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PubMed1988

Effects of chronic toluene exposure on central monoamine and peptide receptors and their interactions in the adult male rat.

The effects of chronic toluene exposure (CTE) (80 ppm, 6 h/day, 5 days/week, 3 months) were studied on neuropeptide and 5-hydroxytryptamine receptors, on protein phosphorylation levels and on catecholamine levels in various brain regions in the 15-month-old male rat. Behavioral parameters and serum levels of hypophyseal hormones and corticosterone were also analyzed. CTE selectively reduced [3H]neurotensin [( 3H]NT) binding in the basal layers of the orbital cortex. Instead, CTE increased the binding of [3H]etorphine in the nucleus accumbens and of [125I]vasoactive intestinal polypeptide [( 125I]VIP) in the area postrema and hypoglossal nucleus. Acute treatment with the irreversible monoamine receptor antagonist N-ethoxycarboxyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) increased the binding of [3H]NT in the orbital cortex in toluene exposed rats as compared with the reduced [3H]NT binding obtained in air exposed rats treated with EEDQ. Furthermore, the EEDQ induced increase in [125I]VIP binding in the area postrema and the hypoglossal nucleus was replaced by a reduced binding of [125I]VIP in EEDQ-treated CTE rats. CTE produced an overall increase in calcium-induced back phosphorylation and an overall decrease in cyclic adenosine monophosphate-induced back phosphorylation in the frontoparietal cortex. Noradrenaline stores tended to be reduced within various hypothalamic subnuclei and the serum prolactin levels were increased following CTE. However, no marked effects of CTE were seen on the behavioral parameters. In conclusion, the regional selectivity of CTE in disturbing [3H]NT and [125I]VIP binding may be due to the demonstrated vulnerability of monoamine-neuropeptide interactions to toluene.

Animals↗
PubMed1997

The simian retrovirus-1 constitutive transport element, unlike the HIV-1 RRE, uses factors required for cellular mRNA export.

BACKGROUND: A hallmark of retroviral gene expression is that unspliced retroviral genomic RNA is exported to the cytoplasm, whereas endogenous intron-containing cellular RNAs are usually retained in the nucleus. In complex retroviruses, such as human immunodeficiency virus-1 (HIV-1), nuclear export is accomplished by the interaction of a virally encoded protein, Rev, with a cis-acting RNA element, the Rev-responsive element (RRE). In type D retroviruses, such as the simian retrovirus type 1 (SRV-1), however, genomic RNA is exported by cellular factor(s) that interact with a conserved cis-acting RNA element, the constitutive transport element (CTE). RESULTS: We found that the CTE was exported in a specific and saturable fashion from Xenopus oocyte nuclei. When inserted into the intron of an adenovirus-derived pre-mRNA, the CTE did not affect splicing efficiency but promoted the nuclear export of the excised intron lariat that is normally retained within the nucleus. Export of CTE-containing RNAs to the cytoplasm was not affected by the heterogeneous nuclear ribonucleoprotein A1 or an excess of peptides corresponding to the Rev nuclear export signal. Microinjection of saturating amounts of CTE RNA did not affect tRNA export or Rev-mediated export but did inhibit mRNA export. CTE-mediated export was found to be dependent on Ran-mediated GTP hydrolysis. CONCLUSION: The Rev-RRE system and the CTE direct intron-containing RNAs to distinct export pathways. Although previous data have suggested that Rev uses the same export pathway as uracil-rich small nuclear RNAs and 5S ribosomal RNA, the CTE seems to interact with evolutionarily conserved factors that are essential for cellular mRNA export.

Animals↗
PubMed2000

Multiple copies of the Mason-Pfizer monkey virus constitutive RNA transport element lead to enhanced HIV-1 Gag expression in a context-dependent manner.

Retroviral gene expression requires nuclear export and translation of incompletely spliced RNA. In the case of human immunodeficiency virus (HIV), this is facilitated by the viral Rev protein binding to its cognate RNA response element (RRE), while other retroviruses contain constitutive transport elements (CTE) binding to cellular factors. These CTE can substitute for the HIV-1 Rev/RRE system, albeit with reduced efficiency. Here, we show that multimeric copies of the CTE restore HIV-1 protein expression to levels comparable to or higher than Rev/RRE in various cell lines from different species. We suggest that multimerization of export factors is important for CTE function, as reported for Rev. CTE function was not affected when the element was displaced from its natural position close to the poly(A) signal, while insertion of an intron into the 3'-untranslated region (3'-UTR) severely reduced CTE activity. In this case, cytoplasmic RNA degradation was observed, which may be mediated by nonsense-mediated RNA decay. In contrast, Rev-dependent gene expression was insensitive to an intron in the 3'-UTR. Finally, we show that the putative CTE-binding protein RNA helicase A is not specifically translocated into the cytoplasm upon overexpression of CTE-containing RNA.

