We present the Runaways and Isolated O-Type Star Spectroscopic Survey of the SMC (RIOTS4), a spatially complete survey of uniformly selected field OB stars that covers the entire star-forming body of ...the Small Magellanic Cloud (SMC). Using the IMACS (Inamori-Magellan Areal Camera and Spectrograph) multislit spectrograph and MIKE (Magellan Inamori Kyocera Echelle) echelle spectrograph on the Magellan telescopes, we obtained spectra of 374 early-type field stars that are at least 28 pc from any other OB candidates. We also obtained spectra of an additional 23 field stars in the SMC bar identified from slightly different photometric criteria. RIOTS4 confirmed a steep upper initial mass function in the field, apparently caused by the inability of the most massive stars to form in the smallest clusters. Our survey also yields evidence for in situ field OB star formation, and properties of field emission-line star populations, including sgBe stars and classical Oe/Be stars. We also discuss the radial velocity distribution and its relation to SMC kinematics and runaway stars.
Natural environments are filled with multiple, often competing, signals. In contrast, biological systems are often studied in “well-controlled” environments where only a single input is varied, ...potentially missing important interactions between signals. Catabolite repression of galactose by glucose is one of the best-studied eukaryotic signal integration systems. In this system, it is believed that galactose metabolic (GAL) genes are induced only when glucose levels drop below a threshold. In contrast, we show that GAL gene induction occurs at a constant external galactose:glucose ratio across a wide range of sugar concentrations. We systematically perturbed the components of the canonical galactose/glucose signaling pathways and found that these components do not account for ratio sensing. Instead we provide evidence that ratio sensing occurs upstream of the canonical signaling pathway and results from the competitive binding of the two sugars to hexose transporters. We show that a mutant that behaves as the classical model expects (i.e., cannot use galactose above a glucose threshold) has a fitness disadvantage compared with wild type. A number of common biological signaling motifs can give rise to ratio sensing, typically through negative interactions between opposing signaling molecules. We therefore suspect that this previously unidentified nutrient sensing paradigm may be common and overlooked in biology.
Significance Almost all biological systems need to respond to multiple simultaneous inputs. In yeast catabolite repression, a textbook model for signaling integration, the preferred carbohydrate glucose is thought to inhibit the induction of galactose genes when above a threshold concentration. Instead, we show that galactose metabolic genes induction depends on the ratio of galactose and glucose. Surprisingly, a critical portion of the information processing that determines the ratio response occurs upstream of the canonical signaling pathway. The use of modern combinatorial approaches has thus revealed a new signal processing paradigm that may be common throughout biology.
Massive urbanization and increasing disposable incomes favor a rapid transition in diets and lifestyle in sub-Saharan Africa (SSA). As a result, the SSA population is becoming increasingly vulnerable ...to the double burden of malnutrition and obesity. This, combined with the increasing pressure to produce sufficient food and provide employment for this growing population together with the threat of climate change-induced declining crop yields, requires urgent sustainable solutions. Can an increase in the cultivation of climate-resilient crops (CRCs) and their utilization to produce attractive, convenient and nutritious bread products contribute to climate change adaptation and healthy and sustainable diets? A food system analysis of the bread food value chain in SSA indicates that replacement of refined, mostly imported, wheat in attractive bread products could (1) improve food and nutrition security, (2) bring about a shift to more nutritionally balanced diets, (3) increase economic inclusiveness and equitable benefits, and (4) improve sustainability and resilience of the food system. The food system analysis also provided systematic insight into the challenges and hurdles that need to be overcome to increase the availability, affordability and uptake of CRCs. Proposed interventions include improving the agronomic yield of CRCs, food product technology, raising consumer awareness and directing policies. Overall, integrated programs involving all stakeholders in the food system are needed.
Objective: Asymptomatic primary hyperparathyroidism (PHPT) is a common clinical problem. The purpose of this report is to guide the use of diagnostic tests for this condition in clinical practice.
