Catálogo de publicaciones - revistas

<jats:title>Playing Hide and Seek</jats:title> <jats:p> Targeted cancer therapies have shown promising results in patients, but few of these drugs provide long-term benefits because tumor cells rapidly develop drug resistance. <jats:bold> Nathanson <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="6166" page="72" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1241328">72</jats:related-article> , published online 5 December) show that glioblastoma cells can become resistant to erlotinib, an epidermal growth factor receptor (EGFR)–targeted drug, by eliminating extrachromosomal copies of the mutant <jats:italic>EGFR</jats:italic> gene. After a period of drug withdrawal, the mutant <jats:italic>EGFR</jats:italic> gene reappears on extrachromosomal DNA and the tumor cells become resensitized. The discovery that cancer cells can evade drug therapy by this “hide and seek” mechanism may help to optimize the dosing schedule of erlotinib in glioblastoma patients. </jats:p>

<jats:title>Chromosome Condensation</jats:title> <jats:p> The forces that shape the structure of the highly condensed metaphase chromosomes seen during cell division in eukaryotes are still largely unknown. In vitro evidence suggests that the amino-terminal tails of the histones—such as interaction of the histone H4 tail with H2A-H2B—play an important role in chromosome hypercondensation. <jats:bold> Wilkins <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="6166" page="77" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1244508">77</jats:related-article> ) used ultraviolet cross-linker amino acids in the histones of bakers' yeast to show that during early mitosis, phosphorylation of H3 threonine 3 by Haspin kinase recruits the chromosome passenger complex (CPC). The subsequent phosphorylation of H3 serine 10 by CPC allows the recruitment of the deacetylase Hst2p to nucleosomes. Hst2p drives the deacetylation of H4 lysine 16, facilitating the interaction between H4 and H2A-H2B in neighboring nucleosomes, promoting chromatin condensation. </jats:p>

<jats:title>Improving Whole-Genome Screens</jats:title> <jats:p> Improved methods are needed for the knockout of individual genes in genome-scale functional screens. <jats:bold> Wang <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="6166" page="80" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1246981">80</jats:related-article> , published online 12 December) and <jats:bold> Shalem <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="6166" page="84" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1247005">84</jats:related-article> , published online 12 December) used the bacterial CRISPR/Cas9 system to power-screen protocols that avoid several of the pitfalls associated with small interfering RNA (siRNA) screens. Genome editing by these methods completely disrupts target genes, thus avoiding weak signals that can occur when transcript abundance is partially decreased by siRNA. Furthermore, gene targeting by the CRISPR system is more precise and appears to produce substantially fewer off-target effects than existing methods. </jats:p>

<jats:title>Improving Whole-Genome Screens</jats:title> <jats:p> Improved methods are needed for the knockout of individual genes in genome-scale functional screens. <jats:bold> Wang <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="6166" page="80" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1246981">80</jats:related-article> , published online 12 December) and <jats:bold> Shalem <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="6166" page="84" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1247005">84</jats:related-article> , published online 12 December) used the bacterial CRISPR/Cas9 system to power-screen protocols that avoid several of the pitfalls associated with small interfering RNA (siRNA) screens. Genome editing by these methods completely disrupts target genes, thus avoiding weak signals that can occur when transcript abundance is partially decreased by siRNA. Furthermore, gene targeting by the CRISPR system is more precise and appears to produce substantially fewer off-target effects than existing methods. </jats:p>

<jats:title>DNA Damage Repair</jats:title> <jats:p> In human cancers, oncogene activation interferes with DNA replication, leading to DNA replication stress and DNA double-strand breaks (DSBs). <jats:bold> Costantino <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="6166" page="88" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1243211">88</jats:related-article> , published online 5 December) identified two subunits of DNA polymerase delta, POL3 and POL4, as critical for survival of DNA replication stress in human cells. Both subunits were required for break-induced replication (BIR), which is required to repair a specific type of DSB, with both subunits possibly required for processive DNA synthesis in BIR. Tandem head-to-tail duplications and fold-back inversions were seen in replication-stressed cells, similar to those seen in human breast and ovarian cancers, suggesting that BIR is important for repairing damaged forks in cancer cells. </jats:p>

<jats:title>Familiarity Does Not Breed Contempt</jats:title> <jats:p> Female mating preference is influenced by social familiarity in various species from fish to primates. <jats:bold> Okuyama <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="6166" page="91" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1244724">91</jats:related-article> ) showed in Japanese rice fish that females prefer to mate with visually familiarized males over unfamiliar males and that this preference is mediated by specific neuromodulatory neurons in the female brain. </jats:p>

<jats:title>Counteracting Cannabis</jats:title> <jats:p> What is the role of steroid hormones in vulnerability to addiction? Working with rodents, <jats:bold> Vallée <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="6166" page="94" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1243985">94</jats:related-article> ) found that all major drugs of abuse (morphine, cocaine, alcohol, nicotine) increase neurosteroid levels, with the active ingredient in cannabis (THC) inducing a particularly large increase. THC and other drugs increased levels of pregnenolone, long thought to be an inactive precursor of downstream active steroids. Pregnenolone antagonized most of the known behavioral and somatic effects of THC. </jats:p>

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

<jats:p>This week’s show focuses on the great stone monuments of prehistoric Britain and includes a roundup of shorts from our daily news site.</jats:p>

<jats:title>Preserving Predators</jats:title> <jats:p> Large-bodied animals play essential roles in ecosystem structuring and stability through both indirect and direct trophic effects. In recent times, humans have disrupted this trophic structure through both habitat destruction and active extirpation of large predators, resulting in large declines in numbers and vast contractions in their geographic ranges. <jats:bold> Ripple <jats:italic>et al.</jats:italic> </jats:bold> ( <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" related-article-type="in-this-issue" xlink:href="10.1126/science.1241484">10.1126/science.1241484</jats:related-article> ; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6167" page="142" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1248646">Roberts</jats:related-article> </jats:bold> ) review the status, threats, and ecological importance of the 31 largest mammalian carnivores globally. These species are responsible for a suite of direct and indirect stabilizing effects in ecosystems. Current levels of decline are likely to result in ecologically ineffective population densities and can lead to ecosystem instability. The preservation of large carnivores can be challenging because of their need for large ranges and their potential for human conflict. However, the authors demonstrate that the preservation of large carnivores is ecologically important and that the need for conservation action is immediate, given the severity of the threats they face. </jats:p>