Laying hens prefer softer over harder mineral-based pecking stones and peck them more at the end of the light period.

Mineral-based pecking stones (PS) are edible enrichments for poultry that comprise a high proportion of calcium. We aimed to determine whether laying hens prefer a Soft (easier to ingest) versus a Hard mineral-based PS with the same calcium content, if pecking at PS follows a diurnal pattern similar to calcium appetite, and whether the PS affects eggshell quality. Shaver White laying hens housed in groups of 3 in furnished cages (N = 38) were given either a Hard or Soft PS for 15 days, followed by a 6-day washout period of no PS, and then the opposite PS type for an additional 15 days (Phase 1).

Efficacy of decentralised home-based antihypertensive treatment in older adults with multimorbidity and polypharmacy (ATEMPT): an open-label randomised controlled pilot trial.

Background: Older patients with multimorbidity and polypharmacy have been under-represented in clinical trials. We aimed to assess the effect of different intensities of antihypertensive treatment on changes in blood pressure, major safety outcomes, and patient-reported outcomes in this population.

Methods: ATEMPT was a decentralised, two-armed, parallel-group, open-label randomised controlled pilot trial conducted in the Thames Valley area, South East England.

Experiences of moral distress in a COVID-19 intensive care unit: A qualitative study of nurses and respiratory therapists in the United States.

The COVID-19 pandemic has placed extraordinary stress on frontline healthcare providers as they encounter significant challenges and risks while caring for patients at the bedside. This study used qualitative research methods to explore nurses and respiratory therapists' experiences providing direct care to COVID-19 patients during the first surge of the pandemic at a large academic medical center in the Northeastern United States. The purpose of this study was to explore their experiences as related to changes in staffing models and to consider needs for additional support.

Encountering the social determinants of health on a COVID-19 ICU: Frontline providers' perspectives on inequality in a time of pandemic.

Efforts to improve health equity may be advanced by understanding health care providers' perceptions of the causes of health inequalities. Drawing on data from in-depth interviews with nurses and registered respiratory therapists (RRTs) who served on intensive care units (ICUs) during the first surge of the pandemic, this paper examines how frontline providers perceive and attribute the unequal impacts of COVID-19. It shows that nurses and RRTs quickly perceived the pandemic's disproportionate burden on Black and Latinx individuals and families.

Integrated analysis of Shank1 PDZ interactions with C-terminal and internal binding motifs.

PDZ domains constitute a large family of modular domains that are well-known for binding C-terminal motifs of target proteins. Some of them also bind to internal PDZ binding motifs (PDZbms), but this aspect of the PDZ interactome is poorly studied. Here we explored internal PDZbm-mediated interactions using the PDZ domain of Shank1 as a model.

Intensive care unit nurses living through COVID-19: A qualitative study.

Aims: To understand how nurses experience providing care for patients hospitalized with COVID-19 in intensive care units.

Background: As hospitals adjust staffing patterns to meet the demands of the pandemic, nurses have direct physical contact with ill patients, placing themselves and their families at physical and emotional risk.

Methods: From June to August 2020, semi-structured interviews were conducted.

Dynamic origins of substrate promiscuity in bacterial galactokinases.

Galactokinase catalyses the ATP-dependent phosphorylation of galactose and structurally related sugars. The enzyme has attracted interest as a potential biocatalyst for the production of sugar 1-phosphates and several attempts have been made to broaden its specificity. In general, bacterial galactokinases have wider substrate ranges than mammalian ones.

Pairwise combinations of chemical compounds that delay yeast chronological aging through different signaling pathways display synergistic effects on the extent of aging delay.

We have recently discovered six plant extracts that delay yeast chronological aging. Most of them affect different nodes, edges and modules of an evolutionarily conserved network of longevity regulation that integrates certain signaling pathways and protein kinases; this network is also under control of such aging-delaying chemical compounds as spermidine and resveratrol. We have previously shown that, if a strain carrying an aging-delaying single-gene mutation affecting a certain node, edge or module of the network is exposed to some of the six plant extracts, the mutation and the plant extract enhance aging-delaying efficiencies of each other so that their combination has a synergistic effect on the extent of aging delay.

Modulation of the mobility of a key region in human galactokinase: Impacts on catalysis and stability.

Galactokinase catalyses the phosphorylation of α-d-galactose and some structurally related monosaccharides. The enzyme is of interest due to its potential as a biocatalyst for the production of sugar 1-phosphates and due to its involvement in the inherited metabolic disease type II galactosemia. It has been previously shown that a region (residues 231-245) in human galactokinase often has altered mobility when active site residues are varied.

A galactokinase-like protein from the liver fluke Fasciola hepatica.

Galactokinase catalyses the ATP-dependent phosphorylation of galactose. A galactokinase-like sequence was identified in a Fasciola hepatica EST library. Recombinant expression of the corresponding protein in Escherichia coli resulted in a protein of approximately 50 kDa.

