A multidimensional perspective on microbial interactions

Beyond being simply positive or negative, beneficial or inhibitory, microbial interactions can involve a diverse set of mechanisms, dependencies and dynamical properties. These more nuanced features have been described in great detail for some specific types of interactions, (e.g. pairwise metabolic cross-feeding, quorum sensing or antibiotic killing), often with the use of quantitative measurements and insight derived from modeling. With a growing understanding of the composition and dynamics of complex microbial communities for human health and other applications, we face the challenge of integrating information about these different interactions into comprehensive quantitative frameworks. Here, we review the literature on a wide set of microbial interactions, and explore the potential value of a formal categorization based on multidimensional vectors of attributes. We propose that such an encoding can facilitate systematic, direct comparisons of interaction mechanisms and dependencies, and we discuss the relevance of an atlas of interactions for future modeling and rational design efforts.R01 GM121950 - NIGMS NIH HHSPublished versio

Costless metabolic secretions as drivers of interspecies interactions in microbial ecosystems

Metabolic exchange mediates interactions among microbes, helping explain diversity in microbial communities. As these interactions often involve a fitness cost, it is unclear how stable cooperation can emerge. Here we use genome-scale metabolic models to investigate whether the release of “costless” metabolites (i.e. those that cause no fitness cost to the producer), can be a prominent driver of intermicrobial interactions. By performing over 2 million pairwise growth simulations of 24 species in a combinatorial assortment of environments, we identify a large space of metabolites that can be secreted without cost, thus generating ample cross-feeding opportunities. In addition to providing an atlas of putative interactions, we show that anoxic conditions can promote mutualisms by providing more opportunities for exchange of costless metabolites, resulting in an overrepresentation of stable ecological network motifs. These results may help identify interaction patterns in natural communities and inform the design of synthetic microbial consortia.We thank Dr. Niels Klitgord for pioneering ideas that inspired launch of this work. We are also grateful to David Bernstein, Joshua E. Goldford, Meghan Thommes, Demetrius DiMucci, and all members of the Segre Lab for helpful discussions. A.R.P. is supported by a National Academies of Sciences, Engineering, and Medicine Ford Foundation Predoctoral Fellowship and a Howard Hughes Medical Institute Gilliam Fellowship. This work was supported by funding from the Defense Advanced Research Projects Agency (purchase request no. HR0011515303, contract no. HR0011-15-C-0091), the U.S. Department of Energy (grants DE-SC0004962 and DE-SC0012627), the NIH (grants 5R01DE024468, R01GM121950, and Sub_P30DK036836_P&F), the National Science Foundation (grants 1457695 and NSFOCE-BSF 1635070), MURI Grant W911NF-12-1-0390, the Human Frontiers Science Program (grant RGP0020/2016), and the Boston University Inter-disciplinary Biomedical Research Office. (National Academies of Sciences, Engineering, and Medicine Ford Foundation Predoctoral Fellowship; Howard Hughes Medical Institute Gilliam Fellowship; HR0011515303 - Defense Advanced Research Projects Agency; HR0011-15-C-0091 - Defense Advanced Research Projects Agency; DE-SC0004962 - U.S. Department of Energy; DE-SC0012627 - U.S. Department of Energy; 5R01DE024468 - NIH; R01GM121950 - NIH; Sub_P30DK036836_PF - NIH; 1457695 - National Science Foundation; NSFOCE-BSF 1635070 - National Science Foundation; W911NF-12-1-0390 - MURI Grant; RGP0020/2016 - Human Frontiers Science Program; Boston University Inter-disciplinary Biomedical Research Office)Published versio

