ALBERT

Description: Hydrocarbon evolution is extremely challenging to determine, both temporally and spatially, in complex tectonic settings. Here we investigate the western margin of the Xuefeng uplift (southern China), which records multiple and protracted tectonic and hydrocarbon-generation events. This timing of initial oil generation is recorded by low-maturity bitumen (type A), which yields an Re-Os bitumen date of ca. 430 Ma, consistent with basin models and a ca. 405 Ma bitumen Rb-Sr date. In contrast, apatite fission-track (AFT) data yield considerably younger dates that reflect the timing and tectonic evolution of the Yanshan orogeny from the northwest (ca. 150 Ma) to the southeast (ca. 70 Ma). The youngest AFT date coincides with the western margin of Xuefeng uplift, where high-maturity bitumen (type B) occurs that yields a ca. 70 Ma Re-Os date. The Re-Os and AFT dates imply that both the last stage of the Yanshan orogeny and, by inference, the cessation of dry gas generation, occurred ca. 70 Ma. The Re-Os data of this study imply that the Re-Os chronometer can aid in constraining the timing of oil generation and secondary and/or more mature hydrocarbon processes (e.g., thermal cracking and/or gas generation) in hydrocarbon systems worldwide.

Description: Acceleration in development of additional conventional hydropower requires tools and methods to perform laboratory and in-field validation of turbine performance and fish passage claims. The new-generation Sensor Fish has been developed with more capabilities to accommodate a wider range of users over a broader range of turbine designs and operating environments. It provides in situ measurements of three-dimensional (3D) linear accelerations, 3D rotational velocities, 3D orientation, pressure, and temperature at a sampling frequency of 2048 Hz. It also has an automatic floatation system and built-in radio-frequency transmitter for recovery. The relative errors of the pressure, acceleration, and rotational velocity were within ±2%, ±5%, and ±5%, respectively. The accuracy of orientation was within ±4° and accuracy of temperature was ±2 °C. The new-generation Sensor Fish is becoming a major technology and being deployed for evaluating the conditions for fish passage of turbines or other hydraulic structures in both the United States and several other countries.

Description: Diacylglycerol lipases (DAGLα and DAGLβ) convert diacylglycerol to the endocannabinoid 2-arachidonoylglycerol. Our understanding of DAGL function has been hindered by a lack of chemical probes that can perturb these enzymes in vivo. Here, we report a set of centrally active DAGL inhibitors and a structurally related control probe and their...

Description: Most mammalian genes have mRNA variants due to alternative promoter usage, alternative splicing, and alternative cleavage and polyadenylation. Expression of alternative RNA isoforms has been found to be associated with tumorigenesis, proliferation and differentiation. Detection of condition-associated transcription variation requires association methods. Traditional association methods such as Pearson chi-square test and Fisher Exact test are single test methods and do not work on count data with replicates. Although the Cochran Mantel Haenszel (CMH) approach can handle replicated count data, our simulations showed that multiple CMH tests still had very low power. To identify condition-associated variation of transcription, we here proposed a ranking analysis of chi-squares (RAX2) for large-scale association analysis. RAX2 is a nonparametric method and has accurate and conservative estimation of FDR profile. Simulations demonstrated that RAX2 performs well in finding condition-associated transcription variants. We applied RAX2 to primary T-cell transcriptomic data and identified 1610 (16.3%) tags associated in transcription with immune stimulation at FDR 〈 0.05. Most of these tags also had differential expression. Analysis of two and three tags within genes revealed that under immune stimulation short RNA isoforms were preferably used.

Description: Salmon recovery and the potential detrimental effects of dams on fish have been attracting national attention due to the environmental and economic implications. In recent years acoustic telemetry has been the primary method for studying salmon passage. However, the size of the existing transmitters limits the minimum size of fish that can be studied, introducing a bias to the study results. We developed the first acoustic fish transmitter that can be implanted by injection instead of surgery. The new injectable transmitter lasts four times longer and weighs 30% less than other transmitters. Because the new transmitter costs significantly less to use and may substantially reduce adverse effects of implantation and tag burden, it will allow for study of migration behavior and survival of species and sizes of fish that have never been studied before. The new technology will lead to critical information needed for salmon recovery and the development of fish-friendly hydroelectric systems. Scientific Reports 5 doi: 10.1038/srep08111