3' Untranslated Regions↗
PubMed2001

Using viral species specificity to define a critical protein/RNA interaction surface.

The Tap protein mediates the sequence-specific nuclear export of mRNAs bearing the retroviral constitutive transport element (CTE) and also plays a critical role in the sequence nonspecific export of cellular mRNAs. Previously, we have demonstrated that CTE function displays species specificity, that is, the CTE functions in human but not quail cells. Here, we demonstrate that quail Tap fails to support CTE function because it cannot bind the CTE. However, changing a single residue in quail Tap, glutamine 246, to arginine, the residue found in human Tap, rescues both CTE function and CTE binding. This residue, which is located on the exterior of a recently reported molecular structure of Tap, defines a surface on Tap that is critical for CTE binding. These data emphasize the potential importance of cross-species genetic complementation in the identification and characterization of cellular factors that are critical for different aspects of viral replication.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1988

Effect of hormones on growth and function of cultured canine tracheal epithelial cells.

Insulin (INS), endothelial cell growth supplement (ECGS), transferrin (TF), cholera toxin (CT), hydrocortisone (HC), triiodothyronine (T3), and epidermal growth factor (EGF) were systematically examined for their effects on proliferation, ion transport activity, and morphological differentiation of canine tracheal epithelial (CTE) cells in culture. INS, ECGS, TF, and CT increase proliferation of CTE cells cultured on plastic Petri dishes but exhibit no acute effect on the bioelectric activity of freshly excised CTE. CT increases amiloride-insensitive transepithelial ion transport across both freshly excised canine trachea and CTE cultures. EGF has no effect on proliferation of CTE cells on plastic but induces hyperplasia of CTE cells on collagen matrices. EGF does not alter basal transepithelial ion transport across cultures but increases cellular responsiveness to beta-adrenergic stimulation. HC and T3 have no effect on proliferation or transepithelial bioelectric properties of CTE cells but improve morphological differentiation yielding cultures of complex epithelia containing cuboidal ciliated and nonciliated cells. These results demonstrate that growth and function of cultured CTE cells are affected by specific growth factors.

Amiloride↗
PubMed1996

Glutathione S-transferase M1 null genotype as a risk modifier for solvent-induced chronic toxic encephalopathy.

OBJECTIVES: Exposure to organic solvents increases the risk of neuropsychiatric disability or chronic toxic encephalopathy (CTE). Polymorphisms in the biotransformation of xenobiotics and solvents may influence individual susceptibility to develop toxic effects. In this study the problem of whether there could be any association between the glutathione S-transferase M1 (GSTM1) null genotype and the risk for CTE, with regard to solvent exposure, was investigated. METHODS: Sixty patients referred to a clinic because of some degree of psychiatric or neurological symptoms, as well as exposure to solvents, were examined by means of a validated questionnaire and psychometric testing. The degree of exposure to solvents was assessed by a thorough interview. According to clinical findings, the patients were classified into three categories as those with solvent-induced CTE, those with incipient CTE, and those who were non-CTE patients. Afterwards, leukocyte DNA (deoxyribonucleic acid) was isolated and the GSTM1 null genotype was determined by an assay based on polymerase chain reaction, blindly with regard to both exposure and disease status. RESULTS: The relative proportion (RP) of GSTM1 null genotypes was significantly increased for patients with a diagnosed CTE when they were compared with non-CTE patients (RP 2.55, 95% confidence interval 1.0-6.2). Dichotomizing the patients by high and low exposure revealed an increased risk for both GSTM1 gene carriers and the GSTM1 null genotype in the high-exposure group, the relative risks (RR) being 4.5 and 7.9, respectively. The chi-square for the Mantel extension for trend was 6.2 (P = 0.025). CONCLUSIONS: The GSTM1 null genotype acts as a risk modifier for CTE among patients occupationally exposed to solvents. The risk seems to increase in a dose-dependent fashion.

