PSEUDO-RESPONSE REGULATORs (PRRs) play overlapping and distinct roles in maintaining circadian rhythms and regulating diverse biological processes, including the photoperiodic control of flowering, ...growth, and abiotic stress responses. PRRs act as transcriptional repressors and associate with chromatin via their conserved C-terminal CCT (CONSTANS, CONSTANS-like, and TIMING OF CAB EXPRESSION 1 TOC1/PRR1) domains by a still-poorly understood mechanism. Here, we identified genome-wide targets of PRR9 using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) and compared them with PRR7, PRR5, and TOC1/PRR1 ChIP-seq data. We found that PRR binding sites are located within genomic regions of low nucleosome occupancy and high DNase I hypersensitivity. Moreover, conserved noncoding regions among Brassicaceae species are enriched around PRR binding sites, indicating that PRRs associate with functionally relevant cis-regulatory regions. The PRRs shared a significant number of binding regions, and our results indicate that they coordinately restrict the expression of target genes to around dawn. A G-box-like motif was overrepresented at PRR binding regions, and we showed that this motif is necessary for mediating transcriptional regulation of CIRCADIAN CLOCK ASSOCIATED 1 and PRR9 by the PRRs. Our results further our understanding of how PRRs target specific promoters and provide an extensive resource for studying circadian regulatory networks in plants.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Cross-sectional studies show that individuals who walk more tend to be thinner than those who walk less. This does not mean, however, that the association between higher step counts and lower weight ...is causal or that encouraging sedentary individuals to increase step counts helps them lose weight.
In this meta-analysis, we searched 6 electronic databases and contacted pedometer experts to identify pedometer-based walking studies without a dietary intervention that reported weight change as an outcome. We included randomized controlled trials and prospective cohort studies published after January 1, 1995, in either English or Japanese, with 5 or more adult participants and at least 1 cohort enrolled in a pedometer-based walking intervention lasting at least 4 weeks.
Nine studies met the study inclusion criteria. Cohort sample size ranged from 15 to 106, for a total of 307 participants, 73% of whom were women and 27% of whom were men. The duration of the intervention ranged from 4 weeks to 1 year, with a median duration of 16 weeks. The pooled estimate of mean weight change from baseline using a fixed-effects model and combining data from all 9 cohorts was -1.27 kg (95% confidence interval, -1.85 to -0.70 kg). Longer intervention duration was associated with greater weight change. On average, participants lost 0.05 kg per week during the interventions.
Pedometer-based walking programs result in a modest amount of weight loss. Longer programs lead to more weight loss than shorter programs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Research shows that a diverse faculty improves academic, clinical, and research outcomes in higher education. Despite that, persons in minority groups, usually categorized by race or ethnicity, are ...underrepresented in academia (URiA). The Nutrition Obesity Research Centers (NORCs), supported by the NIDDK, hosted workshops on five separate days in September and October 2020. NORCs convened these workshops to identify barriers and facilitators for diversity, equity, and inclusion (DEI) and provide specific recommendations to improve DEI within obesity and nutrition for individuals from URiA groups. Recognized experts on DEI presented each day, after which the NORCs conducted breakout sessions with key stakeholders who engage in nutrition and obesity research. The breakout session groups included early-career investigators, professional societies, and academic leadership. The consensus from the breakout sessions was that glaring inequities affect URiA in nutrition and obesity, particularly related to recruitment, retention, and advancement. Recommendations from the breakout sessions to improve DEI across the academe focused on six themes: (1) recruitment, (2) retention, (3) advancement, (4) intersectionality of multiple challenges (e.g., being Black and a woman), (5) funding agencies, and (6) implementation of strategies to address problems related to DEI.
What is already known?Achieving diversity, equity, and inclusion remains a significant challenge in academiaWhat does this study add?This paper adds recommendations for academic universities, professional societies, and funding agencies to correct the underrepresentation in academia of marginalized or minority researchers and faculty.How might these results change the direction of research?These recommendations could improve diversity, equality, and inclusion efforts in the fields of nutrition and obesity.
