Amide proton transfer-weighted imaging of pediatric brainstem glioma and its predicted value for H3 K27 alteration

BACKGROUND: Non-invasive determination of H3 K27 alteration of pediatric brainstem glioma (pedBSG) remains a clinical challenge. PURPOSE: To predict H3 K27-altered pedBSG using amide proton transfer-weighted (APTw) imaging. MATERIAL AND METHODS: This retrospective study included patients with pedBSG who underwent APTw imaging and had the H3 K27 alteration status determined by immunohistochemical staining. The presence or absence of foci of markedly increased APTw signal in the lesion was visually assessed. Quantitative APTw histogram parameters within the entire solid portion of tumors were extracted and compared between H3 K27-altered and wild-type groups using Student's t-test. The ability of APTw for differential diagnosis was evaluated using logistic regression. RESULTS: Sixty pedBSG patients included 48 patients with H3 K27-altered tumor (aged 2-48 years) and 12 patients with wild-type tumor (aged 3-53 years). Visual assessment showed that the foci of markedly increased APTw signal intensity were more common in the H3 K27-altered group than in wild-type group (60% vs. 16%, P = 0.007). Histogram parameters of APTw signal intensity in the H3 K27-altered group were significantly higher than those in the wild-type group (median, 2.74% vs. 2.22%, P = 0.02). The maximum (area under the receiver operating characteristic curve [AUC] = 0.72, P = 0.01) showed the highest diagnostic performance among histogram analysis. A combination of age, median and maximum APTw signal intensity could predict H3 K27 alteration with a sensitivity of 81%, specificity of 75% and AUC of 0.80. CONCLUSION: APTw imaging may serve as an imaging biomarker for H3 K27 alteration of pedBSGs

Povezanost polimorfizma pojedinačnog nukleotida gena ARID4A i kvalitete sperme kineskog vodenog bivola

ARID4A (AT-rich interaction domain 4A) is closely related to animal sperm quality traits. In the present study, the association between ARID4A gene polymorphisms of Chinese water buffalo (Bubalus bubalis) with sperm quality traits was examined, including ejaculate volume, sperm concentration, post-thaw sperm motility, and sperm abnormality of buffalo semen. Seven single-nucleotide polymorphisms (SNPs) of ARID4A gene were detected in 156 Chinese water buffaloes by Sanger sequencing and identifying overlap peaks. Among the SNPs, six were associated with at least one sperm quality trait. In brief, g.21192G>C, g.21285C>G, and g.21364A>G could be used as potential markers for selecting semen with low sperm abnormality, high ejaculate volume, sperm concentration, and sperm motility. Furthermore, 10 haplotypes (H1: -CTCGG, H2: GTGGCA, H3: GCGGCA, H4: GCTGCA, H5: GCTCGA, H6: GTGGGG, H7: GCTCCG, H8: -CGGGA, H9: GCGGCG, and H10: GTTGCA) were formed by the six SNPs through linkage disequilibrium analysis, and then 14 different combined haplotypes were collected. Correlation analysis showed that the combined H1H2 haplotype had the highest genotype frequency. Notably, the combined H1H2 haplotype had low sperm concentration, low sperm motility, and high sperm abnormality. The combined H2H3 haplotype could be used as a potential molecular marker for selecting semen with high sperm motility. In general, we illustrated a significant correlation between SNPs in ARID4A and sperm quality traits of Chinese water buffalo, which may be useful in the marker-assisted selection of buffalo breeding. This study was the first to analyze the genetic polymorphisms of ARID4A and association with sperm qualities of Chinese buffalo.Gen ARID4A (engl AT-rich interaction domain 4A) usko je povezan s kvalitetom sperme. U ovom je radu istraživana povezanost polimorfizma gena ARID4A u kineskih vodenih bivola (Bubalus bubalis) s kvalitetom sperme, uključujući volumen ejakulata, koncentraciju sperme, pokretljivost spermija nakon odmrzavanja i abnormalnost spermija u sjemenu bivola. U 156 kineskih vodenih bivola otkriveno je sedam polimorfizama pojedinačnog nukleotida (SNPs) gena ARID4A Sangerovim sekvenciranjem i identifikacijom preklopljenih vrhova. Među SNP-ovima njih je šest bilo povezano s barem jednim svojstvom kvalitete spermija. Ukratko, g. 21192G>C, g. 21285C>G i g. 21364A>G mogu se upotrijebiti kao potencijalni markeri za selekciju sjemena s niskom abnormalnošću spermija, većim volumenom ejakulata, većom koncentracijom i pokretljivošću spermija. Nadalje, šest SNP-ova formiralo je 10 haplotipova (H1: -CTCGG, H2: GTGGCA, H3: GCGGCA, H4: GCTGCA, H5: GCTCGA, H6: GTGGGG, H7: GCTCCG, H8: -CGGGA, H9: GCGGCG i H10: GTTGCA) analizom povezanosti nepodudarnosti te je ustanovljeno 14 različitih kombiniranih haplotipova. Analiza korelacije pokazala je da kombinirani haplotip H1H2 ima najveću učestalost. Kombinirani haplotip H1H2 imao je najmanju koncentraciju sperme, slabu pokretljivost seprmija i znatnu abnormalnost spermija. Kombinirani haplotip H2H3 može se upotrijebiti kao potencijalni molekularni marker za odabir sjemena s većom pokretljivošću. Općenito je pokazana znakovita korelacija između SNP-ova u ARID4A i kvalitete sperme kineskog vodenog bivola, što može biti korisno u selekciji bivola potpomognutoj markerima. Ovo je prvo istraživanje koje je analiziralo genske polimorfizme ARID4A i njihovu povezanost s kvalitetom sjemena kineskih vodenih bivola

