Colon cancer cell-derived 12(S)-HETE induces the retraction of cancer-associated fibroblast via MLC2, RHO/ROCK and Ca<Superscript>2+</Superscript> signalling

Retraction of mesenchymal stromal cells supports the invasion of colorectal cancer cells (CRC) into the adjacent compartment. CRC-secreted 12(S)-HETE enhances the retraction of cancer-associated fibroblasts (CAFs) and therefore, 12(S)-HETE may enforce invasivity of CRC. Understanding the mechanisms of metastatic CRC is crucial for successful intervention. Therefore, we studied pro-invasive contributions of stromal cells in physiologically relevant three-dimensional in vitro assays consisting of CRC spheroids, CAFs, extracellular matrix and endothelial cells, as well as in reductionist models. In order to elucidate how CAFs support CRC invasion, tumour spheroid-induced CAF retraction and free intracellular Ca²⁺ levels were measured and pharmacological- or siRNA-based inhibition of selected signalling cascades was performed. CRC spheroids caused the retraction of CAFs, generating entry gates in the adjacent surrogate stroma. The responsible trigger factor 12(S)-HETE provoked a signal, which was transduced by PLC, IP3, free intracellular Ca²⁺, Ca²⁺-calmodulin-kinase-II, RHO/ROCK and MYLK which led to the activation of myosin light chain 2, and subsequent CAF mobility. RHO activity was observed downstream as well as upstream of Ca²⁺ release. Thus, Ca²⁺ signalling served as central signal amplifier. Treatment with the FDA-approved drugs carbamazepine, cinnarizine, nifedipine and bepridil HCl, which reportedly interfere with cellular calcium availability, inhibited CAF-retraction. The elucidation of signalling pathways and identification of approved inhibitory drugs warrant development of intervention strategies targeting tumour–stroma interaction.     

Response to seasonal change of insect resources in Changbai Mountain temperate forests by Greater Horseshoe bats

Knowing how bats select different habitats in response to environmental changes provides a framework for anticipating the likely consequences of changes in climate or vegetation. In this study we assessed the presence of greater horseshoe bats (Rhinolophus ferrumequinum) and their foraging behavior. This study depicts an effective approach for seasonal responses of habitat selection by Chiroptera.     

Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study

Calorie restriction (CR), a reduction of 10–40% in intake of a nutritious diet, is often reported as the most robust non-genetic mechanism to extend lifespan and healthspan. CR is frequently used as a tool to understand mechanisms behind ageing and age-associated diseases. In addition to and independently of increasing lifespan, CR has been reported to delay or prevent the occurrence of many chronic diseases in a variety of animals. Beneficial effects of CR on outcomes such as immune function, motor coordination and resistance to sarcopenia in rhesus monkeys have recently been reported. We report here that a CR regimen implemented in young and older age rhesus monkeys at the National Institute on Aging (NIA) has not improved survival outcomes. Our findings contrast with an ongoing study at the Wisconsin National Primate Research Center (WNPRC), which reported improved survival associated with 30% CR initiated in adult rhesus monkeys (7–14?years) and a preliminary report with a small number of CR monkeys. Over the years, both NIA and WNPRC have extensively documented beneficial health effects of CR in these two apparently parallel studies. The implications of the WNPRC findings were important as they extended CR findings beyond the laboratory rodent and to a long-lived primate. Our study suggests a separation between health effects, morbidity and mortality, and similar to what has been shown in rodents, study design, husbandry and diet composition may strongly affect the life-prolonging effect of CR in a long-lived nonhuman primate.     

Universal species-area and endemics-area relationships at continental scales

Despite the broad conceptual and applied relevance of how the number of species or endemics changes with area (the species-area and endemics-area relationships (SAR and EAR)), our understanding of universality and pervasiveness of these patterns across taxa and regions has remained limited. The SAR has traditionally been approximated by a power law, but recent theories predict a triphasic SAR in logarithmic space, characterized by steeper increases in species richness at both small and large spatial scales. Here we uncover such universally upward accelerating SARs for amphibians, birds and mammals across the world’s major landmasses. Although apparently taxon-specific and continent-specific, all curves collapse into one universal function after the area is rescaled by using the mean range sizes of taxa within continents. In addition, all EARs approximately follow a power law with a slope close to 1, indicating that for most spatial scales there is roughly proportional species extinction with area loss. These patterns can be predicted by a simulation model based on the random placement of contiguous ranges within a domain. The universality of SARs and EARs after rescaling implies that both total and endemic species richness within an area, and also their rate of change with area, can be estimated by using only the knowledge of mean geographic range size in the region and mean species richness at one spatial scale.     

