The interspecies exchange of metabolites plays a key role in the spatiotemporal dynamics of microbial communities. This raises the question of whether ecosystem-level behavior of structured ...communities can be predicted using genome-scale metabolic models for multiple organisms. We developed a modeling framework that integrates dynamic flux balance analysis with diffusion on a lattice and applied it to engineered communities. First, we predicted and experimentally confirmed the species ratio to which a two-species mutualistic consortium converges and the equilibrium composition of a newly engineered three-member community. We next identified a specific spatial arrangement of colonies, which gives rise to what we term the “eclipse dilemma”: does a competitor placed between a colony and its cross-feeding partner benefit or hurt growth of the original colony? Our experimentally validated finding that the net outcome is beneficial highlights the complex nature of metabolic interactions in microbial communities while at the same time demonstrating their predictability.
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•Microbial community dynamics can be inferred from intracellular metabolism•Metabolic interactions drive engineered microbial consortia to predictable equilibria•Spatial organization shapes the dynamics of mutualism in a metabolic eclipse scenario•Computation of Microbial Ecosystems in Time and Space (COMETS): a flexible tool
Microbes can interact with the environment and with each other through the uptake and secretion of metabolites. Here, Harcombe et al. ask whether mathematical modeling of the metabolic network of individual species can help forecast the spatiotemporal behavior of two- and three-species engineered microbial ecosystems. In addition to accurately predicting colony growth rates and equilibrium community compositions, their approach sheds new light on the complex nature of cooperation and competition in spatially structured environments.
Plasmon resonances of anisotropic multibranched nanostructures are governed by their geometry, allowing morphology-directed selective manipulation of the optical properties. In this work, we have ...synthesized multibranched gold nanoantennas (MGNs) of variable geometry by a one-step seedless approach using 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) as a capping and reducing agent. This approach enables us to modulate the MGNs’ geometry by controlling three different parameters: concentration of HEPES, concentration of Au3+, and pH of HEPES buffer. By altering the MGNs morphology with minimal increase in the overall dimensions, the plasmon resonances were tuned from the visible to the near-infrared. The MGNs plasmon resonances demonstrated a nonintuitive blue-shift when pH > pK a of HEPES which we attributed to emergence of charge transfer oscillations formed when MGNs cluster to dimers and trimers. Further, due to the presence of multiple sharp protrusions, the MGNs demonstrated a refractive index sensitivity of 373 nm/RIU, which is relatively high for this class of branched nanostructures of similar size. Finally, the sharp protrusions of MGNs also give rise to intense photothermal efficiencies; ∼53 °C was achieved within 5 min of laser illumination, demonstrating the efficacy of MGNs in therapeutic applications. By modulating the mass density of MGNs, the laser flux, and time of illumination, we provide a detailed analysis of the photothermal characteristics of MGNs.
Detecting elevated intracranial pressure in children with subacute conditions, such as craniosynostosis or tumor, may enable timely intervention and prevent neurocognitive impairment, but ...conventional techniques are invasive and often equivocal. Elevated intracranial pressure leads to structural changes in the peripapillary retina. Spectral-domain (SD) optical coherence tomography (OCT) can noninvasively quantify retinal layers to a micron-level resolution.
To evaluate whether retinal measurements from OCT can serve as an effective surrogate for invasive intracranial pressure measurement.
This cross-sectional study included patients undergoing procedures at the Children's Hospital of Philadelphia from September 2014 to June 2015. Three groups of patients (n = 79) were prospectively enrolled from the Craniofacial Surgery clinic including patients with craniosynostosis (n = 40). The positive control cohort consisted of patients with hydrocephalus and suspected intracranial hypertension (n = 5), and the negative control cohort consisted of otherwise healthy patients undergoing a minor procedure (n = 34).
Spectral-domain OCT was performed preoperatively in all cohorts. Children with cranial pathology, but not negative control patients, underwent direct intraoperative intracranial pressure measurement. The primary outcome was the association between peripapillary retinal OCT parameters and directly measured elevated intracranial pressure.
