A Novel 1,4-Dihydropyridine Derivative Improves Spatial Learning and Memory and Modifies Brain Protein Expression in Wild Type and Transgenic APPSweDI Mice

Ca²⁺ blockers, particularly those capable of crossing the blood-brain barrier (BBB), have been suggested as a possible treatment or disease modifying agents for neurodegenerative disorders, e.g., Alzheimer’s disease. The present study investigated the effects of a novel 4-(N-dodecyl) pyridinium group-containing 1,4-dihydropyridine derivative (AP-12) on cognition and synaptic protein expression in the brain. Treatment of AP-12 was investigated in wild type C57BL/6J mice and transgenic Alzheimer’s disease model mice (Tg APP_SweDI) using behavioral tests and immunohistochemistry, as well as mass spectrometry to assess the blood-brain barrier (BBB) penetration. The data demonstrated the ability of AP-12 to cross the BBB, improve spatial learning and memory in both mice strains, induce anxiolytic action in transgenic mice, and increase expression of hippocampal and cortical proteins (GAD67, Homer-1) related to synaptic plasticity. The compound AP-12 can be seen as a prototype molecule for use in the design of novel drugs useful to halt progression of clinical symptoms (more specifically, anxiety and decline in memory) of neurodegenerative diseases, particularly Alzheimer’s disease.     

Pristine Early Eocene Wood Buried Deeply in Kimberlite from Northern Canada

We report exceptional preservation of fossil wood buried deeply in a kimberlite pipe that intruded northwestern Canada’s Slave Province 53.3±0.6 million years ago (Ma), revealed during excavation of diamond source rock. The wood originated from forest surrounding the eruption zone and collapsed into the diatreme before resettling in volcaniclastic kimberlite to depths >300 m, where it was mummified in a sterile environment. Anatomy of the unpermineralized wood permits conclusive identification to the genus Metasequoia (Cupressaceae). The wood yields genuine cellulose and occluded amber, both of which have been characterized spectroscopically and isotopically. From cellulose δ¹⁸O and δ²H measurements, we infer that Early Eocene paleoclimates in the western Canadian subarctic were 12–17°C warmer and four times wetter than present. Canadian kimberlites offer Lagerstätte-quality preservation of wood from a region with limited alternate sources of paleobotanical information.     

Zur Kenntnis der Zell- und Kernteilung in dem primären Meristem

Ohne Zusammenfassung     

Conceptual models for burrow-related, selective dolomitization with textural and isotopic evidence from the Tyndall Stone, Canada

The formation of dolomite is generally explained using models that reflect larger‐scale processes that describe the relationship between the supply and transport of Mg, and geochemical conditions that are amenable to the formation of dolomite. However, heterogeneities in the substrate, such as those made by bioturbating infauna, may play a more important role in dolomitization than has been previously considered. Burrow‐facilitated dolomitization is evident in the Ordovician Tyndall Stone (Red River Group, Selkirk Formation) of central Canada. The diagenetic fabrics present are attributed to dolomitizing fluids that both flowed through and evolved within burrow networks. Petrographic analysis suggests that two phases of dolomite formation took place. The first formed a fine‐grained, fabric‐destructive type that probably accompanied early burial; the second is a fine‐ to medium‐grained, locally sucrosic dolomite that is interpreted to have precipitated during later burial. Isotopic analysis supports the proposed paragenetic history: (1) an apparent linking of the stable isotopes ¹³C and ¹⁸O strongly suggests that the micrite matrix formed during very early diagenesis and was derived from seawater; (2) the initial phase of dolomitization is potentially microbially mediated, as evidenced by the enrichment of ¹³C; and (3) isotopic values for the second generation of dolomite reflect the mixing of ground water and resorbed early dolomite. This paper conceptualizes the physical and chemical conditions required for the formation of dolomite in association with burrow fabrics. The proposed model reveals a composite of biological and inorganic reactions that demonstrates the interdependence of sediment fabric, organic content and microbial interactions in the development of burrow‐mottled dolomitic limestone. It is suggested that where burrow‐associated dolomite occurs, it is most likely to develop in two stages: first, the byproducts of the degradation of organic material in burrows locally increase the permeability and porosity around burrow fabrics in shallow diagenetic depositional environments; and, second, the passing of burrowed media into deeper dysaerobic sediment is accompanied by the establishment of fermenting micro‐organisms whose byproducts mediate dolomitization.     

HSM — a hybrid system based approach for modelling intracellular networks

The paper proposes a hybrid system based approach for modelling of intracellular networks and introduces a restricted subclass of hybrid systems – HSM – with an objective of still being able to provide sufficient power for the modelling of biological systems, while imposing some restrictions that facilitate analysis of systems described by such models.     

Optimized Preparation and Determination of Pea Seedling Diamine Oxidase

The level of diamine oxidase in pea seedling stems has been determined as a function of time after germination in both etiolated and non-etiolated plants. The maximum amount of enzyme per plant is obtained between 11 and 13 days. The amount of activity per gram of tissue appears to be proportional to the rate of growth. We describe an efficient method of isolation of pea seedling stem diamine oxidase from 12-day-old etiolated seedlings, a procedure that brings the enzyme to purity after a 97-fold purification. A new assay procedure for pea seedling diamine oxidase is detailed and compared to previously used methods. The kinetic parameters for three common substrates have also been determined. SDS-acrylamide gel electrophoresis, gel filtration chromatography and copper analyses have been used to determine that pea seedling diamine oxidase exists as a dimer of two apparently identical subunits, the dimer molecular weight being about 190,000. The isoelectric point of this enzyme was determined to be 6.5.     

