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Development of orientation maps in ferret and cat primary visual cortex (V1) has been shown to be stable, in that the earliest measurable maps are similar in form to the eventual adult map, robust, in that similar maps develop in both dark rearing and in a variety of normal visual environments, and yet adaptive, in that the final map pattern reflects the statistics of the specific visual environment. How can these three properties be reconciled? Using mechanistic models of the development of neural connectivity in V1, we show for the first time that realistic stable, robust, and adaptive map development can be achieved by including two low-level mechanisms originally motivated from single-neuron results. Specifically, contrast-gain control in the retinal ganglion cells and the lateral geniculate nucleus reduces variation in the presynaptic drive due to differences in input patterns, while homeostatic plasticity of V1 neuron excitability reduces the postsynaptic variability in firing rates. Together these two mechanisms, thought to be applicable across sensory systems in general, lead to biological maps that develop stably and robustly, yet adapt to the visual environment. The modeling results suggest that topographic map stability is a natural outcome of low-level processes of adaptation and normalization. The resulting model is more realistic, simpler, and far more robust, and is thus a good starting point for future studies of cortical map development.

Based on measuring responses to rat whiskers as they are mechanically stimulated, one recent study suggests that barrel-related areas in layer 2/3 rat primary somatosensory cortex (S1) contain a pinwheel map of whisker motion directions. Because this map is reminiscent of topographic organization for visual direction in primary visual cortex (V1) of higher mammals, we asked whether the S1 pinwheels could be explained by an input-driven developmental process as is often suggested for V1. We developed a computational model to capture how whisker stimuli are conveyed to supragranular S1, and simulate lateral cortical interactions using an established self-organizing algorithm. Inputs to the model each represent the deflection of a subset of 25 whiskers as they are contacted by a moving stimulus object. The subset of deflected whiskers corresponds with the shape of the stimulus, and the deflection direction corresponds with the movement direction of the stimulus. If these two features of the inputs are correlated during the training of the model, a somatotopically aligned map of direction emerges for each whisker in S1. Predictions of the model that are immediately testable include (1) that somatotopic pinwheel maps of whisker direction exist in adult layer 2/3 barrel cortex for every large whisker on the rat's face, even peripheral whiskers; and (2) in the adult, neurons with similar directional tuning are interconnected by a network of horizontal connections, spanning distances of many whisker representations. We also propose specific experiments for testing the predictions of the model by manipulating patterns of whisker inputs experienced during early development. The results suggest that similar intracortical mechanisms guide the development of primate V1 and rat S1.

Purpose: To investigate the association of single-nucleotide polymorphisms (SNPs) in the manganese superoxide dismutase (MnSOD) and two chemokine genes (CCL2 and CCL5) in patients with anterior uveitis (AU)., Methods: Seventy-nine Chinese patients with acute AU were recruited, and genotyping of four SNPs including MnSOD 47, CCL2 -2518, CCL2 -2076, and CCL5 -403 alleles was performed with SNP genotyping assays. The genotype and allele frequencies were compared between patients with AU and 206 healthy control subjects. Analyses were also stratified according to the HLA-B27 status of the patients., Results: There were significant increases in the frequency of the AA homozygosity in the MnSOD 47 SNP (P = 0.049) and in the CCL2 -2518G allele frequency and GG homozygosity in patients with AU compared with control subjects (P = 0.017 and P = 0.024, respectively). No significant association was found between AU with the CCL2 -2076 and CCL5 -403 SNPs. Subgroup analyses showed that the MnSOD 47A polymorphism was significantly associated with AU in HLA-B27-positive patients, but not in HLA-B27-negative patients, whereas the CCL2 -2518G polymorphism was significantly associated with AU in HLA-B27-negative patients, but not in HLA-B27-positive patients., Conclusions: The 47A polymorphism in the MnSOD gene and the -2518G polymorphism in the CCL2 gene are associated with the development of AU in HLA-B27-positive and -negative Chinese patients, respectively. Further studies to evaluate the interactions of the HLA-B27 status and these SNPs are warranted.

