RNA editing signature during myeloid leukemia cell differentiation

Adenosine deaminases acting on RNA (ADARs) are key proteins for hematopoietic stem cell self-renewal and for survival of differentiating progenitor cells. However, their specific role in myeloid cell maturation has been poorly investigated. Here we show that ADAR1 is present at basal level in the primary myeloid leukemia cells obtained from patients at diagnosis as well as in myeloid U-937 and THP1 cell lines and its expression correlates with the editing levels. Upon phorbol-myristate acetate or Vitamin D3/granulocyte macrophage colony-stimulating factor (GM-CSF)-driven differentiation, both ADAR1 and ADAR2 enzymes are upregulated, with a concomitant global increase of A-to-I RNA editing. ADAR1 silencing caused an editing decrease at specific ADAR1 target genes, without, however, interfering with cell differentiation or with ADAR2 activity. Remarkably, ADAR2 is absent in the undifferentiated cell stage, due to its elimination through the ubiquitin–proteasome pathway, being strongly upregulated at the end of the differentiation process. Of note, peripheral blood monocytes display editing events at the selected targets similar to those found in differentiated cell lines. Taken together, the data indicate that ADAR enzymes play important and distinct roles in myeloid cells

The Lunar Lander Neutron and Dosimetry (LND) Experiment on Chang'E 4

Chang'E 4 is the first mission to the far side of the Moon and consists of a lander, a rover, and a relay spacecraft. Lander and rover were launched at 18:23 UTC on December 7, 2018 and landed in the von K\'arm\'an crater at 02:26 UTC on January 3, 2019. Here we describe the Lunar Lander Neutron \& Dosimetry experiment (LND) which is part of the Chang'E 4 Lander scientific payload. Its chief scientific goal is to obtain first active dosimetric measurements on the surface of the Moon. LND also provides observations of fast neutrons which are a result of the interaction of high-energy particle radiation with the lunar regolith and of their thermalized counterpart, thermal neutrons, which are a sensitive indicator of subsurface water content.Comment: 38 pages, submitted to Space Science Review

Distinct control mechanism of fine-grained sediments from Yellow River and Kyushu supply in the northern Okinawa Trough since the last glacial

© 2017. American Geophysical Union. All Rights Reserved. High-resolution multiproxy records, including clay minerals and Sr-Nd-Pb isotopes of the clay-sized silicate fraction of sediments from IODP Site U1429 in the northern Okinawa Trough, provide reliable evidence for distinct control mechanism on fine-grained sediments input from the Yellow River and the southern Japanese Islands to the northern Okinawa Trough since 34 ka BP. Provenance analysis indicates that the sediments were mainly derived from the Yellow River and the island of Kyushu. Since the last glacial, clay-sized sediments transported from the Yellow River to the study site were strongly influenced by sea-level fluctuation. During low sea-level stage (∼34–14 ka BP), the paleo-Yellow River mouth was positioned closer to the northern Okinawa Trough, favoring large fluvial discharge or even direct input of detrital sediments, which resulted about four times more flux of clay-sized sediments supply to the study area as during the relatively high sea-level stage (∼14–0 ka BP). The input of Kyushu-derived clay-sized sediments to the study site was mainly controlled by the Kuroshio Current and Tsushima Warm Current intensity, with increased input in phase with weakened Kuroshio Current/Tsushima Warm Current. Our study suggests that the Kuroshio Current was very likely flowed into the Okinawa Trough and thus influenced the fine-grained sediment transport in the area throughout the last glacial and deglacial. During ∼34–11 ka BP, the Kyushu clay-sized sediment input was mainly controlled by the Kuroshio Current. Since ∼11 ka BP, the occurrence of Tsushima Warm Current became important in influencing the Kyushu fine-grained sediment input to the northern Okinawa Trough

