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A Kiss

Publications and source records attributed to A Kiss.

At least 37 records · Page 2Linked to original sources
PubMed2002

Distribution of neuronal and non-neuronal spliced variants of type 1 IP(3)-receptor in rat hypothalamus and brain stem.

In the nervous system, inositol 1,4,5-trisphosphate (IP(3)) is one of the second messengers produced by PI hydrolysis and triggers IP(3)-receptor (IP(3)R) mediated calcium release from intracellular pools. Throughout the brain, the type 1 IP(3)R is predominantly expressed and its mRNA is widely distributed. Alternative splicing of IP(3)R1 (SI and SII) occurs in two distinct regions. SI splicing in the middle of the ligand binding domain may alter the IP(3) binding activity, while SII splicing probably affects the protein kinase A phosphorylation sites and kinetics. Selective use of IP(3)-receptor subtypes may permit a tissue specific and developmentally specific expression of functionally distinct channels. The present work was focused on detection of the alternatively spliced mRNA of type 1 IP(3)-receptor in individual brain structures and nuclei. Using RT-PCR we detected neuronal (535bp) and non-neuronal (410bp) forms. We identified both spliced variants in the majority of brain structures, except in the cerebellum and medulla. In the cerebellum, the neuronal form of type 1 IP(3)R was found exclusively, while in the medulla, the non-neuronal form was much more abundant. Nevertheless, Western blot analysis and hybridization with specific antibody against IP(3)R revealed no qualitative, but only quantitative differences. Similarly, IP(3) dependent calcium release did not show any differences between the cerebellum and pons. These results demonstrate the distribution of alternatively spliced S2 variants of type 1 IP(3)R in selected brain structures and nuclei. The physiological relevance of these two forms remains to be elucidated by further studies.

Alternative Splicing↗
PubMed2002

[The cerebellum: anatomy, distribution of mediators and their receptors, communication with hypothalamic structures and comparison with the hypothalamic paraventricular nucleus under conditions of stress].

Cerebellum is a profound structure of the central nervous system. Human cerebellum weighs about 150 g which represents around 10% of the total weight of the brain. It receives main input from sensory systems but the cerebellum functions as a part of the motor system. The cerebellum contributes by only few direct connections to motoneurons (therefore it cannot initiate any motor activity) but it projects profusely to all major motor control regions of the cerebral cortex. The cerebellum acts as a controller and coordinator. It compares movement intention with, performance and coordinates the equilibrium, posture and muscle tone necessary for the smooth coordinated motor activity. The number of input projections which exceed considerably the output ones (40:1) speaks out of an enormous analytical and synthetic capacity of the cerebellum. Interneuronal transmission of informations and carriage of afferent and efferent signals are provided by wide variety of chemical messengers (amino acids, biogenic amines and neuropeptides) of the local origin or delivered from the precerebellar nuclei. Direct and reciprocal connections between the hypothalamus and cerebellum have anatomically been well documented but monosynaptic contacts between the cerebellum and the hypothalamic paraventricular nucleus have not been approved yet. Cerebellum can respond to stress, however, this response may not be related only to the primary effect of the stressor but also to its consequences.

Afferent Pathways↗
PubMed2001

Importance of mental health assessment in HIV-infected outpatients.

HIV infection, even when well controlled, may be associated with important mental health problems. We sought to investigate anxiety, depression, and health-related quality of life using screening measurements in patients with HIV infection and to examine their dependency on biosocial parameters relating to HIV. Prospective clinical, virologic, and immunologic data were obtained in a cross-sectional study within the Swiss HIV Cohort Study. Four self-reported questionnaires were used in 397 HIV-infected individuals. The scores for anxiety and depression were high as measured by the Hospital Anxiety and Depression Scale (HADS) and the State Trait Anxiety Inventory (STAI). Half the population scored <75 on a visual analog scale (VAS) Patients were also affected in their quality of life as measured by the HIV Medical Outcome Study (HIV-MOS). Almost all scores were significantly worse for intravenous drug users compared with other transmission groups. People who were employed, with a higher education or with higher CD4 count tended to score better, whereas those who had been hospitalized within the last 6 months, infected for a longer time, with higher viral load, or loss of weight scored significantly worse. A multivariate analysis showed higher education, being employed, low viral load, female gender, and shorter HIV disease duration to be associated with better scores. This study highlights the importance of mental health assessment regardless of HIV-disease parameters.