Microsporidia have been known for some time to possess among the smallest genomes of any eukaryote. There is now a completely sequenced microsporidian genome, as well as several other large-scale sequencing efforts, so the nature of these genomes is becoming apparent. This paper reviews some of the characteristics of microsporidian genomes in general, and some of the recent discoveries made through comparative genomic analyses. In general, microsporidian genomes are both reduced and compacted. Reduction takes place through gene loss, which is understandable in obligate intracellular parasites that rely on their host for many metabolites. Compaction is a more complex process, and is as yet not fully understood. It is clear from genomes surveyed thus far that the remaining genes are tightly packed and that there is little non-coding sequence, resulting in some extraordinary arrangements, including overlapping genes. Compaction also seems to affect certain aspects of genome evolution, like the frequency of rearrangements. The force behind this compaction is not known, and is especially interesting in light of the fact that surveys of genomes that are significantly different in size yield similar complements of protein-coding genes. There are some interesting exceptions, including catalase, photolyase and some mitochondrial proteins, but the rarity of these raises an interesting question as to what accounts for the significant differences seen in the genome sizes among microsporidia.

Background: Laboratory studies have consistently found that competition induces performance goals and affects learning motivation. However, the ecological validity of these results is yet to be established. There is a need for investigation of whether the results hold in both the classroom context and non-Western culture., Aim: The study investigated the effects of competition on learning motivation among Chinese students in an authentic classroom setting., Sample: The participants were 52 students of grade 7 from two Hong Kong secondary schools., Method: They were randomly assigned to either competitive or non-competitive conditions in a 2-hour Chinese typewriting course., Results: Students in the competitive condition performed better in easy tasks than their counterparts in the non-competitive condition. However, they were more performance-oriented and more likely to sacrifice learning opportunities for better performance. They were also prone to have worse self-evaluation after failure. Although there were no statistically significant differences between the two conditions in task enjoyment and achievement attribution, the direction of the differences was consistently unfavourable to students in the competitive condition., Conclusion: The findings were consistent with the predictions of goal theory. Competitiveness induces performance goals and worse self-evaluation after failure among Chinese students in a classroom setting, as was found with Western students in a laboratory setting.

Microsporidian genomes are extraordinary among eukaryotes for their extreme reduction: although they are similar in form to other eukaryotic genomes, they are typically smaller than many prokaryotic genomes. At the same time, their rates of sequence evolution are among the highest for eukaryotic organisms. To explore the effects of compaction on nuclear genome evolution, we sequenced 685,000 bp of the Antonospora locustae genome (formerly Nosema locustae) and compared its organization with the recently completed genome of the human parasite Encephalitozoon cuniculi. Despite being very distantly related, the genomes of these two microsporidian species have retained an unexpected degree of synteny: 13% of genes are in the same context, and 30% of the genes were separated by a small number of short rearrangements. Microsporidian genomes are, therefore, paradoxically composed of rapidly evolving sequences harbored within a slowly evolving genome, although these two processes are sometimes considered to be coupled. Microsporidian genomes show that eukaryotic genomes (like genes) do not evolve in a clock-like fashion, and genome stability may result from compaction in addition to a lack of recombination, as has been traditionally thought to occur in bacterial and organelle genomes.

Microsporidia constitute a group of extremely specialized intracellular parasites that infect virtually all animals. They are highly derived, reduced fungi that lack several features typical of other eukaryotes, including canonical mitochondria, flagella, and peroxisomes. Consistent with the absence of peroxisomes in microsporidia, the recently completed genome of the microsporidian Encephalitozoon cuniculi lacks a gene for catalase, the major enzymatic marker for the organelle. We show, however, that the genome of the microsporidian Nosema locustae, in contrast to that of E. cuniculi, encodes a group II large-subunit catalase. Surprisingly, phylogenetic analyses indicate that the N. locustae catalase is not specifically related to fungal homologs, as one would expect, but is instead closely related to proteobacterial sequences. This finding indicates that the N. locustae catalase is derived by lateral gene transfer from a bacterium. The catalase gene is adjacent to a large region of the genome that appears to be far less compact than is typical of microsporidian genomes, a characteristic which may make this region more amenable to the insertion of foreign genes. The N. locustae catalase gene is expressed in spores, and the protein is detectable by Western blotting. This type of catalase is a particularly robust enzyme that has been shown to function in dormant cells, indicating that the N. locustae catalase may play some functional role in the spore. There is no evidence that the N. locustae catalase functions in a cryptic peroxisome.