...Participants: Interested professional societies selected a representative for the consensus committee and provided funding for a one-day meeting. A subgroup of this committee set the program and developed key questions for review. Consensus was established at a closed meeting that followed. The conclusions were then circulated to the participating professional societies.
Evidence: Each question was addressed by a relevant literature search (on PubMed), and the data were presented for discussion at the group meeting.
Consensus Process: Consensus was achieved by a group meeting. Statements were prepared by all authors, with comments relating to accuracy from the diagnosis subgroup and by representatives from the participating professional societies.
Conclusions: We conclude that: 1) reference ranges should be established for serum PTH in vitamin D-replete healthy individuals; 2) second- and third-generation PTH assays are both helpful in the diagnosis of PHPT; 3) DNA sequence testing can be useful in familial hyperparathyroidism or hypercalcemia; 4) normocalcemic PHPT is a variant of the more common presentation of PHPT with hypercalcemia; 5) serum 25-hydroxyvitamin D levels should be measured and, if vitamin D insufficiency is present, it should be treated as part of any management course; and 6) the estimated glomerular filtration rate should be used to determine the level of kidney function in PHPT: an estimated glomerular filtration rate of less than 60 ml/min · 1.73 m2 should be a benchmark for decisions about surgery in established asymptomatic PHPT.
Responses to key questions about the diagnosis of asymptomatic primary hyperparathyroidism are provided based on the Third International Workshop on primary hyperparathyroidism.
Bacteria increase their metabolic capacity via the acquisition of genetic material or by the mutation of genes already present in the genome. Here, we explore the mechanisms and trade-offs involved ...when
, a bacterium that typically consumes small organic and amino acids, rapidly evolves to expand its metabolic capacity to catabolize glucose after a short period of adaptation to a glucose-rich environment. Using whole-genome sequencing and genetic approaches, we discovered that deletions in a region including the transcriptional repressor (
) that regulates the expression of genes associated with catabolism of
-acetylglucosamine are the common basis for evolved glucose metabolism across populations. The loss of
results in the constitutive expression of genes for an
-acetylglucosamine permease (
) and kinase (
). We demonstrate that promiscuous activities of both NagP and NagK toward glucose allow for the transport and phosphorylation of glucose to glucose-6-phosphate, the initial events of glycolysis otherwise thought to be absent in
C-based metabolic flux analysis uncovered that subsequent utilization was mediated by the Entner-Doudoroff pathway. This is an example whereby gene loss and preexisting enzymatic promiscuity, and not gain-of-function mutations, were the drivers of increased metabolic capacity. However, we observed a significant decrease in the growth rate on lactate after adaptation to glucose catabolism, suggesting that trade-offs may explain why glycolytic function may not be readily observed in
in natural environments despite it being readily accessible through just a single mutational event.
Gains in metabolic capacity are frequently associated with the acquisition of novel genetic material via natural or engineered horizontal gene transfer events. Here, we explored how a bacterium that typically consumes small organic acids and amino acids expands its metabolic capacity to include glucose via a loss of genetic material, a process frequently associated with a deterioration of metabolic function. Our findings highlight how the natural promiscuity of transporters and enzymes can be a key driver in expanding metabolic diversity and that many bacteria may possess a latent metabolic capacity accessible through one or a few mutations that remove regulatory functions. Our discovery of trade-offs between growth on lactate and on glucose suggests why this easily gained trait is not observed in nature.
