Optogenetics and deep brain stimulation neurotechnologies

Brain neural network is composed of densely packed, intricately wired neurons whose activity patterns ultimately give rise to every behavior, thought, or emotion that we experience. Over the past decade, a novel neurotechnique, optogenetics that combines light and genetic methods to control or monitor neural activity patterns, has proven to be revolutionary in understanding the functional role of specific neural circuits. We here briefly describe recent advance in optogenetics and compare optogenetics with deep brain stimulation technology that holds the promise for treating many neurological and psychiatric disorders

A Network Model of Local Field Potential Activity in Essential Tremor and the Impact of Deep Brain Stimulation

Essential tremor (ET), a movement disorder characterised by an uncontrollable shaking of the affected body part, is often professed to be the most common movement disorder, affecting up to one percent of adults over 40 years of age. The precise cause of ET is unknown, however pathological oscillations of a network of a number of brain regions are implicated in leading to the disorder. Deep brain stimulation (DBS) is a clinical therapy used to alleviate the symptoms of a number of movement disorders. DBS involves the surgical implantation of electrodes into specific nuclei in the brain. For ET the targeted region is the ventralis intermedius (Vim) nucleus of the thalamus. Though DBS is effective for treating ET, the mechanism through which the therapeutic effect is obtained is not understood. To elucidate the mechanism underlying the pathological network activity and the effect of DBS on such activity, we take a computational modelling approach combined with electrophysiological data. The pathological brain activity was recorded intra-operatively via implanted DBS electrodes, whilst simultaneously recording muscle activity of the affected limbs. We modelled the network hypothesised to underlie ET using the Wilson-Cowan approach. The modelled network exhibited oscillatory behaviour within the tremor frequency range, as did our electrophysiological data. By applying a DBS-like input we suppressed these oscillations. This study shows that the dynamics of the ET network support oscillations at the tremor frequency and the application of a DBS-like input disrupts this activity, which could be one mechanism underlying the therapeutic benefit

Genetic variation in the microRNA-499 gene and hepatocellular carcinoma risk in a Turkish population: Lack of any association in a case-control study

PubMedID: 22393998MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs with posttranscriptional regulatory functions as tumor suppressors and oncogenes. It has been suggested that the presence of single nucleotide polymorphisms (SNPs) in miRNAs can alter miRNA processing, expression, and/or binding to target mRNA and represent another type of genetic variability that can contribute to susceptibility to cancer development in humans. An adenine to guanine polymorphism (rs3746444), located in the sequence of miR-499, results in a change from A:U to G:U in its stem region. To determine the association of this polymorphism with the risk of hepatocellular carcinoma (HCC) in a Turkish population, a hospital-based case-control study was designed consisting of 222 subjects with HCC and 222 cancer-free control subjects matched for age, gender, smoking and alcohol status. The genotype frequency of the miR-499 rs3746444 polymorphism was determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. No statistically significant differences were found in the allele or genotype distributions of the miR-499 rs3746444 polymorphism among HCC and cancer-free control subjects (P>0.05). Our results demonstrate for the first time that the miR-499 rs3746444 polymorphism does not been any major role in genetic susceptibilty to hepatocellular carcinogenesis, at least in the population studied here. Independent studies are need to validate our findings in a larger series, as well as in patients of different ethnic origins

No association of pre-microRNA-146a rs2910164 polymorphism and risk of hepatocellular carcinoma development in Turkish population: A case-control study

PubMedID: 21807077Aim: MicroRNAs (miRNAs) are an abundant class of small non-protein coding RNAs with posttranscriptional regulatory functions as tumor suppressors and oncogenes. Aberrant expression and structural alteration of miRNAs are considered to participate in tumorigenesis and cancer development. It has been suggested that the presence of single nucleotide polymorphisms in precursor miRNAs (pre-miRNAs) can alter miRNA processing, expression, and/or binding to target mRNA and represent another type of genetic variability that can contribute to the susceptibility of human cancers. A G/C polymorphism (rs2910164), which is located in the sequence of miR-146a precursor, results in a change from G:U to C:U in its stem region. Methods: To determine the association of the miR-146a rs2910164 polymorphism on the risk of hepatocellular carcinoma (HCC) development in Turkish population, a hospital-based case-control study was designed consisting of 222 subjects with HCC and 222 cancer-free control subjects matched on age, gender, smoking and alcohol status. The genotype frequency of miR-146a rs2910164 polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Results: No statistically significant differences were found in the allele or genotype distributions of the miR-146a rs2910164 polymorphism among HCC and cancer-free control subjects (p> 0.05). Conclusion: Our results demonstrate that the miR-146a rs2910164 polymorphism has nomajor role in genetic susceptibility to hepatocellular carcinogenesis, at least in the population studied here. Independent studies are needed to validate our findings in a larger series, as well as in patients of different ethnic origins. © 2011 Elsevier B.V.TF2008BAP22The authors thank all the subjects who participated in this study. We also would like to thank Malik Atış for very helpful English corrections. This work was supported by Çukurova University Research Fund TF2008BAP22

The role of Interleukin 28B gene polymorphism in Turkish patients with hepatocellular carcinoma

