Minireview: The Potential of Enhanced Manganese Redox Cycling for Sediment Oxidation

Both natural and anthropogenic processes are responsible for excessive organic loading of submerged soils, with detrimental environmental consequences. The often insufficient natural attenuation can be enhanced by exploiting microbial manganese cycles. This review describes how an anoxic oxidation of organic matter with concomitant reduction of MnO ₂ can link up with a reoxidation of the resulting, soluble Mn(II) in oxic layers. The potentially attainable oxidation rates through these natural cycles are of the same order as the organic carbon accumulation rates. The microbiology and physiology of the responsible organisms are discussed, as well as examples of naturally occurring manganese cycles and the possibility to engineer this natural phenomenon.     

Activity‐dependent secretion of alpha‐synuclein by enteric neurons

There is growing evidence supporting a role of extracellular alpha‐synuclein in the spreading of Parkinson's disease (PD) pathology. Recent pathological studies have raised the possibility that the enteric nervous system (ENS) is one of the initial sites of alpha‐synuclein pathology in PD. We therefore undertook this survey to determine whether alpha‐synuclein can be secreted by enteric neurons. Alpha‐synuclein secretion was assessed by immunoblot analysis of the culture medium from primary culture of ENS. We show that alpha‐synuclein is physiologically secreted by enteric neurons via a conventional, endoplasmic reticulum/Golgi‐dependent exocytosis, in a neuronal activity‐regulated manner. Our study is the first to evidence that enteric neurons are capable of secreting alpha‐synuclein, thereby providing new insights into the role of the ENS in the pathophysiology of PD.     

A Novel Type of Peptidoglycan-binding Domain Highly Specific for Amidated d-Asp Cross-bridge,Identified in Lactobacillus casei Bacteriophage Endolysins

Peptidoglycan hydrolases (PGHs) are responsible for bacterial cell lysis. Most PGHs have a modular structure comprising a catalytic domain and a cell wall-binding domain (CWBD). PGHs of bacteriophage origin, called endolysins, are involved in bacterial lysis at the end of the infection cycle. We have characterized two endolysins, Lc-Lys and Lc-Lys-2, identified in prophages present in the genome of Lactobacillus casei BL23. These two enzymes have different catalytic domains but similar putative C-terminal CWBDs. By analyzing purified peptidoglycan (PG) degradation products, we showed that Lc-Lys is an N-acetylmuramoyl-l-alanine amidase, whereas Lc-Lys-2 is a γ-d-glutamyl-l-lysyl endopeptidase. Remarkably, both lysins were able to lyse only Gram-positive bacterial strains that possess PG with d-Ala⁴→d-Asx-l-Lys³ in their cross-bridge, such as Lactococcus casei, Lactococcus lactis, and Enterococcus faecium. By testing a panel of L. lactis cell wall mutants, we observed that Lc-Lys and Lc-Lys-2 were not able to lyse mutants with a modified PG cross-bridge, constituting d-Ala⁴→l-Ala-(l-Ala/l-Ser)-l-Lys³; moreover, they do not lyse the L. lactis mutant containing only the nonamidated d-Asp cross-bridge, i.e. d-Ala⁴→d-Asp-l-Lys³. In contrast, Lc-Lys could lyse the ampicillin-resistant E. faecium mutant with 3→3 l-Lys³-d-Asn-l-Lys³ bridges replacing the wild-type 4→3 d-Ala⁴-d-Asn-l-Lys³ bridges. We showed that the C-terminal CWBD of Lc-Lys binds PG containing mainly d-Asn but not PG with only the nonamidated d-Asp-containing cross-bridge, indicating that the CWBD confers to Lc-Lys its narrow specificity. In conclusion, the CWBD characterized in this study is a novel type of PG-binding domain targeting specifically the d-Asn interpeptide bridge of PG.     

