1991 DA: An asteroid in a bizarre orbit

Asteroidal object 1991 DA has an orbit of high inclination, crossing the planets from Mars to Uranus. This is unique for an asteroid, but not unusual for a comet of the Halley-type: it therefore seems likely that 1991 DA is an extinct or dormant comet. Previous CCD imaging has shown no indication of a coma; spectroscopic observations of 1991 DA which lack any evidence of strong comet-like emissions are reported. Numerical integrations of the orbit of this object were performed which show that is has been remarkably stable for the past approximately 20,000 yr, but chaotic before that. This may allow a new estimate to be made of the physical lifetimes of comets

Facile synthesis and proposed mechanism of α,ω‐oxetanyl-telechelic poly(3-nitratomethyl-3-methyl oxetane) by an SN2(i) nitrato displacement method in basic media

The synthesis of a novel heterocyclic–telechelic polymer, α,ω-oxetanyl-telechelic poly(3-nitratomethyl-3-methyl oxetane), is described. Infrared spectroscopy (IR), gel permeation chromatography (GPC), and nuclear magnetic resonance (NMR) spectroscopy have been used to confirm the successful synthesis, demonstrating the presence of the telechelic-oxetanyl moieties. Synthesis of the terminal functionalities has been achieved via displacement of nitrato groups, in a manner similar to that employed with other leaving groups such as azido, bromo, and nitro, initiated by nucleophiles. In the present case, displacement occurs on the ends of a nitrato-functionalized polymer driven by the formation of sodium nitrate, which is supported by the polar aprotic solvent N,N-dimethyl formamide. The formation of an alkoxide at the polymer chain ends is favored and allows internal back-biting to the nearest carbon bearing the nitrato group, intrinsically in an SN2(i) reaction, leading to α,ω-oxetanyl functionalization. The telechelic-oxetanyl moieties have the potential to be cross-linked by chemical (e.g., acidic) or radiative (e.g., ultraviolet) curing methods without the use of high temperatures, usually below 100°C. This type of material was designed for future use as a contraband simulant, whereby it would form the predominant constituent of elastomeric composites comprising rubbery polymer with small quantities of solids, typically crystals of contraband substances, such as explosives or narcotics. This method also provides an alternative approach to ring closure and synthesis of heterocycles

Investigating Bacterial Sources of Toxicity as an Environmental Contributor to Dopaminergic Neurodegeneration

Parkinson disease (PD) involves progressive neurodegeneration, including loss of dopamine (DA) neurons from the substantia nigra. Select genes associated with rare familial forms of PD function in cellular pathways, such as the ubiquitin-proteasome system (UPS), involved in protein degradation. The misfolding and accumulation of proteins, such as α-synuclein, into inclusions termed Lewy Bodies represents a clinical hallmark of PD. Given the predominance of sporadic PD among patient populations, environmental toxins may induce the disease, although their nature is largely unknown. Thus, an unmet challenge surrounds the discovery of causal or contributory neurotoxic factors that could account for the prevalence of sporadic PD. Bacteria within the order Actinomycetales are renowned for their robust production of secondary metabolites and might represent unidentified sources of environmental exposures. Among these, the aerobic genera, Streptomyces, produce natural proteasome inhibitors that block protein degradation and may potentially damage DA neurons. Here we demonstrate that a metabolite produced by a common soil bacterium, S. venezuelae, caused DA neurodegeneration in the nematode, Caenorhabditis elegans, which increased as animals aged. This metabolite, which disrupts UPS function, caused gradual degeneration of all neuronal classes examined, however DA neurons were particularly vulnerable to exposure. The presence of DA exacerbated toxicity because neurodegeneration was attenuated in mutant nematodes depleted for tyrosine hydroxylase (TH), the rate-limiting enzyme in DA production. Strikingly, this factor caused dose-dependent death of human SH-SY5Y neuroblastoma cells, a dopaminergic line. Efforts to purify the toxic activity revealed that it is a highly stable, lipophilic, and chemically unique small molecule. Evidence of a robust neurotoxic factor that selectively impacts neuronal survival in a progressive yet moderate manner is consistent with the etiology of age-associated neurodegenerative diseases. Collectively, these data suggest the potential for exposures to the metabolites of specific common soil bacteria to possibly represent a contributory environmental component to PD

Salmonella bongori provides insights into the evolution of the Salmonellae.

