Mycoplasma arthritidis-derived superantigen (MAM) displays DNase activity

Bacterial superantigens are potent stimulators of the immune system. In this study, we expressed recombinant superantigens, which were then affinity purified and used for growth curves and DNase activity assays. Overexpression of Mycoplasma arthritidis-derived superantigen in Escherichia coli reduced bacterial growth. This is unique, as staphylococcal enterotoxin A and toxic shock syndrome toxin-1, expressed in the same vector system, showed no growth impairment. The observed growth inhibition was caused by the DNase activity of recombinant M. arthritidis-derived superantigen, thus describing the first superantigen showing enzymatic activity, which may be a result of the separate evolution of this toxin.     

Endophenotype properties of niacin sensitivity as marker of impaired prostaglandin signalling in schizophrenia

BACKGROUND: Disruption of arachidonic acid pathways and prostaglandin signalling has been implicated in the pathophysiology of schizophrenia. AIMS: We intended to study prostaglandin signalling in groups of young schizophrenia patients, first-degree relatives, and healthy controls in order to assess effects of heritability on this biological marker-one important endophenotype criterion. METHOD: Namely, we assessed intensity of methylnicotinate skin flushing using optical reflection spectroscopy. Tests were applied to 19 adolescent first-episode schizophrenia patients, 21 first-degree relatives, and groups of age and gender matched healthy controls. RESULTS: Compared to healthy controls, attenuation of skin flushing at low niacin concentrations was found only in schizophrenia patients, but not in first-degree relatives. CONCLUSION: While our results indicate niacin hyposensitivity as reliable biological marker in schizophrenia, they do not provide clear evidence for its heritability. Particularly, the results in adolescent schizophrenia patients are suggestive for the perception of attenuated niacin flushing as secondary to the pathophysiology at the onset of schizophrenic illness, namely increased oxidative stress, alterations of unspecific immune-response or inflammation-like processes.     

Enigmatic dual symbiosis in the excretory organ of Nautilus macromphalus (Cephalopoda: Nautiloidea)

Symbiosis is an important driving force in metazoan evolution and the study of ancient lineages can provide an insight into the influence of symbiotic associations on morphological and physiological adaptations. In the 'living fossil' Nautilus, bacterial associations are found in the highly specialized pericardial appendage. This organ is responsible for most of the excretory processes (ultrafiltration, reabsorption and secretion) and secretes an acidic ammonia-rich excretory fluid. In this study, we show that Nautilus macromphalus pericardial appendages harbour a high density of a beta-proteobacterium and a coccoid spirochaete using transmission electron microscopy, comparative 16S rRNA sequence analysis and fluorescence in situ hybridization (FISH). These two bacterial phylotypes are phylogenetically distant from any known bacteria, with ammonia-oxidizing bacteria as the closest relatives of the beta-proteobacterium (above or equal to 87.5% sequence similarity) and marine Spirochaeta species as the closest relatives of the spirochaete (above or equal to 89.8% sequence similarity), and appear to be specific to Nautilus. FISH analyses showed that the symbionts occur in the baso-medial region of the pericardial villi where ultrafiltration and reabsorption processes take place, suggesting a symbiotic contribution to the excretory metabolism.     

Resistance to a CRISPR-based gene drive at an evolutionarily conserved site is revealed by mimicking genotype fixation

CRISPR-based homing gene drives can be designed to disrupt essential genes whilst biasing their own inheritance, leading to suppression of mosquito populations in the laboratory. This class of gene drives relies on CRISPR-Cas9 cleavage of a target sequence and copying (‘homing’) therein of the gene drive element from the homologous chromosome. However, target site mutations that are resistant to cleavage yet maintain the function of the essential gene are expected to be strongly selected for. Targeting functionally constrained regions where mutations are not easily tolerated should lower the probability of resistance. Evolutionary conservation at the sequence level is often a reliable indicator of functional constraint, though the actual level of underlying constraint between one conserved sequence and another can vary widely. Here we generated a novel adult lethal gene drive (ALGD) in the malaria vector Anopheles gambiae, targeting an ultra-conserved target site in a haplosufficient essential gene (AGAP029113) required during mosquito development, which fulfils many of the criteria for the target of a population suppression gene drive. We then designed a selection regime to experimentally assess the likelihood of generation and subsequent selection of gene drive resistant mutations at its target site. We simulated, in a caged population, a scenario where the gene drive was approaching fixation, where selection for resistance is expected to be strongest. Continuous sampling of the target locus revealed that a single, restorative, in-frame nucleotide substitution was selected. Our findings show that ultra-conservation alone need not be predictive of a site that is refractory to target site resistance. Our strategy to evaluate resistance in vivo could help to validate candidate gene drive targets for their resilience to resistance and help to improve predictions of the invasion dynamics of gene drives in field populations.     

Modelling complexation and electrostatic attraction in heavy metal biosorption by Sargassum biomass

Biosorption, the passive accumulation of metal ions by biomass, can be used for purifying metal bearing wastewater. Seaweeds represent a readily available source of biosorbent material that possesses a high metal binding capacity. For example, Sargassum can accumulate 2 mequiv of Cd per gram of biomass i.e. 10% of its dry weight. Binding of Cd and Cu by Sargassum is an ion exchange process involving both covalent and ionic bonds. The amount of cations bound covalently or by complexation can be predicted using multi-component sorption isotherms involving 2 types of binding sites, carboxyl and sulphate. A Donnan model was used to account for the effect of ionic strength and electrostatic attraction. The use of a multi-component isotherm that included one term for Na binding was less appropriate than the Donnan model for modelling ionic strength effects. It was possible to predict metal and proton binding as a function of the pH value, metal concentration and ionic strength of the solution. This revised version was published online in June 2006 with corrections to the Cover Date.