Frequency-dependent modulation of cerebellar excitability during the application of non-invasive alternating current stimulation

Background: it is well-known that the cerebellum is critical for the integrity of motor and cognitive actions. Applying non-invasive brain stimulation techniques over this region results in neurophysiological and behavioural changes, which have been associated with the modulation of cerebellar-cerebral cortex connectivity. Here, we investigated whether online application of cerebellar transcranial alternating current stimulation (tACS) results in changes to this pathway. Methods: thirteen healthy individuals participated in two sessions of cerebellar tACS delivered at different frequencies (5Hz and 50Hz). We used transcranial magnetic stimulation to measure cerebellar-motor cortex (M1) inhibition (CBI), short-intracortical inhibition (SICI) and short-afferent inhibition (SAI) before, during and after the application of tACS. Results: we found that CBI was specifically strengthened during the application of 5Hz cerebellar tACS. No changes were detected immediately following the application of 5Hz stimulation, nor at any time point with 50Hz stimulation. We also found no changes to M1 intracortical circuits (i.e. SICI) or sensorimotor interaction (i.e. SAI), indicating that the effects of 5Hz tACS over the cerebellum are site-specific. Conclusions: cerebellar tACS can modulate cerebellar excitability in a time- and frequency-dependent manner. Additionally, cerebellar tACS does not appear to induce any long-lasting effects (i.e. plasticity), suggesting that stimulation enhances oscillations within the cerebellum only throughout the stimulation period. As such, cerebellar tACS may have significant implications for diseases manifesting with abnormal cerebellar oscillatory activity and also for future behavioural studies

Novel monoclonal antibodies detect Smad-Interacting Protein 1 (SIP1) in the cytoplasm of human cells from multiple tumor tissue arrays

Cataloged from PDF version of article.Smad-interacting protein 1 (SIP1, also known as ZEB2) represses the transcription of E-cadherin and mediates epithelial-mesenchymal transition in development and tumor metastasis. Due to the lack of human SIP1-specific antibodies, its expression in human tumor tissues has not been studied in detail by immunohistochemistry. Hence, we generated two anti-SIP1 monoclonal antibodies, clones 1C6 and 6E5, with IgG1 and IgG2a isotypes, respectively. The specificity of these antibodies was shown by Western blotting studies using siRNA mediated downregulation of SIP1 and ZEB1 in a human osteosarcoma cell line. In the same context, we also compared them with 5 commercially available SIP1 antibodies. Antibody specificity was further verified in an inducible cell line system by immunofluorescence. By using both antibodies, we evaluated the tissue expression of SIP1 in paraffin-embedded tissue microarrays consisting of 22 normal and 101 tumoral tissues of kidney, colon, stomach, lung, esophagus, uterus, rectum, breast and liver. Interestingly, SIP1 predominantly displayed a cytoplasmic expression, while the nuclear localization of SIP1 was observed in only 6 cases. Strong expression of SIP1 was found in distal tubules of kidney, glandular epithelial cells of stomach and hepatocytes, implicating a co-expression of SIP1 and E-cadherin. Squamous epithelium of the esophagus and surface epithelium of colon and rectum were stained with moderate to weak intensity. Normal uterus, breast and lung tissues remained completely negative. By comparison with their normal tissues, we observed SIP1 overexpression in cancers of the kidney, breast, lung and uterus. However, SIP1 expression was found to be downregulated in tumors from colon, rectum, esophagus, liver and stomach tissues. Finally we did nuclear/cytoplasmic fractionation in 3 carcinoma cell lines and detected SIP1 in both fractions, nucleus being the dominant one. To our best knowledge, this is the first comprehensive immunohistochemical study of the expression of SIP1 in a series of human cancers. Our finding that SIP1 is not exclusively localized to nucleus suggests that the subcellular localization of SIP1 is regulated in normal and tumor tissues. These novel monoclonal antibodies may help elucidate the role of SIP1 in tumor development. © 2010 Elsevier Inc

Ischemia modified albumin and thiol/disulfide balance in patients with Hashimoto’s thyroiditis

Hashimoto thyroiditis is a common cause of goiter and acquired hypothyroidism in individuals residing in areas of no iodine deficiency. The fact that the structure of serum albumin exhibits changes in ischemic conditions has paved the way for the discovery of a new serum cardiac ischemia marker, Ischemia Modified Albumin. The other one, thiol/disulphide homeostasis, plays an important part in antioxidative protection, detoxification, cell growth, and apoptosis. In this study, we aimed to investigate both the relationship between Thiol/Disulphide homeostasis and Ischemia Modified Albumin in patients diagnosed with Hashimoto’s Thyroiditis. A total of 70 Hashimoto’’s thyroiditis patients and 50 healthy ones were included in this study. Age, gender, thyroid-stimulating hormone (TSH), anti-thyroid peroxidase (TPO), anti-thyroglobulin (TG) levels were recorded. Ischemia Modified Albumin and thiol-disulphid homeostasis parameters were measured through automated spectrophotometric methods. The ages of individuals included in the study ranged from 35 to 58 years. The native thiol/total thiol were found to be significantly lower in Hashimoto patients when compared to those enrolled in the control group (P < 0.05), whereas the Ischemia Modified Albumin, disulphide, native thiol, total thiol, disulphide/native thiol, and disulphide/total thiol were found to be significantly higher in Hashimoto patients when compared to those in the control (P < 0.05). Increased Ischemia Modified Albumin, native and total thiol, and disulphide levels are related to increased oxidative stress. Although Ischemia Modified Albumin and Thiol-disulphide defense are important oxidative indicators in Hashimoto’s Thyroiditis, many determinants are known to be involved in this process

Surveillance of Complex Auction Markets: a Market Policy Analytics Approach

The dissertation consists of four essays that investigates the merits of big data-driven decision-making in the surveillance of complex auction markets. In the first essay, Avci and her co-researchers examine the aggregate-level bidding strategies and market efficiency in a multi-time tariff setting by using parametric and semi parametric methods. In the second essay, they address three key forecasting challenges; risk of selection of an inadequate forecasting method and transparency level of the market and market-specific multi-seasonality factors in a semi-transparent auction market. In the third essay, they demonstrate the effect of information feedback mechanisms on bidders’ price expectations in complex auction markets with the existence of forward contracts. They develop a research model that empirically tests the impact of bidders’ attitudes on their price expectation through their trading behavior and tested their hypotheses on real ex-ante forecasts, evaluated ex-post. In the fourth essay, they investigate characterization of bidding strategies in an oligopolistic multi-unit auction and then examine the interactions between different strategies and auction design parameters. This dissertation offers important implications to theory and practice of surveillance of complex auction markets. From the theoretical perspective, this is, to our best knowledge, the first research that systematically examines the interplay of different informational and strategic factors in oligopolistic multi-unit auction markets. From the policy perspective, Avci’s research shows that integration of big data analytics and domain-specific knowledge improves decision-making in surveillance of complex auction markets