Obesity and triple‐negative‐breast‐cancer: Is apelin a new key target?

Epidemiological studies have shown that obese subjects have an increased risk of developing triple‐negative breast cancer (TNBC) and an overall reduced survival. However, the relation between obesity and TNBC remains difficult to understand. We hypothesize that apelin, an adipokine whose levels are increased in obesity, could be a major factor contributing to both tumour growth and metastatization in TNBC obese patients. We observed that development of obesity under high‐fat diet in TNBC tumour‐bearing mice significantly increased tumour growth. By showing no effect of high‐fat diet in obesity‐resistant mice, we demonstrated the necessity to develop obesity‐related disorders to increase tumour growth. Apelin mRNA expression was also increased in the subcutaneous adipose tissue and tumours of obese mice. We further highlighted that the reproduction of obesity‐related levels of apelin in lean mice led to an increased TNBC growth and brain metastases formation. Finally, injections of the apelinergic antagonist F13A to obese mice significantly reduced TNBC growth, suggesting that apelinergic system interference could be an interesting therapeutic strategy in the context of obesity and TNBC.     

Why don't all termite species have a sterile worker caste?

No general theory explains why a sterile worker caste is not found in all species of both Hymenoptera and Isoptera (Insecta). Recent empirical finding show that, in the termites (Isoptera), feeding outside the nest correlates well with the evolution of the sterile (true) worker caste from the non-sterile (false) worker caste. Here we explain the connection between food-nest separation and true worker evolution in termites, providing a general theory on the restricted distribution of the sterile worker caste in the Isoptera. A cost-benefit model suggests that there is a critical level of nest stability above which natural selection favours true workers over false workers, irrespective of genetical relatedness. Because food-nest separation tends to increase nest stability, this theoretical result implies that the less a termite species consumes its nest as food, the more likely is its nest stability to fall above the critical level and a true worker caste will evolve.     

Phylogeography of a high‐dispersal New Zealand sea‐star: does upwelling block gene‐flow?

New Zealand's (NZ) geographical isolation, extensive coastline and well-characterized oceanography offer a valuable system for marine biogeographical research. Here we use mtDNA control region sequences in the abundant endemic sea-star Patiriella regularis to test the following literature-based predictions: that coastal upwelling disrupts north-south gene flow and promotes population differentiation (hypothesis 1); and that an invasive Tasmanian population of the species was introduced anthropogenically from southern New Zealand (hypothesis 2). We sequenced 114 samples from 22 geographical locations, including nine sites from North Island, nine from South Island, one from Stewart Island and three from Tasmania. Our analysis of these sequences revealed an abundance of shallow phylogenetic lineages within P. regularis (68 haplotypes, mean divergence 0.9%). We detected significant genetic heterogeneity between pooled samples from northern vs. southern New Zealand (FST = 0.072; P = 0.0002), consistent with the hypothesis that upwelling disrupts gene flow between these regions (hypothesis 1). However, we are currently unable to rule out the alternative hypothesis that Cook Strait represents a barrier to dispersal (North Island vs. South Island; FST = 0.031; P = 0.0467). The detection of significant spatial structure in NZ samples is consistent with restricted gene flow, and the strong structure evident in northern NZ may be facilitated by distinct ocean current systems. Four shared haplotypes and nonsignificant differentiation (FST = 0.025; P = 0.2525) between southern New Zealand and Tasmanian samples is consistent with an anthropogenic origin for the latter population (hypothesis 2).     

Can a mixed damage interfere with DNA‐prottein cross‐links repair?

