Allylic ionic liquid electrolyte-assisted electrochemical surface passivation of LiCoO2 for advanced, safe lithium-ion batteries

Room-temperature ionic liquid (RTIL) electrolytes have attracted much attention for use in advanced, safe lithium-ion batteries (LIB) owing to their nonvolatility, high conductivity, and great thermal stability. However, LIBs containing RTIL-electrolytes exhibit poor cyclability because electrochemical side reactions cause problematic surface failures of the cathode. Here, we demonstrate that a thin, homogeneous surface film, which is electrochemically generated on LiCoO2 from an RTIL-electrolyte containing an unsaturated substituent on the cation (1-allyl-1-methylpiperidinium bis(trifluoromethanesulfonyl)imide, AMPip-TFSI), can avert undesired side reactions. The derived surface film comprised of a high amount of organic species from the RTIL cations homogenously covered LiCoO2 with a ,25 nm layer and helped suppress unfavorable thermal reactions as well as electrochemical side reactions. The superior performance of the cell containing the AMPip-TFSI electrolyte was further elucidated by surface, electrochemical, and thermal analyses.open1

Ebola and Marburg Hemorrhagic Fevers: Neglected Tropical Diseases?

Ebola hemorrhagic fever (EHF) and Marburg hemorrhagic fever (MHF) are rare viral diseases, endemic to central Africa. The overall burden of EHF and MHF is small in comparison to the more common protozoan, helminth, and bacterial diseases typically referred to as neglected tropical diseases (NTDs). However, EHF and MHF outbreaks typically occur in resource-limited settings, and many aspects of these outbreaks are a direct consequence of impoverished conditions. We will discuss aspects of EHF and MHF disease, in comparison to the “classic” NTDs, and examine potential ways forward in the prevention and control of EHF and MHF in sub-Saharan Africa, as well as examine the potential for application of novel vaccines or antiviral drugs for prevention or control of EHF and MHF among populations at highest risk for disease

Utilizing individual fish biomass and relative abundance models to map environmental niche associations of adult and juvenile targeted fishes

Many fishes undergo ontogenetic habitat shifts to meet their energy and resource needs as they grow. Habitat resource partitioning and patterns of habitat connectivity between conspecific fishes at different life-history stages is a significant knowledge gap. Species distribution models were used to examine patterns in the relative abundance, individual biomass estimates and environmental niche associations of different life stages of three iconic West Australian fishes. Continuous predictive maps describing the spatial distribution of abundance and individual biomass of the study species were created as well predictive hotspot maps that identify possible areas for aggregation of individuals of similar life stages of multiple species (i.e. spawning grounds, fisheries refugia or nursery areas). The models and maps indicate that processes driving the abundance patterns could be different from the body size associated demographic processes throughout an individual's life cycle. Incorporating life-history in the spatially explicit management plans can ensure that critical habitat of the vulnerable stages (e.g. juvenile fish, spawning stock) is included within proposed protected areas and can enhance connectivity between various functional areas (e.g. nursery areas and adult populations) which, in turn, can improve the abundance of targeted species as well as other fish species relying on healthy ecosystem functioning

Finding the Needles in the Metagenome Haystack

In the collective genomes (the metagenome) of the microorganisms inhabiting the Earth’s diverse environments is written the history of life on this planet. New molecular tools developed and used for the past 15 years by microbial ecologists are facilitating the extraction, cloning, screening, and sequencing of these genomes. This approach allows microbial ecologists to access and study the full range of microbial diversity, regardless of our ability to culture organisms, and provides an unprecedented access to the breadth of natural products that these genomes encode. However, there is no way that the mere collection of sequences, no matter how expansive, can provide full coverage of the complex world of microbial metagenomes within the foreseeable future. Furthermore, although it is possible to fish out highly informative and useful genes from the sea of gene diversity in the environment, this can be a highly tedious and inefficient procedure. Microbial ecologists must be clever in their pursuit of ecologically relevant, valuable, and niche-defining genomic information within the vast haystack of microbial diversity. In this report, we seek to describe advances and prospects that will help microbial ecologists glean more knowledge from investigations into metagenomes. These include technological advances in sequencing and cloning methodologies, as well as improvements in annotation and comparative sequence analysis. More significant, however, will be ways to focus in on various subsets of the metagenome that may be of particular relevance, either by limiting the target community under study or improving the focus or speed of screening procedures. Lastly, given the cost and infrastructure necessary for large metagenome projects, and the almost inexhaustible amount of data they can produce, trends toward broader use of metagenome data across the research community coupled with the needed investment in bioinformatics infrastructure devoted to metagenomics will no doubt further increase the value of metagenomic studies in various environments

