A meeting between the Pope, patients and researchers acknowledges how the two sectors can help each other.
The nation needs to end the long-running battle between regulators, lawmakers and industry.
The Department of Energy needs to prioritize the clean-up of nuclear waste.
Rural and struggling areas have benefited from funding that is now at risk.
Researchers and manufacturers face possible jail time — or execution — for fraudulent submissions to nation's drug agency.
Famous bell-shaped pots associated with group of immigrants who may have displaced Neolithic farmers.
Desperate farmers hope scientists can beat pathogen that is wrecking the US orange harvest.
DNA sequences from 100-year-old tumour samples could bolster childhood cancer research.
Large timber buildings are getting safer, stronger and taller. They may also offer a way to slow down global warming.
News & Views
It emerges that tumour cells can give rise to non-dividing cells that form part of the supporting microenvironment known as the niche. These niche cells secrete proteins that drive tumour growth and progression. See Letters p.355 & p.360
Systems of quantum objects can be characterized by the correlations between the objects. A technique that precisely measures even the most delicate of these correlations allows models of quantum systems to be tested. See Letter p.323
Ageing and many diseases are partly driven by the accumulation of damaged cells that no longer divide. It emerges that these senescent cells can be eradicated in mice using a drug that interferes with the activity of the protein FOXO4.
A classic paper in 1967 reported key advances in climate modelling that enabled a convincing quantification of the global-warming effects of carbon dioxide — laying foundations for the models that underpin climate research today.
The chances of solving a problem that involves coordination between people are increased by introducing robotic players that sometimes make mistakes. This finding has implications for real-world coordination problems. See Letter p.370
The authors use computational modelling and a set of chemically synthesized compounds to define the physicochemical properties required for small-molecule accumulation in Gram-negative bacteria.
Lipopolysaccharide derived from gut bacteria can accelerate the formation of cerebral cavernous malformations by activating TLR4 on endothelial cells, and polymorphisms that increase expression of the genes encoding TLR4 or its co-receptor CD14 are associated with higher CCM lesion burden in humans.
In response to nitrate, Ca2+-sensor protein kinases (CPKs) act as master regulators to coordinate downstream signalling responses that are essential for shoot growth and root establishment in Arabidopsis.
The identification of the positions and patterns of amino acids that form the selectivity determinants for the entire human G-protein and G-protein-coupled receptor signalling system.
Experimental measurements of higher-order correlation functions in many-body systems provide insight into a non-trivial quantum field theory and how it can be implemented in a cold-atom quantum simulation.
Cultured stem cells have become a standard platform not only for regenerative medicine and developmental biology but also for biophysical studies. Yet, the characterization of cultured stem cells at the level of morphology and of the macroscopic patterns resulting from cell-to-cell interactions remains largely qualitative. Here we report on the collective dynamics of cultured murine neural progenitor cells (NPCs), which are multipotent stem cells that give rise to cells in the central nervous system. At low densities, NPCs moved randomly in an amoeba-like fashion. However, NPCs at high density elongated and aligned their shapes with one another, gliding at relatively high velocities. Although the direction of motion of individual cells reversed stochastically along the axes of alignment, the cells were capable of forming an aligned pattern up to length scales similar to that of the migratory stream observed in the adult brain. The two-dimensional order of alignment within the culture showed a liquid-crystalline pattern containing interspersed topological defects with winding numbers of +1/2 and −1/2 (half-integer due to the nematic feature that arises from the head–tail symmetry of cell-to-cell interaction). We identified rapid cell accumulation at +1/2 defects and the formation of three-dimensional mounds. Imaging at the single-cell level around the defects allowed us to quantify the velocity field and the evolving cell density; cells not only concentrate at +1/2 defects, but also escape from −1/2 defects. We propose a generic mechanism for the instability in cell density around the defects that arises from the interplay between the anisotropic friction and the active force field.
Modelling of two modes of continental crust formation suggests that before plate tectonics began operating, the Archean early Earth’s tectonic regime was governed by intrusive magmatism.
