Homing endonucleases: from basics to therapeutic applications

Homing endonucleases (HE) are double-stranded DNAses that target large recognition sites (12–40 bp). HE-encoding sequences are usually embedded in either introns or inteins. Their recognition sites are extremely rare, with none or only a few of these sites present in a mammalian-sized genome. However, these enzymes, unlike standard restriction endonucleases, tolerate some sequence degeneracy within their recognition sequence. Several members of this enzyme family have been used as templates to engineer tools to cleave DNA sequences that differ from their original wild-type targets. These custom HEs can be used to stimulate double-strand break homologous recombination in cells, to induce the repair of defective genes with very low toxicity levels. The use of tailored HEs opens up new possibilities for gene therapy in patients with monogenic diseases that can be treated ex vivo. This review provides an overview of recent advances in this field.     

Stanisław Staszic: An Early Surveyor of the Geology of Central and Eastern Europe

In the late eighteenth and early nineteenth centuries the Polish geoscientist, philosopher, and statesman Stanis?aw Staszic (1755–1826) conducted an extensive geological survey of Poland and adjacent areas. In 1815, he completed a book (in Polish), On the geology of the Carpathians and other mountains and lowlands of Poland, complemented by a well-made geological map of Central and Eastern Europe. Early in the nineteenth century, Staszic refined the idea of ‘geological mapping’, though initially he was interested in the exploration of mineral deposits, rock salt, copper and iron ores, and coal. Unlike his predecessors, his book adopted a temporal subdivision of rocks, using a somewhat modified version of Abraham Gottlob Werner's system. He delineated the surface distribution of five rock units and coloured them onto his map. His work gave expression to his view of geological history, and brought the ‘Enlightenment Period’ of geology in Central and Eastern Europe to a close.     

Scorpions are a food item of American black bears in Sonora, Mexico

The remains of the scorpion Diplocentrus peloncillensis Francke were found in 7 scats of black bears ( Ursus americanus ) collected in the Sierra de San Luis, Sonora, Mexico. The collection data and previously reported black bear population estimates for the study area suggested that, although scorpions are not a large part of black bear diets in Sonora, feeding on scorpions is not restricted to a single individual or family unit and is apparently a relatively common behavior in the population. Also, the discovery of D. peloncillensis in Sonora represents a new country record.     

Activation of GCN2 upon HIV-1 infection and inhibition of translation

Higher eukaryotic organisms have a variety of specific and nonspecific defense mechanisms against viral invaders. In animal cells, viral replication may be limited through the decrease in translation. Some viruses, however, have evolved mechanisms that counteract the response of the host. We report that infection by HIV-1 triggers acute decrease in translation. The human protein kinase GCN2 (eIF2AK4) is activated by phosphorylation upon HIV-1 infection in the hours following infection. Thus, infection by HIV-1 constitutes a stress that leads to the activation of GCN2 with a resulting decrease in protein synthesis. We have shown that GCN2 interacts with HIV-1 integrase (IN). Transfection of IN in amino acid-starved cells, where GCN2 is activated, increases the protein synthesis level. These results point to an as yet unknown role of GCN2 as an early mediator in the cellular response to HIV-1 infection, and suggest that the virus is able to overcome the involvement of GCN2 in the cellular response by eliciting methods to maintain protein synthesis.     

The flight periodicity, attack patterns, and life history of Dryocoetes confusus Swaine (Coleoptera: Curculionidae: Scolytinae), the western balsam bark beetle, in north central Colorado

Dryocoetes confusus Swaine, the western balsam bark beetle, is an important bark beetle associated with Abies lasiocarpa (Hook.) Nutt. (subalpine fir) in western North America. Little information is available on the life cycle and ecology of this insect in Colorado. In this study in north central Colorado, we examined its flight periodicity, attack patterns, and life cycle in downed trees. Flight season, as indicated by pheromone-trap catches, began in early June. Peak flight was observed during early to mid-July. A second peak in flight was observed in some years, but its occurrence was not consistent. Preferred attack sites on downed trees were the underside or side of the log and through branch stubs. The life cycle for this beetle was completed in 2 years, consistent with earlier observations from British Columbia. Sex ratio was 1:1, but a higher percentage of males fly earlier in the season.     

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.     

Simultaneous determination of sodium,NPN, and protein in 0.2 ml of blood serum

Zusammenfassung Es wird eine stufenphotometrische Methode beschrieben, welche es ermöglicht, in 0,2 cm³ Blutserum bzw. plasma Natrium, Reststickstoff und Gesamteiweiß nebeneinander zu bestimmen.     

On long memory origins and forecast horizons

Most long memory forecasting studies assume that long memory is generated by the fractional difference operator. We argue that the most cited theoretical arguments for the presence of long memory do not imply the fractional difference operator and assess the performance of the autoregressive fractionally integrated moving average (ARFIMA) model when forecasting series with long memory generated by nonfractional models. We find that ARFIMA models dominate in forecast performance regardless of the long memory generating mechanism and forecast horizon. Nonetheless, forecasting uncertainty at the shortest forecast horizon could make short memory models provide suitable forecast performance, particularly for smaller degrees of memory. Additionally, we analyze the forecasting performance of the heterogeneous autoregressive (HAR) model, which imposes restrictions on high-order AR models. We find that the structure imposed by the HAR model produces better short and medium horizon forecasts than unconstrained AR models of the same order. Our results have implications for, among others, climate econometrics and financial econometrics models dealing with long memory series at different forecast horizons.     

Cosmological Black Holes and the Direction of Time

Macroscopic irreversible processes emerge from fundamental physical laws of reversible character. The source of the local irreversibility seems to be not in the laws themselves but in the initial and boundary conditions of the equations that represent the laws. In this work we propose that the screening of currents by black hole event horizons determines, locally, a preferred direction for the flux of electromagnetic energy. We study the growth of black hole event horizons due to the cosmological expansion and accretion of cosmic microwave background radiation, for different cosmological models. We propose generalized McVittie co-moving metrics and integrate the rate of accretion of cosmic microwave background radiation onto a supermassive black hole over cosmic time. We find that for flat, open, and closed Friedmann cosmological models, the ratio of the total area of the black hole event horizons with respect to the area of a radial co-moving space-like hypersurface always increases. Since accretion of cosmic radiation sets an absolute lower limit to the total matter accreted by black holes, this implies that the causal past and future are not mirror symmetric for any spacetime event. The asymmetry causes a net Poynting flux in the global future direction; the latter is in turn related to the ever increasing thermodynamic entropy. Thus, we expose a connection between four different “time arrows”: cosmological, electromagnetic, gravitational, and thermodynamic.