Molecular evolution of primate immunodeficiency viruses and hepatitis delta virus

Primate immunodeficiency viruses, or lentiviruses (HIV-1, HIV-2, and SIV), and hepatitis delta virus (HDV) are RNA viruses characterized by rapid evolution. Infection by primate immunodeficiency viruses usually results in the development of acquired immunodeficiency syndrome (AIDS) in humans and AIDS-like illnesses in Asian macaques. Similarly, hepatitis delta virus infection causes hepatitis and liver cancer in humans. These viruses are heterogeneous within an infected patient and among individuals. Substitution rates in the virus genomes are high and vary in different lineages and among sites. Methods of phylogenetic analysis were applied to study the evolution of primate lentiviruses and the hepatitis delta virus. The following results have been obtained: (1) The substitution rate varies among sites of primate lentivirus genes according to the two parameter gamma distribution, with the shape parameter $\alpha$ being close to 1. (2) Primate immunodeficiency viruses fall into species-specific lineages. Therefore, viral transmissions across primate species are not as frequent as suggested by previous authors. (3) Primate lentiviruses have acquired or lost their pathogenicity several times in the course of evolution. (4) Evidence was provided for multiple infections of a North American patient by distinct HIV-1 strains of the B subtype. (5) Computer simulations indicate that the probability of committing an error in testing HIV transmission depends on the number of virus sequences and their length, the divergence times among sequences, and the model of nucleotide substitution. (6) For future investigations of HIV-1 transmissions, using longer virus sequences and avoiding the use of distant outgroups is recommended. (7) Hepatitis delta virus strains are usually related according to the geographic region of isolation. (8) Evolution of HDV is characterized by the rate of synonymous substitution being lower than the nonsynonymous substitution rate and the rate of evolution of the noncoding region. (9) There is a strong preference for G and C nucleotides at the third codon positions of the HDV coding region. ^

Characterization of NARJ: A molecular chaperone involved in assembly of nitrate reductase

The major goal of this work was to define the role of accessory protein, NARJ, in assembly of nitrate reductase which is a membrane-bound multisubunit enzyme that can catalyze the reduction of nitrate to nitrite under anaerobic growth in E. coli. Nitrate reductase is encoded by the nar GHJI operon under control of the narG promoter. The purified nitrate reductase is composed of three subunits: $\alpha,\ \beta,$ and $\gamma.$ The NARJ protein which is encoded by the third gene (narJ) is not found to be associated with any of the purified preparations of the enzyme, but is required for active nitrate reductase. In this study the product of the narJ gene was identified. NARJ appeared to be produced at a reduced level, compared to the other proteins encoded by the nar operon. Since NARJ could not be overexpressed to a level for an efficient purification, NARJ was expressed and purified as a recombinant protein with polyhistidine tag. The recombinant protein NARJ-6His could functionally replace native NARJ. Purified NARJ-6His is a dimeric protein which contains no identifiable cofactors or unique secondary structure. NARJ was localized in the cytoplasm, and was not associated with nitrate reductase in the membrane. In vivo NARJ activated the $\alpha\beta$ complex and stabilized the $\alpha$ subunit against protease degradation. In the absence of the membrane-bound $\gamma$ subunit, NARJ formed an intermediate complex with $\alpha\beta$ in the cytosol. Based on these studies, NARJ fits the formal definition of a molecular chaperone. It appears to be required only for the biogenesis of nitrate reductase and, therefore, is defined as a private chaperone specifically involved in the assembly of nitrate reductase system. ^

Molecular mechanisms of chondrocyte-specific expression on the mouse pro$\alpha$1(II) collagen gene

Type II collagen is a major chondrocyte-specific component of the cartilage extracellular matrix and it represents a typical differentiation marker of mature chondrocytes. In order to delineate cis-acting elements of the mouse pro$\alpha1$(II) collagen gene that control chondrocyte-specific expression in intact mouse embryos, we generated transgenic mice harboring chimeric constructions in which varying lengths of the promoter and intron 1 sequences were linked to a $\beta$-galactosidase reporter gene. A construction containing a 3000-bp promoter and a 3020-bp intron 1 fragment directed high levels of $\beta$-galactosidase expression specifically to chondrocytes. Successive deletions of intron 1 delineated a 48-bp fragment which targeted $\beta$-galactosidase expression to chondrocytes with the same specificity as the larger intron 1 fragment. When the Col2a1 promoter was replaced with a minimal $\beta$-globin promoter, the 48-bp intron 1 sequence was still able to target expression of the transgene to chondrocytes, specifically. Therefore a 48-bp intron 1 DNA segment of the mouse Col2a1 gene contains the necessary information to confer high-level, temporally correct, chondrocyte expression to a reporter gene in intact mouse embryos and that Col2a1 promoter sequences are dispensable for chondrocyte expression. Nuclear proteins present selectively in mouse primary chondrocytes and rat chondrosarcoma cells bind to the three putative HMG (High-Mobility-Group) domain protein binding sites in this 48-bp sequence and the chondrocyte-specific proteins likely bind the DNA through minor groove. Together, my results indicate that a 48-bp sequence in Col2a1 intron 1 controls chondrocyte-specific expression in vivo and suggest that chondrocytes contain specific nuclear proteins involved in enhancer activity. ^

