A Mercury Lander Mission Concept Study for the Next Decadal Survey

Mariner 10 provided our first closeup reconnaissance of Mercury during its three flybys in 1974 and 1975. MESSENGERs 20112015 orbital investigation enabled numerous discoveries, several of which led to substantial or complete changes in our fundamental understanding of the planet. Among these were the unanticipated, widespread presence of volatile elements (e.g., Na, K, S); a surface with extremely low Fe abundance whose darkening agent is likely C; a previously unknown landformhollows that may form by volatile sublimation from within rocks exposed to the harsh conditions on the surface; a history of expansive effusive and explosive volcanism; substantial radial contraction of the planet from interior cooling; offset of the dipole moment of the internal magnetic field northward from the geographic equator by ~20% of the planets radius; crustal magnetization, attributed at least in part to an ancient field; unexpected seasonal variability and relationships among exospheric species and processes; and the presence in permanently shadowed polar terrain of water ice and other volatile materials, likely to include complex organic compounds. Mercurys highly chemically reduced and unexpectedly volatile-rich composition is unique among the terrestrial planets and was not predicted by earlier hypotheses for the planets origin. As an end-member of terrestrial planet formation, Mercury holds unique clues about the original distribution of elements in the earliest stages of the Solar System and how planets (and exoplanets) form and evolve in close proximity to their host stars. The BepiColombo mission promises to expand our knowledge of this planet and to shed light on some of the mysteries revealed by the MESSENGER mission. However, several fundamental science questions raised by MESSENGERs pioneering exploration of Mercury can only be answered with in situ measurements from the planets surface

HDAC Inhibitors Act with 5-aza-2′-Deoxycytidine to Inhibit Cell Proliferation by Suppressing Removal of Incorporated Abases in Lung Cancer Cells

5-aza-2′-deoxycytidine (5-aza-CdR) is used extensively as a demethylating agent and acts in concert with histone deacetylase inhibitors (HDACI) to induce apoptosis or inhibition of cell proliferation in human cancer cells. Whether the action of 5-aza-CdR in this synergistic effect results from demethylation by this agent is not yet clear. In this study we found that inhibition of cell proliferation was not observed when cells with knockdown of DNA methyltransferase 1 (DNMT1), or double knock down of DNMT1-DNMT3A or DNMT1-DNMT3B were treated with HDACI, implying that the demethylating function of 5-aza-CdR may be not involved in this synergistic effect. Further study showed that there was a causal relationship between 5-aza-CdR induced DNA damage and the amount of [3H]-5-aza-CdR incorporated in DNA. However, incorporated [3H]-5-aza-CdR gradually decreased when cells were incubated in [3H]-5-aza-CdR free medium, indicating that 5-aza-CdR, which is an abnormal base, may be excluded by the cell repair system. It was of interest that HDACI significantly postponed the removal of the incorporated [3H]-5-aza-CdR from DNA. Moreover, HDAC inhibitor showed selective synergy with nucleoside analog-induced DNA damage to inhibit cell proliferation, but showed no such effect with other DNA damage stresses such as γ-ray and UV, etoposide or cisplatin. This study demonstrates that HDACI synergistically inhibits cell proliferation with nucleoside analogs by suppressing removal of incorporated harmful nucleotide analogs from DNA

Reproducibility of histopathological findings in experimental pathology of the mouse: a sorry tail

Reproducibility of $\textit{in vivo}$ research using the mouse as a model organism depends on many factors, including experimental design, strain or stock, experimental protocols, and methods of data evaluation. Gross and histopathology are often the endpoints of such research and there is increasing concern about the accuracy and reproducibility of diagnoses in the literature. To reproduce histopathological results, the pathology protocol, including necropsy methods and slide preparation, should be followed by interpretation of the slides by a pathologist familiar with reading mouse slides and familiar with the consensus medical nomenclature used in mouse pathology. Likewise, it is important that pathologists are consulted as reviewers of manuscripts where histopathology is a key part of the investigation. The absence of pathology expertise in planning, executing and reviewing $\textit{in vivo}$ research using mice leads to questionable pathology-based findings and conclusions from studies, even in high-impact journals. We discuss the various aspects of this problem, give some examples from the literature and suggest solutions.This work was supported in part by US National Institutes of Health grants R01 AR049288, CA089713 and R21 AR063781 (to J.P.S.) and by The Warden and Fellows of Robinson College, Cambridge (to P.N.S.)

Synthesis:PLUTONS: Investigating the relationship between pluton growth and volcanism in the Central Andes

The Central Andes is a key global location to study the enigmatic relation between volcanism and plutonism because it has been the site of large ignimbrite-forming eruptions during the past several million years and currently hosts the world’s largest zone of silicic partial melt in the form of the Altiplano-Puna Magma (or Mush) Body (APMB) and the Southern Puna Magma Body (SPMB). In this themed issue, results from the recently completed PLUTONS project are synthesized. This project focused an interdisciplinary study on two regions of large-scale surface uplift that have been found to represent ongoing movement of magmatic fluids in the middle to upper crust. The locations are Uturuncu in Bolivia near the center of the APMB and Lazufre on the Chile-Argentina border, on the edge of the SPMB. These studies use a suite of geological, geochemical, geophysical (seismology, gravity, surface deformation, and electromagnetic methods), petrological, and geomorphological techniques with numerical modeling to infer the subsurface distribution, quantity, and movements of magmatic fluids, as well as the past history of eruptions. Both Uturuncu and Lazufre show separate geophysical anomalies in the upper, middle, and lower crust (e.g., low seismic velocity, low resistivity, etc.) indicating multiple distinct reservoirs of magma and/or hydrothermal fluids with different physical properties. The characteristics of the geophysical anomalies differ somewhat depending on the technique used—reflecting the different sensitivity of each method to subsurface melt (or fluid) of different compositions, connectivity, and volatile content and highlight the need for integrated, multidisciplinary studies. While the PLUTONS project has led to significant progress, many unresolved issues remain and new questions have been raised