Phospholipase Cgamma activates Ras on the Golgi apparatus by means of RasGRP1

Ras proteins regulate cellular growth and differentiation, and are mutated in 30% of cancers. We have shown recently that Ras is activated on and transmits signals from the Golgi apparatus as well as the plasma membrane but the mechanism of compartmentalized signalling was not determined. Here we show that, in response to Src-dependent activation of phospholipase Cgamma1, the Ras guanine nucleotide exchange factor RasGRP1 translocated to the Golgi where it activated Ras. Whereas Ca(2+) positively regulated Ras on the Golgi apparatus through RasGRP1, the same second messenger negatively regulated Ras on the plasma membrane by means of the Ras GTPase-activating protein CAPRI. Ras activation after T-cell receptor stimulation in Jurkat cells, rich in RasGRP1, was limited to the Golgi apparatus through the action of CAPRI, demonstrating unambiguously a physiological role for Ras on Golgi. Activation of Ras on Golgi also induced differentiation of PC12 cells, transformed fibroblasts and mediated radioresistance. Thus, activation of Ras on Golgi has important biological consequences and proceeds through a pathway distinct from the one that activates Ras on the plasma membrane.     

Following translation by single ribosomes one codon at a time

We have followed individual ribosomes as they translate single messenger RNA hairpins tethered by the ends to optical tweezers. Here we reveal that translation occurs through successive translocation--and-pause cycles. The distribution of pause lengths, with a median of 2.8 s, indicates that at least two rate-determining processes control each pause. Each translocation step measures three bases--one codon-and occurs in less than 0.1 s. Analysis of the times required for translocation reveals, surprisingly, that there are three substeps in each step. Pause lengths, and thus the overall rate of translation, depend on the secondary structure of the mRNA; the applied force destabilizes secondary structure and decreases pause durations, but does not affect translocation times. Translocation and RNA unwinding are strictly coupled ribosomal functions.     

Positive feedbacks promote power-law clustering of Kalahari vegetation

The concept of local-scale interactions driving large-scale pattern formation has been supported by numerical simulations, which have demonstrated that simple rules of interaction are capable of reproducing patterns observed in nature. These models of self-organization suggest that characteristic patterns should exist across a broad range of environmental conditions provided that local interactions do indeed dominate the development of community structure. Readily available observations that could be used to support these theoretical expectations, however, have lacked sufficient spatial extent or the necessary diversity of environmental conditions to confirm the model predictions. We use high-resolution satellite imagery to document the prevalence of self-organized vegetation patterns across a regional rainfall gradient in southern Africa, where percent tree cover ranges from 65% to 4%. Through the application of a cellular automata model, we find that the observed power-law distributions of tree canopy cluster sizes can arise from the interacting effects of global-scale resource constraints (that is, water availability) and local-scale facilitation. Positive local feedbacks result in power-law distributions without entailing threshold behaviour commonly associated with criticality. Our observations provide a framework for integrating a diverse suite of previous studies that have addressed either mean wet season rainfall or landscape-scale soil moisture variability as controls on the structural dynamics of arid and semi-arid ecosystems.     

Delayed ageing through damage protection by the Arf/p53 pathway

The tumour-suppressor pathway formed by the alternative reading frame protein of the Cdkn2a locus (Arf) and by p53 (also called Trp53) plays a central part in the detection and elimination of cellular damage, and this constitutes the basis of its potent cancer protection activity. Similar to cancer, ageing also results from the accumulation of damage and, therefore, we have reasoned that Arf/p53 could have anti-ageing activity by alleviating the load of age-associated damage. Here we show that genetically manipulated mice with increased, but otherwise normally regulated, levels of Arf and p53 present strong cancer resistance and have decreased levels of ageing-associated damage. These observations extend the protective role of Arf/p53 to ageing, revealing a previously unknown anti-ageing mechanism and providing a rationale for the co-evolution of cancer resistance and longevity.     

Implication of the VRK1 chromatin kinase in the signaling responses to DNA damage: a therapeutic target?

DNA damage causes a local distortion of chromatin that triggers the sequential processes that participate in specific DNA repair mechanisms. This initiation of the repair response requires the involvement of a protein whose activity can be regulated by histones. Kinases are candidates to regulate and coordinate the connection between a locally altered chromatin and the response initiating signals that lead to identification of the type of lesion and the sequential steps required in specific DNA damage responses (DDR). This initiating kinase must be located in chromatin, and be activated independently of the type of DNA damage. We review the contribution of the Ser-Thr vaccinia-related kinase 1 (VRK1) chromatin kinase as a new player in the signaling of DNA damage responses, at chromatin and cellular levels, and its potential as a new therapeutic target in oncology. VRK1 is involved in the regulation of histone modifications, such as histone phosphorylation and acetylation, and in the formation of γH2AX, NBS1 and 53BP1 foci induced in DDR. Induction of DNA damage by chemotherapy or radiation is a mainstay of cancer treatment. Therefore, novel treatments can be targeted to proteins implicated in the regulation of DDR, rather than by directly causing DNA damage.     

