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We investigate fermionic Mott insulators in a geometrically frustrated triangular lattice, a paradigm model system for studying spin liquids and spontaneous time-reversal symmetry breaking. Our study demonstrates the preparation of triangular Mott insulators and reveals antiferromagnetic spin-spin correlations among all nearest neighbors. We employ a real-space triangular-geometry quantum gas microscope to measure density and spin observables. Comparing experimental results with calculations based on numerical linked cluster expansions and quantum Monte Carlo techniques, we demonstrate thermometry in the frustrated system. Our experimental platform introduces an alternative approach to frustrated lattices which paves the way for future investigations of exotic quantum magnetism which may lead to a direct detection of quantum spin liquids in Hubbard systems. 

Diadenosine tetraphosphate (Ap4A) is a putative second messenger molecule that is conserved from bacteria to man. Nevertheless, its physiological role, and the underlying molecular mechanisms, are poorly characterized. We investigated the molecular mechanism by which Ap4A regulates inosine-5’-monophosphate dehydrogenase (IMPDH, a key branching point enzyme for the biosynthesis of adenosine or guanosine nucleotides) in Bacillus subtilis. We solved the crystal structure of BsIMPDH bound to Ap4A at a resolution of 2.45 Å to show that Ap4A binds to the interface between two IMPDH subunits, acting as the glue that switches active IMPDH tetramers into less active octamers. Guided by these insights, we engineered mutant strains of B. subtilis that bypass Ap4A-dependent IMPDH regulation without perturbing intracellular Ap4A pools themselves. We used metabolomics suggesting that these mutants have a dysregulated purine, and in particular GTP, metabolome and phenotypic analysis showing increased sensitivity of B. subtilis IMPDH mutant strains to heat compared with wild-type. Our study identifies a central role for IMPDH in remodelling metabolism and heat resistance, and provides evidence that Ap4A can function as an alarmone. 

Abstract Precise control of gene expression is critical for biological research and biotechnology. However, transient plasmid transfections in mammalian cells produce a wide distribution of copy numbers per cell, and consequently, high expression heterogeneity. Here, we report plasmid-based synthetic circuits – Equalizers – that buffer copy-number variation at the single-cell level. Equalizers couple a transcriptional negative feedback loop with post-transcriptional incoherent feedforward control. Computational modeling suggests that the combination of these two topologies enables Equalizers to operate over a wide range of plasmid copy numbers. We demonstrate experimentally that Equalizers outperform other gene dosage compensation topologies and produce as low cell-to-cell variation as chromosomally integrated genes. We also show that episome-encoded Equalizers enable the rapid generation of extrachromosomal cell lines with stable and uniform expression. Overall, Equalizers are simple and versatile devices for homogeneous gene expression and can facilitate the engineering of synthetic circuits that function reliably in every cell. 

Lode gold deposits, which are currently the world’s major gold supply, have been shown to be generated mostly by phase separation of metamorphic fluids and/or interaction between these fluids and wall rocks. Here we use garnet oxygen isotopes by secondary ion mass spectrometry to document the crucial role of magmatic hydrothermal fluids and their mixing with meteoric water in the formation of the world-class Dongping gold deposit in the North China Craton. Garnet grains from quartz veins of various paragenetic stages and the mineralized alteration envelope at Dongping have dynamic δ 18 O variations of 3.8 to −11.0‰, with large intragrain fluctuations up to 5.3‰. These values correspond to calculated δ 18 O values of 6.1 to −9.1‰ for the hydrothermal fluids from which the garnet formed. The isotope data, notably the cyclic alternation in δ 18 O within individual garnet grains, are best interpreted to reflect multiple pulses of magmatically derived fluids and subsequent mixing of each pulse with variable amounts of meteoric water. The results presented here allow us to quantify the significant interplay between magmatic hydrothermal fluids and meteoric water that spanned the entire mineralization history and triggered gold deposition of a lode gold deposit. This study highlights the potential use of in situ oxygen isotope analysis of garnet in tracing the origin and evolution of hydrothermal fluids in the Earth’s crust that may have formed other giant ore deposits. 

Abstract The alarmone nucleotides guanosine tetraphosphate and pentaphosphate, commonly referred to as (p)ppGpp, regulate bacterial responses to nutritional and other stresses. There is evidence for potential existence of a third alarmone, guanosine-5′-monophosphate-3′-diphosphate (pGpp), with less-clear functions. Here, we demonstrate the presence of pGpp in bacterial cells, and perform a comprehensive screening to identify proteins that interact respectively with pGpp, ppGpp and pppGpp in Bacillus species. Both ppGpp and pppGpp interact with proteins involved in inhibition of purine nucleotide biosynthesis and with GTPases that control ribosome assembly or activity. By contrast, pGpp interacts with purine biosynthesis proteins but not with the GTPases. In addition, we show that hydrolase NahA (also known as YvcI) efficiently produces pGpp by hydrolyzing (p)ppGpp, thus modulating alarmone composition and function. Deletion of nahA leads to reduction of pGpp levels, increased (p)ppGpp levels, slower growth recovery from nutrient downshift, and loss of competitive fitness. Our results support the existence and physiological relevance of pGpp as a third alarmone, with functions that can be distinct from those of (p)ppGpp. 

Living organisms need energy to stay alive; in cells, this energy is supplied in the form of a small molecule called adenosine triphosphate, or ATP, a nucleotide that stores energy in the bonds between its three phosphate groups. ATP is present in all living cells and is often referred to as the energy currency of the cell, because it can be easily stored and transported to where it is needed. However, it is unknown why cells rely so heavily on ATP when a highly similar nucleotide called guanosine triphosphate, or GTP, could also act as an energy currency. There are several examples of proteins that originally used GTP and have since evolved to use ATP, but it is not clear why this switch occurred. One suggestion is that ATP is the more readily available nucleotide in the cell. To test this hypothesis, Updegrove, Harke et al. studied a protein that helps bacteria transition into spores, which are hardier and can survive in extreme environments until conditions become favorable for bacteria to grow again. In modern bacteria, this protein uses ATP to provide energy, but it evolved from an ancestral protein that used GTP instead. First, Updegrove, Harke et al. engineered the protein so that it became more similar to the ancestral protein and used GTP instead of ATP. When this was done, the protein gained the ability to break down GTP and release energy from it, but it no longer performed its enzymatic function. This suggests that both the energy released and the source of that energy are important for a protein’s activity. Further analysis showed that the modern version of the protein has evolved to briefly hold on to ATP after releasing its energy, which did not happen with GTP in the modified protein. Updegrove, Harke et al. also discovered that the levels of GTP in a bacterial cell fall as it transforms into a spore, while ATP levels remain relatively high. This suggests that ATP may indeed have become the source of energy of choice because it was more available. These findings provide insights into how ATP became the energy currency in cells, and suggest that how ATP is bound by proteins can impact a protein’s activity. Additionally, these experiments could help inform the development of drugs targeting proteins that bind nucleotides: it may be essential to consider the entirety of the binding event, and not just the release of energy.