Coexistence of protected avian predators: does a recovering population of White-tailed Eagle threaten to exclude other avian predators?

The processes of competition and predation determine the degree to which species can coexist; the importance of competition in particular has been emphasized at high trophic levels. Competition exclusion will occur when habitat overlap between sympatric species is high. In this study, we investigated nesting habitat overlap between internationally protected diurnal tree-nesting avian predators of central Europe, namely, White-tailed Eagle (Haliaeetus albicilla), Lesser Spotted Eagle (Aquila pomarina), Black Stork (Ciconia nigra), and Osprey (Pandion haliaetus). We found significantly different nesting habitats among the study species and suggest that this could be a consequence of the resource-based segregation, but not a consequence of asymmetrical interspecific competition. The results also show that habitat of the recovering populations of White-tailed Eagle overlapped with the habitat used by the Lesser Spotted Eagle, Black Stork, and Osprey to varying extents with a niche overlap values being below the competition exclusion threshold. Nevertheless, we suggest that competition by White-tailed Eagle at a population level may limit Osprey, though not Lesser Spotted Eagle or Black Stork.     

Membrane connectivity estimated by digital image analysis of HER2 immunohistochemistry is concordant with visual scoring and fluorescence in situ hybridization results: algorithm evaluation on breast cancer tissue microarrays

Because metaplastic carcinoma of the breast encompasses a great variety of histopathology, diagnostic challenges abound, especially within the realm of cytology. The authors compiled and studied an eight-case series comprised of metaplastic breast carcinomas and lesions initially suspicious cytologically for metaplastic carcinoma in order to assess the degree of cytologic-histologic correlation and to identify recurring problematic themes surrounding the cytology-based diagnosis of this neoplasm. The cytologic and histologic slides from eight cases suspicious for metaplastic breast carcinoma diagnosed by fine needle aspiration (FNA) were collected and analyzed through a seven-year retrospective search of case files at our institution. Based on cytologic characteristics, the cases were separated into three groups. Group 1 consisted of three cases presenting with poorly differentiated adenocarcinoma and squamoid components on FNA. Group 2 was composed of two cases that featured a monophasic, malignant ductal cell population on cytology, while the cytologic specimens for the third group of cases presented with a mesenchymal component with or without a malignant glandular constituent. Cytologic-histologic correlation was present in two of three cases demonstrating a mesenchymal component, and there was 100% sensitivity in the cytologic detection of those mesenchymal elements. However, in only one of three cases was there an accurate cytologic diagnosis of metaplastic carcinoma when squamoid changes were present on FNA. Both cases demonstrating only malignant glandular elements on cytologic specimens revealed an additional component of malignant squamous differentiation upon the examination of mastectomy-derived tissue. These results indicate that squamous-like changes identified on FNA should be interpreted with caution and that sampling error remains a problematic recurrence in cytology. Regardless, there appears to be promise concerning the accurate cytologic diagnosis of metaplastic carcinoma when the lesion is characterized by a mesenchymal component. A study implementing a larger case number is essential in determining the significance of these findings.     

Isosteric analogs of lenalidomide and pomalidomide: Synthesis and biological activity

A series of analogs of the immunomodulary drugs lenalidomide (1) and pomalidomide (2), in which the amino group is replaced with various isosteres, was prepared and assayed for immunomodulatory activity and activity against cancer cell lines. The 4-methyl and 4-chloro analogs 4 and 15, respectively, displayed potent inhibition of tumor necrosis factor-α (TNF-α) in LPS-stimulated hPBMC, potent stimulation of IL-2 in a human T cell co-stimulation assay, and anti-proliferative activity against the Namalwa lymphoma cell line. Both of these analogs displayed oral bioavailability in rat.     

Evaluation of 2′-α-fluorine modified nucleoside phosphonates as potential inhibitors of HCV polymerase

Ribonucleoside phosphonate analogues containing 2′-α-fluoro modifications were synthesized and their potency evaluated against HCV RNA polymerase. The diphosphophosphonate (triphosphate equivalent) adenine and cytidine analogues displayed potent inhibition of the HCV polymerase in the range of 1.9–2.1 μM, but only modest cell-based activity in the HCV replicon. Pro-drugs of the parent nucleoside phosphonates improved the cell-based activity.     

