Reliable Neuronal Systems: The Importance of Heterogeneity

For every engineer it goes without saying: in order to build a reliable system we need components that consistently behave precisely as they should. It is also well known that neurons, the building blocks of brains, do not satisfy this constraint. Even neurons of the same type come with huge variances in their properties and these properties also vary over time. Synapses, the connections between neurons, are highly unreliable in forwarding signals. In this paper we argue that both these fact add variance to neuronal processes, and that this variance is not a handicap of neural systems, but that instead predictable and reliable functional behavior of neural systems depends crucially on this variability. In particular, we show that higher variance allows a recurrently connected neural population to react more sensitively to incoming signals, and processes them faster and more energy efficient. This, for example, challenges the general assumption that the intrinsic variability of neurons in the brain is a defect that has to be overcome by synaptic plasticity in the process of learning.     

Inhibition of Mitochondrial Complex III Blocks Neuronal Differentiation and Maintains Embryonic Stem Cell Pluripotency

The mitochondrion is emerging as a key organelle in stem cell biology, acting as a regulator of stem cell pluripotency and differentiation. In this study we sought to understand the effect of mitochondrial complex III inhibition during neuronal differentiation of mouse embryonic stem cells. When exposed to antimycin A, a specific complex III inhibitor, embryonic stem cells failed to differentiate into dopaminergic neurons, maintaining high Oct4 levels even when subjected to a specific differentiation protocol. Mitochondrial inhibition affected distinct populations of cells present in culture, inducing cell loss in differentiated cells, but not inducing apoptosis in mouse embryonic stem cells. A reduction in overall proliferation rate was observed, corresponding to a slight arrest in S phase. Moreover, antimycin A treatment induced a consistent increase in HIF-1α protein levels. The present work demonstrates that mitochondrial metabolism is critical for neuronal differentiation and emphasizes that modulation of mitochondrial functions through pharmacological approaches can be useful in the context of controlling stem cell maintenance/differentiation.     

TGFβs Modulate Permeability of the Blood-Epididymis Barrier in an In Vitro Model

The blood-epididymis barrier (BEB) is formed by epithelial tight junctions mediating selective permeability of the epididymal epithelium. Defective barrier function can disturb the balance of the epididymal milieu, which may result in infertility. The stroma of the epididymis contains high amounts of cytokines of the TGFβ family of unknown function. We screened possible effects of all three TGFβ isoforms on paracellular tightness in a BEB in vitro model based on the strongly polarized mouse epididymal epithelial MEPC5 cells in the transwell system. In this model we found a robust transepithelial electrical resistance (TER) of about 840 Ω x cm². Effects on the paracellular permeability were evaluated by two methods, TER and FITC-Dextran-based tracer diffusion assays. Both assays add up to corresponding results indicating a time-dependent disturbance of the BEB differentially for the three TGFβ isoforms (TGFβ3>TGFβ1>TGFβ2) in a TGFβ-recetor-1 kinase- and Smad-dependent manner. The tight junction protein claudin-1 was found to be reduced by the treatment with TGFβs, whereas occludin was not influenced. Epididymal epithelial cells are predominantly responsive to TGFβs from the basolateral side, suggesting that TGFβ may have an impact on the epididymal epithelium from the stroma in vivo. Our data show for the first time that TGFβs decrease paracellular tightness in epididymal epithelial cells, thus establishing a novel mechanism of regulation of BEB permeability, which is elementary for sperm maturation and male fertility.     

Confronting the Paradox of Enrichment to the Metacommunity Perspective

Resource enrichment can potentially destabilize predator-prey dynamics. This phenomenon historically referred as the "paradox of enrichment" has mostly been explored in spatially homogenous environments. However, many predator-prey communities exchange organisms within spatially heterogeneous networks called metacommunities. This heterogeneity can result from uneven distribution of resources among communities and thus can lead to the spreading of local enrichment within metacommunities. Here, we adapted the original Rosenzweig-MacArthur predator-prey model, built to study the paradox of enrichment, to investigate the effect of regional enrichment and of its spatial distribution on predator-prey dynamics in metacommunities. We found that the potential for destabilization was depending on the connectivity among communities and the spatial distribution of enrichment. In one hand, we found that at low dispersal regional enrichment led to the destabilization of predator-prey dynamics. This destabilizing effect was more pronounced when the enrichment was uneven among communities. In the other hand, we found that high dispersal could stabilize the predator-prey dynamics when the enrichment was spatially heterogeneous. Our results illustrate that the destabilizing effect of enrichment can be dampened when the spatial scale of resource enrichment is lower than that of organismss movements (heterogeneous enrichment). From a conservation perspective, our results illustrate that spatial heterogeneity could decrease the regional extinction risk of species involved in specialized trophic interactions. From the perspective of biological control, our results show that the heterogeneous distribution of pest resource could favor or dampen outbreaks of pests and of their natural enemies, depending on the spatial scale of heterogeneity.     

