RESUMEN
The mitotic checkpoint (also called spindle assembly checkpoint, SAC) is a signaling pathway that safeguards proper chromosome segregation. Correct functioning of the SAC depends on adequate protein concentrations and appropriate stoichiometries between SAC proteins. Yet very little is known about the regulation of SAC gene expression. Here, we show in the fission yeast Schizosaccharomyces pombe that a combination of short mRNA half-lives and long protein half-lives supports stable SAC protein levels. For the SAC genes mad2+ and mad3+ , their short mRNA half-lives are caused, in part, by a high frequency of nonoptimal codons. In contrast, mad1+ mRNA has a short half-life despite a higher frequency of optimal codons, and despite the lack of known RNA-destabilizing motifs. Hence, different SAC genes employ different strategies of expression. We further show that Mad1 homodimers form co-translationally, which may necessitate a certain codon usage pattern. Taken together, we propose that the codon usage of SAC genes is fine-tuned to ensure proper SAC function. Our work shines light on gene expression features that promote spindle assembly checkpoint function and suggests that synonymous mutations may weaken the checkpoint.
Asunto(s)
Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Uso de Codones , Expresión Génica , Cinetocoros/metabolismo , Puntos de Control de la Fase M del Ciclo Celular/genética , Proteínas Mad2/metabolismo , ARN Mensajero/metabolismo , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Huso Acromático/genética , Huso Acromático/metabolismoRESUMEN
Trace soil minerals are a critical determinant of both crop productivity and the mineral concentration of crops, therefore potentially impacting the nutritional status of human populations relying on those crops. We link health data from nearly 0.3 million children and one million adult women across India with over 27 million soil tests drawn from a nationwide soil health program. We find that soil zinc availability is positively associated with children's linear height growth, and soil iron availability is positively associated with hemoglobin levels. The link between soil zinc and childhood stunting is particularly robust-a one standard deviation increase in satisfactory soil zinc tests is associated with approximately 11 fewer children stunted per 1000. We also find that this zinc-stunting relationship is strongest in wealthier households. Our results suggest that soil mineral availability impacts human nutritional status and health in at least some areas of India, and that agronomic fortification may be a beneficial intervention.
Asunto(s)
Micronutrientes , Suelo , Adulto , Niño , Humanos , Femenino , India/epidemiología , Zinc , Trastornos del Crecimiento/epidemiologíaRESUMEN
People living near oil and gas development are exposed to multiple environmental stressors that pose health risks. Some studies suggest these risks are higher for racially and socioeconomically marginalized people, which may be partly attributable to disparities in exposures. We examined whether racially and socioeconomically marginalized people in California are disproportionately exposed to oil and gas wells and associated hazards. We longitudinally assessed exposure to wells during three time periods (2005-2009, 2010-2014, and 2015-2019) using sociodemographic data at the census block group-level. For each block group and time period, we assessed exposure to new, active, retired, and plugged wells, and cumulative production volume. We calculated risk ratios to determine whether marginalized people disproportionately resided near wells (within 1 km). Averaged across the three time periods, we estimated that 1.1 million Californians (3.0%) lived within 1 km of active wells. Nearly 9 million Californians (22.9%) lived within 1 km of plugged wells. The proportion of Black residents near active wells was 42%-49% higher than the proportion of Black residents across California, and the proportion of Hispanic residents near active wells was 4%-13% higher than their statewide proportion. Disparities were greatest in areas with the highest oil and gas production, where the proportion of Black residents was 105%-139% higher than statewide. Socioeconomically marginalized residents also had disproportionately high exposure to wells. Though oil and gas production has declined in California, marginalized communities persistently had disproportionately high exposure to wells, potentially contributing to health disparities.