Levels Of MT Research Articles

Heat indicators of oxidative stress, inflammation and metal transport show dependence of cadmium pollution history in the liver of female zebrafish

Environmental stressors such as high temperature and metal exposure may occur sequentially, simultaneously, previously in aquatic ecosystems. However, information about whether responses to high temperature depend on Cd exposure history is still unknown in fish. Zebrafish were exposed to 0 (group 1), 2.5 (group 2) and 5μg/L (group 3) cadmium (Cd) for 10 weeks, and then each group was subjected to Cd-free water maintained at 26°C and 32°C for 7days respectively. 26 indicators were used to compare differences between 26°C and 32°C in the liver of female zebrafish, including 5 biochemical indicators (activity of Cu/Zn-SOD, CAT and iNOS; LPO; MT protein), 8 molecular indicators of oxidative stress (mRNA levels of Nrf2, Cu/Zn-SOD, CAT, HSF1, HSF2, HSP70, MTF-1 and MT), 5 molecular indicators of inflammation (mRNA levels of IL-6, IL-1β, TNF-α, iNOS and NF-κB), 8 molecular indicators of metal transport (mRNA levels of, ZnT1, ZnT5, ZIP8, ZIP10, ATP7A, ATP7B and CTR1). All biochemical indicators were unchanged in group 1 and changed in group 2 and 3. Contrarily, differences were observed in almost all of molecular indicators of inflammation and metal transport in group 1, about half in group 2, and few in group 3. We also found that all molecular indicators of oxidative stress in group 2 and fewer in group 1 and 3 were significantly affected by heat. Our data indicated that heat indicators of oxidative stress, inflammation and metal transport showed dependence of previous cadmium exposure in the liver of zebrafish, emphasizing metal pollution history should be carefully considered when evaluating heat stress in fish.

Variations in gene expression levels in four European zebra mussel, Dreissena polymorpha, populations in relation to metal bioaccumulation: A field study

The present study was performed to validate the suitability of using gene expression in zebra mussels, Dreissena polymorpha, for biomonitoring of freshwater environment. Mussels were collected in four French rivers (Meuse, Moselle, Oise and Vilaine) in spring and autumn. Relative gene expression of 9 candidate genes involved in cellular metabolic activities (Cytochrome-c-oxidase – cox, and ATP synthase – atp), detoxification process (Metallothionein – mt and Glutathion-S-Transferase – gst), oxidative stress (Catalase – cat, Superoxyde Dismutase – sod and Glutathion peroxidase – gpx) and digestive functions (Amylase – amy and Cellulase – ghf) were measured in digestive gland. Metal bioaccumulation in tissues and morphometric parameters were also analyzed to interpret molecular responses. All our results are consistent with different physiological reactions to environmental condition between zebra mussel populations. In spring, the levels of mt, sod, gpx, cat, atp, amy and ghf relative expression were significantly higher in mussels with the lowest metal bioaccumulation (the Meuse) compared to at least one of the other sites. In autumn, this higher expression levels in Meuse River were still observed for gpx, cat, atp and amy. This study has also pointed out different sources of variability in gene expression (individual size, season, trophic resources and origin of mussels) which are inevitable in natural fluctuant environment. This underlines the importance to take them into account in field study to propose a correct interpretation of biomarker responses.

Differential effects of polyoma virus middle tumor antigen mutants upon gap junctional, intercellular communication