Alterations of Neuromuscular Function after the World's Most Challenging Mountain Ultra-Marathon

We investigated the physiological consequences of the most challenging mountain ultra-marathon (MUM) in the world: a 330-km trail run with 24000 m of positive and negative elevation change. Neuromuscular fatigue (NMF) was assessed before (Pre-), during (Mid-) and after (Post-) the MUM in experienced ultra-marathon runners (n = 15; finish time  = 122.43 hours ±17.21 hours) and in Pre- and Post- in a control group with a similar level of sleep deprivation (n = 8). Blood markers of muscle inflammation and damage were analyzed at Pre- and Post-. Mean ± SD maximal voluntary contraction force declined significantly at Mid- (−13±17% and −10±16%, P<0.05 for knee extensor, KE, and plantar flexor muscles, PF, respectively), and further decreased at Post- (−24±13% and −26±19%, P<0.01) with alteration of the central activation ratio (−24±24% and −28±34% between Pre- and Post-, P<0.05) in runners whereas these parameters did not change in the control group. Peripheral NMF markers such as 100 Hz doublet (KE: −18±18% and PF: −20±15%, P<0.01) and peak twitch (KE: −33±12%, P<0.001 and PF: −19±14%, P<0.01) were also altered in runners but not in controls. Post-MUM blood concentrations of creatine kinase (3719±3045 Ul·¹), lactate dehydrogenase (1145±511 UI·L⁻¹), C-Reactive Protein (13.1±7.5 mg·L⁻¹) and myoglobin (449.3±338.2 µg·L⁻¹) were higher (P<0.001) than at Pre- in runners but not in controls. Our findings revealed less neuromuscular fatigue, muscle damage and inflammation than in shorter MUMs. In conclusion, paradoxically, such extreme exercise seems to induce a relative muscle preservation process due likely to a protective anticipatory pacing strategy during the first half of MUM and sleep deprivation in the second half.     

Early Diagnosis of Neurodegenerative Diseases – The Long Awaited Holy Grail and Bottleneck of Modern Brain Research – 19th HUPO BPP Workshop

The HUPO Brain Proteome Project (HUPO BPP) held its 19th workshop in Dortmund, Germany, from May 22 to 24, 2013. The focus of the spring workshop was on strategies and developments concerning early diagnosis of neurodegenerative diseases     

Why some species cannot colonise restored habitats? The effects of seed and microsite availability

Restoration of calcareous grasslands was promoted as a conservation strategy to reduce the risks imposed by habitat loss and fragmentation. Restoration already provided promising results for several taxa, however some specialist species still fail at colonising restored habitats. We aimed at explaining this lack of colonisation success for three calcareous grasslands specialist species in southern Belgium: Pulsatilla vulgaris; Trifolium montanum; and, Veronica prostrata. We studied: (i) germination in control and outdoor conditions (cold, heat, smoke and litter effects); (ii) in situ seedling emergence patterns (effects of seed addition and germination microsites availability). The three species were able to germinate in Petri dishes in the absence of treatment. Cold enhanced the germination of V. prostrata. Fire-related treatments (heat shock and smoke exposure) did not enhance germination and were deleterious to V. prostrata. Litter cover improved P. vulgaris emergence in outdoor containers, but had a negative effect on V. prostrata. In the field, V. prostrata did not emerge. T. montanum seedlings were observed in the reference grasslands when seeds were added, but not in the restored grasslands. P. vulgaris emerged in the reference grasslands, and to a lower degree in the restored grasslands. The combination of seed addition and microsites availability for seed germination resulted in enhanced seedling emergence for P. vulgaris. Our results suggest that seed and microsite availability can be limiting factors for site colonisation, but the combination of both is likely much more limiting. Lower seedling emergence in restored than in reference grasslands suggests a lower habitat quality in restored grasslands.