Brain Diseases↗
PubMed2003

Novel engineered HIV-1 East African Clade-A gp160 plasmid construct induces strong humoral and cell-mediated immune responses in vivo.

HIV-1 sequences are highly diverse due to the inaccuracy of the viral reverse transcriptase. This diversity has been studied and used to categorize HIV isolates into subtypes or clades, which are geographically distinct. To develop effective vaccines against HIV-1, immunogens representing different subtypes may be important for induction of cross-protective immunity, but little data exist describing and comparing the immunogenicity induced by different subtype-based vaccines. This issue is further complicated by poor expression of HIV structural antigens due to rev dependence. One costly approach is to codon optimize each subtype construct to be examined. Interestingly, cis-acting transcriptional elements (CTE) can also by pass rev restriction by a rev independent export pathway. We reasoned that rev+CTE constructs might have advantages for such expression studies. A subtype A envelope sequence from a viral isolate from east Africa was cloned into a eukaryotic expression vector under the control of the CMV-IE promoter. The utility of inclusion of the Mason-Pfizer monkey virus (MPV)-CTE with/without rev for driving envelope expression and immunogenicity was examined. Expression of envelope (gp120) was confirmed by immunoblot analysis and by pseudotype virus infectivity assays. The presence of rev and the CTE together increased envelope expression and viral infection. Furthermore the CTE+rev construct was significantly more immunogenic then CTE alone vector. Isotype analysis and cytokine profiles showed strong Th1 response in plasmid-immunized mice, which also demonstrated the superior nature of the rev+CTE construct. These responses were of similar or greater magnitude to a codon-optimized construct. The resulting cellular immune responses were highly cross-reactive with a HIV-1 envelope subtype B antigen. This study suggests a simple strategy for improving the expression and immunogenicity of HIV subtype-specific envelope antigens as plasmid or vector-borne immunogens.

AIDS Vaccines↗
PubMed2004

The reliability of horizontally sectioned scalp biopsies in the diagnosis of chronic diffuse telogen hair loss in women.

BACKGROUND: Chronic diffuse telogen hair loss is common in women. Paired 4-mm punch biopsy from the vertex scalp for horizontal and vertical sectioning is commonly used to distinguish between chronic telogen effluvium (CTE) and female pattern hair loss (FPHL). FPHL is now the favored term for androgenetic alopecia in women. OBJECTIVE AND METHODS: To evaluate the reliability of a single horizontally sectioned scalp biopsy in the diagnosis of FPHL, 207 women presenting with chronic diffuse hair loss had three 4-mm punch biopsy specimens taken from immediately adjacent skin on the mid scalp, and all 3 biopsy specimens were sectioned horizontally. Findings were compared with 305 women who underwent two biopsies, with one sectioned horizontally and the other vertically. The terminal to vellus-like hair ratio (T:V) at the mid-isthmus level was used to diagnose FPHL (T:V <4:1), CTE (T:V >8:1), or indeterminate hair loss (T:V=5:1, 6:1, or 7:1). To correlate the histologic diagnosis with the clinical severity, a mid-scalp clinical grading scale was developed. RESULTS: Among the 305 women who had a single horizontal scalp biopsy, 181 (59%) were diagnosed as having FPHL, 54 (18%) having CTE, and 70 (23%) having indeterminate hair loss. Six hundred twenty-one horizontal biopsy specimens were assessed from 207 patients. On the basis of consensus over 3 biopsies, 159 (77%) were diagnosed as having FPHL, 44 (21%) having CTE, and the remaining 4 women (2%) as having indeterminate hair loss. Among these 207 women, 114 were assessed clinically as having stage 1 or 2 hair loss. Sixty-nine (60%) were diagnosed as having FPHL on the basis of triple biopsy, 42 (37%) having CTE, and 2 having indeterminate hair loss. Ninety-three were graded as having stage 3, 4, or 5 hair loss. FPHL was diagnosed in 90 women (97%), CTE in 2, and indeterminate hair loss in one. By using each single biopsy as the criterion for diagnosis, 398 (61%) were classified as FPHL, 99 (16%) as CTE, and 124 (20%) as indeterminate. In 493 biopsies (79%), the single biopsy conclusion was identical to the 3 biopsy conclusions. Where disagreement was seen (21%), most were classified as indeterminate, rather than as a wrong diagnosis (3.3%). CONCLUSION: Application of these diagnostic criteria achieved accurate diagnostic definition in 98% of women with triple horizontal biopsies versus 79% with single horizontal biopsy. Ninety-seven percent of women with a mid-scalp clinical grade of 3, 4, or 5 were given a diagnosis of FPHL on triple biopsy. Scalp biopsy for diagnosis should be reserved for women with a mid-scalp clinical grade of 1 or 2.

