877 research outputs found
Altered serological and cellular reactivity to H-2 antigens after target cell infection with vaccinia virus
MICE generate cytotoxic T lymphocytes (CTL) which are able to lyse virus infected target cells in vitro after infection with lymphocytic choriomeningitis virus (LCMV) and pox-viruses1β3. CTL kill syngeneic and semiallogenic infected cells but not allogenic infected targets. Target cell lysis in these systems seems to be restricted by H-2 antigens, especially by the K or D end of the major histocompatibility complex (MHC). In experiments where virus specific sensitised lymphocytes kill virus infected allogenic target cells4 the effector lymphocytes have not been characterised exactly. Recent investigations suggest that the active cell in this assay, at least in the measles infection, is a non-thymus derived cell (H. Kreth, personal communication). An H-2 restriction of cell mediated cytolysis (CMC) to trinitrophenol (TNP)-modified lymphocytes has also been described5. Zinkernagel and Doherty6 postulated that the CTL is directed against syngeneic H-2 antigens and viral antigens and they suggested an alteration of H-2 induced by the LCMV infection. Earlier7 we found a close topological relationship between H-2 antigens and the target antigen(s) responsible for CMC in the vaccinia system. Here we report experiments which were carried out to prove alteration of H-2 after infection of L-929 fibroblasts with vaccinia virus
T-cell cytotoxicity in the absence of viral protein synthesis in target cells
CYTOTOXIC T cells lyse only those virus infected target cells in vitro which express, in addition to the viral antigen(s), those K or D region products of the major histocompati-bility complex (MHC) which were present during anti-viral sensitisation in vivo. This 'associative recogniton' by cytotoxic T cells could reflect the interaction of two T-cell receptors with specificity for target K or D gene products and independently for the viral antigen, or one receptor with specificity for virally altered K or D region products (see ref. 1 and refs therein). There are various ways that the MHC antigens could be altered, including 'modification from within', where the virus modifies host protein synthesis by interfering with transcription2, translation or post-translational glycosylation; or 'modification from without' where enzymic or chemical alteration of cell membrane proteins are induced by virus activity at the cell surface. In this report we show that inactivated Sendai virus or isolated Sendai virus envelopes can serve to modify a cell and make it a specific target for Sendai-immune T-cell killing, thus excluding the possibility of 'modification from within' in this system
Deconstructing Weight Management Interventions for Young Adults: Looking Inside the Black Box of the EARLY Consortium Trials.
ObjectiveThe goal of the present study was to deconstruct the 17 treatment arms used in the Early Adult Reduction of weight through LifestYle (EARLY) weight management trials.MethodsIntervention materials were coded to reflect behavioral domains and behavior change techniques (BCTs) within those domains planned for each treatment arm. The analytical hierarchy process was employed to determine an emphasis profile of domains in each intervention.ResultsThe intervention arms used BCTs from all of the 16 domains, with an average of 29.3 BCTs per intervention arm. All 12 of the interventions included BCTs from the six domains of Goals and Planning, Feedback and Monitoring, Social Support, Shaping Knowledge, Natural Consequences, and Comparison of Outcomes; 11 of the 12 interventions shared 15 BCTs in common across those six domains.ConclusionsWeight management interventions are complex. The shared set of BCTs used in the EARLY trials may represent a core intervention that could be studied to determine the required emphases of BCTs and whether additional BCTs add to or detract from efficacy. Deconstructing interventions will aid in reproducibility and understanding of active ingredients
Climate warming, marine protected areas and the ocean-scale integrity of coral reef ecosystems
Coral reefs have emerged as one of the ecosystems most vulnerable to climate variation and change. While the contribution
of a warming climate to the loss of live coral cover has been well documented across large spatial and temporal scales, the
associated effects on fish have not. Here, we respond to recent and repeated calls to assess the importance of local
management in conserving coral reefs in the context of global climate change. Such information is important, as coral reef
fish assemblages are the most species dense vertebrate communities on earth, contributing critical ecosystem functions
and providing crucial ecosystem services to human societies in tropical countries. Our assessment of the impacts of the
1998 mass bleaching event on coral cover, reef structural complexity, and reef associated fishes spans 7 countries, 66 sites
and 26 degrees of latitude in the Indian Ocean. Using Bayesian meta-analysis we show that changes in the size structure,
diversity and trophic composition of the reef fish community have followed coral declines. Although the ocean scale
integrity of these coral reef ecosystems has been lost, it is positive to see the effects are spatially variable at multiple scales,
with impacts and vulnerability affected by geography but not management regime. Existing no-take marine protected areas
still support high biomass of fish, however they had no positive affect on the ecosystem response to large-scale disturbance.
