Description: © The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Biogeosciences 15 (2018): 5847-5889, doi:10.5194/bg-15-5847-2018.

Description: Since the start of the industrial revolution, human activities have caused a rapid increase in atmospheric carbon dioxide (CO2) concentrations, which have, in turn, had an impact on climate leading to global warming and ocean acidification. Various approaches have been proposed to reduce atmospheric CO2. The Martin (or iron) hypothesis suggests that ocean iron fertilization (OIF) could be an effective method for stimulating oceanic carbon sequestration through the biological pump in iron-limited, high-nutrient, low-chlorophyll (HNLC) regions. To test the Martin hypothesis, 13 artificial OIF (aOIF) experiments have been performed since 1990 in HNLC regions. These aOIF field experiments have demonstrated that primary production (PP) can be significantly enhanced by the artificial addition of iron. However, except in the Southern Ocean (SO) European Iron Fertilization Experiment (EIFEX), no significant change in the effectiveness of aOIF (i.e., the amount of iron-induced carbon export flux below the winter mixed layer depth, MLD) has been detected. These results, including possible side effects, have been debated amongst those who support and oppose aOIF experimentation, and many questions concerning the effectiveness of scientific aOIF, environmental side effects, and international aOIF law frameworks remain. In the context of increasing global and political concerns associated with climate change, it is valuable to examine the validity and usefulness of the aOIF experiments. Furthermore, it is logical to carry out such experiments because they allow one to study how plankton-based ecosystems work by providing insight into mechanisms operating in real time and under in situ conditions. To maximize the effectiveness of aOIF experiments under international aOIF regulations in the future, we therefore suggest a design that incorporates several components. (1) Experiments conducted in the center of an eddy structure when grazing pressure is low and silicate levels are high (e.g., in the SO south of the polar front during early summer). (2) Shipboard observations extending over a minimum of  ∼ 40 days, with multiple iron injections (at least two or three iron infusions of  ∼ 2000kg with an interval of  ∼ 10–15 days to fertilize a patch of 300km2 and obtain a  ∼ 2nM concentration). (3) Tracing of the iron-fertilized patch using both physical (e.g., a drifting buoy) and biogeochemical (e.g., sulfur hexafluoride, photosynthetic quantum efficiency, and partial pressure of CO2) tracers. (4) Employment of neutrally buoyant sediment traps (NBST) and application of the water-column-derived thorium-234 (234Th) method at two depths (i.e., just below the in situ MLD and at the winter MLD), with autonomous profilers equipped with an underwater video profiler (UVP) and a transmissometer. (5) Monitoring of side effects on marine/ocean ecosystems, including production of climate-relevant gases (e.g., nitrous oxide, N2O; dimethyl sulfide, DMS; and halogenated volatile organic compounds, HVOCs), decline in oxygen inventory, and development of toxic algae blooms, with optical-sensor-equipped autonomous moored profilers and/or autonomous benthic vehicles. Lastly, we introduce the scientific aOIF experimental design guidelines for a future Korean Iron Fertilization Experiment in the Southern Ocean (KIFES).

Description: This research was a part of the project titled the Korean Iron Fertilization Experiment in the Southern Ocean (KOPRI, PM 16060) funded by the Ministry of Oceans and Fisheries, Korea. This work was partly supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (no. 2015R1C1A1A01052051); the Korea-Arctic Ocean Observing System project (K-AOOS) (KOPRI, 20160245) funded by the MOF, Korea; and the KOPRI project (PE18200). Alison M. Macdonald was supported by NOAA grant no. NA11OAR4310063 and internal WHOI funding.

Description: © The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Kim, S., Kalappurakkal, J. M., Mayor, S., & Rosen, M. K. Phosphorylation of nephrin induces phase separated domains that move through actomyosin contraction. Molecular Biology of the Cell, 30(24), (2019): 2996–3012, doi:10.1091/mbc.E18-12-0823.

Description: The plasma membrane of eukaryotic cells is organized into lipid and protein microdomains, whose assembly mechanisms and functions are incompletely understood. We demonstrate that proteins in the nephrin/Nck/N-WASP actin-regulatory pathway cluster into micron-scale domains at the basal plasma membrane upon triggered phosphorylation of transmembrane protein nephrin. The domains are persistent but readily exchange components with their surroundings, and their formation is dependent on the number of Nck SH3 domains, suggesting they are phase separated polymers assembled through multivalent interactions among the three proteins. The domains form independent of the actin cytoskeleton, but acto-myosin contractility induces their rapid lateral movement. Nephrin phosphorylation induces larger clusters at the cell periphery, which are associated with extensive actin assembly and dense filopodia. Our studies illustrate how multivalent interactions between proteins at the plasma membrane can produce micron-scale organization of signaling molecules, and how the resulting clusters can both respond to and control the actin cytoskeleton.

