| | Neuroscience: Untangling autism
A clever dissection of the roles of the Ptchd1 gene in the brains of mice demonstrates one way to untangle the complex relationships between the causes and symptoms of neurodevelopmental disorders. | Cell biology: Calcium contradictions in cilia
Organelles called primary cilia that protrude from cells have been thought to sense the surrounding environment through calcium-channel proteins that respond to force. Two scientists discuss the implications for developmental biology and kidney disease of a study that challenges this hypothesis. | Neuroscience: Making risk-takers settle
In rats, individual differences in risk preference and in sensitivity to gains compared with losses are controlled by a specific neuronal population, stimulation of which neutralizes risk-seeking behaviour. | Molecular biology: Breaks in the brain
A high-throughput approach has found clusters of DNA double-strand breaks in neural cells. Most of the clusters are in large genes that are associated with neural function, which suggests that the breaks may have tissue-specific roles. | Structure of promoter-bound TFIID and model of human pre-initiation complex assembly
A sub-nanometre resolution cryo-EM structure of human TFIID bound to TFIIA and core promoter DNA and a model of the TFIID-based pre-initiation complex. | Thalamic reticular impairment underlies attention deficit in Ptchd1Y/− mice
Ptchd1 deletion in humans leads to attention deficits, intellectual disability, and autism spectrum disorders; mouse PTCHD1 is enriched in the thalamic reticular nucleus (TRN) and TRN-restricted Ptchd1 deletion in mice led to attention-deficit hyperactivity, which could be rescued by modulating calcium-dependent potassium channel activity, suggesting that a TRN deficit may underlie core impairments associated with neurodevelopmental disorders and it may be possible to identify therapeutic targets for individuals with attention disorders. | Nineteen-step total synthesis of (+)-phorbol
Enantiospecific total synthesis of (+)-phorbol in only 19 steps from the abundant monoterpene (+)-3-carene is demonstrated using a two-phase terpene synthesis strategy. | The conformational signature of β-arrestin2 predicts its trafficking and signalling functions
A series of intramolecular fluorescent FlAsH BRET reporters is used to monitor conformational changes in β-arrestin2 following activation of seven G-protein-coupled receptors (GPCRs), showing that different GPCRs produce distinct β-arrestin2 conformational signatures that correlate with the stability of the receptor–arrestin complex and the role of β-arrestin2 in activating or dampening downstream signalling events, which explains how different GPCRs can use a common effector for different purposes. | A specific area of olfactory cortex involved in stress hormone responses to predator odours
Exposure to predator scents triggers an instinctive fear response in mice, including a surge in blood levels of stress hormones; here, the amygdalo-piriform transition area is identified as provoking these hormonal responses. | Bidirectional electromagnetic control of the hypothalamus regulates feeding and metabolism
Activation of glucose-sensing neurons in the ventromedial hypothalamic nucleus using radio waves or magnetic fields remotely and non-invasively in vivo increases plasma glucose and glucagon, and suppresses plasma insulin; conversely, remote inhibition of glucose-sensing neurons decreased blood glucose and increased plasma insulin. | β-Arrestin biosensors reveal a rapid, receptor-dependent activation/deactivation cycle
A series of FRET-based β-arrestin2 biosensors are used to study the dynamics and conformational changes that occur when β-arrestin2 binds to and dissociates from the β2-adrenergic receptor in living cells; results show that after β-arrestin2 dissociates from the β2-adrenergic receptor, it stays at the cell membrane in an active conformation for a while, indicating that β-arrestin is able to signal in a G-protein-coupled receptor (GPCR)-free state. | Nucleus accumbens D2R cells signal prior outcomes and control risky decision-making
Increased activity of dopamine receptor type-2 (D2R)-expressing cells in the nucleus accumbens of rats during a ‘decision’ period reflects a ‘loss’ outcome of the previous decision and predicts a subsequent safe choice; by artificially increasing the activity of D2R neurons during the decision period, risk-seeking rats could be converted to risk-avoiding rats. | R-process enrichment from a single event in an ancient dwarf galaxy
It has long been debated whether elements heavier than zinc are formed continually, for example in core-collapse supernovae, or in rare events, such as neutron star mergers; here, studies of element abundances in a local ultrafaint dwarf galaxy provide evidence that these elements are formed during rare yet prolific stellar events. | Primary cilia are not calcium-responsive mechanosensors
Mechanosensation, if it originates in primary cilia, is not via calcium signalling. | NOD1 and NOD2 signalling links ER stress with inflammation
A novel link between the unfolded protein response and NOD1/2 innate immune signalling, showing that NOD1/2 are required for ER-stress-induced IL-6 production in response to infection with Brucella abortus. | | Corrigendum: An observational radiative constraint on hydrologic cycle intensification | | Corrigendum: Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117 | | | | This animation explores progress in the development of oral anticoagulants that target components of the blood coagulation cascade to inhibit blood clotting in high-risk patients, as well as recent advances with antidotes to reverse the effects of oral anticoagulants when necessary.
