation of critical concentration of proteins, forming membraneless compartments that are physiologically and pathologically relevant. Several proteins have been shown to demix into liquid droplets under in vitro crowding conditions. These studies are mainly conducted in isolation using purified recombinant proteins.

Influence of Care Network Characteristics on Physician Visit Experiences for Black, White, and Hispanic Older Adults With Dementia.

Objectives: Most older adults with dementia are assisted by multiple caregivers, but the relationship of care network structure with health care access and quality is underexamined. We sought to test the associations of care network characteristics with the physician visit experience for older adults with dementia across diverse racial/ethnic groups.

Methods: We used data on Medicare beneficiaries (aged 65+) with dementia from the National Health and Aging Trends Study (2015-2019) to fit logistic regression models to test associations between physician visit outcomes and (a) size of the potential care network and (b) proportion of potential care network members (PCNMs) currently helping with daily functioning tasks.

Structure and Enzymatic Activity of an Intellectual Disability-Associated Ornithine Decarboxylase Variant, G84R.

Ornithine decarboxylase (ODC) is a rate-limiting enzyme for the synthesis of polyamines (PAs). PAs are required for proliferation, and increased ODC activity is associated with cancer and neural over-proliferation. ODC levels and activity are therefore tightly regulated, including through the ODC-specific inhibitor, antizyme AZ1.

Beta2-adrenoreceptor agonist clenbuterol produces transient decreases in alpha-synuclein mRNA but no long-term reduction in protein.

β2-adrenoreceptor (β2AR) agonists have been associated with a decreased risk of developing Parkinson's disease (PD) and are hypothesized to decrease expression of both alpha-synuclein mRNA (Snca) and protein (α-syn). Effects of β2AR agonist clenbuterol on the levels of Snca mRNA and α-syn protein were evaluated in vivo (rats and mice) and in rat primary cortical neurons by two independent laboratories. A modest decrease in Snca mRNA in the substantia nigra was observed after a single acute dose of clenbuterol in rats, however, this decrease was not maintained after multiple doses.

Structural basis of binding and inhibition of ornithine decarboxylase by 1-amino-oxy-3-aminopropane.

Ornithine decarboxylase (ODC) is the rate-limiting enzyme for the synthesis of polyamines (PAs). PAs are oncometabolites that are required for proliferation, and pharmaceutical ODC inhibition is pursued for the treatment of hyperproliferative diseases, including cancer and infectious diseases. The most potent ODC inhibitor is 1-amino-oxy-3-aminopropane (APA).

EFhd2 brain interactome reveals its association with different cellular and molecular processes.

EFhd2 is a conserved calcium-binding protein that is highly expressed in the central nervous system. We have shown that EFhd2 interacts with tau protein, a key pathological hallmark in Alzheimer's disease and related dementias. However, EFhd2's physiological and pathological functions in the brain are still poorly understood.

Structure of an AMPK complex in an inactive, ATP-bound state.

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) regulates metabolism in response to the cellular energy states. Under energy stress, AMP stabilizes the active AMPK conformation, in which the kinase activation loop (AL) is protected from protein phosphatases, thus keeping the AL in its active, phosphorylated state. At low AMP:ATP (adenosine triphosphate) ratios, ATP inhibits AMPK by increasing AL dynamics and accessibility.

Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson's Disease.

The gut microbiome can impact brain health and is altered in Parkinson's disease (PD). The vermiform appendix is a lymphoid tissue in the cecum implicated in the storage and regulation of the gut microbiota. We sought to determine whether the appendix microbiome is altered in PD and to analyze the biological consequences of the microbial alterations.

Partnering with Middle Eastern/Arab American and Latino Immigrant Communities to Increase Participation in Alzheimer's Disease Research.

Purpose: Recruitment and retention of US ethnic groups traditionally underrepresented in research continues to pose challenges. The Michigan Center for Contextual Factors in Alzheimer's Disease (MCCFAD) engages with two underserved immigrant communities in Michigan - Middle Eastern/Arab Americans in metro-Detroit and Latinos in the Grand Rapids area - to recruit and retain two Participant Resource Pools (PRP).

Procedures: We adapt an existing community-based participatory research (CBPR) approach to recruit Middle Eastern/Arab American and Latino adults of all ages for Alzheimer's disease and related dementia (ADRD) research.

Validation of recombinant human protein purified from bacteria: An important step to increase scientific rigor.

E. coli is a common host for generating human recombinant proteins in in vitro studies that seek to understand the biochemical and structural properties of proteins and in drug discovery. Validation of this biological resource is crucial to avoid misinterpretations and assay interference.

Age of Migration and Cognitive Function Among Older Latinos in the United States.

Background: Age of migration has been shown to have a robust association with Latino immigrant health outcomes; however, the relationship between timing of migration and cognition is less understood.

Objective: To examine associations between race/ethnicity, nativity, age of migration, and cognitive aging among US-born (USB) non-Latino Whites (NLW) and USB and foreign-born Latinos 50 years and older.