The effects of chromium (Cr) supplementation on insulin secretion and glucose clearance (KG) during intravenous glucose tolerance tests (IVGTTS) were assessed in rats with impaired glucose tolerance due to dietary Cr deficiency. Male Wistar rats were maintained after weaning on a basal low-Cr diet containing 55% sucrose, 15% lard, 25% casein. American Institute of Nutrition (AIN)-recommended levels of vitamins, no added Cr, and an altered mineral content as required to produce Cr deficiency and impaired glucose tolerance. The Cr-supplemented group ([+Cr] n = 6) were provided with 5 ppm Cr as CrCl3 in the drinking water, and the Cr-deficient group ([-Cr]n = 5) received purified drinking water. At 12 weeks on the diet, both groups of rats were hyperinsulinemic (+Cr, 103 +/- 13; -Cr, 59 +/- 12 microU/mL) and normoglycemic (+Cr, 127 +/- 7; -Cr, 130 +/- 4 mg/dL), indicating insulin resistance. After 24 weeks, insulin levels were normal (+Cr, 19 +/- 5; -Cr, 21 +/- 3 microU/mL) and all rats remained normoglycemic (+Cr, 124 +/- 8; -Cr, 131 +/- 6 mg/dL). KG values during IVGTTS were lower in -Cr rats (KG = 3.58%/min) than in +Cr rats (KG = 5.29%/min), correlating with significantly greater 40-minute glucose areas in the -Cr group (P < .01). Comparisons of 40-minute insulin areas indicated marked insulin hyperresponsiveness in the -Cr group, with insulin-secretory responses increased nearly twofold in -Cr animals (P < .05). Chromium deficiency also led to significant decreases in cyclic adenosine monophosphate (cAMP)-dependent phosphodiesterase (PDE) activity in spleen and testis (P < .01). In these studies, Cr deficiency was characterized by both beta-cell hypersecretion of insulin and tissue insulin resistance that were associated with decreased tissue levels of cAMP PDE activity.

Zinc was measured by flame aspiration atomic absorption spectrophotometry in homogenates and in enriched fractions and subfractions from bovine taste bud membranes and from surrounding control tissues that contained no taste buds. Zinc was found in significantly higher concentrations in tissues containing taste buds and increased in concentration as biochemical and electron microscopic purity increased. The role of zinc in taste bud membranes could relate to its role in membrane stabilization or to its activity in alkaline phosphatase, a zinc-dependent enzyme whose specific activity increased in taste bud membranes in the same manner as did zinc concentration.

Vinblastine selectively inhibits the activation of brain cyclic AMP phosphodiesterase activity by Ca++-protein activator (50% inhibition by 2 x 10(-5) M). This inhibitory effect was reversed by excessive amounts of the activator, whereas large quantities of Ca++ caused only a slight suppression of the vinblastine effect. This result of vinblastine suggests a new site of its action and also suggests the possible role of protein activator, phosphodiesterase proteins or cyclic nucleotides in the previously known effects of vinblastine in vivo and in vitro.

We describe seven women with asthma induced by occupational exposure to an acid anhydride, tetrachlorophthalic anhydride (TCPA), an epoxy resin hardening agent. Inhalation tests with TCPA at atmospheric concentrations of less than one tenth of a manufacturer's recommended exposure limit provoked asthmatic reactions in the four women tested. None had evidence of pretest bronchial hyperreactivity. Immediate skin prick test reactions were elicited in the seven subjects by a conjugate of TCPA with human serum albumin (TCPA-HSA) but not in others tested. Specific IgE antibody levels to TCPA-HSA, measured by radioallergosorbent test scores, were significantly elevated in the seven, but not in TCPA-exposed and unexposed comparison groups. These results imply that occupational asthma caused by TCPA is an allergic reaction mediated by specific IgE antibody.

Human salivary gustin stimulated activity of brain calmodulin-dependent cyclic nucleotide phosphodiesterase (cAMP PDEase; 3',5'-cyclic-nucleotide phosphodiesterase, EC 3.1.4.17) in a dose-dependent manner in the absence of calmodulin. At physiological levels found in human saliva, gustin activated cAMP PDEase 5- to 6-fold. Activation of PDEase occurred with as little as 500 ng of gustin. Comparative sensitivity of activation of PDEase by gustin was intermediate between calmodulin and lysophosphatidylcholine with maximal activation and half-maximal activation (indicated in parentheses) at 3 X 10(-8) M (4.3 X 10(-9) M), 3.4 X 10(-6) M (3.4 X 10(-7) M), and 2.5 X 10(-3) M (4.0 X 10(-5) M) for calmodulin, gustin, and lysophosphatidylcholine, respectively. No other major salivary protein activated PDEase. Anticalmodulin antibody completely inhibited calmodulin-activated cAMP PDEase activity, but the antibody had no effect on gustin-activated cAMP PDEase activity. A sensitive calmodulin RIA indicated that no calmodulin was detected in any gustin preparation that activated cAMP PDEase. Both gustin and calmodulin rendered cAMP PDEase thermally labile to a similar extent and increased Vmax without affecting the apparent Km for the substrate cAMP. Activation by gustin and calmodulin was unaffected by lubrol-PX, trypsin inhibitor, pepstatin A, or leupeptin. In the presence of 1 mM EGTA, gustin activated cAMP PDE 5- to 6-fold, but the activating ability was completely lost after gustin was heated at 100 degrees C for 5 min. In contrast, calmodulin lost all activating ability in the presence of 1 mM EGTA, whereas heating calmodulin at 100 degrees C for 5 min did not affect its activation of cAMP PDEase. Lysophosphatidylcholine-activation of cAMP PDEase, like gustin activation, was unaffected by EGTA, but lysophosphatidylcholine-activation of cAMP PDEase, like calmodulin activation, was unaffected by heating at 100 degrees C for 5 min.

