Fast-Charging and High Volumetric Capacity Anode Based on Co3 O4 /CuO@TiO2 Composites for Lithium-Ion Batteries.

This paper presents an investigation of anodic TiO2 nanotube arrays (TNAs), with a Co3 O4 /CuO coating, for lithium-ion batteries (LIBs). The coated TNAs are investigated using various analytical techniques, with the results clearly suggesting that the molar ratio of Co3 O4 /CuO in the TiO2 nanotubes substantially influences its battery performance. In particular, a cobalt/copper molar ratio of 2:1 on the TNAs (Co2 Cu1 @TNAs) features the best LIBs anode performance, exhibiting high reversible capacity and enhanced cycling stability. Noticeably, Co2 Cu1 @TNAs achieve excellent rate capability even after quite a high current density of 20.0 A g-1 (≈25 C, where C corresponds to complete discharge in 1 h) and superior volumetric reversible capacity of ≈3330 mA h-1 cm-3 . This value is approximately seven times higher than those of a graphite-based anode. This outstanding performance is attributed to the synergistic effects of Co2 Cu1 @TNAs: 1) the structural advantage of TNAs, with their large amount of free space to accommodate the large volume expansion during Li+ insertion/extraction and 2) the optimized ratio of Co3 O4 and CuO in the composite for improved capacity. In addition, no binder or conductive agent is used, which is partly responsible for the overall improved volumetric capacity and electrochemical performance.

A pathway-based approach for identifying biomarkers of tumor progression to trastuzumab-resistant breast cancer.

Although trastuzumab is a successful targeted therapy for breast cancer patients with tumors expressing HER2 (ERBB2), many patients eventually progress to drug resistance. Here, we identified subpathways differentially expressed between trastuzumab-resistant vs. -sensitive breast cancer cells, in conjunction with additional transcriptomic preclinical and clinical gene datasets, to rigorously identify overexpressed, resistance-associated genes. From this approach, we identified 32 genes reproducibly upregulated in trastuzumab resistance. 25 genes were upregulated in drug-resistant JIMT-1 cells, which also downregulated HER2 protein by >80% in the presence of trastuzumab. 24 genes were downregulated in trastuzumab-sensitive SKBR3 cells. Trastuzumab sensitivity was restored by siRNA knockdown of these genes in the resistant cells, and overexpression of 5 of the 25 genes was found in at least one of five refractory HER2 + breast cancer. In summary, our rigorous computational approach, followed by experimental validation, significantly implicate ATF4, CHEK2, ENAH, ICOSLG, and RAD51 as potential biomarkers of trastuzumab resistance. These results provide further proof-of-concept of our methodology for successfully identifying potential biomarkers and druggable signal pathways involved in tumor progression to drug resistance.

Automated genome-wide visual profiling of cellular proteins involved in HIV infection.

Recent genome-wide RNAi screens have identified >842 human genes that affect the human immunodeficiency virus (HIV) cycle. The list of genes implicated in infection differs between screens, and there is minimal overlap. A reason for this variance is the interdependence of HIV infection and host cell function, producing a multitude of indirect or pleiotropic cellular effects affecting the viral infection during RNAi screening. To overcome this, the authors devised a 15-dimensional phenotypic profile to define the viral infection block induced by CD4 silencing in HeLa cells. They demonstrate that this phenotypic profile excludes nonspecific, RNAi-based side effects and viral replication defects mediated by silencing of housekeeping genes. To achieve statistical robustness, the authors used automatically annotated RNAi arrays for seven independent genome-wide RNAi screens. This identified 56 host genes, which reliably reproduced CD4-like phenotypes upon HIV infection. The factors include 11 known HIV interactors and 45 factors previously not associated with HIV infection. As proof of concept, the authors confirmed that silencing of PAK1, Ku70, and RNAseH2A impaired HIV replication in Jurkat cells. In summary, multidimensional, visual profiling can identify genes required for HIV infection.

Visual genome-wide RNAi screening to identify human host factors required for Trypanosoma cruzi infection.

The protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a neglected tropical infection that affects millions of people in the Americas. Current chemotherapy relies on only two drugs that have limited efficacy and considerable side effects. Therefore, the development of new and more effective drugs is of paramount importance. Although some host cellular factors that play a role in T. cruzi infection have been uncovered, the molecular requirements for intracellular parasite growth and persistence are still not well understood. To further study these host-parasite interactions and identify human host factors required for T. cruzi infection, we performed a genome-wide RNAi screen using cellular microarrays of a printed siRNA library that spanned the whole human genome. The screening was reproduced 6 times and a customized algorithm was used to select as hits those genes whose silencing visually impaired parasite infection. The 162 strongest hits were subjected to a secondary screening and subsequently validated in two different cell lines. Among the fourteen hits confirmed, we recognized some cellular membrane proteins that might function as cell receptors for parasite entry and others that may be related to calcium release triggered by parasites during cell invasion. In addition, two of the hits are related to the TGF-beta signaling pathway, whose inhibition is already known to diminish levels of T. cruzi infection. This study represents a significant step toward unveiling the key molecular requirements for host cell invasion and revealing new potential targets for antiparasitic therapy.

