Morphology and Phylogeny of Calyptospora paranaidji n. sp. (Eimeriorina: Calyptosporidae), an Apicomplexan Parasite of the Hepatic Tissue of Cichla piquiti Kullander & Ferreira, 2006, From a Reservoir in the Brazilian Amazon Region

The coccidians of the family Calyptosporidae are parasites of the tissue and organs of fish and aquatic invertebrates, in particular in the tropical region. In contrast with other apicomplexans of the suborder Eimeriorina, the diversity and ecology of the species of the genus Calyptospora have been poorly investigated, resulting in a lacuna that restricts the understanding of the distribution and prevalence of this group of eukaryote microparasites in the Amazon region. In the present study, the integrated comparative analysis of morphological characteristics, histological and structural traits, and the sequences of a fragment of the 18S rRNA gene, provides support for the identification of a new species of Calyptospora, found parasitizing the hepatic tissue of the piscivorous blue peacock bass, Cichla piquiti, captured in the reservoir of the Estreito hydroelectric dam on the middle Tocantins River in northern Brazil. This new species was named Calyptospora paranaidji n. sp.     

Dimeric argininamide-type neuropeptide Y receptor antagonists: Chiral discrimination between Y1 and Y4 receptors

The structurally related peptides neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) are endogenous agonists of the NPY receptor (YR) family, which in humans comprises four functionally expressed subtypes, designated Y₁R, Y₂R, Y₄R and Y₅R. Nonpeptide antagonists with high affinity and selectivity have been described for the Y₁R, Y₂R and Y₅R, but such compounds are still lacking for the Y₄R. In this work, the structures of the high affinity selective (R)-argininamide-type Y₁R antagonists BIBP3226 and BIBO3304 were linked via the guanidine or urea moieties to give homo-dimeric argininamides with linker lengths ranging from 31 to 41 atoms. Interestingly, the twin compounds proved to be by far less selective for the Y₁R than the R-configured monovalent parent compounds. The decrease in selectivity ratio was most pronounced for Y₁R versus Y₄R subtype, resulting in comparable affinities of bivalent ligands for Y₁R and Y₄R (e.g. UR-MK177 ((R,R)-49): K_i = 230 nM (Y₁R) and 290 nM (Y₄R)). With a K_i value of 130 nM and a K_b value of 20 nM, UR-MK188 ((R,R)-51) was superior to all Y₄R antagonists known to date. The S,S-configured optical antipodes of UR-MK177 and UR-MK188 (UR-MEK381 ((S,S)-49) and UR-MEK388 ((S,S)-51)) were synthesized to investigate the stereochemical discrimination by the different receptor subtypes. Whereas preference for R,R-configured argininamides was characteristic of the Y₁R, stereochemical discrimination by the Y₄R was not observed. This may pave the way to selective Y₄R antagonists.     

Neuropeptides Control the Dynamic Behavior of Airway Mucosal Dendritic Cells

The airway mucosal epithelium is permanently exposed to airborne particles. A network of immune cells patrols at this interface to the environment. The interplay of immune cells is orchestrated by different mediators. In the current study we investigated the impact of neuronal signals on key functions of dendritic cells (DC). Using two-photon microscopic time-lapse analysis of living lung sections from CD11c-EYFP transgenic mice we studied the influence of neuropeptides on airway DC motility. Additionally, using a confocal microscopic approach, the phagocytotic capacity of CD11c⁺ cells after neuropeptide stimulation was determined. Electrical field stimulation (EFS) leads to an unspecific release of neuropeptides from nerves. After EFS and treatment with the neuropeptides vasoactive intestinal peptide (VIP) or calcitonin gene-related peptide (CGRP), airway DC in living lung slices showed an altered motility. Furthermore, the EFS-mediated effect could partially be blocked by pre-treatment with the receptor antagonist CGRP_8–37. Additionally, the phagocytotic capacity of bone marrow-derived and whole lung CD11c⁺ cells could be inhibited by neuropeptides CGRP, VIP, and Substance P. We then cross-linked these data with the in vivo situation by analyzing DC motility in two different OVA asthma models. Both in the acute and prolonged OVA asthma model altered neuropeptide amounts and DC motility in the airways could be measured. In summary, our data suggest that neuropeptides modulate key features motility and phagocytosis of mouse airway DC. Therefore altered neuropeptide levels in airways during allergic inflammation have impact on regulation of airway immune mechanisms and therefore might contribute to the pathophysiology of asthma.     

