(−)-trans-7(S)-Methoxytetradec-4-enoic acid and related amides from the marine cyanophyte Lyngbya majuscula

(?)-trans-7(S)-Methoxytetradec-4-enoic acid and the related amides, malyngamides A, B and C, were found as constituents of shallow-water varieties of the marine blue-green alga Lyngbya majuscule.     

Neoplasia in the Siberian weasel (<Emphasis Type="Italic">Mustela sibirica</Emphasis>): two case reports of fibrosarcoma and interstitial cell tumour

Two cases of neoplasia occurred in two adult Siberian weasels (Mustela sibirica) in a game reserve in southern Lower Saxony, Germany. The first case, a male weasel, showed an enlargement of the right testicle, which was surgically removed. The tumour was classified as an interstitial cell tumour. One year after surgery, the male weasel died by accident and revealed tumour lesions of uncertain histogenesis within the abdominal cavity and the spleen at necropsy. The second case, a female animal, became suspicious by a dermal mass in the upper left hind limb, which was also surgically excised. Pathological examinations revealed a fibrosarcoma that recurred twice after removal of the original mass. These two cases of neoplasia in the Siberian weasel are demonstrated with regard to clinical aspects and discussed on the basis of their pathomorphological features.     

From sediment to soil: floodplain phosphorus transformations at the Danube River

Substantial transformations of biogeochemical phosphorus (P) fractions can occur within a few hundreds of years under humid and tropical conditions; however, slower changes are expected under dry and temperate climate. The objective of this study was to infer P transformations over time by comparing suspended sediments in the Danube River to floodplain soils developed from such sediments over different time periods in the continental climate of Central Europe. We analyzed suspended sediments from 20 flood events between 1990 and 2006, and floodplain soils from seven sites along a chronosequence covering about 500 yrs. The studied flood sediments had similar characteristics over the 16-yr observation period. Total phosphorus (TP) averaged 732 mg kg⁻¹, and biogeochemical fractionation yielded important primary mineral contributions (apatite phosphorus, AP, ~80% of TP). The TP concentrations of the floodplain soils were in the range of the Danube sediments and showed little variation along the chronosequence. However, the distribution of P among biogeochemical fractions changed considerably in less than 500 yrs of soil development. The youngest soils (<20 yrs) were dominated by AP, as was observed for the Danube sediments. In less than 250 yrs of pedogenesis, AP markedly decreased and organic phosphorus (OP) increased, and in less than 500 yrs, OP reached AP levels. This shows that while P biogeochemistry in very young floodplain soils is strongly related to the river sediments, significant transformations can occur in less than 250 yrs of soil development in the dry and temperate climate of Central Europe.     

Adenoviral hepatitis in a SIV-infected rhesus monkey (Macaca mulatta)

BACKGROUND: A 5-year-old female rhesus monkey infected with simian immunodeficiency virus became clinically suspicious with anorexia, increasing weakness and apathy eighty-five weeks after the tonsillar virus inoculation and was euthanised due to a poor prognosis. METHODS AND RESULTS: Postmortal examinations revealed a severe multifocal to coalescing necotizing hepatitis with numerous intranuclear basophilic inclusion bodies. Transmission electron microscopy of the liver resulted in the finding of adenovirus like particles arranged in paracrystalline arrays within the nuclei of hepatocytes.CONCLUSION: The SIV infected rhesus monkey suffered from an adenovirus included necortizing hepatitis, an extremely rare organ manifestation of adenovirus infection in nonhuman primates.     

Structural stability of wild type and mutated alpha-keratin fragments: molecular dynamics and free energy calculations

The objective of this study is to investigate the influence of point mutations on the structural stability of coiled coil fragments of the human hair intermediate filament by molecular dynamics simulations and free energy calculations. Mutations in the helix termination motif of human hair keratin gene hHb6 seem to be connected to the hereditary hair dystrophy Monilethrix. The most common mutations reported are Glu413Lys and Glu413Asp, located at the C-terminal end of the coiled coil 2B rod domain of the IF. According to our simulations, significant conformational changes of the side chains at the mutation and neighboring sites occur due to the Glu413Lys mutation. Furthermore, the differences in electrostatic interactions cause a large change in free energy during transformation of Glu413 to Lys calculated by the thermodynamic integration approach. It is speculated that the structural rearrangement necessary to adapt the interactions in the mutated coiled coil leads to changes in the IF assembly or its stability. The second mutation, Glu413Asp, only leads to a small value of the calculated free energy difference that is within the error limits of the simulations. Thus, it has to be concluded that this mutation does not affect the coiled coil stability.     

Tyrosine phosphorylation of protein kinase D in the pleckstrin homology domain leads to activation

Protein kinase D (PKD) is a member of the AGC family of Ser/Thr kinases and is distantly related to protein kinase C (PKC). Formerly known as PKCmu, PKD contains protein domains not found in conventional PKC isoforms. A functional pleckstrin homology (PH) domain is critical for the regulation of PKD activity. Here we report that PKD is tyrosine-phosphorylated within the PH domain, leading to activation. This phosphorylation is mediated by a pathway that consists of the Src and Abl tyrosine kinases and occurs in response to stimulation with pervanadate and oxidative stress. Mutational analysis revealed three tyrosine phosphorylation sites (Tyr(432), Tyr(463), and Tyr(502)), which are regulated by the Src-Abl pathway, and phosphorylation of only one of these (Tyr(463)) leads to PKD activation. By using a phospho-specific antibody, we show that Abl directly phosphorylates PKD at Tyr(463) in vitro, and in cells phosphorylation of this site is sufficient to mediate full activation of PKD. Mutation of the other two sites, Tyr(432) and Tyr(502), had no significant influence on PKD activity. These data reveal a tyrosine phosphorylation-dependent activation mechanism for PKD and suggest that this event contributes to the release of the autoinhibitory PKD PH domain leading to kinase activation and downstream responses.     

