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Novel technology to rapidly clone patient-specific, ‘ground state’ stem cells of columnar epithelia reveals their proliferative potential, remarkably precise and origin-dependent lineage commitment as well as genomic stability, despite extensive culturing, thereby skirting limitations associated with pluripotent stem cells.
A new hominin species, Australopithecus deyiremeda, which lived between 3.5 and 3.3 million years ago, at around the same time as species such as Au. afarensis (‘Lucy’), is discovered in Ethiopia; its morphology suggests that some dental features traditionally associated with later genera such as Paranthropus and Homo emerged earlier than previously thought.
The mechanism for chromothripsis, “shattered” chromosomes that can be observed in cancer cells, is unknown; here, using live-cell imaging and single-cell sequencing, chromothripsis is shown to occur after a chromosome is isolated into a micronucleus, an abnormal nuclear structure.
Whole-genome sequencing of tumour and germline DNA samples from 92 patients with high-grade serous ovarian cancer identifies frequent gene breakages that inactivate the tumour suppressors RB1, NF1, RAD51B and PTEN, and contribute to chemotherapy resistance; acquired resistance was associated with diverse mechanisms such as reversions of germline BRCA1/2 mutations and overexpression of the drug efflux pump MDR1.
Trajectory-dependent firing of neurons within the nucleus reuniens of the thalamus–hippocampus circuit predicted subsequent running direction, and disruption of this circuit reduced predictive firing in the hippocampus, suggesting that the thalamus is a key node in the integration of signals during goal-oriented navigation.
The lymphatic system is thought to be derived by transdifferentiation of venous endothelium; this study shows that the origin of cardiac lymphatics is in fact more heterogeneous, including both venous and non-venous origins and that lymphangiogenesis occurs in the adult heart following myocardial infarction and can be enhanced to improve heart function.
The lymphatic endothelium is thought to arise entirely from trans-differentiation of the venous endothelium; a new mechanism of lymphatic vessel formation is identified in zebrafish, whereby the lymphatic vessels derive from specialized angioblasts within the floor of the cardinal vein.
Tool making has been considered to be an attribute of the genus Homo; this paper reports 3.3-million-year-old stone tools and the early timing of these tools provides evidence that the making and use of stone tools by hominins occurred before the evolution of our own genus.
Calcium imaging of the brain of tethered flies walking in a virtual reality arena showed that a population of neurons with dendrites that tile the ‘ellipsoid body’ use information from visual landmarks and the fly's own rotation to compute heading; this suggests insects possess neurons with similarities to ‘head direction cells’ known to contribute to spatial navigation in mammalian brains.
Here the X-ray crystal structures of the Drosophila dopamine transporter bound to dopamine, D-amphetamine, methamphetamine and cocaine are solved; these structures show how a neurotransmitter, small molecule stimulants and cocaine bind to a biogenic amine transporter, and are examples of how the ligand binding site of a neurotransmitter transporter can remodel itself to accommodate structurally unrelated small molecules that are different in shape, size and polarity or charge.
A previously unknown type of stem cell that can engraft in specific regions of the mouse epiblast is described; these region-selective pluripotent stem cells display notable intra- and inter-specific chimaera competency and will help to further our understanding of mammalian development.
This study identifies a clade of archaea that is the immediate sister group of eukaryotes in phylogenetic analyses, and that also has a repertoire of proteins otherwise characteristic of eukaryotes—proteins that would have provided the first eukaryotes with a ‘starter kit’ for the genomic and cellular complexity characteristic of the eukaryotic cell.
Using the CRISPR/Cas9 system, up to four frequently occurring colorectal cancer mutations were introduced alone or in combination into stem cell organoids derived from human small intestinal or colon tissue, allowing an in-depth investigation of the contribution of these mutations to cancer progression.
Cell-type-specific electrical activity manipulations and deep-brain imaging in mice of neuronal populations associated with homeostasis of nutrient or fluid intake reveals that learning is conditioned by a negative-valence signal from the hunger-mediating AGRP neurons and also from the thirst-mediating neurons in the subfornical organ.
The structure of the human ribosome at high resolution has been solved; by combining single-particle cryo-EM and atomic model building, local resolution of 2.9 Å was achieved within the most stable areas of the structure.
Combining neural manipulation in freely behaving animals, physiological studies and electron microscopy reconstruction in the Drosophila larva identifies a complex multilsensory circuit involved in the selection of larval escape modes that exhibits a multilevel multimodal convergence architecture.
A study of pup retrieval behaviour in mice shows that oxytocin modulates cortical responses to pup calls specifically in the left auditory cortex; in virgin females, call-evoked responses were enhanced, thus increasing their salience, by pairing oxytocin delivery in the left auditory cortex with the calls, suggesting enhancement was a result of balancing the magnitude and timing of inhibition with excitation.
The high-resolution electron cryo-microscopy structure of the full-length human TRPA1 ion channel is presented; the structure reveals a unique ankyrin repeat domain arrangement, a tetrameric coiled-coil in the centre of the channel that acts as a binding site for inositol hexakisphosphate, an outer poor domain with two pore helices, and a new drug binding site, findings that collectively provide mechanistic insight into TRPA1 regulation.
