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The very first days of mammalian embryonic development are accompanied by epigenetic reprogramming and extensive changes in nuclear organization. In particular, genomic regions located at the periphery of the nucleus, termed lamina-associated domains (LADs), undergo major rearrangements after fertilization. However, the role of LADs in regulating gene expression as well as the interplay with various chromatin marks during preimplantation development remains elusive. In this study, we obtained single-cell LAD profiles coupled with the corresponding gene expression readout throughout the first days of mouse development. We detect extensive cell-cell LAD variability at the 2-cell stage, which surprisingly does not seem to functionally affect gene expression. This suggests an unusual uncoupling between 3D-nuclear genome organization and gene expression during totipotent developmental stages. By analyzing LAD dynamics and chromatin states across early developmental stages in an allelic-specific manner, we identify genomic regions that transiently detach from the nuclear lamina and are enriched by non-canonical H3K27me3. Upon maternal knock-out of a component of the Polycomb repressive complex 2 and concomitant loss of H3K27me3 during early embryogenesis, these regions relocate to the lamina at the 2-cell stage. Our results suggest that H3K27me3 is the prime determinant in establishing the atypical distribution of the genome at the nuclear periphery during the first days of embryonic development. This study provides insight into the molecular mechanisms regulating nuclear organization of parental genomes during very early mammalian development.

Spatial genome organization is considered to play an important role in mammalian cells, by guiding gene expression programs and supporting lineage specification. Yet it is still an outstanding question in the field what the direct impact of spatial genome organization on gene expression is. To elucidate this relationship further, we have recently developed scDamT-seq, a method that simultaneously quantifies protein-DNA interactions and transcriptomes in single cells. This method efficiently combines two preexisting methods: DamID for measuring protein-DNA contacts and CEL-Seq2 for quantification of the transcriptome in single cells. scDamT-seq has been successfully applied to measure DNA contacts with the nuclear lamina, while at the same time revealing the effect of these contacts on gene expression. This method is applicable to many different proteins of interest and can thereby aid in studying the relationship between protein-DNA interactions and gene expression in single cells.

We investigate how firms adjust their target quality levels when they - or their competitors - become subject to an information disclosure requirement. Our setting is the U.S. airline industry, where all large domestic carriers are required to report their on-time performance (OTP). OTP is measured by comparing a flight’s actual arrival time to its scheduled arrival time, which is chosen by the airline. Therefore, airlines can improve their OTP by simply increasing their scheduled flight times. We study three airlines which become subject to the disclosure requirement and find that they lengthen their schedule times by 1.4 min on average. Moreover, other airlines also increase their schedule times on routes where they compete with newly reporting airlines, by about 2.3 min, while actual flight times remain unchanged. While these numbers are small, the longer schedule times translate into a 15% improvement in OTP for previously reporting airlines. We conclude that newly reporting airlines and their direct competitors adjust their quality targets when they become subject to quality disclosure, which improves their reported quality without improving the actual time that it takes to travel from gate to gate.

Since 1987, the U.S. Department of Transportation (DOT) has required all large domestic airlines to report on the on-time performance of their flights. Using the data collected by the DOT, we analyze how schedule times, actual flight times and on-time performance have changed in the industry between 1990 and 2016. We find that schedule times have increased in most years, with the largest increases occurring after 2008. In 2016, schedules were about 8 minutes longer than they were in 1990, for flights by the same airline on the same route in the same month of the year. We find that actual flight times and total travel times have also increased over this period but by less than the increase in schedule times and with the gap growing over time. This has resulted in reduced arrival delays despite the fact that flights are taking longer to complete. We discuss the implications of these findings for quality provision and information disclosure within the airline industry.

Protein-DNA interactions are essential for establishing cell type-specific chromatin architecture and gene expression. We recently developed scDam&T-seq, a multi-omics method that can simultaneously quantify protein-DNA interactions and the transcriptome in single cells. The method effectively combines two existing methods: DNA adenine methyltransferase identification (DamID) and CEL-Seq2. DamID works through the tethering of a protein of interest (POI) to the Escherichia coli DNA adenine methyltransferase (Dam). Upon expression of this fusion protein, DNA in proximity to the POI is methylated by Dam and can be selectively digested and amplified. CEL-Seq2, in contrast, makes use of poly-dT primers to reverse transcribe mRNA, followed by linear amplification through in vitro transcription. scDam&T-seq is the first technique capable of providing a combined readout of protein-DNA contact and transcription from single-cell samples. Once suitable cell lines have been established, the protocol can be completed in 5 d, with a throughput of hundreds to thousands of cells. The processing of raw sequencing data takes an additional 1-2 d. Our method can be used to understand the transcriptional changes a cell undergoes upon the DNA binding of a POI. It can be performed in any laboratory with access to FACS, robotic and high-throughput-sequencing facilities.

The nuclear lamina (NL) is a thin meshwork of filaments that lines the inner nuclear membrane, thereby providing a platform for chromatin binding and supporting genome organization. Genomic regions contacting the NL are lamina associated domains (LADs), which contain thousands of genes that are lowly transcribed, and enriched for repressive histone modifications. LADs are dynamic structures that shift spatial positioning in accordance with cell-type specific gene expression changes during differentiation and development. Furthermore, recent studies have linked the disruption of LADs and alterations in the epigenome with the onset of diseases such as cancer. Here we focus on the role of LADs and the NL in gene regulation during development and cancer.

