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Wind variability has a major impact on water cycles, wind energy, and natural hazards and disasters such as hurricanes and typhoons. In the past decades, the global and regional mean near-surface wind speed (sfcWind) has shown a significantly downward trend, especially in the mid-latitudes in the Northern Hemisphere (Wu et al. 2018). The global mean terrestrial sfcWind has decreased linearly at a rate of 0.08 m s−1 per decade during 1981–2011. Vautard et al. (2010) analyzed changes in sfcWind at stations across the globe and found that 73% of the total stations presented a decrease in the annual mean sfcWind, with linear trends of −0.09, −0.16, −0.12, and −0.07 m s−1 per decade in Europe, Central Asia, East Asia, and North America, respectively. In addition, a pronounced reduction in extreme sfcWind has also been observed in Europe and the United States (Yan et al. 2002; Pryor et al. 2012). However, because long-term observational data are lacking in most land areas and oceans, the uncertainty in the long-term trend of sfcWind is high, particularly in the Southern Hemisphere and over oceans.

SummaryGenetically encoded DNA recorders noninvasively convert transient biological events into durable mutations in a cell’s genome, allowing for the later reconstruction of cellular experiences using high-throughput DNA sequencing1. Existing DNA recorders have achieved high-information recording2–14, durable recording3,5–10,13,15–18, prolonged recording over multiple timescales3,5,8,10, multiplexed recording of several user-selected signals5–8,18, and temporally resolved signal recording5–8,18, but not all at the same time. We present a DNA recorder called peCHYRON (prime editing19 Cell HistorY Recording by Ordered iNsertion) that does. In peCHYRON, prime editor guide RNAs19 (pegRNAs) insert a variable triplet DNA sequence alongside a constant propagation sequence that deactivates the previous and activates the next step of insertion. This process results in the sequential accumulation of regularly spaced insertion mutations at a synthetic locus. Accumulated insertions are permanent throughout editing because peCHYRON uses a prime editor that avoids cutting both DNA strands, which risks deletions. Editing continues indefinitely because each insertion adds the complete sequence needed to initiate the next step. Constitutively expressed pegRNAs generate insertion patterns that support straightforward reconstruction of cell lineage relationships. Pulsed expression of different pegRNAs enables the reconstruction of pulse sequences, which may be coupled to biological stimuli for temporally-resolved multiplexed event recording.

Background Accurate early detection of pregnancy status is a prerequisite for effective monitoring of fertility in pig. In the early phase of pregnancy, because the embryo is small and in a free state, it is difficult to determine whether it is pregnant based on B-ultrasound examination. This calls for development of novel tools to accurately diagnose early pregnancy. Metabolomics reveal the metabolic status of cells, tissues and organisms. Results In this study, we investigated urinary metabolites in sows during early pregnancy. A total of 32 samples from 8 sows were collected at estrus and each phase of early pregnancy (days 9, 12, and 15 of gestation). Metabolites in urine samples from different sows obtained from gestation and estrus phases were analyzed via ultra-high performance liquid chromatography/mass spectrometry. A total of 530 metabolites were identified with high confidence in all samples. Compared with samples collected during the estrus phase, 269 differential metabolites were found in samples obtained during early pregnancy. Conclusions These metabolites included lipids and lipid-like molecules, organic acids and their derivatives, organic oxygen compounds, organoheterocyclic compounds, benzenoids, among others. These metabolites, such as choline and pregnanediol-3-glucuronide, play a very important role in pregnancy. They also regulate pregnancy in other animals. Our results provide novel insights into the metabolic changes in the urine of sows in the early pregnancy phase. The level of different metabolites in urine can be used to diagnosis pregnancy in sows. Understanding these metabolic changes is helpful for better management of pregnant sows.

