Recurrent DNMT3A R882 Mutations in Chinese Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome

Somatic mutations of DNMT3A gene have recently been reported in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We examined the entire coding sequences of DNMT3A gene by high-resolution melting analysis and sequencing in Chinese patients with myeloid malignancies. R882 mutations were found in 12/182 AML and in 4/51 MDS, but not in either 79 chronic myeloid leukemia (CML), or 57 myeloproliferative neoplasms (MPNs), or 4 chronic monomyelocytic leukemia. No other DNMT3A mutations were detected in all patients. R882 mutations were associated with old age and more frequently present in monoblastic leukemia (M4 and M5, 7/52) compared to other subtypes (5/130). Furthermore, 14/16 (86.6%) R882 mutations were observed in patients with normal karyotypes. The overall survival of mutated MDS patients was shorter than those without mutation (median 9 and 25 months, respectively). We conclude that DNMT3A R882 mutations are recurrent molecular aberrations in AML and MDS, and may be an adverse prognostic event in MDS

Ultrahigh mobility and efficient charge injection in monolayer organic thin-film transistors on boron nitride

Organic thin-film transistors (OTFTs) with high mobility and low contact resistance have been actively pursued as building blocks for low-cost organic electronics. In conventional solution-processed or vacuum-deposited OTFTs, due to interfacial defects and traps, the organic film has to reach a certain thickness for efficient charge transport. Using an ultimate monolayer of 2,7-dioctyl[1]benzothieno[3,2-b][1]benzothiophene (C8-BTBT) molecules as an OTFT channel, we demonstrate remarkable electrical characteristics, including intrinsic hole mobility over 30 cm2/Vs, Ohmic contact with 100 Ω · cm resistance, and band-like transport down to 150 K. Compared to conventional OTFTs, the main advantage of a monolayer channel is the direct, nondisruptive contact between the charge transport layer and metal leads, a feature that is vital for achieving low contact resistance and current saturation voltage. On the other hand, bilayer and thicker C8-BTBT OTFTs exhibit strong Schottky contact and much higher contact resistance but can be improved by inserting a doped graphene buffer layer. Our results suggest that highly crystalline molecular monolayers are promising form factors to build high-performance OTFTs and investigate device physics. They also allow us to precisely model how the molecular packing changes the transport and contact properties

Chinese herb related molecules of cancer-cell-apoptosis: a minireview of progress between Kanglaite injection and related genes

Many kinds of Chinese herb had been confirmed to have the character of anti-tumor, clinical reports about anti-tumor effects of Chinese herb had also been found in recent years, but most of the reports were focused on the clinical treatment of effectiveness for Chinese herb, on the other hand, review about Chinese herbal related with molecules on cancer-cell-apoptosis was seldom, many scientists could not believe such kinds of clinical describes about anti-tumor effects for Chinese herb, because these describes were lack of molecular biology evidence. Kanglaite(KLT) injection is an anti-tumor new drug which extracts from Chinese medicine-coix seed with modern advanced pharmaceutical technology, it is also a new biphase extended-spectrum anticancer medicine, the food and drug administration(FDA) of United States also approved a phase II trial of KLT to test its efficacy in treating non-small-cell lung cancer. Some studies show it could inhibit some anti-apoptotic gene and activate some pro-apoptotic gene, its injection solution is one of the new anticancer medicine that can significantly inhibit a various kinds of tumor cells, so it has become the core of research that how to further explore KLT injection to promote tumor cell apoptosis by impacting on related genes. In this review, the relationship between KLT and some tumor cell apoptosis molecules had been discussed and reviewed generally

Molecular Characterization of Tb, a New Approach for an Ancient Brucellaphage

Tb (Tbilisi), the reference Brucellaphage strain, was classified as a member of the Podoviridae family with icosahedral capsids (57 ± 2 nm diameter) and short tails (32 ± 3 nm long). Brucellaphage DNA was double stranded and unmethylated; its molecular size was 34.5 kilobase pairs. Some sequences were found through RAPD analysis, TA cloning technology, and structural proteins were observed by using SDS-PAGE. Thus, the results have laid the foundation for the wider use of Brucellaphage’s basic mechanisms and practical applications

Natural Coevolution of Tumor and Immunoenvironment in Glioblastoma.

Isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) has a dismal prognosis. A better understanding of tumor evolution holds the key to developing more effective treatment. Here we study GBM\u27s natural evolutionary trajectory by using rare multifocal samples. We sequenced 61,062 single cells from eight multifocal IDH wild-type primary GBMs and defined a natural evolution signature (NES) of the tumor. We show that the NES significantly associates with the activation of transcription factors that regulate brain development, including MYBL2 and FOSL2. Hypoxia is involved in inducing NES transition potentially via activation of the HIF1A-FOSL2 axis. High-NES tumor cells could recruit and polarize bone marrow-derived macrophages through activation of the FOSL2-ANXA1-FPR1/3 axis. These polarized macrophages can efficiently suppress T-cell activity and accelerate NES transition in tumor cells. Moreover, the polarized macrophages could upregulate CCL2 to induce tumor cell migration. SIGNIFICANCE: GBM progression could be induced by hypoxia via the HIF1A-FOSL2 axis. Tumor-derived ANXA1 is associated with recruitment and polarization of bone marrow-derived macrophages to suppress the immunoenvironment. The polarized macrophages promote tumor cell NES transition and migration. This article is highlighted in the In This Issue feature, p. 2711

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 <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

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Graphene and Related Materials for Resistive Random Access Memories

Graphene and related materials (GRMs) are promising candidates for the fabrication of resistive random access memories (RRAM). Here, we analyze, classify and evaluate this emerging field, and summarize the performance of the RRAM prototypes using GRMs. Graphene oxide, amorphous carbon films, transition metal dichalcogenides, hexagonal boron nitride and black phosphorous can be used as resistive switching media, in which the switching can be governed either by the migration of intrinsic species or penetration of metallic ions from adjacent layers. Graphene can be used as electrode to provide flexibility and transparency, as well as an interface layer between the electrode and dielectric to block atomic diffusion, reduce power consumption, suppress surface effects, limit the number of conductive filaments in the dielectric, and improve device integration. GRMs-based RRAMs fit some non-volatile memory technological requirements like low operating voltages 10 years, endurance >109 cycles and power consumption ~10 pJ/transition still remain a challenge. More technology-oriented studies including reliability and variability analyses may lead to the development of GRMs-based RRAMs with realistic possibilities of commercialization.We acknowledge support from the Young 1000 Global Talent Recruitment Program of the Ministry of Education of China, the National Natural Science Foundation of China (grants no. 61502326, 41550110223), the Jiangsu Government (grant no. BK20150343), the Ministry of Finance of China (grant no. SX21400213), the Young 973 National Program of the Chinese Ministry of Science and Technology (grant no. 2015CB932700), the Collaborative Innovation Center of Suzhou Nano Science & Technology, the Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, the Priority Academic Program Development of Jiangsu Higher Education Institutions, the National Natural Science Foundation of China under Grant Nos. 61521064, 61322408, 61422407, the Beijing Training Project for the Leading Talents in S&T under Grant No. ljrc201508, the Opening Project of Key Laboratory of Microelectronic Devices & Integrated Technology, Institute of Microelectronics, Chinese Academy of Sciences, the EU Graphene Flagship, FP7 Grant CARERAMM, ERC Grants Hetero2D and Highgraink, EPSRC Grants EP/K01711X/1, EP/K017144/1, EP/N010345/1, EP/M507799/1, EP/L016087/1, EP/M013243/1