Adolescent↗
PubMed2001

Reduction of wild type p53 function confers a hormone resistant phenotype on LNCaP prostate cancer cells.

BACKGROUND: The protein encoded by the p53 gene is required for some forms of apoptosis and loss or mutations in this gene are found with increased frequency in advanced and hormone resistant human prostate cancers. In order to better appreciate whether reduction of wildtype p53 function in prostate cancer cells might contribute to the development of therapeutic-resistance by these cells, we created stable variants of the androgen-responsive, wild type p53-expressing human prostate cancer cell line, LNCaP, by transfection with expression vectors designed to reduce expression or function of wildtype p53 in them. These cells were then tested for their ability to form tumors in castrated male nude mice. METHODS: A conditional eukaryotic expression vector (under tetracycline regulation) expressing antisense p53 cDNA was constructed and either directly transfected into LNCaP cells or tranduced into these cells using recombinant retroviruses containing the vector. Stably transfected/transduced cells (LNCaP/Asp53) were evaluated by Western blot analysis for the ability of doxycycline to reduce p53 protein expression and for their ability to form tumors in castrated male nude mice treated or untreated with doxycycline. Additionally, we derived an LNCaP subline (LNCaP/DD) stably expressing a dominant-negative form of p53 and tested these cells for their ability to form tumors in castrated male nude mice. RESULTS: LNCaP/Asp53 cells showed reduced expression of p53 protein when cultured in a medium containing doxycycline and tested sublines were able to efficiently form tumors in castrated male nude mice only when the mice were treated with doxycycline. LNCaP/DD cells were readily able to form tumors in castrated male nude mice whereas parental LNCaP cells or control-transfected LNCaP cells were not. CONCLUSION: Loss of wildtype p53 function can contribute to the phenotype of hormone resistance of prostate cancer cells.

Animals↗
PubMed2001

Role of DNA minor groove interactions in substrate recognition by the M.SinI and M.EcoRII DNA (cytosine-5) methyltransferases.

The SinI and EcoRII DNA methyltransferases recognize sequences (GG(A)/(T)CC and CC(A)/(T)GG, respectively), which are characterized by an (A)/(T) ambiguity. Recognition of the A.T and T.A base pair was studied by in vitro methyltransferase assays using oligonucleotide substrates containing a hypoxanthine.C base pair in the central position of the recognition sequence. Both enzymes methylated the substituted oligonucleotide with an efficiency that was comparable to methylation of the canonical substrate. These observations indicate that M.SinI and M.EcoRII discriminate between their canonical recognition site and the site containing a G.C or a C.G base pair in the center of the recognition sequence (GG(G)/(C)CC and CC(G)/(C)GG, respectively) by interaction(s) in the DNA minor groove. M.SinI mutants displaying a decreased capacity to discriminate between the GG(A)/(T)CC and GG(G)/(C)CC sequences were isolated by random mutagenesis and selection for the relaxed specificity phenotype. These mutations led to amino acid substitutions outside the variable region, previously thought to be the sole determinant of sequence specificity. These observations indicate that (A)/(T) versus (G)/(C) discrimination is mediated by interactions between the large domain of the methyltransferase and the minor groove surface of the DNA.

Amino Acid Sequence↗
PubMed2001

Covalent joining of the subunits of a homodimeric type II restriction endonuclease: single-chain PvuII endonuclease.

The PvuII restriction endonuclease has been converted from its natural homodimeric form into a single polypeptide chain by tandemly linking the two subunits through a short peptide linker. The arrangement of the single-chain PvuII (sc PvuII) is (2-157)-GlySerGlyGly-(2-157), where (2-157) represents the amino acid residues of the enzyme subunit and GlySerGlyGly is the peptide linker. By introducing the corresponding tandem gene into Escherichia coli, PvuII endonuclease activity could be detected in functional in vivo assays. The sc enzyme was expressed at high level as a soluble protein. The purified enzyme was shown to have the molecular mass expected for the designed sc protein. Based on the DNA cleavage patterns obtained with different substrates, the cleavage specificity of the sc PvuII is indistinguishable from that of the wild-type (wt) enzyme. The sc enzyme binds specifically to the cognate DNA site under non-catalytic conditions, in the presence of Ca2+, with the expected 1:1 stoichiometry. Under standard catalytic conditions, the sc enzyme cleaves simultaneously the two DNA strands in a concerted manner. Steady-state kinetic parameters of DNA cleavage by the sc and wt PvuII showed that the sc enzyme is a potent, but somewhat less efficient catalyst; the k(cat)/K(M) values are 1.11 x 10(9) and 3.50 x 10(9) min(-1) M(-1) for the sc and wt enzyme, respectively. The activity decrease is due to the lower turnover number and to the lower substrate affinity. The sc arrangement provides a facile route to obtain asymmetrically modified heterodimeric enzymes.

