It is well documented that long term potentiation (LTP) is impaired in the hippocampus of the aged animal. Among the changes that contribute to this impairment is an increase in hippocampal ...concentration of the pro-inflammatory cytokine interleukin-1β (IL-1β), and increased IL-1β-induced signaling. In this study we investigated the possibility that these changes were a consequence of decreased concentration of the anti-inflammatory cytokine, IL-4, and decreased IL-4-stimulated signaling. We report that functional IL-4 receptors are expressed on granule cells of the dentate gyrus and that receptor activation results in phosphorylation of JAK1 and STAT6. Hippocampal IL-4 concentration was decreased with age, and this was accompanied by a decrease in phosphorylation of JAK1 and STAT6. The evidence indicates that IL-4 modulates expression of IL-1β mRNA and protein and that it attenuates IL-1β-induced impairment of LTP and phosphorylation of JNK and c-Jun. We argued that, if a decrease in hippocampal IL-4 concentration significantly contributed to the age-related impairment in LTP, then restoration of IL-4 should restore LTP. To test this, we treated rats with VP015 (phospholipid microparticles-incorporating phosphatidylserine), which increases IL-4 concentration in hippocampus. The data indicate that the VP015-induced increase in IL-4 concentration in hippocampus of aged rats and lipopolysaccharide (LPS)-treated rats was accompanied by a reversal of the age-related and LPS-induced impairment in LTP in perforant path granule cell synapses. We propose that interplay between pro-inflammatory and anti-inflammatory responses impact significantly on synaptic function in the hippocampus of the aged rat.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
There is compelling evidence to suggest that inflammation significantly contributes to neurodegenerative changes. Consistent with this is the observation that several neurodegenerative disorders are ...accompanied by an increase in the concentration of interleukin (IL)‐1β. IL‐1β has a negative impact on synaptic plasticity and therefore an increased concentration of IL‐1β, such as that in the hippocampus of the aged rat, is associated with a deficit in long‐term potentiation (LTP). IL‐1β is derived mainly from activated microglia but the trigger leading to this activation, specifically in the aged brain, remains to be identified. Here we examined the possiblity that interferon (IFN)γ may stimulate microglial activation and increase IL‐1β concentration, thereby inhibiting LTP. The IFNγ concentration was increased in hippocampus prepared from aged, compared with young, rats and inversely correlated with the ability of rats to sustain LTP. Intracerebroventricular injection of IFNγ inhibited LTP, and increased microglial activation was observed in both IFNγ‐injected and aged rats. The age‐related increase in IFNγ was accompanied by a decrease in the hippocampal concentration of insulin‐like growth factor (IGF)‐1. The evidence presented suggests that IGF‐1 acts to antagonize the IFNγ‐induced microglial activation, the accompanying increase in IL‐1β concentration and the consequent deficit in LTP.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Lipopolysaccharide (LPS) exerts a myriad of effects in rat hippocampus; it increases the concentration of the proinflammatory cytokine, interleukin‐1β (IL‐1β), and signalling via the IL‐1 type I ...receptor (IL‐1RI) resulting in phosphorylation of the stress‐activated protein kinase, c‐jun‐N‐terminal kinase (JNK) and impairment in long‐term potentiation (LTP). This study was designed to establish whether activation of JNK is a pivotal event in mediating the effects of LPS in hippocampus and therefore LPS‐treated rats were injected intracerebroventricularly with saline, the JNK inhibitor D‐JNKI1, or with the anti‐inflammatory cytokine IL‐4, which antagonizes the effects of IL‐1β upstream of JNK activation. We report that IL‐4 blocked the LPS‐induced increase in IL‐1RI expression and associated increases in phosphorylation of JNK and c‐jun, whereas D‐JNKI1 inhibited the LPS‐induced phosphorylation of c‐jun. Both IL‐4 and D‐JNKI1 inhibited the increase in caspase‐3 staining which was associated with LPS treatment, and both abrogated the LPS‐induced inhibition of LTP in perforant path‐granule cell synapses. The data presented are consistent with the proposal that JNK activation, probably as a result of increased IL‐1RI activation, is a critical step in mediating the detrimental effects of LPS in hippocampus.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The Cryogenic Dark Matter Search (CDMS) employs Ge and Si detectors to search for weakly interacting massive particles (WIMPs) via their elastic-scattering interactions with nuclei while ...discriminating against interactions of background particles. CDMS data, accounting for the neutron background, give limits on the spin-independent WIMP-nucleon elastic-scattering cross section that exclude unexplored parameter space above 10 GeV/c2 WIMP mass and, at >75% C.L., the entire 3sigma allowed region for the WIMP signal reported by the DAMA experiment.