Decarboxylative Fluorination of Electron-Rich Heteroaromatic Carboxylic Acids with Selectfluor

A transition-metal-free decarboxylative fluorination of electron-rich five-membered heteroaromatics, including furan-, pyrazole-, isoxazole-, thiophene-, indole-, benzofuran- and indazolecarboxylic acids, with Selectfluor is reported. Fluorinated dimer products were observed for nitrogen-containing heteroaromatic carboxylic acids, such as indole and pyrazole. An effective method has been developed to synthesize the monomer of 2- and 3-fluoroindoles with Li2CO3 as base at low temperature

Effectiveness of lymphoplasmapheresis compared with therapeutic plasma exchange for thrombotic thrombocytopenic purpura: a retrospective evaluation

Thrombotic thrombocytopenic purpura (TTP) is an acute life-threatening disease usually treated with therapeutic plasma exchange (TPE), but some patients are refractory to TPE. The study aimed to compare lymphoplasmapheresis (LPE), an innovative treatment for TTP based on plasma exchange, with TPE in TTP treatment. This retrospective study included patients with TTP treated at Xiang-Ya Hospital in China during 2009-2018. All patients with microangiopathic hemolysis and thrombocytopenia who received either LPE or TPE were included. The treatment outcomes were the number of sessions, volume of plasma, time in hospital, hospital costs, and rates of remission and relapse. All patients attended the hospital for follow-up. Forty-five patients were included in the study; 18 received TPE and 27 LPE. There were no significant differences in sex, etiology of TTP, initial platelet count, schistocyte, LDH, and bilirubin between the two groups. At the time of discharge, patients treated with TPE required more treatment sessions (4.5 vs. 2, P=0.04) and higher plasma volume (7300 vs. 3100 ml, P=0.01) than patients treated with LPE. The proportions of remission (P=0.197) and relapse (P=0.257) were not significantly different between the two groups. The time to remission from admission (P=0.75) and the time to remission from first therapy (P=0.53) were also not significantly different between the two groups. Compared with TPE, LPE reduced the number of treatment sessions and plasma volume needed to treat TTP. Therefore, we propose that LPE might be a suitable treatment for TTP.</p

Mad2 knockdown in G1 cells with impaired APC-Cdh1 activity increases cyclin B1-YFP oscillation frequency.

<p>(A) Box plots of cyclin B1-YFP oscillation peak frequencies in DMSO- and nocodazole-treated cells, respectively. DMSO (oscillations per experiment (OPE)): range, 0.92–8.35; first quartile, 3.71; median, 5.56, third quartile, 6.49. Nocodazole (OPE): range, 0.92–3.71; first quartile, 1.85; median, 1.85; third quartile, 2.78. (B) Box plots of cyclin B1-YFP oscillation amplitudes in DMSO- and nocodazole-treated cells, respectively. DMSO (relative fluorescence units (RFU)): range, 1.9–7.3; first quartile, 2.7; median, 3.6, third quartile, 4.5. Nocodazole (RFU): range, 2.4–10.9; first quartile, 4.4; median, 6.0; third quartile, 8.1. (C, D) Representative cells oscillating at the median frequency in the DMSO and nocodazole treatments, respectively. (E) Box plots of cyclin B1-YFP oscillation peak frequencies in DMSO- and hesperadin-treated cells. DMSO (OPE): range, 0.96–6.74; first quartile, 1.92; median, 2.88, third quartile, 3.85. Hesperadin (OPE): range, 0.96–7.7; first quartile, 2.4; median, 3.85; third quartile, 5.77. (F) Box plots of cyclin B1-YFP oscillation amplitudes in DMSO- and hesperadin-treated cells, respectively. DMSO (RFU): range, 2.0–8.5; first quartile, 3.9; median, 4.4, third quartile, 5.8. Hesperadin (RFU): range, 1.0–11.2; first quartile, 3.5; median, 4.8; third quartile, 6.6. (G, H) Representative cells oscillating at median frequency in the DMSO and hesperadin treatments, respectively. (I) Box plots of cyclin B1-YFP oscillation peak frequencies in GL3- and Mad2 d-siRNA-treated cells. GL3 (OPE): range, 0.99–6.94; first quartile, 1.98; median, 2.97, third quartile, 4.96. Mad2 (OPE): range, 0.99–8.92; first quartile, 3.96; median, 4.96; third quartile, 5.95. (J) Box plots of cyclin B1-YFP oscillation amplitudes in GL3- and Mad2 d-siRNA-treated cells, respectively. GL3 (RFU): range, 3.5–32.4; first quartile, 9.9; median, 18.0, third quartile, 23.2. Mad2 (RFU): range, 0.9–14.9; first quartile, 2.9; median, 6.9; third quartile, 8.3. (K, L) Representative cells oscillating at median frequency in the GL3- and Mad2-d-siRNA treatments, respectively. In (A), (F), and (J), outliers that are at least 1.5 times the interquartile distance away from their respective quartiles are presented as circles.</p

