A Pilot Urinary Proteome Study Reveals Widespread Influences of Circadian Rhythm Disruption by Sleep Deprivation.

It is widely accepted that circadian rhythm disruption caused short- or long-term adverse effects on health. Although many previous studies have focused on exploration of the molecular mechanisms, there is no rapid, convenient, and non-invasive method to reveal the influence on health after circadian rhythm disruption. Here, we performed a high-resolution mass spectrometry-based data-independent acquisition (DIA) quantitative urinary proteomic approach in order to explore whether urine could reveal stress changes to those brought about by circadian rhythm disruption after sleep deprivation. After sleep deprivation, the subjects showed a significant increase in both systolic and diastolic blood pressure compared with routine sleep. More than 2000 proteins were quantified and they contained specific proteins for various organs throughout the body. And a total of 177 significantly up-regulated proteins and 68 significantly down-regulated proteins were obtained after sleep deprivation. These differentially expressed proteins (DEPs) were associated with multiple organs and pathways, which reflected widespread influences of sleep deprivation. Besides, machine learning identified a panel of five DEPs (CD300A, SCAMP3, TXN2, EFEMP1, and MYH11) that can effectively discriminate circadian rhythm disruption. Taken together, our results validate the value of urinary proteome in predicting and diagnosing the changes by circadian rhythm disruption.

Effects of high-intensity focused ultrasound combined with levonorgestrel-releasing intrauterine system on patients with adenomyosis.

It is very important to treat adenomyosis which may cause infertility, menorrhagia, and dysmenorrhea for women at the reproductive age. High-intensity focused ultrasound (HIFU) is effective in destroying target tumor tissues without damaging the path of the ultrasound beam and surrounding normal tissues. The levonorgestrel-releasing intrauterine system (LN-IUS) is a medical system which is inserted into the uterine to provide medicinal treatment for temporary control of the symptoms caused by adenomyosis. This study was to investigate the effect of HIFU combined with the LN-IUS on adenomyosis. In the HIFU treatment, the parameters of the ultrasound were transmission frequency 0.8 MHz and input power 50-400 W (350 ± 30), and the temperature in the target tissue under these conditions would reach 60-100 °C (85 °C ± 6.3 °C). Size reduction and blood flow signal decrease were used to assess the effect of combined treatment. In this study, 131 patients with adenomyosis treated with HIFU combined with LN-IUS were retrospectively enrolled. The clinical and follow-up data were analyzed. After treatment, the volume of the uterine lesion was significantly decreased with an effective rate of 72.1%, and the adenomyosis blood flow signals were significantly reduced, with an effective rate of 71.3%. At six months, the menstrual cycle was significantly (P < 0.05) decreased from 31.4 ± 3.5 days before treatment to 28.6 ± 1.9 days, the menstrual period was significantly shortened from 7.9 ± 1.2 days before HIFU to 6.5 ± 1.3 days, and the menstrual volume was significantly (P < 0.05) decreased from 100 to 49% ± 13%. The serum hemoglobin significantly (P < 0.05) increased from 90.8 ± 6.2 g/L before treatment to 121.6 ± 10.8 g/L at six months for patients with anemia. Among seventy-two (92.3%) patients who finished the six-month follow-up, sixty-five (90.3%) patients had the dysmenorrhea completely relieved, and the other seven (9.7%) patients had only slight dysmenorrhea which did not affect their daily life. Adverse events occurred in 24 (18.3%) patients without causing severe consequences, including skin burns in two (1.5%) patients, skin swelling in four (3.1%), mild lower abdominal pain and low fever in 15 (11.5%), and subcutaneous induration in three (2.3%). Six months after treatment, no other serious side effects occurred in any patients with follow-up. In conclusions, the use of high-intensity focused ultrasound combined with the levonorgestrel-releasing intrauterine system for the treatment of adenomyosis is safe and effective even though the long-term effect remains to be confirmed.

Strigolactone and gibberellin signaling coordinately regulate metabolic adaptations to changes in nitrogen availability in rice.

Modern semi-dwarf rice varieties of the "Green Revolution" require a high supply of nitrogen (N) fertilizer to produce high yields. A better understanding of the interplay between N metabolism and plant developmental processes is required for improved N-use efficiency and agricultural sustainability. Here, we show that strigolactones (SLs) modulate root metabolic and developmental adaptations to low N availability for ensuring efficient uptake and translocation of available N. The key repressor DWARF 53 (D53) of the SL signaling pathway interacts with the transcription factor GROWTH-REGULATING FACTOR 4 (GRF4) and prevents GRF4 from binding to its target gene promoters. N limitation induces the accumulation of SLs, which in turn promotes SL-mediated degradation of D53, leading to the release of GRF4 and thus promoting the expression of genes associated with N metabolism. N limitation also induces degradation of the DELLA protein SLENDER RICE 1 (SLR1) in an D14- and D53-dependent manner, effectively releasing GRF4 from competitive inhibition caused by SLR1. Collectively, our findings reveal a previously unrecognized mechanism underlying SL and gibberellin crosstalk in response to N availability, advancing our understanding of plant growth-metabolic coordination and facilitating the design of the strategies for improving N-use efficiency in high-yield crops.