The year-long unprecedented European heat and drought of 1540 – a worst case

The heat waves of 2003 in Western Europe and 2010 in Russia, commonly labelled as rare climatic anomalies outside of previous experience, are often taken as harbingers of more frequent extremes in the global warming-influenced future. However, a recent reconstruction of spring–summer temperatures for WE resulted in the likelihood of significantly higher temperatures in 1540. In order to check the plausibility of this result we investigated the severity of the 1540 drought by putting forward the argument of the known soil desiccation-temperature feedback. Based on more than 300 first-hand documentary weather report sources originating from an area of 2 to 3 million km2, we show that Europe was affected by an unprecedented 11-month-long Megadrought. The estimated number of precipitation days and precipitation amount for Central and Western Europe in 1540 is significantly lower than the 100-year minima of the instrumental measurement period for spring, summer and autumn. This result is supported by independent documentary evidence about extremely low river flows and Europe-wide wild-, forest- and settlement fires. We found that an event of this severity cannot be simulated by state-of-the-art climate models.

Integration through Land Improvment – Internal Colonization in Switzerland During the First Part of the 20th Century

Internal colonization in Switzerland is often seen in connection with the battle for cultivation in the Second World War, but the history of internal colonization in Switzerland is more complex. The food crisis in the First World War formed the horizon of experience for various actors from industry, consumer protection, the urban population and agriculture to start considering practical strategies for managing agricultural production. In this way, traditional spaces, such as rural and urban areas and economic roles, such as food producer, consumer and trader, overlapped and were newly conceived to some extent: people started thinking about utopias and how a modern society could be designed to be harmonious and resistant to crisis. The aim of this article is to trace some of the key points in this process for the interwar years in neutral Switzerland. In the process, the focus must be on the context of people’s mentalities in the past, although the relationships between the actors of internal colonization and the state also need to be considered. Internal colonization in Switzerland in the twentieth century can be understood as an open process. In principle, the project was driven by private actors, but in times of crisis, the project was claimed by the state as a possible tool for social and economic intervention. In addition, as a result of the planned dissolution of urban and rural spaces, it will be shown that modern societies in the interwar period were on an existential search to overcome the problems of the modern age. Internal colonization can therefore be seen as an attempt to find a third way between a world characterized by an agrarian society and a modern industrial nation.

The largest floods in the High Rhine basin since 1268 assessed from documentary and instrumental evidence

The magnitudes of the largest known floods of the River Rhine in Basel since 1268 were assessed using a hydraulic model drawing on a set of pre-instrumental evidence and daily hydrological measurements from 1808. The pre-instrumental evidence, consisting of flood marks and documentary data describing extreme events with the customary reference to specific landmarks, was “calibrated” by comparing it with the instrumental series for the overlapping period between the two categories of evidence (1808–1900). Summer (JJA) floods were particularly frequent in the century between 1651–1750, when precipitation was also high. Severe winter (DJF) floods have not occurred since the late 19th century despite a significant increase in winter precipitation. Six catastrophic events involving a runoff greater than 6000 m 3 s-1 are documented prior to 1700. They were initiated by spells of torrential rainfall of up to 72 h (1480 event) and preceded by long periods of substantial precipitation that saturated the soils, and/or by abundant snowmelt. All except two (1999 and 2007) of the 43 identified severe events (SEs: defined as having runoff > 5000 and < 6000 m 3 s -1) occurred prior to 1877. Not a single SE is documented from 1877 to 1998. The intermediate 121-year-long “flood disaster gap” is unique over the period since 1268. The effect of river regulations (1714 for the River Kander; 1877 for the River Aare) and the building of reservoirs in the 20th century upon peak runoff were investigated using a one-dimensional hydraulic flood-routing model. Results show that anthropogenic effects only partially account for the “flood disaster gap” suggesting that variations in climate should also be taken into account in explaining these features.

Spring-summer temperatures reconstructed for northern Switzerland and southwestern Germany from winter rye harvest dates, 1454–1970

This paper presents a unique 517-yr long documentary data-based reconstruction of spring-summer (MAMJJ) temperatures for northern Switzerland and southwestern Germany from 1454 to 1970. It is composed of 25 partial series of winter grain (secale cereale) harvest starting dates (WGHD) that are partly based on harvest related bookkeeping of institutions (hospitals, municipalities), partly on (early) phenological observations. The resulting main Basel WGHD series was homogenised with regard to dating style, data type and altitude. The calibration and verification approach was applied using the homogenous HISTALP temperature series from 1774–1824 for calibration (r = 0.78) and from 1920–1970 for verification (r = 0.75). The latter result even suffers from the weak data base available for 1870– 1950. Temperature reconstructions based on WGHD are more influenced by spring temperatures than those based on grape harvest dates (GHD), because rye in contrast to vines already begins to grow as soon as sunlight brings the plant to above freezing. The earliest and latest harvest dates were checked for consistency with narrative documentary weather reports. Comparisons with other European documentarybased GHD and WGHD temperature reconstructions generally reveal significant correlations decreasing with the distance from Switzerland. The new Basel WGHD series shows better skills in representing highly climate change sensitive variations of Swiss Alpine glaciers than available GHD series.