OptCom: A Multi-Level Optimization Framework for the Metabolic Modeling and Analysis of Microbial Communities

Microorganisms rarely live isolated in their natural environments but rather function in consolidated and socializing communities. Despite the growing availability of high-throughput sequencing and metagenomic data, we still know very little about the metabolic contributions of individual microbial players within an ecological niche and the extent and directionality of interactions among them. This calls for development of efficient modeling frameworks to shed light on less understood aspects of metabolism in microbial communities. Here, we introduce OptCom, a comprehensive flux balance analysis framework for microbial communities, which relies on a multi-level and multi-objective optimization formulation to properly describe trade-offs between individual vs. community level fitness criteria. In contrast to earlier approaches that rely on a single objective function, here, we consider species-level fitness criteria for the inner problems while relying on community-level objective maximization for the outer problem. OptCom is general enough to capture any type of interactions (positive, negative or combinations thereof) and is capable of accommodating any number of microbial species (or guilds) involved. We applied OptCom to quantify the syntrophic association in a well-characterized two-species microbial system, assess the level of sub-optimal growth in phototrophic microbial mats, and elucidate the extent and direction of inter-species metabolite and electron transfer in a model microbial community. We also used OptCom to examine addition of a new member to an existing community. Our study demonstrates the importance of trade-offs between species- and community-level fitness driving forces and lays the foundation for metabolic-driven analysis of various types of interactions in multi-species microbial systems using genome-scale metabolic models

Impairments of Gestalt perception in the intact hemifield of hemianopic patients are reflected in gamma-band EEG activity

Gamma-band responses (GBRs) are associated with Gestalt perception processes. In the present EEG study, we investigated the effects of perceptual grouping on the visual GBR in the perimetrically intact visual field of patients with homonymous hemianopia and compared them to healthy participants. All observers were presented either random arrays of Gabor elements or arrays with an embedded circular arrangement. For the hemianopic patients, the circle was presented in their intact hemifield only. For controls, the hemifield for the circle presentation was counterbalanced across subjects. The participants were instructed to detect the circle by pressing a corresponding button. A wavelet transform based on Morlet wavelets was employed for the calculation of oscillatory GBRs. The early evoked GBR exhibited a larger amplitude and shorter latency for the healthy group compared to hemianopic patients and was associated with behavioral measures. The late total GBR between 200 and 400 ms after stimulus onset was significantly increased for Gestalt-like patterns in healthy participants. This effect was not manifested in patients. The present findings indicate deficits in the early and late visual processing of Gestalt patterns even in the intact hemifield of hemianopic patients compared to healthy participants

2,8-Dihydroxyadenine urolithiasis in a patient with considerable residual adenine phosphoribosyltransferase activity in cell extracts but with mutations in both copies of APRT.

We have examined the mutational basis of adenine phosphoribosyltransferase (APRT, EC 2.4.2.7) deficiency (MIM 102600) in a patient of Polish origin who has been passing 2,8-dihydroxyadenine (DHA) stones since birth, but has considerable residual enzyme activity in lymphocyte extracts. The five exons and flanking regions of APRT were amplified by PCR and then sequenced. A single T insertion was identified at the intron 4 splice donor site (TGgtaa to TGgttaa:IVS4+2insT) in one allele from the proband, his mother, and brother. A G-to-T transversion in exon 5 (GTC-to-TTC:c.448G>T, V150F) was identified in the other allele, and this mutation was also present in one allele from the father and the paternal grandmother. Tru91 and AvaII digestions of PCR products spanning exons 4 and 5, respectively, confirmed the mutations. The mother was heterozygous for an intragenic TaqI site, but all other family members were homozygous for the presence of this site. IVS4+2insT, located on the allele containing the TaqI site, has been identified previously in several families from Europe, suggesting a founder effect, but the substitution in exon 5 is a novel mutation. IVS4+2insT is known to result in complete loss of enzyme activity, and our results suggest that V150F produces an enzyme that is nonfunctional in vivo but has considerable residual activity in vitro

MRI-based multiscale models for the haemodynamic and structural evaluation of surgically reconstructed aortic arches

Surgical interventions on the arterial wall may bring forth modification to its tissue characteristics and the addition of synthetic materials of different types can have implications on haemodynamics and blood vessel wall behaviour. This work studies the mid-term effects of end-to-end anastomosis (E/E), Gore-tex graft interposition (GGI) and Gore-tex patch graft aortoplasty (GPGA) in aortic arch reconstruction. The study comprises two groups of healthy sows of Danish breed. The animals in the first group (ST) weighed around 40 kg, underwent a surgical operation and were put down on the same day. The animals in the second group (MT) weighed 5-10 kg, underwent a surgical operation and were then allowed to grow up to a weight of around 30-40 kg, before being sacrificed. One pig in each group was scheduled in for E/E and one for GGI. One pig in ST and two in MT received GPGA. The overall average wall thickness was 1.93 mm. Relaxation constant values were significantly higher for ST (5.221 +/- 1.832 s) than for MT (2.184 +/- 1.216 s). GPGA showed a greater impact on relaxation than other operations, enhancing the viscous character. Working-point Young’s modulus (Epw ) was not significantly different in ST and MT. Circumferential samples had different Epw (0.419 +/- 0.77 MPa) from longitudinal ones (0.902 +/- 0.378 MPa). There also appeared to be a significant difference between samples cut longitudinally on the left and the right sides of the wall. The overall average value of Epw was 0.6609 +/- 0.3641 MPa

Local Approach to Fracture Applied to Reactor Pressure Vessel : Synthesis of a Cooperative Programme Between EDF, CEA, Framatome and AEA

A cooperative research programme in the field of the local approach to cleavage fracture applied to reactor pressure vessels is conducted between EDF, CEA, Framatome and AEA Technology. The purpose of such a programme is to have a better knowledge of this approach for RPV fracture mechanics integrity assessments regarding the risk of brittle fracture. This programme includes both an experimental part conducted by several laboratories in order to identify m and σ parameters of Beremin model on a A508 C13 steel, and numerous numerical computations of specimens and structures. Finite element programs are compared on some reference calculations in order to validate local approach to fracture postprocessors. The capability of Beremin model to explain the shallow flaw effect in cleavage fracture is finally discussed

The complete genome sequence of Bacillus licheniformis DSM13, an organism with great industrial potential

The genome of Bacillus licheniformis DSM13 consists of a single chromosome that has a size of 4,222,748 base pairs. The average G+C ratio is 46.2%. 4,286 open reading frames, 72 tRNA genes, 7 rRNA operons and 20 transposase genes were identified. The genome shows a marked co-linearity with Bacillus subtilis but contains defined inserted regions that can be identified at the sequence as well as at the functional level. B. licheniformis DSM13 has a well-conserved secretory system, no polyketide biosynthesis, but is able to form the lipopeptide lichenysin. From the further analysis of the genome sequence, we identified conserved regulatory DNA motives, the occurrence of the glyoxylate bypass and the presence of anaerobic ribonucleotide reductase explaining that B. licheniformis is able to grow on acetate and 2,3-butanediol as well as anaerobically on glucose. Many new genes of potential interest for biotechnological applications were found in B. licheniformis; candidates include proteases, pectate lyases, lipases and various polysaccharide degrading enzymes