The mean (SD) age was 34.6 (45.2) months in the craniosynostosis cohort (33% female), 48.9 (83.8) months in the hydrocephalus and suspected intracranial hypertension cohort (60% female), and 59.7 (64.4) months in the healthy cohort (47% female). Intracranial pressure correlated with maximal retinal nerve fiber layer thickness (r = 0.60, P ≤ .001), maximal retinal thickness (r = 0.53, P ≤ .001), and maximal anterior retinal projection (r = 0.53, P = .003). Using cut points derived from the negative control patients, OCT parameters yielded 89% sensitivity (95% CI, 69%-97%) and 62% specificity (95% CI, 41%-79%) for detecting elevated intracranial pressure. The SD-OCT measures had high intereye agreement (intraclass correlation, 0.83-0.93) and high intragrader and intergrader agreement (intraclass correlation ≥0.94). Conventional clinical signs had low sensitivity (11%-42%) for detecting intracranial hypertension.
Noninvasive quantitative measures of the peripapillary retinal structure by SD-OCT were correlated with invasively measured intracranial pressure. Optical coherence tomographic parameters showed promise as surrogate, noninvasive measures of intracranial pressure, outperforming other conventional clinical measures. Spectral-domain OCT of the peripapillary region has the potential to advance current treatment paradigms for elevated intracranial pressure in children.
ISHLT members have recognized the importance of a consensus statement on the evaluation and management of patients with chronic thromboembolic pulmonary hypertension. The creation of this document ...required multiple steps, including the engagement of the ISHLT councils, approval by the Standards and Guidelines Committee, identification and selection of experts in the field, and the development of 6 working groups. Each working group provided a separate section based on an extensive literature search. These sections were then coalesced into a single document that was circulated to all members of the working groups. Key points were summarized at the end of each section. Due to the limited number of comparative trials in this field, the document was written as a literature review with expert opinion rather than based on level of evidence.
•Standoff LIBS analysis of Sr and Cs contaminated nuclear plant steel is demonstrated at millimetre distances.•Standoff LIBS has the potential to allow surveying of contamination at much larger ...distances (metres).•Multi pulse LIBS can also provide depth resolved information on contaminant distribution in steel.
Laser Induced Breakdown Spectroscopy (LIBS) has the potential to allow direct, standoff measurement of contaminants on nuclear plant. Here, LIBS is evaluated as an analytical tool for measurement of Sr and Cs contamination on type 304 stainless steel surfaces. Samples were reacted in model acidic (PUREX reprocessing) and alkaline (spent fuel ponds) Sr and Cs bearing liquors, with LIBS multi-pulse ablation also explored to measure contaminant penetration. The Sr II (407.77nm) and Cs I (894.35nm) emission lines could be separated from the bulk emission spectra, though only Sr could be reliably detected at surface loadings >0.5mgcm−2. Depth profiling showed decay of the Sr signal with time, but importantly, elemental analysis indicated that material expelled from LIBS craters is redistributed and may interfere in later laser shot analyses.
Aboveground litter production is an important biogeochemical pathway in forests whereby carbon and nutrients enter soil detrital pools. However, patterns and controls of aboveground litter production ...are often based on an understanding of how autumnal, foliar inputs are related to aboveground tree production. Here we use three separate data sources of aboveground litter production in temperate forests to ask how aboveground woody productivity affects foliar litter production in light of other factors, such as the climate sensitivity of litter production and the seasonality of not only foliar but also fine woody debris and reproductive litter inputs. We find that foliar litter production increases with aboveground woody production, and this relationship is modified both by plant functional group and climate. Basal area also provides a crucial control on litter production. Conifer forests produce approximately half as much foliar litter as broadleaf deciduous forests. Litter production is sensitive to both among-site and among-year variation in climate, such that more litter is produced in warmer, wetter locations and years. On average 72% of aboveground litter is foliar material, with the remaining split about evenly between fine woody debris and reproductive material, and although about 88% of broadleaf litter falls during autumn, only about 61% of needles, 37% of fine woody debris and 43% of reproductive material falls during the same period. Together these results illustrate key differences in the controls of litter production in coniferous and deciduous forests, and highlight the importance of often overlooked litter fluxes, including non-autumn and non-foliar litterfall.
