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X-ray crystal structures of the human serotonin transporter (SERT) bound to the antidepressants (S)-citalopram or paroxetine show that the antidepressants lock the protein in an outward-open conformation, and directly block serotonin from entering its binding site; the structures define the mechanism of antidepressant action in SERT and pave the way for future drug design.
Malignant cells are able to survive and grow in detached conditions, despite the associated increase in reactive oxygen species; here a novel metabolic pathway used by cancer cells as they adapt to anchorage-independent growth is described.
Aged fibroblasts release a Wnt antagonist, sFRP2, which drives a signalling cascade in melanoma cells, leading to increased metastasis and reduced effectiveness of targeted therapy.
A tremor source on the San Andreas Fault produced an unusual sequence of low-frequency earthquakes until it was disrupted by the 2004 Parkfield earthquake; the peculiar recurrence pattern has now been modelled, showing that such slip behaviour occurs when the tremor asperity size is close to the critical nucleation size of earthquakes.
Phylogenetic methods were applied to a cross-cultural database of traditional Austronesian societies to test the link between ritual human sacrifice and the origins of social hierarchy—the presence of sacrifice in a society stabilized social stratification and promoted inherited class systems.
Dense suspensions of hard granular particles can transform from liquid-like to solid-like when perturbed; a state diagram is mapped out that reveals how this transformation can occur via dynamic jamming at sufficiently large shear stress while leaving the particle density unchanged.
The X-ray crystal structures of the human σ1 receptor bound to two different ligands are reported, revealing the overall architecture, oligomerization state, and molecular basis for ligand recognition by this protein.
New excavations in Liang Bua, where the remains of the ‘Hobbit’ (Homo floresiensis) were discovered, show that this diminutive human species used this cave between 190,000 and 50,000 years ago, and not until as recently as 12,000 years ago as previously interpreted; modern humans have been present in Australia since around 50,000 years ago, so whether Homo floresiensis survived long enough to witness the arrival of modern humans is still an open question.
A light-weight, low-cost microelectromechanical system gravimeter is presented with sensitivity and stability high enough to measure the elastic deformation of the Earth’s crust as a result of tidal forces, enabling many applications.
Uncoupling protein 1 (UCP1)-dependent thermogenesis in brown adipose tissue is supported by a burst of mitochondrial reactive oxygen species upon cold exposure.
The crystal structures of the protease domain of separase are reported, showing how separase recognizes cohesin, and how phosphorylation of the cleavage site enhances separase activity.
Relatively rapid changes in island area, isolation and connectivity observed since the Last Glacial Maximum have had measurable effects on present-day biodiversity, with formerly larger and less well connected islands having a greater number of endemic species.
Lypd8 protein derived from intestinal epithelial cells binds to flagellated bacteria to reduce their motility, which limits the entry of Gram-negative bacteria into the inner colonic mucus and prevents invasion of colonic epithelia.
Much of the intracellular protein degradation in eukaryotes is controlled by cullin–RING ubiquitin ligases (CRLs), a vast class of enzymes which are regulated by the COP9 signalosome (CSN); structural characterization of CSN–N8CRL4A complexes by cryo-electron microscopy reveals an induced-fit mechanism of CSN activation triggered only by catalytically activated CRLs without bound substrate, explaining how CSN acts as a global regulator of CRLs.
The prevalence of N6-adenine DNA methylation in mammals was previously unknown; this study reveals that N6-methyladenine can be found in mouse embryonic stem cells, especially at subfamilies of young (<1.5 million years old) LINE-1 transposons.
Gain of MEKK3 signalling is shown to cause cerebral cavernous malformations (CCMs) via activation of the target genes Klf2 and Klf4; endothelial-specific loss of MEKK3, KLF2 or KLF4 prevents lesion formation and lethality in a mouse CCM model.
Luminescence induced by highly localized excitations that are produced by electrons tunnelling from the tip of a scanning tunnelling microscope is used to map the spatial distribution of the excitonic coupling in well-defined arrangements of a few zinc-phthalocyanine molecules and the dependence of this spatial distribution on the relative orientation and phase of the transition dipoles of the individual molecules.
Climate and ice-sheet modelling that includes ice fracture dynamics reveals that Antarctica could contribute more than a metre of sea-level rise by 2100 and more than 13 metres by 2500, if greenhouse gas emissions continue unabated.
Sustained delivery of axon-specific growth factors not typically present in spinal cord lesions allows for robust axonal regrowth only if the astrocytic scar is present—a result that questions the prevailing dogma and suggests that astrocytic scarring aids rather than prevents central nervous system axon regeneration post injury.