Gap junctions are channels that connect the cytoplasm of adjacent cells. Oncogenes such as the middle Tumor antigen of polyoma virus (mT) are known to suppress gap junctional, intercellular communication (GJIC). mT associates with and is tyrosine-phosphorylated by cSrc family members. Specific mT phosphotyrosines provide docking sites for the phosphotyrosine binding domain of Shc (mT-tyr250) or the SH2 domain of the regulatory subunit of the phosphatidylinositol-3 kinase (PI3k, mT-tyr315). Binding results in the activation of their downstream signaling cascades, Ras/Raf/Erk and PI3 kinase/Akt, respectively, both of which are needed for full neoplastic transformation.To examine the effect of mT-initiated pathways upon gap junctional communication, GJIC was quantitated in rat liver epithelial T51B cells expressing mT-mutants, using a novel technique of in situ electroporation. The results demonstrate for the first time that, although even low levels of wild-type mT are sufficient to interrupt gap junctional communication, GJIC suppression still requires an intact tyr-250 site, that is activation of the Ras pathway. In sharp contrast, activation of the PI3k pathway is not required for GJIC suppression, indicating that GJIC suppression is independent of full neoplastic conversion and the concomitant morphological changes. Interestingly, expression of a constitutively active, myristylated form of the catalytic subunit of PI3k, p110, or the constitutively active mutants E545K and H1047R increased GJIC, while pharmacological inhibition of PI3k eliminated communication. Therefore, although PI3k is growth promoting and in an activated form it can act as an oncogene, it actually plays a positive role upon gap junctional, intercellular communication.

The antioxidant profiles, lysosomal and membrane enzymes activity in patients with acute pancreatitis.

Oxidative stress and inflammatory mediators, such as IL-6, play an important role in the pathophysiology of acute pancreatitis. The study was aimed to assess the degree of the pro/antioxidative imbalance and estimate which antioxidant plays a role in the maintenance of pro/antioxidative balance during acute pancreatitis. The study was investigated in the blood of 32 patients with acute pancreatitis and 37 healthy subjects. IL-6 concentration as early marker of inflammation was determinated. The intensity of oxidative stress was assessed by TBARS concentration. To investigate antioxidative status, the GPx and Cu/Zn SOD activities and the levels of GSH, MT, SH groups, and TRAP were measured. The concentrations of Cu and Zn as ions participating in the maintenance of antioxidant enzymes stability and playing a role in the course of disease were determinated. The activities of GGT, AAP, NAG, and β-GD as markers of tissue damage were also measured. An increase in IL-6 concentration, which correlated with Ranson criteria, and an increase in GPx activity, levels of MT, TBARS, or GGT, and NAG activities in patients group compared to healthy subjects were demonstrated. A decrease in GSH level in patients group compared to control group was noted. The studies suggest that GPx/GSH and MT play the role of the first line of defence against oxidative stress and pro/antioxidant imbalance in the course of acute pancreatitis.

Metallothionein and Heat-Shock Protein 70 Induction in Caged and Wild Fathead Minnows (Pimephales promelas) Exposed to the Ouachita River, Louisiana

The purpose of this study was to explore the changes in mRNA expression levels for metallothionein subtype 2 (MT-2) and heat-shock protein 70 (HSP70) in fathead minnows in response to environmental exposure in a mercury (Hg)-contaminated freshwater ecosystem. It was hypothesized that expression levels of both genes may rise concurrent with the bioaccumulation of Hg and possibly other heavy metals during exposure to the Ouachita River. The experimental design incorporated three distinct populations of fathead minnows: (1) a negative control population of laboratory-raised fathead minnows unexposed to heavy metals or other contaminants, (2) laboratory-raised fatheads placed in cages and exposed to a contaminated ecosystem for 2 wk, and (3) wild-caught (native) fathead minnows captured at the same site where caged fatheads tested positive for Hg bioaccumulation. Study endpoints included growth rates and gross pathology at necropsy. Total Hg levels of the water at the exposure sites as well as in whole fish homogenates were determined by cold vapor atomic absorption spectroscopy (AAS). AAS was also used to assay levels of lead (Pb) and copper (Cu), though these were below detectable limits. Hepatic expression levels of MT and HSP70 mRNA were determined by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). As hypothesized, levels of both transcripts were significantly increased in the caged exposure group and native fish group compared to unexposed control fish. In addition, the native fish group had significantly higher levels of expression for both genes when compared to caged exposed fish.