Bipolar spindle maintenance does not require completed DNA replication or condensation.

<p>(A) CDK1-CFP, microtubules (MT), DNA, and the overlay of MT and DNA in CDK1WT mitotic cells and daughters of CDK1AF expressers. Microtubules (green) and DNA (blue) are shown. (B) Histogram of spindle morphology observed in M-phase-like G1 cells (CDK1AF daughters), with percent bipolar (light gray) and monopolar spindles (dark gray). (C) Kinetochores (ACA; magenta), microtubules (MT), and the overlay of both of these plus DNA from cells in the same population described in (A). Scale bars = 10 µM.</p

Premature M-phase initiation can be reduced in G1 cells with impaired APC-Cdh1 activation by enforced non-degradable Wee1 expression.

<p>(A) Fifty-thousand CDK1WT-transfected cells and (B) 50000 CDK1AF-transfected cells on a pseudo-color scatter plot of PI (abscissa) and pHH3 content (ordinate). High DNA and high pHH3 content (M phase) gates (blue “M”) and low DNA and high pHH3 (abnormal G1/S cells) gates (green “G1/S”) are shown with their respective frequencies. (C) Cells gated in (A) are overlaid on a pseudo-color scatter plot of PI (abscissa) and Wee1 content (ordinate) of CDK1WT-transfected cells. (D) Cells gated in (B) are overlaid on a pseudo-color scatter plot of PI (abscissa) and Wee1 content (ordinate) of CDK1AF-transfected cells. The M-phase Wee1 level (gray dashed line) is defined in both (C) and (D) by the horizontal axis centered on the Wee1-stained M-phase population that was gated in (A). (E) Histogram of relative Wee1 contents in CDK1AF-transfected cells in normal S phase (pHH3-negative; red), in normal M phase (pHH3-positive; blue), and in precocious M phase (G1-S DNA content, pHH3-positive; green) (F) Histogram of percent oscillating daughters generated in HeLa cells co-transfected with cyclin B1-YFP and CDK1AF alone, or together along with ΔN214Wee1.</p

Mad2 stabilizes prematurely formed spindles in M-phase-like G1 cells.

<p>(A) Mad2 (green) with kinetochores (ACA; magenta) and DNA (blue) (left), or their overlay of MT (green) and DNA with kinetochores (ACA; magenta) (right) in a representative CDK1WT mitotic cell (top) and daughter produced by division of a CDK1AF-expresser (bottom). Scale bar = 10 µM. (B) Mad2 (top) and tubulin (bottom) immunoblots in a cell line stably expressing histone H2B-GFP (green) and mCherry-α-tubulin (red), following co-transfection with CFP-CDK1AF and Diced siRNA pools to firefly luciferase (GL3) or human Mad2 3′ UTR. (C) Montage of live-cell images from transfections described in (B) showing a representative GL3 d-siRNA-treated cell (top) and Mad2 d-siRNA-treated cell (bottom). White arrowheads indicate prematurely formed spindle; gray arrowheads indicate last image of apparent spindle structure. (D) Scatter plot of spindle duration times for CDK1AF/GL3-siRNA (dark gray) and CDK1AF/Mad2-siRNA (light gray) co-transfected cells (left) and box plot (right). Transfections and imaging were performed in triplicate (N = 3; n_GL3 and n_Mad2 = 167 representative cells). GL3-siRNA spindle duration: range, 60–990 min; first quartile, 225 min; median 345 min; third quartile, 450 min. Mad2-siRNA spindle duration: range, 30–240 min; first quartile, 45 min, median, 60 min; third quartile, 75 min.</p

Overview of stabilized APC-Cdh1 targets and the absence of Wee1 in G1 daughters following division of cells with or without CDK1AF expression.