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CMK, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Our goal was to investigate the effect of a global XYZ median beat construction and the heart vector origin point definition on predictive accuracy of ECG biomarkers of sudden cardiac death (SCD).
...Atherosclerosis Risk In Community study participants with analyzable digital ECGs were included (n = 15,768; 55% female, 73% white, mean age 54.2 ± 5.8 y). We developed an algorithm to automatically detect the heart vector origin point on a median beat. Three different approaches to construct a global XYZ beat and two methods to locate origin point were compared. Global electrical heterogeneity was measured by sum absolute QRST integral (SAI QRST), spatial QRS-T angle, and spatial ventricular gradient (SVG) magnitude, azimuth, and elevation. Adjudicated SCD served as the primary outcome.
There was high intra-observer (kappa 0.972) and inter-observer (kappa 0.984) agreement in a heart vector origin definition between an automated algorithm and a human. QRS was wider in a median beat that was constructed using R-peak alignment than in time-coherent beat (88.1 ± 16.7 vs. 83.7 ± 15.9 ms; P < 0.0001), and on a median beat constructed using QRS-onset as a zeroed baseline, vs. isoelectric origin point (86.7 ± 15.9 vs. 83.7 ± 15.9 ms; P < 0.0001). ROC AUC was significantly larger for QRS, QT, peak QRS-T angle, SVG elevation, and SAI QRST if measured on a time-coherent median beat, and for SAI QRST and SVG magnitude if measured on a median beat using isoelectric origin point.
Time-coherent global XYZ median beat with physiologically meaningful definition of the heart vector's origin point improved predictive accuracy of SCD biomarkers.
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•We developed a method to identify the heart vector's origin on vectorcardiogram.•Origin of the heart vector corresponds to an isoelectric TP (or TQ) segment on ECG.•Time-coherent global XYZ beat properly describes electrophysiology.•Proper beat improves the predictive accuracy of sudden cardiac death biomarkers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The transfer of mitochondrial DNA (mtDNA) into nuclear genomes is a regularly occurring process that has been observed in many species. Few studies, however, have focused on the variation of ...nuclear-mtDNA sequences (NUMTs) within a species. This study examined mtDNA insertions within chromosomes of a diverse set of Zea mays ssp. mays (maize) inbred lines by the use of fluorescence in situ hybridization. A relatively large NUMT on the long arm of chromosome 9 (9L) was identified at approximately the same position in four inbred lines (B73, M825, HP301, and Oh7B). Further examination of the similarly positioned 9L NUMT in two lines, B73 and M825, indicated that the large size of these sites is due to the presence of a majority of the mitochondrial genome; however, only portions of this NUMT (~252 kb total) were found in the publically available B73 nuclear sequence for chromosome 9. Fiber-fluorescence in situ hybridization analysis estimated the size of the B73 9L NUMT to be ~1.8 Mb and revealed that the NUMT is methylated. Two regions of mtDNA (2.4 kb and 3.3 kb) within the 9L NUMT are not present in the B73 mitochondrial NB genome; however, these 2.4-kb and 3.3-kb segments are present in other Zea mitochondrial genomes, including that of Zea mays ssp. parviglumis, a progenitor of domesticated maize.
Pseudo-response regulators associate with overlapping sets of putative target genes and require G-box-like cis-regulatory elements for transcriptional activity.
