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The mammalian Zc3h12a/MCPIP1/Regnase‐1, an extensively studied regulator of inflammatory response, is the founding member of a ribonuclease family, which includes proteins related by the presence of the so‐called Zc3h12a‐like NYN domain. Recently, several related proteins have been described in Caenorhabditis elegans, allowing comparative evaluation of molecular functions and biological roles of...
Galectin‐3 and LTB4 are pro‐inflammatory molecules recently shown to directly cause insulin resistance in mouse and human cells. They are highly expressed in the obese state, and can be targeted both genetically and pharmacologically to improve insulin sensitivity in vivo. This expands on previous research showing that targeting inflammatory cytokines can be insulin sensitizing in animal models....
Cell size impacts cellular and organismal function through metabolism: The cover illustrates that cell size is intimately connected to mitochondrial metabolism and cellular fitness. In article 1700058, Mikael Björklund and co‐workers discuss how metabolism is often cell‐size dependent due to biophysical constrains imposed by cell size and shape. As cell size defines cellular fitness, this has potential...
The maintenance of cell size homeostasis has been studied for years in different cellular systems. With the focus on ‘what regulates cell size’, the question ‘why cell size needs to be maintained’ has been largely overlooked. Recent evidence indicates that animal cells exhibit nonlinear cell size dependent growth rates and mitochondrial metabolism, which are maximal in intermediate sized cells within...
In this review, we discuss how two evolutionarily conserved pathways at the interface of DNA replication and repair, template switching and break‐induced replication, lead to the deleterious large‐scale expansion of trinucleotide DNA repeats that cause numerous hereditary diseases. We highlight that these pathways, which originated in prokaryotes, may be subsequently hijacked to maintain long DNA...
After a vertebrate dies, many of its organ systems, tissues, and cells remain functional while its body no longer works as a whole. We define this state as the “twilight of death” − the transition from a living body to a decomposed corpse. We claim that the study of the twilight of death is important to ethical, legal and medical science. We examined gene expression at the twilight of death in the...
The functions of the Bloom syndrome helicase (BLM) and its orthologs are well characterized in mitotic DNA damage repair, but their roles within the context of meiotic recombination are less clear. In meiotic recombination, multiple repair pathways are used to repair meiotic DSBs, and current studies suggest that BLM may regulate the use of these pathways. Based on literature from Saccharomyces cerevisiae...
Recently, the group of McBride reported a stunning observation regarding peroxisome biogenesis: newly born peroxisomes are hybrids of mitochondrial and ER‐derived pre‐peroxisomes. What was stunning? Studies performed with the yeast Saccharomyces cerevisiae had convincingly shown that peroxisomes are ER‐derived, without indications for mitochondrial involvement. However, the recent finding using fibroblasts...
Precarious maintenance of simple DNA repeats in eukaryotes:In article number 1700077, Sergei M. Mirkin and co‐workers present a model for replication fork uncoupling at expandable (GAA)n repeats responsible for Friedreich's ataxia. Lagging strand synthesis by DNA polymerase δ (blue oval) is stalled when the repetitive 5‵‐flap of an Okazaki fragment (green strand) folds forward forming a triplex with...
Can mammalian mothers adaptively control the sex of their offspring? The influential Trivers‐Willard hypothesis (TWH) proposes that when maternal condition increases the fitness of sons more than that of daughters, the proportion of sons produced should increase with maternal condition. Studies of mammals, however, often fail to support this hypothesis. This article highlights recent advances, including...
Here we review concepts related to an ensemble description of G‐protein‐coupled receptors (GPCRs). The ensemble is characterized by both inactive and active states, whose equilibrium populations and exchange rates depend sensitively on ligand, environment, and allosteric factors. This review focuses on the adenosine A2 receptor (A2AR), a prototypical class A GPCR. 19F Nuclear Magnetic Resonance (NMR)...
Alzheimer's disease (AD) is the most common form of dementia that gradually disrupts the brain network to impair memory, language and cognition. While the amyloid hypothesis remains the leading proposed mechanism to explain AD pathophysiology, anti‐amyloid therapeutic strategies have yet to translate into useful therapies, suggesting that amyloid β‐protein and its precursor, the amyloid precursor...
General theories (GT) are reductionist explications of apparently independent facts. Here, in reviewing the literature, I develop a GT to simplify the cluttered landscape of cancer therapy targets by revealing they cluster parsimoniously according to only a few underlying principles. The first principle is that targets can be only exploited by either or both of two fundamentally different approaches:...
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