Description: Human Epidermal Growth Factor Receptor 2-positive (HER2+) breast cancer (BC) is a highly aggressive disease commonly treated with chemotherapy and anti-HER2 drugs, including trastuzumab. There is currently no way to predict which HER2+ BC patients will benefit from these treatments. Previous prognostic signatures for HER2+ BC were developed irrespective of the subtype or the hierarchical organization of cancer in which only a fraction of cells, tumor-initiating cells (TICs), can sustain tumor growth. Here, we used serial dilution and single-cell transplantation assays to identify MMTV-Her2/Neu mouse mammary TICs as CD24+:JAG1− at a frequency of 2–4.5%. A 17-gene Her2-TIC-enriched signature (HTICS), generated on the basis of differentially expressed genes in TIC versus non-TIC fractions and trained on one HER2+ BC cohort, predicted clinical outcome on multiple independent HER2+ cohorts. HTICS included up-regulated genes involved in S/G2/M transition and down-regulated genes involved in immune response. Its prognostic power was independent of other predictors, stratified lymph node+ HER2+ BC into low and high-risk subgroups, and was specific for HER2+:estrogen receptor alpha-negative (ERα−) patients (10-y overall survival of 83.6% for HTICS− and 24.0% for HTICS+ tumors; hazard ratio = 5.57; P = 0.002). Whereas HTICS was specific to HER2+:ERα− tumors, a previously reported stroma-derived signature was predictive for HER2+:ERα+ BC. Retrospective analyses revealed that patients with HTICS+ HER2+:ERα− tumors resisted chemotherapy but responded to chemotherapy plus trastuzumab. HTICS is, therefore, a powerful prognostic signature for HER2+:ERα− BC that can be used to identify high risk patients that would benefit from anti-HER2 therapy.

Description: Seedling photomorphogenesis is a sophisticated developmental process that is controlled by both the transcriptional and posttranscriptional regulation of gene expression. Here, we identify an Arabidopsis noncoding RNA, designated HIDDEN TREASURE 1 (HID1), as a factor promoting photomorphogenesis in continuous red light (cR). We show that HID1 acts through PHYTOCHROME-INTERACTING FACTOR...

Description: Abstract An ion‐scale flux rope (FR), embedded in a high‐speed electron flow (possibly an electron vortex), is investigated in the magnetotail using observations from the Magnetospheric Multiscale (MMS) spacecraft. Intense electric field and current and abundant waves are observed in the exterior and interior regions of the FR. Comparable parallel and perpendicular currents in the interior region imply that the FR has a non‐force‐free configuration. Electron demagnetization occurs in some subregions of the FR. It is surprising that strong dissipation (J × E' up to 2,000 pW/m3) occurs in the center of the FR without signatures of secondary reconnection or coalescence of two FRs, implying that FR may provide another important channel for energy dissipation in space plasmas. These features indicate that the observed FR is still highly dynamical, and hosts multiscale coupling processes, even though the FR has a very large scale and is far away from the reconnection site.

Description: The major facilitator superfamily glucose transporters, exemplified by human GLUT1-4, have been central to the study of solute transport. Using lipidic cubic phase crystallization and microfocus X-ray diffraction, we determined the structure of human GLUT3 in complex with D-glucose at 1.5 A resolution in an outward-occluded conformation. The high-resolution structure allows discrimination of both alpha- and beta-anomers of D-glucose. Two additional structures of GLUT3 bound to the exofacial inhibitor maltose were obtained at 2.6 A in the outward-open and 2.4 A in the outward-occluded states. In all three structures, the ligands are predominantly coordinated by polar residues from the carboxy terminal domain. Conformational transition from outward-open to outward-occluded entails a prominent local rearrangement of the extracellular part of transmembrane segment TM7. Comparison of the outward-facing GLUT3 structures with the inward-open GLUT1 provides insights into the alternating access cycle for GLUTs, whereby the C-terminal domain provides the primary substrate-binding site and the amino-terminal domain undergoes rigid-body rotation with respect to the C-terminal domain. Our studies provide an important framework for the mechanistic and kinetic understanding of GLUTs and shed light on structure-guided ligand design.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deng, Dong -- Sun, Pengcheng -- Yan, Chuangye -- Ke, Meng -- Jiang, Xin -- Xiong, Lei -- Ren, Wenlin -- Hirata, Kunio -- Yamamoto, Masaki -- Fan, Shilong -- Yan, Nieng -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Oct 15;526(7573):391-6. doi: 10.1038/nature14655. Epub 2015 Jul 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉State Key Laboratory of Membrane Biology, Tsinghua University, Beijing 100084, China. ; Center for Structural Biology, Tsinghua University, Beijing 100084, China. ; Tsinghua-Peking Center for Life Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China. ; Advanced Photon Technology Division, Research Infrastructure Group, SR Life Science Instrumentation Unit, RIKEN/SPring-8 Center, 1-1-1 Kouto Sayo-cho Sayo-gun, Hyogo 679-5148 Japan. ; Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26176916" target="_blank"〉PubMed〈/a〉