Project description:IntroductionAgricultural workers laboring in thermally stressful environments are at increased risk for kidney injury and chronic kidney disease of unknown origin (CKDu), and their environmental and occupational exposures have been considered to be important risk factors. This study examined the effects of repeated kidney stress from the simultaneous strain of work and other factors experienced by workers in Guatemala during a typical workweek.MethodsWe collected data from 107 sugarcane workers across 7 consecutive work shifts. Data included information on daily occupational, meteorological, environmental, and lifestyle factors. We used multivariable linear mixed models to evaluate associations of these factors with percent change in creatinine.ResultsWe observed that increasing wet bulb globe temperature (β = 2.5%, 95% confidence interval [CI] = 0.3%, 4.7%) and increasing diastolic blood pressure (β = 6.2%, 95% CI = 0.9%, 11.6%) were associated with increases in creatinine across the shift, whereas consumption of water from chlorinated dormitory tanks as compared to artesian well water (β = -17.5%, 95% CI = -29.6%, -5.4%) and increasing number of rest breaks (β = -5.8%, 95% CI = -9.0%, -2.6%) were found to be protective against increases in creatinine. Workers reporting drinking tank water had lower concentrations of urine creatinine-corrected arsenic, lead, uranium, and glyphosate compared to workers reporting the use of well water or municipal water.ConclusionThese results reinforce the need to focus on preventive actions that reduce kidney injury among this worker population, including strategies to reduce heat stress, managing blood pressure, and examining water sources of workers for nephrotoxic contaminants.
Project description:Some metals are beneficial to plants and contribute to critical physiological processes. Some metals, however, are not. The presence of aluminum ions (Al3+) can be very toxic, especially in acidic soils. Considerable parts of the world's arable land are acidic in nature; mechanistically elucidating a plant's response to aluminum stress is critical to mitigating this stress and improving the quality of plants. To identify the genes involved in sugarcane response to aluminum stress, we generated 372 million paired-end RNA sequencing reads from the roots of CTC-2 and RB855453, which are two contrasting cultivars. Data normalization resulted in 162,161 contigs (contiguous sequences) and 97,335 genes from a de novo transcriptome assembly (trinity genes). A total of 4858 and 1307 differently expressed genes (DEGs) for treatment versus control were identified for the CTC-2 and RB855453 cultivars, respectively. The DEGs were annotated into 34 functional categories. The majority of the genes were upregulated in the CTC-2 (tolerant cultivar) and downregulated in RB855453 (sensitive cultivar). Here, we present the first root transcriptome of sugarcane under aluminum stress. The results and conclusions of this study are a crucial launch pad for future genetic and genomic studies of sugarcane. The transcriptome analysis shows that sugarcane tolerance to aluminum may be explained by an efficient detoxification mechanism combined with lateral root formation and activation of redox enzymes. We also present a hypothetical model for aluminum tolerance in the CTC-2 cultivar.
Project description:OBJECTIVE:Identify early biomarkers and mechanisms of acute kidney injury in workers at risk of developing chronic kidney disease of unknown origin (CKDu). METHODS:We assessed cross-shift changes in kidney function and biomarkers of injury in 105 healthy sugarcane workers. We obtained pre-harvest clinical data as well as daily environmental, clinical, and productivity data for each worker. RESULTS:The average percent decline in cross-shift estimated glomerular filtration rate (eGFR) was 21.8% (standard deviation [SD] 13.6%). Increasing wet bulb globe temperature (WBGT), high uric acid, decreased urine pH, urinary leukocyte esterase, and serum hyperosmolality were risk factors for decline in kidney function. CONCLUSIONS:Sugarcane workers with normal kidney function experience recurrent subclinical kidney injury, associated with elevations in biomarkers of injury that suggest exposure to high temperatures and extreme physical demands.
