Radioiodinated Phenylalkyl Malonic Acid Derivatives as pH-Sensitive SPECT Tracers

pH imaging has been a field of interest for molecular imaging for many years. This is especially important for determining tumor acidity, an important driving force of tumor invasion and metastasis formation, but also in the process of apoptosis.I]IPM was evaluated in an anti-Fas monoclonal antibody (mAb) apoptosis model. In addition a mouse RIF-1 tumor model was explored in which tumor pH was decreased from 7.0 to 6.5 by means of induction of hyperglycemia in combination with administration of meta-iodobenzylguanidine.I]IPM showed a clear pH-related uptake pattern in the RIF-1 tumor model. which allows to visualize regional acidosis. However, these compounds are not suitable for detection of apoptosis due to a poor acidosis effect

External tufted cells drive the output of olfactory bulb glomeruli.

Odors synchronize the activity of olfactory bulb mitral cells that project to the same glomerulus. In vitro, a slow rhythmic excitation intrinsic to the glomerular network persists, even in the absence of afferent input. We show here that a subpopulation of juxtaglomerular cells, external tufted (ET) cells, may trigger this rhythmic activity. We used paired whole-cell recording and Ca(2+) imaging in bulb slices from wild-type and transgenic mice expressing the fluorescent Ca(2+) indicator protein GCaMP-2. Slow, periodic population bursts in mitral cells were synchronized with spontaneous discharges in ET cells. Moreover, activation of a single ET cell was sufficient to evoke population bursts in mitral cells within the same glomerulus. Stimulation of the olfactory nerve induced similar population bursts and activated ET cells at a lower threshold than mitral cells, suggesting that ET cells mediate feedforward excitation of mitral cells. We propose that ET cells act as essential drivers of glomerular output to the olfactory cortex.journal articleresearch support, non-u.s. gov't2009 Feb 18importe

Monosynaptic and polysynaptic feed-forward inputs to mitral cells from olfactory sensory neurons.

Olfactory sensory neurons (OSNs) expressing the same odorant receptor converge in specific glomeruli where they transmit olfactory information to mitral cells. Surprisingly, synaptic mechanisms underlying mitral cell activation are still controversial. Using patch-clamp recordings in mouse olfactory bulb slices, we demonstrate that stimulation of OSNs produces a biphasic postsynaptic excitatory response in mitral cells. The response was initiated by a fast and graded monosynaptic input from OSNs and followed by a slower component of feedforward excitation, involving dendro-dendritic interactions between external tufted, tufted and other mitral cells. The mitral cell response occasionally lacked the fast OSN input when few afferent fibers were stimulated. We also show that OSN stimulation triggers a strong and slow feedforward inhibition that shapes the feedforward excitation but leaves unaffected the monosynaptic component. These results confirm the existence of direct OSN to mitral cells synapses but also emphasize the prominence of intraglomerular feedforward pathways in the mitral cell response.journal articleresearch support, non-u.s. gov't2011 Jun 15importe

Health effects of environmental exposure to cadmium: objectives, design and organization of the cadmibel study: a cross-sectional morbidity study carried out in Belgium from 1985 to 1989

Cadmium is a cumulative environmental pollutant. For the general population mainly exposed by the oral route and through tobacco smoke inhalation, the kidney is the critical organ. Belgium is the principal producer of cadmium in Europe, and certain areas of the country are polluted by cadmium mainly because of past emissions from nonferrous industries. Preliminary studies carried out in one polluted area have suggested that environmental pollution might lead to an increased uptake of cadmium by the human body and possibly to health effects. Thus, a large-scale morbidity study has been initiated to assess the validity of this hypothesis. The present paper describes the protocol of this study. Its main objectives are to determine to what extent environmental exposure to cadmium resulting from industrial emissions may lead to accumulation of the metal in the human organism; to establish whether or not environmental exposure may induce renal changes and/or influence blood pressure; and to assess the acceptable internal dose of cadmium for the general population. The study design takes advantage of the fact that biological indicators of exposure, body burden, and early nephrotoxic effects of cadmium are available, which increase the likelihood of detecting a cause-effect relationship

