Light- and ink-based three-dimensional (3D) printing methods allow the rapid design and fabrication of materials without the need for expensive tooling, dies or lithographic masks. They have led to an era of manufacturing in which computers can control the fabrication of soft matter that has tunable mechanical, electrical and other functional properties. The expanding range of printable materials, coupled with the ability to programmably control their composition and architecture across various length scales, is driving innovation in myriad applications. This is illustrated by examples of biologically inspired composites, shape-morphing systems, soft sensors and robotics that only additive manufacturing can produce.

Cells grow well only in a narrow range of physiological conditions. Surviving extreme conditions requires the instantaneous expression of chaperones that help to overcome stressful situations. To ensure the preferential synthesis of these heat-shock proteins, cells inhibit transcription, pre-mRNA processing and nuclear export of non-heat-shock transcripts, while stress-specific mRNAs are exclusively exported and translated. How cells manage the selective retention of regular transcripts and the simultaneous rapid export of heat-shock mRNAs is largely unknown. In Saccharomyces cerevisiae, the shuttling RNA adaptor proteins Npl3, Gbp2, Hrb1 and Nab2 are loaded co-transcriptionally onto growing pre-mRNAs. For nuclear export, they recruit the export-receptor heterodimer Mex67-Mtr2 (TAP-p15 in humans). Here we show that cellular stress induces the dissociation of Mex67 and its adaptor proteins from regular mRNAs to prevent general mRNA export. At the same time, heat-shock mRNAs are rapidly exported in association with Mex67, without the need for adapters. The immediate co-transcriptional loading of Mex67 onto heat-shock mRNAs involves Hsf1, a heat-shock transcription factor that binds to heat-shock-promoter elements in stress-responsive genes. An important difference between the export modes is that adaptor-protein-bound mRNAs undergo quality control, whereas stress-specific transcripts do not. In fact, regular mRNAs are converted into uncontrolled stress-responsive transcripts if expressed under the control of a heat-shock promoter, suggesting that whether an mRNA undergoes quality control is encrypted therein. Under normal conditions, Mex67 adaptor proteins are recruited for RNA surveillance, with only quality-controlled mRNAs allowed to associate with Mex67 and leave the nucleus. Thus, at the cost of error-free mRNA formation, heat-shock mRNAs are exported and translated without delay, allowing cells to survive extreme situations.

NLRs (nucleotide-binding domain and leucine-rich repeats) belong to a large family of cytoplasmic sensors that regulate an extraordinarily diverse range of biological functions. One of these functions is to contribute to immunity against infectious diseases, but dysregulation of their functional activity leads to the development of inflammatory and autoimmune diseases. Cytoplasmic innate immune sensors, including NLRs, are central regulators of intestinal homeostasis. NLRC3 (also known as CLR16.2 or NOD3) is a poorly characterized member of the NLR family and was identified in a genomic screen for genes encoding proteins bearing leucine-rich repeats (LRRs) and nucleotide-binding domains. Expression of NLRC3 is drastically reduced in the tumour tissue of patients with colorectal cancer compared to healthy tissues, highlighting an undefined potential function for this sensor in the development of cancer. Here we show that mice lacking NLRC3 are hyper-susceptible to colitis and colorectal tumorigenesis. The effect of NLRC3 is most dominant in enterocytes, in which it suppresses activation of the mTOR signalling pathways and inhibits cellular proliferation and stem-cell-derived organoid formation. NLRC3 associates with PI3Ks and blocks activation of the PI3K-dependent kinase AKT following binding of growth factor receptors or Toll-like receptor 4. These findings reveal a key role for NLRC3 as an inhibitor of the mTOR pathways, mediating protection against colorectal cancer.

Proxy-based indicators of past climate change show that current global climate models systematically underestimate Holocene-epoch climate variability on centennial to multi-millennial timescales, with the mismatch increasing for longer periods. Proposed explanations for the discrepancy include ocean-atmosphere coupling that is too weak in models, insufficient energy cascades from smaller to larger spatial and temporal scales, or that global climate models do not consider slow climate feedbacks related to the carbon cycle or interactions between ice sheets and climate. Such interactions, however, are known to have strongly affected centennial- to orbital-scale climate variability during past glaciations, and are likely to be important in future climate change. Here we show that fluctuations in Antarctic Ice Sheet discharge caused by relatively small changes in subsurface ocean temperature can amplify multi-centennial climate variability regionally and globally, suggesting that a dynamic Antarctic Ice Sheet may have driven climate fluctuations during the Holocene. We analysed high-temporal-resolution records of iceberg-rafted debris derived from the Antarctic Ice Sheet, and performed both high-spatial-resolution ice-sheet modelling of the Antarctic Ice Sheet and multi-millennial global climate model simulations. Ice-sheet responses to decadal-scale ocean forcing appear to be less important, possibly indicating that the future response of the Antarctic Ice Sheet will be governed more by long-term anthropogenic warming combined with multi-centennial natural variability than by annual or decadal climate oscillations.