Project description:Statistical learning (SL) is a powerful learning mechanism that supports word segmentation and language acquisition in infants and young adults. However, little is known about how this ability changes over the life span and interacts with age-related cognitive decline. The aims of this study were to: (a) examine the effect of aging on speech segmentation by SL, and (b) explore core mechanisms underlying SL. Across four testing sessions, young, middle-aged, and older adults were exposed to continuous speech streams at two different speech rates, both with and without cognitive load. Learning was assessed using a two-alterative forced-choice task in which words from the stream were pitted against either part-words, which occurred across word boundaries in the stream, or nonwords, which never appeared in the stream. Participants also completed a battery of cognitive tests assessing working memory and executive functions. The results showed that speech segmentation by SL was remarkably resilient to aging, although age effects were visible in the more challenging conditions, namely, when words had to be discriminated from part-words, which required the formation of detailed phonological representations, and when SL was performed under cognitive load. Moreover, an analysis of the cognitive test data indicated that performance against part-words was predicted mostly by memory updating, whereas performance against nonwords was predicted mostly by working memory storage capacity. Taken together, the data show that SL relies on a combination of implicit and explicit skills, and that age effects on SL are likely to be linked to an age-related selective decline in memory updating. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
Project description:BackgroundChronic kidney disease of unknown origin (CKDu) is an epidemic that disproportionately affects young agriculture workers in hot regions. It has been hypothesized that repeated acute kidney injury (AKI) may play a role in the development of disease.MethodsLatent class mixed models were used to identify groups of Guatemalan sugarcane harvesters based on their daily changes in creatinine over 6 consecutive days in 2018. Exponential smoothing state space models were used to forecast end-of-season creatinine between the identified groups. Percent change in estimated glomerular filtration rate (eGFR) across the harvest was compared between groups.ResultsTwenty-nine percent (n = 30) of the 103 workers experienced repeated severe fluctuations in creatinine across shift. The model with multiplicative error, multiplicative trend, and multiplicative seasonality was able to accurately forecast end-of-season creatinine in the severe group (mean percentage error [MPE]: -4.7%). eGFR of workers in the severe group on average decreased 20% across season compared to 11% decline for those in the moderate group (95% confidence interval for difference: -17% to 0%).ConclusionsDaily fluctuations in creatinine can be used to forecast end-of-season creatinine in sugarcane harvesters. Workers who experience repeat severe daily fluctuations in creatinine, on average, experience a greater reduction in kidney function across the season.
Project description:Raised albumin-creatinine ratio (ACR) is an indicator of microvascular damage and renal disease. We aimed to identify genetic variants associated with raised ACR and study the implications of carrying multiple ACR-raising alleles with metabolic and vascular-related disease. We performed a genome-wide association study of ACR using 437 027 individuals from the UK Biobank in the discovery phase, 54 527 more than previous studies, and followed up our findings in independent studies. We identified 62 independent associations with ACR across 56 loci (P < 5 × 10-8), of which 20 were not previously reported. Pathway analyses and the identification of 20 of the 62 variants (at r2 > 0.8) coinciding with signals for at least 16 related metabolic and vascular traits, suggested multiple pathways leading to raised ACR levels. After excluding variants at the CUBN locus, known to alter ACR via effects on renal absorption, an ACR genetic risk score was associated with a higher risk of hypertension, and less strongly, type 2 diabetes and stroke. For some rare genotype combinations at the CUBN locus, most individuals had ACR levels above the microalbuminuria clinical threshold. Contrary to our hypothesis, individuals carrying more CUBN ACR-raising alleles, and above the clinical threshold, had a higher frequency of vascular disease. The CUBN allele effects on ACR were twice as strong in people with diabetes-a result robust to an optimization-algorithm approach to simulating interactions, validating previously reported gene-diabetes interactions (P ≤ 4 × 10-5). In conclusion, a variety of genetic mechanisms and traits contribute to variation in ACR.
