Myelinosome formation represents an early stage of oligodendrocyte damage in multiple sclerosis and its animal model

Oligodendrocyte damage is a central event in the pathogenesis of the common neuro-inflammatory condition, multiple sclerosis (MS). Where and how oligodendrocyte damage is initiated in MS is not completely understood. Here, we use a combination of light and electron microscopy techniques to provide a dynamic and highly resolved view of oligodendrocyte damage in neuroinflammatory lesions. We show that both in MS and in its animal model structural damage is initiated at the myelin sheaths and only later spreads to the oligodendrocyte cell body. Early myelin damage itself is characterized by the formation of local myelin out-foldings-'myelinosomes'-, which are surrounded by phagocyte processes and promoted in their formation by anti-myelin antibodies and complement. The presence of myelinosomes in actively demyelinating MS lesions suggests that oligodendrocyte damage follows a similar pattern in the human disease, where targeting demyelination by therapeutic interventions remains a major open challenge

KRAS/BRAF mutation status and ERK1/2 activation as biomarkers for MEK1/2 inhibitor therapy in colorectal cancer

Phase II clinical trials of MEK inhibitors are ongoing and ERK1/2 activation is frequently used as a biomarker. In light of the mutational activation of BRAF and KRAS in colorectal cancer (CRC), inhibitors of the Raf-MEK-ERK mitogen-activated protein kinase are anticipated to be promising. Previous studies in pancreatic cancer have found little correlation between BRAF/KRAS mutation status and ERK1/2 activation, suggesting that identifying biomarkers of MEK inhibitor response may be more challenging than previously thought. The purpose of this study was to evaluate the effectiveness of MEK inhibitor therapy for CRC and BRAF/KRAS mutation status and ERK1/2 activation as biomarkers for MEK inhibitor therapy. First, we found that MEK inhibitor treatment impaired the anchorage-independent growth of nearly all KRAS/BRAF mutant, but not wild-type, CRC cells. There was a correlation between BRAF, but not KRAS, mutation status and ERK1/2 activation. Second, neither elevated ERK1/2 activation nor reduction of ERK1/2 activity correlated with MEK inhibition of anchorage-independent growth. Finally, we validated our cell line observations and found that ERK1/2 activation correlated with BRAF, but not KRAS, mutation status in 190 patient CRC tissues. Surprisingly, we also found that ERK activation was elevated in normal colonic epithelium, suggesting that normal cell toxicity may be a complication for CRC treatment. Our results suggest that although MEK inhibitors show promise in CRC, KRAS/BRAF mutation status, but not ERK activation as previously thought, may be useful biomarkers for MEK inhibitor sensitivity

Single-layer graphene modulates neuronal communication and augments membrane ion currents

The use of graphenebased materials to engineer sophisticated biosensing interfaces that can adapt to the central nervous system requires a detailed understanding of how such materials behave in a biological context. Graphene's peculiar properties can cause various cellular changes, but the underlying mechanisms remain unclear. Here, we show that singlelayer graphene increases neuronal firing by altering membraneassociated functions in cultured cells. Graphene tunes the distribution of extracellular ions at the interface with neurons, a key regulator of neuronal excitability. The resulting biophysical changes in the membrane include stronger potassium ion currents, with a shift in the fraction of neuronal firing phenotypes from adapting to tonically firing. By using experimental and theoretical approaches, we hypothesize that the graphene\u2013ion interactions that are maximized when singlelayer graphene is deposited on electrically insulating substrates are crucial to these effects

Integrated global assessment of the natural forest carbon potential

Forests are a substantial terrestrial carbon sink, but anthropogenic changes in land use and climate have considerably reduced the scale of this system 1. Remote-sensing estimates to quantify carbon losses from global forests 2–5 are characterized by considerable uncertainty and we lack a comprehensive ground-sourced evaluation to benchmark these estimates. Here we combine several ground-sourced 6 and satellite-derived approaches 2,7,8 to evaluate the scale of the global forest carbon potential outside agricultural and urban lands. Despite regional variation, the predictions demonstrated remarkable consistency at a global scale, with only a 12% difference between the ground-sourced and satellite-derived estimates. At present, global forest carbon storage is markedly under the natural potential, with a total deficit of 226 Gt (model range = 151–363 Gt) in areas with low human footprint. Most (61%, 139 Gt C) of this potential is in areas with existing forests, in which ecosystem protection can allow forests to recover to maturity. The remaining 39% (87 Gt C) of potential lies in regions in which forests have been removed or fragmented. Although forests cannot be a substitute for emissions reductions, our results support the idea 2,3,9 that the conservation, restoration and sustainable management of diverse forests offer valuable contributions to meeting global climate and biodiversity targets

Climatic controls of decomposition drive the global biogeography of forest-tree symbioses