A Second-Generation Device for Automated Training and Quantitative Behavior Analyses of Molecularly-Tractable Model Organisms

A deep understanding of cognitive processes requires functional, quantitative analyses of the steps leading from genetics and the development of nervous system structure to behavior. Molecularly-tractable model systems such as Xenopus laevis and planaria offer an unprecedented opportunity to dissect the mechanisms determining the complex structure of the brain and CNS. A standardized platform that facilitated quantitative analysis of behavior would make a significant impact on evolutionary ethology, neuropharmacology, and cognitive science. While some animal tracking systems exist, the available systems do not allow automated training (feedback to individual subjects in real time, which is necessary for operant conditioning assays). The lack of standardization in the field, and the numerous technical challenges that face the development of a versatile system with the necessary capabilities, comprise a significant barrier keeping molecular developmental biology labs from integrating behavior analysis endpoints into their pharmacological and genetic perturbations. Here we report the development of a second-generation system that is a highly flexible, powerful machine vision and environmental control platform. In order to enable multidisciplinary studies aimed at understanding the roles of genes in brain function and behavior, and aid other laboratories that do not have the facilities to undergo complex engineering development, we describe the device and the problems that it overcomes. We also present sample data using frog tadpoles and flatworms to illustrate its use. Having solved significant engineering challenges in its construction, the resulting design is a relatively inexpensive instrument of wide relevance for several fields, and will accelerate interdisciplinary discovery in pharmacology, neurobiology, regenerative medicine, and cognitive science

Abstract P2-09-22: Use of a functional signal profiling test with high sensitivity and specificity to determine the prevalence of abnormal HER2-driven signaling activity in the HER2-negative breast cancer patient population: New patient group may benefit from HER2 therapy

Abstract Background: Biological factors, such as HER2 signaling activity, may be important to measure in addition to expression and amplification of HER2 when identifying patients eligible for HER2 therapies. The CELx HER2 Signaling Function (CELx HSF) Test measures HER2 signaling activity in live tumor cells using a label-free impedance biosensor to identify HER2-negative breast cancer patients likely to be responsive to treatment with anti-HER2 therapies. Previous studies quantified HER2-driven signaling activity in a training set (N=34) of primary tissue samples from HER2-negative breast cancer patients and found 21% of the samples had abnormal HER2 signaling. Other studies confirmed that anti-HER2 therapies, such as trastuzumab, pertuzumab, afatinib, and neratinib, are as effective in inhibiting HER2-driven signaling activity in HER2- tumor cells as they are in HER2+ tumor cells. This study set out to confirm the prevalence of abnormal HER2 signaling amongst HER2-negative breast cancer patients in a larger sample (N=114) and to characterize the sensitivity and specificity of the CELx HSF Test. Methods: A validation set of de-identified fresh breast tumor specimens were obtained from 114 HER2- breast cancer patients. Real time live cell response to specific HER2 agonists (NRG1b or EGF) with or without an antagonist (HER2 dimerization inhibitor) was measured using an impedance biosensor. From these responses, the net amount of HER2 participation in HER2 signaling initiated by the HER2 agonists was quantified. Samples with HER2 signaling activity levels above a previously determined cut-off value were identified as abnormal. Results: Of the HER2- breast tumor cell samples tested, 27 of 114 patients (23.7%; 95% CI=17%-32%) had abnormal HER2 signaling activity. Little or no correlation was found between a patient's HER2 signaling activity and their estrogen receptor status or tumor grade. To compare the results obtained from the training set of 34 patients and the current set of 114 patients, the Kolmogorov-Smirnov two-sample test was applied (D=0.17, P-value 0.45) and found no significant difference between the training and validation sets. A normal mixture model was fitted to the new 114 patient data set and found that HER2- breast cancer patients fall into three distinct groups (abnormal, normal, low). Patients falling into the abnormal group had mean HER2 signaling scores 4.5 standard deviations above the mean score of the normal group. A ROC curve constructed with this data projects that both the sensitivity and specificity of the CELx HSF Test would be greater than 90%. Conclusions: These results confirm that a clinically relevant proportion of HER2- breast cancer patients, approximately 20%, have tumors with abnormal HER2-signaling activity and may benefit from HER2 therapy. With high specificity and sensitivity, the CELx HSF test may be suitable as a companion diagnostic to identify new patients eligible to receive HER2 therapies. An interventional trial to evaluate the efficacy of trastuzumab and pertuzumab in HER2- patients selected with the CELx HSF test is underway. Citation Format: Laing LG, Burns DJ, MacNeil IA, Rich BE, Myhre S, Soltani S, Sullivan BF. Use of a functional signal profiling test with high sensitivity and specificity to determine the prevalence of abnormal HER2-driven signaling activity in the HER2-negative breast cancer patient population: New patient group may benefit from HER2 therapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-09-22.</jats:p

