Oxidative Stress Responses and Nutrient Starvation in MCHM Treated Saccharomyces cerevisiae

In 2014, the coal cleaning chemical 4-methylcyclohexane methanol (MCHM) spilled into the water supply for 300,000 West Virginians. Initial toxicology tests showed relatively mild results, but the underlying effects on cellular biology were underexplored. Treated wildtype yeast cells grew poorly, but there was only a small decrease in cell viability. Cell cycle analysis revealed an absence of cells in S phase within thirty minutes of treatment. Cells accumulated in G1 over a six-hour time course, indicating arrest instead of death. A genetic screen of the haploid knockout collection revealed 329 high confidence genes required for optimal growth in MCHM. These genes encode three major cell processes: mitochondrial gene expression/translation, the vacuolar ATPase, and aromatic amino acid biosynthesis. The transcriptome showed an upregulation of pleiotropic drug response genes and amino acid biosynthetic genes and downregulation in ribosome biosynthesis. Analysis of these datasets pointed to environmental stress response activation upon treatment. Overlap in datasets included the aromatic amino acid genes ARO1, ARO3, and four of the five TRP genes. This implicated nutrient deprivation as the signal for stress response. Excess supplementation of nutrients and amino acids did not improve growth on MCHM, so the source of nutrient deprivation signal is still unclear. Reactive oxygen species and DNA damage were directly detected with MCHM treatment, but timepoints showed these accumulated slower than cells arrested. We propose that wildtype cells arrest from nutrient deprivation and survive, accumulating oxidative damage through the implementation of robust environmental stress responses

Saccharomyces arboricola and Its Hybrids’ Propensity for Sake Production: Interspecific Hybrids Reveal Increased Fermentation Abilities and a Mosaic Metabolic Profile

The use of interspecific hybrids during the industrial fermentation process has been well established, positioning the frontier of advancement in brewing to capitalize on the potential of Saccharomyces hybridization. Interspecific yeast hybrids used in modern monoculture inoculations benefit from a wide range of volatile metabolites that broaden the organoleptic complexity. This is the first report of sake brewing by Saccharomyces arboricola and its hybrids. S. arboricola x S. cerevisiae direct-mating generated cryotolerant interspecific hybrids which increased yields of ethanol and ethyl hexanoate compared to parental strains, important flavor attributes of fine Japanese ginjo sake rice wine. Hierarchical clustering heatmapping with principal component analysis for metabolic profiling was used in finding low levels of endogenous amino/organic acids clustered S. arboricola apart from the S. cerevisiae industrial strains. In sake fermentations, hybrid strains showed a mosaic profile of parental strains, while metabolic analysis suggested S. arboricola had a lower amino acid net uptake than S. cerevisiae. Additionally, this research found an increase in ethanolic fermentation from pyruvate and increased sulfur metabolism. Together, these results suggest S. arboricola is poised for in-depth metabolomic exploration in sake fermentation

Outcome in patients with cystic fibrosis liver disease

AbstractBackgroundLiver disease is an important complication in CF.AimsTo determine if CFLD is a risk factor for mortality in CF, and which baseline characteristics predict all-cause mortality.MethodsIrish children with CFLD, and their age and gender matched controls were enrolled at baseline and reviewed after 10years to determine which characteristics predict mortality.Results72/84 (85.71%) participants were followed, (mean age Cases 21.71yrs SD 6.5, CF controls 23.62 SD 5.6, 22 (61%) males), with no difference in duration of follow-up. Nineteen participants (26.4%) died, 38.9% (14/36) with CFLD and 13.89% (5/36) CF controls (Odds Ratio (OR) 3.94 95% CI:1.23–12.56 p=0.005). In logistic regression, liver disease (OR 4.28 95% CI 1.07–17.16) female gender (OR 12.25 95% CI 2.37–63.24), reduced pulmonary function, (OR 5.11 95% CI 1.09–23.81) were each independent risk factors for mortality in CF.ConclusionsLiver disease is an independent risk factor for mortality in CF

Central deficiency of IL-6Ra in mice impairs glucose-stimulated insulin secretion