Amino Acid Sequence↗
PubMed2001

[Molecular biology examination in chronic lymphocytic leukemia].

Chronic lymphocytic leukaemia (CLL) is the most common adult leukaemia characterised by the accumulation of monoclonal CD5 + B-lymphocytes. The pathogenesis and the biology of CLL is complex and many details are still unknown. Several molecular biological methods have been used in the investigation of CLL, among them the study of apoptosis appears to be one of the most important. Initial experiences obtained by the spontaneous and fludarabine induced apoptosis, multidrug resistance (MDR)-test and fluorescent in situ hybridization (FISH) are reported by the authors. Apoptosis of CLL cells could be induced by fludarabine, while more studies should be performed to determine the exact role of MDR-test and FISH.

Adult↗
PubMed2001

Hepatic regeneration induces transient acute phase reaction: systemic elevation of acute phase reactants and soluble cytokine receptors.

The growth factors present during liver regeneration partially overlap with the regulators of the hepatic acute phase response. We analysed the acute phase reaction and changes in soluble cytokine receptors after partial hepatectomy, when tissue injury inducing acute phase reaction and major reduction of liver mass occur simultaneously. Three acute phase proteins and mRNAs were determined by ELISA and northern blot hybridisation in rats. Serum levels of IL-6 and three soluble cytokine receptors (sTNF-alpha R I and II, sIL-6R) were detected by ELIBA or dot-blot assay. Time-course profiles of fibrinogen, alpha(2)-macroglobulin and haptoglobin proteins and mRNA are presented. Elevation of IL-6, soluble TNF-alpha receptors and soluble IL-6 receptor levels were also detected. The time-course of changes in haptoglobin concentration and elevation of soluble cytokine receptors is described by this in vivo experimental system. The results show good correlation with (post)transcriptional activation of immediate and delayed early gene products. These data suggest the involvement of both acute phase proteins and soluble cytokine receptors in the regulation of liver regeneration.

Acute-Phase Proteins↗
PubMed2001

Effect of myelopoietic and pleiotropic cytokines on colony formation by blast cells of children with acute lymphoblastic leukemia.

The aim of this study was to see whether pleiotropic or myeloid hematopoietic growth factors, which do not stimulate normal lymphoid cells, can induce proliferation of blast cells of the acute lymphoid leukemia (ALL) of childhood. Bone marrow cells of 13 children with untreated ALL (nine common ALL, two myeloid antigen positive ALL and two early T-cell ALL) formed colonies of leukemic blast cells in primary methylcellulose cultures. Spontaneous growth was observed in three of 13 cases, whereas phytohemagglutinin-stimulated leukocyte conditioned medium (PHA-LCM), a conventional source of various natural human cytokines, induced colony formation in ten of 13 cases. A similar rate of responsiveness was seen with recombinant human granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and stem cell factor (SCF); a combination of these three cytokines induced colony formation in all cases studied. The effect of these growth factors on colony formation seemed to be dose-dependent in some cases. Of the stimuli studied, GM-CSF induced the smallest number of colonies, whereas the effects of G-CSF, SCF and PHA-LCM were similar in this respect. Combination of cytokines proved to be even more efficient in inducing clonal proliferation of leukemic lymphoblasts. In double combinations, G-CSF and GM-CSF as well as G-CSF and SCF were able to potentiate each other's effects. Triple combination of these cytokines mediated the most potent growth stimulus. Our results demonstrate that myeloid and pleiotropic cytokines are able to stimulate clonal proliferation of pediatric leukemic lymphoblasts. This may present a potential hazard to children with ALL while on adjuvant therapy with hematopoietic growth factors. In vitro colony assays performed prior to or in parallel with the administration of hematopoietic growth factors to ALL patients may help to forecast their possible effects on leukemic cells in vivo.