Measureable rates of genome evolution are well documented in human pathogens but are less well understood in bacterial pathogens in the wild, particularly during and after host switches. Mycoplasma ...gallisepticum (MG) is a pathogenic bacterium that has evolved predominantly in poultry and recently jumped to wild house finches (Carpodacus mexicanus), a common North American songbird. For the first time we characterize the genome and measure rates of genome evolution in House Finch isolates of MG, as well as in poultry outgroups. Using whole-genome sequences of 12 House Finch isolates across a 13-year serial sample and an additional four newly sequenced poultry strains, we estimate a nucleotide diversity in House Finch isolates of only ∼2% of ancestral poultry strains and a nucleotide substitution rate of 0.8-1.2×10(-5) per site per year both in poultry and in House Finches, an exceptionally fast rate rivaling some of the highest estimates reported thus far for bacteria. We also found high diversity and complete turnover of CRISPR arrays in poultry MG strains prior to the switch to the House Finch host, but after the invasion of House Finches there is progressive loss of CRISPR repeat diversity, and recruitment of novel CRISPR repeats ceases. Recent (2007) House Finch MG strains retain only ∼50% of the CRISPR repertoire founding (1994-95) strains and have lost the CRISPR-associated genes required for CRISPR function. Our results suggest that genome evolution in bacterial pathogens of wild birds can be extremely rapid and in this case is accompanied by apparent functional loss of CRISPRs.
Metabolic networks revolve around few metabolites recognized by diverse enzymes and involved in myriad reactions. Though hub metabolites are considered as stepping stones to facilitate the ...evolutionary expansion of biochemical pathways, changes in their production or consumption often impair cellular physiology through their system-wide connections. How does metabolism endure perturbations brought immediately by pathway modification and restore hub homeostasis in the long run? To address this question we studied laboratory evolution of pathway-engineered Escherichia coli that underproduces the redox cofactor NADPH on glucose. Literature suggests multiple possibilities to restore NADPH homeostasis. Surprisingly, genetic dissection of isolates from our twelve evolved populations revealed merely two solutions: (1) modulating the expression of membrane-bound transhydrogenase (mTH) in every population; (2) simultaneously consuming glucose with acetate, an unfavored byproduct normally excreted during glucose catabolism, in two subpopulations. Notably, mTH displays broad phylogenetic distribution and has also played a predominant role in laboratory evolution of Methylobacterium extorquens deficient in NADPH production. Convergent evolution of two phylogenetically and metabolically distinct species suggests mTH as a conserved buffering mechanism that promotes the robustness and evolvability of metabolism. Moreover, adaptive diversification via evolving dual substrate consumption highlights the flexibility of physiological systems to exploit ecological opportunities.
While microbiologists often make the simplifying assumption that genotype determines phenotype in a given environment, it is becoming increasingly apparent that phenotypic heterogeneity (in which one ...genotype generates multiple phenotypes simultaneously even in a uniform environment) is common in many microbial populations. The importance of phenotypic heterogeneity has been demonstrated in a number of model systems involving binary phenotypic states (e.g., growth/non-growth); however, less is known about systems involving phenotype distributions that are continuous across an environmental gradient, and how those distributions change when the environment changes. Here, we describe a novel instance of phenotypic diversity in tolerance to a metabolic toxin within wild-type populations of Methylobacterium extorquens, a ubiquitous phyllosphere methylotroph capable of growing on the methanol periodically released from plant leaves. The first intermediate in methanol metabolism is formaldehyde, a potent cellular toxin that is lethal in high concentrations. We have found that at moderate concentrations, formaldehyde tolerance in M. extorquens is heterogeneous, with a cell's minimum tolerance level ranging between 0 mM and 8 mM. Tolerant cells have a distinct gene expression profile from non-tolerant cells. This form of heterogeneity is continuous in terms of threshold (the formaldehyde concentration where growth ceases), yet binary in outcome (at a given formaldehyde concentration, cells either grow normally or die, with no intermediate phenotype), and it is not associated with any detectable genetic mutations. Moreover, tolerance distributions within the population are dynamic, changing over time in response to growth conditions. We characterized this phenomenon using bulk liquid culture experiments, colony growth tracking, flow cytometry, single-cell time-lapse microscopy, transcriptomics, and genome resequencing. Finally, we used mathematical modeling to better understand the processes by which cells change phenotype, and found evidence for both stochastic, bidirectional phenotypic diversification and responsive, directed phenotypic shifts, depending on the growth substrate and the presence of toxin.
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