Toxoplasma gondii effectors are master regulators of the inflammatory response

Toxoplasma is a highly successful parasite that establishes a life-long chronic infection. To do this, it must carefully regulate immune activation and host cell effector mechanisms. Here we review the latest developments in our understanding of how Toxoplasma counteracts the immune response of the host, and in some cases provokes it, through the use of specific parasite effector proteins. An emerging theme from these discoveries is that Toxoplasma effectors are master regulators of the pro-inflammatory response, which elicits many of the toxoplasmacidal mechanisms of the host. We speculate that combinations of these effectors present in certain Toxoplasma strains work to maintain an optimal parasite burden in different hosts to ensure parasite transmission.Knights Templar Eye Foundation, Inc.American Heart Association (0835099N)Massachusetts Life Sciences Center (New Investigator Award)Singapore-MIT Alliance for Research and Technology (SMART)National Institutes of Health (U.S.) (NIH RO1-AI080621)New England Regional Center of Excellence for Biodefense and Emerging Infectious Diseases (NERCE Developmental Grant)National Cancer Institute (U.S.) (Irvington Postdoctoral Fellowship Program

Detector Description and Performance for the First Coincidence Observations between LIGO and GEO

For 17 days in August and September 2002, the LIGO and GEO interferometer gravitational wave detectors were operated in coincidence to produce their first data for scientific analysis. Although the detectors were still far from their design sensitivity levels, the data can be used to place better upper limits on the flux of gravitational waves incident on the earth than previous direct measurements. This paper describes the instruments and the data in some detail, as a companion to analysis papers based on the first data.Comment: 41 pages, 9 figures 17 Sept 03: author list amended, minor editorial change

Multiple drivers of decline in the global status of freshwater crayfish (Decapoda: Astacidea)

International audienceRates of biodiversity loss are higher in freshwater ecosystems than in most terrestrial or marine ecosystems, making freshwater conservation a priority. However, prioritization methods are impeded by insufficient knowledge on the distribution and conservation status of freshwater taxa, particularly invertebrates. We evaluated the extinction risk of the world's 590 freshwater crayfish species using the IUCN Categories and Criteria and found 32% of all species are threatened with extinction. The level of extinction risk differed between families, with proportionally more threatened species in the Parastacidae and Astacidae than in the Cambaridae. Four described species were Extinct and 21% were assessed as Data Deficient. There was geographical variation in the dominant threats affecting the main centres of crayfish diversity. The majority of threatened US and Mexican species face threats associated with urban development, pollution, damming and water management. Conversely, the majority of Australian threatened species are affected by climate change, harvesting, agriculture and invasive species. Only a small proportion of crayfish are found within the boundaries of protected areas, suggesting that alternative means of long-term protection will be required. Our study highlights many of the significant challenges yet to come for freshwater biodiversity unless conservation planning shifts from a reactive to proactive approach

Neuropathological Findings In Chronic Relapsing Experimental Allergic Neuritis Induced In The Lewis Rat By Inoculation With Intradural Root Myelin And Treatment With Low Dose Cyclosporin A

Experimental allergic neuritis (EAN) was induced in Lewis rats by inoculation with bovine intradural root myelin and adjuvants. Rats treated with subcutaneous cyclosporin A (CsA) (4mg/kg on 3 days per week from the day of inoculation until day 29) developed a chronic relapsing course. Tissues from the spinal cord, nerve roots, dorsal root ganglia and sciatic nerve of CsA-treated rats sampled during relapses and remissions were studied during or after episodes of acute EAN. Both control and CsA-treated animals studied in the first episode of EAN had evidence of inflammation and primary demyelination of the nerve roots and dorsal root ganglia. In control and CsA-treated animals in the second episode there was severe inflammation and demyelination and remyelination in the spinal nerves and sciatic nerves and dorsal columns of the spinal cord, particularly in later stages of the disease. In later episodes there was less inflammation, but there was continuing demyelination and onion bulbs were present. In animals sampled after recovery from chronic relapsing EAN onion bulbs were present. Occasional small onion bulbs were also observed in control animals that were inoculated with higher doses of myelin. Plasma cells were present in the inflammatory lesions of later episodes. Mast cells were also observed at different stages of the disease. We conclude that the CsA form of chronic relapsing EAN has clinical and pathological similarities with the human disease, chronic inflammatory demyelinating polyradiculoneuropathy