Almost perfect nonlinear power functions with exponents expressed as fractions

Let $F$ be a finite field, let $f$ be a function from $F$ to $F$, and let $a$ be a nonzero element of $F$. The discrete derivative of $f$ in direction $a$ is $\Delta_a f \colon F \to F$ with $(\Delta_a f)(x)=f(x+a)-f(x)$. The differential spectrum of $f$ is the multiset of cardinalities of all the fibers of all the derivatives $\Delta_a f$ as $a$ runs through $F^*$. The function $f$ is almost perfect nonlinear (APN) if the largest cardinality in the differential spectrum is $2$. Almost perfect nonlinear functions are of interest as cryptographic primitives. If $d$ is a positive integer, the power function over $F$ with exponent $d$ is the function $f \colon F \to F$ with $f(x)=x^d$ for every $x \in F$. There is a small number of known infinite families of APN power functions. In this paper, we re-express the exponents for one such family in a more convenient form. This enables us to give the differential spectrum and, even more, to determine the sizes of individual fibers of derivatives.Comment: 30 page

PubhD UMinho: a investigação científica e a sociedade juntas num bar

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\u3cem\u3eShewanella oneidensis\u3c/em\u3e Cytochrome c Nitrite Reductase (ccNiR) Does Not Disproportionate Hydroxylamine to Ammonia and Nitrite, Despite a Strongly Favorable Driving Force

Cytochrome c nitrite reductase (ccNiR) from Shewanella oneidensis, which catalyzes the six-electron reduction of nitrite to ammonia in vivo, was shown to oxidize hydroxylamine in the presence of large quantities of this substrate, yielding nitrite as the sole free nitrogenous product. UV–visible stopped-flow and rapid-freeze-quench electron paramagnetic resonance data, along with product analysis, showed that the equilibrium between hydroxylamine and nitrite is fairly rapidly established in the presence of high initial concentrations of hydroxylamine, despite said equilibrium lying far to the left. By contrast, reduction of hydroxylamine to ammonia did not occur, even though disproportionation of hydroxylamine to yield both nitrite and ammonia is strongly thermodynamically favored. This suggests a kinetic barrier to the ccNiR-catalyzed reduction of hydroxylamine to ammonia. A mechanism for hydroxylamine reduction is proposed in which the hydroxide group is first protonated and released as water, leaving what is formally an NH2+ moiety bound at the heme active site. This species could be a metastable intermediate or a transition state but in either case would exist only if it were stabilized by the donation of electrons from the ccNiR heme pool into the empty nitrogen p orbital. In this scenario, ccNiR does not catalyze disproportionation because the electron-donating hydroxylamine does not poise the enzyme at a sufficiently low potential to stabilize the putative dehydrated hydroxylamine; presumably, a stronger reductant is required for this

Prospective scenarios for water quality and ecological status in Lake Sete Cidades (Portugal) : the integration of mathematical modelling in decision processes

The design of alternative strategies for water and ecological quality protection at the Lake Verde of Sete Cidades should be coupled with the assessment of future trophic states. Therefore, a mathematical model was developed to make prospective scenarios to reduce the risk of environmental degradation of the lake, and a modified Psenner scheme was used to characterize P distribution in the sediments. The model was able to describe thermal stratification, nutrient cycling (P, NH4 and NO3), dissolved O2, and phytoplankton dynamics in the water column and adjacent sediment layers. Internal P recycling, resulting from thermal stratification and sediment anoxia, was identified as the main cause for the increase of P concentration in the hypolimnion followed by slow transfer to the epilimnion (about 20 lg/L annual average). Cyanobacteria blooms during spring were explained by the availability of P and increased water temperature verified during this season. The most sensitive model parameter was sediment porosity. This parameter has a direct effect in dissolved O2 and P profiles and also in phytoplankton biomass. Finally, different water quality restoration scenarios were identified and their effectiveness assessed. Without the adoption of remediation measures (scenario control), Lake Verde water quality would deteriorate with annual average concentrations of total P and phytoplankton biomass (dry matter) reaching 34 lg/L and 2 mg/L, respectively, after 10 years of simulation. The reduction of P loads (scenario PORAL) into the lake would improve water quality comparatively to the scenario control, reducing the annual average concentrations of total P from 34 lg/L to 26 lg/L and of phytoplankton from 2 mg/L down to 1.4 mg/L after 10 years of simulation. In scenario sediments, corresponding to a decrease in the organic content of the sediments, a reduction in the concentrations of total P and phytoplankton is expected in the first two years of simulation, but this effect, would be attenuated throughout the years due to organic matter sedimentation. The best strategy is obtained by combining external and internal measures for P remediation. Finally, it is recommended that the model be used to integrate the results of water quality monitoring and watershed management plans.Regional Department of Water Resources and Land Planning; Regional Secretary of Environment and Sea; Science and Technology Foundation

