The arabidopsis RCC1 family protein TCF1 regulates freezing tolerance and cold acclimation through modulating lignin biosynthesis

Cell water permeability and cell wall properties are critical to survival of plant cells during freezing, however the underlying molecular mechanisms remain elusive. Here, we report that a specifically cold-induced nuclear protein, Tolerant to Chilling and Freezing 1 (TCF1), interacts with histones H3 and H4 and associates with chromatin containing a target gene, BLUE-COPPER-BINDING PROTEIN (BCB), encoding a glycosylphosphatidylinositol-anchored protein that regulates lignin biosynthesis. Loss of TCF1 function leads to reduced BCB transcription through affecting H3K4me2 and H3K27me3 levels within the BCB gene, resulting in reduced lignin content and enhanced freezing tolerance. Furthermore, plants with knocked-down BCB expression (amiRNA-BCB) under cold acclimation had reduced lignin accumulation and increased freezing tolerance. The pal1pal2 double mutant (lignin content reduced by 30% compared with WT) also showed the freezing tolerant phenotype, and TCF1 and BCB act upstream of PALs to regulate lignin content. In addition, TCF1 acts independently of the CBF (C-repeat binding factor) pathway. Our findings delineate a novel molecular pathway linking the TCF1-mediated cold-specific transcriptional program to lignin biosynthesis, thus achieving cell wall remodeling with increased freezing tolerance

H2AX Deficiency is Associated with Erythroid Dysplasia and Compromised Haematopoietic Stem Cell Function

Myelodysplastic syndromes (MDS) are clonal disorders of haematopoiesis characterised by dysplastic changes of major myeloid cell lines. However, the mechanisms underlying these dysplastic changes are poorly understood. Here, we used a genetically modified mouse model and human patient data to examine the physiological roles of H2AX in haematopoiesis and how the loss of H2AX contributes to dyserythropoiesis in MDS. H2AX knockout mice showed cell-autonomous anaemia and erythroid dysplasia, mimicking dyserythropoiesis in MDS. Also, dyserythropoiesis was increased in MDS patients with the deletion of chromosome 11q23, where H2AX is located. Although loss of H2AX did not affect the early stage of terminal erythropoiesis, enucleation was decreased. H2AX deficiency also led to the loss of quiescence of hematopoietic stem and progenitor cells, which dramatically compromised their bone marrow engraftment. These results reveal important roles of H2AX in late-stage terminal erythropoiesis and hematopoietic stem cell function

Automatic Insertion of Hot Keywords to Drive Traffic on Advertisements

Product titles and descriptions that include appropriate keywords, when used in an online advertisement, can improve the shopping feed quality and resultant traffic to the advertiser. However, online merchants lack knowledge of currently trending or popular keywords, and lacking keyword ideation, may choose suboptimal product titles. This disclosure describes techniques that enable online merchants to automatically optimize product titles or descriptions, e.g., as used in online ads. Trending or popular keywords relevant to the product are automatically added to the product title or description. Unique, product-specific insights gleaned from searched terms are utilized to improve title effectiveness automatically and at scale

Correction: Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios.

An important detail was omitted in the Method of the original Article, I.E, The CARS and other evaluations were conducted 'blind' to condition (Bumetanide or no treatment) by experienced clinicians. This has now been updated in the HTML and PDF versions of this Article

Correction: Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios

An important detail was omitted in the Method of the original Article, I.E, The CARS and other evaluations were conducted ‘blind' to condition (Bumetanide or no treatment) by experienced clinicians. This has now been updated in the HTML and PDF versions of this Article

Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios

Funder: Shanghai Municipal Commission of Health and Family Planning Shanghai Shenkang Hospital Development Center Shanghai Municipal Education Commission National Natural Science Foundation of China Shanghai Committee of Science and Technology Xinhua Hospital of Shanghai Jiao Tong University School of Medicine Guangdong Key Project in "Development of new tools for diagnosis and treatment of Autism "Funder: Shanghai Municipal Commission of Health and Family Planning Shanghai Municipal Education Commission National Natural Science Foundation of China the National Key Research and Development Program of China ZJ LabFunder: National Human Genetic Resources Sharing Service Platform 111 Project ZJ LabFunder: National Natural Science Foundation of China ZJ LabAbstract: Bumetanide has been reported to alter synaptic excitation–inhibition (E-I) balance by potentiating the action of γ-aminobutyric acid (GABA), thereby attenuating the severity of autism spectrum disorder (ASD) in animal models. However, clinical evidence of its efficacy in young patients with ASD is limited. This was investigated in the present clinical trial of 83 patients, randomised to the bumetanide group (bumetanide treatment, 0.5 mg twice daily) or the control group (no bumetanide treatment). Primary [Children Autism Rating Scale (CARS)], secondary [Clinical Global Impressions (CGI)], and exploratory [inhibitory (γ-aminobutyric acid, GABA) and excitatory (glutamate, Glx) neurotransmitter concentrations measured in the insular cortex (IC) and visual cortex (VC) by magnetic resonance spectroscopy (MRS)] outcome measures were evaluated at baseline and at the 3-month follow-up. Side effects were monitored throughout the treatment course. Compared with the control group, the bumetanide group showed significant reduction in symptom severity, as indicated by both total CARS score and number of items assigned a score ≥ 3. The improvement in clinical symptoms was confirmed by CGI. GABA/Glx ratio in both the IC and VC decreased more rapidly over the 3-month period in the bumetanide group than that in the control group. This decrease in the IC was associated with the symptom improvement in the bumetanide group. Our study confirmed the clinical efficacy of bumetanide on alleviating the core symptoms of ASD in young children and it is the first demonstration that the improvement is associated with reduction in GABA/Glx ratios. This study suggests that the GABA/Glx ratio measured by MRS may provide a neuroimaging biomarker for assessing treatment efficacy for bumetanide

