WT1 Recruits TET2 to Regulate Its Target Gene Expression and Suppress Leukemia Cell Proliferation

The TET2 DNA dioxygenase regulates cell identity and suppresses tumorigenesis by modulating DNA methylation and expression of a large number of genes. How TET2, like most other chromatin modifying enzymes, is recruited to specific genomic sites is unknown. Here we report that WT1, a sequence-specific transcription factor, is mutated in a mutually exclusive manner with TET2, IDH1 and IDH2 in acute myeloid leukemia (AML). WT1 physically interacts with and recruits TET2 to its target genes to activate their expression. The interaction between WT1 and TET2 is disrupted by multiple AML-derived TET2 mutations. TET2 suppresses leukemia cell proliferation and colony formation in a manner dependent on WT1. These results provide a mechanism for targeting TET2 to specific DNA sequence in the genome. Our results also provide an explanation for the mutual exclusivity of WT1 and TET2 mutations in AML and suggest an IDH1/2-TET2-WT1 pathway in suppressing AML

Dysregulation of PRMT5 in chronic lymphocytic leukemia promotes progression with high risk of Richter's transformation

: Richter's Transformation (RT) is a poorly understood and fatal progression of chronic lymphocytic leukemia (CLL) manifesting histologically as diffuse large B-cell lymphoma. Protein arginine methyltransferase 5 (PRMT5) is implicated in lymphomagenesis, but its role in CLL or RT progression is unknown. We demonstrate herein that tumors uniformly overexpress PRMT5 in patients with progression to RT. Furthermore, mice with B-specific overexpression of hPRMT5 develop a B-lymphoid expansion with increased risk of death, and Eµ-PRMT5/TCL1 double transgenic mice develop a highly aggressive disease with transformation that histologically resembles RT; where large-scale transcriptional profiling identifies oncogenic pathways mediating PRMT5-driven disease progression. Lastly, we report the development of a SAM-competitive PRMT5 inhibitor, PRT382, with exclusive selectivity and optimal in vitro and in vivo activity compared to available PRMT5 inhibitors. Taken together, the discovery that PRMT5 drives oncogenic pathways promoting RT provides a compelling rationale for clinical investigation of PRMT5 inhibitors such as PRT382 in aggressive CLL/RT cases

A Numerical Simulation of the “1907” Kaiyuan Tornado Weather Process in Liaoning, Northeast China

From 17:00 to 18:00 local standard time (LST) on 3 July 2019, a rare strong tornado occurred in Kaiyuan, Liaoning Province, northeast China. NCEP/NCAR 0.25° × 0.25° reanalysis data and WRF4.0 numerical prediction models were used to carry out the numerical simulation. Double nesting was adopted, and the horizontal grid distance was 9 km by 3 km. Based on the observation data of China meteorological observation stations, surface and upper charts, Doppler radar data, Himawari(HMW)-8 satellite images and numerical simulation results, the mesoscale structure and mechanism of the tornado were studied. The results show that: (1) At the northwest edge of the subtropical high, and the northeast cold vortex located in Northeast China, when the transverse trough moves southward, cold air is supplied continuously. Under the joint influence of the surface northeast cyclone, these are the main synoptic features of the tornado; (2) The northeast cold vortex cloud system was located at the junction of Heilongjiang and Jilin Provinces, and a squall line cloud system is formed. The tornado occurred at the tail of the squall line, and the strongest echo reached 65 dBZ. A mesocyclone, a 20 km northwest–southeast convergence belt, V-shaped gap, echo overhang structure and tornado vortex feature (TVS) were detected by the Doppler radar; (3) Before the tornado occurred, dry and cold air intruded from the northwest of the cold vortex, and a water vapor convergence zone appeared south of the squall line. The water vapor saturation zone with 80% relative humidity in northeast China was concentrated at 700 hPa, and the 20% dry column dropped down to 500 hPa between 115 and 124° E from the west. On the 850 hPa physical fields, there was a −20 × 10−5 s−1 convergence zone, and a 16 × 10−5 s−1 divergence belt appeared south and north of the squall line. A negative vorticity belt and a positive vorticity belt appeared south and north of the squall line, respectively. Kaiyuan is located at the smallest vertical shear, which is the junction place of three large vertical shear belts; (4) After 10:00 LST, the westerly wind 20 (10) m·s−1 dropped to 400 (800) hPa between 126 and 127° E. The northerly gale at 300 hPa north of 45° N moved southward. The rising center of the low level at 17:00 LST at approximately 45° N moved southward, and a sinking center appeared above it; (5) Several pairs of positive and negative vorticity columns formed between the lower troposphere and the place where the tornado occurred. There was convective instability at the lower level. CAPE increased, 0–3 km vertical wind shear increased, and LCL decreased remarkably during the afternoon

A Numerical Simulation of the “1907” Kaiyuan Tornado Weather Process in Liaoning, Northeast China