A half-marathon and a marathon run induce oxidative DNA damage, reduce antioxidant capacity to protect DNA against damage and modify immune function in hobby runners

This study investigated whether a 21.1 km (half-marathon) or a 42.195 km (marathon) run modulates DNA damage, antioxidant capacity in lymphocytes and plasma, and the immune system in healthy hobby runners. Ten and 12 volunteers who completed the Baden-Marathon race in Karlsruhe with a running distance of 21.1 km and 41.195 km, respectively, were assessed 10 days before and immediately after the finish. There was no increase in the levels of endogenous DNA strand breaks immediately after half-marathon or marathon races. A statistically significant increase in the levels of oxidative DNA damage in lymphocytes was found using endonuclease III but not formamidopyrimidine glycolase (Fpg). The resistance of DNA to oxidative damage induced by hydrogen peroxide in isolated lymphocytes was significantly decreased after both races. The levels of plasma antioxidants such as alpha-tocopherol, beta-carotene and lycopene were close to, or higher than, those considered optimal for reducing the risk of cardiovascular diseases and there were no significant changes after the races in antioxidant capacity of LDL (lag-time test) or plasma in ORAC, TEAC or paraoxonase assays. The number and percentage of granulocytes and monocytes able to generate oxidative burst were significantly increased after both races, but the lytic activity of NK cells was significantly increased at the end of the half-marathon; no effect was observed in the marathon runners. Thus, oxidative DNA damage in lymphocytes, decreased the antioxidant capacity to protect lymphocytes against DNA strand breaks and increased the formation of reactive species by phagocytes in well-nourished hobby runners indicating moderate oxidative damage during such high-intensity exercise.     

Carotenoids in petals of perennial Medicago species

The carotenoid content in the petals of fourteen Medicago species was examined, together with eight species studied previously, caratenoids in all the known perennials of the genus are reported. The species can be arranged in relationship groups on the basis of their interfertility. No major carotenoid was species- or groupspecific; a few minor pigments, however, were group- or species-specific. The amount of carotenoids ranged from 7 μg/g dry matter in violet-flowered M. sativa to 2120 μg/g in brownish-yellow M. platycarpos. Xanthophylls constituted 76–99% of the total, with lutein as the major component. β-Carotene, lutein and flavoxanthin were ubiquitous in petals. In M sativa leaves β-carotene, lutein, violaxanthin and neoxanthin constituted 88% of the total. The xanthophylls were esterified in petals but not in leaves.     

A new proposal concerning the botanical origin of Baltic amber

Baltic amber constitutes the largest known deposit of fossil plant resin and the richest repository of fossil insects of any age. Despite a remarkable legacy of archaeological, geochemical and palaeobiological investigation, the botanical origin of this exceptional resource remains controversial. Here, we use taxonomically explicit applications of solid-state Fourier-transform infrared (FTIR) microspectroscopy, coupled with multivariate clustering and palaeobotanical observations, to propose that conifers of the family Sciadopityaceae, closely allied to the sole extant representative, Sciadopitys verticillata, were involved in the genesis of Baltic amber. The fidelity of FTIR-based chemotaxonomic inferences is upheld by modern–fossil comparisons of resins from additional conifer families and genera (Cupressaceae: Metasequoia; Pinaceae: Pinus and Pseudolarix). Our conclusions challenge hypotheses advocating members of either of the families Araucariaceae or Pinaceae as the primary amber-producing trees and correlate favourably with the progressive demise of subtropical forest biomes from northern Europe as palaeotemperatures cooled following the Eocene climate optimum.     

Sabkha and Burrow-Mediated Dolomitization in the Mississippian Debolt Formation,Northwestern Alberta,Canada

Dolomitized burrows in the Mississippian (Visean) Debolt Formation of northwestern Alberta, Canada form the primary reservoir intervals in the Dunvegan gas field. Sedimentological and ichnological analyses suggest a carbonate ramp setting that includes subenvironments such as sabkhas, hypersaline lagoons, restricted subtidal lagoons, intertidal mud flats, and peloidal shoals. Dolomitization occurs primarily within oxidized muds and highly bioturbated sediments, with the primary mode being sabkha-associated precipitation. In this context, dolomitization within the burrows also appears to be mediated by sulfate-reducing bacteria. δ¹⁸O values for dolomite within burrows (mean 2.4‰) are enriched by 1.3‰ relative to calcite values (mean 1.1‰) within the burrows. This degree of fractionation is similar for dolomite and calcite that have precipitated from the same solution. It is therefore suggested that the protodolomite precipitated in equilibrium with calcite rather than by replacement of pre-existing calcite. Isotopic values of δ¹³C measured for dolomite associated with burrows (mean 3.4‰) and matrix (mean 3.5‰) is slightly enriched relative to measured calcite values (mean 3.2‰ for matrix; mean 3.1‰ for burrows). These isotopic trends are common for modern dolomite that has precipitated in equilibrium with seawater where concomitant sulfate reduction and organic carbon-oxidation is inferred to occur near the surface.