Interleukin-6 and the hypothalamic-pituitary-adrenal activation in a tumor bearing mouse.

Tumor derived cytokines have been suggested to activate the hypothalamic-pituitary-adrenal (HPA) axis; that is, increase the hypothalamic releases of corticotropin-releasing hormone (CRH) and adrenocorticotrophic hormone. The authors previously reported that tumor mice bearing a human oral squamous cell carcinoma exhibit an anorectic phenotype with increased expression of CRH mRNA in their hypothalamic paraventricular nuclei. This study examined the plasma levels of tumor-derived cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), in order to determine potential mediator(s) implicated in CRH expression in this tumor mouse model. Plasma corticosterone levels were assayed as well to confirm the HPA activation. In the results, plasma levels of IL-6, but not TNF-alpha, were increased significantly in the tumor mice compared with age-matching non-tumor controls. Plasma corticosterone levels were also increased in the tumor mice. These results together with the previous findings suggest IL-6 as a potential mediator in the control of hypothalamic CRH expression in the authors' tumor mouse model.

Dexamethasone reduces food intake, weight gain and the hypothalamic 5-HT concentration and increases plasma leptin in rats.

This study was conducted to define the regulatory mechanisms underlying stress-induced decreases in food intake and weight gain. Rats received a single or 4 daily injections of dexamethasone (0.1 or 1 mg/kg). Food intake and weight gain were recorded, and plasma leptin, brain contents of serotonin (5-hydroxytryptamine; 5-HT), 5-hydroxy-indole-acetic acid (5-HIAA) and the raphe expression of tryptophan hydroxylase (TPH), monoamine oxidase A (MAO-A) and 5-HT reuptake transporter (5-HTT) genes were examined. A single injection of dexamethasone did not acutely affect food intake, but cumulative food intake and weight gain were suppressed dose-dependently by daily injections of dexamethasone. Both a single and repeated injections of dexamethasone elevated plasma leptin in a dose dependent manner. 5-HT contents in the hypothalamus was decreased, but 5-HIAA increased, both by a single and repeated dexamethasone. A single injection of dexamethasone did not affect mRNA expressions of TPH, MAO-A and 5-HTT genes, but repeated dexamethasone increased them in the dorsal raphe nucleus. These results suggest that plasma leptin may play a role in dexamethasone-induced anorexia. Additionally, increased expression of MAO-A and 5-HTT genes by repeated dexamethasone appears to be implicated in decreases of the brain 5-HT contents.

Ovariectomy ameliorates dextromethorphan--induced memory impairment in young female rats.

We have previously found that dextromethorphan (DM), over-the-counter cough suppressant, impairs memory retention in water maze task, when it is repeatedly administrated to adolescent female rats at high doses. In this study we examined first if ovariectomy ameliorates the DM-induced memory impairment in female rats, and then whether or not the DM effect is revived by estrogen replacement in ovariectomized female rats. Female rat pups received bilateral ovariectomy or sham operation on postnatal day (PND) 21, and then intraperitoneal DM (40 mg/kg) daily during PND 28-37. Rats were subjected to the Morris water maze task from PND 38, approximately 24 h after the last DM injection. In probe trial, goal quadrant dwell time was significantly reduced by DM in the sham operated group, however, the reduction by DM did not occur in the ovariectomy group. When 17beta-estradiol was supplied to ovariectomized females during DM treatment, the goal quadrant dwell time was significantly decreased, compared to the vehicle control group. Furthermore, a major effect of estrogen replacement was found in the escape latency during the last 3 days of initial learning trials. These results suggest that ovariectomy may ameliorate the adverse effect of DM treatment on memory retention in young female rats, and that estrogen replacement may revive it, i.e. estrogen may take a major role in DM-induced memory impairment in female rats.

Serotonin transporter mRNA expression in the dorsal raphe nucleus of a tumor bearing mouse.

This study was conducted to determine if an oral squamous cell carcinoma alters mRNA expression of serotonin transporter (5-HTT) in the central nervous system. KB cell line derived from a human oral squamous cell carcinoma was inoculated into nude mice, and mRNA expression level of 5-HTT in the dorsal raphe nucleus (DRN) was examined by in situ hybridization when the tumor mass reached to -10% of total body weight. Plasma leptin levels were determined by radioimmunoassay method using a commercial kit. 5-HTT mRNA level was significantly decreased in the DRN of tumor bearing mice, compared to the age-matching non-tumor control. Plasma leptin level decreased concomitantly in tumor bearing mice. These results suggest that oral carcinoma may suppress 5-HTT gene expression in the central nervous system, perhaps in relation with decreased plasma leptin level.