Highlights • The activity of miRNAs is essential for animal development and viability. • Deletion of individual miRNAs often leads to subtle or no phenotypic consequences. • miRNAs can have high ...levels of redundancy and are often placed in regulatory loops. • miRNAs can buffer gene expression against internal and external perturbations.
MicroRNAs (miRNAs) may be important regulators of gene expression. By modulating oncogenic and tumor suppressor pathways they could, in principle, contribute to tumorigenesis. Consistent with this ...hypothesis, recurrent genetic and epigenetic alterations of individual miRNAs are found in some tumors. Functional studies are now elucidating the mechanism of action of putative oncogenic and tumor suppressor miRNAs.
The primary outcome was to compare the effects of dopamine or epinephrine in severe sepsis on 28-day mortality; secondary outcomes were the rate of healthcare-associated infection, the need for other ...vasoactive drugs, and the multiple organ dysfunction score.
Double-blind, prospective, randomized controlled trial from February 1, 2009, to July 31, 2013.
PICU, Hospital Universitário da Universidade de São Paulo, Brazil.
Consecutive children who are 1 month to 15 years old and met the clinical criteria for fluid-refractory septic shock. Exclusions were receiving vasoactive drug(s) prior to hospital admission, having known cardiac disease, having already participated in the trial during the same hospital stay, refusing to participate, or having do-not-resuscitate orders.
Patients were randomly assigned to receive either dopamine (5-10 μg/kg/min) or epinephrine (0.1-0.3 μg/kg/min) through a peripheral or intraosseous line. Patients not reaching predefined stabilization criteria after the maximum dose were classified as treatment failure, at which point the attending physician gradually stopped the study drug and started another catecholamine.
Physiologic and laboratory data were recorded. Baseline characteristics were described as proportions and mean (± SD) and compared using appropriate statistical tests. Multiple regression analysis was performed, and statistical significance was defined as a p value of less than 0.05. Baseline characteristics and therapeutic interventions for the 120 children enrolled (63, dopamine; 57, epinephrine) were similar. There were 17 deaths (14.2%): 13 (20.6%) in the dopamine group and four (7%) in the epinephrine group (p=0.033). Dopamine was associated with death (odds ratio, 6.5; 95% CI, 1.1-37.8; p=0.037) and healthcare-associated infection (odds ratio, 67.7; 95% CI, 5.0-910.8; p=0.001). The use of epinephrine was associated with a survival odds ratio of 6.49.
Dopamine was associated with an increased risk of death and healthcare-associated infection. Early administration of peripheral or intraosseous epinephrine was associated with increased survival in this population. Limitations should be observed while interpreting these results.
The CRISPR-Cas9 system is a powerful tool to edit eukaryotic genomes that has recently been adapted for functional screens. Several of its applications--including the disruption of genes using ...Cas9-nickase and the generation of large deletions--require co-expression of two distinct guide RNAs (gRNAs). However, the lack of experimental approaches to generate pools of paired gRNA vectors prevents these applications from being scalable. Here we report a simple, inexpensive, one-step method that allows for the rapid and efficient cloning of gRNA pairs into expression vectors. We show that this method can be used to generate pooled libraries and is therefore suitable for in vivo and in vitro functional screens.
Overcoming intrinsic and extrinsic tumor-suppressive barriers is an essential feature of tumor progression. In this issue of Developmental Cell, Michael et al. (2019) use the RIP-Tag mouse model to ...show that pro-apoptotic signals mediated by the Activin B-ALK7 axis suppress ectopic proliferation and metastasis during pancreatic neuroendocrine cancer development.
Overcoming intrinsic and extrinsic tumor-suppressive barriers is an essential feature of tumor progression. In this issue of Developmental Cell, Michael et al. (2019) use the RIP-Tag mouse model to show that pro-apoptotic signals mediated by the Activin B-ALK7 axis suppress ectopic proliferation and metastasis during pancreatic neuroendocrine cancer development.