Methods: We used longitudinal biennial data from the Health and Retirement Study (HRS; 2006-2014) to fit generalized linear and linear latent growth curve models for: 1) global cognition (Modified Telephone Interview for Cognitive Status; TICS-M); 2) memory and attention subdomains of TICS-M; and 3) cognitive dysfunction.

Glycosylated hemoglobin level, race/ethnicity, and cognition in midlife and early old age.

Empirical evidence linking racial/ethnic differences in glycosylated hemoglobin levels (HbA1c) to cognitive function in midlife and early old age is limited. We use biomarker data from the Health and Retirement Study (HRS, 2006-2014), on adults 50-64 years at baseline (57-73 years by 2014), and fit multinomial logistic regression models to assess the association between baseline HbA1c, cognitive function (using Langa-Weir classifications) and mortality across 8-years. Additionally, we test for modification effects by race/ethnicity.

EFhd2 Affects Tau Liquid-Liquid Phase Separation.

The transition of tau proteins from its soluble physiological conformation to the pathological aggregate forms found in Alzheimer's disease and related dementias, is poorly understood. Therefore, understanding the process that modulates the formation of toxic tau oligomers and their conversion to putative neuroprotective neurofibrillary tangles will lead to better therapeutic strategies. We previously identified that EFhd2 is associated with aggregated tau species in AD brains and the coiled-coil domain in EFhd2 mediates the interaction with tau.

Tau13 Antibody Preferentially Immunoprecipitates High Molecular Weight Tau Proteins.

The accumulation of tau protein aggregates is a pathological hallmark in Alzheimer's disease (AD) and other neurodegenerative diseases. However, the identity of the toxic tau conformation that propagates and induces neurodegeneration is still unknown. Anti-tau antibodies are a common tool used to differentiate between normal and pathological-associated tau forms or as passive immunotherapy in the quest to interfere with tau-mediated neurodegeneration.

Tau's Three-Repeat Domain and EFhd2 Co-incubation Leads to Increased Thioflavin Signal.

Aggregation of the protein tau is a pathological hallmark of Alzheimer's disease (AD) and related disorders. However, the molecular mechanisms that lead to tau protein aggregation are still unclear. Previously, we showed that EFhd2 protein is associated with pathological aggregated forms of tau in AD brain.

A functional proteomics platform to reveal the sequence determinants of lysine methyltransferase substrate selectivity.

Lysine methylation is a key regulator of histone protein function. Beyond histones, few connections have been made to the enzymes responsible for the deposition of these posttranslational modifications. Here, we debut a high-throughput functional proteomics platform that maps the sequence determinants of lysine methyltransferase (KMT) substrate selectivity without a priori knowledge of a substrate or target proteome.

EF Hand Domain Family Member D2 Is Required for T Cell Cytotoxicity.

Programmed cell death 1 (PD-1) is a major coinhibitory receptor and a member of the immunological synapse (IS). To uncover proteins that regulate PD-1 recruitment to the IS, we searched for cytoskeleton-related proteins that also interact with PD-1 using affinity purification mass spectrometry. Among these proteins, EF hand domain family member D2 (EFHD2), a calcium binding adaptor protein, was functionally and mechanistically analyzed for its contribution to PD-1 signaling.

Ezrin Expression is Increased During Disease Progression in a Tauopathy Mouse Model and Alzheimer's Disease.

Background: The lack of diagnostic tools and disease-modifying treatments against Alzheimer's disease (AD) and related disorders, collectively known as tauopathies, has led to a socioeconomic burden of epidemic proportion. Proteomics approaches can be used to identify novel proteome changes that could help us understand the pathogenesis of tau-related pathological hallmarks and/or cellular stress responses associated with tauopathy. These studies, however, need to be conducted taking into consideration brain region specificity and stage of neurodegeneration in order to provide insights about the pathological role of the identified proteins.

A START-domain-containing protein is a novel marker of nervous system components of the sea cucumber Holothuria glaberrima.

One of the main challenges faced by investigators studying the nervous system of members of the phylum Echinodermata is the lack of markers to identify nerve cells and plexi. Previous studies have utilized an antibody, RN1, that labels most of the nervous system structures of the sea cucumber Holothuria glaberrima and other echinoderms. However, the antigen recognized by RN1 remained unknown.

Alzheimer's Disease in the Latino Community: Intersection of Genetics and Social Determinants of Health.

Alzheimer's disease (AD) is the most common type of dementia among individuals 65 or older. There are more than 5 million diagnosed cases in the US alone and this number is expected to triple by 2050. Therefore, AD has reached epidemic proportions with significant socioeconomic implications.

Biomarkers for the Early Detection and Progression of Alzheimer's Disease.

The recent failures of potential disease-modifying drugs for Alzheimer's disease (AD) may reflect the fact that the enrolled participants in clinical trials are already too advanced to derive a clinical benefit. Thus, well-validated biomarkers for the early detection and accurate diagnosis of the preclinical stages of AD will be crucial for therapeutic advancement. The combinatorial use of biomarkers derived from biological fluids, such as cerebrospinal fluid (CSF), with advanced molecular imaging and neuropsychological testing may eventually achieve the diagnostic sensitivity and specificity necessary to identify people in the earliest stages of the disease when drug modification is most likely possible.