Development of wirelessly-powered, extracranial brain activator (ECBA) in a large animal model for the future non-invasive human neuromodulation

As transcranial electrical stimulation (tES) is an emerging and promising technique for neuromodulation, we developed a novel device; wirelessly-powered, extracranial brain activator (ECBA), which is mounted subcutaneously, and its neuromodulation effect was investigated. The oscillatory changes in electrocorticography (EcoG) were analyzed from two types of stimulation. Two weeks prior to the recording experiment, we underwent surgery for implantation of subdural strips and ECBA module over centroparietal regions of anesthetized beagles. Low-frequency stimulation (LFS) and subsequent high-frequency stimulation (HFS) protocols (600 pulses respectively) were applied. Then, the power changes before and after each stimulation in five different bands were compared. A significantly larger voltage difference with subcutaneous than transcutaneous stimulation measured at EcoG channels indicated a substantial current attenuation between the skin and skull. Compared with the baseline, all subjects showed consistently decreased delta power and increased gamma power after HFS. LFS also induced a similar, but opposite, pattern of power change in four beagles. The results from this study indicate that LFS and HFS with our novel ECBA can consistently and effectively modulate neural activity of the cortex, inducing neural inhibition and facilitation functions, respectively. Future studies are necessary to further ensuring a consistent efficacy and long-term safety.11Ysciescopu

Free carrier screening in coupled asymmetric GaN quantum discs

We present an investigation of free-carrier screening in coupled asymmetric GaN quantum discs with embedded AlGaN barriers using time-integrated and time-resolved micro-photoluminescence measurements, supported by three-dimensional multi-band k.p computational modeling. We observe that with increasing optical excitation the carrier lifetime decreases and emission energy blue-shifts. This originates from the screening of built-in piezo- and pyroelectric fields in the quantum discs by photo-generated free-carriers. Due to non-resonant tunneling of carriers from the smaller disc to the larger disc, free carrier screening is enhanced in the larger disc. The non-resonant tunneling was found to have a significant role in samples with a thin barrier, as the screening decreased with barrier thickness (i.e. decreased tunneling). Computational modeling, was in good agreement with the experimental results

Ptch2/Gas1 and Ptch1/Boc differentially regulate Hedgehog signalling in murine primordial germ cell migration.

Gas1 and Boc/Cdon act as co-receptors in the vertebrate Hedgehog signalling pathway, but the nature of their interaction with the primary Ptch1/2 receptors remains unclear. Here we demonstrate, using primordial germ cell migration in mouse as a developmental model, that specific hetero-complexes of Ptch2/Gas1 and Ptch1/Boc mediate the process of Smo de-repression with different kinetics, through distinct modes of Hedgehog ligand reception. Moreover, Ptch2-mediated Hedgehog signalling induces the phosphorylation of Creb and Src proteins in parallel to Gli induction, identifying a previously unknown Ptch2-specific signal pathway. We propose that although Ptch1 and Ptch2 functionally overlap in the sequestration of Smo, the spatiotemporal expression of Boc and Gas1 may determine the outcome of Hedgehog signalling through compartmentalisation and modulation of Smo-downstream signalling. Our study identifies the existence of a divergent Hedgehog signal pathway mediated by Ptch2 and provides a mechanism for differential interpretation of Hedgehog signalling in the germ cell niche

Effectiveness of flow obstructions in enhancing electro-osmotic flow

In this paper the influence of obstructions on micro-channel electroosmotic flow is investigated for the first time. To carry out such a study, regular obstructions are introduced into micro-channels and flow rates are numerically calculated. The effect of channel width on flow rates is analysed on both free and obstructed channels. The solid material considered for channel walls and obstructions is silicon and the electrolyte is de-ionised water. The parameters studied include channel width, obstruction size and effective porosity of the channel. The effective porosity is varied between 0.4 and 0.8 depending on other chosen parameters. The results clearly demonstrate that, under the analysed conditions, introduction of obstructions into channels wider than100 micro meters enhances the flow rate induced by electro-osmosis

Simultaneous development of adenocarcinoma and gastrointestinal stromal tumor (GIST) in the stomach: case report

<p>Abstract</p> <p>Background</p> <p>Gastrointestinal stromal tumors (GISTs) and adenocarcinoma are distinct neoplasms originating from different cell layers. Approximately 20% of patients with GIST develop other cancers.</p> <p>Case presentation</p> <p>We report a case of the coexistence of adenocarcinoma and gastrointestinal stromal tumor (GIST). Gastric endoscopy showed the ulcerated tumor with bleeding along the lesser curvature of the proximal stomach and a submucosal nodule that measured about 3 cm in diameter in the lower part of the stomach body. Their pathological examination showed gastric cancer (poorly differentiated diffuse adenocarcinoma) and GIST (low-risk category). Further, immunohistochemical staining for C-kit and CD34 was positive, while that for SMA and S-100 was negative.</p> <p>Conclusion</p> <p>Although it is not easy to speculate on the coexistence of adenocarcinoma and GIST, pre-and post-operative diagnoses may be essential, and such cancer development is not considered to be unusual.</p

Microevolution of Helicobacter pylori during prolonged infection of single hosts and within families

