After Recess: Historical Practice, Textual Ambiguity, and Constitutional Adverse Possession

The Supreme Court’s interpretation of the Recess Appointments Clause in NLRB v. Noel Canning stands as one of the Supreme Court’s most significant endorsements of the relevance of “historical gloss” to the interpretation of the separation of powers. This Article uses the decision as a vehicle for examining the relationship between interpretive methodology and historical practice, and between historical practice and textual ambiguity. As the Article explains, Noel Canning exemplifies how the constitutional text, perceptions about clarity or ambiguity, and “extra-textual” considerations such as historical practice operate interactively rather than as separate elements of interpretation. The decision also provides a useful entry point into critically analyzing the concept of constitutional “liquidation,” which the majority in Noel Canning seemed to conflate with historical gloss but which seems more consistent with the approach to historical practice reflected in Justice Scalia’s concurrence in the judgment. Finally, this Article argues that the historical gloss approach, when applied cautiously and with sensitivity to the potential concerns raised by Justice Scalia and others, is not vulnerable to the charge of licensing executive aggrandizement by “adverse possession.

Human genetics and genomics meetings going virtual: practical lessons learned from two international meetings in early 2020

The recent coronavirus disease 2019 (COVID-19) pandemic has caused worldwide disruption which also extends to the arena of scientific meetings around the world. Here, we explore the lessons learned from moving two human genetics and genomics meetings quickly to an online format in early 2020. The tips presented herein may be useful not only for future virtual meetings but may also enrich future physical if not hybrid meetings once they resum

Ethical ePunditry? The role of expertise in online opinion-making

The use of blogs to communicate ideas, opinions and knowledge has grown over the past two decades. Social media platforms have facilitated the rise of hybridised forms of written, verbal and visual communication and opinion-making, output which we designate as ‘ePunditry’. The connectivity of Web 2.0 technologies has meant that anyone with access to the internet can now write and speak publicly about a subject that interests them, whether or not they are regarded as an expert in their area. However, with anyone being able to declare their opinion on the topic of their choice, can this form of public knowledge be considered ethical? This article reflects on the production and ethical dimensions of ePunditry across four distinct subject domains: parenting, science, sport and fashion. Using data from 15 interviews with ePundits, it explores the paradigm shift surrounding expert knowledge in the internet age, examining the multifaceted ways in which expertise is now communicated

Regulatory interdependence of myeloid transcription factors revealed by Matrix RNAi analysis

The knockdown of 78 transcription factors in differentiating human THP-1 cells using matrix RNAi reveals their interdependenc

In‐Depth Extracorporeal Cardiopulmonary Resuscitation in Adult Out‐of‐Hospital Cardiac Arrest

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RECLU:a pipeline to discover reproducible transcriptional start sites and their alternative regulation using capped analysis of gene expression (CAGE)

BACKGROUND: Next generation sequencing based technologies are being extensively used to study transcriptomes. Among these, cap analysis of gene expression (CAGE) is specialized in detecting the most 5’ ends of RNA molecules. After mapping the sequenced reads back to a reference genome CAGE data highlights the transcriptional start sites (TSSs) and their usage at a single nucleotide resolution. RESULTS: We propose a pipeline to group the single nucleotide TSS into larger reproducible peaks and compare their usage across biological states. Importantly, our pipeline discovers broad peaks as well as the fine structure of individual transcriptional start sites embedded within them. We assess the performance of our approach on a large CAGE datasets including 156 primary cell types and two cell lines with biological replicas. We demonstrate that genes have complicated structures of transcription initiation events. In particular, we discover that narrow peaks embedded in broader regions of transcriptional activity can be differentially used even if the larger region is not. CONCLUSIONS: By examining the reproducible fine scaled organization of TSS we can detect many differentially regulated peaks undetected by previous approaches

The miR-17-5p microRNA is a key regulator of the G1/S phase cell cycle transition

Novel targets of the oncogenic miR-17-92 cluster have been identified and the mechanism of regulation of proliferation at the G1/S phase cell cycle transition via the miR-17-5p microRNA has been elucidated

Alternate transcription of the Toll-like receptor signaling cascade

BACKGROUND: Alternate splicing of key signaling molecules in the Toll-like receptor (Tlr) cascade has been shown to dramatically alter the signaling capacity of inflammatory cells, but it is not known how common this mechanism is. We provide transcriptional evidence of widespread alternate splicing in the Toll-like receptor signaling pathway, derived from a systematic analysis of the FANTOM3 mouse data set. Functional annotation of variant proteins was assessed in light of inflammatory signaling in mouse primary macrophages, and the expression of each variant transcript was assessed by splicing arrays. RESULTS: A total of 256 variant transcripts were identified, including novel variants of Tlr4, Ticam1, Tollip, Rac1, Irak1, 2 and 4, Mapk14/p38, Atf2 and Stat1. The expression of variant transcripts was assessed using custom-designed splicing arrays. We functionally tested the expression of Tlr4 transcripts under a range of cytokine conditions via northern and quantitative real-time polymerase chain reaction. The effects of variant Mapk14/p38 protein expression on macrophage survival were demonstrated. CONCLUSION: Members of the Toll-like receptor signaling pathway are highly alternatively spliced, producing a large number of novel proteins with the potential to functionally alter inflammatory outcomes. These variants are expressed in primary mouse macrophages in response to inflammatory mediators such as interferon-γ and lipopolysaccharide. Our data suggest a surprisingly common role for variant proteins in diversification/repression of inflammatory signaling

Conserved temporal ordering of promoter activation implicates common mechanisms governing the immediate early response across cell types and stimuli

Conserved temporal precedence between IEGs (light blue nodes) and other protein-coding genes (green nodes) is shown by directed edges. Genes annotated with the GO term 'response to endoplasmic reticulum stress' (GO:003497) have a red rectangle around the gene name; red squares indicate genes with CAGE clusters enriched for XBP1 transcription factor binding sites