Treeio: An R Package for Phylogenetic Tree Input and Output with Richly Annotated and Associated Data.

Phylogenetic trees and data are often stored in incompatible and inconsistent formats. The outputs of software tools that contain trees with analysis findings are often not compatible with each other, making it hard to integrate the results of different analyses in a comparative study. The treeio package is designed to connect phylogenetic tree input and output. It supports extracting phylogenetic trees as well as the outputs of commonly used analytical software. It can link external data to phylogenies and merge tree data obtained from different sources, enabling analyses of phylogeny-associated data from different disciplines in an evolutionary context. Treeio also supports export of a phylogenetic tree with heterogeneous-associated data to a single tree file, including BEAST compatible NEXUS and jtree formats; these facilitate data sharing as well as file format conversion for downstream analysis. The treeio package is designed to work with the tidytree and ggtree packages. Tree data can be processed using the tidy interface with tidytree and visualized by ggtree. The treeio package is released within the Bioconductor and rOpenSci projects. It is available at https://www.bioconductor.org/packages/treeio/.

What Can Utilities Expect from New Lead Fifth-Liter Sampling Based on Historic First-Draw Data?

The United States Environmental Protection Agency recently released their most sweeping overhaul to the Lead and Copper Rule in three decades. One of the most significant changes is requiring a fifth-liter (L5) sample at homes with lead service lines (LSLs) rather than the original first-liter (L1) sample for a demonstration of compliance with water lead level (WLL) limits. We analyzed sequential sampling data from three large water systems and compliance data from Michigan utilities-which base compliance on the 90th percentile of the greater of L1 and L5 samples-to evaluate whether L5 WLLs better represent water in contact with LSLs and to explore regulatory impacts of including L5 samples in compliance monitoring. The sequential sampling data demonstrated that it is impossible to use a single sample volume within a sequential profile to universally capture the volume of water in an LSL. While L5 is not always a reliable indicator of water in contact with an LSL, Michigan compliance data showed that the L5 sample is more likely to be from an LSL and can identify utilities that benefit from an improved corrosion control treatment. Michigan compliance data indicate that it is likely that L5 sampling will result in more systems having a higher 90th percentile WLL and that a high proportion of the systems likely to exceed regulatory action levels based on L5 samples can be identified through a retrospective analysis of historic L1 data. The impact of the switch to L5 sampling on the effectiveness of corrosion control treatment over time has yet to be determined.

Nucleoporins in cardiovascular disease.

Cardiovascular disease is a pressing health problem with significant global health, societal, and financial burdens. Understanding the molecular basis of polygenic cardiac pathology is thus essential to devising novel approaches for management and treatment. Recent identification of uncharacterized regulatory functions for a class of nuclear envelope proteins called nucleoporins offers the opportunity to understand novel putative mechanisms of cardiac disease development and progression. Consistent reports of nucleoporin deregulation associated with ischemic and dilated cardiomyopathies, arrhythmias and valvular disorders suggests that nucleoporin impairment may be a significant but understudied variable in cardiopathologic disorders. This review discusses and converges existing literature regarding nuclear pore complex proteins and their association with cardiac pathologies, and proposes a role for nucleoporins as facilitators of cardiac disease.

Nucleoporin insufficiency disrupts a pluripotent regulatory circuit in a pro-arrhythmogenic stem cell line.

Nucleoporins have been reported to regulate pluripotent biology, but how they do so remains partially characterized. This study examined the effects of nup155 gene disruption on mouse embryonic stem cells to gain insights into possible mechanisms by which nucleoporins regulate pluripotency in a pro-arrhythmogenic stem cell line. Embryonic stem cells with gene-trapped nup155 exhibited aberrant colony morphology underscored by abnormal transcriptome remodeling. Bioinformatic analysis of whole transcriptome data from nup155+/- embryonic stem cells revealed changes in a variety of non-coding RNA elements, with significant under expression of miR291a, miR291b, miR293, and miR294. These miRNAs are members of the larger regulatory miR290-295 cluster that regulates pluripotency and are controlled by the canonical stem cell-related factors SOX2, OCT4, and NANOG. Expression analysis of these factors revealed downregulation in all three, supported by biochemical profiling and image analysis. These data implicate disruption of the miR-SOX2/OCT4/NANOG regulatory circuit occurs downstream of nup155 gene lesion.