Overwhelming experimental evidence accumulated over the past decade indicates that microRNAs (miRNAs) are key regulators of gene expression in animals and plants and play important roles in ...development, homeostasis, and disease. The miR-17-92 family of miRNA clusters is composed of 3 related, highly conserved, polycistronic miRNA genes that collectively encode for a total of 15 miRNAs. We discuss recent studies demonstrating that these miRNAs are essential for vertebrate development and homeostasis. We also show how their mutation or deregulation contributes to the pathogenesis of a variety of human diseases, including cancer and congenital developmental defects. Finally, we discuss the current evidence suggesting how the different miRNAs encoded by these 3 clusters can functionally cooperate to fine-tune signaling and developmental pathways.
•A geometric method for wood-leaves separation from TLS point clouds is proposed.•Classification of wood points is highly accurate in broad leaved non-decidous trees.•The accuracy of classification ...drops for fine branches and twigs (diameter <3 cm).•Our approach requires only spatial coordinates of each point, not intensity value.•The separation method could be potentially applied to different TLS systems and tree species.
The terrestrial light detection and ranging (LiDAR) technique has been recently used to provide 3D structural information of forest canopy at the individual tree level. However, the operational use of Terrestrial Laser Scanner (TLS) for canopy characterization of broadleaf non-deciduous forests needs further investigations. The estimation of wood volume, above-ground woody biomass, tree canopy characteristics and leaf area index often requires separation of photosynthetically active material and non-photosynthetically active material. This article describes an automated wood-leaves separation method, based on spatial geometric information of TLS point clouds, for broad leaved non-deciduous trees. Scans of seven individuals of Quercus suber L. trees were acquired by using the TLS phase-based Leica HDS6100. Point clouds were partitioned in cubic volumes (voxels) that were used as input to generate clusters through the point density algorithm DBSCAN. The clustering process led to the identification of wood and non-wood voxels. A specific automatic routine was written to process data from the point clouds to the visualization of clustering results. The analysis of results showed good performance for this approach, with the overall accuracy in classifying wood components of trees ranging from 95% to 97%. The largest accuracies were observed for branches larger than 5 cm in diameter whereas the accuracy of classification dropped, as expected, for branches with diameter lower than 3 cm.
The results suggest that the proposed method can be conveniently used to extract woody components from point clouds of broad leaved non-deciduous trees.
We present GuideScan software for the design of CRISPR guide RNA libraries that can be used to edit coding and noncoding genomic regions. GuideScan produces high-density sets of guide RNAs (gRNAs) ...for single- and paired-gRNA genome-wide screens. We also show that the trie data structure of GuideScan enables the design of gRNAs that are more specific than those designed by existing tools.
In the last decades, several clinical scores have been developed and currently used to improve the diagnosis and risk management of patients with suspected acute appendicitis (AA). However, some of ...them exhibited different values of sensitivity and specificity. We conducted a systematic review and metanalysis of epidemiological studies, which compared RIPASA and Alvarado scores for the diagnosis of AA. This systematic review was conducted using PubMed and Web of Science databases. Selected studies had to compare RIPASA and Alvarado scores on patients with suspected AA and reported diagnostic parameters. Summary estimates of sensitivity and specificity were calculated by the Hierarchical Summary Receiver Operating Curve (HSROC) using STATA 17 (STATA Corp, College Station, TX) and MetaDiSc (version 1.4) software. We included a total of 33 articles, reporting data from 35 studies. For the Alvarado score, the Hierarchical Summary Receiver Operating Curve (HSROC) model produced a summary sensitivity of 0.72 (95%CI = 0.66-0.77), and a summary specificity of 0.77 (95%CI = 0.70-0.82). For the RIPASA score, the HSROC model produced a summary sensitivity of 0.95 (95%CI = 0.92-0.97), and a summary specificity of 0.71 (95%CI = 0.60-0.80). RIPASA score has higher sensitivity, but low specificity compared to Alvarado score. Since these scoring systems showed different sensitivity and specificity parameters, it is still necessary to develop novel scores for the risk assessment of patients with suspected AA.
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