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"Tang, Y"
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Non-equilibrium conditions inside rock pores drive fission, maintenance and selection of coacervate protocells
Key requirements for the first cells on Earth include the ability to compartmentalize and evolve. Compartmentalization spatially localizes biomolecules from a dilute pool and an evolving cell, which, as it grows and divides, permits mixing and propagation of information to daughter cells. Complex coacervate microdroplets are excellent candidates as primordial cells with the ability to partition and concentrate molecules into their core and support primitive and complex biochemical reactions. However, the evolution of coacervate protocells by fusion, growth and fission has not yet been demonstrated. In this work, a primordial environment initiated the evolution of coacervate-based protocells. Gas bubbles inside heated rock pores perturb the coacervate protocell distribution and drive the growth, fusion, division and selection of coacervate microdroplets. Our findings provide a compelling scenario for the evolution of membrane-free coacervate microdroplets on the early Earth, induced by common gas bubbles within heated rock pores.
Complex coacervate microdroplets have been proposed as primordial cells, but their ability to evolve by fusion, growth and fission has not yet been demonstrated. Now, it has been shown that gas bubbles inside heated rock pores can drive the growth, fusion, division and selection of coacervate microdroplets.
Journal Article
Charge-density reduction promotes ribozyme activity in RNA–peptide coacervates via RNA fluidization and magnesium partitioning
It has long been proposed that phase-separated compartments can provide a basis for the formation of cellular precursors in prebiotic environments. However, we know very little about the properties of coacervates formed from simple peptides, their compatibility with ribozymes or their functional significance. Here we assess the conditions under which functional ribozymes form coacervates with simple peptides. We find coacervation to be most robust when transitioning from long homopeptides to shorter, more pre-biologically plausible heteropeptides. We mechanistically show that these RNA–peptide coacervates display peptide-dependent material properties and cofactor concentrations. We find that the interspacing of cationic and neutral amino acids increases RNA mobility, and we use isothermal calorimetry to reveal sequence-dependent Mg
2+
partitioning, two critical factors that together enable ribozyme activity. Our results establish how peptides of limited length, homogeneity and charge density facilitate the compartmentalization of active ribozymes into non-gelating, magnesium-rich coacervates, a scenario that could be applicable to cellular precursors with peptide-dependent functional phenotypes.
Phase-separated compartments have long been proposed as precursors to cellular life. Now, it has been shown that RNA–peptide protocells are more robust when formed using shorter (rather than longer) peptides, and that peptide sequence determines the functional materials properties of these compartments.
Journal Article
Noninvasive Prenatal Diagnosis of Fetal Trisomy 18 and Trisomy 13 by Maternal Plasma DNA Sequencing
Massively parallel sequencing of DNA molecules in the plasma of pregnant women has been shown to allow accurate and noninvasive prenatal detection of fetal trisomy 21. However, whether the sequencing approach is as accurate for the noninvasive prenatal diagnosis of trisomy 13 and 18 is unclear due to the lack of data from a large sample set. We studied 392 pregnancies, among which 25 involved a trisomy 13 fetus and 37 involved a trisomy 18 fetus, by massively parallel sequencing. By using our previously reported standard z-score approach, we demonstrated that this approach could identify 36.0% and 73.0% of trisomy 13 and 18 at specificities of 92.4% and 97.2%, respectively. We aimed to improve the detection of trisomy 13 and 18 by using a non-repeat-masked reference human genome instead of a repeat-masked one to increase the number of aligned sequence reads for each sample. We then applied a bioinformatics approach to correct GC content bias in the sequencing data. With these measures, we detected all (25 out of 25) trisomy 13 fetuses at a specificity of 98.9% (261 out of 264 non-trisomy 13 cases), and 91.9% (34 out of 37) of the trisomy 18 fetuses at 98.0% specificity (247 out of 252 non-trisomy 18 cases). These data indicate that with appropriate bioinformatics analysis, noninvasive prenatal diagnosis of trisomy 13 and trisomy 18 by maternal plasma DNA sequencing is achievable.
Journal Article
The living interface between synthetic biology and biomaterial design
Recent far-reaching advances in synthetic biology have yielded exciting tools for the creation of new materials. Conversely, advances in the fundamental understanding of soft-condensed matter, polymers and biomaterials offer new avenues to extend the reach of synthetic biology. The broad and exciting range of possible applications have substantial implications to address grand challenges in health, biotechnology and sustainability. Despite the potentially transformative impact that lies at the interface of synthetic biology and biomaterials, the two fields have, so far, progressed mostly separately. This Perspective provides a review of recent key advances in these two fields, and a roadmap for collaboration at the interface between the two communities. We highlight the near-term applications of this interface to the development of hierarchically structured biomaterials, from bioinspired building blocks to ‘living’ materials that sense and respond based on the reciprocal interactions between materials and embedded cells.
This Perspective reviews the complementary developments in synthetic biology and biomaterials and discusses how convergence of these two fields creates a promising design strategy for the fabrication of tailored living materials for medicine and biotechnology.
