Sexually selected male weapon is associated with lower inbreeding load but higher sex load in the bulb mite

Elaborate sexually selected ornaments and armaments are costly but increase the reproductive success of their bearers (usually males). It has been postulated that high-quality males can invest disproportionately more in such traits, making those traits honest signals of genetic quality. However, genes associated with such traits may have sexually antagonistic effects on fitness. Here, using a bulb mite Rhizoglyphus robini, a species in which a distinct dimorphism exists between males in the expression of a sexually selected weapon, we compare inbreeding and gender load between lines derived from armed fighters and unarmed scramblers. After four generations of sib-mating, inbreeding depression for female fitness was significantly lower in fighter-derived lines compared to scrambler-derived lines, suggesting that fighter males had significantly higher genetic quality. However, outbred females from fighter-derived lines had significantly lower fitness compared to outbred females from scrambler-derived lines, demonstrating significant gender load associated with the presence of a sexually selected male weapon. Our results imply that under outbreeding, genetic benefits of mating with bearers of elaborate sexually selected traits might be swamped by the costs of decreased fitness of female progeny due to sexually antagonistic effects.     

PFGE and AFLP genotyping of Staphylococcus aureus subsp. anaerobius isolated from goats with Morel’s disease

Staphylococcus aureus subsp. anaerobius is the etiological agent of the Morel’s disease in sheep and goats. The disease presents with subcutaneous abscesses, located mainly in the superficial lymph nodes. Forty-one isolates of S. aureus subsp. anaerobius were collected from two outbreaks of the Morel’s disease in Poland in years 2006–2008. Analysis of DNA SmaI digests by PFGE showed that 35 of 41 isolates belonged to the same PFGE type, identical to the type strain of S. aureus subsp. anaerobius ATCC 35844, confirming high level of clonality of the species. The DNA patterns of the remaining identical 6 isolates, different from the reference strain only by two bands, were found closely related. Genotyping performed with AFLP technique revealed two clonal groups including 16 and 25 isolates, respectively. The study indicated that AFLP technique might be a better discriminatory tool for genetic analysis of S. aureus subsp. anaerobius isolates, when compared to PFGE.     

An integrated approach to the ligand binding specificity of Neisseria meningitidis M1 alanine aminopeptidase by fluorogenic substrate profiling,inhibitory studies and molecular modeling

Neisseria meningitides is a gram-negative diplococcus bacterium and is the main causative agent of meningitis and other meningococcal diseases. Alanine aminopeptidase from N. meningitides (NmAPN) belongs to the family of metallo-exopeptidase enzymes, which catalyze the removal of amino acids from the N-terminus of peptides and proteins, and are found among all the kingdoms of life. NmAPN is suggested to be mostly responsible for proteolysis and nutrition delivery, similar to the orthologs from other bacteria.     

Heterogeneity of 11q13 region rearrangements in laryngeal squamous cell carcinoma analyzed by microarray platforms and fluorescence in situ hybridization

We reinvestigated rearrangements occurring in region q13 of chromosome 11 aiming to: (i) describe heterogeneity of the observed structural alterations, (ii) estimate amplicon size and (iii) identify of oncogenes involved in laryngeal cancer progression as potential targets for therapy. The study included 17 cell lines derived from laryngeal cancers and 34 specimens from primary laryngeal tumors. The region 11q13 was analyzed by fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH) and gene expression microarray. Next, quantitative real time PCR was used for chosen genes to confirm results from aCGH and gene expression microarray. The observed pattern of aberrations allows to distinguish three ways, in which gain and amplification involving 11q13 region may occur: formation of a homogeneously staining region; breakpoints in/near 11q13, which lead to the three to sevenfold increase of the copy number of 11q13 region; the presence of additional copies of the whole chromosome 11. The minimal altered region of gain and/or amplification was limited to ~1.8 Mb (chr.11:69,395,184–71,209,568) and comprised mostly 11q13.3 band which contain 12 genes. Five, out of these genes (CCND1, ORAOV1, FADD, PPFIA1, CTTN) had higher expression levels in comparison to healthy controls. Apart from CCND1 gene, which has an established role in pathogenesis of head and neck cancers, CTTN, ORAOV1 and FADD genes appear to be oncogene-candidates in laryngeal cancers, while a function of PPFIA1 requires further studies.     

