Production and Processing of siRNA Precursor Transcripts from the Highly Repetitive Maize Genome

Mutations affecting the maintenance of heritable epigenetic states in maize identify multiple RNA–directed DNA methylation (RdDM) factors including RMR1, a novel member of a plant-specific clade of Snf2-related proteins. Here we show that RMR1 is necessary for the accumulation of a majority of 24 nt small RNAs, including those derived from Long-Terminal Repeat (LTR) retrotransposons, the most common repetitive feature in the maize genome. A genetic analysis of DNA transposon repression indicates that RMR1 acts upstream of the RNA–dependent RNA polymerase, RDR2 (MOP1). Surprisingly, we show that non-polyadenylated transcripts from a sampling of LTR retrotransposons are lost in both rmr1 and rdr2 mutants. In contrast, plants deficient for RNA Polymerase IV (Pol IV) function show an increase in polyadenylated LTR RNA transcripts. These findings support a model in which Pol IV functions independently of the small RNA accumulation facilitated by RMR1 and RDR2 and support that a loss of Pol IV leads to RNA Polymerase II–based transcription. Additionally, the lack of changes in general genome homeostasis in rmr1 mutants, despite the global loss of 24 nt small RNAs, challenges the perceived roles of siRNAs in maintaining functional heterochromatin in the genomes of outcrossing grass species

Liquid atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry adds enhanced functionalities to MALDI MS profiling for disease diagnostics

A liquid matrix-assisted laser desorption/ionization (liquid MALDI) method has been developed for high-throughput atmospheric pressure (AP) mass spectrometry (MS) analysis of the molecular content of crude bioliquids for disease diagnostics. The presented method is rapid and highly robust, enabling its application in environments where speed and low-cost high-throughput analyses are required. Importantly, because of the creation of multiply charged analyte ions, it provides additional functionalities that conventional solid MALDI MS profiling is lacking, including the use of high-performance mass analyzers with limited m/z range. The concomitant superior MS/MS performance that is achieved similar to ESI MS/MS adds greater analytical power and specificity to MALDI MS profiling while retaining the advantages of a fast laser-based analysis system and off-line large-scale sample preparation. The potential of this MALDI MS profiling method is demonstrated on the detection of dairy cow mastitis, which is a substantial economic burden on the dairy industry with losses of hundreds of dollars per diseased cow per year, equating to a total annual loss of billions of dollars, as well as leading to the use of large quantities of antibiotics, adding to the proliferation of antimicrobial resistance. Only small amounts of aliquots obtained from the daily farm milking process were prepared for liquid MALDI MS profiling using a simple one-pot/two-step analyte extraction. Automated analysis was performed using a custom-built AP-MALDI ion source, enabling the simultaneous detection of lipids, peptides, and proteins. Diagnostic, multiply charged, proteinaceous ions were easily sequenced and identified by MS/MS experiments. Samples were classified according to mastitis status using multivariate analysis, achieving 98.5% accuracy (100% specificity) determined by “leave 20% out” cross-validation. The methodology is generally applicable to AP-MALDI MS profiling on most commercial high-resolution mass spectrometers, with the potential for expansion into hospitals for rapid assessment of human and other biofluids

Does acute exercise affect the performance of whole-body, psychomotor skills in an inverted-U fashion?:a meta-analytic investigation

The primary purpose of this study was to examine, using meta-analytical measures, whether research into the performance of whole-body, psychomotor tasks following moderate and heavy exercise demonstrates an inverted-U effect. A secondary purpose was to compare the effects of acute exercise on tasks requiring static maintenance of posture versus dynamic, ballistic skills. Moderate intensity exercise was determined as being between 40% and 79% maximum power output (ẆMAX) or equivalent, while ≥ 80% ẆMAX was considered to be heavy. There was a significant difference (Zdiff = 4.29, p = 0.001, R2 = 0.42) between the mean effect size for moderate intensity exercise (g = 0.15) and that for heavy exercise size (g = − 0.86). These data suggest a catastrophe effect during heavy exercise. Mean effect size for static tasks (g = − 1.24) was significantly different (Zdiff = 3.24, p = 0.001, R2 = 0.90) to those for dynamic/ballistic tasks (g = − 0.30). The result for the static versus dynamic tasks moderating variables point to perception being more of an issue than peripheral fatigue for maintenance of static posture. The difference between this result and those found in meta-analyses examining the effects of acute exercise on cognition shows that, when perception and action are combined, the complexity of the interaction induces different effects to when cognition is detached from motor performance

A Socio-Spatial Approach to Enable Inclusive Well-Being in Cities: A Case Study of Birmingham, UK

This article examines density and deprivation, the two important parameters that define health and well-being in cities. Discussions are drawn from a case study conducted in Birmingham in four neighborhoods characterized by their different population density and deprivation levels. Data were collected through questionnaires developed from a set of subjective well-being measures and built environment audits, based on the Irvine Minnesota Inventory that evaluates the quality of streets and walkability in neighborhoods. The inferences from the study support the need for linking health, planning, policy and design research and decision-making to the socio-spatial practices of people, impacting well-being at the everyday level. The findings provide a holistic approach health and well-being research and suggests a conceptual framework for inclusive well-being in cities, which signifies the role of social and spatial parameters in determining peoples’ health and well-being. The study also highlights the lack of interdisciplinary research in understanding the association between well-being and social and behavioral practices in diverse communities

