An enrichment method for temperature-sensitive and auxotrophic mutants of yeast

An enrichment procedure that exploits the difference in heat-sensitivity between exponentially growing and stationary phase cells has been developed for the isolation of yeast mutants. Enrichments of up to 12-fold for temperature-sensitive lethal mutants and of up to 15-fold for auxotrophs have been obtained with single cycles of selection. Still higher enrichments (to frequencies of greater than 90% and 80% for temperature-sensitive lethals and auxotrophs, respectively) have been obtained with multiple cycles of selection. The method requires no special parent strain, and seems adaptable to the selection of a wide variety of types of mutants.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47545/1/438_2004_Article_BF00274022.pd

Disparate phospho-Smad2 levels in advanced type 2 diabetes patients with diabetic neuropathy and early experimental db/db mouse model

Cancer Signaling networks and Molecular Therapeutic

Association of Thyroid dysfunction with cognitive function an individual participant data analysis

IMPORTANCE In clinical guidelines, overt and subclinical thyroid dysfunction are mentioned as causal and treatable factors for cognitive decline. However, the scientific literature on these associations shows inconsistent findings.OBJECTIVE To assess cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia.DESIGN, SETTING, AND PARTICIPANTS This multicohort individual participant data analysis assessed 114 267 person-years (median, 1.7-11.3 years) of follow-up for cognitive function and 525 222 person-years (median, 3.8-15.3 years) for dementia between 1989 and 2017. Analyses on cognitive function included 21 cohorts comprising 38 144 participants. Analyses on dementia included eight cohorts with a total of 2033 cases with dementia and 44 573 controls. Data analysis was performed from December 2016 to January 2021.EXPOSURES Thyroid function was classified as overt hyperthyroidism, subclinical hyperthyroidism, euthyroidism, subclinical hypothyroidism, and overt hypothyroidism based on uniform thyrotropin cutoff values and study-specific free thyroxine values.MAIN OUTCOMES AND MEASURES The primary outcome was global cognitive function, mostly measured using the Mini-Mental State Examination. Executive function, memory, and dementia were secondary outcomes. Analyses were first performed at study level using multivariable linear regression and multivariable Cox regression, respectively. The studies were combined with restricted maximum likelihood meta-analysis. To overcome the use of different scales, results were transformed to standardized mean differences. For incident dementia, hazard ratios were calculated.RESULTS Among 74 565 total participants, 66 567 (89.3%) participants had normal thyroid function, 577 (0.8%) had overt hyperthyroidism, 2557 (3.4%) had subclinical hyperthyroidism, 4167 (5.6%) had subclinical hypothyroidism, and 697 (0.9%) had overt hypothyroidism. The study-specific median age at baseline varied from 57 to 93 years; 42 847 (57.5%) participants were women. Thyroid dysfunction was not associated with global cognitive function; the largest differences were observed between overt hypothyroidism and euthyroidism-cross-sectionally (-0.06 standardized mean difference in score; 95% CI, -0.20 to 0.08; P = .40) and longitudinally (0.11 standardized mean difference higher decline per year; 95% CI, -0.01 to 0.23; P = .09). No consistent associations were observed between thyroid dysfunction and executive function, memory, or risk of dementia.CONCLUSIONS AND RELEVANCE In this individual participant data analysis of more than 74 000 adults, subclinical hypothyroidism and hyperthyroidism were not associated with cognitive function, cognitive decline, or incident dementia. No rigorous conclusions can be drawn regarding the role of overt thyroid dysfunction in risk of dementia. These findings do not support the practice of screening for subclinical thyroid dysfunction in the context of cognitive decline in older adults as recommended in current guidelines.Molecular Epidemiolog

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities 1,2 . This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity 3�6 . Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55 of the global rise in mean BMI from 1985 to 2017�and more than 80 in some low- and middle-income regions�was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing�and in some countries reversal�of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories. © 2019, The Author(s)

Portable Chemical Sensors for Monitoring Infection-Specific Volatiles in Asymptomatic Citrus

Volatile organic compounds (VOCs) are emitted from all plants, and there is mounting evidence these VOCs reflect internal health status and change in response to pathogen infection and other cues. Our group has developed a portable chemical sensing platform that can monitor for VOC emission changes that result from citrus bacterial and viral infections. To date, our VOC library includes putative signal fingerprints for Huanglongbing (HLB), citrus tristeza virus (CTV) and citrus variegated chlorosis (CVC). Our mobile platform is robust and capable of operating in field conditions. We have also developed customized data analysis methods to compare data from unknown samples to our database and to determine the probability of infection for a newly sampled tree

Smad2 Phosphorylation in Diabetic Kidney Tubule Epithelial Cells Is Associated with Modulation of Several Transforming Growth Factor-beta Family Members

Cancer Signaling networks and Molecular Therapeutic