Some photochemical and photobiological properties of 4,5',8-trimethylpsoralen (TMP) have been studied in comparison with 1,4,6,8-tetramethyl-2H-furo[2,3-h]quinolin-2 one (FQ) and 8-methoxypsoralen (8-MOP). TMP and FQ can photobind to mammalian cell DNA in vivo , by UVA irradiation, forming DNA-protein cross-links (DPC), but only TMP shows a strong capacity of inducing interstrand cross-links (ISC). The mechanism of DPC formation was studied using the double irradiation method in Chinese hamster ovary (CHO) cells, and DPC were detected by alkaline elution. Both TMP and FQ induce covalent diadducts linking together DNA and proteins. Studying the formation of double strand breaks (DSB) in CHO cells we observed that TMP induced a low amount of DSB, similar to 8-MOP. TMP and 8-MOP induced chromosomal aberrations in CHO cells to the same extent, while FQ appeared to be more active. Our data suggest that the ISC induced by TMP could trap enzymes involved in DPC repair.     

Proteasomal dysfunction induced by 4‐hydroxy‐2,3‐trans‐nonenal,an end‐product of lipid peroxidation: a mechanism contributing to neurodegeneration?

4-Hydroxy-2,3-trans-nonenal (HNE) is a neurotoxic unsaturated aldehyde end-product of lipid peroxidation. The addition of HNE to NT-2 and SK-N-MC cell lines induces apoptosis and we now investigated the time-course of events occurring prior to apoptosis. Treatment of both NT-2 and SK-N-MC cell lines with HNE led to HNE association with the proteasome, increased levels of protein carbonyls and ubiquitinated proteins, and decreased proteasomal function. There was also decreased metabolic activity, cytochrome c release and activation of caspase 3, followed by apoptotic changes including chromatin condensation, cell shrinkage and DNA fragmentation and laddering. Overexpression of mutant superoxide dismutase 1 proteins associated with amyotrophic lateral sclerosis decreased proteasomal activities in the absence of HNE and accelerated the apoptosis induced by HNE. By contrast, overexpression of wild-type superoxide dismutase 1 did not affect basal levels of proteasomal activity. The data suggest that accumulation of ubiquitinated proteins and impairment of proteasomal function are important events in HNE toxicity. We propose that the proteasomal system is a significant target of HNE neurotoxicity in a wide range of neurodegenerative diseases, especially if abnormal proteins are being expressed.     

Post‐dispersal seed recovery by animals: is it a plant‐ or an animal‐driven process?

The ability of animals to find and consume hoarded seeds (i.e. seed recovery) is a key stage within the seed dispersal process. However, the ecology of seed recovery is still poorly understood. Here, we analyze the factors controlling seed recovery by scatter‐hoarding rodents in an oak‐dominated temperate forest. We examined the relative importance of intrinsic seed traits (i.e. plant‐driven) and extrinsic seed factors (i.e. animal‐driven) on the probability of seed recovery. We found that seed recovery is mainly driven by extrinsic seed factors, mostly related to animal behavior (pilfering frequency, microsite preference, predation risk, burial depth and cache size). Important intrinsic traits such as seed size, seed quality and seed‐drop timing were, on average, of lower significance in the probability of seed recovery (2.8‐times less important than extrinsic factors); only seed quality was an important intrinsic trait. On the other hand, larger and nutritionally more valuable seeds showed a removal–recovery tradeoff as they enhance seed removal and hoarding (increasing dispersal quality) but also favour seed recovery (increasing predation). We find that other mechanisms beyond seed traits (e.g. masting) are needed to decrease seed recovery and, thus, increase seed survival. We conclude that, as seed recovery is mostly driven by animal behavioural factors, it substantially differs from other previous stages of the seed dispersal process that are more dependent on seed traits. We argue that seed recovery needs further attention to advance our understanding of the ecology of seed dispersal and the role of secondary dispersers as a selective force for seeds.     

Does anti‐parasitoid defense explain host‐plant selection by a polyphagous caterpillar?

