Loss of T Cell Progenitor Checkpoint Control Underlies Leukemia Initiation in Rag1-Deficient Nonobese Diabetic Mice

NOD mice exhibit major defects in the earliest stages of T cell development in the thymus. Genome-wide genetic and transcriptome analyses were used to investigate the origins and consequences of an early T cell developmental checkpoint breakthrough in Rag1-deficient NOD mice. Quantitative trait locus analysis mapped the presence of checkpoint breakthrough cells to several known NOD diabetes susceptibility regions, particularly insulin-dependent diabetes susceptibility genes (Idd)9/11 on chromosome 4, suggesting common genetic origins for T cell defects affecting this trait and autoimmunity. Genome-wide RNA deep-sequencing of NOD and B6 Rag1-deficient thymocytes revealed the effects of genetic background prior to breakthrough, as well as the cellular consequences of the breakthrough. Transcriptome comparison between the two strains showed enrichment in differentially expressed signal transduction genes, prominently tyrosine kinase and actin-binding genes, in accord with their divergent sensitivities to activating signals. Emerging NOD breakthrough cells aberrantly expressed both stem cell–associated proto-oncogenes, such as Lmo2, Hhex, Lyl1, and Kit, which are normally repressed at the commitment checkpoint, and post–β-selection checkpoint genes, including Cd2 and Cd5. Coexpression of genes characteristic of multipotent progenitors and more mature T cells persists in the expanding population of thymocytes and in the thymic leukemias that emerge with age in these mice. These results show that Rag1-deficient NOD thymocytes have T cell defects that can collapse regulatory boundaries at two early T cell checkpoints, which may predispose them to both leukemia and autoimmunity

Twinning-assisted static recrystallization and texture evolution in a Mg-Gd-Y-Zr alloy

The formability and mechanical properties of magnesium (Mg) alloys are strongly related to the crystallographic basal texture. Twins play critical roles in adjusting crystallographic orientation of grains during both deformation and annealing treatment via deformation twinning and twinning-assisted recrystallization. In this study, cold rolling and subsequent annealing were conducted on a Mg-5.9Gd-3.3Y-0.5Zr alloy to investigate the recrystallization behavior and texture evolution. Electron backscatter diffraction and transmission electron microscopy techniques were applied to characterize the nucleation of recrystallized grains, especially the twinning-assisted recrystallization, at multi-scales. The results indicated that a large number of {10-12}, {10-11} twins and {10-11} - {10-12} double twins were introduced after cold rolling. The {10-11} - {10-12} double twins, double twin - grain boundary intersections and dense twin-twin intersections acted as the preferential nucleation sites for recrystallization during annealing treatment, while the coarse and parallel {10-12} twins were unfavorable for the nucleation of recrystallized grains. Although {10-12} tension twins are the most common twins in Mg alloys, the interface of this type of twin has strong mobility and is easy to expand. Therefore, it is generally difficult for a single {10-12} twin to recrystallize. However, the {10-11} compression twins and {10-11} - {10-12} double twins are generally difficult to expand and can store high deformation energy, so they are conducive to becoming nucleation sites for recrystallization. During the recrystallization process, the texture type (basal texture) of the cold rolled sample remained unchanged, but the overall texture intensity was significantly reduced due to the dispersion of grain orientations brought by new grains generated by twinning recrystallization

Targeting epithelial-mesenchymal transition and cancer stem cells for chemoresistant ovarian cancer

Chemoresistance is the main challenge for the recurrent ovarian cancer therapy and responsible for treatment failure and unfavorable clinical outcome. Understanding mechanisms of chemoresistance in ovarian cancer would help to predict disease progression, develop new therapies and personalize systemic therapy. In the last decade, accumulating evidence demonstrates that epithelial-mesenchymal transition and cancer stem cells play important roles in ovarian cancer chemoresistance and metastasis. Treatment of epithelial-mesenchymal transition and cancer stem cells holds promise for improving current ovarian cancer therapies and prolonging the survival of recurrent ovarian cancer patients in the future. In this review, we focus on the role of epithelial-mesenchymal transition and cancer stem cells in ovarian cancer chemoresistance and explore the therapeutic implications for developing epithelial-mesenchymal transition and cancer stem cells associated therapies for future ovarian cancer treatment

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Panax ginseng leaf aqueous extract mediated green synthesis of AgNPs under ultrasound condition and investigation of its anti-lung adenocarcinoma effects

