New species of the Hygrobates salamandrarum-group (Acari, Hydrachnidia, Hygrobatidae) from Southeast Asia

Two new water mite species of the genus Hygrobates Koch, 1837 (Acari, Hydrachnidia, Hygrobatidae) were found to live parasitic on newts of the genus Paramesotriton Chang, 1935 (Amphibia, Caudata, Salamandridae) from Vietnam and Laos: Hygrobates forcipifer sp. nov. and H. ancistrophorus sp. nov. The H. salamandrarum-group is defined, that now includes three species from Southeast Asia. Males and females of both new species are described, as well as larvae and deutonymphs of the Vietnamese species. These data provide the first record of males, nymphs and larvae of the species-group. The systematic position of the group, as well as the parasite-host association and the lifecycle of the species are discussed. Furthermore, the character states of the striking mouthparts, particularly modified as an adaptation for penetrating the amphibian skin, the genital skeleton and the larval morphology are examined.     

Genetic manipulation of CD74 in mouse strains of different backgrounds can result in opposite responses to central nervous system injury

The ability to recover from CNS injuries is strain dependent. Transgenic mice that weakly express the p41 CD74 isoform (an integral membrane protein functioning as a MHC class II chaperone) on an I-A(b) genetic background have normal CD4(+) T cell populations and normal surface expression of MHC class II, but their B cell development is arrested while the cells are still immature. After a CNS injury, these mice recover better than their matched wild-type controls. We generated p41-transgenic mice on an I-A(d) background (p41-I-A(d) mice), and found that their recovery from CNS injuries was worse than that of controls. A correlative inverse effect was seen with respect to the kinetics of T cell and B cell recruitment to the injured CNS and the expression of insulin-like growth factor at the lesion site. These results, besides verifying previous findings that B cells function in the damaged CNS, demonstrate that the outcome of a particular genetic manipulation may be strain dependent.     

Analysis of methylarginine metabolism in the cardiovascular system identifies the lung as a major source of ADMA

Protein arginine methylation is catalyzed by a family of enzymes called protein arginine methyltransferases (PRMTs). Three forms of methylarginine have been identified in eukaryotes: monomethylarginine (l-NMMA), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA), all characterized by methylation of one or both guanidine nitrogen atoms of arginine. l-NMMA and ADMA, but not SDMA, are competitive inhibitors of all nitric oxide synthase isoforms. SDMA is eliminated almost entirely by renal excretion, whereas l-NMMA and ADMA are further metabolized by dimethylarginine dimethylaminohydrolase (DDAH). To explore the interplay between methylarginine synthesis and degradation in vivo, we determined PRMT expression and DDAH activity in mouse lung, heart, liver, and kidney homogenates. In addition, we employed HPLC-based quantification of protein-incorporated and free methylarginine, combined with immunoblotting for the assessment of tissue-specific patterns of arginine methylation. The salient findings of the present investigation can be summarized as follows: 1) pulmonary expression of type I PRMTs was correlated with enhanced protein arginine methylation; 2) pulmonary ADMA degradation was undertaken by DDAH1; 3) bronchoalveolar lavage fluid and serum exhibited almost identical ADMA/SDMA ratios, and 4) kidney and liver provide complementary routes for clearance and metabolic conversion of circulating ADMA. Together, these observations suggest that methylarginine metabolism by the pulmonary system significantly contributes to circulating ADMA and SDMA levels.     

Bicarbonate and active site zinc modulate the self-peroxidation of bovine copper-zinc superoxide dismutase

Peroxidation reactions of copper-zinc superoxide dismutase (CuZn-SOD1) or its zinc-depleted form (CuE-SOD1) that likely also involve a component of bicarbonate buffer have been implicated in the pathophysiology of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS), Alzheimer's Disease and Parkinson's Disease. Neither removal of the zinc ion nor adding bicarbonate had large effects on the self-peroxidation reaction of bovine SOD1, but the combination of zinc-deficiency and added bicarbonate caused major changes to the spin trapped SOD1-centred free radical. Removal of the active site zinc ion greatly decreased the formation of an unassigned SOD1-centred free radical in the reaction with the inorganic peroxide peroxynitrite. The results suggest that under cellular conditions ( approximately 5 mM bicarbonate) zinc-deficient SOD1 peroxidation could play a pathogenic role in neurodegenerative diseases.     