Yeast Cells Exposed to Exogenous Palmitoleic Acid Either Adapt to Stress and Survive or Commit to Regulated Liponecrosis and Die.

A disturbed homeostasis of cellular lipids and the resulting lipotoxicity are considered to be key contributors to many human pathologies, including obesity, metabolic syndrome, type 2 diabetes, cardiovascular diseases, and cancer. The yeast has been successfully used for uncovering molecular mechanisms through which impaired lipid metabolism causes lipotoxicity and elicits different forms of regulated cell death. Here, we discuss mechanisms of the "liponecrotic" mode of regulated cell death in .

Some Metabolites Act as Second Messengers in Yeast Chronological Aging.

The concentrations of some key metabolic intermediates play essential roles in regulating the longevity of the chronologically aging yeast . These key metabolites are detected by certain ligand-specific protein sensors that respond to concentration changes of the key metabolites by altering the efficiencies of longevity-defining cellular processes. The concentrations of the key metabolites that affect yeast chronological aging are controlled spatially and temporally.

Lipid metabolism and transport define longevity of the yeast Saccharomyces cerevisiae.

Emergent evidence indicates that certain aspects of lipid synthesis, degradation and interorganellar transport play essential roles in modulating the pace of cellular aging in the budding yeast Saccharomyces cerevisiae. The molecular mechanisms underlying the vital roles of lipid metabolism and transport in defining yeast longevity have begun to emerge. The scope of this review is to critically analyze recent progress in understanding such mechanisms.

Mechanisms Underlying the Essential Role of Mitochondrial Membrane Lipids in Yeast Chronological Aging.

The functional state of mitochondria is vital to cellular and organismal aging in eukaryotes across phyla. Studies in the yeast have provided evidence that age-related changes in some aspects of mitochondrial functionality can create certain molecular signals. These signals can then define the rate of cellular aging by altering unidirectional and bidirectional communications between mitochondria and other organelles.

Specific changes in mitochondrial lipidome alter mitochondrial proteome and increase the geroprotective efficiency of lithocholic acid in chronologically aging yeast.

We have previously found that exogenously added lithocholic acid delays yeast chronological aging. We demonstrated that lithocholic acid enters the yeast cell, is sorted to mitochondria, resides in both mitochondrial membranes, changes the relative concentrations of different membrane phospholipids, triggers changes in the concentrations of many mitochondrial proteins, and alters some key aspects of mitochondrial functionality. We hypothesized that the lithocholic acid-driven changes in mitochondrial lipidome may have a causal role in the remodeling of mitochondrial proteome, which may in turn alter the functional state of mitochondria to create a mitochondrial pattern that delays yeast chronological aging.

Insight into the mechanism of galactokinase: Role of a critical glutamate residue and helix/coil transitions.

Galactokinase, the enzyme which catalyses the first committed step in the Leloir pathway, has attracted interest due to its potential as a biocatalyst and as a possible drug target in the treatment of type I galactosemia. The mechanism of the enzyme is not fully elucidated. Molecular dynamics (MD) simulations of galactokinase with the active site residues Arg-37 and Asp-186 altered predicted that two regions (residues 174-179 and 231-240) had different dynamics as a consequence.

Modulating Mobility: a Paradigm for Protein Engineering?

Proteins are highly mobile structures. In addition to gross conformational changes occurring on, for example, ligand binding, they are also subject to constant thermal motion. The mobility of a protein varies through its structure and can be modulated by ligand binding and other events.

Six plant extracts delay yeast chronological aging through different signaling pathways.

Our recent study has revealed six plant extracts that slow yeast chronological aging more efficiently than any chemical compound yet described. The rate of aging in yeast is controlled by an evolutionarily conserved network of integrated signaling pathways and protein kinases. Here, we assessed how single-gene-deletion mutations eliminating each of these pathways and kinases affect the aging-delaying efficiencies of the six plant extracts.

Discovery of plant extracts that greatly delay yeast chronological aging and have different effects on longevity-defining cellular processes.

We discovered six plant extracts that increase yeast chronological lifespan to a significantly greater extent than any of the presently known longevity-extending chemical compounds. One of these extracts is the most potent longevity-extending pharmacological intervention yet described. We show that each of the six plant extracts is a geroprotector which delays the onset and decreases the rate of yeast chronological aging by eliciting a hormetic stress response.

Galactokinase promiscuity: a question of flexibility?

Galactokinase catalyses the first committed step of the Leloir pathway, i.e. the ATP-dependent phosphorylation of α-D-galactose at C1-OH.

A deterministic oscillatory model of microtubule growth and shrinkage for differential actions of short chain fatty acids.

Short chain fatty acids (SCFA), principally acetate, propionate, butyrate and valerate, are produced in pharmacologically relevant concentrations by the gut microbiome. Investigations indicate that they exert beneficial effects on colon epithelia. There is increasing interest in whether different SCFAs have distinct functions which may be exploited for prevention or treatment of colonic diseases including colorectal cancer (CRC), inflammatory bowel disease and obesity.