Eisosomes mark static sites of endocytosis

Endocytosis functions to recycle plasma membrane components, to regulate cell-surface expression of signalling receptors and to internalize nutrients in all eukaryotic cells. Internalization of proteins, lipids and other cargo can occur by one of several pathways that have different, but often overlapping, molecular requirements. To mediate endocytosis, effectors assemble transiently underneath the plasma membrane, carry out the mechanics of membrane deformation, cargo selection and vesicle internalization, and then disassemble. The mechanism by which endocytosis initiates at particular locations on the plasma membrane has remained unknown. Sites of endocytosis might be formed randomly, induced by stochastic protein and/or lipid clustering. Alternatively, endocytosis might initiate at specific locations. Here we describe large immobile protein assemblies at the plasma membrane in the yeast Saccharomyces cerevisiae that mark endocytic sites. These structures, termed eisosomes (from the Greek 'eis', meaning into or portal, and 'soma', meaning body), are composed primarily of two cytoplasmic proteins, Pil1 and Lsp1. A plasma membrane protein, Sur7, localizes to eisosomes. These structures colocalize with sites of protein and lipid endocytosis, and their components genetically interact with known endocytic effectors. Loss of Pil1 leads to clustering of eisosome remnants and redirects endocytosis and endocytic effector proteins to these clusters.     

Structure and function of the GroE chaperone

The Escherichia coli proteins GroEL and GroES were the first chaperones to be studied in detail and have thus become a role model for assisted protein folding in general. A wealth of both structural and functional data on the GroE system has been accumulated over the past years, enabling us now to understand the basic principles of how this fascinating protein-folding machine accomplishes its task. According to the current model, GroE processes a nonnative polypeptide in a cycle consisting of three steps. First, the polypeptide substrate is captured by GroEL. Upon binding of the co-chaperone GroES and ATP, the substrate is then discharged into a unique microenvironment inside of the chaperone, which promotes productive folding. After hydrolysis of ATP, the polypeptide is released into solution. Moreover, GroE may actively increase the folding efficiency, e.g. by unfolding of misfolded protein molecules. The mechanisms underlying these features, however, are yet not well characterized.     

Evidence for low sulphate and anoxia in a mid-Proterozoic marine basin

Many independent lines of evidence document a large increase in the Earth's surface oxidation state 2,400 to 2,200 million years ago, and a second biospheric oxygenation 800 to 580 million years ago, just before large animals appear in the fossil record. Such a two-staged oxidation implies a unique ocean chemistry for much of the Proterozoic eon, which would have been neither completely anoxic and iron-rich as hypothesized for Archaean seas, nor fully oxic as supposed for most of the Phanerozoic eon. The redox chemistry of Proterozoic oceans has important implications for evolution, but empirical constraints on competing environmental models are scarce. Here we present an analysis of the iron chemistry of shales deposited in the marine Roper Basin, Australia, between about 1,500 and 1,400 million years ago, which record deep-water anoxia beneath oxidized surface water. The sulphur isotopic compositions of pyrites in the shales show strong variations along a palaeodepth gradient, indicating low sulphate concentrations in mid-Proterozoic oceans. Our data help to integrate a growing body of evidence favouring a long-lived intermediate state of the oceans, generated by the early Proterozoic oxygen revolution and terminated by the environmental transformation late in the Proterozoic eon.     

Ethene／norbornene copolymerization by[Me2Si（3—^tertBuCp）（N^tertBu）]TiCl2／MAO—catalyst

Ethene/norbomene copolymerization by the catalyat system [Me2Si(3-^tertBuCp)(N^tertBu)]TiCl2/MAO was investigated in detail at 30℃,60℃,and 90℃,A mass flow controller was used in this work to ob-tain kinetic data and investigate temperature‘‘‘‘‘‘‘‘s effects on activity, norbomene incorporation,copolymerization parameter,microgtructure,glass transition temperature,and molar masses were described.High copolymer-izstion values rE and high altemation are determined.The number of isotactic altemating sequences is much higher than that of the syndiotactic altemating sequences.