RNA sequencing and proteomics approaches reveal novel deficits in the cortex of Mecp2-deficient mice, a model for Rett syndrome

BACKGROUND: Rett syndrome (RTT) is an X-linked neurodevelopmental disorder caused by mutations in the transcriptional regulator MeCP2. Much of our understanding of MeCP2 function is derived from transcriptomic studies with the general assumption that alterations in the transcriptome correlate with proteomic changes. Advances in mass spectrometry-based proteomics have facilitated recent interest in the examination of global protein expression to better understand the biology between transcriptional and translational regulation. METHODS: We therefore performed the first comprehensive transcriptome-proteome comparison in a RTT mouse model to elucidate RTT pathophysiology, identify potential therapeutic targets, and further our understanding of MeCP2 function. The whole cortex of wild-type and symptomatic RTT male littermates (n = 4 per genotype) were analyzed using RNA-sequencing and data-independent acquisition liquid chromatography tandem mass spectrometry. Ingenuity(R) Pathway Analysis was used to identify significantly affected pathways in the transcriptomic and proteomic data sets. RESULTS: Our results indicate these two omics data sets supplement one another. In addition to confirming previous works regarding mRNA expression in Mecp2-deficient animals, the current study identified hundreds of novel protein targets. Several selected protein targets were validated by Western blot analysis. These data indicate RNA metabolism, proteostasis, monoamine metabolism, and cholesterol synthesis are disrupted in the RTT proteome. Hits common to both data sets indicate disrupted cellular metabolism, calcium signaling, protein stability, DNA binding, and cytoskeletal cell structure. Finally, in addition to confirming disrupted pathways and identifying novel hits in neuronal structure and synaptic transmission, our data indicate aberrant myelination, inflammation, and vascular disruption. Intriguingly, there is no evidence of reactive gliosis, but instead, gene, protein, and pathway analysis suggest astrocytic maturation and morphological deficits. CONCLUSIONS: This comparative omics analysis supports previous works indicating widespread CNS dysfunction and may serve as a valuable resource for those interested in cellular dysfunction in RTT

The epochs of early-type galaxy formation as a function of environment

The aim of this paper is to set constraints of the epochs of early-type galaxy formation through the 'archaeology' of the stellar populations in local galaxies. Using our models of absorption line indices that account for variable abundance ratios, we derive the stellar population parameters of 124 early-type galaxies in high and low density environments. We find that all three parameters age, metallicity, and alpha/Fe ratio are correlated with velocity dispersion. We further find evidence for an influence of the environment on the stellar population properties. Massive early-type galaxies in low-density environments appear on average ~2 Gyrs younger and slightly more metal-rich than their counterparts in high density environments. No offsets in the alpha/Fe ratios, instead, are detected. We translate the derived ages and alpha/Fe ratios into star formation histories. We show that most star formation activity in early-type galaxies is expected to have happened between redshifts 3 and 5 in high density and between redshifts 1 and 2 in low density environments. We conclude that at least 50 per cent of the total stellar mass density must have already formed at z 1, in good agreement with observational estimates of the total stellar mass density as a function of redshift. Our results suggest that significant mass growth in the early-type galaxy population below z 1 must be restricted to less massive objects, and a significant increase of the stellar mass density between redshifts 1 and 2 should be present caused mainly by the field galaxy population. The results of this paper further imply vigorous star formation episodes in massive objects at z 2-5 and the presence of evolved ellipticals around z 1, both observationally identified as SCUBA galaxies and EROs.Comment: 20 pages, 10 figures, plus appendix, accepted by Ap