Tid1 functions as a tumour suppressor in head and neck squamous cell carcinoma

Human tumourous imaginal disc (Tid1), a human homologue of the Drosophila tumour suppressor protein Tid56, is involved in multiple intracellular signalling pathways such as apoptosis, cell proliferation, and cell survival. Here, we investigated the anti‐tumourigenic activity of Tid1 in head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo. Firstly, the clinical association between Tid1 expression and progression of HNSCC was explored. It was found that expression of Tid1 was negatively associated with tumour status, recurrence, and survival prognosis using immunohistochemical analysis of primary HNSCC patient tumour tissue. Secondly, ectopic expression of Tid1 in HNSCC cells was shown to significantly inhibit cell proliferation, migration, invasion, anchorage‐independent growth, and xenotransplantation tumourigenicity. Thirdly, we showed that overexpression of Tid1 attenuated EGFR activity and blocked the activation of AKT in HNSCC cells, which are known to be involved in the regulation of survival in HNSCC cells. On the other hand, ectopic expression of constitutively active AKT greatly reduced apoptosis induced by Tid1 overexpression. Together, these findings suggest that Tid1 functions as a tumour suppressor in HNSCC tumourigenesis. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Impaired gist memory in patients with temporal lobe epilepsy and hippocampal sclerosis

Purpose: Temporal lobe epilepsy (TLE) is the most common focal epilepsy and frequently causes memory problems. It is often associated with hippocampal sclerosis (HS) and is useful in exploring memory functions. We aimed to examine the effect of restricted hippocampal lesions on gist memory function in patients with TLE. Methods: Forty‐five patients with TLE and HS (16 left, 15 right, and 14 bilateral lesions) and 22 control subjects were recruited. Patients with magnetic resonance imaging (MRI) or electroencephalography (EEG) evidence of extratemporal lesions were excluded. All participants performed a gist‐based recognition task following the Deese‐Roediger‐McDermott paradigm and were tested for verbal IQ and memory functions. We conducted hippocampal volumetry on MRI of all the participants. Results: Patients showed multidomain memory impairments. Gist memory was impaired in patients with bilateral HS and probably in patients with right HS. Hippocampal volumetry supported such findings that total volume of hippocampi and volume of right hippocampus correlated positively with gist memory function. Discussion: HS has a dose effect and a probable right dominance effect on gist memory; good item memory supports gist memory performance; and a disproportionate deficit was noted in tasks with high relational demand but not in tasks with simple association. We should develop memory skills for patients with TLE by enhancing performance of gist memory related to simple association task.     

Kv7.2 regulates the function of peripheral sensory neurons

The Kv7 (KCNQ) family of voltage‐gated K⁺ channels regulates cellular excitability. The functional role of Kv7.2 has been hampered by the lack of a viable Kcnq2‐null animal model. In this study, we generated homozygous Kcnq2‐null sensory neurons using the Cre‐Lox system; in these mice, Kv7.2 expression is absent in the peripheral sensory neurons, whereas the expression of other molecular components of nodes (including Kv7.3), paranodes, and juxtaparanodes is not altered. The conditional Kcnq2‐null animals exhibit normal motor performance but have increased thermal hyperalgesia and mechanical allodynia. Whole‐cell patch recording technique demonstrates that Kcnq2‐null sensory neurons have increased excitability and reduced spike frequency adaptation. Taken together, our results suggest that the loss of Kv7.2 activity increases the excitability of primary sensory neurons. J. Comp. Neurol. 522:3262–3280, 2014. © 2014 Wiley Periodicals, Inc.     

Structural abnormalities revealed by magnetic resonance imaging in rats prenatally exposed to methylazoxymethanol acetate parallel cerebral pathology in schizophrenia

