Diethyl 2,6-(2,4-dichloro­phen­yl)-4,8-dioxo-2,3,6,7-tetra­hydro-1H,5H-2,3a,4a,6,7a,8a-hexa­azacyclo­penta­[def]fluorene-8b,8c-dicarboxyl­ate

The title mol­ecule, C28H28Cl4N6O6, is built up from four fused rings, viz. two nearly planar imidazole five-membered rings which adopt envelope conformations with the C=O groups at the flap position, and two triazine six-membered rings which adopt chair conformations. Each six-membered ring has a 2,4-dichloro­benzyl substituent attached to an N atom. In the mol­ecule, the two ethyl groups are each disordered between two orientations in 0.784 (16)/0.216 (16) and 0.631 (10)/0.37 (10) ratios. Weak inter­molecular C—H⋯O hydrogen bonds help to stabilize the crystal packing

Apatite-glaucony association in the Ediacaran Doushantuo Formation, South China and implications for marine redox conditions

Major phosphogenic events took place in the late Paleoproterozoic and the Ediacaran, both of which followed an episode of atmospheric oxygenation. These apparent coincidences have led to suggestions that the Precambrian phosphorus cycle was partly regulated by oceanic redox conditions, although direct evidence is lacking. In this paper, we report the discovery of glaucony in drill cores from the phosphorite-rich Ediacaran Doushantuo Formation at Weng'an, South China, which provides new insights into redox conditions and geochemical cycles during the deposition and early diagenesis of the lower Doushantuo Formation. The presence of flaser and lenticular bedding in the sandstones suggests deposition in a tidally-influenced shallow water environment. Apatite is present as millimeter-scale flasers in sandstones, but more commonly as intraclastic grains. Glaucony typically occurs as interstitial aggregates cementing and replacing detrital minerals and phosphatic grains, with an upsection decrease in abundance. The Doushantuo glauconies have consistently high K2O (7.5–9.6 wt%). In particular, phosphorite-hosted glaucony has generally higher total iron (TFe2O3) than sandstone-hosted glaucony, consistent with Al3+–Fe3+ substitution in the octahedral site, as supported by Raman peaks slightly shifted towards lower wavenumbers for higher Fe content. A decrease in detrital input probably resulted in limited Al availability during early diagenesis, which in turn led to the waning of glaucony upsection. The phosphate grains do not show any negative Ce anomalies, consistent with precipitation of authigenic apatite in suboxic environments with insignificant preferential remobilisation of Ce during deposition and early diagenesis. REE + Y features show variable diagenetic REE enrichment in phosphorites, but identical concave-down patterns. The wide occurrence of glaucony cement further documents the presence of a generally suboxic early diagenetic environment on the seafloor, which was in active exchange with bottom seawater. Slight fluctuations of redox states in the porewater and bottom water would have promoted the cycling of Fe, enrichment of phosphate and REE, and extensive glaucony authigenesis. Therefore, the glaucony-bearing phosphorites in the Doushantuo Formation are a direct result of Fe-redox driven diagenesis. Apatite-glaucony association likely forms in suboxic environments and is considered as a useful mineralogical proxy for paleoredox conditions on the Precambrian ocean floors

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Cutting improves the productivity of lucerne-rich stands used in the revegetation of degraded arable land in a semi-arid environment

Understanding the relationships between vegetative and environmental variables is important for revegetation and ecosystem management on the Loess Plateau, China. Lucerne (Medicago sativa L.) has been widely used in the region to improve revegetation, soil and water conservation, and to enhance livestock production. However, there is little information on how environmental factors influence long-term succession in lucerne-rich vegetation. Our objective was to identify the main environmental variables controlling the succession process in lucerne-rich vegetation such that native species are not suppressed after sowing on the Loess Plateau. Vegetation and soil surveys were performed in 31 lucerne fields (three lucerne fields without any management from 2003-2013 and 28 fields containing 11-year-old lucerne with one cutting each year). Time after planting was the most important factor affecting plant species succession. Cutting significantly affected revegetation characteristics, such as aboveground biomass, plant density and diversity. Soil moisture content, soil organic carbon, soil available phosphorus and slope aspect were key environmental factors affecting plant species composition and aboveground biomass, density and diversity. Long-term cutting can cause self-thinning in lucerne, maintain the stability of lucerne production and slow its degradation. For effective management of lucerne fields, phosphate fertilizer should be applied and cutting performed

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead