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.     

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     

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.     

Predecessors of the giant 1960 Chile earthquake

It is commonly thought that the longer the time since last earthquake, the larger the next earthquake's slip will be. But this logical predictor of earthquake size, unsuccessful for large earthquakes on a strike-slip fault, fails also with the giant 1960 Chile earthquake of magnitude 9.5 (ref. 3). Although the time since the preceding earthquake spanned 123 years (refs 4, 5), the estimated slip in 1960, which occurred on a fault between the Nazca and South American tectonic plates, equalled 250-350 years' worth of the plate motion. Thus the average interval between such giant earthquakes on this fault should span several centuries. Here we present evidence that such long intervals were indeed typical of the last two millennia. We use buried soils and sand layers as records of tectonic subsidence and tsunami inundation at an estuary midway along the 1960 rupture. In these records, the 1960 earthquake ended a recurrence interval that had begun almost four centuries before, with an earthquake documented by Spanish conquistadors in 1575. Two later earthquakes, in 1737 and 1837, produced little if any subsidence or tsunami at the estuary and they therefore probably left the fault partly loaded with accumulated plate motion that the 1960 earthquake then expended.     

Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice

We targeted the locus encoding the cyclin-dependent kinase 2 (CDK2) by homologous recombination in mouse embryonic stem (ES) cells. Embryonic fibroblasts lacking CDK2 proliferate normally and become immortal after continuous passage in culture. Elimination of a conditional Cdk2 allele in immortal cells does not have a significant effect on proliferation. Cdk2-/- mice are viable and survive for up to two years, indicating that CDK2 is also dispensable for proliferation and survival of most cell types. But CDK2 is essential for completion of prophase I during meiotic cell division in male and female germ cells, an unforeseen role for this cell cycle kinase.     

Quantum teleportation between light and matter

Quantum teleportation is an important ingredient in distributed quantum networks, and can also serve as an elementary operation in quantum computers. Teleportation was first demonstrated as a transfer of a quantum state of light onto another light beam; later developments used optical relays and demonstrated entanglement swapping for continuous variables. The teleportation of a quantum state between two single material particles (trapped ions) has now also been achieved. Here we demonstrate teleportation between objects of a different nature--light and matter, which respectively represent 'flying' and 'stationary' media. A quantum state encoded in a light pulse is teleported onto a macroscopic object (an atomic ensemble containing 10 caesium atoms). Deterministic teleportation is achieved for sets of coherent states with mean photon number (n) up to a few hundred. The fidelities are 0.58 +/- 0.02 for n = 20 and 0.60 +/- 0.02 for n = 5--higher than any classical state transfer can possibly achieve. Besides being of fundamental interest, teleportation using a macroscopic atomic ensemble is relevant for the practical implementation of a quantum repeater. An important factor for the implementation of quantum networks is the teleportation distance between transmitter and receiver; this is 0.5 metres in the present experiment. As our experiment uses propagating light to achieve the entanglement of light and atoms required for teleportation, the present approach should be scalable to longer distances.