Genetic variation in the carbonic anhydrase isozymes of macaque monkeys. I. The radioimmunosorbent assay

A radioimmunosorbent technique is described which is capable of independently detecting both isozymes of carbonic anhydrase, CA I and CA II, in concentrations as low as 1 ng/ml. The technique is used to quantitate the different electrophoretic variants of red cell CA I as well as levels of CA II in the pig-tailed macaque, Macaca nemestrina .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44181/1/10528_2004_Article_BF00485543.pd

Genetic variation in the carbonic anhydrase isozymes of macaque monkeys : III. Biosynthesis of carbonic anhydrases in bone marrow erythroid cells and peripheral blood reticulocytes of Macaco nemestrina

The carbonic anhydrase isozymes (CA I and CA II) of the pig-tailed macaque, Macaca nemestrina, have been chosen to study the regulation of enzyme levels in red blood cells. Two quantitative variants of CA I that are ideal for studies of enzyme regulation exist in this species. One variant is one of four known electrophoretic types of CA I, designated CA Ia, which is present at levels about 30% of those of the other electrophoretic types. The other is a deficiency variant of CA I which, in homozygotes, reduces the product of the CA I locus about 5000-fold and reduces the product of the CA II locus by about 60%. -[14C]Serine was used to study the biosynthesis of CA I and CA II isozymes in the reticulocytes of animals carrying these CA I variants. Specific radioactivity and total incorporation data from bone marrow erythroid cells, and peripheral blood reticulocytes indicate that the reduced CA Ia concentration is probably the result of degradation. This degradation appears to occur for only a short time before the reticulocytes enter the peripheral blood. It was not possible to determine whether the 5000-fold reduction of CA I in the CA I-deficient animals is due to reduced transcription, reduced translation, or degradation. The effect of the CA I-deficiency mutation on the synthesis of CA II was also studied. For each dose of CA I-deficiency gene, there appears to be a 30% reduction in the rate of -[14C]serine incorporation into CA II, thereby accounting for the reduced CA II concentration in CA I-deficient animals.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33820/1/0000077.pd

Retinotopic Mapping of Categorical and Coordinate Spatial Relation Processing in Early Visual Cortex

Spatial relations are commonly divided in two global classes. Categorical relations concern abstract relations which define areas of spatial equivalence, whereas coordinate relations are metric and concern exact distances. Categorical and coordinate relation processing are thought to rely on at least partially separate neurocognitive mechanisms, as reflected by differential lateralization patterns, in particular in the parietal cortex. In this study we address this textbook principle from a new angle. We studied retinotopic activation in early visual cortex, as a reflection of attentional distribution, in a spatial working memory task with either a categorical or a coordinate instruction. Participants were asked to memorize a dot position, with regard to a central cross, and to indicate whether a subsequent dot position matched the first dot position, either categorically (opposite quadrant of the cross) or coordinately (same distance to the centre of the cross). BOLD responses across the retinotopic maps of V1, V2, and V3 indicate that the spatial distribution of cortical activity was different for categorical and coordinate instructions throughout the retention interval; a more local focus was found during categorical processing, whereas focus was more global for coordinate processing. This effect was strongest for V3, approached significance in V2 and was absent in V1. Furthermore, during stimulus presentation the two instructions led to different levels of activation in V3 during stimulus encoding; a stronger increase in activity was found for categorical processing. Together this is the first demonstration that instructions for specific types of spatial relations may yield distinct attentional patterns which are already reflected in activity early in the visual cortex

Lateral specialization in unilateral spatial neglect : a cognitive robotics model

In this paper, we present the experimental results of an embodied cognitive robotic approach for modelling the human cognitive deficit known as unilateral spatial neglect (USN). To this end, we introduce an artificial neural network architecture designed and trained to control the spatial attentional focus of the iCub robotic platform. Like the human brain, the architecture is divided into two hemispheres and it incorporates bio-inspired plasticity mechanisms, which allow the development of the phenomenon of the specialization of the right hemisphere for spatial attention. In this study, we validate the model by replicating a previous experiment with human patients affected by the USN and numerical results show that the robot mimics the behaviours previously exhibited by humans. We also simulated recovery after the damage to compare the performance of each of the two hemispheres as additional validation of the model. Finally, we highlight some possible advantages of modelling cognitive dysfunctions of the human brain by means of robotic platforms, which can supplement traditional approaches for studying spatial impairments in humans

Genetic control of quantitative variation in carbonic anhydrase isozymes of mammals. I. The concentration within single erythrocytes of the mouse