Cadmium exposure affects the expression of genes involved in skeletogenesis and stress response in gilthead sea bream larvae

Gilthead sea bream larvae (Sparus aurata) aged 47 days post hatching (dph) (11.6-12.8 mg in wet weight) were exposed to several sublethal concentrations of Cd(2+) (0.1, 5 and 10 mg/L) during 6 days in order to investigate the effects of this heavy metal on the expression of selected genes involved in detoxification (metallothionein-mt, glutathione peroxidase 1-gpx1), stress response (heat shock protein 70-hsp70, tumour necrosis factor α-tnfα) and ossification (osteocalcin-oc) processes. For this purpose, specimens of 47 dph were exposed first for 72 h from 0.1 to 20 mg/L of Cd(2+) in order to evaluate the median lethal concentration (LC(50)) for this metal, which was determined at 15.32 mg/L. Considering the results regarding the relative transcript levels of gpx1 and hsp70, Cd(2+) at any of the tested levels (0.1, 5 and 10 mg/L) did not induce oxidative stress in gilthead sea bream larvae, whereas relative transcript levels of mt were increased at 5 and 10 mg/L of Cd(2+) probably to detoxify this metal excess. Relative transcript levels of tnfα were not level dependent and were down-regulated in larvae exposed to 5 and 10 mg/L of Cd(2+). At those concentrations, transcript levels of oc were down-regulated suggesting a disruption in bone mineralization. Results from this study provided insights in some molecular mechanisms underlying Cd(2+)-induced toxicity in fish at early stages of development. This is the first study to show that cadmium contamination can depress oc expression in teleosts.

Short-term physiological effects of a xenobiotic mixture on the freshwater mussel Elliptio complanata exposed to municipal effluents

The aim of this study was to investigate the short-term effects of tertiary-treated municipal effluents on the freshwater mussel Elliptio complanata. Caged mussels were immersed during 2 weeks in a river located North of Montreal Island, upstream/downstream the outfall and in one reference site located at the beginning of the Rivière des Prairies. A selection of biomarkers was analyzed to depict changes on various physiological systems: general physiology (mussel viability, condition index and gonado-somatic index), immune status (hemocyte viability, cellularity, phagocytosis efficiency, NK-like cytotoxic activity and lysozyme activity), inflammation (cyclo-oxygenase activity), detoxification (glutathione-S-transferases activity) and vitellogenesis (alkali-labile phosphate level). The analysis of total and fecal coliform counts in water and of heterotrophic bacteria levels in mussel tissues showed that the bacteriological quality of the water strongly decreased from the reference site to the downstream site. This was correlated with a significant loss of weight and an increase of mussel mortality. Cellularity and phagocytosis efficiency were significantly increased in the downstream site compared to the reference site. Though not statistically significant, lysozyme activity was also increased. NK-like cytotoxicity, activity of the pro-inflammatory enzyme COX and the levels of ALP and MT were not significantly changed. Conversely, the municipal effluents induced a significant increase of GST activity in downstream site, indicating a stimulation of detoxification metabolism. Altogether, these results confirm that a short-term exposure to a mixture of bacterial and chemical compounds released by the wastewater treatment plant La Pinière induces adverse physiological effects in E. complanata, as observed with the modulation of immune response and induction of detoxification metabolism.

Blocking of melatonin synthesis and MT(1) receptor impairs the activation of Jurkat T cells.

Melatonin has been proposed as regulating the immune system by affecting cytokine production in immunocompetent cells, enhancing the production of several T helper (Th)1 cytokines. To further investigate the melatonin's role in IL-2/IL-2R system, we established an inducible T-REx expression system in Jurkat cells in which the protein levels of HIOMT enzyme or MT(1) receptor were significantly down-regulated upon tetracycline incubation. We found that T-REx Jurkat cells with lower levels of HIOMT activity, and consequently lower content of endogenous melatonin, showed IL-2 production decrease after activation with lectin. Likewise, tetracycline-inducible stable cell line expressing MT(1) antisense produced decreased amounts of IL-2 (mRNA and protein levels) after stimulation. Moreover, in T-Rex-MT(1) cells incubated with tetracycline, a sub-optimal PHA dose failed to induce the early activation marker CD25 on the cell surface. The results shown here support the relevance of endogenous melatonin and its signaling in T cell activation.

