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Differential Requirements (differential + requirement)

Distribution by Scientific Domains

Life Sciences	60%
Medical Sciences	40%

Selected Abstracts

Differential Requirement of CD27 Costimulatory Signaling for Naïve Versus Alloantigen-Primed Effector/Memory CD8+ T Cells

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2010
K. Yamaura
CD8+ memory T cells endanger allograft survival by causing acute and chronic rejection and prevent tolerance induction. We explored the role of CD27:CD70 T-cell costimulatory pathway in alloreactive CD8+/CD4+ T-cell activation. CD27-deficient (CD27,/,) and wild-type (WT) B6 mice rejected BALB/c cardiac allografts at similar tempo, with or without depletion of CD4+ or CD8+ T cells, suggesting that CD27 is not essential during primary T-cell alloimmune responses. To dissect the role of CD27 in primed effector and memory alloreactive T cells, CD27,/, or WT mice were challenged with BALB/c hearts either 10 or 40 days after sensitization with donor-type skin grafts. Compared to WT controls, allograft survival was prolonged in day 40- but not day 10-sensitized CD27,/, recipients. Improved allograft survival was accompanied by diminished secondary responsiveness of memory CD8+ T cells, which resulted from deficiency in memory formation rather than their lack of secondary expansion. Chronic allograft vasculopathy and fibrosis were diminished in CD27,/, recipients of class I- but not class II-mismatched hearts as compared to WT controls. These data establish a novel role for CD27 as an important costimulatory molecule for alloreactive CD8+ memory T cells in acute and chronic allograft rejection. [source]

Dopaminergic neurotoxicity by 6-OHDA and MPP+: Differential requirement for neuronal cyclooxygenase activity

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2005
Emilce Carrasco
Abstract Cyclooxygenase (COX), a key enzymatic mediator of inflammation, is present in microglia and surviving dopaminergic neurons in Parkinson's disease (PD), but its role and place in the chain of neurodegenerative events is unclear. Epidemiologic evidence showed that regular use of nonsteroidal antiinflammatory drugs (NSAIDs), specifically non-aspirin COX inhibitors like ibuprofen, lowers the risk for PD; however, the putative cause-and-effect relationship between COX activity in activated microglia and neuronal loss was challenged recently. We examined whether neuronal COX activity is involved directly in dopaminergic cell death after neurotoxic insult. Using low concentrations of 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridium ion (MPP+), neurotoxicants used to model selective dopaminergic cell loss in PD, and cultures of embryonic rat mesencephalic neurons essentially devoid of glia, we tested whether the nonselective COX inhibitor ibuprofen attenuated 6-OHDA and MPP+ neurotoxicity. At levels close to its IC50 for both COX isoforms, ibuprofen protected dopaminergic neurons against 6-OHDA but not MPP+ toxicity. Experiments with selective inhibitors of COX-1 (SC-560) and COX-2 (NS-398 and Cayman 10404), indicated that COX-2, but not COX-1, was involved in 6-OHDA toxicity. Accordingly, 6-OHDA, but not MPP+, increased prostaglandin (PG) levels twofold and this increase was blocked by ibuprofen. At concentrations well above its IC50 for COX, ibuprofen also prevented MPP+ toxicity, but had only limited efficacy against loss of structural complexity. Taken together, our data suggest that selective 6-OHDA toxicity to dopaminergic neurons is associated with neuronal COX-2, whereas MPP+ toxicity is COX independent. This difference may be important for understanding and manipulating mechanisms of dopaminergic cell death. © 2005 Wiley-Liss, Inc. [source]

Differential requirements for interleukin (IL)-4 and IL-13 in protein contact dermatitis induced by Anisakis

ALLERGY, Issue 9 2009
N. Nieuwenhuizen
Background:, Exposure to antigens of the fish parasite Anisakis is associated with the development of protein contact dermatitis in seafood-processing workers. Understanding the basic mechanisms controlling allergic sensitization through the skin is critical for designing therapies that will prevent the progression of allergic disease. Objective:, To investigate the roles of interleukin (IL)-4, IL-13 and the IL-4R, in both local skin pathology and systemic sensitization following epicutaneous exposure to Anisakis proteins. Methods:, BALB/c wild-type (WT) mice and mice deficient in IL-4, IL-13 or IL-4 and IL-13, as well as mice with cell-specific impairment of IL-4R, expression, were sensitized to Anisakis antigen by repeated epicutaneous application of Anisakis extract. Following this sensitization, skin pathology was recorded and systemic responses were investigated. Intravenous challenge with Anisakis extract was performed to test for the development of biologically relevant systemic sensitization. Results:, In WT mice, epicutaneous sensitization with Anisakis larval antigens induced localized inflammation, epidermal hyperplasia, production of TH2 cytokines, antigen-specific IgE and IgG1. Intravenous challenge of sensitized mice resulted in anaphylactic shock. Interestingly, IL-13 deficient mice failed to develop epidermal hyperplasia and inflammation, whilst anaphylaxis was reduced only in strains deficient either in IL-4 only, or deficient in IL-4 and IL-13 concurrently, as well as in mice deficient in IL-4R, or with impaired IL-4R, expression on CD4+ T cells. Conclusions:, Interleukin-13 plays a central role in protein contact dermatitis associated with repeated epicutaneous exposure to Anisakis extract, whereas IL-4 drives systemic sensitization and resultant anaphylactic shock. [source]

Early onset of deafening-induced song deterioration and differential requirements of the pallial-basal ganglia vocal pathway

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2008
Haruhito Horita
Abstract Similar to humans, songbirds rely on auditory feedback to maintain the acoustic and sequence structure of adult learned vocalizations. When songbirds are deafened, the learned features of song, such as syllable structure and sequencing, eventually deteriorate. However, the time-course and initial phases of song deterioration have not been well studied, particularly in the most commonly studied songbird, the zebra finch. Here, we observed previously uncharacterized subtle but significant changes to learned song within a few days following deafening. Syllable structure became detectably noisier and silent intervals between song motifs increased. Although song motif sequences remained stable at 2 weeks, as previously reported, pronounced changes occurred in longer stretches of song bout sequences. These included deletions of syllables between song motifs, changes in the frequency at which specific chunks of song were produced and stuttering for birds that had some repetitions of syllables before deafening. Changes in syllable structure and song bout sequence occurred at different rates, indicating different mechanisms for their deterioration. The changes in syllable structure required an intact lateral part but not the medial part of the pallial-basal ganglia vocal pathway, whereas changes in the song bout sequence did not require lateral or medial portions of the pathway. These findings indicate that deafening-induced song changes in zebra finches can be detected rapidly after deafening, that acoustic and sequence changes can occur independently, and that, within this time period, the pallial-basal ganglia vocal pathway controls the acoustic structure changes but not the song bout sequence changes. [source]

Notch and affinity boundaries in Drosophila

BIOESSAYS, Issue 2 2006
Héctor Herranz
Cells in multicellular organisms often do not intermingle freely with each other. Differential cell affinities can contribute to organizing cells into different tissues. Drosophila limbs and the vertebrate central nervous system are subdivided into compartments. Cells in adjacent compartments do not mix. Cell interactions mediated by Notch-family receptors have been implicated in the specification of these compartment boundaries. Two recent reports analyze the role of the Notch signaling pathway in the generation of an affinity boundary in the Drosophila wing.1,2 The first report1 analyzes the connection between Notch and the actin cytoskeleton. The second report2 analyzes the differential requirements of Notch and the transcription factor Supressor of Hairless in generating the affinity boundary. BioEssays 28: 113,116, 2006. © 2006 Wiley periodicals, Inc. [source]