Adolescent↗
PubMed2001

Corticotropin-releasing hormone mRNA levels in response to chronic mild stress rise in male but not in female rats while tyrosine hydroxylase mRNA levels decrease in both sexes.

Corticotropin-releasing hormone (CRH) and catecholamines are suggested to play a significant role in the pathophysiology of depression. In the present study we investigated gene expression of CRH in the hypothalamic paraventricular nucleus (PVN) and tyrosine hydroxylase (TH) in the locus coeruleus (LC) in an experimental model of depression. A chronic mild stress model was applied in rats of both genders for a three-week period. Anhedonic behaviour, a typical sign of depression-like state, was measured by a sucrose preference test. The chronic mild stress induced a decrease in sucrose preference in both genders. The body weight gain was reduced in males only. The total activity in the open field test was unchanged, however, male rats exposed to chronic mild stress showed enhanced locomotor activity during the first minute of the session, suggesting increased anxiety. Basal plasma corticosterone levels, thymus and adrenal weights measured on the third day after cessation of the stress regimen, were not affected by the stress procedure. Evaluation of CRH mRNA levels in the PVN by in situ hybridisation revealed a significant rise in response to chronic mild stress in males. In females, the basal CRH mRNA levels were higher compared to those in males, but the stress-induced rise was absent. Chronic mild stress resulted in a decrease in TH mRNA levels in the LC. These data demonstrate that chronic mild stress model of depression induces a specific stress response with a reduction of TH gene expression in the LC and clear gender differences in gain of body weight, anxiety-like behaviour, and CRH mRNA levels in the PVN.

Adrenal Cortex↗
PubMed2001

Immunohistochemical analysis of atypical ductular reaction in the human liver, with special emphasis on the presence of growth factors and their receptors.

AIMS/BACKGROUND: The objective of this study was to characterize the expression of transforming growth factor-alpha/epidermal growth factor receptor, hepatocyte growth factor/c-met, transforming growth factor-beta/Type I-II transforming growth factor-beta receptors, stem cell factor, urokinase plasminogen activator, smooth muscle actin, CD34 and alpha-fetoprotein in human liver samples with (sub)massive necrosis of different etiology containing atypical ductular reaction. METHODS: Their presence was studied by immunohistochemistry on paraffin-embedded tissue sections. RESULTS: Transforming growth factor-alpha and -beta, hepatocyte growth factor and their receptors were demonstrated in the ductules; additionally stem cell factor and urokinase plasminogen activator were also expressed. The atypical ductules were surrounded by smooth muscle actin-positive activated stellate cells. CONCLUSION: These phenotypic similarities confirm that the atypical ductules in the human liver may be equivalent of oval cells in the rat liver, which are regarded as the progeny of stem cells. That is, the atypical ductular proliferation may correspond to a stem cell-fed regenerative process.

Adolescent↗
PubMed2001

Calcein assay for multidrug resistance reliably predicts therapy response and survival rate in acute myeloid leukaemia.

In this study, we evaluated the suitability of the calcein assay as a routine clinical laboratory method for the identification of multidrug-resistant phenotype in acute leukaemia. This study presents the results of the calcein tests obtained in two large haematological centres in Hungary. Assays were performed with blast cells of 93 de novo acute leukaemia patients, including 65 patients with acute myeloid leukaemia (AML). Results were expressed as multidrug resistance activity factor (MAF) values. AML patients were divided into responders and non-responders and MAF values were calculated for each group. In both centres, responder patients displayed significantly lower MAF values than non-responders (P = 0.0045 and P = 0.0454). Cut-off values were established between the MAFR + SEM and MAFNR - SEM values. On the basis of these cut-off levels, multidrug resistance (MDR) negativity showed a 72% predictive value for the response to chemotherapy, whereas MDR positivity was found to have an average predictive value of 69% for therapy failure. MDR activity was a prognostic factor for survival rate and the test was suitable for detecting patients at relapse. The calcein assay can be used as a quantitative, standardized, inexpensive screening test in a routine clinical laboratory setting. The assay detects both P-glycoprotein and multidrug resistance-associated protein activities, and identifies AML patients with unfavourable therapy responses.