The levels of the carbonic anhydrase isozymes (CA and CA II) in single erythrocytes of DBA/2J mice were assayed by measuring the specific immunofluorescence of CA I and CA II with a microspectrofluorometric technique. Measurements of 100 randomly selected cells showed a range (in relative fluorescence units) of 21–52 (mean 31.3±7.5) for CA I and 30–80 (mean 45.6±10.7) for CA II. The CA II/CA I ratio of the means obtained by the single-cell fluorescence assay was similar to the ratios obtained for the two isozymes from hemolysates of DBA/2J mice using an immunodiffusion assay. The influence of cell age on the variation in carbonic anhydrase levels was determined by separating red cells into several fractions by a gravity sedimentation procedure. The younger cells showed higher levels of CA I and CA II than the older cells; however, the extensive overlap in the variability between the cells from the different fractions indicated that although cell age was contributing to the overall heterogeneity, its influence was not pronounced.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44126/1/10528_2004_Article_BF00483984.pd

Local iontophoretic administration of cytotoxic therapies to solid tumors

Parenteral and oral routes have been the traditional methods of administering cytotoxic agents to cancer patients. Unfortunately, the maximum potential effect of these cytotoxic agents has been limited because of systemic toxicity and poor tumor perfusion. In an attempt to improve the efficacy of cytotoxic agents while mitigating their side effects, we have developed modalities for the localized iontophoretic delivery of cytotoxic agents. These iontophoretic devices were designed to be implanted proximal to the tumor with external control of power and drug flow. Three distinct orthotopic mouse models of cancer and a canine model were evaluated for device efficacy and toxicity. Orthotopic patient-derived pancreatic cancer xenografts treated biweekly with gemcitabine via the device for 7 weeks experienced a mean log2 fold change in tumor volume of −0.8 compared to a mean log2 fold change in tumor volume of 1.1 for intravenous (IV) gemcitabine, 3.0 for IV saline, and 2.6 for device saline groups. The weekly coadministration of systemic cisplatin therapy and transdermal device cisplatin therapy significantly increased tumor growth inhibition and doubled the survival in two aggressive orthotopic models of breast cancer. The addition of radiotherapy to this treatment further extended survival. Device delivery of gemcitabine in dogs resulted in more than 7-fold difference in local drug concentrations and 25-fold lower systemic drug levels than the IV treatment. Overall, these devices have potential paradigm shifting implications for the treatment of pancreatic, breast, and other solid tumors

Vocational teachers and workplace learning: integrative, complementary and implicit accounts of boundary crossing

Where young people’s upper-secondary education spans work and institutional domains, questions arise about learning across both spheres and its guidance. Theoretical accounts of ‘boundary crossing’ have explored how vocational teachers can integrate learning across domains by drawing on extended concepts and theoretical knowledge to solve workplace problems; whilst empirical accounts have validated the role of vocational educators by describing the workplace and schools as equally valid, complementary spheres. Different understandings, described here as ‘integrative’, ‘complementary’ and ‘implicit’, appear to reflect different national patterns of vocational education. The paper reports a qualitative study conducted around two case studies, located in Germany and England, of the way vocational teachers’ understandings of facilitating learning across domains are constructed. Vocational teachers working in Germany’s ‘dual training’ claimed to provide advanced knowledge that they compared to practical work skills, reflecting ‘implicit’ or ‘complementary’ approaches to learning across domains. Teachers in England, where workplace learning elements are more unevenly developed and lack institutional foundations, nevertheless described colleges and workplaces as distinctive, little-connected spheres. These differences suggest that teachers’ approaches are less shaped by the potential or necessity for ‘integrative’ approaches than by the way different systems enable or constrain their conceptualisation of ‘possible futures’.N/

Incremental grouping of image elements in vision

One important task for the visual system is to group image elements that belong to an object and to segregate them from other objects and the background. We here present an incremental grouping theory (IGT) that addresses the role of object-based attention in perceptual grouping at a psychological level and, at the same time, outlines the mechanisms for grouping at the neurophysiological level. The IGT proposes that there are two processes for perceptual grouping. The first process is base grouping and relies on neurons that are tuned to feature conjunctions. Base grouping is fast and occurs in parallel across the visual scene, but not all possible feature conjunctions can be coded as base groupings. If there are no neurons tuned to the relevant feature conjunctions, a second process called incremental grouping comes into play. Incremental grouping is a time-consuming and capacity-limited process that requires the gradual spread of enhanced neuronal activity across the representation of an object in the visual cortex. The spread of enhanced neuronal activity corresponds to the labeling of image elements with object-based attention

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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