Mechanisms underlying pathogenic processes in mycoplasma infections are poorly understood, mainly because of limited sequence similarities with classical, bacterial virulence factors. Recently, large-scale transposon mutagenesis in the ruminant pathogen Mycoplasma agalactiae identified the NIF locus, including nifS and nifU, as essential for mycoplasma growth in cell culture, while dispensable in axenic media. To evaluate the importance of this locus in vivo, the infectivity of two knock-out mutants was tested upon experimental infection in the natural host. In this model, the parental PG2 strain was able to establish a systemic infection in lactating ewes, colonizing various body sites such as lymph nodes and the mammary gland, even when inoculated at low doses. In these PG2-infected ewes, we observed over the course of infection (i) the development of a specific antibody response and (ii) dynamic changes in expression of M. agalactiae surface variable proteins (Vpma), with multiple Vpma profiles co-existing in the same animal. In contrast and despite a sensitive model, none of the knock-out mutants were able to survive and colonize the host. The extreme avirulent phenotype of the two mutants was further supported by the absence of an IgG response in inoculated animals. The exact role of the NIF locus remains to be elucidated but these data demonstrate that it plays a key role in the infectious process of M. agalactiae and most likely of other pathogenic mycoplasma species as many carry closely related homologs. 相似文献
Species of Erythroneurini (Cicadellidae: Typhlocybinae) currently placed in the genus Zygina and found in Australia, New Zealand and some neighbouring islands are transferred to the new genus Anzygina , type species Erythroneura sidnica Kirkaldy, following comparison with the type species of the genus: Typhlocyba nivea Mulsant and Rey. New combinations are Anzygina sidnica (Kirkaldy), Anzygina honiloa (Kirkaldy), Anzygina melanogaster (Kirkaldy) and Anzygina sativae (Evans) from Australia, Anzygina toetoe (Cumber), Anzygina agni (Knight), Anzygina dumbletoni (Ghauri) and Anzygina ramsayi (Knight) from New Zealand, Anzygina zealandica (Myers) from Australia and New Zealand, Anzygina jowettae (Knight) from Norfolk Island and Anzygina medioborealis (Ghauri) from Papua New Guinea. Lectotypes are designated for Erythroneura honiloa Kirkaldy and E. sidnica Kirkaldy. Anzygina billi sp.n. is described from SE Qld, and Anzygina barrattae sp.n. is described from the South Island of New Zealand. A. agni is a new record for Australia and is presumed to be Australian in origin. A. dumbletoni has a distribution which suggests that it also is introduced to New Zealand although its origins are not known. A. ramsayi, A. barrattae and A. toetoe , all of which appear to be New Zealand endemics, show affinity with each other based on aedeagal structure. A key to these species, based on males, is provided. The lack of male syntypes for Erythroneura honiala Kirkaldy and Erythroneura lubra Kirkaldy precludes establishment of their identities relative to other species of the genus, and both names are regarded as having nomen dubium status. Australian species not transferred to Anzygina are Zygina evansi (Ross) and Zygina ipoloa (Kirkaldy), both of which belong elsewhere. 相似文献
Stressful events promote several neuroendocrine and neurotransmitter changes that might contribute to the provocation of psychological and physical pathologies. Perhaps, because of its apparent ecological validity and its simple application, there has been increasing use of social defeat (resident-intruder) paradigms as a stressor. The frequency of stress-related psychopathology is much greater in females than in males, but the typical resident-intruder paradigm is less useful in assessing stressor effects in females. An alternative, but infrequently used procedure in females involves exposing a mouse to a lactating dam, resulting in threatening gestures being expressed by the resident. In the present investigation we demonstrated the utility of this paradigm, showing that the standard resident-intruder paradigm in males and the modified version in females promoted elevated anxiety in a plus-maze test. The behavioral effects that reflected anxiety were more pronounced 2 weeks after the stressor treatment than they were 2 hr afterward, possibly reflecting the abatement of the stress-related of hyper-arousal. These treatments, like a stressor comprising physical restraint, increased plasma corticosterone and elicited variations of norepinephrine and serotonin levels and turnover within the prefrontal cortex, hippocampus and central amygdala. Moreover, the stressor effects were exaggerated among mice that had been exposed to a chronic or subchronic-intermittent regimen of unpredictable stressors. Indeed, some of the monoamine changes were more pronounced in females than in males, although it is less certain whether this represented compensatory changes to deal with chronic stressors that could result in excessive strain on biological systems (allostatic overload). 相似文献
Planar cell polarity (PCP) signaling controls a number of morphogenetic processes including convergent extension during gastrulation and neural tube formation. Defects in this pathway cause neural tube defects (NTD), the most common malformations of the central nervous system. The Looptail (Lp) mutant mouse was the first mammalian mutant implicating a PCP gene (Vangl2) in the pathogenesis of NTD. We report on a novel chemically induced mutant allele at Vangl2 called Curly Bob that causes a missense mutation p.Ile268Asn (I268N) in the Vangl2 protein. This mutant segregates in a semi-dominant fashion with heterozygote mice displaying a looped tail appearance, bobbing head, and a circling behavior. Homozygote mutant embryos suffer from a severe form of NTD called craniorachischisis, severe PCP defects in the inner hair cells of the cochlea and posterior cristae, and display a distinct defect in retinal axon guidance. This mutant genetically interacts with the Lp allele (Vangl2S464N) in neural tube development and inner ear hair cell polarity. The Vangl2I268N protein variant is expressed at very low levels in affected neural and retinal tissues of mutant homozygote embryos. Biochemical studies show that Vangl2I268N exhibits impaired targeting to the plasma membrane and accumulates in the endoplasmic reticulum. The Vangl2I268N variant no longer physically interacts with its PCP partner DVL3 and has a reduced protein half-life. This mutant provides an important model for dissecting the role of Vangl2 in the development of the neural tube, establishment of polarity of sensory cells of the auditory and vestibular systems, and retinal axon guidance.
Summary The light chain of tetanus neurotoxin (TeNTL chain) has been shown to be endowed with zine endopeptidase activity, selectively
directed towards the Gln76-Phe77 bond of synaptobrevin, a vesicle-associated membrane protein critically involved in neuroexocytosis. In previous reports,
truncations at the NH2- and COOH-terminus of synaptobrevin have shown that the sequence 39–88 of synaptobrevin is the minimum substrate of TeNT,
suggesting either the requirement of a well-defined three-dimensional structure of synaptobrevin or a role in the mechanism
of substrate hydrolysis for residues distal from the cleavage site. In this study, the addition of NH2- and COOH-terminal peptides of synaptobrevin, S 27–55 (S1) and S 82–93 (S2), to the synaptobrevin fragment S 56–81 allowed the cleavage of this latter peptide by TeNT to occur. This appears to result
from an activation process mediated by the simultaneous binding of S1 and S2 with complementary sites present on TeNT as shown by surface plasmon resonance experiments. All these results favor an exosite-controlled
hydrolysis of synaptobrevin by TeNT probably involving a conformational change of the toxin. This could accound for the high
degree of substrate specificity of TeNT and, probably, botulinum neurotoxins. 相似文献