Improving Crop Nitrogen Use Efficiency Toward Sustainable Green Revolution.

The Green Revolution of the 1960s improved crop yields in part through the widespread cultivation of semidwarf plant varieties, which resist lodging but require a high-nitrogen (N) fertilizer input. Because environmentally degrading synthetic fertilizer use underlies current worldwide cereal yields, future agricultural sustainability demands enhanced N use efficiency (NUE). Here, we summarize the current understanding of how plants sense, uptake, and respond to N availability in the model plants that can be used to improve sustainable productivity in agriculture. Recent progress in unlocking the genetic basis of NUE within the broader context of plant systems biology has provided insights into the coordination of plant growth and nutrient assimilation and inspired the implementation of a new breeding strategy to cut fertilizer use in high-yield cereal crops. We conclude that identifying fresh targets for N sensing and response in crops would simultaneously enable improved grain productivity and NUE to launch a new Green Revolution and promote future food security.

C. elegans BLMP-1 controls apical epidermal cell morphology by repressing expression of mannosyltransferase bus-8 and molting signal mlt-8.

Skin epidermis secretes apical extracellular matrix (aECM) as a protective barrier from the external environment. The aECM is highly dynamic and constantly undergoes remodeling during animal development. How aECM dynamics is temporally regulated during development, and whether and how its mis-regulation may impact epidermal cell morphology or function remains to be fully elucidated. Here, we report that the conserved Zn-finger transcription factor BLMP-1/Blimp1, which regulates epidermal development in C. elegans, controls apical cell shape of the epidermis by downregulation of aECM remodeling. Loss of blmp-1 causes upregulation of genes essential for molting, including bus-8 and mlt-8, in adult, leading to an abnormal shape in the apical region of adult epidermal cells. The apical epidermal morphological defect is suppressed by reduction of bus-8 or mlt-8. BUS-8 is a key mannosyltransferase, which functions in glycosylation of N-linked glycoproteins; MLT-8 has a ganglioside GM2 lipid-binding domain and is implicated in signaling during molting, a process where the old cuticle is shed and synthesized anew. Overexpression of bus-8 or mlt-8 induces an apical epidermal cell defect as observed in blmp-1 mutants. MLT-8::GFP fusion protein is localized to lysosomes and secreted to aECM. BUS-8 is important for MLT-8 stability and lysosomal targeting, which may be regulated by BUS-8-mediated glycosylation of MLT-8 and function as a molting signaling cue in aECM remodeling. We propose that BLMP-1 represses MLT-8 expression and glycosylation in the epidermis to prevent inappropriate aECM remodeling, which is essential for maintenance of apical epidermal cell morphology during larva-to-adult transition.

The complete chloroplast genome sequence of Japanese buttercup Ranunculus japonicus Thunb.

Ranunculus japonicus is an important medicinal herb widely used in East Asia. In this study, we report the first complete chloroplast genome sequence of Ranunculus japonicus using next-generation sequencing technology. The chloroplast genome size of R. japonicus was 156,981 bp. A total of 129 genes were included, consisting 84 protein-coding genes, eight rRNA genes, and 37 tRNA genes. Thirteen protein-coding genes had intron (ycf3 gene, rps12 gene, rps12 gene, clpP gene contained two introns). A further phylogenomic analysis of Ranunculaceae, including 10 taxa, was conducted for assessing the placement of R. japonicus. It will provide valuable genetic information for this medicinally important species.

BLMP-1 promotes developmental cell death in C. elegans by timely repression of ced-9 transcription.

Programmed cell death (PCD) is a common cell fate in metazoan development. PCD effectors are extensively studied, but how they are temporally regulated is less understood. Here, we report a mechanism controlling tail-spike cell death onset during Caenorhabditis elegans development. We show that the zinc-finger transcription factor BLMP-1, which controls larval development timing, also regulates embryonic tail-spike cell death initiation. BLMP-1 functions upstream of CED-9 and in parallel to DRE-1, another CED-9 and tail-spike cell death regulator. BLMP-1 expression is detected in the tail-spike cell shortly after the cell is born, and blmp-1 mutations promote ced-9-dependent tail-spike cell survival. BLMP-1 binds ced-9 gene regulatory sequences, and inhibits ced-9 transcription just before cell-death onset. BLMP-1 and DRE-1 function together to regulate developmental timing, and their mammalian homologs regulate B-lymphocyte fate. Our results, therefore, identify roles for developmental timing genes in cell-death initiation, and suggest conservation of these functions.

The complete chloroplast genome sequence of wild Japanese pepper Tubocapsicum anomalum Makino (Solanaceae).

As an important medicinal herb, no complete organelle molecular data has been reported for Tubocapsicum anomalum. In this study, the first complete chloroplast genome of Tubocapsicum anomalum Makino was sequenced and assembled. The genome is 155,802 bp in length and contained 124 encoded genes in total, including 75 protein-coding genes, 10 ribosomal RNA genes, and 39 transfer RNA genes. The phylogenomic analysis showed that Tubocapsicum anomalum was closely related to Withania somnifera according the current sampling extent.