Watch now and download a poster on Anticoagulant drugs.
Produce with the support from: Boehringer Ingelheim
| | | | | | | | | | | Direct synthesis of Z-alkenyl halides through catalytic cross-metathesis
One shortcoming of olefin metathesis has been that acyclic alkenyl halides could not be generated efficiently and stereoselectively; but now halo-substituted molybdenum alkylidene species are shown to be able to participate in high-yielding olefin metathesis reactions that afford acyclic 1,2-disubstituted Z-alkenyl halides.
Ming Joo Koh, Thach T. Nguyen, Hanmo Zhang et al. | Lytic to temperate switching of viral communities
An analysis of 24 coral reef viromes challenges the view that lytic phage are believed to predominate when the density of their hosts increase and shows instead that lysogeny is more important at high host densities; the authors also show that this model is consistent with predator–prey dynamics in a range of other ecosystems, such as animal-associated, sediment and soil systems.
B. Knowles, C. B. Silveira, B. A. Bailey et al. | Deletions linked to TP53 loss drive cancer through p53-independent mechanisms
The loss of the TP53 gene is often involved in the development of human cancer; here, the deletion of other genes in the vicinity is shown also to contribute to cancer progression in a mouse model.
Yu Liu, Chong Chen, Zhengmin Xu et al. | | Modes of surface premelting in colloidal crystals composed of attractive particles
Incomplete premelting at the edges of monolayer colloidal crystals is triggered by a bulk solid–solid phase transition and truncated by a mechanical instability that induces homogeneous bulk melting of the crystal; these observations challenge existing theories of two-dimensional melting.
Bo Li, Feng Wang, Di Zhou et al. | Acceleration of petaelectronvolt protons in the Galactic Centre
Deep γ-ray observations of the Galactic Centre with arcminute angular resolution show traces of petaelectronvolt protons within the central ten parsecs of our Galaxy; the accelerator of these particles could have provided a substantial contribution to Galactic cosmic rays in the past.
HESS Collaboration, A. Abramowski, F. Aharonian et al. | Mycocerosic acid synthase exemplifies the architecture of reducing polyketide synthases
A hybrid crystal structure of Mycobacterium smegmatis mycocerosic acid synthase, a multienzyme involved in the biosynthesis of mycobacterial branched-chain fatty acids, exemplifies the organization of fully-reducing polyketide synthases.
Dominik A. Herbst, Roman P. Jakob, Franziska Zähringer et al. | Lunar true polar wander inferred from polar hydrogen
Polar hydrogen deposits on the Moon provide evidence that its spin axis has shifted; analysis of the locations of these deposits and of the lunar figure suggests that the shift occurred as a result of changes in the Moon’s moments of inertia caused by a low-density thermal anomaly beneath the Procellarum region.