Description: We thank Hongtao Yu (University of Texas Southwestern Medical Center [UTSW]) for providing the HeLa cell line used in this work; Dan Billadeau and Timothy Gomez (Mayo Clinic) for providing antibodies; Nico Stuurman (University of California, San Francisco) for assistance with STORM imaging; Kate Luby-Phelps and Abhijit Bugde (UTSW Live Cell Imaging Core Facility) for their assistance in epifluorescence and spinning disk confocal experiments; Sudeep Banjade for advice on designing the S3, S2, S1 constructs; Khuloud Jaqaman (UTSW) for advice on cluster motility analysis; Salman Banani and Jonathan Ditlev (UTSW) for critical reading of the manuscript; and members of the Rosen lab and participants in the MBL/HHMI Summer Institutes for advice and helpful discussions. This work was supported by a Howard Hughes Medical Institute Collaborative Innovation Award; the Welch Foundation (I-1544 to M.K.R.); a J.C. Bose Fellowship from the Department of Science and Technology, government of India (to S.M.); a Margadarshi Fellowship from the Wellcome Trust—Department of Biotechnology, India Alliance (IA/M/15/1/502018 to S.M.). Research in the Rosen lab is supported by the Howard Hughes Medical Institute.

Description: Thymidylate synthase (TS), a critical enzyme for DNA synthesis and repair is both a potential tumor prognostic biomarker as well as a tumorgenic oncogene in animal models. We have now studied the clinical implications of TS expression in gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) and compared these results with other cell cycle biomarker genes. Protein tissue arrays were used to study TS, Ki-67, Rb, pRb, E2F1, p18, p21, p27, and menin expression in 320 human GEP-NETs samples. Immunohistochemical expression was correlated with univariate and multivariate predictors of survival utilizing Kaplan Meier and Cox proportional hazards models. Real time RT-PCR was used to validate these findings. We found that 78 of 320 GEP-NETs (24.4%) expressed TS. NETs arising in the colon, stomach, and pancreas showed the highest expression of TS (47.4%, 42.6%, and 37.3%, respectively), whereas NETs of the appendix, rectum, and duodenum displayed low TS expression (3.3%, 12.9%, and 15.4%, respectively). TS expression in GEP-NETs was associated with poorly differentiated endocrine carcinoma, angiolymphatic invasion, lymph node metastasis, and distant metastasis (p 〈 0.05). Patients with TS-positive NETs had markedly worse outcomes than TS-negative NETs as shown by univariate (p 〈 0.001) and multivariate (p = 0.01) survival analyses. Expression of p18 predicted survival in TS-positive patients that received chemotherapy (p = 0.015). In conclusion, TS protein expression was an independent prognostic biomarker for GEP-NETs. The strong association of increased TS expression with aggressive disease and early death supports the role of TS as a cancer promoting agent in these tumors. © 2013 Wiley Periodicals, Inc.

Description: Background: The role of omega-3 polyunsaturated fatty acids (omega3-PUFAs) in cancer prevention has been demonstrated; however, the exact molecular mechanisms underlying the anticancer activity of omega3-PUFAs are not fully understood. Here, we investigated the relationship between the anticancer action of a specific omega3-PUFA docosahexaenoic acid (DHA), and the conventional mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK), c-JUN N-terminal kinase (JNK) and p38 whose dysregulation has been implicated in human cancers. Methods: MTT assays were carried out to determine cell viability of cancer cell lines (PA-1, H1299, D54MG and SiHa) from different origins. Apoptosis was confirmed by TUNEL staining, DNA fragmentation analysis and caspase activity assays. Activities of the conventional MAPKs were monitored by their phosphorylation levels using immunoblotting and immunocytochemistry analysis. Reactive oxygen species (ROS) production was measured by flow cytometry and microscopy using fluorescent probes for general ROS and mitochondrial superoxide. Results: DHA treatment decreased cell viability and induced apoptotic cell death in all four studied cell lines. DHA-induced apoptosis was coupled to the activation of the conventional MAPKs, and knockdown of ERK/JNK/p38 by small interfering RNAs reduced the apoptosis induced by DHA, indicating that the pro-apoptotic effect of DHA is mediated by MAPKs activation. Further study revealed that the DHA-induced MAPKs activation and apoptosis was associated with mitochondrial ROS overproduction and malfunction, and that ROS inhibition remarkably reversed these effects of DHA. Conclusion: Together, these results indicate that DHA-induced MAPKs activation is dependent on its capacity to provoke mitochondrial ROS generation, and accounts for its cytotoxic effect in human cancer cells.

Description: Organic Letters DOI: 10.1021/acs.orglett.6b00300

Description: Pancreatic ductal adenocarcinomas are among the most malignant neoplasms and have very poor prognosis. Our understanding of various cancers has recently improved the survival of patients with cancer, except fo...

Description: Pancreatic ductal adenocarcinomas are among the most malignant neoplasms and have very poor prognosis. Our understanding of various cancers has recently improved the survival of patients with cancer, except fo...