Nuclear bodies: concentrating at an aqueous site.

The second FASEB conference on Nuclear Bodies: Hubs of Genome Activity was held June 2-7, 2024, at Niagara Falls, NY. The central theme was how these protein and RNA-protein complexes that are situated in the nucleus outside the genome support and regulate gene expression. Topics included their relevance to disease, especially cancer, their molecular dynamics, and their phase separation transition properties.

Tributaries of the 2023 Nobel Prize in Physiology or Medicine, and lessons learned.

Almost without exception, scientific breakthroughs are not epistemological orphans. Historians of science have developed a body of scholarship on this, and the cases arising in our era continue to confirm the phenomenon. The work by Katalin Karikó and Drew Weissman that proved foundational for the subsequent development of mRNA vaccines for COVID-19 had its antecedent roots yet is also a striking example of both serendipity and their persistence.

Nucleolar structure connects with global nuclear organization.

The nucleolus is a multifunctional nuclear body. To tease out the roles of nucleolar structure without resorting to the use of multi-action drugs, we knocked down the RNA polymerase I subunit RPA194 in HeLa cells by siRNA. Loss of RPA194 resulted in nucleolar-structural segregation and effects on both nucleolus-proximal and distal-nuclear components.

An Intermittent Cytochemist.

I wanted to be a cytochemist but encountered detours and then, in some of my work, became one of a different kind than classically defined. I recount this here to discourage young scientists from regarding cytochemistry as something that peaked in the past, but rather to be viewed as an entirely new form of the discipline, and so rich with opportunities. (J Histochem Cytochem 71: 475-480, 2023).

Nucleolar structure connects with global nuclear organization.

The nucleolus is a multi-functional nuclear body. To tease out the roles of nucleolar structure without resorting to multi-action drugs, we knocked down RNA polymerase I subunit RPA194 in HeLa cells by siRNA. Loss of RPA194 resulted in nucleolar structural segregation and effects on both nucleolus-proximal and distal nuclear components.

"Mechanism"-a misused term?

Many of us use the term "mechanism" when we shouldn't. Here I offer some thoughts, especially as guidance for young scientists.

A conundrum in 3-D genome organization and expression?

Recent advances in our understanding of how the genome is folded within the nucleus have included cases in which this positioning correlates with gene expression, either positively or negatively. But is the 3-D location of a gene a cause or an effect of its expression? In this I articulate the problem and then cite as guideposts recent cases where causation has indeed been arguably established. The hope is to critically illuminate this issue for continued consideration in this important, evolving field.

The nuclear bodies conference: Hubs of genomic activity, June 24-28, Western Shore, Nova Scotia, Canada.

This conference brought together leaders in the investigation of various bodies that populate the nucleus, a field that complements research on chromosome biology. These nuclear bodies had been receiving increasing attention as hubs of genome activity and the new findings reported at the conference strongly confirmed and significantly expanded this principle.

Dissecting cellular diversity of cortical GABAergic cells across multiple modalities: A turning point in neuronal taxonomy.

Decoding the complexity of the brain requires an understanding of the architecture, function, and development of its neuronal circuits. Neuronal classifications that group neurons based on specific features/behaviors have become essential to further analyze the different subtypes in a systematic and reproducible way. A comprehensive taxonomic framework, accounting for multiple defining and quantitative features, will provide the reference to infer generalized rules for cells ascribed to the same neuronal type, and eventually predict cellular behaviors, even in the absence of experimental measures.

The UVSSA protein is part of a genome integrity homeostasis network with links to transcription-coupled DNA repair and ATM signaling.

SignificanceTranscription-coupled repair (TCR) involves four core proteins: CSA, CSB, USP7, and UVSSA. CSA and CSB are mutated in the severe human neurocutaneous disease Cockayne syndrome. In contrast UVSSA is a mild photosensitive disease in which a mutated protein sequence prevents recruitment of USP7 protease to deubiquitinate and stabilize CSB.