Adolescent↗
PubMed1996

Chronic telogen effluvium: increased scalp hair shedding in middle-aged women.

BACKGROUND: Diffuse loss of scalp hair is a common problem in middle-aged women. A segment of these cases represents idiopathic chronic telogen effluvium (CTE). OBJECTIVE: The purpose was to establish distinctive clinical and pathologic criteria for the diagnosis of CTE to facilitate its differentiation from androgenetic alopecia (AGA) and systemic causes of chronic diffuse hair loss. METHODS: A group of 355 patients (346 females, 9 males) with diffuse generalized thinning of scalp hair of unknown origin were classified as having CTE and were included in the study. Characteristically they presented with a history of hair loss with both increased shedding and thinning of abrupt onset and fluctuating course and showed diffuse thinning of hair all over the scalp, frequently accompanied by bitemporal recession. Two 4 mm punch biopsy specimens were taken mostly from the mid or posterior parietal scalp of these patients. The biopsies were performed at these same areas in 412 patients with AGA (193 male, 219 female). Similar paired biopsy specimens were also taken from 22 normal control subjects (13 males, nine females). Specimens were sectioned horizontally and vertically and were examined for terminal and velluslike (miniaturized) hairs, follicular stelae, follicular units, and perifollicular inflammation and fibrosis. RESULTS: In horizontal sections of 4 mm punch biopsy specimens from patients with CTE the average number of hairs was 39, the terminal/velluslike hair ratio was 9:1, 89% of the terminal hairs were in anagen, and 11% were in telogen. In AGA these values were 35, 1.9:1, 83.2%, and 16.8%, respectively, and in normal control subjects 40, 7:1, 93.5%, and 6.5%, respectively. Significant degrees of inflammation and fibrosis were present in only 10% to 12% of cases of CTE and normal controls, but occurred in 37% of cases of AGA. CTE ran a prolonged and fluctuating course in many patients. CONCLUSION: CTE, which usually affects 30- to 60-year-old women, starts abruptly with or without a recognizable initiating factor. It may be distinguished from classic acute telogen effluvium by its long fluctuating course and from AGA by its clinical and histologic findings.

Adolescent↗
PubMed2001

Mapping the functional domains of HAP95, a protein that binds RNA helicase A and activates the constitutive transport element of type D retroviruses.

The complex retroviruses such as human immunodeficiency virus, type 1, employ a virally encoded protein, Rev, to mediate the nuclear export of unspliced and partially spliced mRNA. In contrast, the simian type D retroviruses act through a cis-acting constitutive transport element (CTE) that presumably interacts directly with cellular export proteins. We first reported that RNA helicase A (RHA) is a shuttle protein that binds to functional CTE in vitro and in vivo. Recently, we isolated a novel protein, HAP95, that specifically binds to the nuclear transport domain of RHA and up-regulates CTE-mediated gene expression. Here, using truncation and deletion mutations, we mapped the domains of HAP95 that are important for RHA binding, transactivation of CTE, and nuclear cytoplasmic shuttling. We report evidence for a novel nuclear export signal in HAP95 and showed that the domains involved in RHA binding and nuclear localization are required for CTE activation. Finally, we showed that HAP95 synergizes significantly with RHA on CTE-mediated reporter gene expression and promotes nuclear export of unspliced mRNA in transfected cells. Taken together, these data support the proposal that HAP95 specifically facilitates CTE-mediated gene expression by directly binding to RHA.

Active Transport, Cell Nucleus↗
PubMed1997

A cellular cofactor for the constitutive transport element of type D retrovirus.

A human nuclear protein that specifically interacts with the constitutive transport element (CTE) of simian retrovirus was identified as adenosine 5'-triphosphate-dependent RNA helicase A. This protein could bind to functional CTE but not to inactive CTE mutants. The interaction of helicase A with CTE was distinct from previously described helicase activity of this protein. Helicase A shuttled from the nucleus to the cytoplasm in the presence of a transcription inhibitor or in cells transiently overexpressing CTE-containing RNA. In vivo colocalization of helicase A and CTE was observed in experiments that combined in situ hybridization and immunostaining. These results suggest that helicase A plays a role in the nuclear export of CTE-containing RNA.

