Catálogo de publicaciones - revistas

<jats:title>Signaling Differentiation</jats:title> <jats:p> The six-transmembrane protein GDE2 promotes differentiation through extracellular glycerophosphodiester phosphodiesterase (GDPD) activity and induces neuronal differentiation through inhibition of Notch signaling—a major pathway that maintains stem or progenitor cell states and is implicated in multiple cancers. How then, does GDPD activity inhibit Notch signaling, given that GDPD enzymes are known to metabolize glycerophosphodiesters into glycerol-3-phosphate and corresponding alcohols? <jats:bold> Park <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6117" page="324" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1231921">324</jats:related-article> ) show that the six-transmembrane GDPDs such as GDE2, do not function as conventional GDPD enzymes, but instead cleave the glycosylphosphatidylinositol (GPI) anchors of GPI-anchored proteins. GDE2 GDPD activity cleaves and inactivates the GPI-anchored protein RECK, which normally acts to prevent shedding of the Notch ligand Delta. Accordingly, RECK inactivation stimulates Delta shedding leading to Notch inactivation in progenitors and the initiation of cellular differentiation. </jats:p>

<jats:title>A Well-Defined Path</jats:title> <jats:p> Although chemokines have long been thought to direct immune cell movements within tissues, a formal in vivo demonstration and detailed understanding are lacking. By tracking dendritic cell movements in the ears of mice, <jats:bold> Weber <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6117" page="328" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1228456">328</jats:related-article> ) were able to provide both. Endogenous gradients of the chemokine CCL21 were observed in ear tissue and, at distances of up 90 µm, dendritic cells were able to use these gradients to migrate directionally toward lymphatic vessels. The CCL21 gradient was immobilized on heparan sulfates and disruption of the gradient inhibited dendritic cell migration. </jats:p>

<jats:title>Defeat, Distress, and Glucocorticoids</jats:title> <jats:p> Understanding how individuals control emotions and cope with stressful events is a major clinical concern and of importance for the treatment of psychiatric illnesses (see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6117" page="279" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1233713">McEwen</jats:related-article> </jats:bold> ). <jats:bold> Barik <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6117" page="332" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1226767">332</jats:related-article> ) discovered that aggressive defeat stress in mice caused glucocortioid release and increased activity in the dopamine system. Deleting the glucocorticoid receptors in dopaminoceptive neurons completely prevented the social avoidance that usually follows aggressive defeat. How the combination of genetic factors and environmental stressors during adolescence determines adult behavior and how their disturbance results in neuropsychiatric disorders is poorly understood. <jats:bold> Niwa <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6117" page="335" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1226931">335</jats:related-article> ) found that isolation stress during adolescence, which does not cause any long-lasting changes in wild-type mice, induced significant neurochemical and behavioral alterations in mutant mice expressing a dominant-negative variant of the <jats:italic>disrupted in schizophrenia 1</jats:italic> gene under the control of the prion protein promoter. These deficits could be reversed by a glucocorticoid receptor antagonist. </jats:p>

<jats:title>Defeat, Distress, and Glucocorticoids</jats:title> <jats:p> Understanding how individuals control emotions and cope with stressful events is a major clinical concern and of importance for the treatment of psychiatric illnesses (see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6117" page="279" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1233713">McEwen</jats:related-article> </jats:bold> ). <jats:bold> Barik <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6117" page="332" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1226767">332</jats:related-article> ) discovered that aggressive defeat stress in mice caused glucocortioid release and increased activity in the dopamine system. Deleting the glucocorticoid receptors in dopaminoceptive neurons completely prevented the social avoidance that usually follows aggressive defeat. How the combination of genetic factors and environmental stressors during adolescence determines adult behavior and how their disturbance results in neuropsychiatric disorders is poorly understood. <jats:bold> Niwa <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6117" page="335" related-article-type="in-this-issue" vol="339" xlink:href="10.1126/science.1226931">335</jats:related-article> ) found that isolation stress during adolescence, which does not cause any long-lasting changes in wild-type mice, induced significant neurochemical and behavioral alterations in mutant mice expressing a dominant-negative variant of the <jats:italic>disrupted in schizophrenia 1</jats:italic> gene under the control of the prion protein promoter. These deficits could be reversed by a glucocorticoid receptor antagonist. </jats:p>

<jats:p>It's been 20 years since Francis Crick and Edward Jones, in the midst of the so-called Decade of the Brain, lamented science's lack of even a basic understanding of human neuroanatomy. "Clearly what is needed for a modern human brain anatomy is the introduction of some radically new techniques," the pair wrote in 1993. Clearly, researchers were listening. Today, they are using novel technologies and automation to map neural circuitry with unparalleled resolution and completeness. The NIH has dedicated nearly $40 million to chart the wiring of the human brain, and the Allen Brain Institute has poured in millions more to map the mouse brain. The data will take years to compile, and even longer to understand. But the results may reveal nothing less than the nature of human individuality. As MIT neuroscientist Sebastian Seung writes, "You are more than your genes. You are your connectome."</jats:p>

<jats:p>Listen to stories on innovative imaging, anonymous genomes, the promise and perils of oxytocin, and more.</jats:p>

<jats:p>A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.</jats:p>