Visualising spatio-temporal health data: the importance of capturing the 4th dimension

Confronted by a rapidly evolving health threat, such as an infectious disease outbreak, it is essential that decision-makers are able to comprehend the complex dynamics not just in space but also in the 4th dimension, time. In this paper this is addressed by a novel visualisation tool, referred to as the Dynamic Health Atlas web app, which is designed specifically for displaying the spatial evolution of data over time while simultaneously acknowledging its uncertainty. It is an interactive and open-source web app, coded predominantly in JavaScript, in which the geospatial and temporal data are displayed side-by-side. The first of two case studies of this visualisation tool relates to an outbreak of canine gastroenteric disease in the United Kingdom, where many veterinary practices experienced an unusually high case incidence. The second study concerns the predicted COVID-19 reproduction number along with incidence and prevalence forecasts in each local authority district in the United Kingdom. These studies demonstrate the effectiveness of the Dynamic Health Atlas web app at conveying geospatial and temporal dynamics along with their corresponding uncertainties.Comment: 4 Figures, 27 page

MTHFD1 controls DNA methylation in Arabidopsis.

DNA methylation is an epigenetic mechanism that has important functions in transcriptional silencing and is associated with repressive histone methylation (H3K9me). To further investigate silencing mechanisms, we screened a mutagenized Arabidopsis thaliana population for expression of SDCpro-GFP, redundantly controlled by DNA methyltransferases DRM2 and CMT3. Here, we identify the hypomorphic mutant mthfd1-1, carrying a mutation (R175Q) in the cytoplasmic bifunctional methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase (MTHFD1). Decreased levels of oxidized tetrahydrofolates in mthfd1-1 and lethality of loss-of-function demonstrate the essential enzymatic role of MTHFD1 in Arabidopsis. Accumulation of homocysteine and S-adenosylhomocysteine, genome-wide DNA hypomethylation, loss of H3K9me and transposon derepression indicate that S-adenosylmethionine-dependent transmethylation is inhibited in mthfd1-1. Comparative analysis of DNA methylation revealed that the CMT3 and CMT2 pathways involving positive feedback with H3K9me are mostly affected. Our work highlights the sensitivity of epigenetic networks to one-carbon metabolism due to their common S-adenosylmethionine-dependent transmethylation and has implications for human MTHFD1-associated diseases

Know The Star, Know the Planet. IV. A Stellar Companion to the Host star of the Eccentric Exoplanet HD 8673b

HD 8673 hosts a massive exoplanet in a highly eccentric orbit (e=0.723). Based on two epochs of speckle interferometry a previous publication identified a candidate stellar companion. We observed HD 8673 multiple times with the 10 m Keck II telescope, the 5 m Hale telescope, the 3.63 m AEOS telescope and the 1.5m Palomar telescope in a variety of filters with the aim of confirming and characterizing the stellar companion. We did not detect the candidate companion, which we now conclude was a false detection, but we did detect a fainter companion. We collected astrometry and photometry of the companion on six epochs in a variety of filters. The measured differential photometry enabled us to determine that the companion is an early M dwarf with a mass estimate of 0.33-0.45 M?. The companion has a projected separation of 10 AU, which is one of the smallest projected separations of an exoplanet host binary system. Based on the limited astrometry collected, we are able to constrain the orbit of the stellar companion to a semi-major axis of 35{60 AU, an eccentricity ? 0.5 and an inclination of 75{85?. The stellar companion has likely strongly in uenced the orbit of the exoplanet and quite possibly explains its high eccentricity.Comment: Accepted to the Astronomical Journal, 6 Pages, 5 Figure

Somatic PDGFRB activating variants in fusiform cerebral aneurysms

The role of somatic genetic variants in the pathogenesis of intracranial-aneurysm formation is unknown. We identified a 23-year-old man with progressive, right-sided intracranial aneurysms, ipsilateral to an impressive cutaneous phenotype. The index individual underwent a series of genetic evaluations for known connective-tissue disorders, but the evaluations were unrevealing. Paired-sample exome sequencing between blood and fibroblasts derived from the diseased areas detected a single novel variant predicted to cause a p.Tyr562Cys (g.149505130T>C [GRCh37/hg19]; c.1685A>G) change within the platelet-derived growth factor receptor β gene (PDGFRB), a juxtamembrane-coding region. Variant-allele fractions ranged from 18.75% to 53.33% within histologically abnormal tissue, suggesting post-zygotic or somatic mosaicism. In an independent cohort of aneurysm specimens, we detected somatic-activating PDGFRB variants in the juxtamembrane domain or the kinase activation loop in 4/6 fusiform aneurysms (and 0/38 saccular aneurysms; Fisher's exact test, p < 0.001). PDGFRB-variant, but not wild-type, patient cells were found to have overactive auto-phosphorylation with downstream activation of ERK, SRC, and AKT. The expression of discovered variants demonstrated non-ligand-dependent auto-phosphorylation, responsive to the kinase inhibitor sunitinib. Somatic gain-of-function variants in PDGFRB are a novel mechanism in the pathophysiology of fusiform cerebral aneurysms and suggest a potential role for targeted therapy with kinase inhibitors