OBJECTIVE: IL-6 is an important contributor to glucose and energy homeostasis through changes in whole-body glucose disposal, insulin sensitivity, food intake and energy expenditure. However, the relative contributions of peripheral versus central IL-6 signaling to these metabolic actions are presently unclear. A conditional mouse model with reduced brain IL-6Ra expression was used to explore how blunted central IL-6 signaling alters metabolic status in lean and obese mice. METHODS: Transgenic mice with reduced levels of central IL-6 receptor alpha (IL-6Ra) (IL-6Ra KD mice) and Nestin Cre controls (Cre(+/-) mice) were fed standard chow or high-fat diet for 20 weeks. Obese and lean mouse cohorts underwent metabolic phenotyping with various measures of energy and glucose homeostasis determined. Glucose-stimulated insulin secretion was assessed in vivo and ex vivo in both mouse groups. RESULTS: IL-6Ra KD mice exhibited altered body fat mass, liver steatosis, plasma insulin, IL-6 and NEFA levels versus Cre(+/-) mice in a diet-dependent manner. IL-6Ra KD mice had increased food intake, higher RER, decreased energy expenditure with diminished cold tolerance compared to Cre(+/-) controls. Standard chow-fed IL-6Ra KD mice displayed reduced plasma insulin and glucose-stimulated insulin secretion with impaired glucose disposal and unchanged insulin sensitivity. Isolated pancreatic islets from standard chow-fed IL-6Ra KD mice showed comparable morphology and glucose-stimulated insulin secretion to Cre(+/-) controls. The diminished in vivo insulin secretion exhibited by IL-6Ra KD mice was recovered by blockade of autonomic ganglia. CONCLUSIONS: This study shows that central IL-6Ra signaling contributes to glucose and energy control mechanisms by regulating food intake, energy expenditure, fuel flexibility and insulin secretion. A plausible mechanism linking central IL-6Ra signaling and pancreatic insulin secretion is through the modulation of autonomic output activity. Thus, brain IL-6 signaling may contribute to the central adaptive mechanisms engaged in response to metabolic stress

Formulation and fluoride content of dentifrices: a review of current patterns

Introduction Consumer oral hygiene products play a key role in improving and maintaining population oral health. The oral personal care market is rapidly diversifying; a growing number of dentifrices marketed a 'natural' and fluoride-free are entering mainstream retailers, which may have implications for the oral health of the population 'with regards to caries risk. Aims To investigate the range of fluoride concentrations, flavour formulations and delivery mechanisms of dentifrices available on the UK market. Methods A cross-sectional survey was used to catalogue dentifrices sold in a range of supermarkets, high-street pharmacy and health chains, and specialist online retailers. In addition, a standard search engine was used to examine dentifrice brands being sold in the UK. The fluoride content was recorded as parts per million (ppm) and the product name data were analysed for key terms using Microsoft Excel. Excluded from the survey were mouthwashes, rinses and non-dentifrice whitening products. Results Five hundred different toothpaste, tooth powder and tablet products from 95 different brands were recorded. Sixty percent of these contained a fluoride concentration of 1,000 ppm or above. Forty-five percent of all products had the recommended adult concentration of at least 1,350 ppm. Almost one-third (31%) contained no fluoride and 4% of products did not specify the absence, presence or concentration of fluoride. Conclusions This study has quantified and confirmed the increasingly diverse range of dentifrices for sale in the UK. A large number of fluoride-free products exist within a growing 'natural' and 'organic market'. The study also gives oral health professionals an insight into the diverse types of products available to consumers in order to appropriately advise patients on caries prevention

Dental periodontal procedures: a systematic review of contamination (splatter, droplets and aerosol) in relation to COVID-19

Introduction The emergence of the SARS-CoV-2 virus and subsequent COVID-19 pandemic has had a significant effect on the delivery of routine dentistry; and in particular, periodontal care across the world. This systematic review examines the literature relating to splatter, droplet settle and aerosol for periodontal procedures and forms part of a wider body of research to understand the risk of contamination in relation to periodontal care procedures relevant to COVID-19. Methods A search of the literature was carried out using key terms and MeSH words relating to the review questions. Sources included Medline (OVID), Embase (OVID), Cochrane Central Register of Controlled Trials, Scopus, Web of Science and LILACS, ClinicalTrials.Gov. Studies meeting inclusion criteria were screened in duplicate and data extraction was carried out using a template. All studies were assessed for methodological quality and sensitivity. Narrative synthesis was undertaken. Results Fifty studies were included in the review with procedures including ultrasonic scaling (n = 44), air polishing (n = 4), prophylaxis (n = 2) and hand scaling (n = 3). Outcomes included bacterial (colony-forming units e.g. on settle plates) or blood contamination (e.g. visible splatter) and non bacterial, non blood (e.g. chemiluminescence or coloured dyes) contamination. All studies found contamination at all sites although the contamination associated with hand scaling was very low. Contamination was identified in all of the studies even where suction was used at baseline. Higher power settings created greater contamination. Distribution of contamination varied in relation to operator position and was found on the operator, patient and assistant with higher levels around the head of the operator and the mouth and chest of the patient. Settle was identified 30 min after treatments had finished but returned to background levels when measured at or after an hour. The evidence was generally low to medium quality and likely to underestimate contamination. Conclusion Ultrasonic scaling, air polishing and prophylaxis procedures produce contamination (splatter, droplets and aerosol) in the presence of suction, with a small amount of evidence showing droplets taking between 30 min and 1 h to settle. Consideration should be given to infection control, areas of cleaning particularly around the patient and appropriate personal protective equipment, with particular attention to respiratory, facial and body protection for these procedures. In addition, the use of lower power settings should be considered to reduce the amount and spread of contamination

Aerosol and splatter generation with rotary handpieces used in restorative and orthodontic dentistry:a systematic review

