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Differentiated cells can be reprogrammed to an embryonic-like state by transfer of nuclear contents into oocytes or by fusion with embryonic stem (ES) cells. Little is known about factors that induce this reprogramming. Here, we demonstrate induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture...
In this issue of Cell, Lee et al. (2006) report that the parasite Trypanosoma brucei synthesizes fatty acids in an unconventional way. T. brucei and two other trypanosomes use enzymes called elongases to synthesize myristate, a fourteen carbon (C14) fatty acid essential for pathogenesis. This is an unexpected finding as these enzymes were thought only to elongate already long (C16 or C18) acyl chains.
A specific and unexpected distribution pattern of polygonal cell shapes in proliferating epithelia is revealed in a recent study that combines mathematical modeling with experimental data (Gibson et al., 2006). This pattern is conserved in epithelia from diverse species, suggesting that this distribution is a fundamental property of proliferating epithelial sheets.
In multicellular organisms, the ability to regulate reproduction, development, and nutrient utilization coincided with the evolution of nuclear receptors (NRs), transcription factors that utilize lipophilic ligands to mediate their function. Studying the expression profile of NRs offers a simple, powerful way to obtain highly relational information about their physiologic functions as individual proteins...
Studying the molecular mechanisms that make the senses respond precisely to external stimuli continues to generate surprising results. This issue's Neurobiology Select discusses studies of the five senses that reveal new insights into protein function, physiology, and animal behavior.
The ER's capacity to process proteins is limited, and stress caused by accumulation of unfolded and misfolded proteins (ER stress) contributes to human disease. ER stress elicits the unfolded protein response (UPR), whose components attenuate protein synthesis, increase folding capacity, and enhance misfolded protein degradation. Here, we report that P58 IPK /DNAJC3, a UPR-responsive gene...
The mitochondrial RNA binding proteins MRP1 and MRP2 form a heteromeric complex that functions in kinetoplastid RNA editing. In this process, MRP1/MRP2 serves as a matchmaker by binding to guide RNAs and facilitating their hybridization with cognate preedited mRNAs. To understand the mechanism by which this complex performs RNA matchmaking, we determined structures of Trypanosoma brucei apoMRP1/MRP2...
A key challenge in stem cell research is to learn how to direct the differentiation of stem cells toward specific fates. In this issue of Cell, Engler et al. (2006) identify a new factor regulating stem cell fate: the elasticity of the matrix microenvironment. By changing the stiffness of the substrate, human mesenchymal stem cells could be directed along neuronal, muscle, or bone lineages.
The exon junction complex (EJC) plays a major role in posttranscriptional regulation of mRNA in metazoa. The EJC is deposited onto mRNA during splicing and is transported to the cytoplasm where it influences translation, surveillance, and localization of the spliced mRNA. The complex is formed by the association of four proteins (eIF4AIII, Barentsz [Btz], Mago, and Y14), mRNA, and ATP. The 2.2 Å resolution...
The tight junction is an intricate seal between adjoining epithelial cells that also separates the apical and basolateral membranes within these cells. A paper in this issue of Cell by Umeda et al. (2006) demonstrates that loss of the ZO scaffolding proteins prevents the formation of tight junctions but surprisingly does not perturb apico-basal polarity.
Positive feedback is a ubiquitous feature of networks that establish and maintain cellular decisions. In this issue of Cell, Laslo et al. (2006) demonstrate how a feedback loop comprised of two mutual repressors regulates the differentiation of myeloid progenitors into either macrophages or neutrophils.
All eukaryotic and prokaryotic organisms are thought to synthesize fatty acids using a type I or type II synthase. In addition, eukaryotes extend pre-existing long chain fatty acids using microsomal elongases (ELOs). We have found that Trypanosoma brucei, a eukaryotic human parasite that causes sleeping sickness, uses three elongases instead of type I or type II synthases for the synthesis of nearly...
The neuronal ubiquitin/proteasomal pathway has been implicated in the pathogenesis of Alzheimer's disease (AD). We now show that a component of the pathway, ubiquitin C-terminal hydrolase L1 (Uch-L1), is required for normal synaptic and cognitive function. Transduction of Uch-L1 protein fused to the transduction domain of HIV-transactivator protein (TAT) restores normal enzymatic activity and synaptic...
Yersinia spp. cause gastroenteritis and the plague, representing historically devastating pathogens that are currently an important biodefense and antibiotic resistance concern. A critical virulence determinant is the Yersinia protein kinase A, or YpkA, a multidomain protein that disrupts the eukaryotic actin cytoskeleton. Here we solve the crystal structure of a YpkA-Rac1 complex and find that YpkA...
Glycans are central to many biological processes, but efforts to define their functions at the molecular level have been frustrated by a lack of suitable technologies. Here we highlight chemical tools that are beginning to address this need.
The stomata of plants regulate gas exchange and water transpiration in response to changing environmental conditions. New work reveals that stomata also have an important role in host defense. In this issue of Cell, Melotto et al. (2006) show that stomata close upon detection of potential microbial pathogens to prevent the infection of the leaf interior. Moreover, pathogenic bacteria have evolved...
Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder. Mutations in presenilins 1 and 2 (PS1 and PS2) account for ∼40% of familial AD (FAD) cases. FAD mutations and genetic deletions of presenilins have been associated with calcium (Ca 2+ ) signaling abnormalities. We demonstrate that wild-type presenilins, but not PS1-M146V and PS2-N141I FAD mutants, can form...
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