Endogenous viral elements are increasingly found in eukaryotic genomes, yet little is known about their origins, dynamics, or function. Here we provide a compelling example of a DNA virus that readily integrates into a eukaryotic genome where it acts as an inducible antiviral defence system. We found that the virophage mavirus, a parasite of the giant Cafeteria roenbergensis virus (CroV), integrates at multiple sites within the nuclear genome of the marine protozoan Cafeteria roenbergensis. The endogenous mavirus is structurally and genetically similar to eukaryotic DNA transposons and endogenous viruses of the Maverick/Polinton family. Provirophage genes are not constitutively expressed, but are specifically activated by superinfection with CroV, which induces the production of infectious mavirus particles. Virophages can inhibit the replication of mimivirus-like giant viruses and an anti-viral protective effect of provirophages on their hosts has been hypothesized. We find that provirophage-carrying cells are not directly protected from CroV; however, lysis of these cells releases infectious mavirus particles that are then able to suppress CroV replication and enhance host survival during subsequent rounds of infection. The microbial host-parasite interaction described here involves an altruistic aspect and suggests that giant-virus-induced activation of provirophages might be ecologically relevant in natural protist populations.

The Greenland Ice Sheet (GIS) contains the equivalent of 7.4 metres of global sea-level rise. Its stability in our warming climate is therefore a pressing concern. However, the sparse proxy evidence of the palaeo-stability of the GIS means that its history is controversial (compare refs 2 and 3 to ref. 4). Here we show that Greenland was deglaciated for extended periods during the Pleistocene epoch (from 2.6 million years ago to 11,700 years ago), based on new measurements of cosmic-ray-produced beryllium and aluminium isotopes (10Be and 26Al) in a bedrock core from beneath an ice core near the GIS summit. Models indicate that when this bedrock site is ice-free, any remaining ice is concentrated in the eastern Greenland highlands and the GIS is reduced to less than ten per cent of its current volume. Our results narrow the spectrum of possible GIS histories: the longest period of stability of the present ice sheet that is consistent with the measurements is 1.1 million years, assuming that this was preceded by more than 280,000 years of ice-free conditions. Other scenarios, in which Greenland was ice-free during any or all Pleistocene interglacials, may be more realistic. Our observations are incompatible with most existing model simulations that present a continuously existing Pleistocene GIS. Future simulations of the GIS should take into account that Greenland was nearly ice-free for extended periods under Pleistocene climate forcing.

Unlike spiral galaxies such as the Milky Way, the majority of the stars in massive elliptical galaxies were formed in a short period early in the history of the Universe. The duration of this formation period can be measured using the ratio of magnesium to iron abundance ([Mg/Fe]) in spectra, which reflects the relative enrichment by core-collapse and type Ia supernovae. For local galaxies, [Mg/Fe] probes the combined formation history of all stars currently in the galaxy, including younger and metal-poor stars that were added during late-time mergers. Therefore, to directly constrain the initial star-formation period, we must study galaxies at earlier epochs. The most distant galaxy for which [Mg/Fe] had previously been measured is at a redshift of z ≈ 1.4, with [Mg/Fe] = . A slightly earlier epoch (z ≈ 1.6) was probed by combining the spectra of 24 massive quiescent galaxies, yielding an average [Mg/Fe] = 0.31 ± 0.12 (ref. 7). However, the relatively low signal-to-noise ratio of the data and the use of index analysis techniques for both of these studies resulted in measurement errors that are too large to allow us to form strong conclusions. Deeper spectra at even earlier epochs in combination with analysis techniques based on full spectral fitting are required to precisely measure the abundance pattern shortly after the major star-forming phase (z > 2). Here we report a measurement of [Mg/Fe] for a massive quiescent galaxy at a redshift of z = 2.1, when the Universe was three billion years old. With [Mg/Fe] = 0.59 ± 0.11, this galaxy is the most Mg-enhanced massive galaxy found so far, having twice the Mg enhancement of similar-mass galaxies today. The abundance pattern of the galaxy is consistent with enrichment exclusively by core-collapse supernovae and with a star-formation timescale of 0.1 to 0.5 billion years-characteristics that are similar to population II stars in the Milky Way. With an average past star-formation rate of 600 to 3,000 solar masses per year, this galaxy was among the most vigorous star-forming galaxies in the Universe.