Abstract: Introduction: The COVID-19 pandemic has caused major disruptions in dental care globally, in part due to the potential for contaminated aerosol to be generated by dental activities. This systematic review assesses the literature for changes in aerosol-contamination levels when rotary instruments are used, (1) as distance increases from patient’s mouth; (2) as time passes after the procedure; and (3) when using different types of handpieces. Methods: The review methods and reporting are in line with PRISMA statements. A structured search was conducted over five platforms (September 2021). Studies were assessed independently by two reviewers. To be eligible studies had to assess changes in levels of aerosol contamination over different distances, and time points, with rotary hand instruments. Studies’ methodologies and the sensitivity of the contamination-measurement approaches were evaluated. Results are presented descriptively. Results: From 422 papers identified, 23 studies were eligible. All investigated restorative procedures using rotary instruments and one study additionally looked at orthodontic bracket adhesive material removal. The results suggest contamination is significantly reduced over time and distance. However, for almost all studies that investigated these two factors, the sizes of the contaminated particles were not considered, and there were inconclusive findings regarding whether electric-driven handpieces generate lower levels of contaminated particles. Conclusion: Aerosol contamination levels reduce as distances, and post-procedure times increase. However, there was sparce and inconsistent evidence on the clearing time and no conclusions could be drawn. High-speed handpieces produce significantly higher levels of contamination than slow-speed ones, and to a lesser extent, micro-motor handpieces. However, when micro-motor handpieces were used with water, the contamination levels rose and were similar to high-speed handpiece contamination levels

Project-Based Learning in Introductory Statistics: Comparing Course Experiences and Predicting Positive Outcomes for Students from Diverse Educational Settings

In order to evaluate the acceptability and potential impact of the Passion-Driven Statistics curriculum, this article describes background characteristics, and course experiences and outcomes of students enrolled in the multidisciplinary, introductory, project-based course in liberal arts colleges, large state universities, regional college/universities, and community colleges. We found that the course could be successfully delivered across these diverse educational settings. After controlling for educational setting and pre-survey responses to individual outcome measures, consistent predictors of positive course outcomes included student’s initial interest in conducting research, their higher likelihood of enrolling in a statistics course if it were not required, finding the project-based course less challenging, and finding the research project more rewarding than other students. Regional college/university, and community college students reported working significantly harder in the course and finding the course more challenging than students taking the course at liberal arts colleges or state universities. Students from liberal arts colleges generally reported more positive course experiences than students from other educational settings. However, when compared to students from both liberal arts colleges and large state universities, those from regional colleges/universities reported being more likely to have learned more in the project-based course than in other college courses they had taken. Taken together, the project-based course was successfully delivered across diverse post-secondary educational settings and provides a promising model for getting students hooked on the power and excitement of applied statistics

Hierarchical Star Formation in Nearby LEGUS Galaxies

Hierarchical structure in ultraviolet images of 12 late-type LEGUS galaxies is studied by determining the numbers and fluxes of nested regions as a function of size from ~1 to ~200 pc, and the number as a function of flux. Two starburst dwarfs, NGC 1705 and NGC 5253, have steeper number-size and flux-size distributions than the others, indicating high fractions of the projected areas filled with star formation. Nine subregions in 7 galaxies have similarly steep number-size slopes, even when the whole galaxies have shallower slopes. The results suggest that hierarchically structured star-forming regions several hundred parsecs or larger represent common unit structures. Small galaxies dominated by only a few of these units tend to be starbursts. The self-similarity of young stellar structures down to parsec scales suggests that star clusters form in the densest parts of a turbulent medium that also forms loose stellar groupings on larger scales. The presence of super star clusters in two of our starburst dwarfs would follow from the observed structure if cloud and stellar subregions more readily coalesce when self-gravity in the unit cell contributes more to the total gravitational potential.Comment: 9 pages, 4 figures, accepted for ApJ

Is the pharmacy profession innovative enough?: meeting the needs of Australian residents with chronic conditions and their carers using the nominal group technique

Background Community pharmacies are ideally located as a source of support for people with chronic conditions. Yet, we have limited insight into what innovative pharmacy services would support this consumer group to manage their condition/s. The aim of this study was to identify what innovations people with chronic conditions and their carers want from their ideal community pharmacy, and compare with what pharmacists and pharmacy support staff think consumers want. Methods We elicited ideas using the nominal group technique. Participants included people with chronic conditions, unpaid carers, pharmacists and pharmacy support staff, in four regions of Australia. Themes were identified via thematic analysis using the constant comparison method. Results Fifteen consumer/carer, four pharmacist and two pharmacy support staff groups were conducted. Two overarching themes were identified: extended scope of practice for the pharmacist and new or improved pharmacy services. The most innovative role for Australian pharmacists was medication continuance, within a limited time-frame. Consumers and carers wanted improved access to pharmacists, but this did not necessarily align with a faster or automated dispensing service. Other ideas included streamlined access to prescriptions via medication reminders, electronic prescriptions and a chronic illness card. Conclusions This study provides further support for extending the pharmacist’s role in medication continuance, particularly as it represents the consumer’s voice. How this is done, or the methods used, needs to optimise patient safety. A range of innovative strategies were proposed and Australian community pharmacies should advocate for and implement innovative approaches to improve access and ensure continuity of care