The complete chloroplast genome of balsam aster (Aster ageratoides Turcz. var. scaberulus (Miq.) Ling., Asteraceae).

The first complete chloroplast genome of Aster ageratoides Turcz. var. scaberulus (Miq.) Ling. is reported in this study. The total chloroplast genome size of A. ageratoides var. scaberulus was 153,071 bp and comprised of a large single-copy region (LSC with 84,896 bp), a small single-copy region (SSC with 18,269 bp), and two inverted repeat regions (IR with 24,953 bp). A total of 122 genes were included in the genome, including 83 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. Eleven protein-coding genes had intron (ycf3, clpP and rps12 gene contained two introns. Further phylogenomic analysis of Asteraceae, including 13 taxa, was conducted for the placement of A. ageratoides var. scaberulus.

Two receptor-like protein kinases, MUSTACHES and MUSTACHES-LIKE, regulate lateral root development in Arabidopsis thaliana.

Receptor-like protein kinases (RLKs) play key roles in regulating plant growth, development and stress adaptations. There are at least 610 RLKs (including receptor-like cytoplasmic kinases) in Arabidopsis. The functions of the majority of RLKs have not yet been determined. We previously generated promoter::GUS transgenic plants for all leucine-rich repeat (LRR)-RLKs in Arabidopsis and analyzed their expression patterns during various developmental stages. We found the expression of two LRR-RLKs, MUSTACHES (MUS) and MUSTACHES-LIKE (MUL), are overlapped in lateral root primordia. Independent mutants, mus-3 mul-1 and mus-4 mul-2, show a significantly decreased emerged lateral root phenotype. Our analyses indicate that the defects of the double mutant occur mainly at stage I of lateral root development. Exogenous application of auxin can dramatically enhance the transcription of MUS, which is largely dependent on AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19. MUS and MUL are inactive kinases in vitro but are phosphorylated in planta, possibly by an unknown kinase. The kinase activity of MUS is dispensable for its function in lateral root development. Many cell wall related genes are down regulated in mus-3 mul-1. In conclusion, we identified MUS and MUL, two kinase-inactive RLKs, in controlling the early development of lateral root primordia likely via regulating cell wall synthesis and remodeling.

Genome-Wide Expression Pattern Analyses of the Arabidopsis Leucine-Rich Repeat Receptor-Like Kinases.

Receptor-like protein kinases (RLKs) are a large group of transmembrane proteins playing critical roles in cell-cell and cell-environment communications. Based on extracellular domain structures, RLKs were classified into more than 21 subfamilies, among which leucine-rich repeat RLKs (LRR-RLKs) belong to the largest subfamily in plants such as Arabidopsis and rice. In Arabidopsis, there are approximately 223 LRR-RLKs, but only about 60 of which have been functionally described to date. To systematically investigate the roles of LRR-RLKs in regulating plant growth, development, and stress adaptations, we generated promoter::GUS transgenic plants for all 223 LRR-RLK genes in Arabidopsis and analyzed their detailed expression patterns at various developmental stages. The results provide valuable resources for functionally elucidating this large and essential signaling protein subfamily.

BLMP-1/Blimp-1 regulates the spatiotemporal cell migration pattern in C. elegans.

Spatiotemporal regulation of cell migration is crucial for animal development and organogenesis. Compared to spatial signals, little is known about temporal signals and the mechanisms integrating the two. In the Caenorhabditis elegans hermaphrodite, the stereotyped migration pattern of two somatic distal tip cells (DTCs) is responsible for shaping the gonad. Guidance receptor UNC-5 is necessary for the dorsalward migration of DTCs. We found that BLMP-1, similar to the mammalian zinc finger transcription repressor Blimp-1/PRDI-BF1, prevents precocious dorsalward turning by inhibiting precocious unc-5 transcription and is only expressed in DTCs before they make the dorsalward turn. Constitutive expression of blmp-1 when BLMP-1 would normally disappear delays unc-5 transcription and causes turn retardation, demonstrating the functional significance of blmp-1 down-regulation. Correct timing of BLMP-1 down-regulation is redundantly regulated by heterochronic genes daf-12, lin-29, and dre-1, which regulate the temporal fates of various tissues. DAF-12, a steroid hormone receptor, and LIN-29, a zinc finger transcription factor, repress blmp-1 transcription, while DRE-1, the F-Box protein of an SCF ubiquitin ligase complex, binds to BLMP-1 and promotes its degradation. We have therefore identified a gene circuit that integrates the temporal and spatial signals and coordinates with overall development of the organism to direct cell migration during organogenesis. The tumor suppressor gene product FBXO11 (human DRE-1 ortholog) also binds to PRDI-BF1 in human cell cultures. Our data suggest evolutionary conservation of these interactions and underscore the importance of DRE-1/FBXO11-mediated BLMP-1/PRDI-BF1 degradation in cellular state transitions during metazoan development.