Long food chains are in general chaotic

The question whether chaos exists in nature is much debated. In this paper we prove that chaotic parameter regions exist generically in food chains of length greater than three. While nonchaotic dynamics is also possible, the presence of chaotic parameter regions indicates that chaotic dynamics is likely. We show that the chaotic regions survive even at high exponents of closure. Our results have been obtained using a general food chain model that describes a large class of different food chains. The existence of chaos in models of such generality can be deduced from the presence of certain bifurcations of higher codimension.     

Reprogramming Substrate and Catalytic Promiscuity of Tryptophan Prenyltransferases

Prenylation is a process widely prevalent in primary and secondary metabolism, contributing to functionality and chemical diversity in natural systems. Due to their high regio- and chemoselectivities, prenyltransferases are also valuable tools for creation of new compounds by chemoenzymatic synthesis and synthetic biology. Over the last ten years, biochemical and structural investigations shed light on the mechanism and key residues that control the catalytic process, but to date crucial information on how certain prenyltransferases control regioselectivity and chemoselectivity is still lacking. Here, we advance a general understanding of the enzyme family by contributing the first structure of a tryptophan C5-prenyltransferase 5-DMATS. Additinally, the structure of a bacterial tryptophan C6-prenyltransferase 6-DMATS was solved. Analysis and comparison of both substrate-bound complexes led to the identification of key residues for catalysis. Next, site-directed mutagenesis was successfully implemented to not only modify the prenyl donor specificity but also to redirect the prenylation, thereby switching the regioselectivity of 6-DMATS to that of 5-DMATS. The general strategy of structure-guided protein engineering should be applicable to other related prenyltransferases, thus enabling the production of novel prenylated compounds.     

Investigation of a New Electrode Array Technology for a Central Auditory Prosthesis

Ongoing clinical studies on patients recently implanted with the auditory midbrain implant (AMI) into the inferior colliculus (IC) for hearing restoration have shown that these patients do not achieve performance levels comparable to cochlear implant patients. The AMI consists of a single-shank array (20 electrodes) for stimulation along the tonotopic axis of the IC. Recent findings suggest that one major limitation in AMI performance is the inability to sufficiently activate neurons across the three-dimensional (3-D) IC. Unfortunately, there are no currently available 3-D array technologies that can be used for clinical applications. More recently, there has been a new initiative by the European Commission to fund and develop 3-D chronic electrode arrays for science and clinical applications through the NeuroProbes project that can overcome the bulkiness and limited 3-D configurations of currently available array technologies. As part of the NeuroProbes initiative, we investigated whether their new array technology could be potentially used for future AMI patients. Since the NeuroProbes technology had not yet been tested for electrical stimulation in an in vivo animal preparation, we performed experiments in ketamine-anesthetized guinea pigs in which we inserted and stimulated a NeuroProbes array within the IC and recorded the corresponding neural activation within the auditory cortex. We used 2-D arrays for this initial feasibility study since they were already available and were sufficient to access the IC and also demonstrate effective activation of the central auditory system. Based on these encouraging results and the ability to develop customized 3-D arrays with the NeuroProbes technology, we can further investigate different stimulation patterns across the ICC to improve AMI performance.     

Increased Concentrations of Fructose 2,6-Bisphosphate Contribute to the Warburg Effect in Phosphatase and Tensin Homolog (PTEN)-deficient Cells