Schizophrenia is a highly familial, neurodevelopmental disorder that is associated with several neuropsychiatric, psychological, and neuropathological features. Although pharmacological animal models of dopaminergic and glutamatergic dysfunction have helped advance our understanding of the disease biology, there is a clear need for translational models that capture the neuropathological and functional manifestations associated with the intermediate phenotype and the clinical illness. Neuroimaging of preclinical neurodevelopmental approaches such as methylazoxymethanol acetate (MAM) exposure may afford a powerful translational tool to establish endpoints with greater congruency across animals and humans. Using in vivo volumetric magnetic resonance imaging (MRI), manganese‐enhanced MRI, and diffusion tensor imaging (DTI), we investigated morphological and cytoarchitectural changes of brain structures in MAM‐exposed rats, a neurodevelopmental model of schizophrenia. Compared to saline‐exposed controls, MAM‐exposed rats showed significant enlargement of lateral and third ventricles as well as reduced hippocampal volumes, which is consistent with findings observed in schizophrenia. In addition, DTI revealed that diffusion fractional anisotropy retrieved from corpus callosum and cingulum were significantly decreased in MAM‐exposed rats, suggesting that demyelination occurred in these white‐matter fiber tracts. Imaging findings were confirmed by conducting histological analysis using hematoxylin and eosin and Luxol fast blue stainings. In summary, structural abnormalities resulting from a MAM environmental challenge parallel cerebral pathology observed in schizophrenia. The MAM model incorporating noninvasive imaging techniques may therefore serve as an improved translational research tool for assessing new treatments for schizophrenia. Synapse, 2010. © 2010 Wiley‐Liss, Inc.     

Family Income and Parenting: The Role of Parental Depression and Social Support

This study examined the relations among family income, social support, parental depression, and parenting among 290 predominantly rural families with children at risk for disruptive or socially withdrawn behaviors. Structural equation modeling and multiple regression were used, and the results showed that low family income was related to high levels of parental depression, which in turn were associated with disruptive parenting. The findings also showed that social support mediated the adverse relationship between low family income and parental depression. Social support was directly related to positive parenting and indirectly related to parent‐child relational frustration via parental depression. Social support also moderated the indirect relationship between low family income and parenting. Implications for prevention intervention are discussed.     

Progression of Idiopathic Eruptive Macular Pigmentation in a Girl from Childhood to Adolescence: Case Report and Literature Review

A 14‐year‐old girl developed brownish round macules and patches over the face, trunk, and proximal limbs with extensive progression since she was 7 years old. Electron microscopy examination revealed an increase in the number and maturity of melanosomes in basal and suprabasal keratinocytes, although the number of melanocytes was within the normal range. A diagnosis of idiopathic eruptive macular pigmentation was made. We describe the unusual disease progression of this case of idiopathic eruptive macular pigmentation, which was thought to be self‐limited.     

Expression and purification of a recombinant form of human aromatase from Escherichia coli

Aromatase converts androgen to estrogen, a hormone that plays an important role in the development of breast cancer. Aromatase inhibitors have been shown to be a useful endocrine regimen for estrogen-dependent breast cancer. Structure-function studies of aromatase can generate critical structural information for designing highly potent and specific inhibitors. However, aromatase structure-function studies have been hampered by a lack of purified protein. In this report, we describe the construction and expression of a recombinant derivative of human aromatase in Escherichia coli using the pET vector system, and the purification of the enzyme by means of nickel-agarose affinity chromatography. We examined the expression of the full-length, Del-38, C-6xHis-tagged Del-38, and NC-6xHis-tagged Del-38 forms of aromatase. The recombinant aromatase without the first 38 amino acids from the amino-terminus (i.e. Del-38) was found to have a higher activity than the full-length enzyme. Moreover, the addition of two separate hexameric histidine tags at both the amino and the carboxyl-termini (i.e. NC-6xHis-tagged Del-38) increased the binding affinity of the recombinant enzyme to the nickel-agarose. The expressed aromatase (i.e. NC-6xHis-tagged Del-38 aromatase) was eluted from the nickel-agarose with 80 mM EDTA. The total aromatase activity of the 80 mM EDTA-eluted fractions was significantly higher than the detergent-solubilized protein extract, indicating a renaturation process during the nickel-agarose affinity chromatography. Purified aromatase exhibited a single band when analyzed by SDS-PAGE, and activity up to 5.8 nmol/mg/min was obtained using the tritiated water release assay. The K(m) value for androstenedione was determined to be 62+/-24 nM by enzyme kinetic analysis. The recombinant aromatase preparation was also characterized by reduced CO-difference spectral analysis, reaction product extraction assay, and inhibition studies using two aromatase inhibitors (letrozole and anastrozole). The results indicate that the recombinant aromatase from E. coli has catalytic properties identical to those of the enzyme expressed in human tissue and will be very useful for further structure-function studies of aromatase.