Combining ontogenetic and evolutionary scales of morphological disparity: a study of early Jurassic ammonites

Two major research themes in Evolutionary Developmental Biology and in Paleobiology, respectively, have each become central for the analysis and interpretation of morphological changes in evolution: the study of ontogeny/phylogeny connections, mainly within the widespread and controversial framework of heterochrony; and the study of morphological disparity, the morphological signal of biodiversity, describing secular changes in morphospace occupation during the history of any given clade. Although enriching in their respective fields, these two themes have remained rather isolated to date, despite the potential value of integrating them as some recent studies begin to suggest. Here, we explore the recent notion of developmental morphospace-morphospace carrying ontogenetic information-as a potential tool for bridging the gap between disparity dynamics and developmental dynamics. We elaborate this approach with a case study of Early Jurassic ammonite family Hildoceratidae (Mollusca, Cephalopoda). Morphometric analyses of the shell shape of 20 species spanning the morphological spectrum of the family are used to quantify and contrast juvenile and adult disparity levels. Adult disparity is significantly greater than juvenile disparity at the family level; yet, some subclades also display different patterns. In addition, comparisons of ontogenetic trajectories underline the prevalence of heterochrony-based evolutionary modifications within subfamilies (via ontogenetic scaling); they also point to the probable existence of pervasive developmental constraints structuring inhomogeneous morphospace occupation.     

A Secreted Effector Protein of Ustilago maydis Guides Maize Leaf Cells to Form Tumors

The biotrophic smut fungus Ustilago maydis infects all aerial organs of maize (Zea mays) and induces tumors in the plant tissues. U. maydis deploys many effector proteins to manipulate its host. Previously, deletion analysis demonstrated that several effectors have important functions in inducing tumor expansion specifically in maize leaves. Here, we present the functional characterization of the effector See1 (Seedling efficient effector1). See1 is required for the reactivation of plant DNA synthesis, which is crucial for tumor progression in leaf cells. By contrast, See1 does not affect tumor formation in immature tassel floral tissues, where maize cell proliferation occurs independent of fungal infection. See1 interacts with a maize homolog of SGT1 (Suppressor of G2 allele of skp1), a factor acting in cell cycle progression in yeast (Saccharomyces cerevisiae) and an important component of plant and human innate immunity. See1 interferes with the MAPK-triggered phosphorylation of maize SGT1 at a monocot-specific phosphorylation site. We propose that See1 interferes with SGT1 activity, resulting in both modulation of immune responses and reactivation of DNA synthesis in leaf cells. This identifies See1 as a fungal effector that directly and specifically contributes to the formation of leaf tumors in maize.     

The Drosophila L1CAM homolog Neuroglian signals through distinct pathways to control different aspects of mushroom body axon development

The spatiotemporal integration of adhesion and signaling during neuritogenesis is an important prerequisite for the establishment of neuronal networks in the developing brain. In this study, we describe the role of the L1-type CAM Neuroglian protein (NRG) in different steps of Drosophila mushroom body (MB) neuron axonogenesis. Selective axon bundling in the peduncle requires both the extracellular and the intracellular domain of NRG. We uncover a novel role for the ZO-1 homolog Polychaetoid (PYD) in axon branching and in sister branch outgrowth and guidance downstream of the neuron-specific isoform NRG-180. Furthermore, genetic analyses show that the role of NRG in different aspects of MB axonal development not only involves PYD, but also TRIO, SEMA-1A and RAC1.     

Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

Background  

Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics.