Genomic characterization of the Taylorella genus

The Taylorella genus comprises two species: Taylorella equigenitalis, which causes contagious equine metritis, and Taylorella asinigenitalis, a closely-related species mainly found in donkeys. We herein report on the first genome sequence of T. asinigenitalis, analyzing and comparing it with the recently-sequenced T. equigenitalis genome. The T. asinigenitalis genome contains a single circular chromosome of 1,638,559 bp with a 38.3% GC content and 1,534 coding sequences (CDS). While 212 CDSs were T. asinigenitalis-specific, 1,322 had orthologs in T. equigenitalis. Two hundred and thirty-four T. equigenitalis CDSs had no orthologs in T. asinigenitalis. Analysis of the basic nutrition metabolism of both Taylorella species showed that malate, glutamate and alpha-ketoglutarate may be their main carbon and energy sources. For both species, we identified four different secretion systems and several proteins potentially involved in binding and colonization of host cells, suggesting a strong potential for interaction with their host. T. equigenitalis seems better-equipped than T. asinigenitalis in terms of virulence since we identified numerous proteins potentially involved in pathogenicity, including hemagluttinin-related proteins, a type IV secretion system, TonB-dependent lactoferrin and transferrin receptors, and YadA and Hep_Hag domains containing proteins. This is the first molecular characterization of Taylorella genus members, and the first molecular identification of factors potentially involved in T. asinigenitalis and T. equigenitalis pathogenicity and host colonization. This study facilitates a genetic understanding of growth phenotypes, animal host preference and pathogenic capacity, paving the way for future functional investigations into this largely unknown genus.     

Crucial role of aspartic acid at position 265 in the CH2 domain for murine IgG2a and IgG2b Fc-associated effector functions

Replacement of aspartic acid by alanine at position 265 (D265A) in mouse IgG1 results in a complete loss of interaction between this isotype and low-affinity IgG Fc receptors (Fc gammaRIIB and Fc gammaRIII). However, it has not yet been defined whether the D265A substitution could exhibit similar effects on the interaction with two other Fc gammaR (Fc gammaRI and Fc gammaRIV) and on the activation of complement. To address this question, 34-3C anti-RBC IgG2a and IgG2b switch variants bearing the D265A mutation were generated, and their effector functions and in vivo pathogenicity were compared with those of the respective wild-type Abs. The introduction of the D265A mutation almost completely abolished the binding of 34-3C IgG2a and IgG2b to all four classes of Fc gammaR and the activation of complement. Consequently, these mutants were hardly pathogenic. Although oligosaccharide side chains of these mutants were found to contain higher levels of sialic acids than those of wild-type Abs, the analysis of enzymatically desialylated D265A variants ruled out the possibility that very poor Fc-associated effector functions of the D265A mutants were due to an increased level of the mutant Fc sialylation. Thus, our results demonstrate that aspartic acid at position 265 is a residue critically implicated in triggering the Fc-associated effector functions of IgG, probably by defining a crucial three-dimensional structure of the Fc region.     

Impact of a three amino acid deletion in the CH2 domain of murine IgG1 on Fc-associated effector functions

Four murine IgG subclasses display markedly different Fc-associated effector functions because of their differential binding to three activating IgG Fc receptors (FcgammaRI, FcgammaRIII, and FcgammaRIV) and C1q. Previous analysis of IgG subclass switch variants of 34-3C anti-RBC monoclonal autoantibodies revealed that the IgG1 subclass, which binds only to FcgammaRIII and fails to activate complement, displayed the poorest pathogenic potential. This could be related to the presence of a three amino acid deletion at positions 233-235 in the CH2 domain uniquely found in this subclass. To address this question, IgG1 insertion and IgG2b deletion mutants at positions 233-235 of 34-3C anti-RBC Abs were generated, and their ability to initiate effector functions and their pathogenicity were compared with those of the respective wild-type Abs. The insertion of amino acid residues at positions 233-235 enabled the IgG1 subclass to bind FcgammaRIV but did not improve the binding to C1q. Accordingly, its pathogenicity was enhanced but still inferior to that of IgG2b. In contrast, the IgG2b deletion mutant lost its ability to bind to FcgammaRIV and activate complement. Consequently, its pathogenicity was markedly diminished to a level comparable to that of IgG1. Our results demonstrated that the initiation of FcgammaR- and complement-mediated effector functions of IgG2b was profoundly affected by the three amino acid deletion at positions 233-235, but that this natural three amino acid deletion could only partially explain the poor binding of IgG1 to FcgammaRIV and C1q. This indicates the lack in the IgG1 subclass of as yet unknown motifs promoting efficient interaction with FcgammaRIV and C1q.     

The Isothiocyanate Sulforaphane Depends on the Nrf2/γ-GCL/GSH Axis to Prevent Mitochondrial Dysfunction in Cells Exposed to Methylglyoxal

Neurochemical Research - Methylglyoxal (MG) is a reactive dicarbonyl presenting both endogenous (e.g. glycolysis) and exogenous (e.g. food cooking) sources. MG induces neurotoxicity, at least in...     

Elevational gradients in plant defences and insect herbivory: recent advances in the field and prospects for future research

Classic research on elevational gradients in plant–herbivore interactions holds that insect herbivore pressure is stronger under warmer, less seasonal climates characteristic of low elevations, and that this in turn selects for increased defence in low‐ (relative to high‐) elevation plants. However, recent work has questioned this paradigm, arguing that it overly simplifies the ecological complexity in which plant–insect herbivore interactions are embedded along elevational gradients. Numerous biotic and abiotic factors vary with elevation, and their simultaneous influences are the focus of current work on elevational gradients in insect herbivory and plant defences. The present review 1) synthesizes current knowledge on elevational gradients in plant–insect herbivore interactions; 2) critically analyses research gaps and highlights recent advances that contribute to filling these gaps; and 3) outlines new research opportunities to uncover underlying mechanisms and build towards a unified theory on elevational gradients. We conclude that the next generation of studies should embrace community complexity – including multi‐trophic dynamics and the multivariate nature of plant defence – and to do so by combining observational data, manipulative experiments and emerging analytical tools.     

Projected distributions of Southern Ocean albatrosses,petrels and fisheries as a consequence of climatic change

Given the major ongoing influence of environmental change on the oceans, there is a need to understand and predict the future distributions of marine species in order to plan appropriate mitigation to conserve vulnerable species and ecosystems. In this study we use tracking data from seven large seabird species of the Southern Ocean (black‐browed albatross Thalassarche melanophris, grey‐headed albatross T. chrysostoma, northern giant petrel Macronectes halli, southern giant petrel M. giganteus, Tristan albatross Diomedea dabbenena, wandering albatross D. exulans and white‐chinned petrel Procellaria aequinoctialis, and on fishing effort in two types of fisheries (characterised by low or high‐bycatch rates), to model the associations with environmental variables (bathymetry, chlorophyll‐a concentration, sea surface temperature and wind speed) through ensemble species distribution models. We then projected these distributions according to four climate change scenarios built by the Intergovernmental Panel for Climate Change for 2050 and 2100. The resulting projections were consistent across scenarios, indicating that there is a strong likelihood of poleward shifts in distribution of seabirds, and several range contractions (resulting from a shift in the northern, but no change in the southern limit of the range in four species). Current trends for southerly shifts in fisheries distributions are also set to continue under these climate change scenarios at least until 2100; some of these may reflect habitat loss for target species that are already over‐fished. It is of particular concern that a shift in the distribution of several highly threatened seabird species would increase their overlap with fisheries where there is a high‐bycatch risk. Under such scenarios, the associated shifts in distribution of seabirds and increases in bycatch risk will require much‐improved fisheries management in these sensitive areas to minimise impacts on populations in decline.     

Probe signal correction for differential methylation hybridization experiments

Background  

Non-biological signal (or noise) has been the bane of microarray analysis. Hybridization effects related to probe-sequence composition and DNA dye-probe interactions have been observed in differential methylation hybridization (DMH) microarray experiments as well as other effects inherent to the DMH protocol.     

Species distribution and <Emphasis Type="Italic">in vitro</Emphasis> antifungal susceptibility of oral yeast isolates from Tanzanian HIV-infected patients with primary and recurrent oropharyngeal candidiasis

Background  

In Tanzania, little is known on the species distribution and antifungal susceptibility profiles of yeast isolates from HIV-infected patients with primary and recurrent oropharyngeal candidiasis.     

Mental practice-based rehabilitation training to improve arm function and daily activity performance in stroke patients: a randomized clinical trial

Background  

Over 50% of patients with upper limb paresis resulting from stroke face long-term impaired arm function and ensuing disability in daily life. Unfortunately, the number of effective treatments aimed at improving arm function due to stroke is still low. This study aims to evaluate a new therapy for improving arm function in sub-acute stroke patients based on mental practice theories and functional task-oriented training, and to study the predictors for a positive treatment result. It is hypothesized that a six-week, mental practice-based training program (additional to regular therapy) targeting the specific upper extremity skills important to the individual patient will significantly improve both arm function and daily activity performance, as well as being cost effective.