Endotoxin recognition: in fish or not in fish?

The interaction between pathogens and their multicellular hosts is initiated by activation of pathogen recognition receptors (PRRs). These receptors, that include most notably members of the toll-like receptor (TLR) family, recognize specific pathogen-associated molecular patterns (PAMPs). TLR4 is a central part of the receptor complex that is involved in the activation of the immune system by lipopolysaccharide (LPS) through the specific recognition of its endotoxic moiety (Lipid A). This is a critical event that is essential for the immune response to Gram-negative bacteria as well as the etiology of endotoxic shock. Interestingly, compared to mammals, fish are resistant to endotoxic shock. This in vivo resistance concurs with in vitro studies demonstrating significantly lowered sensitivity of fish leukocytes to LPS activation. Further, our in vitro analyses demonstrate that in trout mononuclear phagocytes, LPS fails to induce antiviral genes, an event that occurs downstream of TLR4 and is required for the development of endotoxic shock. Finally, an in silico approach that includes mining of different piscine genomic and EST databases, reveals the presence in fish of all of the major TLR signaling elements except for the molecules specifically involved in TLR4-mediated endotoxin recognition and signaling in mammals. Collectively, our analysis questions the existence of TLR4-mediated cellular responses to LPS in fish. We further speculate that other receptors, in particular beta-2 integrins, may play a primary role in the activation of piscine leukocytes by LPS.     

TPX or not TPX?

An Aurora A regulatory module has been identified in two different proteins: TPX2 in Xenopus laevis and TPXL-1 in C. elegans. The diverse roles of these two proteins in spindle assembly leave us to beckon the true C. elegans TPX2 ortholog to center stage.     

Autism: not interested or not 'tuned-in'?

Recent studies of perceptual adaptation to faces have revolutionised our understanding of neural mechanisms that support face recognition. A new study has applied this approach to autistic spectrum disorders, revealing severe deficits in such adaptation.     

Extinction debt in fragmented grasslands: paid or not?

Fragmentation of grasslands and forests is considered a major threat to biodiversity. In the case of plants, the effect of fragmentation or landscape context is still unclear and published results are divergent. One explanation for this divergence is the slow response of long‐lived plants, creating an extinction debt. However, this has not been empirically confirmed. In this study, data were compiled from broad‐scale studies of grasslands from throughout the world that relate plant diversity to fragmentation effects. Only seven studies from northern Europe, out of a total 61, gave any information on actual habitat fragmentation in time and space. In landscapes with >10% grassland remaining, present‐day species richness was related to past landscape or habitat pattern. In landscapes with <10% grassland remaining, in contrast, plant species richness was more related to contemporary landscape or habitat pattern. Studies from landscapes with >10% grassland remaining supported the concept of an extinction debt, while studies from more fragmented landscapes did not provide any evidence of an extinction debt. In order to make generalisations about historical legacies on species diversity in grasslands it is important to consider a range of highly transformed landscapes, and not only landscapes with a high amount of grassland remaining.     

Pup mortality in laboratory mice – infanticide or not?

Background

Despite being the most commonly used mammal in biomedical research, problems with perinatal mortality in mice have received little attention and the causes of pup death are still poorly known. Females are often housed alone with their litters and since the lost pups are generally eaten, it is commonly assumed that the mother has killed them. However, more detailed observations than have been reported previously in the literature are required to establish if the cause of death is infanticide. Litter loss can only be prevented efficiently after underlying causes have been carefully investigated and interpreted. The aim of this study was to investigate if females actively kill their pups by observing the behaviour of females and pups in litters that later were lost. We used video recordings of females that lost their entire litter to observe females in detail from parturition until the pups died. In total, 10 C57BL/6 females (wildtype and the knockouts Hfe^?/? and β2m^?/?) were studied, housed in Makrolon II cages with or without access to a small amount of nesting material.

Results

Three of the females had pups that were never seen moving, and another three females had one or two pups that never moved, indicating that some pups were most likely still-born. In five females with live-born pups, detailed observations from the time when a pup was last seen moving until it died were possible to carry out. We observed females eating dead offspring and interacting with both moving and dead pups. However, we never observed a pup stop moving when manipulated by the female, nor were any wounds seen in the pups. Hence, we found no evidence of infanticide when studying females that had lost their entire litter.

Conclusion

These results suggest that other causes than infanticide plays a major role in mouse pup death, and stress the need for more systematic and careful investigations of the causality of litter loss.

     

Beneficial or not? Decoding carnivore roles in plant protection

Carnivores indirectly protect plants by reducing herbivory. This important ecosystem service can be undermined, however, as carnivores feed upon fellow carnivores. Such intraguild predation is exceedingly common, yet measurement of the degree to which this occurs has remained elusive due to difficulties in measuring the trophic tendencies of free-roaming animals. Conventional molecular methods, such as bulk-isotopic analyses, do not produce reliably accurate trophic position estimates, and often the inaccuracy is substantial. With the advent of compound-specific isotopic analysis (CSIA), it is now possible to accurately quantify the lifetime trophic tendencies of wild carnivore populations. Unfortunately, CSIA is extraordinarily expensive and time-consuming, limiting the number of samples that can be analyzed. The need for high-quality trophic information has to be balanced with the inaccessibility of CSIA. Here, we propose coupling CSIA-derived trophic position estimates with conventional bulk-¹⁵N analysis, effectively calibrating site-specific bulk-¹⁵N data and thereby allowing for trophic position estimation using bulk data alone. We also create a framework that uses trophic position as a basis to characterize carnivores as beneficial for crop protection. Within an agricultural field, we demonstrated the utility of this new approach by measuring the trophic positions of six common arthropod species. We then compare these trophic position estimates to those deriving from conventional bulk-¹⁵N analysis. Our hybrid approach produced more accurate trophic position estimates than the stand-alone bulk-¹⁵N method. Ultimately, we were able to examine enough specimens to determine which carnivore populations were likely beneficial for plant protection, and which were not.     