Adenosine Triphosphate↗
PubMed2001

Routine diagnostic procedures for chronic encephalopathy induced by solvents: survey of experts.

OBJECTIVES: To study the routine diagnostic procedures used in different countries for chronic toxic encephalopathy (CTE) induced by solvents. METHODS: By means of a postal questionnaire selected international experts were asked about the methods they use to diagnose patients suspected of having CTE induced by solvents, the number of patients, entrance criteria, and the results of these diagnostic procedures. RESULTS: 18 Experts working in 18 diagnostic centres responded. Most of them agreed that a diagnostic procedure for CTE induced by solvents should contain an interview and neurological, physical, and neuropsychological examinations. However, the tests used were very different, as were the classifications for CTE. Depending on the institute, a diagnosis of CTE was made in 6%--70% of the referred patients. The proportion of patients with CTE stage I ranged from 0% to 33%, stage II from 5% to 100%, and stage III from 0% to 95%. CONCLUSION: The intentions of the two 1985 conferences that aimed at clarity and uniformity of diagnosis of CTE induced by solvents are far from reached. It is possible, now the conditions are more favourable, to aim at this important goal and recommend some refinement of the then proposed criteria.

Brain Damage, Chronic↗
PubMed1991

Aerobic dehalogenation of halothane showing different substrate dependency from anaerobic dehalogenation in liver microsomes of guinea pig.

The formation of trifluoroacetic acid (TFAA) from halothane under aerobic conditions and that of chlorotrifluoroethane (CTE) and chlorodifluoroethylene (CDE) from halothane under anaerobic conditions were studied using guinea pig liver microsomes. The formation of TFAA was inhibited by specific inhibitors of cytochrome P450 (P450), such as carbon monoxide and metyrapone and was dependent upon P450 contents. The maximum activity of the TFAA formation was obtained at pH 6.0. On the other hand, the maximum activity to form CTE and CDE was obtained at pH 7.4. The formation of TFAA reached a plateau at a halothane concentration above 0.17 mM, but the rate of formation of CDE and CTE was dependent upon a halothane concentration up to 1.5 mM. The values of apparent Michaelis-Menten constant (Km) and maximum velocity (Vmax) for TFAA formation were 0.067 mM and 0.349 nmol/nmol P450/min respectively, those for CDE formation were 0.983 mM and 0.326 nmol/nmol P450/min respectively, and those for CTE formation were 1.71 mM and 0.752 nmol/nmol P450/min respectively. These results showed clearly that the formation of TFAA, CDE and CTE was catalyzed by the P450 system in guinea pig liver microsomes. Under optimal conditions, saturation was observed in the formation of TFAA from halothane at a halothane concentration above 0.17 mM but the formation of CDE and CTE was not saturated at this concentration, and the value of apparent Km for TFAA formation was lower than those for CDE and CTE formation.

Aerobiosis↗
PubMedDate not supplied

[Localization of fluorescent analogs of cholesterol and its esters in lipid models of membranes and lipoproteins].

The localization of the fluorescent cholesterol analogue--delta 5,7,9(11)-cholestatrien-3 beta-ol (B-CTE) and its methyl (M-CTE) and stearoyl (St-CTE) esters in model lipid particles were investigated by the radiationless energy transfer. It is shown that 67-100% of B-CTE molecules localize in the phospholipid monolayer of particles containing phosphatidylcholine and triolein (1:2 w/w). The replacement of a hydrogen atom in the hydroxyl by methyl resulted in immersion of 2/3 of the M-CTE molecules to the triolein core. This fact confirmed distribution of the fluorescent probe molecules in the whole volume of lipid particles. St-CTE was practically completely localized in the core of lipid particles. The results obtained evidence for the important role of 3-OH group in keeping the B-CTE molecules in the phospholipid monolayer of the investigated particles.

Cholestenes↗
PubMed1999

Analysis of the RNA binding specificity of the human tap protein, a constitutive transport element-specific nuclear RNA export factor.

