Bone morphogenetic protein-9 activates Smad and ERK pathways and supports human osteoclast function and survival in vitro

BMP-9 is a potent osteogenic factor; however, its effects on osteoclasts, the bone-resorbing cells, remain unknown. To determine the effects of BMP-9 on osteoclast formation, activity and survival, we used human cord blood monocytes as osteoclast precursors that form multinucleated osteoclasts in the presence of RANKL and M-CSF in long-term cultures. BMP-9 did not affect osteoclast formation, but adding BMP-9 at the end of the culture period significantly increased bone resorption compared to untreated cultures, and reduced both the rate of apoptosis and caspase-9 activity. BMP-9 also significantly downregulated the expression of pro-apoptotic Bid, but only after RANKL and M-CSF, which are both osteoclast survival factors, had been eliminated from the culture medium. To investigate the mechanisms involved in the effects of BMP-9, we first showed that osteoclasts expressed some BMP receptors, including BMPR-IA, BMPR-IB, ALK1, and BMPR-II. We also found that BMP-9 was able to induce the phosphorylation of Smad-1/5/8 and ERK 1/2 proteins, but did not induce p38 phosphorylation. Finally, knocking down the BMPR-II receptor abrogated the BMP-9-induced ERK-signaling, as well as the increase in bone resorption. In conclusion, these results show for the first time that BMP-9 directly affects human osteoclasts, enhancing bone resorption and protecting osteoclasts against apoptosis. BMP-9 signaling in human osteoclasts involves the canonical Smad-1/5/8 pathway, and the ERK pathway.     

Philopatry and faithfulness to nest site in Cory's Shearwaters Calonectris diomedea at Selvagem Grande

Mougin, J.-L., Granadeiro, J. P., Jouanin, C. & Roux, F. 1999. Philopatry and faithfulness to nest site in Cory's Shearwaters Calonectris diomedea at Selvagem Grande. Ostrich 70 (3&4): 229–232.

Nearly fledged Cory's Shearwater Calonectris diomedea chicks at Selvagem Grande occasionally desert their nest sites during the night, but generally return before dawn. The temporary use of other nest sites is rare and lasts less than two days. Almost all chicks from Selvagem Grande return to the island for their first breeding attempt; very few breed at islands outside the archipelago. On Selvagem Grande, almost half the males return to their native colony whereas more than 90% of females recruit to other colonies. Inter-colony movements sometimes exceed 1 km, but, if they return to their native colony, both sexes settle within 20 m of their natal site. From the second breeding attempt onwards, most birds of both sexes are faithful to the nest site. On average, less than 20% of birds desert their former nest site each year, with a shift of about 4 m only. Most nest shifts follow a breeding failure or a temporary respite from breeding, and are accompanied by a switch in partners.

Mougin, J.-L., Granadeiro, J. P. Jouanin, C. & Roux, F. 1999. Philopatrie et fidélité au nid chez le Puffin cendré Calonectris diomedea de Selvagem Grande. Ostrich 70 (3&4): 229–232.

Le poussin en fin de croissance du Puffin cendré Calonectris diomedea de Selvagem Grande déserte parfois son nid pendant la nuit, mais y revient généralement avant le jour. L'utilisation temporaire d'un autre site de nid est rare et dure moins de deux jours. Les jeunes adultes nés à Selvagem Grande reviennent presque toujours nicher sur l'île et extrêmement rarement en dehors de l'archipel. A Selvagem Grande, près de la moitié des mâles reviennent à leur colonie de naissance, mais moins de 10% des femelles. Le déplacement est parfois supérieur à 1 km mais, s'ils reviennent à leur colonie natale, les deux sexes s'établissent à moins de 20 m du nid où ils sont nés. A partir de leur deuxième reproduction, les deux sexes sont fidèles à leur nid. Moins de 20% des oiseaux changent de nid d'une année à l'autre, avec un déplacement de 4 m seulement, le plus souvent à la suite d'un échec ou d'une interruption temporaire de la reproduction, ce déplacement étant le plus souvent accompagne d'un changement de partenaire.     

