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Objectives: Guided by a life course perspective and fundamental cause theory, this study aims to visualize co-trajectories of health between partners and examine how changes in one spouse's cognitive status can cohesively impact the health of the other spouse along three dimensions (functional, mental, and cognitive). Methods: Drawing longitudinal data from the Health and Retirement Study 2000–2016 (N = 3582), we measure women's health profiles by functional limitation (physical health), depression (mental health), and cognitive function (cognitive health). We use multivariate linear mixed models to summarize these paths in the same visual representation. Results: The approach provides a visualization tool that depicts data and model in the same spatial representation allowing assessment of model fit and comparison. This study advances the traditional life course studies by representing underlying processes as a multidimensional time vector of health outcomes. Discussion: The described approach provides a blueprint for studying complex health profiles or trajectories. [ABSTRACT FROM AUTHOR]

One third of inherited genetic diseases are caused by mRNAs harboring premature termination codons as a result of nonsense mutations. These aberrant mRNAs are degraded by the Nonsense-Mediated mRNA Decay (NMD) pathway. A central component of the NMD pathway is Upf1, an RNA-dependent ATPase and helicase. Upf1 is a known phosphorylated protein, but only portions of this large protein have been examined for phosphorylation sites and the functional relevance of its phosphorylation has not been elucidated in Saccharomyces cerevisiae. Using tandem mass spectrometry analyses, we report the identification of 11 putative phosphorylated sites in S. cerevisiae Upf1. Five of these phosphorylated residues are located within the ATPase and helicase domains and are conserved in higher eukaryotes, suggesting a biological significance for their phosphorylation. Indeed, functional analysis demonstrated that a small carboxy-terminal motif harboring at least three phosphorylated amino acids is important for three Upf1 functions: ATPase activity, NMD activity and the ability to promote translation termination efficiency. We provide evidence that two tyrosines within this phospho-motif (Y-738 and Y-742) act redundantly to promote ATP hydrolysis, NMD efficiency and translation termination fidelity.

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. Our previous work revealed EFhd2's association with pathological tau in animal models and tauopathy brains. Herein, we examined the impact of EFhd2 on monomeric and filamentous tau in vitro. The results demonstrated that EFhd2 incubation with monomeric full length human tau (hTau40) formed amorphous aggregates, where both EFhd2 and hTau40 colocalized. Moreover, EFhd2 is entangled with arachidonic acid (ARA)-induced filamentous hTau40. Furthermore, EFhd2-induced aggregation with monomeric and filamentous hTau40 is EFhd2 concentration dependent. Using sandwich ELISA assays, we assessed the reactivity of TOC1 and Alz50--two conformation-specific tau antibodies--to EFhd2-hTau40 aggregates (in absence and presence of ARA). No TOC1 signal was detected in EFhd2 aggregates with monomeric hTau40 whereas EFhd2 aggregates with hTau in the presence of ARA showed a higher signal compared to hTau40 filaments. In contrast, EFhd2 aggregates with both monomeric and filamentous hTau40 reduced Alz50 reactivity. Taken together, our results illustrate for the first time that EFhd2, a tau-associated protein, interacts with monomeric and filamentous hTau40 to form large aggregates that are starkly different from tau oligomers and filaments. Given these findings and previous research, we hypothesize that EFhd2 may play a role in the formation of tau aggregates. Nevertheless, further in vivo studies are imperative to test this hypothesis. [ABSTRACT FROM AUTHOR]

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. We also tested for modifications by race/ethnicity. Results Hispanic respondents had the largest potential care networks (M = 6.89, standard deviation [ SD ] = 3.58) and the smallest proportion of PCNMs providing help with daily functioning (M = 29.89%, SD = 22.29). In models adjusted for demographics and dementia classification, both network size and proportional involvement of PCNMs were positively associated with the presence of a PCNM and assistance during the visit. Associations remained significant at 4-year follow-up for the presence of PCNM at the visit and were robust to further adjustments for insurance type, income, and health factors. Associations were not modified by race/ethnicity. Discussion Larger networks and a higher proportion of PCNMs providing assistance predicted caregiver presence and assistance at the physician visit but not access to care. Findings suggest that strengthening care networks early in the disease may support improved health care outcomes for persons with dementia across diverse populations. [ABSTRACT FROM AUTHOR]

The Rad23 evolutionarily conserved protein is important in nucleotide excision repair. A study shows that Rad23 interacts with the 26S proteasome via an amino-terminal ubiquitin-like domain (UblR23). A link is created between the DNA repair and proteasome pathways. It is thought that the ultraviolet sensitivity due to deletion of the UbLR23 domain, could be due to its lack of interaction with the proteasome.