Many recent gene knockout experiments cause anatomical changes to the jaw region of mice that several investigators claim are evolutionary reversals. Here we evaluate these mutant phenotypes and the assertions of atavism. We argue that following the knockout of Hoxa-2, Dlx-2, MHox, Otx2, and RAR genes, ectopic cartilages arise as secondary consequences of disruptions in normal processes of cell...

Serotonergic (5HT) neurons modulate diverse behaviors and physiology and are implicated in distinct clinical disorders. Corresponding diversity in 5HT neuronal phenotypes is becoming apparent and is likely rooted in molecular differences, yet a comprehensive approach characterizing molecular variation across the 5HT system is lacking, as is concomitant linkage to cellular phenotypes. Here we co...

The sets of compounds that can support growth of an organism are defined by the presence of transporters and metabolic pathways that convert nutrient sources into cellular components and energy for growth. A collection of known nutrient sources can therefore serve both as an impetus for investigating new metabolic pathways and transporters and as a reference for computational modeling of known ...

Predicting the metabolic state of an organism after a gene knockout is a challenging task, because the regulatory system governs a series of transient metabolic changes that converge to a steady-state condition. Regulatory on/off minimization (ROOM) is a constraint-based algorithm for predicting the metabolic steady state after gene knockouts. It aims to minimize the number of significant flux ...

The 2007 Nobel Prize in Physiology or Medicine has been awarded to Mario Capecchi, Martin Evans, and Oliver Smithies for developing specific gene modification techniques and mouse embryonic stem cell technology that, when combined, enable the creation of "knockout" mice. Analyses of these mutant animals have revolutionized the elucidation of gene functions, and these mice have proved to be valu...

Abstract Proper development of the mammalian cerebral cortex relies on precise gene expression regulation, which is controlled by genetic, epigenetic, and epitranscriptomic factors. Here we generate RNA demethylase Fto methyltransferase Mettl3 cortical-specific conditional knockout mice, detect severe brain defects caused deletion but not knockout. Transcriptomic profiles using sequencing indic...

Systems biology aims to understand biological phenomena in terms of complex biological and molecular interactions, and thus proteomics plays an important role in elucidating protein networks. However, many proteomic methods have suffered from their high variability, resulting in only showing altered protein names. Here, we propose a strategy for elucidating cellular protein networks based on an...

OBJECTIVES Recent increases in triazole resistance in Aspergillus fumigatus have been attributed primarily to target site (cyp51A) mutations. A recent survey of resistant isolates in Manchester showed that >50% of resistant isolates had no mutation in cyp51A or its promoter. We investigated the mechanisms of resistance in clinical azole-resistant isolates without cyp51A mutations. METHODS Twe...

Pattern completion, the ability to retrieve complete memories initiated by subsets of external cues, has been a major focus of many computation models. A previously study reports that such pattern completion requires NMDA receptors in the hippocampus. However, such a claim was derived from a non-inducible gene knockout experiment in which the NMDA receptors were absent throughout all stages of ...

Because of the development of gene knockout and transgenic technologies, small animals, such as mice and rats, have become the most widely used animals for cardiovascular imaging studies. Imaging can provide a method to serially evaluate the effect of a particular genetic mutation or pharmacologic therapy (1). In addition, imaging can be used as a noninvasive screening tool for particular cardi...