This suggests a need for future conservation and management efforts to identify and protect regional refugia, which should
be integrated into existing management frameworks and combined with policies to improve system-wide resilience to
climate variation and change
The ATP-Binding Cassette Proteins of the Deep-Branching Protozoan Parasite Trichomonas vaginalis
The ATP binding cassette (ABC) proteins are a family of membrane transporters and regulatory proteins responsible for diverse and critical cellular process in all organisms. To date, there has been no attempt to investigate this class of proteins in the infectious parasite Trichomonas vaginalis. We have utilized a combination of bioinformatics, gene sequence analysis, gene expression and confocal microscopy to investigate the ABC proteins of T. vaginalis. We demonstrate that, uniquely among eukaryotes, T. vaginalis possesses no intact full-length ABC transporters and has undergone a dramatic expansion of some ABC protein sub-families. Furthermore, we provide preliminary evidence that T. vaginalis is able to read through in-frame stop codons to express ABC transporter components from gene pairs in a head-to-tail orientation. Finally, with confocal microscopy we demonstrate the expression and endoplasmic reticulum localization of a number of T. vaginalis ABC transporters
Biomechanical comparison of screw-based zoning of PHILOS and Fx proximal humerus plates
Background Treatment of proximal humerus fractures with locking plates is associated with complications. We aimed to compare the biomechanical effects of removing screws and blade of a fixed angle locking plate and hybrid blade plate, on a two-part fracture model. Methods Forty-five synthetic humeri were divided into nine groups where four were implanted with a hybrid blade plate and the remaining with locking plate, to treat a two-part surgical neck fracture. Platesβ head screws and blades were divided into zones based on their distance from fracture site. Two groups acted as a control for each plate and the remaining seven had either a vacant zone or blade swapped with screws. For elastic cantilever bending, humeral head was fixed and the shaft was displaced 5 mm in extension, flexion, valgus and varus direction. Specimens were further loaded in varus direction to investigate their plastic behaviour. Results In both plates, removal of inferomedial screws or blade led to a significantly larger drop in varus construct stiffness than other zones. In blade plate, insertion of screws in place of blade significantly increased the mean extension, flexion valgus and varus bending stiffness (24.458%/16.623%/19.493%/14.137%). In locking plate, removal of screw zones proximal to the inferomedial screws reduced extension and flexion bending stiffness by 26β33%. Conclusions Although medial support improved varus stability, two inferomedial screws were more effective than blade. Proximal screws are important for extension and flexion. Mechanical consequences of screw removal should be considered when deciding the number and choice of screws and blade in clinic
Effects of supervised exercise training on lower-limb cutaneous microvascular reactivity in adults with venous ulcers
Purpose: To investigate the effects of a 12-week supervised exercise programme on lower-limb cutaneous microvascular reactivity in adults with venous leg ulceration.
Methods: Thirty-eight adults with unilateral venous ulceration who were being treated with lower-limb compression therapy (58% male; mean age 65 years; median ulcer size 5 cm2) were randomly allocated to exercise or control groups. Exercise participants (n=18) were invited to attend thrice weekly sessions of lower-limb aerobic and resistance exercise for 12 weeks. Cutaneous microvascular reactivity was assessed in the gaiter region of ulcerated and non-ulcerated legs at baseline and 3 months using laser Doppler fluxmetry coupled with iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). Cutaneous vascular conductance (CVC) was calculated as laser Doppler flux (AU)/mean arterial pressure (mmHg).
Results: Thirty-seven participants completed follow-up assessments. Median class attendance was 36 (range 2 to 36). Analyses of covariance revealed greater peak CVC responses to ACh in the exercise group at 3 months in both the ulcerated (adjusted difference = 0.944 AU/mmHg; 95% CI 0.504 to 1.384) and non-ulcerated (adjusted difference = 0.596 AU/mmHg; 95% CI 0.028 to 1.164) legs. Peak CVC responses to SNP were also greater in the exercise group at 3 months in the ulcerated leg (adjusted difference = 0.882 AU/mmHg; 95% CI 0.274 to 1.491), but not the non-ulcerated leg (adjusted difference = 0.392 AU/mmHg; 95% CI -0.377 to 1.161).
Conclusion: Supervised exercise training improves lower-limb cutaneous microvascular reactivity in adults with venous leg ulceration.
Keywords
Randomized controlled trial; Exercise; Ulceration; Vascular function; Laser Doppler fluxmetry; Iontophoresi
Learning with a network of competing synapses
Competition between synapses arises in some forms of correlation-based
plasticity. Here we propose a game theory-inspired model of synaptic
interactions whose dynamics is driven by competition between synapses in their
weak and strong states, which are characterized by different timescales. The
learning of inputs and memory are meaningfully definable in an effective
description of networked synaptic populations. We study, numerically and
analytically, the dynamic responses of the effective system to various signal
types, particularly with reference to an existing empirical motor adaptation
model. The dependence of the system-level behavior on the synaptic parameters,
and the signal strength, is brought out in a clear manner, thus illuminating
issues such as those of optimal performance, and the functional role of
multiple timescales.Comment: 16 pages, 9 figures; published in PLoS ON
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