Unlike normal differentiated cells, tumor cells metabolize glucose via glycolysis under aerobic conditions, a hallmark of cancer known as the Warburg effect. Cells lacking the commonly mutated tumor suppressor PTEN exhibit a glycolytic phenotype reminiscent of the Warburg effect. This has been traditionally attributed to the hyperactivation of PI3K/Akt signaling that results from PTEN loss. Here, we propose a novel mechanism whereby the loss of PTEN negatively affects the activity of the E3 ligase APC/C-Cdh1, resulting in the stabilization of the enzyme PFKFB3 and increased synthesis of its product fructose 2,6-bisphosphate (F2,6P₂). We discovered that when compared with wild-type cells, PTEN knock-out mouse embryonic fibroblasts (PTEN KO MEF) have 2–3-fold higher concentrations of F2,6P₂, the most potent allosteric activator of the glycolytic enzyme phosphofructokinase-1 (PFK-1). Reintroduction of either wild-type or phosphatase mutant PTEN in the PTEN KO cells effectively lowers F2,6P₂ to the wild-type levels and reduces their lactate production. PTEN KO cells were found to have high protein levels of PFKFB3, which directly contribute to the increased concentrations of F2,6P₂. PTEN enhances interaction between PFKFB3 and Cdh1, and overexpression of Cdh1 down-regulates the PFKFB3 protein level in wild-type, but not in PTEN-deficient cells. Importantly, we found that the degradation of endogenous PFKFB3 in PTEN KO cells occurs at a slower rate than in wild-type cells. Our results suggest an important role for F2,6P₂ in the metabolic reprogramming of PTEN-deficient cells that has important consequences for cell proliferation.     

Environmental drivers interactively affect individual tree growth across temperate European forests

Forecasting the growth of tree species to future environmental changes requires a better understanding of its determinants. Tree growth is known to respond to global‐change drivers such as climate change or atmospheric deposition, as well as to local land‐use drivers such as forest management. Yet, large geographical scale studies examining interactive growth responses to multiple global‐change drivers are relatively scarce and rarely consider management effects. Here, we assessed the interactive effects of three global‐change drivers (temperature, precipitation and nitrogen deposition) on individual tree growth of three study species (Quercus robur/petraea, Fagus sylvatica and Fraxinus excelsior). We sampled trees along spatial environmental gradients across Europe and accounted for the effects of management for Quercus. We collected increment cores from 267 trees distributed over 151 plots in 19 forest regions and characterized their neighbouring environment to take into account potentially confounding factors such as tree size, competition, soil conditions and elevation. We demonstrate that growth responds interactively to global‐change drivers, with species‐specific sensitivities to the combined factors. Simultaneously high levels of precipitation and deposition benefited Fraxinus, but negatively affected Quercus’ growth, highlighting species‐specific interactive tree growth responses to combined drivers. For Fagus, a stronger growth response to higher temperatures was found when precipitation was also higher, illustrating the potential negative effects of drought stress under warming for this species. Furthermore, we show that past forest management can modulate the effects of changing temperatures on Quercus’ growth; individuals in plots with a coppicing history showed stronger growth responses to higher temperatures. Overall, our findings highlight how tree growth can be interactively determined by global‐change drivers, and how these growth responses might be modulated by past forest management. By showing future growth changes for scenarios of environmental change, we stress the importance of considering multiple drivers, including past management and their interactions, when predicting tree growth.     

Interacting effects of warming and drought on regeneration and early growth of Acer pseudoplatanus and A. platanoides

Climate change is acting on several aspects of plant life cycles, including the sexual reproductive stage, which is considered amongst the most sensitive life‐cycle phases. In temperate forests, it is expected that climate change will lead to a compositional change in community structure due to changes in the dominance of currently more abundant forest tree species. Increasing our understanding of the effects of climate change on currently secondary tree species recruitment is therefore important to better understand and forecast population and community dynamics in forests. Here, we analyse the interactive effects of rising temperatures and soil moisture reduction on germination, seedling survival and early growth of two important secondary European tree species, Acer pseudoplatanus and A. platanoides. Additionally, we analyse the effect of the temperature experienced by the mother tree during seed production by collecting seeds of both species along a 2200‐km long latitudinal gradient. For most of the responses, A. platanoides showed higher sensitivity to the treatments applied, and especially to its joint manipulation, which for some variables resulted in additive effects while for others only partial compensation. In both species, germination and survival decreased with rising temperatures and/or soil moisture reduction while early growth decreased with declining soil moisture content. We conclude that although A. platanoides germination and survival were more affected after the applied treatments, its initial higher germination and larger seedlings might allow this species to be relatively more successful than A. pseudoplatanus in the face of climate change.     