Panax ginseng has many therapeutic uses in medicine. In the recent research, silver nanoparticles (AgNPs) were formulated by the Panax ginseng aqueous extract. The synthesized AgNPs’ characterization was analyzed using UV-Vis spectrophotometry, energy dispersive X-ray spectroscopy, scanning electron microscopy, fourier transformed infrared spectroscopy, transmission electron microscopy, and elemental mapping. The AgNPs were analyzed for their surface morphology by SEM. The successful synthesis of AgNPs was evident with TEM images. The AgNPs had a uniform distribution and homogenous spherical shaped morphology with mean diameter in the range of 20–30 nm. The cytotoxic and anti-lung adenocarcinoma ‎potentials of biologically formulated AgNPs‎ against NCI-H1563‎, NCI-H1437‎, NCI-H1299‎, and NCI-H2126 cells were determined. The anti-lung adenocarcinoma ‎ properties of the AgNPs ‎ removed NCI-H1563‎, NCI-H1437‎, NCI-H1299‎, and NCI-H2126 cells. The AgNPs’ IC50‎ were 193, 156, 250, and 278 µg/mL against NCI-H1563‎, NCI-H1437‎, NCI-H1299‎, and NCI-H2126 cells, respectively. Also, AgNPs presented high antioxidant potential

Monitoring Prostate Tumor Growth in an Orthotopic Mouse Model Using Three-Dimensional Ultrasound Imaging Technique

Prostate cancer (CaP) is the most commonly diagnosed and the second leading cause of death from cancer in males in USA. Prostate orthotopic mouse model has been widely used to study human CaP in preclinical settings. Measurement of changes in tumor size obtained from noninvasive diagnostic images is a standard method for monitoring responses to anticancer modalities. This article reports for the first time the usage of a three-dimensional (3D) ultrasound system equipped with photoacoustic (PA) imaging in monitoring longitudinal prostate tumor growth in a PC-3 orthotopic NODSCID mouse model (n = 8). Two-dimensional and 3D modes of ultrasound show great ability in accurately depicting the size and shape of prostate tumors. PA function on two-dimensional and 3D images showed average oxygen saturation and average hemoglobin concentration of the tumor. Results showed a good fit in representative exponential tumor growth curves (n = 3; r2 = 0.948, 0.955, and 0.953, respectively) and a good correlation of tumor volume measurements performed in vivo with autopsy (n = 8, r = 0.95, P < .001). The application of 3D ultrasound imaging proved to be a useful imaging modality in monitoring tumor growth in an orthotopic mouse model, with advantages such as high contrast, uncomplicated protocols, economical equipment, and nonharmfulness to animals. PA mode also enabled display of blood oxygenation surrounding the tumor and tumor vasculature and angiogenesis, making 3D ultrasound imaging an ideal tool for preclinical cancer research

Development of antibodies to human embryonic stem cell antigens

<p>Abstract</p> <p>Background</p> <p>Using antibodies to specific protein antigens is the method of choice to assign and identify cell lineage through simultaneous analysis of surface molecules and intracellular markers. Embryonic stem cell research can be benefited from using antibodies specific to transcriptional factors/markers that contribute to the "stemness" phenotype or critical for cell lineage.</p> <p>Results</p> <p>In this report, we have developed and validated antibodies (either monoclonal or polyclonal) specific to human embryonic stem cell antigens and early differentiation transcriptional factors/markers that are critical for cell differentiation into definite lineage.</p> <p>Conclusion</p> <p>These antibodies enable stem cell biologists to conveniently identify stem cell characteristics and to quantitatively assess differentiation.</p

Comparing Soil Organic Carbon Dynamics in PerennialGrasses and Shrubs in a Saline-Alkaline Arid Region,Northwestern China

BACKGROUND: Although semi-arid and arid regions account for about 40% of terrestrial surface of the Earth and contain approximately 10% of the global soil organic carbon stock, our understanding of soil organic carbon dynamics in these regions is limited. METHODOLOGY/PRINCIPAL FINDINGS: A field experiment was conducted to compare soil organic carbon dynamics between a perennial grass community dominated by Cleistogenes squarrosa and an adjacent shrub community co-dominated by Reaumuria soongorica and Haloxylon ammodendron, two typical plant life forms in arid ecosystems of saline-alkaline arid regions in northwestern China during the growing season 2010. We found that both fine root biomass and necromass in two life forms varied greatly during the growing season. Annual fine root production in the perennial grasses was 45.6% significantly higher than in the shrubs, and fine root turnover rates were 2.52 and 2.17 yr(−1) for the perennial grasses and the shrubs, respectively. Floor mass was significantly higher in the perennial grasses than in the shrubs due to the decomposition rate of leaf litter in the perennial grasses was 61.8% lower than in the shrubs even though no significance was detected in litterfall production. Soil microbial biomass and activity demonstrated a strong seasonal variation with larger values in May and September and minimum values in the dry month of July. Observed higher soil organic carbon stocks in the perennial grasses (1.32 Kg C m(−2)) than in the shrubs (1.12 Kg C m(−2)) might be attributed to both greater inputs of poor quality litter that is relatively resistant to decay and the lower ability of microorganism to decompose these organic matter. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the perennial grasses might accumulate more soil organic carbon with time than the shrubs because of larger amounts of inputs from litter and slower return of carbon through decomposition