The genus Salmonella contains two species, S. bongori and S. enterica. Compared to the well-studied S. enterica there is a marked lack of information regarding the genetic makeup and diversity of S. bongori. S. bongori has been found predominantly associated with cold-blooded animals, but it can infect humans. To define the phylogeny of this species, and compare it to S. enterica, we have sequenced 28 isolates representing most of the known diversity of S. bongori. This cross-species analysis allowed us to confidently differentiate ancestral functions from those acquired following speciation, which include both metabolic and virulence-associated capacities. We show that, although S. bongori inherited a basic set of Salmonella common virulence functions, it has subsequently elaborated on this in a different direction to S. enterica. It is an established feature of S. enterica evolution that the acquisition of the type III secretion systems (T3SS-1 and T3SS-2) has been followed by the sequential acquisition of genes encoding secreted targets, termed effectors proteins. We show that this is also true of S. bongori, which has acquired an array of novel effector proteins (sboA-L). All but two of these effectors have no significant S. enterica homologues and instead are highly similar to those found in enteropathogenic Escherichia coli (EPEC). Remarkably, SboH is found to be a chimeric effector protein, encoded by a fusion of the T3SS-1 effector gene sopA and a gene highly similar to the EPEC effector nleH from enteropathogenic E. coli. We demonstrate that representatives of these new effectors are translocated and that SboH, similarly to NleH, blocks intrinsic apoptotic pathways while being targeted to the mitochondria by the SopA part of the fusion. This work suggests that S. bongori has inherited the ancestral Salmonella virulence gene set, but has adapted by incorporating virulence determinants that resemble those employed by EPEC.We thank the core sequencing and informatics teams at the Sanger Institute for their assistance and The Wellcome Trust for its support of the Sanger Institute Pathogen Genomics and Biology groups and the MRC for their support of GF, KSR and GNS. MCF, GCL, TRC, HSS, GSV, MS, NKP, RAK, JP, GD and NRT were supported by Wellcome Trust grant 076964 and MICROME, an EU Framework Programme 7 Collaborative Project, Grant Agreement Number 222886-2. Work was also supported by Grant ADI-08/2006 from Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) and The World Bank, and grant 1100092 from Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT). CJB was supported by fellowships from CONICYT (21080373 and AT-24091015)

Can employment positively affect the recovery of people with psychiatric disabilities?

Objective: This study explored the relationship between employment and recovery in individuals with psychiatric disabilities and proposed that participants who were employed would have higher levels of recovery than participants who were not employed. Methods: Data were analysed from a pre-existing data-set produced in a large scale NHMRC project conducted as part of the Australian Integrated Mental Health Initiative (AIMhi), High Support Stream. Participants were 344 people with a range of psychiatric illnesses who received support from 11 public sector and non-government mental health organizations in Queensland and New South Wales, Australia. Scores on the Recovery Assessment Scale (RAS) were compared between those participants who were engaged in paid employment and those who were not. Results: The results revealed that there was no difference in total recovery scores between those who worked and those who did not work. This finding indicated that higher recovery scores were not associated with participants who were employed. Also contrary to expectations, the results showed that workers scored lower than non-workers on the RAS factor described as "reliance on others" and there was a trend towards significance in the same direction on the factor "willingness to ask for help." Conclusions and Implications for Practice: Further research needs to be conducted to determine if the differences between workers and non-workers on the above factors represent a personal variable such as independence or self-determination that is associated with individuals with psychiatric disabilities that are engaged in employment. Rehabilitation interventions aimed at increasing levels of employment in people with psychiatric disabilities could improve recovery and employment outcomes through focusing on these personal variables. Copyright 2011 Trustees of Boston University