While studies of tri-trophic interactions have uncovered a variety of mechanisms influencing the dietary specialization of insect herbivores, such studies have neglected host-plant selection by generalists. Here, we report an initial investigation on how host-plant quality and a tachinid parasitoid interact to affect the survival and host-plant selection by a polyphagous herbivore. This herbivore, Grammia geneura (Strecker) (Lepidoptera: Arctiidae), is a food-mixing caterpillar that feeds preferentially on forbs. A previous study suggested that G. geneura might eat certain host species for reasons other than benefits of physiological utilization. We hypothesized that host-plant mediated defenses could act against parasitoids, the major mortality agents of late instar G. geneura . Field observations indicated that caterpillars sometimes survived an attack by the parasitoid Exorista mella Walker (Diptera: Tachinidae) in nature. Laboratory experiments showed that the survival of parasitized caterpillars increased on acceptable but nutritionally inferior host-plant species, indicating that anti-parasitoid defense may explain host-plant selection in this dietary generalist. We found no indication that host-plant selection changed according to the parasitism status of individual caterpillars.     

Can a few non‐coding mutations make a human brain?

The recent finding that the human version of a neurodevelopmental enhancer of the Wnt receptor Frizzled 8 (FZD8) gene alters neural progenitor cell cycle timing and brain size is a step forward to understanding human brain evolution. The human brain is distinctive in terms of its cognitive abilities as well as its susceptibility to neurological disease. Identifying which of the millions of genomic changes that occurred during human evolution led to these and other uniquely human traits is extremely challenging. Recent studies have demonstrated that many of the fastest evolving regions of the human genome function as gene regulatory enhancers during embryonic development and that the human‐specific mutations in them might alter expression patterns. However, elucidating molecular and cellular effects of sequence or expression pattern changes is a major obstacle to discovering the genetic bases of the evolution of our species. There is much work to do before human‐specific genetic and genomic changes are linked to complex human traits. Also watch the Video Abstract .     

Germline stem cell maintenance as a proximate mechanism of life‐history trade‐offs?

We suggest that the commonly observed trade-offs between early- and late-life reproduction may be mediated by genetic variation in germline stem cell maintenance. Stem cell biology provides a natural framework and experimental methods for understanding the mechanistic basis of life-history evolution. At the same time, natural variation in life-history strategies can serve as a powerful tool for identifying the genes and molecular pathways involved in the maintenance of stem cells in aging adults. We illustrate the connections between life-history and stem cells with examples drawn primarily from Drosophila melanogaster and Caenorhabditis elegans, and suggest a number of testable hypotheses and avenues for future investigation that can be addressed with existing models and tools.     

Is non‐loglinear allometry a statistical artifact?

The allometric equation, y = ax^b, is commonly fitted to data indirectly by transforming predictor (x) and response (y) variables to logarithms, fitting a straight line to the transformations, and then back‐transforming (exponentiating) the resulting equation to the original arithmetic scale. Sometimes, however, transformation fails to linearize the observations, thereby giving rise to what has come to be known as non‐loglinear allometry. A smooth curve for observations displayed on a log–log plot is usually interpreted to mean that the scaling exponent in the allometric equation is a continuously changing function of body size, whereas a breakpoint between two (or more) linear segments on a log–log plot is typically taken to mean that the exponent changes abruptly, coincident with some important milestone in development. I applied simple graphical and statistical procedures in re‐analyses of three well‐known examples of non‐loglinear allometry, and showed in every instance that the relationship between predictor and response can be described in the original scale by simple functions with constant values for the exponent b. In no instance does the allometric exponent change during the course of development. Transformation of data to logarithms created new distributions that actually obscured the relationships between predictor and response variables in these investigations, and led to erroneous perceptions of growth. Such confounding effects of transformation are not limited to non‐loglinear allometry but are common to all applications of the allometric method. © 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, ?? , ??–??.     

Bombus terrestris in a mass‐flowering pollinator‐dependent crop: A mutualistic relationship?