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Abstract Resistance to lethal encephalitis in mice infected with HSV-1 via the oral mucosa is mouse strain dependent. In susceptible BALB/c, HSV-1 spreads throughout the CNS but in resistant BL/6 ...mice, virus is restricted to the brainstem. To examine the contribution of cellular immunity in restricting viral spread, we used a combination of antibody depleted and KO mice. Individually, NK/NKT, iNKT, CD4+ , CD8+ , and γδ T-cells do not restrict HSV-1 spread. In contrast, virus spreads throughout the CNS of BL/6 CL I KO mice and BL/6 mice treated with either anti-asialoGM1 Ab or both anti-CD8 and anti-NK1.1 mAbs. The results highlight the importance of redundancy in the immune system in restricting viral spread in the CNS, argue for a role of NK/NKT and CD8+ T-cells in mediating the restriction, and provide a hierarchical order of the individual elements in controlling virus in BL/6 mice infected with HSV-1 via the oral mucosa.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: In this article, we describe the education model used to integrate population health learning into a new 4-year medical program at the University of Sydney.
Method: Our two-pronged ...approach aims to prepare third-year students to integrate population health thinking into their day-to-day clinical reasoning and to equip them with skills to investigate specific population health topics. We provide an example of a student-led, small-group session on health issues for disadvantaged populations, along with an outline of our assessment and evaluation methods. This innovative course illustrates one approach to the challenge of motivating students to bridge the gap between their interest in the medical care of individual patients and the healthcare needs of whole populations.
Results/Conclusions: Students performed adequately in the assessments required for progression to the next year of the program. Students rated the case-based exercises; self-directed learning; on-line and library resources; tutor facilitation; and student-led, small-group sessions as effective methods for learning.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
8.
Design of QET phonon sensors for the CDMS ZIP detectors Saab, T.; Clarke, R.M.; Cabrera, B. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
04/2000, Volume:
444, Issue:
1
Journal Article
Peer reviewed
The Cryogenic Dark Matter Search (CDMS) ZIP detectors utilize quasiparticle trapping as the mechanism for coupling the energy of a particle interaction in the Ge (or Si) absorber into a tungsten (W) ...transition edge sensor (TES). Consequently, the dynamics of quasiparticle propagation and loss significantly impact the energy collection and resolution of the detector. This paper describes the considerations necessary in optimizing the detector surface geometry in order to have maximal quasiparticle collection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The Neurosurgical Advanced Training curriculum of the Royal Australasian College of Surgeons (RACS) is currently undergoing change. Given the high standard of neurosurgery in Australia and New ...Zealand, it may be questioned why such change is necessary. However, the curriculum has not kept pace with developments in professional practice, educational practice or educational theory, particularly in the assessment of medical competence and performance. The curriculum must also adapt to the changing training environment, particularly the effects of reduced working hours, reducing caseloads due to shorter inpatient hospital stays and restricted access to public hospital beds and operating theatres, and the effects of subspecialisation. A formal review of the curriculum is timely.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The way in which students approach their learning is dependent on a variety of factors including the characteristics of the departments and teaching to which they are exposed. These factors appear to ...influence whether the students adopt a surface, deep or strategic approach. In order to explore further the relationship between educational context and approach to learning, a comparison was made between students attending a traditional medical school and those attending a problem-based medical school. The results showed marked differences, with the problem-based school being higher on deep approach and lower on surface approach than the traditional school. This study provides one of the first pieces of evidence of a difference between students in the two types of medical school which can be directly attributed to the educational environment. Students in the problem-based school appear to have an approach to learning which more closely approximates the aims of most medical schools. The results provide support for the philosophies and strategies of the problem-based schools.
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