Aβ efflux impairment and inflammation linked to cerebrovascular accumulation of amyloid-forming amylin secreted from pancreas

Impairment of vascular pathways of cerebral β-amyloid (Aβ) elimination contributes to Alzheimer disease (AD). Vascular damage is commonly associated with diabetes. Here we show in human tissues and AD-model rats that bloodborne islet amyloid polypeptide (amylin) secreted from the pancreas perturbs cerebral Aβ clearance. Blood amylin concentrations are higher in AD than in cognitively unaffected persons. Amyloid-forming amylin accumulates in circulating monocytes and co-deposits with Aβ within the brain microvasculature, possibly involving inflammation. In rats, pancreatic expression of amyloid-forming human amylin indeed induces cerebrovascular inflammation and amylin-Aβ co-deposits. LRP1-mediated Aβ transport across the blood-brain barrier and Aβ clearance through interstitial fluid drainage along vascular walls are impaired, as indicated by Aβ deposition in perivascular spaces. At the molecular level, cerebrovascular amylin deposits alter immune and hypoxia-related brain gene expression. These converging data from humans and laboratory animals suggest that altering bloodborne amylin could potentially reduce cerebrovascular amylin deposits and Aβ pathology

Extinction Debt in Source-Sink Metacommunities

In an increasingly modified world, understanding and predicting the consequences of landscape alteration on biodiversity is a challenge for ecologists. To this end, metacommunity theory has developed to better understand the complexity of local and regional interactions that occur across larger landscapes. While metacommunity ecology has now provided several alternative models of species coexistence at different spatial scales, predictions regarding the consequences of landscape alteration have been done exclusively for the competition-colonization trade off model (CC). In this paper we investigate the effects of landscape perturbation on source-sink metacommunities. We show that habitat destruction perturbs the equilibria among species competitive effects within the metacommunity, driving both direct extinctions and an indirect extinction debt. As in CC models, we found a time lag for extinction following habitat destruction that varied in length depending upon the relative importance of direct and indirect effects. However, in contrast to CC models, we found that the less competitive species are more affected by habitat destruction. The best competitors can sometimes even be positively affected by habitat destruction, which corresponds well with the results of field studies. Our results are complementary to those results found in CC models of metacommunity dynamics. From a conservation perspective, our results illustrate that landscape alteration jeopardizes species coexistence in patchy landscapes through complex indirect effects and delayed extinctions patterns

Characterization of LINE-1 Ribonucleoprotein Particles

The average human genome contains a small cohort of active L1 retrotransposons that encode two proteins (ORF1p and ORF2p) required for their mobility (i.e., retrotransposition). Prior studies demonstrated that human ORF1p, L1 RNA, and an ORF2p-encoded reverse transcriptase activity are present in ribonucleoprotein (RNP) complexes. However, the inability to physically detect ORF2p from engineered human L1 constructs has remained a technical challenge in the field. Here, we have employed an epitope/RNA tagging strategy with engineered human L1 retrotransposons to identify ORF1p, ORF2p, and L1 RNA in a RNP complex. We next used this system to assess how mutations in ORF1p and/or ORF2p impact RNP formation. Importantly, we demonstrate that mutations in the coiled-coil domain and RNA recognition motif of ORF1p, as well as the cysteine-rich domain of ORF2p, reduce the levels of ORF1p and/or ORF2p in L1 RNPs. Finally, we used this tagging strategy to localize the L1–encoded proteins and L1 RNA to cytoplasmic foci that often were associated with stress granules. Thus, we conclude that a precise interplay among ORF1p, ORF2p, and L1 RNA is critical for L1 RNP assembly, function, and L1 retrotransposition

The biogeography of abundant and rare bacterioplankton in the lakes and reservoirs of China.