Bumblebees (Bombus spp.) rely on an abundant and diverse selection of floral resources to meet their nutritional requirements. In farmed landscapes, mass‐flowering crops can provide an important forage resource for bumblebees, with increased visitation from bumblebees into mass‐flowering crops having an additional benefit to growers who require pollination services. This study explores the mutualistic relationship between Bombus terrestris L. (buff‐tailed bumblebee), a common species in European farmland, and the mass‐flowering crop courgette (Cucurbita pepo L.) to see how effective B. terrestris is at pollinating courgette and in return how courgette may affect B. terrestris colony dynamics. By combining empirical data on nectar and pollen availability with model simulations using the novel bumblebee model Bumble‐BEEHAVE, we were able to quantify and simulate for the first time, the importance of courgette as a mass‐flowering forage resource for bumblebees. Courgette provides vast quantities of nectar to ensure a high visitation rate, which combined with abundant pollen grains, enables B. terrestris to have a high pollination potential. While B. terrestris showed a strong fidelity to courgette flowers for nectar, courgette pollen was not found in any pollen loads from returning foragers. Nonetheless, model simulations showed that early season courgette (nectar) increased the number of hibernating queens, colonies, and adult workers in the modeled landscapes. Synthesis and applications. Courgette has the potential to improve bumblebee population dynamics; however, the lack of evidence of the bees collecting courgette pollen in this study suggests that bees can only benefit from this transient nectar source if alternative floral resources, particularly pollen, are also available to fulfill bees’ nutritional requirements in space and time. Therefore, providing additional forage resources could simultaneously improve pollination services and bumblebee populations.     

Retromer and the cation‐independent mannose 6‐phosphate receptor—Time for a trial separation?

The retromer cargo‐selective complex (CSC) comprising Vps35, Vps29 and Vps26 mediates the endosome‐to‐Golgi retrieval of the cation‐independent mannose 6‐phosphate receptor (CIMPR). Or does it? Recently published data have questioned the validity of this long‐established theory. Here, the evidence for and against a role for the retromer CSC in CIMPR endosome‐to‐Golgi retrieval is examined in the light of the new data that the SNX‐BAR dimer is actually responsible for CIMPR retrieval.      

Comparison of X‐ray and NMR structures: Is there a systematic difference in residue contacts between X‐ray‐ and NMR‐resolved protein structures?

We have compared structures of 78 proteins determined by both NMR and X-ray methods. It is shown that X-ray and NMR structures of the same protein have more differences than various X-ray structures obtained for the protein, and even more than various NMR structures of the protein. X-ray and NMR structures of 18 of these 78 proteins have obvious large-scale structural differences that seem to reflect a difference of crystal and solution structures. The other 60 pairs of structures have only small-scale differences comparable with differences between various X-ray or various NMR structures of a protein; we have analyzed these structures more attentively. One of the main differences between NMR and X-ray structures concerns the number of contacts per residue: (1) NMR structures presented in PDB have more contacts than X-ray structures at distances below 3.0 A and 4.5-6.5 A, and fewer contacts at distances of 3.0-4.5 A and 6.5-8.0 A; (2) this difference in the number of contacts is greater for internal residues than for external ones, and it is larger for beta-containing proteins than for all-alpha proteins. Another significant difference is that the main-chain hydrogen bonds identified in X-ray and NMR structures often differ. Their correlation is 69% only. However, analogous difference is found for refined and rerefined NMR structures, allowing us to suggest that the observed difference in interresidue contacts of X-ray and NMR structures of the same proteins is due mainly to a difference in mathematical treatment of experimental results.     

Lipopolysaccharide‐induced increase in signalling in hippocampus is abrogated by IL‐10 – a role for IL‐1β?

