Vapor phase synthesis of ferroelectric microislands on PVDF thin films.

The interest in patterned polyvinylidene fluoride (PVDF) surfaces has grown significantly in the recent years due to ability to control the ferroelectric behavior through the size and shape of the surface structures. However, forming micron sized structures on the PVDF surface generally requires laborious lithography based methods or use of templates which complicates the process. In this study, we report spontaneous formation of microislands with ferroelectric response during PVDF growth via initiated chemical vapor deposition. Depositions performed under continuous and no flow conditions show that laminar precursor flow to the surface yield homogenous thin films, whereas no flow conditions of the batch mode result in the growth of surface protrusions (microislands) with higher polar phase content. Formation of these surface instabilities after an incubation time indicates the presence of local stress fields building with time, resulting in formation of the islands with higherßphase fraction to release the stress. Furthermore, the increased mobility of the polymer chains at high temperatures reduces the stress field, leading to lowerß/αphase ratios in smaller microislands.

Caveolin-1 promotes gastric cancer progression by up-regulating epithelial to mesenchymal transition by crosstalk of signalling mechanisms under hypoxic condition.

Gastric cancer is the second most fatal common form of cancer. The crosstalk among signalling pathways that results in the acceleration of epithelial to mesenchymal transition (EMT) plays a pivotal role in the molecular mechanism of gastric carcinogenesis. To understand the role of caveolin-1 (Cav-1), the expression pattern was studied in human gastric adenocarcinoma tissues and also in AGS and KATO III cell lines. Here, we show that during hypoxic condition, the increase in the levels of hypoxia-inducible factor-1α (HIF-1α) results in a significant decrease in the expression of caveolin-1 which is regulated by heat shock protein 90 (HSP90). The reduced levels of Cav-1 correlated with the increased epidermal growth factor receptor (EGFR) activation resulting in the significant activation of its downstream target STAT3. Accumulation of pSTAT3 in the nucleus results in the decreased expression of E-cadherin and increased expression of mesenchymal markers (Slug, α-SMA, N-cadherin and vimentin). Crosstalk of EGFR and transforming growth factor ß (TGF-ß) signalling with Wnt signalling enhances cell proliferation, cell survival and upregulates EMT. There was no significant alteration in the expression of epithelial and mesenchymal molecules in both the cell lines studied. Thus, we provide evidence that Cav-1 was modulated by HSP90 and functions as a crucial regulator of EMT in gastric cancer.

Developmental changes in BDNF protein in the song control nuclei of zebra finches.

The zebra finch song system provides an excellent model to study the mechanisms underlying the development of sex difference in brain structure and function. Only male zebra finches sing and the brain nuclei controlling song learning and production are considerably larger than in females. Sexual differentiation may in part be regulated by estrogen, but other molecules including neurotrophic factors likely also affect masculinization. Brain derived neurotrophic factor (BDNF) plays a crucial role in numerous aspects of vertebrate brain development and function, including neurogenesis, cell survival, growth of axonal projections, synaptogenesis and processes linked to learning and memory. The current study investigated the expression of BDNF protein in juvenile males and females at four ages, as well as in adults, to begin to evaluate the potential roles of endogenous BDNF in particular stages of structural and functional development of the song system. In both HVC and the robust nucleus of the arcopallium (RA), males had more BDNF+ cells than females. The number of immunopositive cells increased in males and decreased in females as they matured, in a pattern generally consistent with a role for BDNF in sensorimotor integration of song learning. In addition, in HVC (but not RA) the ratio of mature BDNF compared to its precursor proBDNF was greater in adult males than those at post-hatching day 25, indicating a region-specific shift in the relative availability of the two forms. Collectively, the data suggest that changes in BDNF protein expression across development may be associated with song system maturation, particularly during the sensorimotor integration of masculine vocalizations.

The Hsp90 inhibitor SNX-2112, induces apoptosis in multidrug resistant K562/ADR cells through suppression of Akt/NF-κB and disruption of mitochondria-dependent pathways.

Heat shock protein 90 (Hsp90) serves as an ATP-dependent molecular chaperone for numerous cell signaling proteins, including many oncogenes and clinically validated cancer targets that are involved in cell proliferation and survival. Recent studies have shown that the Hsp90 inhibitor, SNX-2112, effectively inhibits tumor cell growth and angiogenesis in hematological and solid tumors. However, little is known about the effects of SNX-2112 on leukemias that are resistant to chemotherapy, which is emerging as a major clinical problem. In this study, the effects of SNX-2112 on the multidrug-resistant human chronic myeloid leukemia (CML) K562/ADR cell line were investigated. We observed that SNX-2112 exhibited dose- and time-dependent inhibitory activities against K562/ADR cells. These effects included the induction of apoptosis and secondary necrosis in addition to cell cycle arrest at the G1 and G2 phases. Furthermore, SNX-2112-induced apoptosis was predominantly mediated by the mitochondrial pathway, initiated by the release of cytochrome c and the participation of Bcl-2 family proteins. SNX-2112 also induced the activation of the caspase-3, -8 and -9 cascade and the subsequent cleavage of PARP in K562/ADR cells. Moreover, the inactivation of the Akt and NF-κB signaling pathways may be involved in SNX-2112-induced apoptosis. The expression levels of P-glycoprotein (P-gp) and several chaperons related to drug resistance and apoptosis were also shown to be inhibited, including the Grp78 and Hsp90 isoforms, Grp94 and Trap1. Taken together, these results provide a possible molecular mechanism for the anti-cancer effect of SNX-2112 on K562/ADR cells and provide new insights into the future application of SNX-2112 as a therapeutic agent for anti-multidrug-resistant leukemias.

Effect of leptin treatment on mitochondrial function in obese leptin-deficient ob/ob mice.

OBJECTIVE: Leptin stimulates peripheral lipid oxidation, but the influence on mitochondrial function is partly unknown. We investigated tissue-specific mitochondrial function in leptin-deficient obese C57BL/6J-ob/ob mice compared to lean littermates following leptin treatment. MATERIALS AND METHODS: Lean and obese ob/ob mice were treated with saline or leptin for 5 days. At day six, liver, extensor digitorum longus (EDL) and soleus muscle were dissected and mitochondrial respiration analyzed in freshly dissected tissues. Expression of key proteins in the regulation of mitochondrial function was determined. RESULTS: In liver, mitochondrial respiration was reduced in ob/ob mice compared to lean mice. Expression of mitochondrial transcription factor A (TFAM) was decreased in ob/ob mice, but increased with leptin treatment. In glycolytic EDL muscle, mitochondrial respiration was increased in ob/ob mice. Protein markers of complex II, IV and ATP synthase were increased in EDL muscle from both saline- and leptin-treated ob/ob mice. TFAM protein abundance was decreased, while dynamin-1-like protein was increased in EDL muscle from saline-treated ob/ob mice and restored by leptin treatment. In oxidative soleus muscle, mitochondrial respiration and electron transport system protein abundance were unchanged, while TFAM was reduced in ob/ob mice. CONCLUSIONS: In conclusion, leptin-deficient ob/ob mice display tissue-specific mitochondrial adaptations under basal conditions and in response to leptin treatment. Mitochondrial respiration was decreased in liver, increased in glycolytic muscle and unaltered in oxidative muscle from ob/ob mice. Insight into the tissue-specific regulation of mitochondrial function in response to energy supply and demand may provide new opportunities for the treatment of insulin resistance.