The human Tap protein has been proposed to mediate Mason Pfizer monkey virus constitutive transport element (CTE)-dependent nuclear RNA export and may also play a role in global mRNA export. Here, we have used in vivo assays, in both yeast and human cells, together with in vitro assays, to further characterize the RNA binding properties of Tap, which has been proposed to contain a novel leucine-rich RNA binding motif. Using the yeast three hybrid assay, we selected RNA molecules that retain Tap binding activity from a pool of randomized CTE sequences. The recovered RNA sequences differed only minimally from the wild-type CTE yet all displayed lower affinity for Tap both in vivo and in vitro. Analysis of the RNA export activity of the recovered CTE variants revealed that Tap affinity was highly predictive of CTE biological activity. Together, these observations provide additional evidence supporting the identification of Tap as the direct cofactor for CTE function and demonstrate that RNA binding by Tap is highly sequence specific.

Animals↗
PubMed2000

Criteria for solvent-induced chronic toxic encephalopathy: a systematic review.

In 1985, a WHO Working Group presented diagnostic criteria and a classification for solvent-induced chronic toxic encephalopathy (CTE). In the same year, the "Workshop on neurobehavioral effects of solvents" in Raleigh, N.C., USA introduced a somewhat different classification for CTE. The objective of this review is to study the diagnostic procedures that are used to establish the diagnosis of CTE, and the extent to which the diagnostic criteria and classification of the WHO, and the classification of the Raleigh Working Group, are applied. A systematic search of studies on CTE was performed, and the diagnostic criteria and use of the WHO and Raleigh classifications were listed. We retrieved 30 original articles published in English from 1985 to 1998, in which CTE was diagnosed. Only two articles did not report the duration of solvent exposure. The type of solvent(s) involved was described in detail in four articles, poorly in 17 articles, and not at all in nine articles. Tests of general intelligence were used in 19 articles, and tests of both attention and mental flexibility and of learning and memory were used in 18 articles. Exclusion, by interview, of potentially confounding conditions, such as somatic diseases with central nervous effects and psychiatric diseases, was reported in 21 and 16 articles, respectively. In only six of the articles were both the WHO diagnostic criteria and the WHO or Raleigh classifications used. In the future, parameters of exposure, psychological test results, and use of medication that possibly affects psychological test results should always be described. We list some advantages and disadvantages of the Raleigh and WHO classifications. To aid inter-study comparisons, the diagnosis of CTE should be categorized and reported according to an internationally accepted classification.

Brain Damage, Chronic↗
PubMed1984

Reductive halothane metabolite formation and halothane binding in rat hepatic microsomes.

The production of the reductive [14C]halothane metabolites, 2-chloro-1, 1,1-trifluoroethane ( CTE ) and 2-chloro-1,1- difluoroethylene (CDE), was determined in anaerobic microsomal incubations by high pressure liquid chromatography (HPLC). The HPLC technique used allowed accurate measurements of low levels of [14C]halothane metabolites. Comparisons of metabolic profiles and halothane binding in microsomes reduced with NADPH and sodium dithionite show that dithionite stimulates CDE production and total halothane degradation, but inhibits CTE formation and [14C]halothane binding. Similarly, the addition of isoflurane, but not enflurane, to microsomes increases CDE production and decreases CTE formation and [14C]halothane-lipid binding. Measurement of fluoride in similar incubations show that fluoride release from halothane correlates with the formation of CDE and not CTE . The results demonstrate that the relative production of CTE and CDE may not remain constant in microsomal preparations, and that halothane binding correlates with CTE formation and not CDE and fluoride production.

Animals↗
PubMedDate not supplied

Attentional states and the degree of visual adaptation to gratings.

We studied top-down attentional effects on adaptation to two aspects of sinusoidal gratings: contrast (CTE: contrast threshold elevation for detection) and orientation (TAE: tilt aftereffect, bias in perceived orientation). Adaptation was examined under five different behavioral conditions designed to assess the effect of alertness, spatial attention and the dimension attended. Alertness increased CTE, but had no effect on TAE. Spatial attention increased TAE, but had no effect on CTE. TAE (but not CTE) was also sensitive to the attended dimension. It was greater when gratings' contrast rather than orientation was attended. The different patterns of top-down effects on CTE compared with TAE are consistent with these two types of adaptation taking place at different levels along the visual hierarchy: CTE occurs at very low-levels, where activity is affected by alertness but not by spatial attention, whereas TAE occurs at subsequent stages, which are modulated by selective attention.

Acclimatization↗