p38alpha suppresses normal and cancer cell proliferation by antagonizing the JNK-c-Jun pathway

The mitogen-activated protein kinase (MAPK) p38alpha controls inflammatory responses and cell proliferation. Using mice carrying conditional Mapk14 (also known as p38alpha) alleles, we investigated its function in postnatal development and tumorigenesis. When we specifically deleted Mapk14 in the mouse embryo, fetuses developed to term but died shortly after birth, probably owing to lung dysfunction. Fetal hematopoietic cells and embryonic fibroblasts deficient in p38alpha showed increased proliferation resulting from sustained activation of the c-Jun N-terminal kinase (JNK)-c-Jun pathway. Notably, in chemical-induced liver cancer development, mice with liver-specific deletion of Mapk14 showed enhanced hepatocyte proliferation and tumor development that correlated with upregulation of the JNK-c-Jun pathway. Furthermore, inactivation of JNK or c-Jun suppressed the increased proliferation of Mapk14-deficient hepatocytes and tumor cells. These results demonstrate a new mechanism whereby p38alpha negatively regulates cell proliferation by antagonizing the JNK-c-Jun pathway in multiple cell types and in liver cancer development.     

Late Neoproterozoic to early Cambrian sulphur cycle-An isotopic investigation of sedimentary rocks from the Yangtze Platform

The sulphur cycle responds to changes in seawater chemistry, biological evolution and tectonic activity. We follow an isotopic approach in order to constrain the state of the ocean/atmosphere system during late Neoproterozoic and early Cambrian. For this purpose, a sedimentary succession deposited on the Yangtze Platform, South China, was analysed for its sulphur isotopic composition in different S-bearing phases. Redox changes were defined by the degree of pyritization (DOP) values in order to show variations in the oxygenation of the depositional environment. The sulphur isotopic composition of late Neoproterozoic to early Cambrian seawater sulphate ranges from +30‰ to +35‰ as evident from trace sulphate in unaltered carbonates and phosphorites. The isotopic composition for pyrite and organic sulphur varies between -16‰ and +23‰. The apparent sulphur isotopic fractionation between seawater sulphate and pyrite as well as organically bound sulphur varies between 7‰ and 50‰. This large fractionation, as well as its variability suggests a biological origin for pyrite and organically bound sulphur. The temporal evolution of different geochemical proxy signals is comparable for different successions across the Yangtze Platform.     

Alzheimer’s disease risk factor lymphocyte-specific protein tyrosine kinase regulates long-term synaptic strengthening, spatial learning and memory

The lymphocyte-specific protein tyrosine kinase (Lck), which belongs to the Src kinase-family, is expressed in neurons of the hippocampus, a structure critical for learning and memory. Recent evidence demonstrated a significant downregulation of Lck in Alzheimer’s disease. Lck has additionally been proposed to be a risk factor for Alzheimer’s disease, thus suggesting the involvement of Lck in memory function. The neuronal role of Lck, however, and its involvement in learning and memory remain largely unexplored. Here, in vitro electrophysiology, confocal microscopy, and molecular, pharmacological, genetic and biochemical techniques were combined with in vivo behavioral approaches to examine the role of Lck in the mouse hippocampus. Specific pharmacological inhibition and genetic silencing indicated the involvement of Lck in the regulation of neuritic outgrowth. In the functional pre-established synaptic networks that were examined electrophysiologically, specific Lck-inhibition also selectively impaired the long-term hippocampal synaptic plasticity without affecting spontaneous excitatory synaptic transmission or short-term synaptic potentiation. The selective inhibition of Lck also significantly altered hippocampus-dependent spatial learning and memory in vivo. These data provide the basis for the functional characterization of brain Lck, describing the importance of Lck as a critical regulator of both neuronal morphology and in vivo long-term memory.     

Ferns diversified in the shadow of angiosperms

The rise of angiosperms during the Cretaceous period is often portrayed as coincident with a dramatic drop in the diversity and abundance of many seed-free vascular plant lineages, including ferns. This has led to the widespread belief that ferns, once a principal component of terrestrial ecosystems, succumbed to the ecological predominance of angiosperms and are mostly evolutionary holdovers from the late Palaeozoic/early Mesozoic era. The first appearance of many modern fern genera in the early Tertiary fossil record implies another evolutionary scenario; that is, that the majority of living ferns resulted from a more recent diversification. But a full understanding of trends in fern diversification and evolution using only palaeobotanical evidence is hindered by the poor taxonomic resolution of the fern fossil record in the Cretaceous. Here we report divergence time estimates for ferns and angiosperms based on molecular data, with constraints from a reassessment of the fossil record. We show that polypod ferns (> 80% of living fern species) diversified in the Cretaceous, after angiosperms, suggesting perhaps an ecological opportunistic response to the diversification of angiosperms, as angiosperms came to dominate terrestrial ecosystems.     

Geochemistry of Sinian tillites from Hunan Province, South China--A test of the Snowball Earth hypothesis

A glaciomarine succession of Neoproterozoic age (between 748～584 Ma) is widespread on the Yangtze Platform, South China. The deposition took place during an intermediate to low paleolatitude position of the Yangtze Platform. The Snowball Earth hypothesis offers an explanation for the occurrence of low-latitude tillites in general. It is based on records obtained of deposits underlying and overlying the tillites. In contrast, we focused on the tillites themselves by using geochemistry to obtain detailed information about the conditions during the glaciation. Of particular interest are environmental conditions, which are closely related to the climate development. Additionally, stable isotope geochemistry was used for a paleoclimate interpretation. The geochemical results of the Sinian glacial succession on the Yangtze Platform are compared to the predictions made by the Snowball Earth hypothesis.