An Archaean heavy bombardment from a destabilized extension of the asteroid belt

The barrage of comets and asteroids that produced many young lunar basins (craters over 300 kilometres in diameter) has frequently been called the Late Heavy Bombardment (LHB). Many assume the LHB ended about 3.7 to 3.8 billion years (Gyr) ago with the formation of Orientale basin. Evidence for LHB-sized blasts on Earth, however, extend into the Archaean and early Proterozoic eons, in the form of impact spherule beds: globally distributed ejecta layers created by Chicxulub-sized or larger cratering events4. At least seven spherule beds have been found that formed between 3.23 and 3.47?Gyr ago, four between 2.49 and 2.63?Gyr ago, and one between 1.7 and 2.1?Gyr ago. Here we report that the LHB lasted much longer than previously thought, with most late impactors coming from the E belt, an extended and now largely extinct portion of the asteroid belt between 1.7 and 2.1 astronomical units from Earth. This region was destabilized by late giant planet migration. E-belt survivors now make up the high-inclination Hungaria asteroids. Scaling from the observed Hungaria asteroids, we find that E-belt projectiles made about ten lunar basins between 3.7 and 4.1?Gyr ago. They also produced about 15 terrestrial basins between 2.5 and 3.7?Gyr ago, as well as around 70 and four Chicxulub-sized or larger craters on the Earth and Moon, respectively, between 1.7 and 3.7?Gyr ago. These rates reproduce impact spherule bed and lunar crater constraints.     

Climate sensitivity constrained by temperature reconstructions over the past seven centuries

The magnitude and impact of future global warming depends on the sensitivity of the climate system to changes in greenhouse gas concentrations. The commonly accepted range for the equilibrium global mean temperature change in response to a doubling of the atmospheric carbon dioxide concentration, termed climate sensitivity, is 1.5-4.5 K (ref. 2). A number of observational studies, however, find a substantial probability of significantly higher sensitivities, yielding upper limits on climate sensitivity of 7.7 K to above 9 K (refs 3-8). Here we demonstrate that such observational estimates of climate sensitivity can be tightened if reconstructions of Northern Hemisphere temperature over the past several centuries are considered. We use large-ensemble energy balance modelling and simulate the temperature response to past solar, volcanic and greenhouse gas forcing to determine which climate sensitivities yield simulations that are in agreement with proxy reconstructions. After accounting for the uncertainty in reconstructions and estimates of past external forcing, we find an independent estimate of climate sensitivity that is very similar to those from instrumental data. If the latter are combined with the result from all proxy reconstructions, then the 5-95 per cent range shrinks to 1.5-6.2 K, thus substantially reducing the probability of very high climate sensitivity.     

Eukaryotic evolution, changes and challenges

The idea that some eukaryotes primitively lacked mitochondria and were true intermediates in the prokaryote-to-eukaryote transition was an exciting prospect. It spawned major advances in understanding anaerobic and parasitic eukaryotes and those with previously overlooked mitochondria. But the evolutionary gap between prokaryotes and eukaryotes is now deeper, and the nature of the host that acquired the mitochondrion more obscure, than ever before.     

(In)consistency of airsea heat flux estimates; ocean heat uptake anomalies and top of atmosphere radiation budgets

This paper introduces the consistency between top of atmosphere （TOA） imbalances and ocean heat uptake, and the inconsistency between ocean heat uptake estimates and flux climatologies, and then gives some recommendations and outlook.     

蛋白聚糖NG2中硫酸软骨素糖胺聚糖链调节稳定转染NG2的U251细胞迁移能力

应用PCR反应使编码蛋白聚糖NG2的核苷酸在3064-3065位置的AG突变成为GC, 构建突变型NG2/S999A. 用表达野生型NG2和突变型NG2/S999A及空白表达载体分别稳定转染人成胶质细胞瘤U251. 应用Western Blot方法鉴定转染后的U251细胞表达野生型及突变型NG2的状态, 证实突变型NG2A999稳定转染的U251细胞株表达的NG2缺失硫酸软骨素葡糖胺聚糖链（C S-GAG）. 比较了3种U251细胞株的迁移, 表明蛋白聚糖NG2中CS-GAG链影响细胞的迁移能 力.     