Adaptation to stress in yeast: to translate or not?

For most eukaryotic organisms, including Saccharomyces cerevisiae, the rapid inhibition of protein synthesis forms part of a response to stress. In order to balance the changing conditions, precise stress-specific alterations to the cell's proteome are required. Therefore, in the background of a global down-regulation in protein synthesis, specific proteins are induced. Given the level of plasticity required to enable stress-specific alterations of this kind, it is surprising that the mechanisms of translational regulation are not more diverse. In the present review, we summarize the impact of stress on translation initiation, highlighting both the similarities and distinctions between various stress responses. Finally, we speculate as to how yeast cells generate stress-responsive programmes of protein production when regulation is focused on the same steps in the translation pathway.     

Myosins in melanocytes: to move or not to move?

The actin network has been implicated in the intracellular transport and positioning of the melanosomes, organelles that are specialized in the biosynthesis and the storage of melanin. It contributes also to molecular mechanisms that underlie the intracellular membrane dynamics and thereby can control the biogenesis of melanosomes. Two mechanisms for actin-based movements have been identified: one is dependent on the motors associated to actin namely the myosins; the other is dependent on actin polymerization. This review will focus on to the role of the actin cytoskeleton and myosins in the transport and in the biogenesis of melanosomes. Myosins involved in membrane traffic are largely seen as transporters of organelles or membrane vesicles containing cargos along the actin networks. Yet increasing evidence suggests that some of the myosins contribute to the dynamics of internal membrane by using other mechanisms. The role of the myosins and the different molecular mechanisms by which they contribute or may contribute to the distribution, the movement and the biogenesis of the melanosomes in epidermal melanocytes and retinal pigmented epithelial (RPE) cells will be discussed.     

Myosins in melanocytes: to move or not to move?

The actin network has been implicated in the intracellular transport and positioning of the melanosomes, organelles that are specialized in the biosynthesis and the storage of melanin. It contributes also to molecular mechanisms that underlie the intracellular membrane dynamics and thereby can control the biogenesis of melanosomes. Two mechanisms for actin‐based movements have been identified: one is dependent on the motors associated to actin namely the myosins; the other is dependent on actin polymerization. This review will focus on to the role of the actin cytoskeleton and myosins in the transport and in the biogenesis of melanosomes. Myosins involved in membrane traffic are largely seen as transporters of organelles or membrane vesicles containing cargos along the actin networks. Yet increasing evidence suggests that some of the myosins contribute to the dynamics of internal membrane by using other mechanisms. The role of the myosins and the different molecular mechanisms by which they contribute or may contribute to the distribution, the movement and the biogenesis of the melanosomes in epidermal melanocytes and retinal pigmented epithelial (RPE) cells will be discussed.     

To model or not to model?

In theory, the combination of mathematical modeling with experimental studies can be a powerful and compelling approach to understanding cell biology. In practice, choosing appropriate problems, identifying willing and able collaborators, and publishing the resulting research can be remarkably challenging. To provide perspective on the question of whether and when to combine modeling and experiments, a panel of experts at the 2010 ASCB Annual Meeting shared their personal experiences and advice on how to use modeling effectively.     

Tbf1 or not Tbf1?

In this issue of Molecular Cell, Hogues et al. (2008) demonstrate a wholesale shift in the key regulatory protein involved in ribosomal protein (RP) synthesis during the evolution of S. cerevisiae and, en passant, raise interesting questions about the relationship between RP genes and telomeres.     

To charge or not to charge?

The ability to engineer proteins with increased thermostability will profoundly broaden their practical applications. Recent experimental results show that optimization of charge-charge interactions on the surface of proteins can be a useful strategy in the design of thermostable enzymes. Results also indicate a possibility that such optimized interactions provide structural determinants for enhanced stability of proteins from thermophilic organisms. In this article, the general strategy for design of thermostable proteins and perspectives for future studies are discussed.     

Do not use epinephrine in digital blocks: myth or truth?

The purpose of this study was to examine the role for epinephrine augmentation of digital block anesthesia by safely prolonging its duration of action and providing a temporary hemostatic effect. After obtaining approval from the review board of the authors' institution, 60 digital block procedures were performed in a prospective randomized double-blinded study. The digital blocks were performed using the dorsal approach. All anesthetics were delivered to treat either posttraumatic injuries or elective conditions. Of the 60 digital block procedures, 31 were randomized to lidocaine with epinephrine and 29 to plain lidocaine. Of the procedures performed using lidocaine with epinephrine, one patient required an additional injection versus five of the patients who were given plain lidocaine (p = 0.098). The need for control of bleeding required digital tourniquet use in 20 of 29 block procedures with plain lidocaine and in 9 of 31 procedures using lidocaine with epinephrine (p < 0.002). Two patients experienced complications after plain lidocaine blocks, while no complications occurred after lidocaine with epinephrine blocks (p = 0.23). By prolonging lidocaine's duration of action, epinephrine may prevent the need for an additional injection and prolong post-procedure pain relief. This study demonstrated that the temporary hemostatic effect of epinephrine decreased the need for, and thus the potential risk of, using a digital tourniquet (p < 0.002). As the temporary vasoconstrictor effect is reversible, the threat of complication from vasoconstrictor-induced ischemia is theoretical.