<p>Dark gray inhibitory symbols represent complete activation of APC-Cdh1; light gray inhibitory symbols (with CDK1AF expression) and light gray APC-Cdh1 represent a lack of sustained activation. Asterisks represent active CDK.</p

Table1_Integration of Transcriptome and Methylome Analyses Provides Insight Into the Pathway of Floral Scent Biosynthesis in Prunus mume.xlsx

DNA methylation is a common epigenetic modification involved in regulating many biological processes. However, the epigenetic mechanisms involved in the formation of floral scent have rarely been reported within a famous traditional ornamental plant Prunus mume emitting pleasant fragrance in China. By combining whole-genome bisulfite sequencing and RNA-seq, we determined the global change in DNA methylation and expression levels of genes involved in the biosynthesis of floral scent in four different flowering stages of P. mume. During flowering, the methylation status in the “CHH” sequence context (with H representing A, T, or C) in the promoter regions of genes showed the most significant change. Enrichment analysis showed that the differentially methylated genes (DMGs) were widely involved in eight pathways known to be related to floral scent biosynthesis. As the key biosynthesis pathway of the dominant volatile fragrance of P. mume, the phenylpropane biosynthesis pathway contained the most differentially expressed genes (DEGs) and DMGs. We detected 97 DMGs participated in the most biosynthetic steps of the phenylpropane biosynthesis pathway. Furthermore, among the previously identified genes encoding key enzymes in the biosynthesis of the floral scent of P. mume, 47 candidate genes showed an expression pattern matching the release of floral fragrances and 22 of them were differentially methylated during flowering. Some of these DMGs may or have already been proven to play an important role in biosynthesis of the key floral scent components of P. mume, such as PmCFAT1a/1c, PmBEAT36/37, PmPAL2, PmPAAS3, PmBAR8/9/10, and PmCNL1/3/5/6/14/17/20. In conclusion, our results for the first time revealed that DNA methylation is widely involved in the biosynthesis of floral scent and may play critical roles in regulating the floral scent biosynthesis of P. mume. This study provided insights into floral scent metabolism for molecular breeding.</p

Additional file 1 of Targeted sequencing of high-density SNPs provides an enhanced tool for forensic applications and genetic landscape exploration in Chinese Korean ethnic group

Additional file 1. Fig. S1: Sequencing depths and allele coverage ratios of the SNP loci in the Chinese Korean ethnic group. A Distribution of the 1993 SNP loci in the 22 autosomes; B Histogram of the average sequencing depths for 1993 SNP loci in 161 Chinese Korean individuals; C Boxplot of the sequencing depths for SNP loci with a sequencing depth less than 500×; D Histogram of the average allele coverage ratios for the heterozygous SNP loci in the Korean ethnic group. Fig. S2: Forensic efficiencies of the 1946 SNPs in the Chinese Korean ethnic group. A Forensic statistical parameters, encompassing gene diversity (GD), Hobs (Observed heterozygosity), PD (Power of discrimination), PE (Power of exclusion) and PM (Probability of match) of the 1946 SNPs; B Distribution of 1-CPD and 1-CPE values estimated with the increase of SNP loci. Fig. S3: ADMIXTURE results for K = 2 ~10, with the K denoting the pre-assumed ancestry components represented by different colors. The ancestry composition of each population is proportional to the height of different colors. Fig. S4: Principal component analyses (PCA) of the Chinese Korean ethnic group and the reference populations. Each dot represents a single individual and is colored according to its continental origin. A PCA of the Chinese Korean ethnic group and all the reference populations from eight major geographic regions worldwide. The Chinese Korean ethnic group and East Asian populations are marked with black box; B PCA of the Chinese Korean ethnic group and the East Asian reference populations. Fig. S5: Phylogenetic reconstruction of Treemix results for one to seven (except for four) migration events between the Chinese Korean ethnic group and the reference populations. Fig. S6: Pairwise residuals of Treemix results for one to seven (except for four) migration events between the Chinese Korean ethnic group and the reference populations