PSEUDO-RESPONSE REGULATORs (PRRs) play ...overlapping and distinct roles in maintaining circadian rhythms and regulating diverse biological processes, including the photoperiodic control of flowering, growth, and abiotic stress responses. PRRs act as transcriptional repressors and associate with chromatin via their conserved C-terminal CCT (CONSTANS, CONSTANS-like, and TIMING OF CAB EXPRESSION 1 TOC1/PRR1) domains by a still-poorly understood mechanism. Here, we identified genome-wide targets of PRR9 using chromatin immunoprecipitation followed by high-throughput sequencing (
ChIP-seq
) and compared them with PRR7, PRR5, and TOC1/PRR1 ChIP-seq data. We found that PRR binding sites are located within genomic regions of low nucleosome occupancy and high DNase I hypersensitivity. Moreover, conserved noncoding regions among Brassicaceae species are enriched around PRR binding sites, indicating that PRRs associate with functionally relevant cis-regulatory regions. The PRRs shared a significant number of binding regions, and our results indicate that they coordinately restrict the expression of target genes to around dawn. A G-box-like motif was overrepresented at PRR binding regions, and we showed that this motif is necessary for mediating transcriptional regulation of
CIRCADIAN CLOCK ASSOCIATED 1
and
PRR9
by the PRRs. Our results further our understanding of how PRRs target specific promoters and provide an extensive resource for studying circadian regulatory networks in plants.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Despite some notable successes in the control of infectious diseases, transmissible pathogens still pose an enormous threat to human and animal health. The ecological and evolutionary dynamics of ...infections play out on a wide range of interconnected temporal, organizational, and spatial scales, which span hours to months, cells to ecosystems, and local to global spread. Moreover, some pathogens are directly transmitted between individuals of a single species, whereas others circulate among multiple hosts, need arthropod vectors, or can survive in environmental reservoirs. Many factors, including increasing antimicrobial resistance, increased human connectivity and changeable human behavior, elevate prevention and control from matters of national policy to international challenge. In the face of this complexity, mathematical models offer valuable tools for synthesizing information to understand epidemiological patterns, and for developing quantitative evidence for decision-making in global health.
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This study tested the efficacy of two school‐based programs for prevention of body weight/fat gain in comparison to a control group, in all participants and in overweight children. The Louisiana (LA) ...Health study utilized a longitudinal, cluster randomized three‐arm controlled design, with 28 months of follow‐up. Children (N = 2,060; mean age = 10.5 years, SD = 1.2) from rural communities in grades 4–6 participated in the study. Seventeen school clusters (mean = 123 children/cluster) were randomly assigned to one of three prevention arms: (i) primary prevention (PP), an environmental modification (EM) program, (ii) primary + secondary prevention (PP+SP), the environmental program with an added classroom and internet education component, or (iii) control (C). Primary outcomes were changes in percent body fat and BMI z scores. Secondary outcomes were changes in behaviors related to energy balance. Comparisons of PP, PP+SP, and C on changes in body fat and BMI z scores found no differences. PP and PP+SP study arms were combined to create an EM arm. Relative to C, EM decreased body fat for boys (−1.7 ± 0.38% vs. −0.14 ± 0.69%) and attenuated fat gain for girls (2.9 ± 0.22% vs. 3.93 ± 0.37%), but standardized effect sizes were relatively small (<0.30). In conclusion, this school‐based EM programs had modest beneficial effects on changes in percent body fat. Addition of a classroom/internet program to the environmental program did not enhance weight/fat gain prevention, but did impact physical activity and social support in overweight children.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The mitochondrial energy score (MES) protocol, developed by the Myhill group, is marketed as a diagnostic test for chronic fatigue syndrome/Myalgic Encephalomyelitis (CFS/ME). This study assessed the ...reliability and reproducibility of the test, currently provided by private clinics, to assess its potential to be developed as an NHS accredited laboratory test. We replicated the MES protocol using neutrophils and peripheral blood mononuclear cells (PBMCs) from CFS/ME patients (10) and healthy controls (13). The protocol was then repeated in PBMCs and neutrophils from healthy controls to investigate the effect of delayed sample processing time used by the Myhill group. Experiments using the established protocol showed no differences between CFS/ME patients and healthy controls in any of the components of the MES (p ≥ 0.059). Delaying blood sample processing by 24 hours (well within the 72 hour time frame quoted by the Myhill group) significantly altered many of the parameters used to calculate the MES in both neutrophils and PBMCs. The MES test does not have the reliability and reproducibility required of a diagnostic test and therefore should not currently be offered as a diagnostic test for CFS/ME. The differences observed by the Myhill group may be down to differences in sample processing time between cohorts.
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