Integrated barcode chips for rapid, multiplexed analysis of proteins in microliter quantities of blood

As the tissue that contains the largest representation of the human proteome [1], blood is the most important fluid for clinical diagnostics [2, 3, 4]. However, although changes of plasma protein profiles reflect physiological or pathological conditions associated with many human diseases, only a handful of plasma proteins are routinely used in clinical tests. Reasons for this include the intrinsic complexity of the plasma proteome [1], the heterogeneity of human diseases and the rapid degradation of proteins in sampled blood [5]. We report an integrated microfluidic system, the integrated blood barcode chip that can sensitively sample a large panel of protein biomarkers over broad concentration ranges and within 10 min of sample collection. It enables on-chip blood separation and rapid measurement of a panel of plasma proteins from quantities of whole blood as small as those obtained by a finger prick. Our device holds potential for inexpensive, noninvasive and informative clinical diagnoses, particularly in point-of-care settings

Sonic Hedgehog Pathway Is Essential for Maintenance of Cancer Stem-Like Cells in Human Gastric Cancer

Abnormal activation of the Sonic hedgehog (SHH) pathway has been described in a wide variety of human cancers and in cancer stem cells (CSCs), however, the role of SHH pathway in gastric CSCs has not been reported. In this study, we investigated the possibility that abnormal activation of the SHH pathway maintained the characteristics of gastric CSCs. First, we identified cancer stem-like cells (CSLCs) from human gastric cancer cell lines (HGC-27, MGC-803 and MKN-45) using tumorsphere culture. Compared with adherent cells, the floating tumorsphere cells had more self-renewing capacity and chemoresistance. The cells expressing CSCs markers (CD44, CD24 and CD133) were also significantly more in tumorsphere cells than in adherent cells. More importantly, in vivo xenograft studies showed that tumors could be generated with 2×104 tumorsphere cells, which was 100-fold less than those required for tumors seeding by adherent cells. Next, RT-PCR and Western blot showed that the expression levels of Ptch and Gli1 (SHH pathway target genes) were significantly higher in tumorsphere cells than in adherent cells. The results of quantitative real-time PCR were similar to those of RT-PCR and Western blot. Further analysis revealed that SHH pathway blocked by cyclopamine or 5E1 caused a higher reduction in self-renewing capacity of HGC-27 tumorsphere cells than that of adherent cells. We also found that SHH pathway blocking strongly enhanced the efficacy of chemotherapeutic drugs in HGC-27 tumorsphere cells in vitro and in vivo but had no significant effect in adherent cells. Finally, we isolated the tumorspheres from gastric cancer specimen, these cells also had chemoresistance and tumorigenic capacity, and SHH pathway maintained the gastric CSLCs characteristics of tumorsphere cells from primary tumor samples. In conclusion, our data suggested that SHH pathway was essential for maintenance of CSLCs in human gastric cancer

Evenness mediates the global relationship between forest productivity and richness

1. Biodiversity is an important component of natural ecosystems, with higher species richness often correlating with an increase in ecosystem productivity. Yet, this relationship varies substantially across environments, typically becoming less pronounced at high levels of species richness. However, species richness alone cannot reflect all important properties of a community, including community evenness, which may mediate the relationship between biodiversity and productivity. If the evenness of a community correlates negatively with richness across forests globally, then a greater number of species may not always increase overall diversity and productivity of the system. Theoretical work and local empirical studies have shown that the effect of evenness on ecosystem functioning may be especially strong at high richness levels, yet the consistency of this remains untested at a global scale. 2. Here, we used a dataset of forests from across the globe, which includes composition, biomass accumulation and net primary productivity, to explore whether productivity correlates with community evenness and richness in a way that evenness appears to buffer the effect of richness. Specifically, we evaluated whether low levels of evenness in speciose communities correlate with the attenuation of the richness–productivity relationship. 3. We found that tree species richness and evenness are negatively correlated across forests globally, with highly speciose forests typically comprising a few dominant and many rare species. Furthermore, we found that the correlation between diversity and productivity changes with evenness: at low richness, uneven communities are more productive, while at high richness, even communities are more productive. 4. Synthesis. Collectively, these results demonstrate that evenness is an integral component of the relationship between biodiversity and productivity, and that the attenuating effect of richness on forest productivity might be partly explained by low evenness in speciose communities. Productivity generally increases with species richness, until reduced evenness limits the overall increases in community diversity. Our research suggests that evenness is a fundamental component of biodiversity– ecosystem function relationships, and is of critical importance for guiding conservation and sustainable ecosystem management decisions

Evenness mediates the global relationship between forest productivity and richness

1. Biodiversity is an important component of natural ecosystems, with higher species richness often correlating with an increase in ecosystem productivity. Yet, this relationship varies substantially across environments, typically becoming less pronounced at high levels of species richness. However, species richness alone cannot reflect all important properties of a community, including community evenness, which may mediate the relationship between biodiversity and productivity. If the evenness of a community correlates negatively with richness across forests globally, then a greater number of species may not always increase overall diversity and productivity of the system. Theoretical work and local empirical studies have shown that the effect of evenness on ecosystem functioning may be especially strong at high richness levels, yet the consistency of this remains untested at a global scale. 2. Here, we used a dataset of forests from across the globe, which includes composition, biomass accumulation and net primary productivity, to explore whether productivity correlates with community evenness and richness in a way that evenness appears to buffer the effect of richness. Specifically, we evaluated whether low levels of evenness in speciose communities correlate with the attenuation of the richness–productivity relationship. 3. We found that tree species richness and evenness are negatively correlated across forests globally, with highly speciose forests typically comprising a few dominant and many rare species. Furthermore, we found that the correlation between diversity and productivity changes with evenness: at low richness, uneven communities are more productive, while at high richness, even communities are more productive. 4. Synthesis. Collectively, these results demonstrate that evenness is an integral component of the relationship between biodiversity and productivity, and that the attenuating effect of richness on forest productivity might be partly explained by low evenness in speciose communities. Productivity generally increases with species richness, until reduced evenness limits the overall increases in community diversity. Our research suggests that evenness is a fundamental component of biodiversity–ecosystem function relationships, and is of critical importance for guiding conservation and sustainable ecosystem management decisions

The global biogeography of tree leaf form and habit

Understanding what controls global leaf type variation in trees is crucial for comprehending their role in terrestrial ecosystems, including carbon, water and nutrient dynamics. Yet our understanding of the factors influencing forest leaf types remains incomplete, leaving us uncertain about the global proportions of needle-leaved, broadleaved, evergreen and deciduous trees. To address these gaps, we conducted a global, ground-sourced assessment of forest leaf-type variation by integrating forest inventory data with comprehensive leaf form (broadleaf vs needle-leaf) and habit (evergreen vs deciduous) records. We found that global variation in leaf habit is primarily driven by isothermality and soil characteristics, while leaf form is predominantly driven by temperature. Given these relationships, we estimate that 38% of global tree individuals are needle-leaved evergreen, 29% are broadleaved evergreen, 27% are broadleaved deciduous and 5% are needle-leaved deciduous. The aboveground biomass distribution among these tree types is approximately 21% (126.4 Gt), 54% (335.7 Gt), 22% (136.2 Gt) and 3% (18.7 Gt), respectively. We further project that, depending on future emissions pathways, 17–34% of forested areas will experience climate conditions by the end of the century that currently support a different forest type, highlighting the intensification of climatic stress on existing forests. By quantifying the distribution of tree leaf types and their corresponding biomass, and identifying regions where climate change will exert greatest pressure on current leaf types, our results can help improve predictions of future terrestrial ecosystem functioning and carbon cycling

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