Aging of TiO2 Nanoparticles Transiently Increases Their Toxicity to the Pelagic Microcrustacean Daphnia magna

During their aquatic life cycle, nanoparticles are subject to environmentally driven surface modifications (e.g. agglomeration or coating) associated with aging. Although the ecotoxicological potential of nanoparticles might be affected by these processes, only limited information about the potential impact of aging is available. In this context, the present study investigated acute (96 h) and chronic (21 d) implications of systematically aged titanium dioxide nanoparticles (nTiO₂; ~90 nm) on the standard test species Daphnia magna by following the respective test guidelines. The nTiO₂ were aged for 0, 1, 3 and 6 d in media with varying ionic strengths (Milli-Q water: approx. 0.00 mmol/L and ASTM: 9.25 mmol/L) in the presence or absence of natural organic matter (NOM). Irrespective of the other parameters, aging in Milli-Q did not change the acute toxicity relative to an unaged control. In contrast, 6 d aged nTiO₂ in ASTM without NOM caused a fourfold decreased acute toxicity. Relative to the 0 d aged particles, nTiO₂ aged for 1 and 3 d in ASTM with NOM, which is the most environmentally-relevant setup used here, significantly increased acute toxicity (by approximately 30%), while a toxicity reduction (60%) was observed for 6 d aged nTiO₂. Comparable patterns were observed during the chronic experiments. A likely explanation for this phenomenon is that the aging of nTiO₂ increases the particle size at the start of the experiment or the time of the water exchange from <100 nm to approximately 500 nm, which is the optimal size range to be taken up by filter feeding D. magna. If subjected to further agglomeration, larger nTiO₂ particles, however, cannot be retained by the daphnids’ filter apparatus ultimately reducing their ecotoxicological potential. This non-linear pattern of increasing and decreasing nTiO₂ related toxicity over the aging duration, highlights the knowledge gap regarding the underlying mechanisms and processes. This understanding seems, however, fundamental to predict the risks of nanoparticles in the field.     

Sexual dimorphism in immune defense

ABSTRACT Sex differences in parasitism are common and may depend on sex differences in intensity of sexual competition, immunosuppression, or exposure to parasites. We used a large data set on the mass of two immune defense organs in birds (the bursa of Fabricius and the spleen) to test for consistent sex differences in immune defense. Males had a relative spleen mass that was consistently smaller, but more variable, than that of females across species of birds. A sex difference in the size of the spleen was not present among juveniles but was large and statistically significant among adults. The suppression of spleen mass in adult males increased with a measure of intensity of sexual selection: the frequency of extra-pair paternity. These findings suggest that sexdifferences in parasitism may arise as a consequence of sex differences in immune function, as mediated by sexual selection.     

Characterization of bacterial NMN deamidase as a Ser/Lys hydrolase expands diversity of serine amidohydrolases

NMN deamidase (PncC) is a bacterial enzyme involved in NAD biosynthesis. We have previously demonstrated that PncC is structurally distinct from other known amidohydrolases. Here, we extended PncC characterization by mutating all potential catalytic residues and assessing their individual roles in catalysis through kinetic analyses. Inspection of these residues’ spatial arrangement in the active site, allowed us to conclude that PncC is a serine-amidohydrolase, employing a Ser/Lys dyad for catalysis. Analysis of the PncC structure in complex with a modeled NMN substrate supported our conclusion, and enabled us to propose the catalytic mechanism.     

Glutamine versus ammonia utilization in the NAD synthetase family

NAD is a ubiquitous and essential metabolic redox cofactor which also functions as a substrate in certain regulatory pathways. The last step of NAD synthesis is the ATP-dependent amidation of deamido-NAD by NAD synthetase (NADS). Members of the NADS family are present in nearly all species across the three kingdoms of Life. In eukaryotic NADS, the core synthetase domain is fused with a nitrilase-like glutaminase domain supplying ammonia for the reaction. This two-domain NADS arrangement enabling the utilization of glutamine as nitrogen donor is also present in various bacterial lineages. However, many other bacterial members of NADS family do not contain a glutaminase domain, and they can utilize only ammonia (but not glutamine) in vitro. A single-domain NADS is also characteristic for nearly all Archaea, and its dependence on ammonia was demonstrated here for the representative enzyme from Methanocaldococcus jannaschi. However, a question about the actual in vivo nitrogen donor for single-domain members of the NADS family remained open: Is it glutamine hydrolyzed by a committed (but yet unknown) glutaminase subunit, as in most ATP-dependent amidotransferases, or free ammonia as in glutamine synthetase? Here we addressed this dilemma by combining evolutionary analysis of the NADS family with experimental characterization of two representative bacterial systems: a two-subunit NADS from Thermus thermophilus and a single-domain NADS from Salmonella typhimurium providing evidence that ammonia (and not glutamine) is the physiological substrate of a typical single-domain NADS. The latter represents the most likely ancestral form of NADS. The ability to utilize glutamine appears to have evolved via recruitment of a glutaminase subunit followed by domain fusion in an early branch of Bacteria. Further evolution of the NADS family included lineage-specific loss of one of the two alternative forms and horizontal gene transfer events. Lastly, we identified NADS structural elements associated with glutamine-utilizing capabilities.     

