Catálogo de publicaciones - revistas

<jats:p>T cell responses are initiated by antigen and promoted by a range of costimulatory signals. Understanding how T cells integrate alternative signal combinations and make decisions affecting immune response strength or tolerance poses a considerable theoretical challenge. Here, we report that T cell receptor (TCR) and costimulatory signals imprint an early, cell-intrinsic, division fate, whereby cells effectively count through generations before returning automatically to a quiescent state. This autonomous program can be extended by cytokines. Signals from the TCR, costimulatory receptors, and cytokines add together using a linear division calculus, allowing the strength of a T cell response to be predicted from the sum of the underlying signal components. These data resolve a long-standing costimulation paradox and provide a quantitative paradigm for therapeutically manipulating immune response strength.</jats:p>

<jats:p>DNA interstrand cross-links (ICLs) are highly toxic lesions associated with cancer and degenerative diseases. ICLs can be repaired by the Fanconi anemia (FA) pathway and through FA-independent processes involving the FAN1 nuclease. In this work, FAN1-DNA crystal structures and biochemical data reveal that human FAN1 cleaves DNA successively at every third nucleotide. In vitro, this exonuclease mechanism allows FAN1 to excise an ICL from one strand through flanking incisions. DNA access requires a 5′-terminal phosphate anchor at a nick or a 1- or 2-nucleotide flap and is augmented by a 3′ flap, suggesting that FAN1 action is coupled to DNA synthesis or recombination. FAN1’s mechanism of ICL excision is well suited for processing other localized DNA adducts as well.</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>On this week's show: The Black Beauty meteorite and a news roundup.</jats:p>

<jats:p>Concerns about incorrectly or insufficiently characterized antibodies employed in biomedical research have been raised by recent reports of nonreproducible research studies. Reproducibility issues have resulted in loss of time, resources, and scientific reputation, with publication retractions occurring in certain cases. This webinar will highlight the challenges surrounding how antibody specificity affects reproducibility in biomedical research and introduce viewers to the key requirements for proper antibody validation. Panelists, including a journal editor, an academic researcher, a pharmaceutical company investigator, and an antibody supplier will share their views and unique perspectives. This forum is intended to serve as one step along an ongoing path toward building consensus on best practices for antibody validation and possible guidelines for reporting of antibody-based data in research manuscripts. By registering in advance for this webinar you can pose your specific questions for consideration by the panelists.</jats:p>

<jats:p>Horizon 2020, the European Union's new funding mechanism, is the concrete translation of Europe 2020, a 10-year strategy proposed by the European Commission to advance Europe's economy in a "smart, inclusive, and sustainable" way. It reflects the widespread sentiment that Europe has fallen behind the rest of the world in innovation. By supporting areas in which Europe already shows strong competence, especially at the near market stage where crucial funding tends to falls short, the European Union aims to emerge as a world leader in the areas targeted and grow its economy at the same time. Along the way, it is creating new opportunities for scientists.</jats:p>

<jats:p> Developing tissues that contain mutant or compromised cells present risks to animal health. Accordingly, the appearance of a population of suboptimal cells in a tissue elicits cellular interactions that prevent their contribution to the adult. Here we report that this quality control process, cell competition, uses specific components of the evolutionarily ancient and conserved innate immune system to eliminate <jats:italic>Drosophila</jats:italic> cells perceived as unfit. We find that Toll-related receptors (TRRs) and the cytokine Spätzle (Spz) lead to NFκB-dependent apoptosis. Diverse “loser” cells require different TRRs and NFκB factors and activate distinct pro-death genes, implying that the particular response is stipulated by the competitive context. Our findings demonstrate a functional repurposing of components of TRRs and NFκB signaling modules in the surveillance of cell fitness during development. </jats:p>

<jats:sec> <jats:title>BACKGROUND</jats:title> <jats:p>It is unknown whether the Moon has a fully differentiated and melted structure with a metallic core or retains a partially primordial, unmelted interior. The differentiation history of the Moon is manifested by its record of past magnetism (paleomagnetism). Although the Moon today does not have a global magnetic field, the discovery of remanent magnetization in lunar rocks and in the lunar crust demonstrated that there was a substantial lunar surface field billions of years ago. However, the origin, intensity, and lifetime of this field have been uncertain. As a result, it has been unclear whether this magnetization was produced by a dynamo in the Moon’s advecting metallic core or by fields generated externally to the Moon. Establishing whether the Moon formed a core dynamo would have major implications for understanding its interior structure, thermal history, and mechanism of formation, as well for our understanding of the physics of planetary magnetic field generation.</jats:p> </jats:sec> <jats:sec> <jats:title>ADVANCES</jats:title> <jats:p>A new generation of laboratory magnetic studies of lunar rocks and spacecraft measurements of lunar crustal magnetic fields have produced major advances in our understanding of the evolution of ancient magnetic fields on the Moon. It has now been established that a dynamo magnetic field likely existed on the Moon from at least 4.5 billion to 3.56 billion years ago, with an intensity similar to that at the surface of Earth today. The field then declined by at least an order of magnitude by 3.3 billion years ago. The early epoch of high field intensities may require an exceptionally energetic power source such as mechanical stirring from mantle precession. The extended history of the lunar dynamo appears to demand long-lived power sources such as mantle precession and core crystallization.</jats:p> </jats:sec> <jats:sec> <jats:title>OUTLOOK</jats:title> <jats:p>Measurements of the intensity of the ancient lunar dynamo have shown that it was surprisingly intense and long-lived. The next phase of lunar magnetic exploration will be to obtain more accurate measurements of field paleointensities and to determine when the dynamo initiated and finally disappeared. This will be coupled with the continued development of magnetohydrodynamic models for characterizing mechanical and other unusual dynamo mechanisms and further investigations into the thermal, structural, and geodynamical history of the lunar core and mantle. The eventual availability of absolutely oriented samples and in situ spacecraft measurements of bedrock should enable the first measurements of the paleo-orientation of lunar magnetic fields. Such directional data could determine the lunar field’s geometry and reversal frequency, as well as constrain ancient local and global-scale tectonic events.</jats:p> </jats:sec>

<jats:p>Each year, $1.4 trillion are invested in research by governments, foundations, and corporations. Hundreds if not thousands of high-profile prizes and medals are awarded to the best researchers, boosting their careers. Therefore, establishing a reliable predictor of future performance is a trillion-dollar matter. Last month, the Alexander von Humboldt Foundation convened an international assembly of leaders in academia, research management, and policy to discuss “Beyond Bibliometrics: Identifying the Best.” Current assessment is largely based on counting publications, counting citations, taking note of the impact factor of the journals where researchers publish, and derivatives of these such as the h-index. These approaches were severely criticized for numerous reasons, with shortcomings particularly apparent when assessing young scientists for prestigious, interdisciplinary awards. It is time to develop more appropriate measures and to use the scientific method itself to help in this endeavor.</jats:p>