Phenotypic noise and the cost of complexity

Experimental studies demonstrate the existence of phenotypic diversity despite constant genotype and environment. Theoretical models based on a single phenotypic character predict that during an adaptation event, phenotypic noise should be positively selected far from the fitness optimum because it increases the fitness of the genotype, and then be selected against when the population reaches the optimum. It is suggested that because of this fitness gain, phenotypic noise should promote adaptive evolution. However, it is unclear how the selective advantage of phenotypic noise is linked to the rate of evolution, and whether any advantage would hold for more realistic, multidimensional phenotypes. Indeed, complex organisms suffer a cost of complexity, where beneficial mutations become rarer as the number of phenotypic characters increases. Using a quantitative genetics approach, we first show that for a one-dimensional phenotype, phenotypic noise promotes adaptive evolution on plateaus of positive fitness, independently from the direct selective advantage on fitness. Second, we show that for multidimensional phenotypes, phenotypic noise evolves to a low-dimensional configuration, with elevated noise in the direction of the fitness optimum. Such a dimensionality reduction of the phenotypic noise promotes adaptive evolution and numerical simulations show that it reduces the cost of complexity.     

Indirect N2O emissions from shallow groundwater in an agricultural catchment (Seine Basin, France)

Production and accumulation of nitrous oxide (N₂O), a major greenhouse gas, in shallow groundwater might contribute to indirect N₂O emissions to the atmosphere (e.g., when groundwater flows into a stream or a river). The Intergovernmental Panel on Climate Change (IPCC) has attributed an emission factor (EF_5g) for N₂O, associated with nitrate leaching in groundwater and drainage ditches—0.0025 (corresponding to 0.25% of N leached which is emitted as N₂O)—although this is the subject of considerable uncertainty. We investigated and quantified the transport and fate of nitrate (NO₃ ^?) and dissolved nitrous oxide from crop fields to groundwater and surface water over a 2-year period (monitoring from April 2008 to April 2010) in a transect from a plateau to the river with three piezometers. In groundwater, nitrate concentrations ranged from 1.0 to 22.7 mg NO₃ ^?–N l^?1 (from 2.8 to 37.5 mg NO₃ ^?–N l^?1 in the river) and dissolved N₂O from 0.2 to 101.0 μg N₂O–N l^?1 (and from 0.2 to 2.9 μg N₂O–N l^?1 in the river). From these measurements, we estimated an emission factor of EF_5g = 0.0026 (similar to the value currently used by the IPCC) and an annual indirect N₂O flux from groundwater of 0.035 kg N₂O–N ha^?1 year^?1, i.e., 1.8% of the previously measured direct N₂O flux from agricultural soils.     

Stimulation of Cortical Myosin Phosphorylation by p114RhoGEF Drives Cell Migration and Tumor Cell Invasion

Actinomyosin activity is an important driver of cell locomotion and has been shown to promote collective cell migration of epithelial sheets as well as single cell migration and tumor cell invasion. However, the molecular mechanisms underlying activation of cortical myosin to stimulate single cell movement, and the relationship between the mechanisms that drive single cell locomotion and those that mediate collective cell migration of epithelial sheets are incompletely understood. Here, we demonstrate that p114RhoGEF, an activator of RhoA that associates with non-muscle myosin IIA, regulates collective cell migration of epithelial sheets and tumor cell invasion. Depletion of p114RhoGEF resulted in specific spatial inhibition of myosin activation at cell-cell contacts in migrating epithelial sheets and the cortex of migrating single cells, but only affected double and not single phosphorylation of myosin light chain. In agreement, overall elasticity and contractility of the cells, processes that rely on persistent and more constant forces, were not affected, suggesting that p114RhoGEF mediates process-specific myosin activation. Locomotion was p114RhoGEF-dependent on Matrigel, which favors more roundish cells and amoeboid-like actinomyosin-driven movement, but not on fibronectin, which stimulates flatter cells and lamellipodia-driven, mesenchymal-like migration. Accordingly, depletion of p114RhoGEF led to reduced RhoA, but increased Rac activity. Invasion of 3D matrices was p114RhoGEF-dependent under conditions that do not require metalloproteinase activity, supporting a role of p114RhoGEF in myosin-dependent, amoeboid-like locomotion. Our data demonstrate that p114RhoGEF drives cortical myosin activation by stimulating myosin light chain double phosphorylation and, thereby, collective cell migration of epithelial sheets and amoeboid-like motility of tumor cells.     

Protist Biodiversity and Biogeography in Lakes From Four Brazilian River–Floodplain Systems

The biodiversity and biogeography of protists inhabiting many ecosystems have been intensely studied using different sequencing approaches, but tropical ecosystems are relatively under‐studied. Here, we sampled planktonic waters from 32 lakes associated with four different river–floodplains systems in Brazil, and sequenced the DNA using a metabarcoding approach with general eukaryotic primers. The lakes were dominated by the largely free‐living Discoba (mostly the Euglenida), Ciliophora, and Ochrophyta. There was low community similarity between lakes even within the same river–floodplain. The protists inhabiting these floodplain systems comprise part of the large and relatively undiscovered diversity in the tropics.     