S100B causes apoptosis in a myoblast cell line in a RAGE-independent manner

S100B, a Ca(2+)-modulated protein with both intracellular and extracellular regulatory roles, is most abundant in astrocytes, is expressed in various amounts in several non-nervous cells and is also found in normal serum. Astrocytes secrete S100B, and extracellular S100B exerts trophic and toxic effects on neurons depending on its concentration, in part by interacting with the receptor for advanced glycation end products (RAGE). The presence of S100B in normal serum and elevation of its serum concentration in several non-nervous pathological conditions suggest that S100B-expressing cells outside the brain might release the protein and S100B might affect non-nervous cells. Recently we reported that at picomolar to nanomolar doses S100B inhibits rat L6 myoblast differentiation via inactivation of p38 kinase in a RAGE-independent manner. We show here that at >or=5 nM in the absence of and at >100 nM in the presence of serum S100B causes myoblast apoptosis via stimulation of reactive oxygen species (ROS) production and inhibition of the pro-survival kinase, extracellular signal-regulated kinase (ERK)1/2, again in a RAGE-independent manner. Together with our previous data, the present results suggest that S100B might participate in the regulation of muscle development and regeneration by two independent mechanism, i.e., by inhibiting crucial steps of the myogenic program at the physiological levels found in serum and by causing elevation of ROS production and myoblast apoptosis following accumulation in serum and/or muscle extracellular space. Our data also suggest that RAGE has no role in the transduction of S100B effects on myoblasts, implying that S100B can interact with more than one receptor to affect its target cells.     

Parent-offspring regression suggests heritable susceptibility to ectoparasites in a natural population of kittiwake Rissa tridactyla

Little information is available on the genetic variability of host susceptibility to parasites in natural populations despite its importance for the understanding of the evolution of host-parasite interactions. A long-term demographic and epidemiologic survey of a seabird population allowed us to investigate the potential correlation between parent and offspring ectoparasite load, while controlling for various environmental factors. In particular, parasite loads were measured for all individuals (i.e., parents and offspring) when they were nestlings and the effect of the year and breeding cliff were taken into account. The positive correlation found between parent and offspring parasite loads suggests a heritable susceptibility to ectoparasitism by ticks in this host population and that this character has the potential to respond to natural selection.     

Social environment affects female and egg testosterone levels in the house sparrow (Passer domesticus)

Maternal effects can have an adaptive value if they improve the performance of offspring. As such, the transfer of maternal testosterone (T) to the eggs has been suggested as a mechanism for adaptive maternal control of offspring phenotype in birds, although recent studies have shown negative effects of testosterone on hatching rate and chick survival. Here, we experimentally investigated whether socially stressful conditions experienced by female house sparrows during egg laying affected their circulating levels of androgens and the amount transferred to the eggs. Social stress was simulated by the intrusion of a foreign male placed near the nest box during the egg‐laying sequence. We found that (1) both female and yolk testosterone titres were positively related to breeding density; (2) yolk testosterone was negatively correlated with maternal testosterone; (3) yolk testosterone was positively correlated with the behavioural response of females towards the intruder and (4) the interaction between social intrusion and breeding density affected the amount of testosterone transferred to the eggs. Altogether, our results suggest that females may be able to modulate the amount of testosterone they allocate to their eggs according to the social environment they experience during egg laying.     

A fuzzy anomaly indicator for environmental monitoring at continental scale

Environmental status assessment and monitoring can be performed by the integration of multi-source datasets at continental and global scales. We propose a methodology for the development of a new anomaly indicator (AI) which can highlight the occurrence of anomalous conditions in a synthetic fashion by analysis of a set of spatial input data. Anomalous conditions are defined relative to long-term average assumed as normal or reference status of the vegetated land surface. The indicator is defined according to fuzzy set theory which is a powerful means of handling uncertain and imprecise knowledge of environmental systems. The indicator integrates, in an innovative way, the anomaly scores of a set of contributing factors extracted from the analysis of historical time series, mainly of Earth observations data. These time series are used to automatically derive the fuzzy membership functions that quantify the contribution of each factor to the final indicator. No reference data and expert knowledge are strictly required for the implementation of the AI although the methodology allows customization where this type of information is available. The method was tested over the African continent for the period 1996–2002; monthly AI values were derived with input datasets of vegetation phenology and rainfall estimates. The output AI continental maps bring new information by integrating multiple factors and they highlight patterns of anomalous conditions of the status of the environment. The analysis of the correlation with the El Niño Southern Oscillation (ENSO) shows that the AI is able to identify the effects of this phenomenon and its spatio-temporal dynamics. The 1997–1998 and 2000–2001 ENSO events are clearly highlighted by the highest AI values in specific regions of the continent. The indicator proposed is a valuable tool which can help guide in depth and detailed investigations of environmental conditions at local scale.     

BayMeth: improved DNA methylation quantification for affinity capture sequencing data using a flexible Bayesian approach

Affinity capture of DNA methylation combined with high-throughput sequencing strikes a good balance between the high cost of whole genome bisulfite sequencing and the low coverage of methylation arrays. We present BayMeth, an empirical Bayes approach that uses a fully methylated control sample to transform observed read counts into regional methylation levels. In our model, inefficient capture can readily be distinguished from low methylation levels. BayMeth improves on existing methods, allows explicit modeling of copy number variation, and offers computationally efficient analytical mean and variance estimators. BayMeth is available in the Repitools Bioconductor package.