Daytime levels of melatonin in patients with age‐related macular degeneration

Melatonin (N-acetyl-5-methoxytryptamine) (MT) is a hormone that acts as an antioxidant. It is produced by the pineal gland and within the retina; its release is blocked by light entering the eye. We examined whether MT daytime levels differ between pseudophakic patients with age-related macular degeneration (ARMD) and pseudophakic subjects without any ocular pathology of the same age. A prospective, cross-sectional, observational study was performed. Pseudophakic patients of the same age group were included. Patients underwent complete ophthalmic examinations and blood sampling between 08:00 and 10:00 hr. MT daytime value in the serum was the main outcome measure. Sixty-nine pseudophakic patients were included. Fifty patients with exudative and non-exudative ARMD were in the study group while 19 patients were controls. Patients with ARMD had significantly higher daytime levels of MT (P = 0.003). There were significant differences in MT daytime levels between the exudative and non-exudative forms (P = 0.009). MT values also correlated with the best-corrected visual acuity (r = -0.285, P = 0.019). These data indicate that pseudophakic patients with ARMD produce more MT during the day compared to pseudophakic subjects without ARMD. This may be caused by the reduced visual acuity in patients with ARMD, whereby less light reaches the photoreceptors, allowing MT secretion to continue during the day. Because MT also acts as an antioxidant and daytime levels are higher in patients with ARMD, these results might be interpreted as a rescue factor.

Effect of Chronic Intoxication with Cadmium on the Level of Metallothionein in the Rat Hippocampus

Long-lasting intoxication with cadmium induced by inhalation of 0.1% CdCl 2 dispersed in air (19 weeks, twice a week, 1-h-long sessions) resulted in differentiated changes in the level of metallothionein I + II (MT I + II) in different structures of the rat brain. A most dramatic (more than fourfold) drop in the content of MT I + II was observed in the hippocampus, while in the cerebral cortex the respective decrease was less than twofold, and the levels of MT I + II did not significantly change in the cerebellum and thalamus/hypothalamus. These data allow us to believe that reduction of MT-dependent defensive mechanisms in the hippocampus is one of the most important neurological consequences of long-lasting cadmium intoxication.

Metallothionein (MT) expression increases in skeletal muscle following tourniquet‐induced ischemia/reperfusion (I/R) injury

Increased MT and extracellular matrix (ECM) metalloprotease (MMP) activity has been documented in skeletal muscle following trauma. MTs bind zinc and MMPs, possibly affecting activation of the zinc‐dependent mTOR pathway and MMP‐dependent tissue repair post‐injury. Tourniquet (TK) application is used to control bleeding post‐injury, although I/R episodes associated with TK use result in skeletal muscle proteolysis. This study investigated TK‐induced I/R injury on MT, MMP, and mTOR pathway activation in rat extensor digitorum longus (EDL). A TK was applied to the hind limb of 14 male rats for 3 h, and then deflated, resulting in I/R injury. EDLs were harvested 2 h post‐reperfusion for analysis. I/R resulted in a significant (p<0.05) upregulation of MT (4.7‐ fold) and MMP‐9 (2.6‐ fold) mRNA, with no change in MMP‐2. Immunoblot analysis revealed that protein levels of MT were increased 24 ± 11.1 % (p<0.05). The mTOR protein level, its phosphorylation on Ser2448, and the activity of S6K1 were unaffected 2 h post‐I/R injury. Immunohistochemistry confirmed results. MT production is likely related to I/R‐induced oxidative‐stress, which potentially affects ECM integrity, explaining our observed increase in MMP‐9. These data suggest that oxidative‐mediated ECM disruption is a potential mechanism for increased skeletal muscle proteolysis in response to TK‐induced I/R‐injury.

