Inferring the mode of colonization of the rapid range expansion of a solitary bee from multilocus DNA sequence variation

Rapid geographic range expansions can have dramatic effects on the distribution of genetic diversity, both within and among populations. Based on field records collected over the past two decades in Western Europe, we report on the rapid geographic range expansion in Colletes hederae, a solitary bee species. To characterize how this expansion shaped the distribution of genetic diversity within and among populations, we performed a genetic analysis based on the sequencing of three nuclear loci (RNAp, CAD and WgL). We then simulated the evolution of DNA sequences under a spatially explicit model of coalescence to compare different hypotheses regarding the mode of colonization associated with this rapid expansion and to identify those that are most consistent with the observed molecular data. Our genetic analyses indicate that the range expansion was not associated with an important reduction in genetic diversity, even in the most recently colonized area in the United Kingdom. Moreover, little genetic differentiation was observed among populations. Our comparative analysis of simulated data sets indicates that the observed genetic data are more consistent with a demographic scenario involving relatively high migration rates than with a scenario based on a high reproduction rate associated with few migrants. In the light of these results, we discuss the factors that might have contributed to the rapid geographic range expansion of this pollen‐specialist solitary bee species across Western Europe.     

Inverted sand dollars actively orient themselves in flow to increase likelihood of righting

The fact that sand dollars are often dislodged and inverted is an inescapable consequence of living at or slightly below the sediment–water interface. Once inverted, however, how do sand dollars effectively right themselves, given their small spines and stiff internal skeletons? Here, we examined the possibility that individuals of Mellita quinquiesperforata and Dendraster excentricus may take advantage of the interaction of their morphology and flow to increase the likelihood of righting. Based on flow tank observations, the critical velocity required to flip an inverted sand dollar varies with orientation and increases with test size. For both species, the critical velocity was lower when inverted sand dollars were oriented with the posterior margin facing directly downstream, compared with when the posterior margin was positioned in an upstream orientation. To test whether inverted sand dollars would actively rotate into a more advantageous position for flipping, we exposed inverted animals in three starting orientations – with their posterior edge directed upstream (the least favored position for flipping), perpendicular, and downstream to flow – to the minimum flow expected to induce flipping and compared their responses. Time‐lapse photography showed that regardless of initial orientation, within one hour, a majority of individuals of both species rotated into positions that were not statistically different from the downstream orientation (the most favored position for flipping). These results for D. excentricus were further confirmed in a field experiment. Taken together, these data suggest that inverted sand dollars are able to recognize flow direction and respond by modifying their orientation to maximize lift and drag for righting.     

Assessing Global Marine Biodiversity Status within a Coupled Socio-Ecological Perspective

People value the existence of a variety of marine species and habitats, many of which are negatively impacted by human activities. The Convention on Biological Diversity and other international and national policy agreements have set broad goals for reducing the rate of biodiversity loss. However, efforts to conserve biodiversity cannot be effective without comprehensive metrics both to assess progress towards meeting conservation goals and to account for measures that reduce pressures so that positive actions are encouraged. We developed an index based on a global assessment of the condition of marine biodiversity using publically available data to estimate the condition of species and habitats within 151 coastal countries. Our assessment also included data on social and ecological pressures on biodiversity as well as variables that indicate whether good governance is in place to reduce them. Thus, our index is a social as well as ecological measure of the current and likely future status of biodiversity. As part of our analyses, we set explicit reference points or targets that provide benchmarks for success and allow for comparative assessment of current conditions. Overall country-level scores ranged from 43 to 95 on a scale of 1 to 100, but countries that scored high for species did not necessarily score high for habitats. Although most current status scores were relatively high, likely future status scores for biodiversity were much lower in most countries due to negative trends for both species and habitats. We also found a strong positive relationship between the Human Development Index and resilience measures that could promote greater sustainability by reducing pressures. This relationship suggests that many developing countries lack effective governance, further jeopardizing their ability to maintain species and habitats in the future.     

A loss of function mutation of presenilin-2 interferes with amyloid beta-peptide production and notch signaling.