Two groups of male Sprague-Dawley rats, one fed zinc-deficient diet, ad libitum, the other, pair-fed with the same diet, but given supplemental zinc in the drinking water (8 mg Zn++/ml) were studied. After ten weeks of diet, rats were exsanguinated and zinc and calmodulin concentrations in brain and testis were measured. Mean zinc concentration in testis was significantly decreased in rats fed zinc-deficient diet without supplemental Zn++, but mean zinc concentration in brain was not different. Similarly, mean calmodulin concentration in testis was decreased in rats fed zinc-deficient diet without supplemental Zn++ whereas mean calmodulin concentration in brain was not different. Distribution studies of zinc and calmodulin showed that both zinc and calmodulin were released more freely into soluble fractions of testis in rats fed zinc-deficient diet without supplemental Zn++. These results indicate, for the first time in in vivo studies, that zinc influences the calmodulin content of testis.

Calmodulin is higher in particulate fractions from bovine taste buds containing taste bud membranes which specifically bind sweet tastants compared to corresponding fractions from control non-taste bud bearing lingual epithelial tissue. As biochemical purity (i.e., membrane enzyme marker activity) of these membrane enriched fractions increased (P4B greater than P3B greater than P2B) calmodulin correspondingly increased (P4B greater than P3B greater than P2B); these increases also correlated with increased membrane purity as demonstrated by electron microscopy. All PB subfractions from taste buds contained a greater membrane concentration than those from PD subfractions and calmodulin was significantly increased in each corresponding subfraction. The presence of calmodulin in taste bud membranes, its correlation with membrane purification and reports that numerous drugs which induce taste loss are potent inhibitors of calmodulin suggest a role for calmodulin in taste function.

Plasma-membrane-enriched fractions of canine aortic smooth muscle possess an ATP-supported Ca2+ accumulation which has an absolute requirement for Mg2+ and a high affinity for Ca2+ (Km approximately 0.5 microM). The rate of ATP-supported Ca2+ transport is not affected by several calmodulin antagonists, but is stimulated by exogenously added calmodulin. The maximal effect of calmodulin on the rate of ATP-dependent Ca2+ transport (at 5.0 microM Ca2+) occurs at 10 micrograms/ml calmodulin and represents an approximately 3-fold stimulation. This calmodulin stimulation of Ca2+ transport does not require pretreatment of the membranes by EGTA and is an intrinsic property of the plasma membranes. A high-affinity Ca2+-ATPase (Km for Ca2+ approximately 0.5 microM) is also present in the aortic smooth muscle plasma membrane. This high-affinity Ca2+-ATPase does not require Mg2+ for catalytic activity, but is in fact inhibited by increasing Mg2+ concentrations. Calmodulin at concentrations effective for the stimulation of the ATP-dependent Ca2+ transport has no effect on the high-affinity Ca2+-ATPase activity or on the basal ATPase activity stimulated by 5 mM Mg2+ or Ca2+. Our results indicate that isolated plasma membranes of canine aortic smooth muscle contain no endogenous calmodulin. The ability of exogenously added calmodulin to stimulate the rate of ATP-dependent Ca2+ transport by vascular smooth muscle plasma membranes suggests that calmodulin may play a role in lowering the cytoplasmic concentration of ionized calcium during vasodilatation. An Mg2+-independent, but not an Mg2+-dependent high-affinity Ca2+-ATPase, was identified in the plasma membranes. This may be separate from the plasmalemmal Ca2+-pump.