Status of evaluated data files for 238U in the resonance region

Experimental data and evaluated data libraries related to neutron induced reaction cross sections for 238U in the resonance region are reviewed. Based on this review a set of test files is produced to study systematic effects such as the impact of the upper boundary of the resolved resonance region (RRR) and the representation of the infinite diluted capture and in-elastic cross section in the unresolved resonance region (URR). A set of Benchmark experiments was selected and used to verify the test files. Based on these studies recommendations to perform a new evaluation have been defined. This report has been prepared in support to the CIELO (Collaborative International Evaluated Library Organisation) project. The objective of this project is the creation of a world-wide recognised nuclear data file with a focus on six nuclides, i.e. 1H, 16O, 56Fe, 235U, 238U and 239Pu. Within the CIELO project, the Joint Research Centre (JRC) at Geel (B) is in charge of the production of an evaluated cross section data file for neutron induced reaction of 238U in the resonance region.JRC.D.4-Standards for Nuclear Safety, Security and Safeguard

Intraglomerular lateral inhibition promotes spike timing variability in principal neurons of the olfactory bulb.

The activity of mitral and tufted cells, the principal neurons of the olfactory bulb, is modulated by several classes of interneurons. Among them, diverse periglomerular (PG) cell types interact with the apical dendrites of mitral and tufted cells inside glomeruli at the first stage of olfactory processing. We used paired recording in olfactory bulb slices and two-photon targeted patch-clamp recording in vivo to characterize the properties and connections of a genetically identified population of PG cells expressing enhanced yellow fluorescent protein (EYFP) under the control of the Kv3.1 potassium channel promoter. Kv3.1-EYFP(+) PG cells are axonless and monoglomerular neurons that constitute ∼30% of all PG cells and include calbindin-expressing neurons. They respond to an olfactory nerve stimulation with a short barrage of excitatory inputs mediated by mitral, tufted, and external tufted cells, and, in turn, they indiscriminately release GABA onto principal neurons. They are activated by even the weakest olfactory nerve input or by the discharge of a single principal neuron in slices and at each respiration cycle in anesthetized mice. They participate in a fast-onset intraglomerular lateral inhibition between principal neurons from the same glomerulus, a circuit that reduces the firing rate and promotes spike timing variability in mitral cells. Recordings in other PG cell subtypes suggest that this pathway predominates in generating glomerular inhibition. Intraglomerular lateral inhibition may play a key role in olfactory processing by reducing the similarity of principal cells discharge in response to the same incoming input.journal articleresearch support, non-u.s. gov't2015 Mar 11importe

Reappraisal of Vipera aspis Venom Neurotoxicity

BACKGROUND: The variation of venom composition with geography is an important aspect of intraspecific variability in the Vipera genus, although causes of this variability remain unclear. The diversity of snake venom is important both for our understanding of venomous snake evolution and for the preparation of relevant antivenoms to treat envenomations. A geographic intraspecific variation in snake venom composition was recently reported for Vipera aspis aspis venom in France. Since 1992, cases of human envenomation after Vipera aspis aspis bites in south-east France involving unexpected neurological signs were regularly reported. The presence of genes encoding PLA(2) neurotoxins in the Vaa snake genome led us to investigate any neurological symptom associated with snake bites in other regions of France and in neighboring countries. In parallel, we used several approaches to characterize the venom PLA(2) composition of the snakes captured in the same areas. [br/] METHODOLOGY/PRINCIPAL FINDINGS: We conducted an epidemiological survey of snake bites in various regions of France. In parallel, we carried out the analysis of the genes and the transcripts encoding venom PLA(2)s. We used SELDI technology to study the diversity of PLA(2) in various venom samples. Neurological signs (mainly cranial nerve disturbances) were reported after snake bites in three regions of France: Languedoc-Roussillon, Midi-Pyrénées and Provence-Alpes-Côte d'Azur. Genomes of Vipera aspis snakes from south-east France were shown to contain ammodytoxin isoforms never described in the genome of Vipera aspis from other French regions. Surprisingly, transcripts encoding venom neurotoxic PLA(2)s were found in snakes of Massif Central region. Accordingly, SELDI analysis of PLA(2) venom composition confirmed the existence of population of neurotoxic Vipera aspis snakes in the west part of the Massif Central mountains. [br/] CONCLUSIONS/SIGNIFICANCE: The association of epidemiological studies to genetic, biochemical and immunochemical analyses of snake venoms allowed a good evaluation of the potential neurotoxicity of snake bites. A correlation was found between the expression of neurological symptoms in humans and the intensity of the cross-reaction of venoms with anti-ammodytoxin antibodies, which is correlated with the level of neurotoxin (vaspin and/or ammodytoxin) expression in the venom. The origin of the two recently identified neurotoxic snake populations is discussed according to venom PLA(2) genome and transcriptome data