Shapes of Differential Pulse Voltammograms and Level of Metallothionein at Different Animal Species.

Metallothioneins play a key role in maintaining homeostasis of essential metalsand in protecting of cells against metal toxicity as well as oxidative damaging. Exceptinghumans, blood levels of metallothionein have not yet been reported from any animalspecies. Blood plasma samples of 9 animal species were analysed by the adsorptive transferstripping technique to obtain species specific voltammograms. Quite distinct records wereobtained from the Takin (Budorcas taxicolor), while other interesting records were observedin samples from the European Bison (Bison bonasus bonasus) and the Red-eared Slider(Trachemys scripta elegans). To quantify metallothionein the catalytic peak Cat2 was used,well developed in the Domestic Fowl (Gallus gallus f. domestica) and showing a very lowsignal in the Red Deer (Cervus elaphus). The highest levels of metallothionein reachingover 20 μM were found in the Domestic Fowl. High levels of MT were also found in theBearded Dragon (Pogona vitticeps) and the Grey Wolf (Canis lupus lupus). The lowestvalues of about 1-3 μM were determined in the Red-eared Slider, Takin and Red Deer. Employing a simple electrochemical detection it was possible to examine variation in blood metallothionein in different species of vertebrates.

Vesicular stomatitis virus infection triggers apoptosis associated with decreased ΔNp63α and increased Bax levels in the immortalized HaCaT keratinocyte cell line

In view of the powerful inherent oncolytic activity exhibited by the vesicular stomatitis virus (VSV) in several tumor types, we set out to investigate the susceptibility of the immortalized HaCaT keratinocyte cell line to VSV, and analyzed the role of apoptosis in the VSV-mediated induction of cell death. Indirect immunofluorescence assays, Western blot analyses and plaque titrations demonstrated that the HaCaT cell line was permissive to VSV replication. The results of ELISA for detection of the enrichment of nucleosomes in the cytoplasm of apoptotic cells revealed that VSV infection elicits the apoptotic death of HaCaT cells. Mock-infected HaCaT cells displayed the endogenous expression of ΔNp63α, p53 mutated on UV hot spots (p53 mt), Bcl-2 and p21 Bax. The levels of ΔNp63α and p53 mt were decreased, Bcl-2 remained unaffected, while the expressions of p21Bax and p18 Bax were increased in VSV-infected HaCaT cells. Together, these data demonstrate that VSV replicates efficiently and triggers apoptosis in the immortalized HaCaT keratinocyte cell line. The VSV-mediated alterations in the expressions of ΔNp63α and Bax may be implicated in the apoptotic responses of infected cells and may also sensitize to other apoptotic stimuli. These findings may stimulate further studies with the goal of developing VSV-based virotherapy into an effective modality for the treatment of epithelial-derived malignant tumors of the skin.

Human melatonin MT 1 receptor induction by valproic acid and its effects in combination with melatonin on MCF-7 breast cancer cell proliferation

We have reported that valproic acid upregulates melatonin MT 1 receptor expression in rat C6 glioma cells. In addition to its anticonvulsant and mood stabilizing properties, valproic acid can also inhibit the growth of cancer cells. Since the melatonin MT 1 receptor has been implicated in the oncostatic action of melatonin on human MCF-7 breast cancer cells, the effect of valproic acid on its expression was examined in this cell line. Treatment of MCF-7 cells with valproic acid (0.5 or 1 mM) for 24 or 72 h caused a significant increase in melatonin MT 1 receptor mRNA or protein expression, as shown by reverse transcription-polymerase chain reaction (RT-PCR) analysis and western blotting, respectively. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays revealed a concentration-dependent inhibition of MCF-7 cell proliferation by valproic acid (0.5, 1.0 or 5 mM), but melatonin (1 or 10 nM) was ineffective alone or in combination with valproic acid, in the first (MCF-7A) subline examined. However, in subsequent experiments using a different (MCF-7B) subline, which expressed higher levels of MT 1 receptor mRNA and showed modest sensitivity to melatonin, a combination of this hormone with valproic acid produced a significant synergistic inhibition of cell proliferation. These findings indicate that clinically relevant concentrations of valproic acid upregulate melatonin MT 1 receptor expression in human breast cancer cells. Moreover, the enhanced antiproliferative effect observed with a combination of valproic acid and melatonin suggests that a similar therapeutic approach may be beneficial in breast cancer.