TET1 is a tumor suppressor of hematopoietic malignancy

The methylcytosine dioxygenase TET1 (‘ten-eleven translocation 1’) is an important regulator of 5-hydroxymethylcytosine (5hmC) in embryonic stem cells. The diminished expression of TET proteins and loss of 5hmC in many tumors suggests a critical role for the maintenance of this epigenetic modification. Here we found that deletion of Tet1 promoted the development of B cell lymphoma in mice. TET1 was required for maintenance of the normal abundance and distribution of 5hmC, which prevented hypermethylation of DNA, and for regulation of the B cell lineage and of genes encoding molecules involved in chromosome maintenance and DNA repair. Whole-exome sequencing of TET1-deficient tumors revealed mutations frequently found in non-Hodgkin B cell lymphoma (B-NHL), in which TET1 was hypermethylated and transcriptionally silenced. Our findings provide in vivo evidence of a function for TET1 as a tumor suppressor of hematopoietic malignancy.National Institutes of Health (U.S.) (5RO1HD045022)National Institutes of Health (U.S.) (5R37CA084198

A random forest model for the prediction of spudcan penetration resistance in stiff-over-soft clays

Punch-through is a major threat to the jack-up unit, especially at well sites with layered stiff-over-soft clays. A model is proposed to predict the spudcan penetration resistance in stiff-over-soft clays, based on the random forest (RF) method. The RF model was trained and tested with numerical simulation results obtained through the Finite Element model, implemented with the Coupled Eulerian Lagrangian (CEL) approach. With the proposed CEL model, the effects of the stiff layer thickness, undrained shear strength ratio, and the undrained shear strength of the soft layer on the bearing characteristics, as well as the soil failure mechanism, were numerically studied. A simplified resistance profile model of penetration in stiff-over-soft clays is proposed, divided into three sections by the peak point and the transition point. The importance of soil parameters to the penetration resistance was analysed. Then, the trained RF model was tested against the test set, showing a good prediction of the numerical cases. Finally, the trained RF was validated against centrifuge tests. The RF model successfully captured the punch-through potential, and was verified using data recorded in the field, showing advantages over the SNAME guideline. It is supposed that the trained RF model should give a good prediction of the spudcan penetration resistance profile, especially if trained with more field data

Growth, Nutritional Quality and Health-Promoting Compounds in Chinese Kale Grown under Different Ratios of Red:Blue LED Lights

Chinese kale (Brassica alboglabra Bailey) is one of the healthiest vegetables which is rich in health-promoting phytochemicals, including carotenoids, vitamin C, amino acid, glucosinolates, anthocyanin, flavonoids and phenolic compounds. The effects of different LEDs (white LED, 8R1B (red:blue = 8:1), 6R3B (red:blue = 6:3)) on nutritional quality in flower stalks and leaves of Chinese kale were investigated in this study. 8R1B and 6R3B were more effective than white LED light for improvement of growth and quality of Chinese kale. Flower stalk contained a higher content of nutritional compounds than leaves in Chinese kale. 8R1B significantly promoted plant growth, accumulation of biomass and soluble sugar content in flower stalks. In contrast, 6R3B significantly reduced plant dry matter, but it promoted nutritional compounds accumulation in flower stalks, such as soluble proteins, total glucosinolate, total anthocyanin, flavonoid, antioxidant activity. In addition, 6R3B enable to increase the amount of sourness and umami tasty amino acids, as well as precursor amino acids of glucosinolate. Accumulation balance of biomass and nutritional compounds is related to the ratio of red to blue light. Generally, 6R3B was more conducive to the enrichment of health-promoting compounds, as well as umami in Chinese kale