Acute Disease↗
PubMed2001

Identification of P-selectin glycoprotein ligand-1 as a useful marker in acute myeloid leukaemias.

Immunophenotyping is considered to be less valuable in the diagnosis of acute myeloid leukaemias (AML) compared with acute lymphoid leukaemias. Here, we present data on the use of quantitative flow cytometry (QFC) of P-selectin glycoprotein ligand 1 (PSGL-1, CD162) and three-colour immunophenotyping including CD162 staining in the identification of myeloid precursors in AML. Analysis of normal peripheral blood (n = 20) and normal bone marrow (n = 5) samples and on 20 samples from de novo M1, M2, M4 and M5 AML patients demonstrated that PSGL-1 is differentially expressed on various mature and immature leucocyte subsets. It was found by QFC that neutrophils expressed 26500 +/- 4500 and monocytes 47200 +/- 9900 copies of PSGL-1 on their surface, whereas AML blasts from M1 and M2 AML patients expressed significantly less PSGL-1 (12 000 +/- 5300) than mature neutrophils (P < 0.001). In M4 and M5 leukaemias, however, the amount of PSGL-1 on monocytic precursors is displayed in a fairly broad range that is not significantly different from that of mature monocytes (P = 0.084). Using three-colour immunophenotyping PSGL-1-dim staining was co-expressed with CD7 and C34 positivity and PSGL-1 staining intensity on immature myeloid cells paralleled with CD45 expression. This would imply a differential expression of PSGL-1 during myeloid haematopoietic development and suggests that quantification of surface PSGL-1 may aid in differentiating myeloblasts from monoblasts by immunophenotyping in different AML subsets.

Acute Disease↗
PubMed2001

Evidence that reduction of hepatocyte growth factor (HGF) is not required for peroxisome proliferator-induced hepatocyte proliferation.

The mechanisms underlying peroxisome proliferator-induced hepatocarcinogenesis are not understood. Because of the uncertainty of human cancer risk associated with peroxisome proliferators, delineating the mechanisms of carcinogenesis by these agents is of great interest. Alterations in liver growth factors were postulated to contribute to the carcinogenic effect of peroxisome proliferators. Administration of these compounds to rodents results in down-regulation of hepatocyte growth factor (HGF) and supplementing culture medium with HGF is reported to suppress cell proliferation of preneoplastic and neoplastic cells from WY-14,643-treated livers. Combined, these observations suggest that reduced levels of hepatic HGF contribute to the mechanisms underlying peroxisome proliferator-induced hepatocarcinogenesis. To determine if HGF can prevent the effects of peroxisome proliferators in liver, the short-term influence of WY-14,643 in two different lines of HGF transgenic mice was examined. Mice were fed either a control diet or one containing 0.1% WY-14-643 for one week. Hepatomegaly was found in both HGF transgenic mouse lines fed WY-14,643 compared with controls. Additionally, hepatic expression of typical mRNA markers of peroxisome proliferation including those encoding peroxisomal fatty acid metabolizing enzymes and cell cycle control proteins were all significantly elevated in HGF transgenic mice fed WY-14,643 compared with controls. Down-regulation of HGF was found to be dependent on PPARalpha since lower levels of HGF mRNA and protein were observed in wild-type mice fed WY-14,643 for 1 week and not in similarly treated PPARalpha-null mice. These results demonstrate that the early increase in hepatic mRNAs associated with peroxisome and cell proliferation induced by WY-14,643 treatment can not be prevented by overexpression of HGF in vivo.

Animals↗
PubMed2001

The response of balanitis xerotica obliterans to local steroid application compared with placebo in children.

