Discovery and significance of protein-protein interactions in health and disease.

The identification of individual protein-protein interactions (PPIs) began more than 40 years ago, using protein affinity chromatography and antibody co-immunoprecipitation. As new technologies emerged, analysis of PPIs increased to a genome-wide scale with the introduction of intracellular tagging methods, affinity purification (AP) followed by mass spectrometry (MS), and co-fractionation MS (CF-MS). Now, combining the resulting catalogs of interactions with complementary methods, including crosslinking MS (XL-MS) and cryogenic electron microscopy (cryo-EM), helps distinguish direct interactions from indirect ones within the same or between different protein complexes.

Proteolytic regulation of calcium channels - avoiding controversy.

The publication of papers containing data obtained with suboptimal rigor in the experimental design and choice of key reagents, such as antibodies, can result in a lack of reproducibility and generate controversy that can both needlessly divert resources and, in some cases, damage public perception of the scientific enterprise. This exemplary paper by Buonarati (2018) shows how a previously published, potentially important paper on calcium channel regulation falls short of the necessary mark, and aims to resolve the resulting controversy.

Redo college intro science.

The rapid development of highly effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was a monumental achievement, yet a large fraction of the public rejected this means of defense, resulting in far too many preventable deaths. This response reflects a shocking failure of science to produce citizens who understand and respect scientific evidence, and it demands a rethinking of science education goals.

Why science education is more important than most scientists think.

The COVID-19 pandemic has revealed that a shockingly large fraction of the public is willing to ignore scientific judgements on issues such a vaccines and mask wearing. For far too many, scientific findings are viewed as what scientists believe, rather than as the product of an elaborate community process that produces reliable knowledge. This widespread misunderstanding should serve as a wake-up call for scientists, clearly demonstrating that the standard way that we teach science - as a large collection of "facts" that scientists have discovered about the world - needs major change.

In vitro reconstitution of DNA replication initiated by genetic recombination: a T4 bacteriophage model for a type of DNA synthesis important for all cells.

Using a mixture of 10 purified DNA replication and DNA recombination proteins encoded by the bacteriophage T4 genome, plus two homologous DNA molecules, we have reconstituted the genetic recombination-initiated pathway that initiates DNA replication forks at late times of T4 bacteriophage infection. Inside the cell, this recombination-dependent replication (RDR) is needed to produce the long concatemeric T4 DNA molecules that serve as substrates for packaging the shorter, genome-sized viral DNA into phage heads. The five T4 proteins that catalyze DNA synthesis on the leading strand, plus the proteins required for lagging-strand DNA synthesis, are essential for the reaction, as are a special mediator protein (gp59) and a Rad51/RecA analogue (the T4 UvsX strand-exchange protein).

Publishing confirming and non-confirming data.

This editorial introduces the Preclinical Reproducibility and Robustness channel on F1000Research, which has been created to encourage and facilitate open and transparent publication and discussion of confirmatory and non-confirmatory studies in biomedical research.

Rescuing US biomedical research from its systemic flaws.

The long-held but erroneous assumption of never-ending rapid growth in biomedical science has created an unsustainable hypercompetitive system that is discouraging even the most outstanding prospective students from entering our profession--and making it difficult for seasoned investigators to produce their best work. This is a recipe for long-term decline, and the problems cannot be solved with simplistic approaches. Instead, it is time to confront the dangers at hand and rethink some fundamental features of the US biomedical research ecosystem.