SNP and haplotype mapping for genetic analysis in the rat

The laboratory rat is one of the most extensively studied model organisms. Inbred laboratory rat strains originated from limited Rattus norvegicus founder populations, and the inherited genetic variation provides an excellent resource for the correlation of genotype to phenotype. Here, we report a survey of genetic variation based on almost 3 million newly identified SNPs. We obtained accurate and complete genotypes for a subset of 20,238 SNPs across 167 distinct inbred rat strains, two rat recombinant inbred panels and an F2 intercross. Using 81% of these SNPs, we constructed high-density genetic maps, creating a large dataset of fully characterized SNPs for disease gene mapping. Our data characterize the population structure and illustrate the degree of linkage disequilibrium. We provide a detailed SNP map and demonstrate its utility for mapping of quantitative trait loci. This community resource is openly available and augments the genetic tools for this workhorse of physiological studies.     

Comparison of distribution and habitat characteristics between an endemic and a wide-ranging cryptic species of Peromyscus on the Baja California Peninsula

Peromyscus eva and Peromyscus fraterculus are 2 morphologically similar species of the Peromyscus eremicus group occurring on the Baja California Peninsula. Due to the similarity between these 2 species, their ranges have been greatly confused; consequently, the specific habitat characteristics for each group are not well known. The goal of this study was to assess distribution ranges and characteristics of preferred habitats for P. eva and P. fraterculus in more detail. We identified taxonomy of individuals by evaluating genetic patterns produced by restriction fragment length polymorphisms (RFLPs). We evaluated the banding pattern generated by Alu I and Bam HI restriction enzymes in an 850-bp cytochrome b fragment. Consistent differences in number and size of fragments allowed for discrimination of individuals to species. The heterogeneity and evenness indexes showed that the microhabitat of P. fraterculus contained less-diverse soil types and is more homogeneous than the microhabitat of P. eva. In the state of Baja California Sur, P. eva occurs exclusively in the flat areas along the Pacific coast from the Vizcaino Desert to the south, including Margarita Island, with one small population in the Loreto area adjacent to Carmen Island. The habitats occupied by P. eva were heterogeneous (areas with friable, soft sandy soil and a low percentage of small stones). Peromyscus fraterculus occurs mostly in Baja California Norte, with some populations distributed in Baja California Sur, particularly in the western areas of the Vizcaino Desert along the mountain range, in the gulf side of the peninsula south of the city of La Paz, and in a small area on the eastern side of Sierra de Las Cruces. This species was mostly found on hard soil with high medium-size stone content.     

Cyclic nucleotide-dependent relaxation pathways in vascular smooth muscle

Vascular smooth muscle tone is controlled by a balance between the cellular signaling pathways that mediate the generation of force (vasoconstriction) and release of force (vasodilation). The initiation of force is associated with increases in intracellular calcium concentrations, activation of myosin light-chain kinase, increases in the phosphorylation of the regulatory myosin light chains, and actin-myosin crossbridge cycling. There are, however, several signaling pathways modulating Ca²⁺ mobilization and Ca²⁺ sensitivity of the contractile machinery that secondarily regulate the contractile response of vascular smooth muscle to receptor agonists. Among these regulatory mechanisms involved in the physiological regulation of vascular tone are the cyclic nucleotides (cAMP and cGMP), which are considered the main messengers that mediate vasodilation under physiological conditions. At least four distinct mechanisms are currently thought to be involved in the vasodilator effect of cyclic nucleotides and their dependent protein kinases: (1) the decrease in cytosolic calcium concentration ([Ca²⁺]c), (2) the hyperpolarization of the smooth muscle cell membrane potential, (3) the reduction in the sensitivity of the contractile machinery by decreasing the [Ca²⁺]c sensitivity of myosin light-chain phosphorylation, and (4) the reduction in the sensitivity of the contractile machinery by uncoupling contraction from myosin light-chain phosphorylation. This review focuses on each of these mechanisms involved in cyclic nucleotide-dependent relaxation of vascular smooth muscle under physiological conditions.     

A new deep-sea Psammogammarus species (Crustacea: Amphipoda: Eriopisidae) from the continental slope of the SE Gulf of Mexico

A new deep-sea species of amphipod collected at a depth of 1317 m from the soft bottom of the Bay of Campeche, SW Gulf of Mexico, is herein described. The sediment included a high proportion of silt and organic carbon. The specimen examined in this study was collected during the Oceanographic Expedition Xcambó-4, along the Bay of Campeche, aboard the RV Justo Sierra. The new species represents the sixteenth known species of the genus Psammogammarus worldwide. This new species is the second Psammogammarus recorded from the deep sea, and the first record of the genus for the Gulf of Mexico. Identification keys to males and females of Psammogammarus species are provided. Psammogammarus barrerai sp. nov. is characterised by head with anteroventral notch present; gnathopods 1 and 2 palmar margins oblique, and basis of pereopod 7 forming a wide serrated posterior lobe.

www.zoobank.org/urn:lsid:zoobank.org:pub:C843777B-FF15-4AEC-B046-6513A96A9BFF