Assessment of the observing system fitness for HAB warning bulletin in the Atlantic

This work received support and funding from • The BOHAB project (Biological Oceanography of Harmful Algal Blooms off the west coast of Ireland) through the National Development Plan 2000 – 2006 with the support of the Marine Institute and the Marine RTDI (Research, Technology, Development and Innovation) Measure, Productive Sector Operational Programme, Grant-aid Agreement No. ST/02/01. • the ASIMUTH project (Applied simulations and Integrated modelling for the understanding of toxic and harmful algal blooms) through the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) for Research and Technological Development - EC FP7 Programme, Space Theme, Grant Agreement No. 261860 • the MyOcean 2 project through the EC FP7 Programme, Space Theme, Grant Agreement No. 283367 • the AtlantOS project through the European Union's Horizon 2020 research and innovation programme, Grant Agreement No. 633211 • The PRIMROSE (Predicting the impact of regional scale events on the aquaculture sector) project, co-financed by the European Regional Development Fund through the Interreg Atlantic Area Programme, EAPA_182/2016 • The CoCliME (Co-development of climate services for adaptation to changing marine ecosystems) project is part of the European Research Area for Climate Services (ERA4CS), an ERA-NET initiated by JPI Climate, and funded by EPA (IE), ANR (FR), BMBF (DE), UEFISCDI (RO), RCN (NO) and FORMAS (SE), with co-funding by the European Union (Grant Agreement No. 690462)., This document describes the procedural steps in creating an information product focused on toxic and harmful phytoplankton. The product is an online Harmful Algal Bloom (HAB) bulletin for aquaculturists, who can face serious operational challenges in the days after a HAB event. Data from satellite, numerical hydrodynamic models and In-situ ocean observations are organised and presented into visual information products. These products are enhanced through local expert evaluation and their interpretation is summarised in the bulletin. This document aims to provide both process overviews (the “what” of the Best Practice in producing the bulletins) and detail procedures (the “how” of the Best Practice”) so that the bulletins may be replicated in other geographic regions., European Commission

Prokaryotes encode various host defense systems that provide protection against mobile genetic elements. Restriction–modification (R–M) and CRISPR–Cas systems mediate host defense by sequence specific targeting of invasive DNA. T-even bacteriophages employ covalent modifications of nucleobases to avoid binding and therefore cleavage of their DNA by restriction endonucleases. Here, we describe that DNA glucosylation of bacteriophage genomes affects interference of some but not all CRISPR–Cas systems. We show that glucosyl modification of 5-hydroxymethylated cytosines in the DNA of bacteriophage T4 interferes with type I-E and type II-A CRISPR–Cas systems by lowering the affinity of the Cascade and Cas9–crRNA complexes for their target DNA. On the contrary, the type V-A nuclease Cas12a (also known as Cpf1) is not impaired in binding and cleavage of glucosylated target DNA, likely due to a more open structural architecture of the protein. Our results suggest that CRISPR–Cas systems have contributed to the selective pressure on phages to develop more generic solutions to escape sequence specific host defense systems.

BackgroundInsufficient postmatch recovery in elite players may cause an increased risk of injuries, illnesses and non-functional over-reaching.ObjectiveTo evaluate postmatch recovery time courses of physical performance and biochemical markers in team ball sport players.Study designSystematic review.Data sourcesPubMed and Web of Science.Eligibility criteria for selecting studiesThis systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Critical Review Form for Quantitative Studies was used to evaluate quality. Studies were included if they met the following criteria: (1) original research evaluated players’ physical recovery postmatch; (2) team/intermittent sports; and (3) at least two postmeasurements were compared with baseline values.ResultsTwenty-eight studies were eligible. Mean methodological quality was 11.2±1.11. Most used performance tests and biochemical markers were the countermovement jump test, sprint tests and creatine kinase (CK), cortisol (C) and testosterone (T), respectively.Summary/conclusionsThe current evidence demonstrates that underlying mechanisms of muscle recovery are still in progress while performance recovery is already reached. CK recovery time courses are up to ≥72 hours. Soccer and rugby players need more time to recover for sprint performance, CK and C in comparison to other team ball sports. There are more high-quality studies needed regarding recovery in various team sports and recovery strategies on an individual level should be evaluated.Clinical relevanceOngoing insufficient recovery can be prevented by the use of the presented recovery time courses as specific practical recovery guidelines.

Disclosure programs exist in many industries in which consumers are poorly informed about product quality. We study a disclosure program for airline on-time performance, which ranks airlines based on the fraction of their flights that arrive less than 15 minutes late. The program creates incentives for airlines to focus their efforts on flights close to this threshold. We find that firms in this industry are heterogeneous in how they respond to these incentives. Moreover, this heterogeneity correlates with internal firm characteristics. Our findings highlight the importance of interactions between incentives created by a disclosure program and firms' internal organizational practices. (JEL D22, L15, L25, L93)