Research articles

Medulloblastoma is a malignant childhood brain tumour presenting major clinical challenges; here, a comprehensive genome-wide DNA methylation data set from human and mouse tumours, coupled with analysis of histone modifications, RNA transcripts and genome sequencing, uncovers a wealth of alterations that provide insights into the epigenetic regulation of transcription and genome organization in medulloblastoma pathogenesis.

The structure of human GLUT1 in an inward-open conformation is reported; access to the structure of the human protein, instead of just a bacterial homologue, made it possible to map (inactivating) mutations associated with GLUT1 deficiency syndrome onto the structure.

Several proteins localized at membrane contact sites contain an SMP domain, which has been proposed to act as a lipid-binding module; here, the crystal structure of a fragment of the extended synaptotagmin 2 protein, including its SMP, is presented, and indicates that this protein may have a direct role in lipid transport.

Analysis of global historical data in the Northern and Southern hemispheres reveals a statistically significant, poleward migration of 1° per decade in the average latitude at which tropical cyclones have achieved their lifetime-maximum intensity over the past 30 years.

Five classical Cepheids have been detected in the outer parts of our Galaxy beyond the Galactic bulge; they are probably associated with the gas in the flared disk and, if so, they are the first stars to be identified in the flare.

T cells develop from thymic precursor cells that are constantly replaced with newly arriving bone marrow progenitor cells, and the ‘old’ and ‘new’ cells are shown here to compete; in the absence of cell competition, when the influx of new bone marrow progenitor cells is blocked, the old cells acquire the ability to self-renew and eventually become transformed, leading to the development of a form of leukaemia.

Ageing in the worm Caenorhabditis elegans is shown to be delayed by supplementation with α-ketoglutarate, an effect that is probably mediated by ATP synthase—which is identified as a direct target of α-ketoglutarate—and target of rapamycin (TOR).

Mfsd2a is the major transporter of the omega-3 fatty acid docosahexaenoic acid (DHA) into brain, with Mfsd2a-knockout mice showing reduced DHA in brain, neuronal cell loss in hippocampus and cerebellum, behavioural disorders and reduced brain size; DHA is transported in a sodium-dependent manner, in the form of lysophosphatidylcholines (LPCs) carrying long-chain fatty acids.

Sensory modality-specific thalamic inputs are shown to instruct the differentiation and function of postsynaptic target neurons in the cortex, thus controlling the development and functional segregation of cortical circuits.

Mfsd2a is a key regulator of blood–brain barrier (BBB) formation and function in mice: Mfsd2a is selectively expressed in BBB-containing blood vessels in the CNS; Mfsd2a^−/− mice have a leaky BBB and increased vesicular transcytosis in CNS endothelial cells; and Mfsd2a endothelial expression is regulated by pericytes to facilitate BBB integrity.

A novel combined NMR and EPR spectroscopy approach reveals the structure and assembly mechanism of a 70-kDa bacterial ribonucleoprotein complex acting as a protein sponge in translational regulation.

Natural products citrinalin B and cyclopiamine B, which contain basic nitrogen atoms that are susceptible to oxidation during synthesis, can be synthesized by the selective introduction and removal of functional groups.

Sexual experience brings radical changes in how male mice behave with pups—virgin males attack them whereas mature fathers display parental care; here the authors identify a subset of hypothalamic neurons whose ablation leads to parental deficits in both males and females, and whose activation in virgin males suppresses aggression and induces pup grooming.

Human-caused groundwater depletion in California’s San Joaquin Valley contributes to uplift of the surrounding mountains and may affect the stability of the San Andreas Fault.

It is known that in the silkworm (Bombyx mori), males have two Z sex chromosomes whereas females have Z and W and the W chromosome has a dominant role in female determination; here a single female-specific W-chromosome-derived PIWI-interacting RNA is shown to be the feminizing factor in B. mori.

Recordings from monkeys during motor learning suggest that durations of complex-spike (CS) responses to climbing-fibre inputs are meaningful signals correlated across the Purkinje-cell population during motor learning; longer climbing-fibre bursts lead to longer-duration CS responses, larger synaptic depression and stronger learning, thus forming a graded instruction.

How sulphur is incorporated into sulphur-containing secondary metabolites is poorly understood; here, the bacterium Amycolatopsis orientalis is shown to co-opt sulphur-carrier proteins from primary metabolic pathways to facilitate the biosynthesis of sulphur-containing natural products.

Plasticity within neuronal microcircuits is believed to be the substrate of learning, and this study identifies two distinct disinhibitory mechanisms involving interactions between PV⁺ and SOM⁺ interneurons that dynamically regulate principal neuron activity in the amygdala and thereby control auditory fear learning.

CFIm25 is identified as a factor that prevents messenger RNAs being shortened due to altered 3′ polyadenylation, which typically occurs when cells undergo high proliferation and correlates with increased tumorigenic activity in glioblastoma tumours.

Crystal structures of human and prokaryotic ribosomal oxygenases reported here, with and without their ribosomal protein substrates, support their assignments as hydroxylases, and provide insights into the evolution of the JmjC-domain-containing hydroxylases and demethylases.