Bacteria play key roles in the ecology of both aquatic and terrestrial ecosystems; however, little is known about their diversity and biogeography, especially in the rare microbial biosphere of inland freshwater ecosystems. Here we investigated aspects of the community ecology and geographical distribution of abundant and rare bacterioplankton using high-throughput sequencing and examined the relative influence of local environmental variables and regional (spatial) factors on their geographical distribution patterns in 42 lakes and reservoirs across China. Our results showed that the geographical patterns of abundant and rare bacterial subcommunities were generally similar, and both of them showed a significant distance-decay relationship. This suggests that the rare bacterial biosphere is not a random assembly, as some authors have assumed, and that its distribution is most likely subject to the same ecological processes that control abundant taxa. However, we identified some differences between the abundant and rare groups as both groups of bacteria showed a significant positive relationship between sites occupancy and abundance, but the abundant bacteria exhibited a weaker distance-decay relationship than the rare bacteria. Our results implied that rare subcommunities were mostly governed by local environmental variables, whereas the abundant subcommunities were mainly affected by regional factors. In addition, both local and regional variables that were significantly related to the spatial variation of abundant bacterial community composition were different to those of rare ones, suggesting that abundant and rare bacteria may have discrepant ecological niches and may play different roles in natural ecosystems

Deep-Sea Nematodes Actively Colonise Sediments, Irrespective of the Presence of a Pulse of Organic Matter: Results from an In-Situ Experiment

A colonisation experiment was performed in situ at 2500 m water depth at the Arctic deep-sea long-term observatory HAUSGARTEN to determine the response of deep-sea nematodes to disturbed, newly available patches, enriched with organic matter. Cylindrical tubes,laterally covered with a 500 µm mesh, were filled with azoic deep-sea sediment and 13C-labelled food sources (diatoms and bacteria). After 10 days of incubation the tubes were analysed for nematode response in terms of colonisation and uptake. Nematodes actively colonised the tubes,however with densities that only accounted for a maximum of 2.13% (51 ind.10 cm−2) of the ambient nematode assemblages. Densities did not differ according to the presence or absence of organic matter, nor according to the type of organic matter added. The fact that the organic matter did not function as an attractant to nematodes was confirmed by the absence of notable 13C assimilation by the colonising nematodes. Overall, colonisationappears to be a process that yields reproducible abundance and diversity patterns, with certain taxa showing more efficiency. Together with the high variability between the colonising nematode assemblages, this lends experimental support to the existence of a spatio-temporal mosaic that emerges from highly localised, partially stochastic community dynamics

Urban Biodiversity and Landscape Ecology: Patterns, Processes and Planning

Effective planning for biodiversity in cities and towns is increasingly important as urban areas and their human populations grow, both to achieve conservation goals and because ecological communities support services on which humans depend. Landscape ecology provides important frameworks for understanding and conserving urban biodiversity both within cities and considering whole cities in their regional context, and has played an important role in the development of a substantial and expanding body of knowledge about urban landscapes and communities. Characteristics of the whole city including size, overall amount of green space, age and regional context are important considerations for understanding and planning for biotic assemblages at the scale of entire cities, but have received relatively little research attention. Studies of biodiversity within cities are more abundant and show that longstanding principles regarding how patch size, configuration and composition influence biodiversity apply to urban areas as they do in other habitats. However, the fine spatial scales at which urban areas are fragmented and the altered temporal dynamics compared to non-urban areas indicate a need to apply hierarchical multi-scalar landscape ecology models to urban environments. Transferring results from landscape-scale urban biodiversity research into planning remains challenging, not least because of the requirements for urban green space to provide multiple functions. An increasing array of tools is available to meet this challenge and increasingly requires ecologists to work with planners to address biodiversity challenges. Biodiversity conservation and enhancement is just one strand in urban planning, but is increasingly important in a rapidly urbanising world

Energy efficient sparse connectivity from imbalanced synaptic plasticity rules

It is believed that energy efficiency is an important constraint in brain evolution. As synaptic transmission dominates energy consumption, energy can be saved by ensuring that only a few synapses are active. It is therefore likely that the formation of sparse codes and sparse connectivity are fundamental objectives of synaptic plasticity. In this work we study how sparse connectivity can result from a synaptic learning rule of excitatory synapses. Information is maximised when potentiation and depression are balanced according to the mean presynaptic activity level and the resulting fraction of zero-weight synapses is around 50%. However, an imbalance towards depression increases the fraction of zero-weight synapses without significantly affecting performance. We show that imbalanced plasticity corresponds to imposing a regularising constraint on the L1-norm of the synaptic weight vector, a procedure that is well-known to induce sparseness. Imbalanced plasticity is biophysically plausible and leads to more efficient synaptic configurations than a previously suggested approach that prunes synapses after learning. Our framework gives a novel interpretation to the high fraction of silent synapses found in brain regions like the cerebellum