M. A. Siegler, R. S. Miller, J. T. Keane et al. | On-surface synthesis of graphene nanoribbons with zigzag edge topology
Synthesis of atomically precise zigzag edges in graphene nanoribbons is demonstrated using a bottom-up strategy based on surface-assisted arrangement and reaction of precursor monomers; these nanoribbons have edge-localized states with large energy splittings.
Pascal Ruffieux, Shiyong Wang, Bo Yang et al. | The past, present and future of African dust
Variability in North African dust dispersal, which affects air quality and the amount of radiation reaching the ground, is captured by the wind patterns over the Sahara; climate models suggest a downward trend in dust concentration with increasing greenhouse gas emissions.
Amato T. Evan, Cyrille Flamant, Marco Gaetani et al. | Intrinsic honesty and the prevalence of rule violations across societies
To test whether there is a relationship between the level of national corruption and the intrinsic honesty of individuals, a behavioural test of the honesty of people from 23 countries was conducted; the authors found that high national scores on an index of rule-breaking are linked with reduced personal honesty.
Simon Gächter, Jonathan F. Schulz | Impact of meat and Lower Palaeolithic food processing techniques on chewing in humans
The genus Homo had considerably smaller cheek teeth, chewing muscles and jaws than earlier hominins; here, the introduction of raw but processed meat, from which energy could more easily be extracted, is shown to have possibly been responsible for this change.
Katherine D. Zink, Daniel E. Lieberman | Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease
Experiments in transgenic mouse models of early Alzheimer’s disease show that the amnesia seen at this stage of the disease is probably caused by a problem with memory retrieval from the hippocampus rather than an encoding defect.
Dheeraj S. Roy, Autumn Arons, Teryn I. Mitchell et al. | Visualization of immediate immune responses to pioneer metastatic cells in the lung
Tracing the fate of circulating tumour cells by intravital two-photon lung imaging shows that tumours produce microparticles as they arrive and these migrate along the lung vasculature and are mostly taken up by interstitial myeloid cells, in a process that contributes to metastatic seeding; a minor subset of microparticles is engulfed by conventional dendritic cells, which are thought to contribute to the initiation of an anti-tumour immune response in lung-draining lymph nodes.
Mark B. Headley, Adriaan Bins, Alyssa Nip et al. | Nuclear DNA sequences from the Middle Pleistocene Sima de los Huesos hominins
Nuclear DNA sequences from Middle Pleistocene Sima de los Huesos hominins show they were more closely related to Neanderthals than to Denisovans, and indicate a population divergence between Neanderthals and Denisovans that predates 430,000 years ago.
Matthias Meyer, Juan-Luis Arsuaga, Cesare de Filippo et al. | Melanoma addiction to the long non-coding RNA SAMMSON
A known oncogene, MITF, resides in a region of chromosome 3 that is amplified in melanomas and associated with poor prognosis; now, a long non-coding RNA gene, SAMMSON, is shown to also lie in this region, to also act as a melanoma-specific survival oncogene, and to be a promising therapeutic target for anti-melanoma therapy.
Eleonora Leucci, Roberto Vendramin, Marco Spinazzi et al. | The amino acid sensor GCN2 controls gut inflammation by inhibiting inflammasome activation
The GCN2 kinase is shown to have a protective role in the regulation of intestinal inflammation during amino acid starvation in a mouse model of colitis.
Rajesh Ravindran, Jens Loebbermann, Helder I. Nakaya et al. | PGC1α drives NAD biosynthesis linking oxidative metabolism to renal protection
PGC1α protects against kidney injury by upregulating enzymes that enhance nicotinamide adenine dinucleotide (NAD) and driving local accumulation of the fatty acid breakdown product β-hydroxybutyrate, which leads to increased production of the renoprotective prostaglandin E2.
Mei T. Tran, Zsuzsanna K. Zsengeller, Anders H. Berg et al. | | | | |