RANK ligand mediates progestin-induced mammary epithelial proliferation and carcinogenesis

RANK ligand (RANKL), a TNF-related molecule, is essential for osteoclast formation, function and survival through interaction with its receptor RANK. Mammary glands of RANK- and RANKL-deficient mice develop normally during sexual maturation, but fail to form lobuloalveolar structures during pregnancy because of defective proliferation and increased apoptosis of mammary epithelium. It has been shown that RANKL is responsible for the major proliferative response of mouse mammary epithelium to progesterone during mammary lactational morphogenesis, and in mouse models, manipulated to induce activation of the RANK/RANKL pathway in the absence of strict hormonal control, inappropriate mammary proliferation is observed. However, there is no evidence so far of a functional contribution of RANKL to tumorigenesis. Here we show that RANK and RANKL are expressed within normal, pre-malignant and neoplastic mammary epithelium, and using complementary gain-of-function (mouse mammary tumour virus (MMTV)-RANK transgenic mice) and loss-of function (pharmacological inhibition of RANKL) approaches, define a direct contribution of this pathway in mammary tumorigenesis. Accelerated pre-neoplasias and increased mammary tumour formation were observed in MMTV-RANK transgenic mice after multiparity or treatment with carcinogen and hormone (progesterone). Reciprocally, selective pharmacological inhibition of RANKL attenuated mammary tumour development not only in hormone- and carcinogen-treated MMTV-RANK and wild-type mice, but also in the MMTV-neu transgenic spontaneous tumour model. The reduction in tumorigenesis upon RANKL inhibition was preceded by a reduction in pre-neoplasias as well as rapid and sustained reductions in hormone- and carcinogen-induced mammary epithelial proliferation and cyclin D1 levels. Collectively, our results indicate that RANKL inhibition is acting directly on hormone-induced mammary epithelium at early stages in tumorigenesis, and the permissive contribution of progesterone to increased mammary cancer incidence is due to RANKL-dependent proliferative changes in the mammary epithelium. The current study highlights a potential role for RANKL inhibition in the management of proliferative breast disease.     

TRIM24 links a non-canonical histone signature to breast cancer

Recognition of modified histone species by distinct structural domains within 'reader' proteins plays a critical role in the regulation of gene expression. Readers that simultaneously recognize histones with multiple marks allow transduction of complex chromatin modification patterns into specific biological outcomes. Here we report that chromatin regulator tripartite motif-containing 24 (TRIM24) functions in humans as a reader of dual histone marks by means of tandem plant homeodomain (PHD) and bromodomain (Bromo) regions. The three-dimensional structure of the PHD-Bromo region of TRIM24 revealed a single functional unit for combinatorial recognition of unmodified H3K4 (that is, histone H3 unmodified at lysine 4, H3K4me0) and acetylated H3K23 (histone H3 acetylated at lysine 23, H3K23ac) within the same histone tail. TRIM24 binds chromatin and oestrogen receptor to activate oestrogen-dependent genes associated with cellular proliferation and tumour development. Aberrant expression of TRIM24 negatively correlates with survival of breast cancer patients. The PHD-Bromo of TRIM24 provides a structural rationale for chromatin activation through a non-canonical histone signature, establishing a new route by which chromatin readers may influence cancer pathogenesis.     

Hydatellaceae are water lilies with gymnospermous tendencies

The flowering plant family Hydatellaceae was recently discovered to be allied to the ancient angiosperm lineage Nymphaeales (water lilies). Because of its critical phylogenetic position, members of the Hydatellaceae have the potential to provide insights into the origin and early diversification of angiosperms. Here I report that Hydatella expresses several rare embryological features that, in combination, are found only in members of the Nymphaeales. At maturity, the female gametophyte is four-celled, four-nucleate and will produce a diploid endosperm, as is characteristic of most early divergent angiosperm lineages. As with all members of the Nymphaeales, endosperm in Hydatella is minimally developed and perisperm is the major embryo-nourishing tissue within the seed. Remarkably, Hydatella exhibits a maternal seed-provisioning strategy that is unique among flowering plants, but common to all gymnosperms: pre-fertilization allocation of nutrients to the embryo-nourishing tissue. This exceptional case of pre-fertilization maternal provisioning of a seed in Hydatella may well be an apomorphic feature of Hydatellaceae alone but, given the newly discovered phylogenetic position of this family, potentially represents a plesiomorphic and transitional condition associated with the origin of flowering plants from gymnospermous ancestors.