Surveillance in the lab? : How datafication is changing the research landscape.

Scientific research is increasingly becoming datafied through the use of electronic lab notebooks and smart instruments. This has significant implications for surveillance at work and research itself. [Image: see text]

Messing with Merton: The intersection between open science practices and Mertonian values.

Although adherence to Mertonian values of science (i.e., communism, universalism, organized skepticism, disinterestedness) is desired and promoted in academia, such adherence can cause friction with the normative structures and practices of Open Science.

Covid-19 and the need for more history and philosophy of RNA.

RNA is central to the COVID-19 pandemic-it shapes how the SARS Coronavirus 2 (SARS-CoV-2) behaves, and how researchers investigate and fight it. However, RNA has received relatively little attention in the history and philosophy of the life sciences. By analysing RNA biology in more detail, philosophers and historians of science could gain new and powerful tools to assess the current pandemic, and the biological sciences more generally.

Characterizing scientific failure: Putting the replication crisis in context.

A better understanding of the nature and causes of failure in research could inform policies to improve the reproducibility of biomedical research.

The anti-vaccination debate and the microbiome: How paradigm shifts in the life sciences create new challenges for the vaccination debate.

Anti‐vaccine activists misuse findings from microbiome research to push their agenda. It requires a concerted response by the scientific community to confront the misinformation. [Image: see text]

Trust in Science: CRISPR-Cas9 and the Ban on Human Germline Editing.

In 2015 scientists called for a partial ban on genome editing in human germline cells. This call was a response to the rapid development of the CRISPR-Cas9 system, a molecular tool that allows researchers to modify genomic DNA in living organisms with high precision and ease of use. Importantly, the ban was meant to be a trust-building exercise that promises a 'prudent' way forward.

Viruses as living processes.

The view that life is composed of distinct entities with well-defined boundaries has been undermined in recent years by the realisation of the near omnipresence of symbiosis. What had seemed to be intrinsically stable entities have turned out to be systems stabilised only by the interactions between a complex set of underlying processes (Dupré, 2012). This has not only presented severe problems for our traditional understanding of biological individuality but has also led some to claim that we need to switch to a process ontology to be able adequately to understand biological systems.

The double-stranded RNA binding domain of human Dicer functions as a nuclear localization signal.

Dicer is a key player in microRNA (miRNA) and RNA interference (RNAi) pathways, processing miRNA precursors and double-stranded RNA into ∼21-nt-long products ultimately triggering sequence-dependent gene silencing. Although processing of substrates in vertebrate cells occurs in the cytoplasm, there is growing evidence suggesting Dicer is also present and functional in the nucleus. To address this possibility, we searched for a nuclear localization signal (NLS) in human Dicer and identified its C-terminal double-stranded RNA binding domain (dsRBD) as harboring NLS activity.

Creating parts that allow for rational design: synthetic biology and the problem of context-sensitivity.

The parts-based engineering approach in synthetic biology aims to create pre-characterised biological parts that can be used for the rational design of novel functional systems. Given the context-sensitivity of biological entities, a key question synthetic biologists have to address is what properties these parts should have so that they give a predictable output even when they are used in different contexts. In the first part of this paper I will analyse some of the answers that synthetic biologists have given to this question and claim that the focus of these answers on parts and their properties does not allow us to tackle the problem of context-sensitivity.

The cytotoxic styryl lactone goniothalamin is an inhibitor of nucleocytoplasmic transport.

An in vivo nuclear export assay (immunostaining of Rio2 in HeLa cells) demonstrated that (R)-goniothalamin is an inhibitor of nucleocytoplasmic transport above 500 nM, which was rationalized also by molecular modeling. The cytotoxic styryl lactone natural product was prepared via an enantioselective Cr(III) catalyzed hetero Diels-Alder reaction and a Sonogashira coupling. A series of analogs was synthesized and only the oxidized goniothalamin derivative featuring an alkyne spacer was found active.

Anguinomycins and derivatives: total syntheses, modeling, and biological evaluation of the inhibition of nucleocytoplasmic transport.

The preparation of the polyketide natural products anguinomycin C and D is reported based on key steps such as Negishi stereoinversion cross coupling, Jacobsen Cr(III)-catalyzed Hetero Diels-Alder reaction, Evans B-mediated syn-aldol chemistry, and B-alkyl Suzuki-Miyaura cross coupling. The configuration of both natural products was established as (5R,10R,16R,18S,19R,20S). Biological evaluation demonstrated that these natural products are inhibitors of the nuclear export receptor CRM1, leading to shutdown of CRM1-mediated nuclear protein export at concentrations above 10 nM.

Orchestrating nuclear envelope disassembly and reassembly during mitosis.

Cell division in eukaryotes requires extensive architectural changes of the nuclear envelope (NE) to ensure that segregated DNA is finally enclosed in a single cell nucleus in each daughter cell. Higher eukaryotic cells have evolved 'open' mitosis, the most extreme mechanism to solve the problem of nuclear division, in which the NE is initially completely disassembled and then reassembled in coordination with DNA segregation. Recent progress in the field has now started to uncover mechanistic and molecular details that underlie the changes in NE reorganization during open mitosis.

The conserved transmembrane nucleoporin NDC1 is required for nuclear pore complex assembly in vertebrate cells.

Nuclear pore complexes (NPCs) are large proteinaceous channels embedded in the nuclear envelope (NE), through which exchange of molecules between the nucleus and cytosol occurs. Biogenesis of NPCs is complex and poorly understood. In particular, almost nothing is known about how NPCs are anchored in the NE.

Nuclear envelope localization of human UNC84A does not require nuclear lamins.

The SUN proteins are a conserved family of proteins in eukaryotes. Human UNC84A (Sun1) is a homolog of Caenorhabditis elegans UNC-84, a protein involved in nuclear anchorage and migration. We have analyzed targeting of UNC84A to the nuclear envelope (NE) and show that the N-terminal 300 amino acids are crucial for efficient NE localization of UNC84A whereas the conserved C-terminal SUN domain is not required.

Leucine-rich nuclear-export signals: born to be weak.

CRM1 mediates the nuclear export of proteins exposing leucine-rich nuclear-export signals (NESs). Most NESs bind to CRM1 with relatively low affinity. Recently, higher-affinity NESs were selected from a 15-mer random peptide library.

Transportin2 functions as importin and mediates nuclear import of HuR.

The RanGTP-binding nuclear transport receptors transportin1 (TRN1) and transportin2 (TRN2) are highly similar in sequence but are reported to function in nuclear import and export, respectively. Here we show that TRN2 possesses properties of a nuclear import receptor. TRN1/2 both interacted with a similar set of RNA-binding proteins in a RanGTP-sensitive manner.

Nuclear export of microRNA precursors.

MicroRNAs (miRNAs), which function as regulators of gene expression in eukaryotes, are processed from larger transcripts by sequential action of nuclear and cytoplasmic ribonuclease III-like endonucleases. We show that Exportin-5 (Exp5) mediates efficient nuclear export of short miRNA precursors (pre-miRNAs) and that its depletion by RNA interference results in reduced miRNA levels. Exp5 binds correctly processed pre-miRNAs directly and specifically, in a Ran guanosine triphosphate-dependent manner, but interacts only weakly with extended pre-miRNAs that yield incorrect miRNAs when processed by Dicer in vitro.