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Protein quality control (PQC) is critical to maintain a functioning proteome. Misfolded or toxic proteins are either refolded or degraded by a system of temporal quality control and can also be sequestered into aggregates or inclusions by a system of spatial quality control. Breakdown of this concerted PQC network with age leads to an increased risk for the onset of disease, particularly neurological disease. Saccharomyces cerevisiae has been used extensively to elucidate PQC pathways and general evolutionary conservation of the PQC machinery has led to the development of several useful S. cerevisiae models of human neurological diseases. Key to both of these types of studies has been the development of several different model misfolding proteins, which are used to challenge and monitor the PQC machinery. In this review, we summarize and compare the model misfolding proteins that have been used to specifically study spatial PQC in S. cerevisiae, as well as the misfolding proteins that have been shown to be subject to spatial quality control in S. cerevisiae models of human neurological diseases.

When the temperature is increased, the heat shock response is activated to protect the cellular environment. The transcriptomics and proteomics of this process are intensively studied, while information about how the cell responds structurally to heat stress is mostly lacking. Here, Saccharomyces cerevisiae were subjected to a mild continuous heat shock (38°C) and intermittently cryo-immobilized for electron microscopy. Through measuring changes in all distinguishable organelle numbers, sizes, and morphologies in over 2100 electron micrographs a major restructuring of the cell's internal architecture during the progressive heat shock was revealed. The cell grew larger but most organelles within it expanded even more, shrinking the volume of the cytoplasm. Organelles responded to heat shock at different times, both in terms of size and number, and adaptations of certain organelles’ morphology (such as the vacuole), were observed. Multivesicular bodies grew to almost 170% in size, indicating a previously unknown involvement in the heat shock response. A previously undescribed electron translucent structure accumulated close to the plasma membrane. This all-encompassing approach provides a detailed chronological progression of organelle adaptation throughout the cellular heat-stress response.

Women face risks to their wellbeing during the perinatal period of pregnancy. However, there is a dearth of information on perinatal risk factors within the biopsychosocial paradigm. Emphasis is often placed on biological components associated with pregnancy and women’s health. However, psychological and social determinants of health are integral during the perinatal period, and mental wellness is often a determinant for positive maternal and neonatal health outcomes. This article reviews risk factors of perinatal wellness (e.g., physical and nutritional concerns, trauma, discrimination, adverse childhood events) and highlights protective factors for women in their perinatal period. Healthcare professionals can support perinatal health by focusing on culturally and contextually appropriate research and prevention, providing equal access to sexual and reproductive healthcare information and services, providing quality education and training for helping professionals, and supporting policies for positive sexual and reproductive women’s healthcare.

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The yeast Hsp104 protein disaggregase is often used as a reporter for misfolded or damaged protein aggregates and protein quality control and ageing research. Observing Hsp104 fusions with fluorescent proteins is a popular approach to follow post stress protein aggregation, inclusion formation and disaggregation. While concerns that bigger protein tags, such as genetically encoded fluorescent tags, may affect protein behaviour and function have been around for quite some time, experimental evidence of how exactly the physiology of the protein of interest is altered within fluorescent protein fusions remains limited. To address this issue, we performed a comparative assessment of endogenously expressed Hsp104 fluorescent fusions function and behaviour. We provide experimental evidence that molecular behaviour may not only be altered by introducing a fluorescent protein tag but also varies depending on such a tag within the fusion. Although our findings are especially applicable to protein quality control and ageing research in yeast, similar effects may play a role in other eukaryotic systems.

OBJECTIVE To examine the effect of arginine supplementation on wound healing, as measured by wound size and healing rate, in older adults in acute and long-term care (LTC) settings. DATA SOURCES PubMed, CINAHL Plus, Google Scholar, and OpenGrey databases. STUDY SELECTION Randomized clinical trials and clinical studies were considered for this review. Selection criteria included English-language articles published after 2008 that provide data on older adults with pressure injury receiving arginine supplementation in acute care and LTC settings. DATA EXTRACTION Data were extracted from the articles using a predefined checklist including study size and design, participant characteristics (age, pressure injury stage, relevant comorbidities), nutrition intervention and dosage, duration of study, outcomes, and publication year. Studies were appraised using the National Institutes of Health’s Quality Assessment of Controlled Intervention Studies tool. DATA SYNTHESIS A preliminary search yielded 39 articles after removing duplicates. Abstracts and titles of articles were screened, and 23 full-text articles were examined further. Ultimately, six articles met the inclusion criteria. CONCLUSIONS Current evidence suggests that arginine supplementation in conjunction with oral nutrition supplementation may promote wound healing in older adult patients in acute care and LTC settings as evidenced by significant reductions in wound size and improvements in wound healing when compared with oral nutrition supplementation alone. A definitive conclusion about the use of arginine supplementation alone to promote wound healing cannot be drawn because of limitations in the available literature. Additional high-quality studies are needed to examine arginine supplementation alone as a potential therapy for PI.

Spatial Protein Quality Control (sPQC) sequesters misfolded proteins into specific, organelle-associated inclusions within the cell to control their toxicity. To approach the role of sPQC in cellular fitness, neurodegenerative diseases and aging, we report on the construction of Hsp100-based systems in budding yeast cells, which can artificially target protein aggregates to non-canonical locations. We demonstrate that aggregates of mutant huntingtin (mHtt), the disease-causing agent of Huntington’s disease can be artificially targeted to daughter cells as well as to eisosomes and endosomes with this approach. We find that the artificial removal of mHtt inclusions from mother cells protects them from cell death suggesting that even large mHtt inclusions may be cytotoxic, a trait that has been widely debated. In contrast, removing inclusions of endogenous age-associated misfolded proteins does not significantly affect the lifespan of mother cells. We demonstrate also that this approach is able to manipulate mHtt inclusion formation in human cells and has the potential to be useful as an alternative, complementary approach to study the role of sPQC, for example in aging and neurodegenerative disease.