A comparison of the strength of biodiversity effects across multiple functions

In order to predict which ecosystem functions are most at risk from biodiversity loss, meta-analyses have generalised results from biodiversity experiments over different sites and ecosystem types. In contrast, comparing the strength of biodiversity effects across a large number of ecosystem processes measured in a single experiment permits more direct comparisons. Here, we present an analysis of 418 separate measures of 38 ecosystem processes. Overall, 45 % of processes were significantly affected by plant species richness, suggesting that, while diversity affects a large number of processes not all respond to biodiversity. We therefore compared the strength of plant diversity effects between different categories of ecosystem processes, grouping processes according to the year of measurement, their biogeochemical cycle, trophic level and compartment (above- or belowground) and according to whether they were measures of biodiversity or other ecosystem processes, biotic or abiotic and static or dynamic. Overall, and for several individual processes, we found that biodiversity effects became stronger over time. Measures of the carbon cycle were also affected more strongly by plant species richness than were the measures associated with the nitrogen cycle. Further, we found greater plant species richness effects on measures of biodiversity than on other processes. The differential effects of plant diversity on the various types of ecosystem processes indicate that future research and political effort should shift from a general debate about whether biodiversity loss impairs ecosystem functions to focussing on the specific functions of interest and ways to preserve them individually or in combination.     

Cadmium decontamination and reversal potential of teratological forms of the diatom Planothidium frequentissimum (Bacillariophyceae) after experimental contamination

While the induction of teratology by cadmium (Cd) on diatoms is already known, reversal kinetics are not well documented. This study aims to understand the viability of diatoms exhibiting teratological frustules and their reproduction capacities within a Cd‐impacted population to predict their return to normal diatom forms. We worked on a frequently encountered species in French hydrosystems: Planothidium frequentissimum (Lange‐Bertalot) Round & L. Bukhtiyarova. First, a 21‐d contamination phase highlighted increasing inductionof different teratological types in response to two levels of Cd contamination: 20 and 100 μg · L^?1. The deformity counting indicated that Cd firstly generated striae and mixed teratologies, then affected the central area and the valves. Second, a 28‐d decontamination phase demonstrated the Cd depuration capacity of Planothidium frequentissimum. Cd half‐lives appeared relatively low, ~6 d for the 100 μg · L^?1 condition. Moreover, the decontamination phase showed a decrease in teratology abundances, but a still incomplete recovery after 28 d. Deformations of the striae appeared to be the most sustainable phenotype since they were still significantly higher than in reference cultures at the end of the decontamination phase for both Cd cultures.     

Analysis of Allele-Specific Expression in Mouse Liver by RNA-Seq: A Comparison With Cis-eQTL Identified Using Genetic Linkage

We report an analysis of allele-specific expression (ASE) and parent-of-origin expression in adult mouse liver using next generation sequencing (RNA-Seq) of reciprocal crosses of heterozygous F₁ mice from the parental strains C57BL/6J and DBA/2J. We found a 60% overlap between genes exhibiting ASE and putative cis-acting expression quantitative trait loci (cis-eQTL) identified in an intercross between the same strains. We discuss the various biological and technical factors that contribute to the differences. We also identify genes exhibiting parental imprinting and complex expression patterns. Our study demonstrates the importance of biological replicates to limit the number of false positives with RNA-Seq data.     

The Binding of Antibiotics in OmpF Porin

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Highlights? OmpF porin binds antibiotics in the extracellular and periplasmic pore vestibules ? MD simulations show that ionic current through OmpF is blocked by bound ampicillin ? Carbenicillin binding alters ion selectivity of OmpF but not total ionic current ? Disruption of binding increases the susceptibility of E. coli for antibiotics     

Sequestration of DROSHA and DGCR8 by Expanded CGG RNA Repeats Alters MicroRNA Processing in Fragile X-Associated Tremor/Ataxia Syndrome

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Highlights? DGCR8 binds to CGG RNA repeats, cause of the neurodegenerative FXTAS disease ? DGCR8 and its partner, DROSHA, are sequestered within CGG RNA aggregates ? DGCR8 rescues the neuronal cell death induced by expanded CGG RNA repeats ? MicroRNA processing is impaired in patients with FXTAS     

Epistatic Interaction between BANK1 and BLK in Rheumatoid Arthritis: Results from a Large Trans-Ethnic Meta-Analysis

Background

BANK1 and BLK belong to the pleiotropic autoimmune genes; recently, epistasis between BANK1 and BLK was detected in systemic lupus erythematosus. Although BLK has been reproducibly identified as a risk factor in rheumatoid arthritis (RA), reports are conflicting about the contribution of BANK1 to RA susceptibility. To ascertain the real impact of BANK1 on RA genetic susceptibility, we performed a large meta-analysis including our original data and tested for an epistatic interaction between BANK1 and BLK in RA susceptibility.