Structural characterization of Hsp12, the heat shock protein from Saccharomyces cerevisiae, in aqueous solution where it is intrinsically disordered and in detergent micelles where it is locally α-helical

Hsp12 (heat shock protein 12) belongs to the small heat shock protein family, partially characterized as a stress response, stationary phase entry, late embryonic abundant-like protein located at the plasma membrane to protect membrane from desiccation. Here, we report the structural characterization of Hsp12 by NMR and biophysical techniques. The protein was labeled uniformly with nitrogen-15 and carbon-13 so that its conformation could be determined in detail both in aqueous solution and in two membrane-mimetic environments, SDS and dodecylphosphocholine (DPC) micelles. Secondary structural elements determined from assigned chemical shifts indicated that Hsp12 is dynamically disordered in aqueous solution, whereas it gains four helical stretches in the presence of SDS micelles and a single helix in presence of DPC. These conclusions were reinforced by circular dichroism spectra of the protein in all three environments. The lack of long range interactions in NOESY spectra indicated that the helices present in SDS micelles do not pack together. R(1) and R(2), relaxation and heteronuclear NOE measurements showed that the protein is disordered in aqueous solution but becomes more ordered in presence of detergent micelles. NMR spectra collected in presence of paramagnetic spin relaxation agents (5DSA, 16DSA, and Gd(DTPA-BMA)) indicated that the amphipathic α-helices of Hsp12 in SDS micelles lie on the membrane surface. These observations are in agreement with studies suggesting that Hsp12 functions to protect the membrane from desiccation.     

SMALL SUBUNIT rDNA SEQUENCE ANALYSIS OF SYMBIOTIC DINOFLAGELLATES FROM SEVEN SCLERACTINIAN CORALS IN A TAHITIAN LAGOON

The diversity of symbiotic dinoflagellates from reef-building corals collected in the lagoon of Tahiti (South Pacific ocean) was investigated by using a molecular approach. Populations of symbionts (strains or species) of 7 coral species ( Fungia scutaria , F. paumotensis Stutchbury, Pavona cactus Forskål, Leptastrea transversa Kluzinger, Pocillopora verrucosa Ellis and Solender, Montastrea curta Dana, and Acropora formosa Dana) were delimited by phylogenetic analysis of small subunit rDNA sequences. Coral P. verrucosa harbored 2 populations of symbiont SSU rDNA sequences that may correspond to two different Symbiodinium species. Corals F. scutaria and M. curta also seemed to contain two different Symbiodinium species. SSU rDNA dinoflagellate sequences from P. cactus , L. transversa , F. scutaria , F. paumotensis , and P. verrucosa were in the same phylogenetic cluster and showed low variability. For these distantly related coral species, dinoflagellate strains from the same species, rDNA paralogues from the same strain, or closely related Symbiodinium species could not be distinguished because monophyletic subgroups were not observed. SSU rDNA dinoflagellate sequences from A. formosa and M. curta were clearly different from the other Symbiodinium sequences and may represent specific species. This molecular approach highlighted a greater diversity of symbiotic dinoflagellates from corals in South Pacific ( Symbiodinium groups A, B, and C) than that observed in the rest of the Pacific ocean ( Symbiodinium group C). The diversity of symbiotic associations in a restricted area of the lagoon of Tahiti may reflect the complexity of interactions between species of Symbiodinium and corals.     