棕榈酰化修饰对G蛋白偶联受体功能的调节作用

G蛋白偶联受体(G-protein-coupled receptors,GPCRs)作为跨膜蛋白,其结构和功能同时受相互作用的蛋白质和脂质分子调控.S-棕榈酰化(S-palmitoylation)能够影响GPCRs与信号蛋白及膜脂分子的相互作用,在GPCRs相关的多项生理进程中发挥重要调节作用.棕榈酸与GPCRs的半胱氨酸间形成不稳定的硫酯键,其修饰动力学过程受棕榈酰转移酶(protein acly transferases,PATs)与硫酯酶(thioesterases)之间的可逆性双重调控,与受体活性及生理状态密切相关.棕榈酰化修饰多发生在GPCRs的C末端,通过棕榈酸侧链插入到质膜内侧而形成第4和/或第5个胞内环,从而影响GPCRs的构象,促进其正确折叠与成熟,并对GPCRs胞内转运、分选、下游信号转导、失敏、内化、寡聚化等活动产生影响.此外,棕榈酰化还与磷酸化、泛素化及亚硝基化等多种翻译后修饰机制相互作用,共同参与调节GPCRs的功能.GPCRs的棕榈酰化修饰酶学机制以及GPCRs蛋白复合体棕榈酰化修饰胞内动力学过程将是未来的研究热点.     

PP1-mediated moesin dephosphorylation couples polar relaxation to mitotic exit

Animal cells undergo dramatic actin-dependent changes in shape as they progress through mitosis; they round up upon mitotic entry and elongate during chromosome segregation before dividing into two [1-3]. Moesin, the sole Drosophila ERM-family protein [4], plays a critical role in this process, through the construction of a stiff, rounded metaphase cortex [5-7]. At mitotic exit, this rigid cortex must be dismantled to allow for anaphase elongation and cytokinesis through the loss of the active pool of phospho-Thr559moesin from cell poles. Here, in an RNA interference (RNAi) screen for phosphatases involved in the temporal and spatial control of moesin, we identify PP1-87B RNAi as having elevated p-moesin levels and reduced cortical compliance. In mitosis, RNAi-induced depletion of PP1-87B or depletion of a conserved noncatalytic PP1 phosphatase subunit Sds22 leads to defects in p-moesin clearance from cell poles at anaphase, a delay in anaphase elongation, together with defects in bipolar anaphase relaxation and cytokinesis. Importantly, similar cortical defects are seen at anaphase following the expression of a constitutively active, phosphomimetic version of moesin. These data reveal a new role for the PP1-87B/Sds22 phosphatase, an important regulator of the metaphase-anaphase transition, in coupling moesin-dependent cell shape changes to mitotic exit.     

Age-related impairment of HDL-mediated cholesterol efflux

Our aim in this study was to investigate the effect of aging on the capacity of HDLs to promote reverse cholesterol transport. HDLs were isolated from plasma of young (Y-HDL) and elderly (E-HDL) subjects. HDL-mediated cholesterol efflux was studied using THP-1 and J774 macrophages. Our results show that E-HDLs present a lower capacity to promote cholesterol efflux than Y-HDLs (41.7 +/- 1.4% vs. 49.0 +/- 2.2%, respectively; P = 0.013). Reduction in the HDL-mediated cholesterol efflux capacity with aging was more significant with HDL(3) than HDL(2) (Y-HDL(3), 57.3 +/- 1% vs. E-HDL(3), 50.9 +/- 2%; P = 0.012). Moreover, our results show that ABCA1-mediated cholesterol efflux is the more affected pathway in terms of cholesterol-removing capacity. Interestingly, the composition and structure of HDL revealed a reduction in the phosphatidylcholine-sphingomyelin ratio (E-HDL, 32.7 +/- 2.7 vs. Y-HDL, 40.0 +/- 1.9; P = 0.029) and in the phospholipidic layer membrane fluidity in E-HDL compared with Y-HDL as well as an alteration in the apolipoprotein A-I structure and charge. In conclusion, our results shown that E-HDLs present a reduced capacity to promote cholesterol efflux, principally through the ABCA1 pathway, and this may explain the increase of the incidence of cardiovascular diseases observed during aging.     

Rasl11b knock down in zebrafish suppresses one-eyed-pinhead mutant phenotype

The EGF-CFC factor Oep/Cripto1/Frl1 has been implicated in embryogenesis and several human cancers. During vertebrate development, Oep/Cripto1/Frl1 has been shown to act as an essential coreceptor in the TGFbeta/Nodal pathway, which is crucial for germ layer formation. Although studies in cell cultures suggest that Oep/Cripto1/Frl1 is also implicated in other pathways, in vivo it is solely regarded as a Nodal coreceptor. We have found that Rasl11b, a small GTPase belonging to a Ras subfamily of putative tumor suppressor genes, modulates Oep function in zebrafish independently of the Nodal pathway. rasl11b down regulation partially rescues endodermal and prechordal plate defects of zygotic oep(-/-) mutants (Zoep). Rasl11b inhibitory action was only observed in oep-deficient backgrounds, suggesting that normal oep expression prevents Rasl11b function. Surprisingly, rasl11b down regulation does not rescue mesendodermal defects in other Nodal pathway mutants, nor does it influence the phosphorylation state of the downstream effector Smad2. Thus, Rasl11b modifies the effect of Oep on mesendoderm development independently of the main known Oep output: the Nodal signaling pathway. This data suggests a new branch of Oep signaling that has implications for germ layer development, as well as for studies of Oep/Frl1/Cripto1 dysfunction, such as that found in tumors.