Analysis of the transcriptome of Panax notoginseng root uncovers putative triterpene saponin-biosynthetic genes and genetic markers

<p>Abstract</p> <p>Background</p> <p><it>Panax notoginseng </it>(Burk) F.H. Chen is important medicinal plant of the <it>Araliacease </it>family. Triterpene saponins are the bioactive constituents in <it>P. notoginseng</it>. However, available genomic information regarding this plant is limited. Moreover, details of triterpene saponin biosynthesis in the <it>Panax </it>species are largely unknown.</p> <p>Results</p> <p>Using the 454 pyrosequencing technology, a one-quarter GS FLX titanium run resulted in 188,185 reads with an average length of 410 bases for <it>P. notoginseng </it>root. These reads were processed and assembled by 454 GS <it>De Novo </it>Assembler software into 30,852 unique sequences. A total of 70.2% of unique sequences were annotated by Basic Local Alignment Search Tool (BLAST) similarity searches against public sequence databases. The Kyoto Encyclopedia of Genes and Genomes (KEGG) assignment discovered 41 unique sequences representing 11 genes involved in triterpene saponin backbone biosynthesis in the 454-EST dataset. In particular, the transcript encoding dammarenediol synthase (DS), which is the first committed enzyme in the biosynthetic pathway of major triterpene saponins, is highly expressed in the root of four-year-old <it>P. notoginseng</it>. It is worth emphasizing that the candidate cytochrome P450 (Pn02132 and Pn00158) and UDP-glycosyltransferase (Pn00082) gene most likely to be involved in hydroxylation or glycosylation of aglycones for triterpene saponin biosynthesis were discovered from 174 cytochrome P450s and 242 glycosyltransferases by phylogenetic analysis, respectively. Putative transcription factors were detected in 906 unique sequences, including Myb, homeobox, WRKY, basic helix-loop-helix (bHLH), and other family proteins. Additionally, a total of 2,772 simple sequence repeat (SSR) were identified from 2,361 unique sequences, of which, di-nucleotide motifs were the most abundant motif.</p> <p>Conclusion</p> <p>This study is the first to present a large-scale EST dataset for <it>P. notoginseng </it>root acquired by next-generation sequencing (NGS) technology. The candidate genes involved in triterpene saponin biosynthesis, including the putative CYP450s and UGTs, were obtained in this study. Additionally, the identification of SSRs provided plenty of genetic makers for molecular breeding and genetics applications in this species. These data will provide information on gene discovery, transcriptional regulation and marker-assisted selection for <it>P. notoginseng</it>. The dataset establishes an important foundation for the study with the purpose of ensuring adequate drug resources for this species.</p

Dual Characters of GH-IGF1 Signaling Pathways in Radiotherapy and Post-radiotherapy Repair of Cancers

Radiotherapy remains one of the most important cancer treatment modalities. In the course of radiotherapy for tumor treatment, the incidental irradiation of adjacent tissues could not be completely avoided. DNA damage is one of the main factors of cell death caused by ionizing radiation, including single-strand (SSBs) and double-strand breaks (DSBs). The growth hormone-Insulin-like growth factor 1 (GH-IGF1) axis plays numerous roles in various systems by promoting cell proliferation and inhibiting apoptosis, supporting its effects in inducing the development of multiple cancers. Meanwhile, the GH-IGF1 signaling involved in DNA damage response (DDR) and DNA damage repair determines the radio-resistance of cancer cells subjected to radiotherapy and repair of adjacent tissues damaged by radiotherapy. In the present review, we firstly summarized the studies on GH-IGF1 signaling in the development of cancers. Then we discussed the adverse effect of GH-IGF1 signaling in radiotherapy to cancer cells and the favorable impact of GH-IGF1 signaling on radiation damage repair to adjacent tissues after irradiation. This review further summarized recent advances on research into the molecular mechanism of GH-IGF1 signaling pathway in these effects, expecting to specify the dual characters of GH-IGF1 signaling pathways in radiotherapy and post-radiotherapy repair of cancers, subsequently providing theoretical basis of their roles in increasing radiation sensitivity during cancer radiotherapy and repairing damage after radiotherapy

Giant All-Optical Modulation of Second-Harmonic Generation Mediated by Dark Excitons.