Parenterally administered lipopolysaccharide (LPS) increases the concentration of the pro-inflammatory cytokine interleukin-1beta (IL-1beta) in the rat hippocampus and evidence suggests that this effect plays a significant role in inhibiting long-term potentiation (LTP). The anti-inflammatory cytokine IL-10, antagonizes certain effects of IL-1beta, so if the effects of LPS are mediated through an increase in IL-1beta, it might be predicted that IL-10 would also abrogate the effect of LPS. Here, we report that IL-10 reversed the inhibitory effect of LPS on LTP and the data couple this with an inhibitory effect on the LPS-induced increase in IL-1beta. LPS treatment increased hippocampal expression of IL-1 receptor Type I protein. Consistent with the LPS-induced increases in IL-1beta concentration and receptor expression, were downstream changes which included enhanced phosphorylation of IRAK and the stress-activated kinases, JNK and p38; these LPS-induced changes were reversed by IL-10, which concurs with the idea that these events are triggered by increased activation of IL-1RI by IL-1beta. We provide evidence which indicates that LPS treatment leads to evidence of cell death and this was reversed in hippocampus prepared from LPS-treated rats which received IL-10. The evidence is therefore consistent with the idea that IL-10 acts to protect neuronal tissue from the detrimental effects induced by LPS.     

Can the combination of electrochemical regeneration of NAD+, selectivity of L‐α‐amino‐acid dehydrogenase,and reductive amination of α‐keto‐acid be applied to the inversion of configuration of a L‐α‐amino‐acid?

The inversion of configuration of L‐alanine can be carried out by combining its selective oxidation in the presence of NAD⁺ and L‐alanine dehydrogenase, electrochemical regeneration of the NAD⁺ at a carbon felt anode, and reductive amination of pyruvate, i.e., reduction of its imino derivative at a mercury cathode, the reaction mixture being buffered with concentrated ammonium/ammonia (1.28M / 1.28M). The dehydrogenase exhibits astonishing activity and stability under such extreme conditions of pH and ionic strength. The main drawback of the process is its slowness. At best, the complete inversion of a 10 mM solution of L‐alanine requires 140 h. A careful and detailed quantitative analysis of each of the key steps involved shows that the enzyme catalyzed oxidation is so thermodynamically uphill that it can be driven efficiently to completion only when both the coenzyme regeneration and the pyruvate reduction are very effective. The first condition is easily fulfilled. Under the best conditions, it is the rate of the chemical reaction producing the imine which controls the whole process kinetically. © 1999 John Wiley & Sons, Inc. Biotechnol Bioeng 64: 101–107, 1999.     

Could the acid–base status of Antarctic sea urchins indicate a better‐than‐expected resilience to near‐future ocean acidification?

Increasing atmospheric carbon dioxide concentration alters the chemistry of the oceans towards more acidic conditions. Polar oceans are particularly affected due to their low temperature, low carbonate content and mixing patterns, for instance upwellings. Calcifying organisms are expected to be highly impacted by the decrease in the oceans' pH and carbonate ions concentration. In particular, sea urchins, members of the phylum Echinodermata, are hypothesized to be at risk due to their high‐magnesium calcite skeleton. However, tolerance to ocean acidification in metazoans is first linked to acid–base regulation capacities of the extracellular fluids. No information on this is available to date for Antarctic echinoderms and inference from temperate and tropical studies needs support. In this study, we investigated the acid–base status of 9 species of sea urchins (3 cidaroids, 2 regular euechinoids and 4 irregular echinoids). It appears that Antarctic regular euechinoids seem equipped with similar acid–base regulation systems as tropical and temperate regular euechinoids but could rely on more passive ion transfer systems, minimizing energy requirements. Cidaroids have an acid–base status similar to that of tropical cidaroids. Therefore Antarctic cidaroids will most probably not be affected by decreasing seawater pH, the pH drop linked to ocean acidification being negligible in comparison of the naturally low pH of the coelomic fluid. Irregular echinoids might not suffer from reduced seawater pH if acidosis of the coelomic fluid pH does not occur but more data on their acid–base regulation are needed. Combining these results with the resilience of Antarctic sea urchin larvae strongly suggests that these organisms might not be the expected victims of ocean acidification. However, data on the impact of other global stressors such as temperature and of the combination of the different stressors needs to be acquired to assess the sensitivity of these organisms to global change.