PubMedID: 25332265Background and aim. Multiple risk factors lead to hepatocellular carcinoma (HCC) including viral infections, mutation and single nucleotide polymorphisms (SNPs). Interleukin 28B (IL28B) gene rs12979860 polymorphism has been shown to be associated with HCC in the different populations, but its association with HCC has not been investigated in the Turkish population. We investigated whether the rs12979860 polymorphism of IL28B gene affects the risk of HCC. Material and method. We performed genotyping analysis using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a hospital-based case-control study of 187 confirmed HCC patients and 208 healthy subjects (cancer and viral infection negative) in the Turkish population. Results. The allele and genotype analysis showed no significant differences between the risk of HCC and IL28B gene rs12979860 polymorphism (OR = 1.10; 95% 0.59-2.08 P = 0.76 for genotype). However, in the HBV-related HCC subgroup, the TT genotype increased a 1.46-fold the risk of developing HCC, but not statistically significant (OR = 1.46; 95% 0.71-2.97 P = 0.30). Furthermore, no significant differences were found between clinical findings, and sex in comparison with the IL28B genotypes in HCC group (P > 0.05). Conclusion. Our results suggest, for the first time, that no significant association were found between IL28B rs12979860 genotypes with the risk of developing HCC in Turkish patients. Further independent investigations are required to clarify the possible role of IL28B gene rs12979860 polymorphism on the risk of developing HCC in a larger series and also in patients of different ethnic origins. © 2014, Fundacion Clinica Medica Sur. All rights reserved

InVitro Antioxidant Activities of New 4,5-Dihydro-1H-1,2,4-triazol-5-ones having Thiophene Ring with their Acidic Properties

Abstract: Seven new 3-alkyl(aryl)-4-(2-thienymethylenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (2) were synthesized by the reactions of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (1) with thiophene-2-carbaldehyde. In addition, N-acetyl derivatives of compounds 2d-2g were also prepared. The structures of eleven new compounds synthesized were determined by elemental analysis as well as IR, NMR and UV spectral data. In addition, compounds 2a-g and 3a, 3b, 3d-f were also screened for their antioxidant activities and 2a-g were potentiometrically titrated with tetrabutylammonium hydroxide (TBAH) in four nonaqueous solvents (isopropyl alcohol, t-butyl alcohol, acetonitrile and N,N-dimethyl formamide). Also half-neutralization potential values and the corresponding pKa values were determined in all cases

Effect of PON1 gene polymorphisms in Turkish patients with hepatocellular carcinoma

Background: Reactive oxygen species (ROS) can oxidize biological molecules that mediate carcinogenesis by causing metabolic malfunction and damage to DNA. Human serum paraoxonases (PON1, PON2 and PON3) play a role in antioxidant defense and protect the cell against ROS. PON1 polymorphisms Q192R and L55M have been shown to be associated with several human cancers, but their association with hepatocellular carcinoma (HCC) has yet to be investigated. Methods: We performed genotyping analysis using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in a hospital-based case-control study of 217 confirmed HCC patients and 217 age-, gender-, smoking- and alcohol consumption-matched cancer-free controls in Turkish population. Results: Q192R and L55M polymorphisms were in significant linkage disequilibrium (LD) (D' = 0.77). However, allele, genotype and haplotype analysis showed no significant differences between the risks of HCC and PON1 polymorphisms. Moreover, no significant differences were found between clinical findings, clinicopathological features and sex in comparison with the PON1 genotypes in HCC group. Conclusion: Our results suggest for the first time that neither the Q192R polymorphism nor the L55M polymorphism has relationship with the risk of developing HCC. Further independent studies are required to clarify the possible role of PON1 gene Q192R and L55M polymorphisms on the risk of developing HCC in a larger series and also in patients of different ethnic origins. © 2013.TF2011BAP14This study was funded by the Çukurova University Research Fund TF2011BAP14

LIPID LOWERING THERAPY USE IN SECONDARY PREVENTION: AN ANALYSIS OF EPHESUS STUDY

87th Congress of the European-Atherosclerosis-Society (EAS) -- MAY 26-29, 2019 -- Maastricht, NETHERLANDSWOS: 000482110800616European Atherosclerosis So

Critical role of aquaporin-4 (AQP4) in astrocytic Ca2+ signaling events elicited by cerebral edema

Aquaporin-4 (AQP4) is a primary influx route for water during brain edema formation. Here, we provide evidence that brain swelling triggers Ca2+ signaling in astrocytes and that deletion of the Aqp4 gene markedly interferes with these events. Using in vivo two-photon imaging, we show that hypoosmotic stress (20% reduction in osmolarity) initiates astrocytic Ca2+ spikes and that deletion of Aqp4 reduces these signals. The Ca2+ signals are partly dependent on activation of P2 purinergic receptors, which was judged from the effects of appropriate antagonists applied to cortical slices. Supporting the involvement of purinergic signaling, osmotic stress was found to induce ATP release from cultured astrocytes in an AQP4-dependent manner. Our results suggest that AQP4 not only serves as an influx route for water but also is critical for initiating downstream signaling events that may affect and potentially exacerbate the pathological outcome in clinical conditions associated with brain edema