Our understanding of basic evolutionary processes in bacteria is still very limited. For example, multiple recent dating estimates are based on a universal inter-species molecular clock rate, but that rate was calibrated using estimates of geological dates that are no longer accepted. We therefore estimated the short-term rates of mutation and recombination in Helicobacter pylori by sequencing an average of 39,300 bp in 78 gene fragments from 97 isolates. These isolates included 34 pairs of sequential samples, which were sampled at intervals of 0.25 to 10.2 years. They also included single isolates from 29 individuals (average age: 45 years) from 10 families. The accumulation of sequence diversity increased with time of separation in a clock-like manner in the sequential isolates. We used Approximate Bayesian Computation to estimate the rates of mutation, recombination, mean length of recombination tracts, and average diversity in those tracts. The estimates indicate that the short-term mutation rate is 1.4×10−6 (serial isolates) to 4.5×10−6 (family isolates) per nucleotide per year and that three times as many substitutions are introduced by recombination as by mutation. The long-term mutation rate over millennia is 5–17-fold lower, partly due to the removal of non-synonymous mutations due to purifying selection. Comparisons with the recent literature show that short-term mutation rates vary dramatically in different bacterial species and can span a range of several orders of magnitude

The chalcone butein from Rhus verniciflua Stokes inhibits clonogenic growth of human breast cancer cells co-cultured with fibroblasts

BACKGROUND: Butein (3,4,2',4'-tetrahydroxychalone), a plant polyphenol, is a major biologically active component of the stems of Rhus verniciflua Stokes. It has long been used as a food additive in Korea and as an herbal medicine throughout Asia. Recently, butein has been shown to suppress the functions of fibroblasts. Because fibroblasts are believed to play an important role in promoting the growth of breast cancer cells, we investigated the ability of butein to inhibit the clonogenic growth of small numbers of breast cancer cells co-cultured with fibroblasts in vitro. METHODS: We first measured the clonogenic growth of small numbers of the UACC-812 human breast cancer cell line co-cultured on monolayers of serum-activated, human fibroblasts in the presence of butein (2 μg/mL) or various other modulators of fibroblast function (troglitazone-1 μg/mL; GW9662-1 μM; meloxican-1 μM; and 3,4 dehydroproline-10 μg/mL). In a subsequent experiment, we measured the dose-response effect on the clonogenic growth of UACC-812 breast cancer cells by pre-incubating the fibroblasts with varying concentrations of butein (10 μg/ml-1.25 μg/mL). Finally, we measured the clonogenic growth of primary breast cancer cells obtained from 5 clinical specimens with normal fibroblasts and with fibroblasts that had been pre-treated with a fixed dose of butein (2.5 μg/mL). RESULTS: Of the five modulators of fibroblast function that we tested, butein was by far the most potent inhibitor of clonogenic growth of UACC-812 breast cancer cells co-cultured with fibroblasts. Pre-treatment of fibroblasts with concentrations of butein as low as 2.5 μg/mL nearly abolished subsequent clonogenic growth of UACC-812 breast cancer cells co-cultured with the fibroblasts. A similar dose of butein had no effect on the clonogenic growth of breast cancer cells cultured in the absence of fibroblasts. Significantly, clonogenic growth of the primary breast cancer cells was also significantly reduced or abolished when the tumor cells were co-cultured with fibroblasts that had been pre-treated with a fixed dose of butein. CONCLUSION: We conclude that fibroblasts pre-treated with non-toxic doses of butein (a natural herbal compound) no longer support the clonogenic growth of small numbers of primary breast cancer cells seeded into co-cultures. These results suggest that interference with the interaction between fibroblasts and breast cancer cells by the natural herbal compound, butein, should be further investigated as a novel experimental approach for possibly suppressing the growth of micrometastases of breast cancer

Downregulation of TGF-beta receptor types II and III in oral squamous cell carcinoma and oral carcinoma-associated fibroblasts

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to assess the expression levels for TβRI, TβRII, and TβRIII in epithelial layers of oral premalignant lesions (oral leukoplakia, OLK) and oral squamous cell carcinoma (OSCC), as well as in oral carcinoma-associated fibroblasts (CAFs), with the final goal of exploring the roles of various types of TβRs in carcinogenesis of oral mucosa.</p> <p>Methods</p> <p>Normal oral tissues, OLK, and OSCC were obtained from 138 previously untreated patients. Seven primary human oral CAF lines and six primary normal fibroblast (NF) lines were established successfully via cell culture. The three receptors were detected using immunohistochemical (IHC), quantitative RT-PCR, and Western blot approaches.</p> <p>Results</p> <p>IHC signals for TβRII and TβRIII in the epithelial layer decreased in tissue samples with increasing disease aggressiveness (P < 0.05); no expression differences were observed for TβRI, in OLK and OSCC (P > 0.05); and TβRII and TβRIII were significantly downregulated in CAFs compared with NFs, at the mRNA and protein levels (P < 0.05). Exogenous expression of TGF-β1 led to a remarkable decrease in the expression of TβRII and TβRIII in CAFs (P < 0.05).</p> <p>Conclusion</p> <p>This study provides the first evidence that the loss of TβRII and TβRIII expression in oral epithelium and stroma is a common event in OSCC. The restoration of the expression of TβRII and TβRIII in oral cancerous tissues may represent a novel strategy for the treatment of oral carcinoma.</p