Dichotomous development of the gut microbiome in preterm infants.

BackgroundPreterm infants are at risk of developing intestinal dysbiosis with an increased proportion of Gammaproteobacteria. In this study, we sought the clinical determinants of the relative abundance of feces-associated Gammaproteobacteria in very low birth weight (VLBW) infants. Fecal microbiome was characterized at ≤ 2 weeks and during the 3rd and 4th weeks after birth, by 16S rRNA amplicon sequencing. Maternal and infant clinical characteristics were extracted from electronic medical records. Data were analyzed by linear mixed modeling and linear regression.ResultsClinical data and fecal microbiome profiles of 45 VLBW infants (gestational age 27.9 ± 2.2 weeks; birth weight 1126 ± 208 g) were studied. Three stool samples were analyzed for each infant at mean postnatal ages of 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. The average relative abundance of Gammaproteobacteria was 42.5% (0-90%) at ≤ 2 weeks, 69.7% (29.9-86.9%) in the 3rd, and 75.5% (54.5-86%) in the 4th week (p < 0.001). Hierarchical and K-means clustering identified two distinct subgroups: cluster 1 started with comparatively low abundance that increased with time, whereas cluster 2 began with a greater abundance at ≤ 2 weeks (p < 0.001) that decreased over time. Both groups resembled each other by the 3rd week. Single variants of Klebsiella and Staphylococcus described variance in community structure between clusters and were shared between all infants, suggesting a common, hospital-derived source. Fecal Gammaproteobacteria was positively associated with vaginal delivery and antenatal steroids.ConclusionsWe detected a dichotomy in gut microbiome assembly in preterm infants: some preterm infants started with low relative gammaproteobacterial abundance in stool that increased as a function of postnatal age, whereas others began with and maintained high abundance. Vaginal birth and antenatal steroids were identified as predictors of Gammaproteobacteria abundance in the early (≤ 2 weeks) and later (3rd and 4th weeks) stool samples, respectively. These findings are important in understanding the development of the gut microbiome in premature infants

Analysis of parametric biological models with non-linear dynamics

In this paper we present recent results on parametric analysis of biological models. The underlying method is based on the algorithms for computing trajectory sets of hybrid systems with polynomial dynamics. The method is then applied to two case studies of biological systems: one is a cardiac cell model for studying the conditions for cardiac abnormalities, and the second is a model of insect nest-site choice.Comment: In Proceedings HSB 2012, arXiv:1208.315

Pharmacology and clinical drug candidates in redox medicine

SIGNIFICANCE Oxidative stress is suggested to be a disease mechanism common to a wide range of disorders affecting human health. However, so far, the pharmacotherapeutic exploitation of this, for example, based on chemical scavenging of pro-oxidant molecules, has been unsuccessful. Recent Advances: An alternative emerging approach is to target the enzymatic sources of disease-relevant oxidative stress. Several such enzymes and isoforms have been identified and linked to different pathologies. For some targets, the respective pharmacology is quite advanced, that is, up to late-stage clinical development or even on the market; for others, drugs are already in clinical use, although not for indications based on oxidative stress, and repurposing seems to be a viable option. CRITICAL ISSUES For all other targets, reliable preclinical validation and drug ability are key factors for any translation into the clinic. In this study, specific pharmacological agents with optimal pharmacokinetic profiles are still lacking. Moreover, these enzymes also serve largely unknown physiological functions and their inhibition may lead to unwanted side effects. FUTURE DIRECTIONS The current promising data based on new targets, drugs, and drug repurposing are mainly a result of academic efforts. With the availability of optimized compounds and coordinated efforts from academia and industry scientists, unambiguous validation and translation into proof-of-principle studies seem achievable in the very near future, possibly leading towards a new era of redox medicine

Genetic and serological diversity of Flavobacterium psychrophilum isolates from salmonids in United Kingdom

Flavobacterium psychrophilum is one of the most important bacterial pathogens affecting cultured rainbow trout (Oncorhynchus mykiss) and is increasingly causing problems in Atlantic salmon (Salmo salar L.) hatcheries. Little is known about the heterogeneity of F. psychrophilum isolates on UK salmonid farms. A total of 315 F. psychrophilum isolates, 293 of which were collected from 27 sites within the UK, were characterised using four genotyping methods and a serotyping scheme. A high strain diversity was identified among the isolates with 54 pulsotypes, ten (GTG)5-PCR types, two 16S rRNA allele lineages, seven plasmid profiles and three serotypes. Seven PFGE groups and 27 singletons were formed at a band similarity of 80%. PFGE group P (n=75) was found to be numerically predominant in eight sites within the UK. Two major PFGE clusters and 13 outliers were found at the band similarity of 40%. The predominant profile observed within the F. psychrophilum isolates examined was PFGE cluster II − (GTG)5-PCR type r1–16S rRNA lineage II − serotype Th (70/156 isolates examined, 45%). Co-existence of genetically and serologically heterogeneous isolates within each farm was detected, confounding the ability to control RTFS outbreaks. The occurrence over time (up to 11 years) of F. psychrophilum pulsotypes in three representative sites (Scot I, Scot III and Scot V) within Scotland was examined, potentially providing important epidemiological data for farm management and the development of site-specific vaccines