Neutrophil activation by Candida glabrata but not Candida albicans promotes fungal uptake by monocytes

Candida albicans and Candida glabrata account for the majority of candidiasis cases worldwide. Although both species are in the same genus, they differ in key virulence attributes. Within this work, live cell imaging was used to examine the dynamics of neutrophil activation after confrontation with either C. albicans or C. glabrata. Analyses revealed higher phagocytosis rates of C. albicans than C. glabrata that resulted in stronger PMN (polymorphonuclear cells) activation by C. albicans. Furthermore, we observed differences in the secretion of chemokines, indicating chemotactic differences in PMN signalling towards recruitment of further immune cells upon confrontation with Candida spp. Supernatants from co‐incubations of neutrophils with C. glabrata primarily attracted monocytes and increased the phagocytosis of C. glabrata by monocytes. In contrast, PMN activation by C. albicans resulted in recruitment of more neutrophils. Two complex infection models confirmed distinct targeting of immune cell populations by the two Candida spp.: In a human whole blood infection model, C. glabrata was more effectively taken up by monocytes than C. albicans and histopathological analyses of murine model infections confirmed primarily monocytic infiltrates in C. glabrata kidney infection in contrast to PMN‐dominated infiltrates in C. albicans infection. Taken together, our data demonstrate that the human opportunistic fungi C. albicans and C. glabrata are differentially recognized by neutrophils and one outcome of this differential recognition is the preferential uptake of C. glabrata by monocytes.     

High‐definition optical coherence tomography of melanocytic skin lesions

High‐definition optical coherence tomography (HD‐OCT) scanners have recently been developed. We assessed micromorphological HD‐OCT correlates of benign naevi (BN) and malignant melanoma (MM). 28 BN and 20 MM were studied using HD‐OCT and histology. Epidermal honeycomb/cobblestone pattern, regular junctional cell nests, and edged papillae are more often observed in BN, whereas fusion of rete ridges, pagetoid cells and junctional and/or dermal nests with atypical cells are more frequently seen in MM. A high overlap of HD‐OCT features in BN and MM was observed and in 20% of MM we did not find evidence for malignancy in OCT images at all. Using HD‐OCT it is possible to visualize architectural and cellular alterations of melanocytic skin lesions. The overlap of HD‐OCT features seen in BN and MM and the absence of suspicious HD‐OCT features in some MM represents an important limitation of HD‐OCT affecting the sensitivity of HD‐OCT in diagnosing MM.

High‐definition optical coherence tomography and the corresponding vertically sectioned histology of a compound naevus.     

Drivers of temporal changes in temperate forest plant diversity vary across spatial scales

Global biodiversity is affected by numerous environmental drivers. Yet, the extent to which global environmental changes contribute to changes in local diversity is poorly understood. We investigated biodiversity changes in a meta‐analysis of 39 resurvey studies in European temperate forests (3988 vegetation records in total, 17–75 years between the two surveys) by assessing the importance of (i) coarse‐resolution (i.e., among sites) vs. fine‐resolution (i.e., within sites) environmental differences and (ii) changing environmental conditions between surveys. Our results clarify the mechanisms underlying the direction and magnitude of local‐scale biodiversity changes. While not detecting any net local diversity loss, we observed considerable among‐site variation, partly explained by temporal changes in light availability (a local driver) and density of large herbivores (a regional driver). Furthermore, strong evidence was found that presurvey levels of nitrogen deposition determined subsequent diversity changes. We conclude that models forecasting future biodiversity changes should consider coarse‐resolution environmental changes, account for differences in baseline environmental conditions and for local changes in fine‐resolution environmental conditions.