Relative Suppression of Magical Thinking: A Transcranial Magnetic Stimulation Study

The tendency to perceive meaning in noise (apophenia) has been linked to “magical thinking” (MT), a distinctive form of thinking associated with a range of normal cognitive styles, anomalous perceptual experiences and frank psychosis. Important aspects of MT include the propensity to imbue meaning or causality to events that might otherwise be considered coincidental. Structures in the lateral temporal lobes have been hypothesised to be involved in both the clinical and non- clinical aspects of MT. Accordingly, in this study we used single-pulse transcranial magnetic stimulation (TMS) to stimulate either the left or right lateral temporal areas, or the vertex, of 12 healthy participants (balanced for similar levels of MT, delusional ideation and temporal lobe disturbance) while they were required to indicate if they had “detected” pictures, claimed to be present by the experimenters, in visual noise. Relative to the vertex, TMS inhibition of the left lateral temporal area produced significant reduced tendency to report meaningful information, suggesting that left lateral temporal activation may be more important in MT and therefore producing and supporting anomalous beliefs and experiences. The effect cannot simply be explained by TMS induced cognitive slowing as reaction times were not affected.

Metallothionein and hsp70 expression in HepG2 cells after prolonged cadmium exposure

Cadmium is a widely distributed industrial and environmental pollutant. Principle target organs are soft tissues such as the liver, where cadmium accumulates with a biological half-life of approximately 20–30 years causing a variety of toxic responses. In HepG2, CdCl 2 exposure for short periods (from 1 to 24 h) induces differential expression of stress proteins, including MT and hsp70. However, less is known about the stress response during a prolonged exposure to this metal. MTT assay showed a low cytotoxicity of CdCl 2 (0.1, 0.5, 1, 2, 5, 10 μM), over a period of 72 h. Cadmium uptake by ICP–AES technique and the corresponding expression of stress proteins (MT, hsp70) during the same prolonged time were also analysed. Results show that Cd was continuously and increasingly accumulated, at the highest of the concentrations tested. Metallothionein expression was up-regulated with a saturation curve at 48 as well as 72 h after CdCl 2 exposure. High levels of MT probably confer an acquired tolerance to the stress and protection against cell injury as demonstrated by low cytotoxicity values. On the contrary, the unchanged pattern of hsp70 expression suggests that this protective mechanism, unlike other members of the family, is less involved during CdCl 2 prolonged exposure.

Induction and activity of oxidative stress-related proteins during waterborne Cu-exposure in brown trout ( Salmo trutta)

Induction of gene transcription for proteins and enzymes involved in metal-mediated oxidative stress were studied in brown trout transferred to a Cu-contaminated river in the Røros region in Central Norway. In addition to metallothionein (MT-A), Cu/Zn-superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) gene transcription, protein levels of MT and enzyme activities of SOD and CAT were analyzed in gill, liver and kidney. MT-A, SOD and GR transcription increased significantly along with uptake of Cu in gills, while only transcription of MT-A was found to respond in liver and kidney during the exposure. Already present MT proteins in gills seemed to be oxidized during the exposure, probably caused by Cu-mediated oxidative stress, and no increase in MT protein levels were observed in gills. SOD and CAT enzyme levels were affected in all tissues during the exposure. A negative correlation between SOD and CAT activities was observed in gills, and we suggest that the activities of these enzymes were influenced not only through transcription. GPx and GR transcription levels correlated positively with each other in gills and liver, indicating their shared function in GSH-turnover. Levels of MT and activity of SOD and CAT dealing with metal-induced oxidative stress appear to be regulated not only through gene transcription, but also through post-translational mechanisms.