Patients and Methods

We investigated data for 1,915 RA patients and 1,915 ethnically matched healthy controls genotyped for BANK1 rs10516487 and rs3733197 and BLK rs13277113. The association of each SNP and RA was tested by logistic regression. Multivariate analysis was then used with an interaction term to test for an epistatic interaction between the SNPs in the 2 genes.

Results

None of the SNPs tested individually was significantly associated with RA in the genotyped samples. However, we detected an epistatic interaction between BANK1 rs3733197 and BLK rs13277113 (P_interaction = 0.037). In individuals carrying the BLK rs13277113 GG genotype, presence of the BANK1 rs3733197 G allele increased the risk of RA (odds ratio 1.21 [95% confidence interval 1.04–1.41], P = 0.015. Combining our results with those of all other studies in a large trans-ethnic meta-analysis revealed an association of the BANK1 rs3733197 G allele and RA (1.11 [1.02–1.21], P = 0.012).

Conclusion

This study confirms BANK1 as an RA susceptibility gene and for the first time provides evidence for epistasis between BANK1 and BLK in RA. Our results illustrate the concept of pleiotropic epistatic interaction, suggesting that BANK1 and BLK might play a role in RA pathogenesis.     

Bronchiectasis-Associated Hospitalizations in Germany, 2005–2011: A Population-Based Study of Disease Burden and Trends

Background

Representative population-based data on the epidemiology of bronchiectasis in Europe are limited. The aim of the present study was to investigate the current burden and the trends of bronchiectasis-associated hospitalizations and associated conditions in Germany in order to inform focused patient care and to facilitate the allocation of healthcare resources.

Methods

The nationwide diagnosis-related groups hospital statistics for the years 2005–2011 were used in order to identify hospitalizations with bronchiectasis as any hospital discharge diagnosis according to the International Classification of Diseases, 10th revision, code J47, (acquired) bronchiectasis. Poisson log-linear regression analysis was used to assess the significance of trends. In addition, the overall length of hospital stay (LOS) and the in-hospital mortality in comparison to the nationwide overall mortality due to bronchiectasis as the primary diagnosis was assessed.

Results

Overall, 61,838 records with bronchiectasis were extracted from more than 125 million hospitalizations. The average annual age-adjusted rate for bronchiectasis as any diagnosis was 9.4 hospitalizations per 100,000 population. Hospitalization rates increased significantly during the study period, with the highest rate of 39.4 hospitalizations per 100,000 population among men aged 75–84 years and the most pronounced average annual increases among females. Besides numerous bronchiectasis-associated conditions, chronic obstructive pulmonary disease (COPD) was most frequently found in up to 39.2% of hospitalizations with bronchiectasis as the primary diagnosis. The mean LOS was comparable to that for COPD. Overall, only 40% of bronchiectasis-associated deaths occurred inside the hospital.

Conclusions

The present study provides evidence of a changing epidemiology and a steadily increasing prevalence of bronchiectasis-associated hospitalizations. Moreover, it confirms the diversity of bronchiectasis-associated conditions and the possible association between bronchiectasis and COPD. As the major burden of disease may be managed out-of-hospital, prospective patient registries are needed to establish the exact prevalence of bronchiectasis according to the specific underlying condition.     

Science Educational Outreach Programs That Benefit Students and Scientists

Both scientists and the public would benefit from improved communication of basic scientific research and from integrating scientists into education outreach, but opportunities to support these efforts are limited. We have developed two low-cost programs—"Present Your PhD Thesis to a 12-Year-Old" and "Shadow a Scientist”—that combine training in science communication with outreach to area middle schools. We assessed the outcomes of these programs and found a 2-fold benefit: scientists improve their communication skills by explaining basic science research to a general audience, and students'' enthusiasm for science and their scientific knowledge are increased. Here we present details about both programs, along with our assessment of them, and discuss the feasibility of exporting these programs to other universities.