Nutlin-3a, an MDM2 antagonist and p53 activator, helps to preserve the replicative potential of cancer cells treated with a genotoxic dose of resveratrol

Resveratrol is a natural compound that has been intensely studied due to its role in cancer prevention and potential as an anti-cancer therapy. Its effects include induction of apoptosis and senescence-like growth inhibition. Here, we report that two cancer cell lines (U-2 OS and A549) differ significantly in their molecular responses to resveratrol. Specifically, in U-2 OS cells, the activation of the p53 pathway is attenuated when compared to the activation in A549 cells. This attenuation is accompanied by a point mutation (458: CGA→TGA) in the PPM1D gene and overexpression of the encoded protein, which is a negative regulator of p53. Experimentally induced knockdown of PPM1D in U-2 OS cells resulted in slightly increased activation of the p53 pathway, most clearly visible as stronger phosphorylation of p53 Ser³⁷. When treated with nutlin-3a, a non-genotoxic activator of p53, U-2 OS and A549 cells both responded with substantial activation of the p53 pathway. Nutlin-3a improved the clonogenic survival of both cell lines treated with resveratrol. This improvement was associated with lower activation of DNA-damage signaling (phosphorylation of ATM, CHK2, and histone H2AX) and higher accumulation of cells in the G1 phase of the cell cycle. Thus, the hyperactivation of p53 by nutlin-3a helps to preserve the replicative potential of cells exposed to resveratrol.     

The Force-Biased Algorithm for the Irregular Close Packing of Equal Hard Spheres

Abstract

We present a “force-biased” algorithm for generating the irregular close packing of hard spheres. The algorithm is partly based on Jodrey and Tory's ideas [9] and incorporates methods from Molecular Dynamics. Packings generated by means of the two algorithms are consistent up to final packing fraction of 0.65, which seems to be the limit density of Jodrey and Tory's method. Significantly higher densities (up to 0.71) can be achieved for small numbers of spheres by the force-biased algorithm. However the shape of the radial and angle distribution functions implies that a partial short-range ordering occurs in packings of those densities.     

The larval morphology of Arrenurus nobilis Neuman, 1880 and A. robustus Koenike, 1894 (Acari: Parasitengona: Arrenuridae)

The morphology of the larval stages of Arrenurus nobilis and A. robustus is described. Particular attention is given to characters that help to distinguish the two species, and to characters defining the subgenus Arrenurus s. str. The larva of A. robustus resembles the larvae of A. papillator and A. pustulator regarding the shape of dorsal plate, excretory pore plate, coxal plate median margins ratios, and the presence of the IIITa8 seta. The shape of the excretory pore plate in A. nobilis resembles the one in Arrenurus (Megaluracarus) mediorotundatus. The shape of dorsal plate and chelicerae is similar to the ones in the Megaluracarus-species A. globator and A. tubulator. The lack of the IIITa8 seta differs from other species of the subgenus Arrenurus s. str. In the pectinate Lp2 and Mh1 setae A. nobilis resembles representatives of the subgenus Arrenurus s. str. This demonstrates the necessity of verifying the taxonomic status of A. nobilis.     

Cytomegalovirus Vaccine Strain Towne-Derived Dense Bodies Induce Broad Cellular Immune Responses and Neutralizing Antibodies That Prevent Infection of Fibroblasts and Epithelial Cells

Human cytomegalovirus (HCMV), a betaherpesvirus, can cause severe disease in immunosuppressed patients and following congenital infection. A vaccine that induces both humoral and cellular immunity may be required to prevent congenital infection. Dense bodies (DBs) are complex, noninfectious particles produced by HCMV-infected cells and may represent a vaccine option. As knowledge of the antigenicity and immunogenicity of DB is incomplete, we explored characterization methods and defined DB production methods, followed by systematic evaluation of neutralization and cell-mediated immune responses to the DB material in BALB/c mice. DBs purified from Towne-infected cultures treated with the viral terminase inhibitor 2-bromo-5,6-dichloro-1-beta-d-ribofuranosyl benzimidazole riboside (BDCRB) were characterized by nanoparticle tracking analysis (NTA), two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), immunoblotting, quantitative enzyme-linked immunosorbent assay, and other methods. The humoral and cellular immune responses to DBs were compared to the immunogenicity of glycoprotein B (gB) administered with the adjuvant AddaVax (gB/AddaVax). DBs induced neutralizing antibodies that prevented viral infection of cultured fibroblasts and epithelial cells and robust cell-mediated immune responses to multiple viral proteins, including pp65, gB, and UL48. In contrast, gB/AddaVax failed to induce neutralizing antibodies that prevented infection of epithelial cells, highlighting a critical difference in the humoral responses induced by these vaccine candidates. Our data advance the potential for the DB vaccine approach, demonstrate important immunogenicity properties, and strongly support the further evaluation of DBs as a CMV vaccine candidate.