Impaired Leaf Litter Processing in Acidified Streams

Anthropogenic acidification in headwater streams is known to affect microbial assemblages involved in leaf litter breakdown. Far less is known about its potential effects on microbial enzyme activities. To assess the effects of acidification on microbial activities associated with decaying leaves, a 70-day litter bag experiment was conducted in headwater streams at six sites across an acidification gradient. The results revealed that microbial leaf decomposition was strongly and negatively correlated with total Al concentrations (r?=??0.99, p?<?0.001) and positively correlated with Ca²⁺ concentrations (r?=?0.94, p?=?0.005) and pH (r?=?0.93, p?=?0.008). Denaturing gradient gel electrophoresis analyses showed that microbial assemblages differed between non-impacted and impacted sites, whereas fungal biomass associated with decaying leaves was unaffected. The nutrient content of leaf detritus and ecoenzymatic activities of carbon (C), nitrogen (N) and phosphorus (P) acquisition revealed that N acquisition was unaltered, while P acquisition was significantly reduced across the acidification gradient. The P content of leaf litter was negatively correlated with total Al concentrations (r?=??0.94, p?<?0.01) and positively correlated with decomposition rates (r?=?0.95, p?<?0.01). This potential P limitation of microbial decomposers in impacted sites was confirmed by the particularly high turnover activity for phosphatase and imbalanced ratios between the ecoenzymatic activities of C and P acquisition. The toxic form of Al has well-known direct effects on aquatic biota under acidic conditions, but in this study, Al was found to also potentially affect microbially mediated leaf processing by interfering with the P cycle. These effects may in turn have repercussions on higher trophic levels and whole ecosystem functioning.     

Differential modes of MHC class IIB gene evolution in cichlid fishes

Cichlid fishes are emblematic models for the study of adaptive radiation, driven by natural and sexual selection. Parasite mediated selection is an important component in these processes, and the evolution of their immune system therefore merits special attention. In this study, light is shed on the phylogeny of the b family of cichlid major histocompatibility complex (MHC) class IIB genes. Full-length coding sequences were used to reconstruct phylogenies using criteria of maximum parsimony, maximum likelihood and Bayesian inference. All analyses suggest monophyly of the b family of cichlid MHC class IIB genes, although sequences of the cichlid sister taxa are currently not available. Two evolutionary lineages of these genes, respectively encompassing the recently defined genomic regions DBB-DEB-DFB and DCB-DDB, show highly contrasting levels of differentiation. To explore putative causes for these differences, exon 2 sequences were screened for variation in recombination rate and strength of selection. The more diversified lineage of cichlid MHC class IIB b genes was found to have higher levels of both recombination and selection. This is consistent with the observation in other taxa that recombination facilitates the horizontal spread of positively selected sites across MHC loci and hence contributes to fast sequence evolution. In contrast, the lineage that showed low diversification might either be under stabilizing selection or is evolutionary constrained by its low recombination rate. We speculate whether this lineage might include MHC genes with non-classical functions.     

NMR localization of the O-mycoloylation on PorH,a channel forming peptide from Corynebacterium glutamicum

PorH and PorA are two small peptides that, in complex, form a voltage-dependent ion channel in the outer membrane of Corynebacterium glutamicum. Specific post-translational modifications on PorA and PorH are required for the formation of a functional ion channel. The assignment of PorH proton NMR chemical shifts in DMSO, allowed identifying unambiguously the exact position of the PorH O-mycoloylation on Ser 56 side chain. This was further confirmed by site directed mutagenesis and mass spectrometry. Together with the previously published localization of PorA mycoloylation, this provides the complete primary structure characterization of this outer membrane porin.     

A Software Architecture for Multi-Cellular System Simulations on Graphics Processing Units

The first aim of simulation in virtual environment is to help biologists to have a better understanding of the simulated system. The cost of such simulation is significantly reduced compared to that of in vivo simulation. However, the inherent complexity of biological system makes it hard to simulate these systems on non-parallel architectures: models might be made of sub-models and take several scales into account; the number of simulated entities may be quite large. Today, graphics cards are used for general purpose computing which has been made easier thanks to frameworks like CUDA or OpenCL. Parallelization of models may however not be easy: parallel computer programing skills are often required; several hardware architectures may be used to execute models. In this paper, we present the software architecture we built in order to implement various models able to simulate multi-cellular system. This architecture is modular and it implements data structures adapted for graphics processing units architectures. It allows efficient simulation of biological mechanisms.     