Background Embryo implantation in sows is an important event during pregnancy. During this process, blastocysts undergo dramatic morphologic changes, and the endometrium becomes receptive. Studies have shown that developmental changes associated with the crosstalk between peri-implantation embryos and embryo-uterine are driven by various biomolecules secreted by the endometrium and embryos. In sows, changes in the uterus are also reflected in circulating body fluids and urine. Metabolomics reveals the metabolic state of cells, tissues, and organisms. In this study, we collected urine samples from large white sows during the peri-implantation period. The levels of urinary metabolites at different periods were analyzed using ultra-performance liquid chromatography/tandem mass spectrometry (UPLC–MS/MS) analysis techniques. Results A total of 32 samples were collected from 8 sows during the estrus period and at each phase of early pregnancy (9, 12, and 15 days of gestation). A total of 530 metabolites were identified with high confidence in all samples. Compared with samples collected during the estrus phase, 269 differential metabolites were found in samples obtained during early pregnancy. Conclusions The identified metabolites included lipids and lipid-like molecules, organic acids and their derivatives, organic oxygen compounds, organoheterocyclic compounds, benzenoids, among others. Metabolites, such as choline and pregnanediol-3-glucuronide, play important roles in pregnancy in sows and other animals. These results reveal the metabolic changes in urine of sows during early pregnancy phase. The differential urinary metabolites can be used for assessing peri-implantation status in sows. Understanding these metabolic changes may promote the management of pregnant sows through various interventions such as provision of proper nutrition.

Studying cellular and developmental processes in complex multicellular organisms can require the non-destructive observation of thousands to billions of cells deep within an animal. DNA recorders address the staggering difficulty of this task by converting transient cellular experiences into mutations at defined genomic sites that can be sequenced later in high throughput. However, existing recorders act primarily by erasing DNA. This is problematic because, in the limit of progressive erasure, no record remains. We present a DNA recorder called CHYRON (Cell History Recording by Ordered Insertion) that acts primarily by writing new DNA through the repeated insertion of random nucleotides at a single locus in temporal order. To achieve in vivo DNA writing, CHYRON combines Cas9, a homing guide RNA and the template-independent DNA polymerase terminal deoxynucleotidyl transferase. We successfully applied CHYRON as an evolving lineage tracer and as a recorder of user-selected cellular stimuli.

Non-spliceosomal splicing factors are essential, conserved regulators of alternative splicing. They provide concentration-dependent control of diverse pre-mRNAs. Many splicing factors direct unproductive splicing of their own pre-mRNAs through negative autoregulation. However, the impact of such feedback loops on splicing dynamics at the single cell level remains unclear. We developed a system to dynamically, quantitatively analyze negative autoregulatory splicing by the SF2 splicing factor in response to perturbations in single HEK293 cells. Here, we show that negative autoregulatory splicing provides critical functions for gene regulation, establishing a ceiling of SF2 protein concentration, reducing cell-cell heterogeneity in SF2 levels, and buffering variation in SF2 transcription. Most importantly, it adapts SF2 splicing activity to variations in demand from other pre-mRNA substrates. A minimal mathematical model of autoregulatory splicing explains these experimentally observed features, and provides values for effective biochemical parameters. These results reveal the unique functional roles that splicing negative autoregulation plays in homeostatically regulating transcriptional programs.

SummaryThe study of intricate cellular and developmental processes in the context of complex multicellular organisms is difficult because it can require the non-destructive observation of thousands, millions, or even billions of cells deep within an animal. To address this difficulty, several groups have recently reported CRISPR-based DNA recorders that convert transient cellular experiences and processes into changes in the genome, which can then be read by sequencing in high-throughput. However, existing DNA recorders act primarily byerasingDNA: they use the random accumulation of CRISPR-induced deletions to record information. This is problematic because in the limit of progressive deletion, no record remains. Here, we present a new type of DNA recorder that acts primarily bywritingnew DNA. Our system, called CHYRON (Cell HistorY Recording by Ordered iNsertion), inserts random nucleotides at a single locus in temporal orderin vivoand can be applied as an evolving lineage tracer as well as a recorder of user-selected cellular stimuli. As a lineage tracer, CHYRON allowed us to perfectly reconstruct the population lineage relationships among 16 groups of human cells descended from four starting groups that were subject to a series of splitting steps. In this experiment, CHYRON progressively wrote and retained base insertions in 20% percent of cells where the average amount written was 8.4 bp (~14.5 bits), reflecting high information content and density. As a stimulus recorder, we showed that when the CHYRON machinery was placed under the control of a stress-responsive promoter, the frequency and length of writing reflected the dose and duration of the stress. We believe CHYRON represents a conceptual advance in DNA recording technologies where writing rather than erasing becomes the primary mode of information accumulation. With further engineering of CHYRON’s components to increase writing efficiency, CHYRON should lead to single-cell-resolution recording of lineage and other information through long periods of time in complex animals or tumors, advancing the pursuit of a full picture of mammalian development.