PURPOSE: We evaluated the clinical effectiveness of topical steroid application for balanitis xerotica obliterans in children and analyzed the association of any clinical response with histological findings. MATERIALS AND METHODS: Our double-blind, placebo controlled, randomized study included 40 boys in whom balanitis xerotica obliterans was diagnosed clinically by cicatricial phimosis. The severity of phimosis was graded into 4 groups. Patients were randomized to receive the topical application of 0.05% mometasone furoate or placebo. After 5 weeks phimosis severity was reevaluated and all patients underwent circumcision. Surgical specimens were histologically typed as an early, intermediate or late form of balanitis xerotica obliterans. RESULTS: Seven patients were withdrawn from the study. In the steroid group 7 boys had clinical improvement and 10 had no change. Histological study showed an early, intermediate and late form of balanitis xerotica obliterans in 5, 5 and 7 cases, respectively. Of cases with clinical improvement 5 were the early and 2 the intermediate type. In the placebo group 5 cases worsened clinically and 11 did not change. Histological evaluation revealed an early, intermediate and late form of balanitis xerotica obliterans in 3, 7 and 6 boys, respectively. Of the 5 cases with histological worsening, disease was the early, intermediate and late type in 2, 2 and 1, respectively. CONCLUSIONS: Applying a potent topical steroid affects improvement in balanitis xerotica obliterans in the histologically early and intermediate stages of disease, and may inhibit further worsening in the late stage.

Administration, Topical↗
PubMed2001

Changes in angiotensin AT1 receptor mRNA levels in the rat brain after immobilization stress and inhibition of central nitric oxide synthase.

OBJECTIVE: To study functional interactions between angiotensin II AT1 receptors and nitric oxide (NO) activity in different brain areas in rats exposed to immobilization stress. METHODS: Central inhibition of nitric oxide synthase (NOS) was provided by intracerebroventricular (i.c.v.) administration of (N-omega-nitro-L-arginine-methylester) L-NAME and analysis of AT1 receptor mRNA was performed using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) technique. The immobilization in prone position lasted 2 hrs and the rats were sacrificed 24 hr later. The hypothalamus, hippocampus, thalamus, and cortex were isolated from fresh brains. RESULTS: In the cortex, gene expression of AT1 receptors was unaffected either by L-NAME treatment, or by a single exposure to immobilization stress for 2 hours followed by 24 hours of rest. In the hippocampus, the repeated treatment with L-NAME increased mRNA levels of AT1 receptors approximately 9-times compared to those in the control (untreated) group. Immobilization also increased AT1 receptor mRNA levels in the hippocampus which was similar to that induced by the L-NAME. The increase of AT1 receptor mRNA levels in the hippocampus of immobilized rats was not further altered when the animals were pretreated with L-NAME. In control rats, exposure to immobilization resulted in a significant rise in mRNA levels coding for AT1 receptors in the hypothalamus, but not in the thalamus. L-NAME treatment showed a tendency of increase in AT1 receptor mRNA levels in the hypothalamus. Moreover, when animals treated with L-NAME were subjected to immobilization, a further increase in AT1 receptor mRNA levels was observed in the hypothalamus in comparison with corresponding controls. CONCLUSIONS: The present data indicate that a single immobilization stress results in increased gene expression of AT1 receptors in the hypothalamus and hippocampus. The rise in AT1 mRNA levels in the same brain structures after repeated treatment with L-NAME allow to suggest an interaction between the central angiotensin II and nitric oxide.

Animals↗
PubMed2001

Nitric oxide synthase mRNA levels correlate with gene expression of angiotensin II type-1 but not type-2 receptors, renin or angiotensin converting enzyme in selected brain areas.

Recent data suggest that there is interaction between peripheral angiotensin II and nitric oxide. However, sparse information is available on the mutual interaction of these two compounds in the brain. The potential intercourse of nitric oxide with brain neuropeptides needs to be substantiated by assessing its local production and gene expression of the synthesizing enzymes involved. The aim of the present study was to evaluate whether the gene expression of brain nitric oxide synthase (bNOS) is related to the sites of gene expression of different components of the rat brain renin angiotensin system (renin, angiotensin converting enzyme (ACE) or angiotensin receptors of AT1 and AT2 subtypes). The levels of corresponding mRNAs were measured and correlated in nine structures of adult rat brain (hippocampus, amygdala, septum, thalamus, hypothalamus, cortex, pons, medulla and cerebellum). As was expected, positive correlation was observed between renin and angiotensin-converting enzyme mRNAs. Moreover, a significant correlation was found between brain NO synthase and AT1 receptor mRNAs, but not with mRNA of the AT2 receptor, ACE and renin. Parallel distribution of mRNAs coding for bNOS and AT1 receptors in several rat brain structures suggests a possible interaction between brain angiotensin 11 and nitric oxide, which remains to be definitely demonstrated by other approaches.

Amygdala↗