Constitutive Activation of the Calcium Sensor STIM1 Causes Tubular-Aggregate Myopathy

Tubular aggregates are regular arrays of membrane tubules accumulating in muscle with age. They are found as secondary features in several muscle disorders, including alcohol- and drug-induced myopathies, exercise-induced cramps, and inherited myasthenia, but also exist as a pure genetic form characterized by slowly progressive muscle weakness. We identified dominant STIM1 mutations as a genetic cause of tubular-aggregate myopathy (TAM). Stromal interaction molecule 1 (STIM1) is the main Ca²⁺ sensor in the endoplasmic reticulum, and all mutations were found in the highly conserved intraluminal Ca²⁺-binding EF hands. Ca²⁺ stores are refilled through a process called store-operated Ca²⁺ entry (SOCE). Upon Ca²⁺-store depletion, wild-type STIM1 oligomerizes and thereby triggers extracellular Ca²⁺ entry. In contrast, the missense mutations found in our four TAM-affected families induced constitutive STIM1 clustering, indicating that Ca²⁺ sensing was impaired. By monitoring the calcium response of TAM myoblasts to SOCE, we found a significantly higher basal Ca²⁺ level in TAM cells and a dysregulation of intracellular Ca²⁺ homeostasis. Because recessive STIM1 loss-of-function mutations were associated with immunodeficiency, we conclude that the tissue-specific impact of STIM1 loss or constitutive activation is different and that a tight regulation of STIM1-dependent SOCE is fundamental for normal skeletal-muscle structure and function.     

The manifold characters of orbicules: structural diversity,systematic significance,and vectors for allergens

In the anthers of flowering plants, gymnosperms, and seed ferns, tiny (±1?μm) granules might occur on the radial and innermost tangential wall of secretory tapetum cells. These sporopollenin granules develop simultaneously with the pollen exine and are called orbicules or Ubisch bodies. The present paper focuses on two quite different topics associated with orbicules.

The morphological and ultrastructural diversity of orbicules in the order Gentianales is summarized, and it is demonstrated that orbicules are a plesiomorphic feature in the order. Furthermore, orbicule characters seemed to be correlated with evolutionary trends in pollen dispersal unit and tapetum type features.

In the second part, we report on our investigation of Corylus avellana L. (Hazel) pollen, using immunogold electron microscopy to gain an insight into the possible role that orbicules may play as a vector of pollen allergens. During the pollen season orbicules are dispersed into the atmosphere along with Hazel pollen grains. The localisation of homologues of the new birch pollen allergen Bet v 7 was studied at the subcellular level in Hazel anthers. The results of this study indicate that orbicules and pollen of Hazel might act as very effective vectors for homologues of Bet v 7 and that debris of Hazel anthers represent vectors of allergens after the pollen season.     

Synthesis of novel 7-substituted pyrido[2′,3′:4,5]furo[3,2-d]pyrimidin-4-amines and their N-aryl analogues and evaluation of their inhibitory activity against Ser/Thr kinases

The efficient synthesis of 7-substituted pyrido[2′,3′:4,5]furo[3,2-d]pyrimidin-4-amines and their N-aryl analogues is described. 3,5-Dibromopyridine was converted into 3-amino-6-bromofuro[3,2-b]pyridine-2-carbonitrile intermediate which was formylated with DMFDMA. Functionalization at position 7 of the tricyclic scaffold was accomplished, before or after cyclisation step, by palladium-catalyzed Suzuki–Miyaura cross-coupling while the pyrimidin-4-amines and N-aryl counterparts were synthesized by microwave-assisted formamide degradation and Dimroth rearrangement, respectively. The final products were evaluated for their potent inhibition of a series of five Ser/Thr kinases (CDK5/p25, CK1δ/ε, CLK1, DYRK1A, GSK3α/β). Compound 35 showed the best inhibitory activity with an IC₅₀ value of 49 nM and proved to be specific to CLK1 among the panel of tested kinases.