Antimicrobial susceptibility of Flavobacterium psychrophilum isolates from the United Kingdom

Routine application of antimicrobials is the current treatment of choice for rainbow trout fry syndrome (RTFS) or bacterial coldwater disease (BCWD) caused by Flavobacterium psychrophilum. In this study, the antimicrobial susceptibilities of 133 F. psychrophilum isolates, 118 of which were from the UK, were evaluated by broth microdilution and disc diffusion methods following VET04-A2 and VET03-A guidelines of Clinical and Laboratory Standards Institute (CLSI), respectively. Isolates were categorised as wild type (fully susceptible, WT) or non-wild type (NWT) using normalised resistance interpretation (NRI) determined cut-off values (COWT). Broth microdilution testing showed that only 12% of UK isolates were WT to oxolinic acid (MIC COWT ≤0.25 mg L-1) and 42% were WT for oxytetracycline (MIC COWT ≤0.25 mg L-1). In contrast, all the isolates tested were WT (MIC COWT ≤2 mg L-1) for florfenicol, the main antimicrobial for RTFS control in the UK. Disc diffusion-based COWT values were ≥51 mm for 10 µg amoxicillin, ≥44 mm for 30 µg florfenicol, ≥30 mm for 2 µg oxolinic acid and ≥51 mm for 30 µg oxytetracycline. There was a high categorical agreement between the classifications of the isolates by two testing methods for florfenicol (100%), oxytetracycline (93%), and oxolinic acid (99%)

Symmetry Factors of Feynman Diagrams for Scalar Fields

The symmetry factor of Feynman diagrams for real and complex scalar fields is presented. Being analysis of Wick expansion for Green functions, the mentioned factor is derived in a general form. The symmetry factor can be separated into two ones corresponding to that of connected and vacuum diagrams. The determination of symmetry factors for the vacuum diagrams is necessary as they play a role in the effective action and phase transitions in cosmology. In the complex scalar theory the diagrams different in topology may give the same contribution, hence inverse of the symmetry factor (1/S) for total contribution is a summation of each similar ones (1/S_i), i.e., 1/S = \sum_i (1/S_i).Comment: Journal version, new references adde

Wood lignocellulosic stabilizers : effect of their characteristics on stability and rheological properties of emulsions

Lignocellulosic materials from the forest industry have shown potential to be used as sustainable hydrocolloids to stabilize emulsions for many applications in life science and chemical industries. However, the effect of wood species and recovery method on the product’s properties and ability to stabilize emulsions of isolated lignocellulosic compounds is not well understood. Hemicelluloses, abundant lignocellulosic side stream, exhibit differences in their water solubility, anionic character, lignin content, and degree of acetylation. Here, we explored stability and rheological properties of model emulsions (5% hexadecane and 1% stabilizer, w/w) stabilized by different grades of sprucewood galactoglucomannan (GGM) and birchwood glucuronoxylan (GX) hemicelluloses. The results were compared to known soluble, insoluble, charged, and non-charged cellulosic stabilizers, namely methyl cellulose (MC), carboxymethyl cellulose (CMC), anionic- and nonionic-cellulose nanocrystals (aCNC and dCNC). The results showed that GX emulsions were highly stable compared to GGM emulsions, and that deacetylation and lignin removal markedly reduced emulsion stability of GGM. Carboxymethylation to increase anionic characters enhanced the emulsion stabilization capacity of GGM, but not that of GX. Investigating flow behaviors of emulsions indicated that hemicelluloses primarily stabilize emulsions by adsorption of insoluble particles, as their flow behaviors were similar to those of cellulose nanocrystals rather than those of soluble celluloses. Understanding the impact of the variations in composition and properties of hemicellulose stabilizers to stabilize emulsions allows tailoring of their recovery processes to obtain desirable hydrocolloids for different applications.Peer reviewe

Non-canonical chemical feedback self-limits nitric oxide-cyclic GMP signaling in health and disease

Nitric oxide (NO)-cyclic GMP (cGMP) signaling is a vasoprotective pathway therapeutically targeted, for example, in pulmonary hypertension. Its dysregulation in disease is incompletely understood. Here we show in pulmonary artery endothelial cells that feedback inhibition by NO of the NO receptor, the cGMP forming soluble guanylate cyclase (sGC), may contribute to this. Both endogenous NO from endothelial NO synthase and exogenous NO from NO donor compounds decreased sGC protein and activity. This effect was not mediated by cGMP as the NO-independent sGC stimulator, or direct activation of cGMP-dependent protein kinase did not mimic it. Thiol-sensitive mechanisms were also not involved as the thiol-reducing agent N-acetyl-L-cysteine did not prevent this feedback. Instead, both in-vitro and in-vivo and in health and acute respiratory lung disease, chronically elevated NO led to the inactivation and degradation of sGC while leaving the heme-free isoform, apo-sGC, intact or even increasing its levels. Thus, NO regulates sGC in a bimodal manner, acutely stimulating and chronically inhibiting, as part of self-limiting direct feedback that is cGMP independent. In high NO disease conditions, this is aggravated but can be functionally recovered in a mechanism-based manner by apo-sGC activators that re-establish cGMP formatio