The identity of the dominant root-associated microbial symbionts in a forest determines the ability of trees to access limiting nutrients from atmospheric or soil pools1,2, sequester carbon3,4 and withstand the effects of climate change5,6. Characterizing the global distribution of these symbioses and identifying the factors that control this distribution are thus integral to understanding the present and future functioning of forest ecosystems. Here we generate a spatially explicit global map of the symbiotic status of forests, using a database of over 1.1 million forest inventory plots that collectively contain over 28,000 tree species. Our analyses indicate that climate variables—in particular, climatically controlled variation in the rate of decomposition—are the primary drivers of the global distribution of major symbioses. We estimate that ectomycorrhizal trees, which represent only 2% of all plant species7, constitute approximately 60% of tree stems on Earth. Ectomycorrhizal symbiosis dominates forests in which seasonally cold and dry climates inhibit decomposition, and is the predominant form of symbiosis at high latitudes and elevation. By contrast, arbuscular mycorrhizal trees dominate in aseasonal, warm tropical forests, and occur with ectomycorrhizal trees in temperate biomes in which seasonally warm-and-wet climates enhance decomposition. Continental transitions between forests dominated by ectomycorrhizal or arbuscular mycorrhizal trees occur relatively abruptly along climate-driven decomposition gradients; these transitions are probably caused by positive feedback effects between plants and microorganisms. Symbiotic nitrogen fixers—which are insensitive to climatic controls on decomposition (compared with mycorrhizal fungi)—are most abundant in arid biomes with alkaline soils and high maximum temperatures. The climatically driven global symbiosis gradient that we document provides a spatially explicit quantitative understanding of microbial symbioses at the global scale, and demonstrates the critical role of microbial mutualisms in shaping the distribution of plant species

Reading tea leaves worldwide: Decoupled drivers of initial litter decomposition mass-loss rate and stabilization

The breakdown of plant material fuels soil functioning and biodiversity. Currently, process understanding of global decomposition patterns and the drivers of such patterns are hampered by the lack of coherent large-scale datasets. We buried 36,000 individual litterbags (tea bags) worldwide and found an overall negative correlation between initial mass-loss rates and stabilization factors of plant-derived carbon, using the Tea Bag Index (TBI). The stabilization factor quantifies the degree to which easy-to-degrade components accumulate during early-stage decomposition (e.g. by environmental limitations). However, agriculture and an interaction between moisture and temperature led to a decoupling between initial mass-loss rates and stabilization, notably in colder locations. Using TBI improved mass-loss estimates of natural litter compared to models that ignored stabilization. Ignoring the transformation of dead plant material to more recalcitrant substances during early-stage decomposition, and the environmental control of this transformation, could overestimate carbon losses during early decomposition in carbon cycle models

Reading tea leaves worldwide: decoupled drivers of initial litter decomposition mass‐loss rate and stabilization

The breakdown of plant material fuels soil functioning and biodiversity. Currently, process understanding of global decomposition patterns and the drivers of such patterns are hampered by the lack of coherent large‐scale datasets. We buried 36,000 individual litterbags (tea bags) worldwide and found an overall negative correlation between initial mass‐loss rates and stabilization factors of plant‐derived carbon, using the Tea Bag Index (TBI). The stabilization factor quantifies the degree to which easy‐to‐degrade components accumulate during early‐stage decomposition (e.g. by environmental limitations). However, agriculture and an interaction between moisture and temperature led to a decoupling between initial mass‐loss rates and stabilization, notably in colder locations. Using TBI improved mass‐loss estimates of natural litter compared to models that ignored stabilization. Ignoring the transformation of dead plant material to more recalcitrant substances during early‐stage decomposition, and the environmental control of this transformation, could overestimate carbon losses during early decomposition in carbon cycle models

Drying colloidal systems: laboratory models for a wide range of applications

The drying of complex fluids provides a powerful insight into phenomena that take place on time and length scales not normally accessible. An important feature of complex fluids, colloidal dispersions and polymer solutions is their high sensitivity to weak external actions. Thus, the drying of complex fluids involves a large number of physical and chemical processes. The scope of this review is the capacity to tune such systems to reproduce and explore specific properties in a physics laboratory. A wide variety of systems are presented, ranging from functional coatings, food science, cosmetology, medical diagnostics and forensics to geophysics and art

Integrated global assessment of the natural forest carbon potential

Forests are a substantial terrestrial carbon sink, but anthropogenic changes in land use and climate have considerably reduced the scale of this system1. Remote-sensing estimates to quantify carbon losses from global forests2–5 are characterized by considerable uncertainty and we lack a comprehensive ground-sourced evaluation to benchmark these estimates. Here we combine several ground-sourced6 and satellite-derived approaches2,7,8 to evaluate the scale of the global forest carbon potential outside agricultural and urban lands. Despite regional variation, the predictions demonstrated remarkable consistency at a global scale, with only a 12% difference between the ground-sourced and satellite-derived estimates. At present, global forest carbon storage is markedly under the natural potential, with a total deficit of 226 Gt (model range = 151–363 Gt) in areas with low human footprint. Most (61%, 139 Gt C) of this potential is in areas with existing forests, in which ecosystem protection can allow forests to recover to maturity. The remaining 39% (87 Gt C) of potential lies in regions in which forests have been removed or fragmented. Although forests cannot be a substitute for emissions reductions, our results support the idea2,3,9 that the conservation, restoration and sustainable management of diverse forests offer valuable contributions to meeting global climate and biodiversity targets