Project description:Crossmodal studies have demonstrated inhibitory as well as facilitatory neural effects in higher sensory association and primary sensory cortices. A recent human behavioral study reported touch-induced visual perceptual suppression (TIVS). Here, we introduced an experimental setting in which TIVS could occur and investigated brain activities underlying visuo-tactile interactions using a functional magnetic resonance imaging technique. While the suppressive effect of touch on vision was only found for half of the participants who could maintain their baseline performance above chance level (i.e. TIVS was not well replicated here), we focused on individual differences in the effect of touch on vision. This effect could be suppressive or enhancement, and the neuronal basis of these differences was analyzed. We found larger inhibitory responses in the anterior part of the right visual cortex (V1, V2) with higher TIVS magnitude when visuo-tactile stimuli were presented as spatially congruent. Activations in the right anterior superior temporal region, including the secondary somatosensory cortical area, were more strongly related to those in the visual cortex (V1, V2) with higher TIVS magnitude. These results indicate that inhibitory neural modulations from somatosensory to visual cortices and the resulting inhibitory neural responses in the visual cortex could be involved in TIVS.
Project description:Sunlight is the dominant control on phytoplankton biosynthetic activity, and darkness deprives them of their primary external energy source. Changes in the biochemical composition of phytoplankton communities over diel light cycles and attendant consequences for carbon and energy flux in environments remain poorly elucidated. Here we use lipidomic data from the North Pacific subtropical gyre to show that biosynthesis of energy-rich triacylglycerols (TAGs) by eukaryotic nanophytoplankton during the day and their subsequent consumption at night drives a large and previously uncharacterized daily carbon cycle. Diel oscillations in TAG concentration comprise 23?±?11% of primary production by eukaryotic nanophytoplankton representing a global flux of about 2.4 Pg C yr-1. Metatranscriptomic analyses of genes required for TAG biosynthesis indicate that haptophytes and dinoflagellates are active members in TAG production. Estimates suggest that these organisms could contain as much as 40% more calories at sunset than at sunrise due to TAG production.
Project description:Obesity is a complex, multifactorial disease that is a major public health issue worldwide. Currently approved anti-obesity medications and lifestyle interventions lack the efficacy and durability needed to combat obesity, especially in individuals with more severe forms or coexisting metabolic disorders, such as poorly controlled type 2 diabetes. Bariatric surgery is considered an effective therapeutic modality with sustained weight loss and metabolic benefits. Numerous genetic and environmental factors have been associated with the pathogenesis of obesity, while cumulative evidence has highlighted the gut-brain axis as a complex bidirectional communication axis that plays a crucial role in energy homeostasis. This has led to increased research on the roles of neuroendocrine signaling pathways and various gastrointestinal peptides as key mediators of the beneficial effects following weight-loss surgery. The accumulate evidence suggests that the development of gut-peptide-based agents can mimic the effects of bariatric surgery and thus is a highly promising treatment strategy that could be explored in future research. This article aims to elucidate the potential underlying neuroendocrine mechanisms of the gut-brain axis and comprehensively review the observed changes of gut hormones associated with bariatric surgery. Moreover, the emerging role of post-bariatric gut microbiota modulation is briefly discussed.
Project description:The physiological switch in expression of the embryonic, fetal, and adult β-like globin genes has garnered enormous attention from investigators interested in transcriptional mechanisms and the molecular basis of hemoglobinopathies. These efforts have led to the discovery of cell type-specific transcription factors, unprecedented mechanisms of transcriptional coregulator function, genome biology principles, unique contributions of nuclear organization to transcription and cell function, and promising therapeutic targets. Given the vast literature accrued on this topic, this article will focus on the master regulator of erythroid cell development and function GATA-1, its associated proteins, and its frontline role in controlling hemoglobin synthesis. GATA-1 is a crucial regulator of genes encoding hemoglobin subunits and heme biosynthetic enzymes. GATA-1-dependent mechanisms constitute an essential regulatory core that nucleates additional mechanisms to achieve the physiological control of hemoglobin synthesis.