Journal Article
Photooxidation and quantum confinement effects in exfoliated black phosphorus
Thin layers of black phosphorus have recently raised interest owing to their two-dimensional (2D) semiconducting properties, such as tunable direct bandgap and high carrier mobilities. This lamellar crystal of phosphorus atoms can be exfoliated down to monolayer 2D-phosphane (also called phosphorene) using procedures similar to those used for graphene. Probing the properties has, however, been challenged by a fast degradation of the thinnest layers on exposure to ambient conditions. Herein, we investigate this chemistry using
in situ
Raman and transmission electron spectroscopies. The results highlight a thickness-dependent photoassisted oxidation reaction with oxygen dissolved in adsorbed water. The oxidation kinetics is consistent with a phenomenological model involving electron transfer and quantum confinement as key parameters. A procedure carried out in a glove box is used to prepare mono-, bi- and multilayer 2D-phosphane in their pristine states for further studies on the effect of layer thickness on the Raman modes. Controlled experiments in ambient conditions are shown to lower the A
g
1
/A
g
2
intensity ratio for ultrathin layers, a signature of oxidation.
The degradation of exfoliated black phosphorus in ambient conditions may limit its use in electronic devices. The combined effects of light irradiation and exposure to oxygen on mono- and multilayers of this material are now investigated.
Journal Article
Circulating cell-free DNA in serum as a biomarker for diagnosis and prognostic prediction of colorectal cancer
Background:
To verify whether the concentrations and integrity index of circulating cell-free DNA (ccf-DNA) in serum may be clinically useful for the diagnosis and progression monitoring of colorectal cancer (CRC) patients.
Methods:
Serum samples were collected from 104 with primary CRC, 85 with operated CRC, 16 with recurrent/metastatic CRC, 63 patients with intestinal polyps and 110 normal controls. Long (247 bp) and short (115 bp) DNA fragments in serum were detected by real-time quantitative PCR by amplifying the ALU repeats (ALU-qPCR). Serum carcinoembryonic antigen (CEA) level was detected by ARCHITECT assay.
Results:
The median absolute serum ALU115 and ALU247/115 in primary CRC group was significantly higher than those in intestinal polyp and normal control groups (both
P
<0.0001), in recurrent/metastatic CRC was significantly higher compared with primary CRC (
P
=0.0021,
P
=0.0018) or operated CRC (
P
<0.0001, respectively) and during follow-up, ALU115 and ALU247/115 were increased before surgery and decreased significantly after surgery.
Conclusions:
Combined detection of ALU115, ALU247/115 and CEA could improve the diagnostic efficiency for CRC. Serum DNA concentrations and integrity index may be valuable in early complementary diagnosis and monitoring of progression and prognosis of CRC.
Journal Article
Fatty acid membrane assembly on coacervate microdroplets as a step towards a hybrid protocell model
Mechanisms of prebiotic compartmentalization are central to providing insights into how protocellular systems emerged on the early Earth. Protocell models are based predominantly on the membrane self-assembly of fatty-acid vesicles, although membrane-free scenarios that involve liquid–liquid microphase separation (coacervation) have also been considered. Here we integrate these alternative models of prebiotic compartmentalization and develop a hybrid protocell model based on the spontaneous self-assembly of a continuous fatty-acid membrane at the surface of preformed coacervate microdroplets prepared from cationic peptides/polyelectrolytes and adenosine triphosphate or oligo/polyribonucleotides. We show that the coacervate-supported membrane is multilamellar, and mediates the selective uptake or exclusion of small and large molecules. The coacervate interior can be disassembled without loss of membrane integrity, and fusion and growth of the hybrid protocells can be induced under conditions of high ionic strength. Our results highlight how notions of membrane-mediated compartmentalization, chemical enrichment and internalized structuration can be integrated in protocell models via simple chemical and physical processes.
A hybrid protocell model is described in which a fatty acid membrane spontaneously assembles on the surface of coacervate microdroplets with molecularly crowded interiors. The membrane-enclosed protocells exhibit uptake and exclusion properties that differ from the uncoated droplets. The internal structure can be disassembled at high ionic strength without loss of membrane integrity. This model may help to reconcile alternative mechanisms of prebiotic compartmentalization.
Journal Article
IMPACT OF TYPHOONS ON THE OCEAN IN THE PACIFIC
Tropical cyclones (TCs) change the ocean by mixing deeper water into the surface layers, by the direct air–sea exchange of moisture and heat from the sea surface, and by inducing currents, surface waves, and waves internal to the ocean. In turn, the changed ocean influences the intensity of the TC, primarily through the action of surface waves and of cooler surface temperatures that modify the air–sea fluxes. The Impact of Typhoons on the Ocean in the Pacific (ITOP) program made detailed measurements of three different TCs (i.e., typhoons) and their interaction with the ocean in the western Pacific. ITOP coordinated meteorological and oceanic observations from aircraft and satellites with deployments of autonomous oceanographic instruments from the aircraft and from ships. These platforms and instruments measured typhoon intensity and structure, the underlying ocean structure, and the long-term recovery of the ocean from the storms' effects with a particular emphasis on the cooling of the ocean beneath the storm and the resulting cold wake. Initial results show how different TCs create very different wakes, whose strength and properties depend most heavily on the nondimensional storm speed. The degree to which air–sea fluxes in the TC core were reduced by ocean cooling varied greatly. A warm layer formed over and capped the cold wakes within a few days, but a residual cold subsurface layer persisted for 10–30 days.
Journal Article