The motor head of kinesin carries out microtubule binding, ATP hydrolysis, and force generation. Despite a high level of sequence and structural conservation, subtle variations in subdomains of the ...motor head determine family-specific properties. In particular, both Kinesin-1 (Kin-1) and Kinesin-5 (Kin-5) walk processively to the microtubule plus-end, yet show distinct motility characteristics suitable for their functions. We studied chimeric Kin-1/Kin-5 constructs with a combination of single molecule motility assays and molecular dynamics simulations to demonstrate that Kin-5 possesses a force-generating element similar to Kin-1, i.e., the cover-neck bundle. Furthermore, the Kin-5 neck linker makes additional contacts with the core of the motor head via loop L13, which putatively compensates for the shorter cover-neck bundle of Kin-5. Our results indicate that Kin-1 is mechanically optimized for individual cargo transport, whereas Kin-5 does not necessarily maximize its mechanical performance. Its biochemical rates and enhanced force sensitivity may instead be beneficial for operation in a group of motors. Such variations in subdomains would be a strategy for achieving diversity in motility with the conserved motor head.
Small-angle neutron scattering (SANS) is used to measure the conformation and solution thermodynamics of low dispersity, star branched poly(N-isopropylacrylamide) (PNIPAM) in water using a newly ...developed form factor for star-branched polymers with excluded volume, in conjunction with the random phase approximation (RPA). Star PNIPAM is synthesized using both ATRP and RAFT, allowing the terminal group and number of arms to be precisely tuned from f = 3 to 6 arms, with bromine, phenyl, and dodecane terminal moieties. SANS measurements show that both the number of arms (f) and synthetic route (i.e., ATRP or RAFT) play a dominant role in the solution behavior of PNIPAM in relation to the interaction parameters, conformation of the arms of the polymer, and clustering/association of the polymers below the LCST. Dodecane-terminated PNIPAM polymers form small, sub-20 nm globules in solution, whereas phenyl- and bromine-terminated polymers form large, micrometer-scale clusters of nearly-Gaussian polymer chains. Multiangle light scattering (MALS) is used to probe the large clusters, finding that their size increases slightly with temperature but is largely independent of terminal group chemistry.
While resection remains the only curative option for perihilar cholangiocarcinoma, it is well known that such surgery is associated with a high risk of morbidity and mortality. Nevertheless, beyond ...facing life-threatening complications, patients may also develop early disease recurrence, defining a "futile" outcome in perihilar cholangiocarcinoma surgery. The aim of this study is to predict the high-risk category (futile group) where surgical benefits are reversed and alternative treatments may be considered.
The study cohort included prospectively maintained data from 27 Western tertiary referral centers: the population was divided into a development and a validation cohort. The Framingham Heart Study methodology was used to develop a preoperative scoring system predicting the "futile" outcome.
A total of 2271 cases were analyzed: among them, 309 were classified within the "futile group" (13.6%). American Society of Anesthesiology (ASA) score ≥ 3 (OR 1.60; p = 0.005), bilirubin at diagnosis ≥50 mmol/L (OR 1.50; p = 0.025), Ca 19-9 ≥ 100 U/mL (OR 1.73; p = 0.013), preoperative cholangitis (OR 1.75; p = 0.002), portal vein involvement (OR 1.61; p = 0.020), tumor diameter ≥3 cm (OR 1.76; p < 0.001), and left-sided resection (OR 2.00; p < 0.001) were identified as independent predictors of futility. The point system developed, defined three (ie, low, intermediate, and high) risk classes, which showed good accuracy (AUC 0.755) when tested on the validation cohort.
The possibility to accurately estimate, through a point system, the risk of severe postoperative morbidity and early recurrence, could be helpful in defining the best management strategy (surgery vs. nonsurgical treatments) according to preoperative features.
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