Earthquake rupture experiments and mathematical modelling reveal the existence of a torquing mechanism of thrust fault ruptures near the free surface that causes them to dynamically unclamp, open and slip large distances.
The Drosophila rhodopsin Rh7 works with cryptochrome to mediate circadian light entrainment by pacemaker neurons.
A complete larval zebrafish brain is examined and its myelinated axons reconstructed using serial-section electron microscopy, revealing remarkable symmetry and providing a valuable resource.
Preventing netrin secretion from floor-plate cells at the midline does not disrupt axonal guidance; commissural axons develop normally and the data suggest that netrin may influence axons locally by promoting growth cone adhesion.
The heterogeneity of cellular states in cancer has been linked to drug resistance,
cancer progression and the presence of cancer cells with properties of normal tissue
stem cells. Secreted Wnt signals maintain stem cells in various
epithelial tissues, including in lung development and regeneration. Here we show that mouse and human lung adenocarcinomas display
hierarchical features with two distinct subpopulations, one with high Wnt signalling
activity and another forming a niche that provides the Wnt ligand. The Wnt responder
cells showed increased tumour propagation ability, suggesting that these cells have
features of normal tissue stem cells. Genetic perturbation of Wnt production or
signalling suppressed tumour progression. Small-molecule inhibitors targeting
essential posttranslational modification of Wnt reduced tumour growth and markedly
decreased the proliferative potential of lung cancer cells, leading to improved
survival of tumour-bearing mice. These results indicate that strategies for
disrupting pathways that maintain stem-like and niche cell phenotypes can translate
into effective anti-cancer therapies.
In a mouse model of small-cell lung cancer and in human tumours, activation of the Notch pathway can lead to a cell fate switch of neuroendocrine cells to less proliferative non-neuroendocrine cells, generating intratumoural heterogeneity.
The mechanistic target of rapamycin (mTOR) has a key role in the integration of
various physiological stimuli to regulate several cell growth and metabolic
pathways. mTOR primarily functions as a catalytic subunit in two
structurally related but functionally distinct multi-component kinase complexes,
mTOR complex 1 (mTORC1) and mTORC2 (refs 1, 2). Dysregulation of mTOR signalling is associated with a
variety of human diseases, including metabolic disorders and cancer.
Thus, both mTORC1 and mTORC2 kinase activity is tightly controlled in cells. mTORC1
is activated by both nutrients and growth factors, whereas mTORC2 responds primarily to extracellular cues such as
growth-factor-triggered activation of PI3K signalling.
Although both mTOR and GβL (also known as MLST8) assemble into mTORC1
and mTORC2 (refs 11, 12,
13, 14, 15), it remains largely unclear what drives the dynamic
assembly of these two functionally distinct complexes. Here we show, in humans
and mice, that the K63-linked polyubiquitination status of GβL dictates
the homeostasis of mTORC2 formation and activation. Mechanistically, the TRAF2 E3
ubiquitin ligase promotes K63-linked polyubiquitination of GβL, which
disrupts its interaction with the unique mTORC2 component SIN1 (refs 12, 13, 14) to favour mTORC1 formation. By contrast, the OTUD7B
deubiquitinase removes polyubiquitin chains from GβL to promote
GβL interaction with SIN1, facilitating mTORC2 formation in response to
various growth signals. Moreover, loss of critical ubiquitination residues in
GβL, by either K305R/K313R mutations or a melanoma-associated
GβL(ΔW297) truncation, leads to elevated mTORC2 formation,
which facilitates tumorigenesis, in part by activating AKT oncogenic signalling. In
support of a physiologically pivotal role for OTUD7B in the activation of mTORC2/AKT
signalling, genetic deletion of Otud7b in mice suppresses Akt activation and
Kras-driven lung tumorigenesis in vivo. Collectively, our study
reveals a GβL-ubiquitination-dependent switch that fine-tunes the
dynamic organization and activation of the mTORC2 kinase under both physiological
and pathological conditions.
A networked colour coordination game, with humans interacting with autonomous software bots, shows that bots acting with small levels of random noise and being placed centrally in the network improves not only human–bot interactions but also human–human interactions at distant nodes.