Presenilin-1 (PS1) facilitates gamma-secretase cleavage of the beta-amyloid precursor protein and the intramembraneous cleavage of Notch1. Although Alzheimer's disease-associated mutations in the homologous presenilin (PS2) gene elevate amyloid beta-peptide (Abeta42) production like PS1 mutations, here we demonstrate that a gene ablation of PS2 (unlike that of PS1) in mice does not result in a severe phenotype resembling that of Notch-ablated animals. To investigate the amyloidogenic function of PS2 more directly, we mutagenized a conserved aspartate at position 366 to alanine, because the corresponding residue of PS1 is known to be required for its amyloidogenic function. Cells expressing the PS2 D366A mutation exhibit significant deficits in proteolytic processing of beta-amyloid precursor protein indicating a defect in gamma-secretase activity. The reduced gamma-secretase activity results in the almost complete inhibition of Abeta and p3 production in cells stably expressing PS2 D366A, whereas cells overexpressing the wild-type PS2 cDNA produce robust levels of Abeta and p3. Using highly sensitive in vivo assays, we demonstrate that the PS2 D366A mutation not only blocks gamma-secretase activity but also inactivates PS2 activity in Notch signaling by inhibiting the proteolytic release of the cytoplasmic Notch1 domain. These data suggest that PS2 is functionally involved in Abeta production and Notch signaling by facilitating similar proteolytic cleavages.     

Interactions of Neisseria meningitidis with cells of the human meninges

The interaction of Neisseria meningitidis with the meninges that surround and protect the brain is a pivotal event in the progression of bacterial meningitis. Two models of the human meninges were established in vitro, using (i) sections of fresh human brain and (ii) cultures of viable cells grown from human meningiomas. Neisseria meningitidis showed a specific predilection for binding to the leptomeninges and meningeal blood vessels in human brain and not to the cerebral cortex. There was a close correlation between the adherence of different Neisseria species to leptomeninges and cultured cells. The major ligand that mediated adherence was the pilus, and pilin variation modulated the interactions. The presence of Opa protein increased the association of Cap+ meningococci that expressed low-adhesive pili, but did not influence the association of high-adhesive pili. In contrast, Opc did not influence the adherence of Cap+ meningococci, whereas loss of capsule was associated with a more intimate interaction between the bacteria and the meningioma cell that was not apparent with Cap+ meningococci. There was no evidence of internalization of meningococci by meningioma cells in vitro, an observation that is consistent with the barrier properties of the leptomeninges to N. meningitidis observed in vivo.     

Peroxisomal fatty acid beta-oxidation is not essential for virulence of Candida albicans

Phagocytic cells form the first line of defense against infections by the human fungal pathogen Candida albicans. Recent in vitro gene expression data suggest that upon phagocytosis by macrophages, C. albicans reprograms its metabolism to convert fatty acids into glucose by inducing the enzymes of the glyoxylate cycle and fatty acid beta-oxidation pathway. Here, we asked whether fatty acid beta-oxidation, a metabolic pathway localized to peroxisomes, is essential for fungal virulence by constructing two C. albicans double deletion strains: a pex5Delta/pex5Delta mutant, which is disturbed in the import of most peroxisomal enzymes, and a fox2Delta/fox2Delta mutant, which lacks the second enzyme of the beta-oxidation pathway. Both mutant strains had strongly reduced beta-oxidation activity and, accordingly, were unable to grow on media with fatty acids as a sole carbon source. Surprisingly, only the fox2Delta/fox2Delta mutant, and not the pex5Delta/pex5Delta mutant, displayed strong growth defects on nonfermentable carbon sources other than fatty acids (e.g., acetate, ethanol, or lactate) and showed attenuated virulence in a mouse model for systemic candidiasis. The degree of virulence attenuation of the fox2Delta/fox2Delta mutant was comparable to that of the icl1Delta/icl1Delta mutant, which lacks a functional glyoxylate cycle and also fails to grow on nonfermentable carbon sources. Together, our data suggest that peroxisomal fatty acid beta-oxidation is not essential for virulence of C. albicans, implying that the attenuated virulence of the fox2Delta/fox2Delta mutant is largely due to a dysfunctional glyoxylate cycle.     