Effect of Hypothyroidism on Intestinal Zinc Absorption and Renal Zinc Disposal in Five-Sixths Nephrectomized Rats

Both hypothyroid (Hypo) and hypozincemia are commonly observed in patients and animals with chronic renal failure (CRF). In CRF whether the hypothyroid plays a role in the pathogenesis of hypozincemia is unclear. This study is designed to investigate the effects of hypothyroid on intestinal zinc absorption and urinary zinc excretion in 5/6 nephrectomized (Nx) rats, because plasma zinc balance is attained through a controlled rate of intestinal uptake as well as renal reabsorption. Intestinal zinc absorption was carried out in jejunum and ileum segments by an in vivo perfusion technique and the renal zinc disposal was evaluated by a conventional method using a standard formula to calculate the zinc tubular reabsorption and the excretion of urinary zinc in 5/6 Nx rats with hypothyroidism. The Hypo-NxT rats showed a significant decrease in the rate of intestinal zinc absorption and in the response of plasma zinc levels during intestinal zinc perfusion compared with Eu-NxT rats. They also had significantly lower levels of mucosal zinc and MT as well as lower content of liver zinc than Eu-NxT rats after intestinal zinc perfusion for 80 min. Hypo-NxT rats showed low plasma zinc levels, but had a similar output of pancreaticobiliary zinc and excretion of 24-h urine zinc compared with the Eu-NxT rats. When 2% alcohol intestinal perfusion was used to produce water diuresis, the Hypo-NxT rats presented a higher excretion of urinary zinc than the Eu-NxT rats did, especially during 2% alcohol intestinal zinc perfusion. In the Hypo-NxT rats, the lower plasma zinc levels may thus result from the hypothyroid because it reduces intestinal zinc absorption. Increasing the urine flow rate may aggravate the reduction of plasma zinc level in Hypo-NxT rats because of the increased excretion of urinary zinc.

Metallothionein in Bovine Spongiform Encephalopathy

An increase in metallothionein I and II (MT I/II) mRNA concentrations has been reported in the central nervous system of scrapie-infected rodents. In this study we compared cattle with bovine spongiform encephalopathy (BSE), cattle affected by neurological disease other than BSE, and clinically healthy cattle in respect of MT I/II immunoreactivity in brainstem medullary tissue. Marked astrocytic MT I/II immunolabelling was seen in all BSE-affected animals, in contrast to clinically healthy cases, in which no such labelling was detected. In BSE, MT I/II immunoreactive astrocytes were confined specifically to areas of vacuolation or abnormal prion protein (PrPBSE) deposition, or both. MT I/II immunolabelling was also seen in a small number of animals with a neurological disease other than BSE. These findings complement previous studies by demonstrating increased levels of MT I/II in transmissible spongiform encephalopathy (TSE)-infected brain tissue, indicating that MT I/II may play some as yet unidentified role in the response to TSE infection.

Neuronal Basis of the Motion Aftereffect Reconsidered

Several fMRI studies have reported MT+ response increases correlated with perception of the motion aftereffect (MAE). However, attention can strongly affect MT+ responses, and subjects may naturally attend more to the MAE than control trials without MAE. We found that requiring subjects to attend to motion on both MAE and control trials produced equal levels of MT+ response, suggesting that attention may have confounded the interpretation of previous experiments; in our data, attention accounts for the entire effect. After eliminating this confound, we observed that direction-selective motion adaptation produced a direction-selective imbalance in MT+ responses (and earlier visual areas), and yielded a corresponding asymmetry in speed discrimination thresholds. These findings provide physiological evidence that population level response imbalances underlie the MAE, and quantify the relative proportions of direction-selective neurons across human visual areas.