Both chlorophylls a and d are essential for the photochemistry in photosystem II of the cyanobacteria, Acaryochloris marina

We have measured the flash-induced absorbance difference spectrum attributed to the formation of the secondary radical pair, P(+)Q(-), between 270 nm and 1000 nm at 77 K in photosystem II of the chlorophyll d containing cyanobacterium, Acaryochloris marina. Despite the high level of chlorophyll d present, the flash-induced absorption difference spectrum of an approximately 2 ms decay component shows a number of features which are typical of the difference spectrum seen in oxygenic photosynthetic organisms containing no chlorophyll d. The spectral shape in the near-UV indicates that a plastoquinone is the secondary acceptor molecule (Q(A)). The strong C-550 change at 543 nm confirms previous reports that pheophytin a is the primary electron acceptor. The bleach at 435 nm and increase in absorption at 820 nm indicates that the positive charge is stabilized on a chlorophyll a molecule. In addition a strong electrochromic band shift, centred at 723 nm, has been observed. It is assigned to a shift of the Qy band of the neighbouring accessory chlorophyll d, Chl(D1). It seems highly likely that it accepts excitation energy from the chlorophyll d containing antenna. We therefore propose that primary charge separation is initiated from this chlorophyll d molecule and functions as the primary electron donor. Despite its lower excited state energy (0.1 V less), as compared to chlorophyll a, this chlorophyll d molecule is capable of driving the plastoquinone oxidoreductase activity of photosystem II. However, chlorophyll a is used to stabilize the positive charge and ultimately to drive water oxidation.     

Long-term follow-up study on SIV intestinal proviral load in rhesus macaques

After experimental infection with simian immunodeficiency virus (SIV), intestinal endoscopy proved to be an easily tolerated, minimal invasive procedure to obtain biopsies from the gastrointestinal tract of rhesus macaques during all stages of disease. As the GI tract is affected by many opportunistic infections and immunological impairment after SIV/human immunodeficiency virus (HIV) infection, knowledge on the proviral load is an important parameter for a better understanding of disease pathogenesis. In this paper, we describe the set-up and evaluation of a quantitative competitive polymerase chain reaction (PCR) and the quantification of SIV intestinal proviral load in a long-term follow-up study of eight rhesus monkeys ( Macaca mulatta ) after two different routes of virus inoculation. A SIV-specific signal could be detected as early as day 3 after infection. Of 143 biopsies from the follow-up study, 85.3% showed a positive PCR. DNA copy numbers ranged from 300 to 15,000 molecules per 100,000 cells. No significant influence of the inoculation route could be shown on either proviral load or survival time, but higher SIV proviral load was associated with a more rapid progression to disease. Therefore, the amount of proviral load in intestinal biopsies may be an important prognostic value for the further course of the disease.     

Metabolism of 4-hydroxyandrostenedione and 4-hydroxytestosterone: Mass spectrometric identification of urinary metabolites

4-Hydroxyandrost-4-ene-3,17-dione is a second generation, irreversible aromatase inhibitor and commonly used as anti breast cancer medication for postmenopausal women. 4-Hydroxytestosterone is advertised as anabolic steroid and does not have any therapeutic indication. Both substances are prohibited in sports by the World Anti-Doping Agency, and, due to a considerable increase of structurally related steroids with anabolic effects offered via the internet, the metabolism of two representative candidates was investigated. Excretion studies were conducted with oral applications of 100mg of 4-hydroxyandrostenedione or 200mg of 4-hydroxytestosterone to healthy male volunteers. Urine samples were analyzed for metabolic products using conventional gas chromatography-mass spectrometry approaches, and the identification of urinary metabolites was based on reference substances, which were synthesized and structurally characterized by nuclear magnetic resonance spectroscopy and high resolution/high accuracy mass spectrometry. Identified phase-I as well as phase-II metabolites were identical for both substances. Regarding phase-I metabolism 4-hydroxyandrostenedione (1) and its reduction products 3beta-hydroxy-5alpha-androstane-4,17-dione (2) and 3alpha-hydroxy-5beta-androstane-4,17-dione (3) were detected. Further reductive conversion led to all possible isomers of 3xi,4xi-dihydroxy-5xi-androstan-17-one (4, 6-11) except 3alpha,4alpha-dihydroxy-5beta-androstan-17-one (5). Out of the 17beta-hydroxylated analogs 4-hydroxytestosterone (18), 3beta,17beta-dihydroxy-5alpha-androstan-4-one (19), 3alpha,17beta-dihydroxy-5beta-androstan-4-one (20), 5alpha-androstane-3beta,4beta,17beta-triol (21), 5alpha-androstane-3alpha,4beta,17beta-triol (26) and 5alpha-androstane-3alpha,4alpha,17beta-triol (28) were identified in the post administration urine specimens. Furthermore 4-hydroxyandrosta-4,6-diene-3,17-dione (29) and 4-hydroxyandrosta-1,4-diene-3,17-dione (30) were determined as oxidation products. Conjugation was diverse and included glucuronidation and sulfatation.     

Fatal Balamuthia mandrillaris infection in a gorilla - first case of balamuthiasis in Germany

Background A 12‐year‐old female western lowland gorilla died in a zoological garden in Germany after exhibiting general neurological signs. Methods Balamuthia mandrillaris was identified as causative agent by indirect immunofluorescent staining of brain sections and confirmed by PCR and respective sequencing. Results The animal suffered from a chronic progressive necrotizing amebic meningoencephalitis. Conclusion This is the first case of Balamuthia amebic encephalitis in Germany.