From 17:00 to 18:00 local standard time (LST) on 3 July 2019, a rare strong tornado occurred in Kaiyuan, Liaoning Province, northeast China. NCEP/NCAR 0.25° × 0.25° reanalysis data and WRF4.0 numerical prediction models were used to carry out the numerical simulation. Double nesting was adopted, and the horizontal grid distance was 9 km by 3 km. Based on the observation data of China meteorological observation stations, surface and upper charts, Doppler radar data, Himawari(HMW)-8 satellite images and numerical simulation results, the mesoscale structure and mechanism of the tornado were studied. The results show that: (1) At the northwest edge of the subtropical high, and the northeast cold vortex located in Northeast China, when the transverse trough moves southward, cold air is supplied continuously. Under the joint influence of the surface northeast cyclone, these are the main synoptic features of the tornado; (2) The northeast cold vortex cloud system was located at the junction of Heilongjiang and Jilin Provinces, and a squall line cloud system is formed. The tornado occurred at the tail of the squall line, and the strongest echo reached 65 dBZ. A mesocyclone, a 20 km northwest–southeast convergence belt, V-shaped gap, echo overhang structure and tornado vortex feature (TVS) were detected by the Doppler radar; (3) Before the tornado occurred, dry and cold air intruded from the northwest of the cold vortex, and a water vapor convergence zone appeared south of the squall line. The water vapor saturation zone with 80% relative humidity in northeast China was concentrated at 700 hPa, and the 20% dry column dropped down to 500 hPa between 115 and 124° E from the west. On the 850 hPa physical fields, there was a −20 × 10−5 s−1 convergence zone, and a 16 × 10−5 s−1 divergence belt appeared south and north of the squall line. A negative vorticity belt and a positive vorticity belt appeared south and north of the squall line, respectively. Kaiyuan is located at the smallest vertical shear, which is the junction place of three large vertical shear belts; (4) After 10:00 LST, the westerly wind 20 (10) m·s−1 dropped to 400 (800) hPa between 126 and 127° E. The northerly gale at 300 hPa north of 45° N moved southward. The rising center of the low level at 17:00 LST at approximately 45° N moved southward, and a sinking center appeared above it; (5) Several pairs of positive and negative vorticity columns formed between the lower troposphere and the place where the tornado occurred. There was convective instability at the lower level. CAPE increased, 0–3 km vertical wind shear increased, and LCL decreased remarkably during the afternoon

Textbooks History of art culture for art and handicraft of secondary vocational schools: didactic analysis of texts

The thesis "School Textbooks of History of Visual Culture for Secondary Art Schools (Didactic analysis of texts)" is focused on the area of visual culture textbooks for professional secondary art education. The secondary art education in the territory of Czech Republic has a long tradition since the middle of 19th century and art history tuition realized in the school subject History of Visual Culture presents a considerable part of professional training of future artists, artisans and craftsmen. The main aim of the school subject is providing students with a complex and systematically structured knowledge of visual culture evolution, art trends and tendencies from the very beginning until the present days. This knowledge will be essential theoretical background for students' professional activities in the field of visual creation. Powered by TCPDF (www.tcpdf.org

Comparison of storage and lignin accumulation characteristics between two types of snow pea.

Snow pea is a very important vegetable, and its postharvest storage characteristics vary with species. Few studies on the differences in its storage characteristics are available. In this study, postharvest changes in metabolic rate (respiration rate and water loss rate), membrane permeability (relative conductivity), nutrient contents (total sugar, amino acids, starch), lignin, cellulose, β-Glucosidase (β-GC) enzyme activity, texture properties, PG enzyme activity and their relationship were analyzed in large sweet broad peas and small snow peas. On the 8th day of storage, we found that the respiration rate and water loss rate were increased, total sugars and total amino acids were decreased significantly in these two legume vegetables, and that metabolic rate was slower with less nutrients consumed in large sweet broad peas than in small snow peas. Throughout the 8-day whole storage, the lignin and cellulose contents were always lower in large sweet broad peas than in small snow peas. With the increasing storage time, small snow peas were more susceptible to lignification and fibrosis, which was observed in their texture properties. The enzyme activities related to cellulose and pectin degradation (β-GC, PG) also showed the same trend during the storage. At the late stage of storage, the taste of large sweet broad peas was better than that of small snow peas. In conclusion, the storage period of large sweet broad peas was longer than that of the small snow peas, and its lignification degree was lower than that of the small snow peas. Meanwhile, senescence and lignin accumulation led to hardening of snow pea during postharvest storage. Our findings provide a theoretical reference for improving the postharvest storage quality of snow pea and extending the shelf life

Additional file 1: Table S1. of Long non-coding RNA expression profile in minor salivary gland of primary Sjögren’s syndrome

Primer sequences used in validation of lncRNAs. (DOCX 14 kb

Additional file 2: Figure S3. of Long non-coding RNA expression profile in minor salivary gland of primary Sjögren’s syndrome

Characterization of the cellular infiltrate and histomorphologic grading of LSG. (A) Shown are representative examples of grade 1 (G1; <50 periductal lymphocytes); (B,C) grade 2 (G2; >50 periductal lymphocytes): nonsegregated and segregated aggregates (NS-G2 and S-G2, respectively); (D,F) grade 3 (G3; >50 periductal lymphocytes, with GC-like structures). (TIF 58923 kb

Additional file 7: Figure S2. of Long non-coding RNA expression profile in minor salivary gland of primary Sjögren’s syndrome

Immunohistochemistry for TLR9 and CXCR4 in LSG of pSS and healthy controls. (A, E) Infiltrating lymphocytes in LSG of pSS positively stained for TLR9 (200× and 400× magnification); (B, F) glandular epithelial cells from control were negative (200× and 400× magnification); (C, G) infiltrating lymphocytes and adjacent glandular epithelial cells in LSG of pSS were positively stained for CXCR4 (200× and 400× magnification). (D, H) Glandular epithelial cells from control were negative (200× and 400× magnification). (TIF 28419 kb