Optical wireless Ethernet

This paper details the design and testing of an optical wireless Ethernet system. This system is a demonstration unit that grants the user of a mobile computer access to network services usually only available to wired users. The system operates at the full Ethernet rate of 10Mbit/s and has a range of approximately four meters in a typical office environment. Issues concerning the safety of the transmitters has been presented along with details of how the commercial LEDs used in the transmitter were switched at the high speeds and powers required. Also the transmitter/receiver link has been modeled and simulated. These simulations compare well to measurements taken in a test room, the layout of which matches that of a typical office environmen

A review of the ever increasing threat to European crayfish from non-indigenous crayfish species

Non-indigenous crayfish species (NICS) in Europe now outnumber indigenous crayfish species (ICS) 2:1, and it has been predicted that they may dominate completely in the next few decades unless something is done to protect them. Of the ten NICS introduced at least nine have become established in areas occupied by four of the five ICS. A decline in stocks of ICS has been recorded in many countries in the face of increasing populations of NICS. Most European countries retain at least one ICS but all are under threat from habitat loss, deteriorating water quality, overfishing, climate change, and most importantly from NICS and crayfish plague. The threat to ICS is so great in some countries that “ark”sanctuary sites are being established. The three most widely-spread NICS are the North American species: Pacifastacus leniusculus, Orconectes limosus and Procambarus clarkii. These can be considered as “Old NICS”, which were introduced before 1975, compared with the “New NICS”, which were introduced after 1980, such as the North American species: Orconectes immunis, Orconectes juvenilis, Orconectes virilis, Procambarus sp. and Procambarus acutus; and the Australian species: Cherax destructor and Cherax quadricarinatus, all of which have much narrower ranges in Europe. The North American species are potentially capable of acting as vectors of crayfish plague. Outbreaks of this disease occur regularly where there are high concentrations of vectors. In addition to the NICS currently established in the wild, a further threat exists through the aquarium trade, where many American and Australian species are available via the internet and in aquarist centres. Owners of such species may discard them into the freshwater environment when they grow too big as with some Cherax spp. and Orconectes spp., or multiply too frequently as with Procambarus sp. (a parthenogenetic species). A conceptual model is presented as a possible way forward for protecting the future survival of ICS in Europe

Neurokinin B is a paracrine vasodilator in the human fetal placental circulation

Neurokinin (NK) B is a member of the tachykinin family of neurotransmitters, exerting hypotensive or hypertensive effects in the mammalian vasculature through synaptic release from peripheral neurons, according to either NK1 and NK2 or NK3 receptor subtype expression, respectively. There is recent evidence that NKB is expressed by the syncytiotrophoblast of the human placenta, an organ that is not innervated. We hypothesized that NKB is a paracrine modulator of tone in the fetal placental circulation. We tested this hypothesis using the in vitro perfused human placental cotyledon. Our data show that NKB is a dilator of the fetal vasculature, causing a maximal 25.1+/-4.5% (mean+/-SEM; n=5) decrease in fetal-side arterial hydrostatic pressure (5-muM NKB bolus; effective concentration in the circulation, 1.89 nM) after preconstriction with U-46619. RT-PCR demonstrated the presence of mRNA for NK1 and NK2 tachykinin receptors in the placenta. Using selective receptor antagonists, we found that NKB-induced vasodilation is through the NK1 receptor subtype. We found no evidence for the involvement of either nitric oxide or prostacyclin in this response. This study demonstrates a paracrine role for NKB in the regulation of fetal placental vascular tone