CSL311, a novel,potent, therapeutic monoclonal antibody for the treatment of diseases mediated by the common β chain of the IL-3, GM-CSF and IL-5 receptors

The β common-signaling cytokines interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-5 stimulate pro-inflammatory activities of haematopoietic cells via a receptor complex incorporating cytokine-specific α and shared β common (β_c, CD131) receptor. Evidence from animal models and recent clinical trials demonstrate that these cytokines are critical mediators of the pathogenesis of inflammatory airway disease such as asthma. However, no therapeutic agents, other than steroids, that specifically and effectively target inflammation mediated by all 3 of these cytokines exist. We employed phage display technology to identify and optimize a novel, human monoclonal antibody (CSL311) that binds to a unique epitope that is specific to the cytokine-binding site of the human β_c receptor. The binding epitope of CSL311 on the β_c receptor was defined by X-ray crystallography and site-directed mutagenesis. CSL311 has picomolar binding affinity for the human β_c receptor, and at therapeutic concentrations is a highly potent antagonist of the combined activities of IL-3, GM-CSF and IL-5 on primary eosinophil survival in vitro. Importantly, CSL311 inhibited the survival of inflammatory cells present in induced sputum from human allergic asthmatic subjects undergoing allergen bronchoprovocation. Due to its high potency and ability to simultaneously suppress the activity of all 3 β common cytokines, CSL311 may provide a new strategy for the treatment of chronic inflammatory diseases where the human β_c receptor is central to pathogenesis. The coordinates for the β_c/CSL311 Fab complex structure have been deposited with the RCSB Protein Data Bank (PDB 5DWU).     

Magnetic resonance study of 13C reductively methylated glycophorin and glycophorin glycopeptides

¹³C nuclear magnetic resonance (n.m.r.) spectral data for ¹³C reductively methylated N-terminal tryptic glycopeptides and for ¹³C reductively methylated N-terminal glyco-octapeptides derived from homozygous glycophorins A^M and A^N are presented. Their ¹³C chemical shift data are compared with the previously published ¹³C n.m.r. data for ¹³C reductively methylated homozygous glycophorins A^M and A^N in order to investigate the means of display of the MN blood determinants by these species. The pH dependence of the ¹³C resonances of $\text{N}{}^{\mathrm{\alpha }}\text{,N-[}{}^{13}\text{C}\text{]}\text{dimethyl}$ leucine of glyco-octapeptide A^N and of $\text{N}{}^{\mathrm{\alpha }}\text{,N-[}{}^{13}\text{C}\text{]}\text{dimethyl}$ serine of glyco-octapepti A^M indicated that only a slight structural perturbation occurs at the N-terminus when a large portion of the glycoprotein molecule is removed. However, one structural ‘state’ of ¹³C reductively methylated glycophorin A^M is lost when the glyco-octapeptide A^M is produced. The ¹³C resonance of $\text{N}{}^{\mathrm{\alpha }}\text{,N-[}{}^{13}\text{C}\text{]}\text{dimethyl}$ leucine of glycooctapeptide A^N titrated with a $\text{p}\text{K}{}_{\mathrm{<mtext>a</mtext>}}$ of 7.7 (Hill coefficient $\text{～ 1}$). The ¹³C resonance of $\text{N}{}^{\mathrm{\alpha }}\text{,N-[}{}^{13}\text{C}\text{]}\text{dimethyl}$ serine, on the other hand, exhibited an unusual pH dependence, indicating the existence of some possible steric constraints or hydrogen bonding in this molecule. In comparison to the data obtained for ¹³C-labelled glycooctapeptide A^M molecule, the pH dependence of the chemical shift of the ¹³C resonance of $\text{N}{}^{\mathrm{\alpha }}\text{,N-[}{}^{13}\text{C}\text{]}\text{dimethyl}$ serine of tripeptide tri-L-serine is also presented. Circular dichroism (c.d.) spectra indicated that the reductive methylation technique does not cause a large perturbation of the glycophorin A molecule.     

Concomitant transapical transcatheter aortic valve implantation and minimally invasive direct coronary artery bypass

We represent a successful minimally invasive combined off-pump procedure consisting of a transapical aortic valve implantation and a direct coronary artery bypass grafting in a woman with a severe aortic stenosis and a critical coronary artery disease. Due to her comorbidities, she was classified as a high-risk patient qualifying for a transcatheter procedure. We performed this combined procedure in a hybrid operation room, starting with the coronary bypass to maintain a coronary blood flow during the transapical valve implantation. The operation processed without any complications and she was discharged at the seventh postoperative day into the allocating hospital.