Treetop: A Shiny-based application and R package for extracting forest information from LiDAR data for ecologists and conservationists

Individual tree detection (ITD) and crown delineation are two of the most relevant methods for extracting detailed and reliable forest information from LiDAR (Light Detection and Ranging) datasets. However, advanced computational skills and specialized knowledge have been normally required to extract forest information from LiDAR.The development of accessible tools for 3D forest characterization can facilitate rapid assessment by stakeholders lacking a remote sensing background, thus fostering the practical use of LiDAR datasets in forest ecology and conservation. This paper introduces the treetop application, an open-source web-based and R package LiDAR analysis tool for extracting forest structural information at the tree level, including cutting-edge analyses of properties related to forest ecology and management.We provide case studies of how treetop can be used for different ecological applications, within various forest ecosystems. Specifically, treetop was employed to assess post-hurricane disturbance in natural temperate forests, forest homogeneity in industrial forest plantations and the spatial distribution of individual trees in a tropical forest.treetop simplifies the extraction of relevant forest information for forest ecologists and conservationists who may use the tool to easily visualize tree positions and sizes, conduct complex analyses and download results including individual tree lists and figures summarizing forest structural properties. Through this open-source approach, treetop can foster the practical use of LiDAR data among forest conservation and management stakeholders and help ecological researchers to further understand the relationships between forest structure and function.The authors thank Nicholas L. Crookston for co‐developing the web‐LiDAR treetop tool, and the two anonymous reviewers for their helpful suggestions on the first version of the manuscript. This study is based on the work supported by the Department of Defence Strategic Environmental Research and Development Program (SERDP) under grants No. RC‐2243, RC19‐1064 and RC20‐1346 and USDA Forest Service (grand No. PRO00031122

Individual common variants exert weak effects on the risk for autism spectrum disorders.

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest

Protective Effect of Caffeic Acid on Paclitaxel Induced Anti-Proliferation and Apoptosis of Lung Cancer Cells Involves NF-κB Pathway

Caffeic acid (CA), a natural phenolic compound, is abundant in medicinal plants. CA possesses multiple biological effects such as anti-bacterial and anti-cancer growth. CA was also reported to induce fore stomach and kidney tumors in a mouse model. Here we used two human lung cancer cell lines, A549 and H1299, to clarify the role of CA in cancer cell proliferation. The growth assay showed that CA moderately promoted the proliferation of the lung cancer cells. Furthermore, pre-treatment of CA rescues the proliferation inhibition induced by a sub-IC50 dose of paclitaxel (PTX), an anticancer drug. Western blot showed that CA up-regulated the pro-survival proteins survivin and Bcl-2, the down-stream targets of NF-κB. This is consistent with the observation that CA induced nuclear translocation of NF-κB p65. Our study suggested that the pro-survival effect of CA on PTX-treated lung cancer cells is mediated through a NF-κB signaling pathway. This may provide mechanistic insights into the chemoresistance of cancer calls

Genetic Analysis of Completely Sequenced Disease-Associated MHC Haplotypes Identifies Shuffling of Segments in Recent Human History

The major histocompatibility complex (MHC) is recognised as one of the most important genetic regions in relation to common human disease. Advancement in identification of MHC genes that confer susceptibility to disease requires greater knowledge of sequence variation across the complex. Highly duplicated and polymorphic regions of the human genome such as the MHC are, however, somewhat refractory to some whole-genome analysis methods. To address this issue, we are employing a bacterial artificial chromosome (BAC) cloning strategy to sequence entire MHC haplotypes from consanguineous cell lines as part of the MHC Haplotype Project. Here we present 4.25 Mb of the human haplotype QBL (HLA-A26-B18-Cw5-DR3-DQ2) and compare it with the MHC reference haplotype and with a second haplotype, COX (HLA-A1-B8-Cw7-DR3-DQ2), that shares the same HLA-DRB1, -DQA1, and -DQB1 alleles. We have defined the complete gene, splice variant, and sequence variation contents of all three haplotypes, comprising over 259 annotated loci and over 20,000 single nucleotide polymorphisms (SNPs). Certain coding sequences vary significantly between different haplotypes, making them candidates for functional and disease-association studies. Analysis of the two DR3 haplotypes allowed delineation of the shared sequence between two HLA class II–related haplotypes differing in disease associations and the identification of at least one of the sites that mediated the original recombination event. The levels of variation across the MHC were similar to those seen for other HLA-disparate haplotypes, except for a 158-kb segment that contained the HLA-DRB1, -DQA1, and -DQB1 genes and showed very limited polymorphism compatible with identity-by-descent and relatively recent common ancestry (<3,400 generations). These results indicate that the differential disease associations of these two DR3 haplotypes are due to sequence variation outside this central 158-kb segment, and that shuffling of ancestral blocks via recombination is a potential mechanism whereby certain DR–DQ allelic combinations, which presumably have favoured immunological functions, can spread across haplotypes and populations

Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy

Cystatin C (CyC), a secreted cysteine protease inhibitor, has unclear biological functions. Many patients exhibit elevated plasma CyC levels, particularly during glucocorticoid (GC) treatment. This study links GCs with CyC’s systemic regulation by utilizing genome-wide association and structural equation modeling to determine CyC production genetics in the UK Biobank. Both CyC production and a polygenic score (PGS) capturing predisposition to CyC production were associated with increased all-cause and cancer-specific mortality. We found that the GC receptor directly targets CyC, leading to GC-responsive CyC secretion in macrophages and cancer cells. CyC-knockout tumors displayed significantly reduced growth and diminished recruitment of TREM2+ macrophages, which have been connected to cancer immunotherapy failure. Furthermore, the CyC-production PGS predicted checkpoint immunotherapy failure in 685 patients with metastatic cancer from combined clinical trial cohorts. In conclusion, CyC may act as a GC effector pathway via TREM2+ macrophage recruitment and may be a potential target for combination cancer immunotherapy.publishedVersio

Meandering rivers in modern desert basins: Implications for channel planform controls and prevegetation rivers

The influence of biotic processes in controlling the development of meandering channels in fluvial systems is controversial. The majority of the depositional history of the Earth's continents was devoid of significant biogeomorphic interactions, particularly those between vegetation and sedimentation processes. The prevailing perspective has been that prevegetation meandering channels rarely developed and that rivers with braided planforms dominated. However, recently acquired data demonstrate that meandering channel planforms are more widely preserved in prevegetation fluvial successions than previously thought. Understanding the role of prevailing fluvial dynamics in non- and poorly vegetated environments must rely on actualistic models derived from presently active rivers developed in sedimentary basins subject to desert-climate settings, the sparsest vegetated regions experiencing active sedimentation on Earth. These systems have fluvial depositional settings that most closely resemble those present in prevegetation (and extra-terrestrial) environments. Here, we present an analysis based on satellite imagery which reveals that rivers with meandering channel planforms are common in modern sedimentary basins in desert settings. Morphometric analysis of meandering fluvial channel behaviour, where vegetation is absent or highly restricted, shows that modern sparsely and non-vegetated meandering rivers occur across a range of slope gradients and basin settings, and possess a broad range of channel and meander-belt dimensions. The importance of meandering rivers in modern desert settings suggests that their abundance is likely underestimated in the prevegetation rock record, and models for recognition of their deposits need to be improved