Conserved determinants for membrane association of nonstructural protein 5A from hepatitis C virus and related viruses

Nonstructural protein 5A (NS5A) is a membrane-associated essential component of the hepatitis C virus (HCV) replication complex. An N-terminal amphipathic alpha helix mediates in-plane membrane association of HCV NS5A and at the same time is likely involved in specific protein-protein interactions required for the assembly of a functional replication complex. The aim of this study was to identify the determinants for membrane association of NS5A from the related GB viruses and pestiviruses. Although primary amino acid sequences differed considerably, putative membrane anchor domains with amphipathic features were predicted in the N-terminal domains of NS5A proteins from these viruses. Confocal laser scanning microscopy, as well as membrane flotation analyses, demonstrated that NS5As from GB virus B (GBV-B), GBV-C, and bovine viral diarrhea virus, the prototype pestivirus, display membrane association characteristics very similar to those of HCV NS5A. The N-terminal 27 to 33 amino acid residues of these NS5A proteins were sufficient for membrane association. Circular dichroism analyses confirmed the capacity of these segments to fold into alpha helices upon association with lipid-like molecules. Despite structural conservation, only very limited exchanges with sequences from related viruses were tolerated in the context of functional HCV RNA replication, suggesting virus-specific interactions of these segments. In conclusion, membrane association of NS5A by an N-terminal amphipathic alpha helix is a feature shared by HCV and related members of the family Flaviviridae. This observation points to conserved roles of the N-terminal amphipathic alpha helices of NS5A in replication complex formation.     

Clinical Significance of the CCR5delta32 Allele in Hepatitis C

Background

The CCR5 receptor, expressed on Th1 cells, may influence clinical outcomes of HCV infection. We explored a possible link between a CCR5 32-base deletion (CCR5delta32), resulting in the expression of a non-functioning receptor, and clinical outcomes of HCV infection.

Methods

CCR5 and HCV-related phenotypes were analysed in 1,290 chronically infected patients and 160 patients with spontaneous clearance.

Results

Carriage of the CCR5delta32 allele was observed in 11% of spontaneous clearers compared to 17% of chronically infected patients (OR = 0.59, 95% CI interval 0.35–0.99, P = 0.047). Carriage of this allele also tended to be observed more frequently among patients with liver inflammation (19%) compared to those without inflammation (15%, OR = 1.38, 95% CI interval 0.99–1.95, P = 0.06). The CCR5delta32 was not associated with sustained virological response (P = 0.6), fibrosis stage (P = 0.8), or fibrosis progression rate (P = 0.4).

Conclusions

The CCR5delta32 allele appears to be associated with a decreased rate of spontaneous HCV eradication, but not with hepatitis progression or response to antiviral therapy.     

Origin and Characteristics of High Shannon Entropy at the Pivot of Locally Stable Rotors: Insights from Computational Simulation

Background

Rotors are postulated to maintain cardiac fibrillation. Despite the importance of bipolar electrograms in clinical electrophysiology, few data exist on the properties of bipolar electrograms at rotor sites. The pivot of a spiral wave is characterized by relative uncertainty of wavefront propagation direction compared to the periphery. The bipolar electrograms used in electrophysiology recording encode information on both direction and timing of approaching wavefronts.

Objective

To test the hypothesis that bipolar electrograms from the pivot of rotors have higher Shannon entropy (ShEn) than electrograms recorded at the periphery due to the spatial dynamics of spiral waves.

Methods and Results

We studied spiral wave propagation in 2-dimensional sheets constructed using a simple cell automaton (FitzHugh-Nagumo), atrial (Courtemanche-Ramirez-Nattel) and ventricular (Luo-Rudy) myocyte cell models and in a geometric model spiral wave. In each system, bipolar electrogram recordings were simulated, and Shannon entropy maps constructed as a measure of electrogram information content. ShEn was consistently highest in the pivoting region associated with the phase singularity of the spiral wave. This property was consistently preserved across; (i) variation of model system (ii) alterations in bipolar electrode spacing, (iii) alternative bipolar electrode orientation (iv) bipolar electrogram filtering and (v) in the presence of rotor meander. Directional activation plots demonstrated that the origin of high ShEn at the pivot was the directional diversity of wavefront propagation observed in this location.

Conclusions

The pivot of the rotor is consistently associated with high Shannon entropy of bipolar electrograms despite differences in action potential model, bipolar electrode spacing, signal filtering and rotor meander. Maximum ShEn is co-located with the pivot for rotors observed in the bipolar electrogram recording mode, and may be an intrinsic property of spiral wave dynamic behaviour.