The Impact of the COVID-19 Pandemic on Real-world Functioning in Adult Cochlear-implant Users.

Hypothesis: As a result of COVID-19 lockdowns and the associated effects on the auditory-social environments of cochlear-implant (CI) users, we expected that adult CI users would report a decrease in real-world communication abilities, a decrease in social isolation, and a decrease in quality of life (QOL) from pre- to post-pandemic.

Background: The COVID-19 pandemic brought many changes to the environments in which adults with CIs interact and communicate. However, the impact of these changes on CI users' real-world functioning is not well understood.

Effect of Cochlear Implantation on Social Life.

Objective: Explore the effects of hearing loss on social life and identify residual social life deficits that remain after cochlear implantation.

Study Design: Retrospective review of prospectively obtained data.

Setting: Tertiary care adult neurotology center.

Calmodulin regulates protease versus co-chaperone activity of a metacaspase.

Metacaspases are ancestral homologs of caspases that can either promote cell death or confer cytoprotection. Furthermore, yeast (Saccharomyces cerevisiae) metacaspase Mca1 possesses dual biochemical activity: proteolytic activity causing cell death and cytoprotective, co-chaperone-like activity retarding replicative aging. The molecular mechanism favoring one activity of Mca1 over another remains elusive.

The yeast guanine nucleotide exchange factor Sec7 is a bottleneck in spatial protein quality control and detoxifies neurological disease proteins.

ER-to-Golgi trafficking partakes in the sorting of misfolded cytoplasmic proteins to reduce their cytological toxicity. We show here that yeast Sec7, a protein involved in proliferation of the Golgi, is part of this pathway and participates in an Hsp70-dependent formation of insoluble protein deposits (IPOD). Sec7 associates with the disaggregase Hsp104 during a mild heat shock and increases the rate of Hsp104 diffusion in an Hsp70-dependent manner when overproduced.

Calcineurin stimulation by Cnb1p overproduction mitigates protein aggregation and α-synuclein toxicity in a yeast model of synucleinopathy.

The calcium-responsive phosphatase, calcineurin, senses changes in Ca concentrations in a calmodulin-dependent manner. Here we report that under non-stress conditions, inactivation of calcineurin signaling or deleting the calcineurin-dependent transcription factor CRZ1 triggered the formation of chaperone Hsp100p (Hsp104p)-associated protein aggregates in Saccharomyces cerevisiae. Furthermore, calcineurin inactivation aggravated α-Synuclein-related cytotoxicity.

Artificial Hsp104-mediated systems for re-localizing protein aggregates.

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.

Preoperative Reading Efficiency as a Predictor of Adult Cochlear Implant Outcomes.

Hypotheses: 1) Scores of reading efficiency (the Test of Word Reading Efficiency, second edition) obtained in adults before cochlear implant surgery will be predictive of speech recognition outcomes 6 months after surgery; and 2) Cochlear implantation will lead to improvements in language processing as measured through reading efficiency from preimplantation to postimplantation.

Background: Adult cochlear implant (CI) users display remarkable variability in speech recognition outcomes. "Top-down" processing-the use of cognitive resources to make sense of degraded speech-contributes to speech recognition abilities in CI users.

Growth Rate Evaluation of the Budding Yeast Saccharomyces cerevisiae Cells Carrying Endogenously Expressed Fluorescent Protein Fusions.

Fluorescent proteins within fluorescent fusions have been reported to affect cellular growth fitness via altering native protein function and intracellular localization. Here we report in detail a procedure to analyze the growth characteristics of yeast cells expressing such fusions in comparison to unmodified parental strain. This approach can serve as an initial step in fluorescent protein characterization in vivo.

Using reporters of different misfolded proteins reveals differential strategies in processing protein aggregates.

The accumulation of misfolded proteins is a hallmark of aging and many neurodegenerative diseases, making it important to understand how the cellular machinery recognizes and processes such proteins. A key question in this respect is whether misfolded proteins are handled in a similar way regardless of their genetic origin. To approach this question, we compared how three different misfolded proteins, guk1-7, gus1-3, and pro3-1, are handled by the cell.

Large organellar changes occur during mild heat shock in yeast.

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-immobilised for electron microscopy.

Biopsychosocial Factors during the Perinatal Period: Risks, Preventative Factors, and Implications for Healthcare Professionals.

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.

Comparison of endogenously expressed fluorescent protein fusions behaviour for protein quality control and cellular ageing research.

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.

Effectiveness of Arginine Supplementation on Wound Healing in Older Adults in Acute and Chronic Settings: A Systematic Review.

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.

Syntaxin 5 Is Required for the Formation and Clearance of Protein Inclusions during Proteostatic Stress.

Spatial sorting to discrete quality control sites in the cell is a process harnessing the toxicity of aberrant proteins. We show that the yeast t-snare phosphoprotein syntaxin5 (Sed5) acts as a key factor in mitigating proteotoxicity and the spatial deposition and clearance of IPOD (insoluble protein deposit) inclusions associates with the disaggregase Hsp104. Sed5 phosphorylation promotes dynamic movement of COPII-associated Hsp104 and boosts disaggregation by favoring anterograde ER-to-Golgi trafficking.

Studying Spatial Protein Quality Control, Proteopathies, and Aging Using Different Model Misfolding Proteins in .

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.

An integrin inhibiting molecule decreases oxidative damage and improves neurological function after spinal cord injury.

Our previous studies have shown that treatment with an alpha4beta1 integrin blocking antibody after spinal cord injury (SCI) in rats decreases intraspinal inflammation and oxidative damage, improving neurological function. Here, we studied effects of a high affinity small molecule alpha4beta1 inhibitor, BIO5192. First, rats were treated intravenously with BIO5192 (10 mg/kg) or with vehicle (controls) to assess effects of integrin blockade for 24 h or 72 h after thoracic clip-compression SCI.