Towards new antimalarial drugs: synthesis of non-hydrolyzable phosphate mimics as feed for a predictive QSAR study on 1-deoxy-D-xylulose-5-phosphate reductoisomerase inhibitors

The conversion of 1-deoxy-D-xylulose-5-phosphate (DOXP) to 2-C-methyl-D-erythritol-4-phosphate (MEP) is effectively blocked by 1-deoxy-D-xylulose-5-phosphate reductoisomerase (Dxr) inhibitors such as the natural antibiotic fosmidomycin. Prediction of binding affinities for closely related Dxr ligands as well as estimation of the affinities of structurally more distinct inhibitors within this class of non-hydrolyzable phosphate mimics relies on the synthesis of fosmidomycin derivatives with a broad range of target affinity. Maintaining the phosphonic acid moiety, linear modifications of the lead structure were carried out in an effort to expand the SAR of this physicochemically challenging class of compounds. Synthetic access to a set of phosphonic acids with inhibitory activity (IC(50)) in the range from 1 to >30 microM vs. E. coli Dxr and 0.4 to 20 microM against P. falciparum Dxr is reported.     

Ocean Acidification Accelerates Reef Bioerosion

In the recent discussion how biotic systems may react to ocean acidification caused by the rapid rise in carbon dioxide partial pressure (pCO₂) in the marine realm, substantial research is devoted to calcifiers such as stony corals. The antagonistic process – biologically induced carbonate dissolution via bioerosion – has largely been neglected. Unlike skeletal growth, we expect bioerosion by chemical means to be facilitated in a high-CO₂ world. This study focuses on one of the most detrimental bioeroders, the sponge Cliona orientalis, which attacks and kills live corals on Australia’s Great Barrier Reef. Experimental exposure to lowered and elevated levels of pCO₂ confirms a significant enforcement of the sponges’ bioerosion capacity with increasing pCO₂ under more acidic conditions. Considering the substantial contribution of sponges to carbonate bioerosion, this finding implies that tropical reef ecosystems are facing the combined effects of weakened coral calcification and accelerated bioerosion, resulting in critical pressure on the dynamic balance between biogenic carbonate build-up and degradation.     

Potential sources of early-postnatal increase in myofibre number in pig skeletal muscle

In pigs, myogenesis is a biphasic phenomenon with the formation of primary and secondary fibres. Hyperplasia was reported to be accomplished around 90 days of gestation. However, some studies suggest a substantial increase in the total fibre number (TFN) from birth to weaning by counting fibre number in the muscle cross sections. The aim of this study was to establish in which way TFN increases after birth and whether this increase is imputable to new (tertiary) myofibres and/or fibre elongation. The semitendinosus muscle of 128 piglets was examined at days 1 (n = 63), 7 (n = 12), 21 (n = 12), and 28 (n = 41) of age. TFN was increased at days 7, 21 and 28 of age when compared with day 1 (P < 0.01). From day 1 to 28, TFN increased from 463 × 10³ to 825 × 10³. Microscopy of longitudinal and transversal serial sections revealed that at day 7 of age very small fibres expressing the embryonic myosin heavy chain (MyHC) isoform were apparent all over the muscle. In addition, intrafascicular terminations of normal-sized fibres expressed the embryonic MyHC isoform. These data suggest that the TFN in the pig muscle is not fixed at birth and its postnatal increase may be related to both elongation of existing muscle fibres and genesis of tertiary myofibres, mainly between birth and 3 weeks of age.     

Evolution and function of B chromosome 45S rDNA sequences in Brachycome dichromosomatica.

The origin and activity of 45S rDNA located on micro B chromosomes of the daisy Brachycome dichromosomatica were analysed. The internal transcribed spacer 2 (ITS2) of the 45S rRNA gene was sequenced for micro B, large B, and A chromosomes of B. dichromosomatica cytodeme A2, and conserved differences were identified between sequences originating from A and both types of B chromosomes. Phylogenetic analysis did not identify a species containing an ITS2 sequence more similar to either of the B chromosome sequences than the B. dichromosomatica A chromosome sequences. Thus, an origin of the B chromosomes from A chromosomes at a time prior to the divergence of the 4 cytodemes of B. dichromosomatica is suggested. The frequent (70%) nucleolar non-association of micro B chromosomes suggests inactivity of micro B 45S rDNA.