All-optical control of nonlinear photonic processes in nanomaterials is of significant interest from a fundamental viewpoint and with regard to applications ranging from ultrafast data processing to spectroscopy and quantum technology. However, these applications rely on a high degree of control over the nonlinear response, which still remains elusive. Here, we demonstrate giant and broadband all-optical ultrafast modulation of second-harmonic generation (SHG) in monolayer transition-metal dichalcogenides mediated by the modified excitonic oscillation strength produced upon optical pumping. We reveal a dominant role of dark excitons to enhance SHG by up to a factor of ∼386 at room temperature, 2 orders of magnitude larger than the current state-of-the-art all-optical modulation results. The amplitude and sign of the observed SHG modulation can be adjusted over a broad spectral range spanning a few electronvolts with ultrafast response down to the sub-picosecond scale via different carrier dynamics. Our results not only introduce an efficient method to study intriguing exciton dynamics, but also reveal a new mechanism involving dark excitons to regulate all-optical nonlinear photonics

Maternal, neonatal, pregnancy outcome characteristics of pregnant women with high plasma cell-free DNA concentration in non-invasive prenatal screening: a retrospective analysis

ObjectiveCell-free DNA (cfDNA) is a useful biomarker in various clinical contexts. Herein, we aimed to identify maternal characteristics and pregnancy outcomes associated with a failed NIPS test due to high cfDNA concentrations.MethodsA retrospective study of cases with high plasma cfDNA concentration in pregnant women in which NIPS test was performed (from 174,318 cases). We reported the detection of 126 cases (118 with complete clinical information) in which the high amount of cfDNA did not allow the performance of NIPS and study the possible causes of this result.Results622 (0.35%) of 174,318 pregnant women had failed the NIPS test, including 126 (20.3%) cases with high plasma cfDNA concentrations. The failed NIPS due to high plasma cfDNA concentrations was associated with maternal diseases and treatment with low-molecular-weight heparin (LMWH). Further follow-up of the 118 pregnant women in the case group revealed that the pregnancy outcomes included 31 premature deliveries, 21 abortions. The cfDNA concentrations of pregnant women with preterm deliveries were 1.15 (0.89, 1.84), which differed significantly from those who had full-term deliveries.ConclusionsAmong pregnant women with high cfDNA concentrations, systemic autoimmune diseases, pregnancy complications and LMWH were associated with increased incidence of failed NIPS test. High maternal cfDNA concentrations may not be associated with chromosomal abnormalities in the fetus. However, they should be alerted to the possibility of preterm births and stillbirths. Further clinical studies on pregnant women with high cfDNA concentrations are required

Genome Assembly for a Yunnan-Guizhou Plateau “3E” Fish, Anabarilius grahami (Regan), and Its Evolutionary and Genetic Applications

A Yunnan-Guizhou Plateau fish, the Kanglang white minnow (Anabarilius grahami), is a typical “3E” (Endangered, Endemic, and Economic) species in China. Its distribution is limited to Fuxian Lake, the nation’s second deepest lake, with a significant local economic value but a drastically declining wild population. This species has been evaluated as VU (Vulnerable) in the China Species Red List. As one of the “Four Famous Fish” in Yunnan province, the artificial breeding has been achieved since 2003. It has not only re-established its wild natural populations by reintroduction of the artificial breeding stocks, but also brought a wide and popular utilization of this species to the local fish farms. A. grahami has become one of the main native aquaculture species in Yunnan province, and the artificial production has been emerging in steady growth each year. To promote the conservation and sustainable utilization of this fish, we initiated its whole genome sequencing project using an Illumina Hiseq2500 platform. The assembled genome size of A. grahami is 1.006 Gb, accounting for 98.63% of the estimated genome size (1.020 Gb), with contig N50 and scaffold N50 values of 26.4 kb and 4.41 Mb, respectively. Approximately about 50.38% of the genome was repetitive. A total of 25,520 protein-coding genes were subsequently predicted. A phylogenetic tree based on 4,580 single-copy genes from A. grahami and 18 other cyprinids revealed three well-supported subclades within the Cyprinidae. This is the first inter-subfamily relationship of cyprinids at genome level, providing a simple yet useful framework for understanding the traditional but popular subfamily classification systems. Interestingly, a further population demography of A. grahami uncovered a historical relationship between this fish and Fuxian Lake, suggesting that range expansion or shrinkage of the habitat has had a remarkable impact on the population size of endemic plateau fishes. Additionally, a total of 33,836 simple sequence repeats (SSR) markers were identified, and 11 loci were evaluated for a preliminary genetic diversity analysis in this study, thus providing another useful genetic resource for studying this “3E” species

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data