First signals Bonner, John Tyler; Bonner, John Tyler
2000., 20090911, 2009, 2001, 2001-01-01
eBook
The enormous recent success of molecular developmental biology has yielded a vast amount of new information on the details of development. So much so that we risk losing sight of the underlying ...principles that apply to all development. To cut through this thicket, John Tyler Bonner ponders a moment in evolution when development was at its most basic--the moment when signaling between cells began. Although multicellularity arose numerous times, most of those events happened many millions of years ago. Many of the details of development that we see today, even in simple organisms, accrued over a long evolutionary timeline, and the initial events are obscured. The relatively uncomplicated and easy-to-grow cellular slime molds offer a unique opportunity to analyze development at a primitive stage and perhaps gain insight into how early multicellular development might have started.
The tumor microenvironment (TME) is a complex meshwork of extracellular matrix (ECM) macromolecules filled with a collection of cells including cancer-associated fibroblasts (CAFs), blood vessel ...associated smooth muscle cells, pericytes, endothelial cells, mesenchymal stem cells and a variety of immune cells. In tumors the homeostasis governing ECM synthesis and turnover is disturbed resulting in abnormal blood vessel formation and excessive fibrillar collagen accumulations of varying stiffness and organization. The disturbed ECM homeostasis opens up for new types of paracrine, cell-cell and cell-ECM interactions with large consequences for tumor growth, angiogenesis, metastasis, immune suppression and resistance to treatments. As a main producer of ECM and paracrine signals the CAF is a central cell type in these events. Whereas the paracrine signaling has been extensively studied in the context of tumor-stroma interactions, the nature of the numerous integrin-mediated cell-ECM interactions occurring in the TME remains understudied. In this review we will discuss and dissect the role of known and potential CAF interactions in the TME, during both tumorigenesis and chemoresistance-induced events, with a special focus on the “interaction landscape” in desmoplastic breast, lung and pancreatic cancers. As an example of the multifaceted mode of action of the stromal collagen receptor integrin α11β1, we will summarize our current understanding on the role of this CAF-expressed integrin in these three tumor types.
The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and ...shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r
=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
Highlights • Biological neurons and synapses operate with many timescales. • Many computational models of networks are timescale impoverished. • Circuit operation can be understood from interacting ...nonlinear building blocks.
Brain Tissue–Volume Changes in Cosmonauts Van Ombergen, Angelique; Jillings, Steven; Jeurissen, Ben ...
The New England journal of medicine,
10/2018, Volume:
379, Issue:
17
Journal Article, Web Resource
Peer reviewed
Ten cosmonauts, who spent an average of 189 days in space, had changes in brain volumes — mainly decreased cortical volume and increased CSF subarachnoid and ventricular volume — with some changes ...persisting up to an average of 7 months after return to Earth.
Choosing the appropriate neuroimaging phenotype is critical to successfully identify genes that influence brain structure or function. While neuroimaging methods provide numerous potential ...phenotypes, their role for imaging genetics studies is unclear. Here we examine the relationship between brain volume, grey matter volume, cortical thickness and surface area, from a genetic standpoint. Four hundred and eighty-six individuals from randomly ascertained extended pedigrees with high-quality T1-weighted neuroanatomic MRI images participated in the study. Surface-based and voxel-based representations of brain structure were derived, using automated methods, and these measurements were analysed using a variance-components method to identify the heritability of these traits and their genetic correlations. All neuroanatomic traits were significantly influenced by genetic factors. Cortical thickness and surface area measurements were found to be genetically and phenotypically independent. While both thickness and area influenced volume measurements of cortical grey matter, volume was more closely related to surface area than cortical thickness. This trend was observed for both the volume-based and surface-based techniques. The results suggest that surface area and cortical thickness measurements should be considered separately and preferred over gray matter volumes for imaging genetic studies.
Complex behavioral phenotyping techniques are becoming more prevalent in the field of behavioral neuroscience, and thus methods for manipulating neuronal activity must be adapted to fit into such ...paradigms. Here, we present a head-mounted, magnetically activated device for wireless optogenetic manipulation that is compact, simple to construct, and suitable for use in group-living mice in an enriched semi-natural arena over several days. Using this device, we demonstrate that repeated activation of oxytocin neurons in male mice can have different effects on pro-social and agonistic behaviors, depending on the social context. Our findings support the social salience hypothesis of oxytocin and emphasize the importance of the environment in the study of social neuromodulators. Our wireless optogenetic device can be easily adapted for use in a variety of behavioral paradigms, which are normally hindered by tethered light delivery or a limited environment.
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•A small, wireless device is used for optogenetic activation in a complex environment•PVN oxytocin neurons were activated repeatedly over 2 days in a group setting•Repeated activation in a group setting elicited both pro-social and agonistic behavior•Findings support the social salience hypothesis of oxytocin neuro-modulation
Anpilov et al. present a lightweight, easily assembled wireless optogenetic device compatible with group-housed mice in a complex environment. Using this approach, they show that repeated activation of oxytocin neurons elicits both pro-social and aggressive behaviors over time, emphasizing the role of the social setting in modulating behavior.
The cerebral cortex contains layers of neurons sequentially generated by distinct lineage-related progenitors. At the onset of corticogenesis, the first-born progenitors are apical progenitors (APs), ...whose asymmetric division gives birth directly to neurons. Later, they switch to indirect neurogenesis by generating intermediate progenitors (IPs), which give rise to projection neurons of all cortical layers. While a direct lineage relationship between APs and IPs has been established, the molecular mechanism that controls their transition remains elusive. Here we show that interfering with codon translation speed triggers ER stress and the unfolded protein response (UPR), further impairing the generation of IPs and leading to microcephaly. Moreover, we demonstrate that a progressive downregulation of UPR in cortical progenitors acts as a physiological signal to amplify IPs and promotes indirect neurogenesis. Thus, our findings reveal a contribution of UPR to cell fate acquisition during mammalian brain development.
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•The UPR is a homeostat regulating the specification of cortical stem cells•Elp3 loss in cortical stem cells triggers UPR by decreasing codon translation rates•Gradual UPR suppression promotes the switch from direct to indirect neurogenesis
Laguesse, Creppe et al. demonstrate that the unfolded protein response (UPR) contributes to neurogenesis in the developing cerebral cortex. Depletion of the Elongator complex component Elp3 triggers the UPR through interference with codon translation speed. UPR activation impairs the balance between direct and indirect neurogenesis, leading to premature neuron generation.
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