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Specific Loss (specific + loss)
Selected AbstractsFusion of diphtheria toxin and urotensin II produces a neurotoxin selective for cholinergic neurons in the rat mesopontine tegmentumJOURNAL OF NEUROCHEMISTRY, Issue 1 2007S. D. Clark Abstract Urotensin II is a neuropeptide first isolated from fish and later found in mammals: where it has potent cardiovascular, endocrine and behavioral effects. In rat brain the urotensin II receptor (UII-R) is predominately expressed in the cholinergic neurons of the pedunculopontine (PPTg) and laterodorsal tegmental nuclei. Typically, the function of the PPTg has been examined using excitotoxins, destroying both cholinergic and non-cholinergic neurons, which confounds interpretation. We took advantage of UII-R's unique expression profile, by combining UII with diphtheria toxin, to engineer a toxin specific for cholinergic neurons of the PPTg. In vitro, two different toxin constructs were shown to selectively activate UII-R (average EC50 , 30 nmol/L; calcium mobility assay) and to be 10 000-fold more toxic to UII-R expressing CHO cells, than wildtype cells (average LD50 , 2 nmol/L; cell viability). In vivo, pressure injection into the PPTg of rats, resulted in specific loss of choline transporter and NADPH diaphorase positive neurons known to express the UII-R. The lesions developed over time, resulting in the loss of over 80% of cholinergic neurons at 21 days, with little damage to surrounding neurons. This is the first highly selective molecular tool for the depletion of mesopontine cholinergic neurons. The toxin will help to functionally dissect the pedunculopontine and laterodorsal tegmental nuclei, and advance the understanding of the functions of these structures. [source] Laminar specific loss of isocortical presenilin 1 immunoreactivity in Alzheimer's disease.NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 2 2000Correlations with the amyloid load, the density of tau-positive neurofibrillary tangles Presenilin 1 has been shown to be mutated in a high proportion of cases of familial Alzheimer's disease. Immunoreactive epitopes of the protein have been found mainly in neurones devoid of neurofibrillary tangles , an observation that has led to the conclusion that presenilin 1 could have a protective role. In this study, the relationship between deposits of A, peptide (both the 40 and 42 isoforms), tau positive neurofibrillary tangles and presenilin 1-positive neuronal profiles were analysed in three cases of presenilin 1 mutation, four cases of sporadic Alzheimer's disease and five controls. Immunohistochemistry was performed in a sample from the supramarginal gyrus. The proportion of volume occupied by the A,1,40 and A,1,42 deposits (amyloid load) was evaluated by a point-counting technique. Tau-positive neurofibrillary tangles, and presenilin 1-positive neuronal profiles were directly counted. The location of the lesions in the thickness of the cortex was recorded. The density of PS1-positive neuronal profiles in Alzheimer's disease cases was lower than in the controls. The deficit was significant only in the upper layers of the cortex. The density of presenilin 1 neuronal profiles was negatively correlated with A,1,40 and A,1,42 loads, and with the density of tau-positive neurofibrillary tangles. Multivariate analysis showed that the A,1,42 load was the best determinant of the decrease in presenilin 1-positive neuronal profiles. Presenilin 1-positive neurones appear to be lost rather than protected in the course of Alzheimer disease. [source] AtDEK1 is essential for specification of embryonic epidermal cell fateTHE PLANT JOURNAL, Issue 1 2005Kim L. Johnson Summary The specification of epidermal (L1) identity occurs early during plant embryogenesis. Here we show that, in Arabidopsis, AtDEK1 encodes a key component of the embryonic L1 cell-layer specification pathway. Loss of AtDEK1 function leads to early embryo lethality characterized by a severe loss of cell organization in the embryo proper and abnormal cell divisions within the suspensor. Markers for L1 identity, ACR4 and ATML1, are not expressed in homozygous mutant embryos. In order to clarify the function of AtDEK1 further, an RNAi knockdown approach was used. This allowed embryos to partially complete embryogenesis before losing AtDEK1 activity. Resulting seedlings showed a specific loss of epidermal cell identity within large portions of the cotyledons. In addition, meristem structure and function was systematically either reduced or entirely lost. AtDEK1 expression is not restricted to the L1 epidermal cell layer at any stage in development. This is consistent with AtDEK1 playing an upstream role in the continuous generation or interpretation of positional information required for epidermal specification. Our results not only identify a specific role for AtDEK1 during embryogenesis, but underline the potential key importance of L1 specification at the globular stage for subsequent progression through embryogenesis. [source] Regulation of plant water loss by manipulating the expression of phospholipase D,THE PLANT JOURNAL, Issue 2 2001Yongming Sang Summary Phospholipase D (PLD) has been implicated in various processes, including signal transduction, membrane trafficking, and membrane degradation. Multiple forms of PLD with distinct biochemical properties have been described in the cell. In Arabidopsis, PLD, and PLD,, but not PLD,, were detected in guard cells, and antisense suppression resulted in a specific loss of PLD,. The abrogation of PLD, rendered plants less sensitive to abscisic acid and impaired stomatal closure induced by water deficits. PLD,-depleted plants exhibited accelerated transpirational water loss and a decreased ability to tolerate drought stress. Overexpression of PLD, enhanced the leaf's sensitivity to abscisic acid. These findings provide molecular and physiological evidence that PLD, plays a crucial role in regulating stomatal movement and plant-water status. [source] | ||||||||||