Parotid saliva calmodulin was found both in 32 normal volunteers and in 60 patients with taste and smell dysfunction; salivary calmodulin concentration was significantly lower in the patients than in the volunteers. There were no differences in salivary calmodulin concentration with respect to age, sex, or salivary flow rate in either normal volunteers or patients. When patients were categorized by diagnosis, calmodulin concentration was found to be decreased in all patient groups. The concentration of calmodulin in saliva was about 10 times that found in serum, suggesting that the parotid gland is a major source of this protein.

Higher activity of cyclic adenosine 3',5'-monophosphate (cAMP) phosphodiesterase (PDE) was found in homogenates from bovine circumvellate papillae bearing taste buds compared to activity in homogenates from areas surrounding these papillae in which no taste buds were present. With progressive purification of these homogenates cAMP PDE activity increased in the taste bud enriched fractions relative to that measured in the non-taste bud bearing epithelial tissue. The highest levels of cAMP PDE activity were measured in those taste bud fractions in which purification was greatest. Kinetic studies in both taste bud derived and control tissues showed two apparent Km values, one relatively high, the other, lower. cAMP PDE activity of taste bud membranes was enhanced by Mg++, Mn++ and imidazole and inhibited by ethylene-bis (beta-aminoethylether) N,N-tetra-acetic acid (EGTA), isobutyl methyl xanthine (IBMX), theophylline, and cyclic guanosine 3',5'-monophosphate (cGMP). The possible role for cAMP PDE in taste function is discussed.

Thyroid hormone inhibited purified taste bud membrane adenosine 3'5'-monophosphate (cAMP) phosphodiesterase (PDE) activity in a dose-dependent manner. Taste bud membrane cAMP PDE was inhibited most effectively by thyroxine (T4) followed in order by triiodothyionine (T3), diiodotyrosine (DIT) and monoiodotyrosine (MIT). Concentrations required for 50% inhibition (IC50) of enzyme activity were about 1 x 10(-6), 1 x 10(-5), 6 x 10(-4) M and greater than 1 x 10(-3) M for T4, T3, DIT and MIT, respectively. Addition of zinc at physiological concentrations found in serum greatly augmented the inhibitory effects of T4 and T3 at lower concentrations (10(-7) and 10(-6) M, respectively) resulting in further inhibition of cAMP PDE by 40-50%. Inhibition of cAMP PDE by T4 appears to be relatively tissue selective as indicated by the IC50 of 1 x 10(-6) M for the taste bud but only 7 x 10(-6) M, 3 x 10(-5) M, and 4 x 10(-5) M, for heart, kidney and brain cAMP PDE, respectively. Inhibition of taste bud membrane cAMP PDE by T4 was competitive with substrate cAMP with a Ki of 4 microM. These results suggest that inhibition of cAMP PDE, which increases taste bud membrane intracellular cAMP, may participate in the action of thyroid hormone in the taste process.

The effect of zinc deficiency on calmodulin function was investigated by assessing the in vivo activity of two calmodulin regulated enzymes, adenosine 3',5'-monophosphate (c-AMP) and guanosine 3',5'-monophosphate (c-GMP) phosphodiesterase (PDE) in several rat tissues. Enzymatic activities in brain, heart, and testis of rats fed a zinc deficient diet were compared with activities in these tissues from pair fed, zinc supplemented rats. In testis, a tissue in which zinc concentration decreased with zinc deficient diet, enzyme activities were significantly decreased over those in rats who were pair fed zinc supplemented diets. In brain and heart, tissues in which zinc concentrations did not change with either diet, enzymatic activities between the groups were not different. These results indicate that zinc deficiency influences the activity of calmodulin-regulated phosphodiesterases in vivo supporting the hypothesis that zinc plays a role in calmodulin function in vivo in zinc sensitive tissues.

Two fractions from bovine taste buds, the soluble S4 fraction and the membrane P4B fraction, were used to evaluate the effects of divalent metal ions on cyclic adenosine 3', 5' monophosphate (cAMP) phosphodiesterase (PDE) activity. Zn++, Ni++, Cu++, Fe++, Sn++ and Hg++, in the presence of 5mM Mg++, inhibited cAMP PDE activity whereas these divalent metal ions alone did not affect enzyme activity if Mg++ were absent. Zn++ inhibited cAMP PDE activity in S4 and P4B taste bud fractions with Ki values of 100 microM and 90 microM, respectively; this inhibition was noncompetitive with substrate activity but competitive with Mg++. In the presence of Mg++, Zn++ inhibited taste bud cAMP PDE more effectively than any other metal ion studied. Inhibition of taste bud cAMP PDE by divalent metal ions, particularly Zn++, suggests a role for these substances in the taste process through regulation of intracellular concentration of taste bud cAMP.