Integrated Bio-Entity Network: A System for Biological Knowledge Discovery

A significant part of our biological knowledge is centered on relationships between biological entities (bio-entities) such as proteins, genes, small molecules, pathways, gene ontology (GO) terms and diseases. Accumulated at an increasing speed, the information on bio-entity relationships is archived in different forms at scattered places. Most of such information is buried in scientific literature as unstructured text. Organizing heterogeneous information in a structured form not only facilitates study of biological systems using integrative approaches, but also allows discovery of new knowledge in an automatic and systematic way. In this study, we performed a large scale integration of bio-entity relationship information from both databases containing manually annotated, structured information and automatic information extraction of unstructured text in scientific literature. The relationship information we integrated in this study includes protein–protein interactions, protein/gene regulations, protein–small molecule interactions, protein–GO relationships, protein–pathway relationships, and pathway–disease relationships. The relationship information is organized in a graph data structure, named integrated bio-entity network (IBN), where the vertices are the bio-entities and edges represent their relationships. Under this framework, graph theoretic algorithms can be designed to perform various knowledge discovery tasks. We designed breadth-first search with pruning (BFSP) and most probable path (MPP) algorithms to automatically generate hypotheses—the indirect relationships with high probabilities in the network. We show that IBN can be used to generate plausible hypotheses, which not only help to better understand the complex interactions in biological systems, but also provide guidance for experimental designs

Aspergillus Myosin-V Supports Polarized Growth in the Absence of Microtubule-Based Transport

In the filamentous fungus Aspergillus nidulans, both microtubules and actin filaments are important for polarized growth at the hyphal tip. Less clear is how different microtubule-based and actin-based motors work together to support this growth. Here we examined the role of myosin-V (MYOV) in hyphal growth. MYOV-depleted cells form elongated hyphae, but the rate of hyphal elongation is significantly reduced. In addition, although wild type cells without microtubules still undergo polarized growth, microtubule disassembly abolishes polarized growth in MYOV-depleted cells. Thus, MYOV is essential for polarized growth in the absence of microtubules. Moreover, while a triple kinesin null mutant lacking kinesin-1 (KINA) and two kinesin-3s (UNCA and UNCB) undergoes hyphal elongation and forms a colony, depleting MYOV in this triple mutant results in lethality due to a severe defect in polarized growth. These results argue that MYOV, through its ability to transport secretory cargo, can support a significant amount of polarized hyphal tip growth in the absence of any microtubule-based transport. Finally, our genetic analyses also indicate that KINA (kinesin-1) rather than UNCA (kinesin-3) is the major kinesin motor that supports polarized growth in the absence of MYOV

Fish consumption and the risk of gastric cancer: systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Gastric cancer is the fourth most frequently occurring malignancy after lung, breast, and colorectal cancer, and the second most common cause of death from cancer worldwide. Epidemiologic studies have examined the possible association between fish consumption and gastric cancer, but the results were inconclusive. We conducted a systematic review and meta-analysis to examine the association between fish intake and the risk of gastric cancer.</p> <p>Methods</p> <p>PubMed was searched for studies published in English-language journals from 1991 through 2009. We identified 17 epidemiologic studies (15 case-control and 2 cohort studies) that included relative risks (RRs) or odds ratios (ORs) estimates with 95% confidence intervals (CIs) of the relationship between gastric cancer and fish consumption. Data were extracted using standardized data forms. Summary RRs or ORs for the highest versus non/lowest fish consumption levels were calculated using random-effects model. Heterogeneity among studies was examined using Q and I²statistics.</p> <p>Results</p> <p>In this study, 5,323 cases of gastric cancer and over 130,000 non-cases were included. The combined results from all studies indicated that the association between high fish consumption and reduced gastric cancer risk was not statistically insignificant (RR = 0.87, 95% CI = 0.71-1.07).</p> <p>Conclusions</p> <p>Current evidence indicated that the association between fish consumption and risk of gastric cancer remains unclear.</p

Antiphased dust deposition and productivity in the Antarctic Zone over 1.5 million years

The Southern Ocean paleoceanography provides key insights into how iron fertilization and oceanic productivity developed through Pleistocene ice-ages and their role in influencing the carbon cycle. We report a high-resolution record of dust deposition and ocean productivity for the Antarctic Zone, close to the main dust source, Patagonia. Our deep-ocean records cover the last 1.5 Ma, thus doubling that from Antarctic ice-cores. We find a 5 to 15-fold increase in dust deposition during glacials and a 2 to 5-fold increase in biogenic silica deposition, reflecting higher ocean productivity during interglacials. This antiphasing persisted throughout the last 25 glacial cycles. Dust deposition became more pronounced across the Mid-Pleistocene Transition (MPT) in the Southern Hemisphere, with an abrupt shift suggesting more severe glaciations since ~0.9 Ma. Productivity was intermediate pre-MPT, lowest during the MPT and highest since 0.4 Ma. Generally, glacials experienced extended sea-ice cover, reduced bottom-water export and Weddell Gyre dynamics, which helped lower atmospheric CO2 levels