Potential emigration of Siberian cattle germplasm on Chirikof Island, Alaska

Feral cattle residing in Chirikof Island, Alaska, are relatively distinct from breeds used in commercial production in North America. However, preliminary evidence suggested that they exhibit substantial genetic relationship with cattle from Yakutian region of Siberia. Thus, our objective was to further elucidate quantify the origins, admixture and divergence of the Chirikof Island cattle relative to cattle from Siberia and USA. Subject animals were genotyped at 15 microsatellite loci. Compared with Turano–Mongolian and North American cattle, Chirikof Island cattle had similar variation, with slightly less observed heterozygosity, fewer alleles per locus and a positive fixation index. Analysis of the genetic distances revealed two primary clusters; one that contained the North American breeds and the Kazakh White head, and a second that contained the Yakutian and Kalmyk breeds, and the Chirikof population. Thus, it is suggested that Chirikof Island cattle may be a composite of British breeds emanating from North America and Turano–Mongolian cattle. A potential founder effect, consistent with historical records of the Russian–American period, may contribute to the adaptation of the Chirikof Island cattle to their harsh high-latitude environment. Further study of adaptive mechanisms manifest by these cattle is warranted.published versionpeerReviewe

Regulation of Interleukin-10 Gene Expression in Macrophages Engulfing Apoptotic Cells

Apoptosis and the rapid clearance of apoptotic cells (ACs) by professional or nonprofessional phagocytes are normal and coordinated processes that ensure controlled cell growth and stress response with nonpathological outcomes. Uptake of ACs by phagocytes is thought to suppress autoimmune responses through the release of anti-inflammatory cytokines such as interleukin-10 (IL-10), transforming growth factor-β (TGF-β), and inhibition of proinflammatory cytokines. The production of pro- and anti-inflammatory cytokines by phagocytes is highly regulated as part of an intrinsic mechanism to prevent inflammatory and autoimmune reactions in a physiological state. Production of IL-10 by phagocytes during clearance of ACs is critical to ensuring cellular homeostasis and suppression of autoimmunity. The molecular mechanism whereby IL-10 production is induced by ACs is only beginning to be understood. This review summarizes our recent work in this aspect of an essential physiological and homeostatic process

Dietary n-3 polyunsaturated fatty acids suppress splenic CD4(+) T cell function in interleukin (IL)-10(–/–) mice

Our laboratory has demonstrated that down-regulation of proliferation and cytokine synthesis by CD4(+) T cells in mice fed diets rich in n-3 polyunsaturated fatty acids (PUFA) is highly dependent on the involvement of the co-stimulatory molecule, CD28. It has been reported that the inhibitory cytokine interleukin (IL)-10 acts directly on T cells which up-regulate IL-10 receptor (IL-10R) expression following stimulation via CD28 by efficiently blocking proliferation and cytokine production. Thus, it was hypothesized that dietary n-3 PUFA would suppress T cell function through the effects of IL-10. The proliferation of purified splenic CD4(+) T cells activated in vitro with anti-CD3 and anti-CD28 (αCD3/CD28) from conventional mice (C57BL/6) fed either a control corn oil (CO)-enriched diet devoid of n-3 PUFA, docosahexaenoic acid (DHA; 22 : 6) or eicosapentaenoic acid (EPA; 20 : 5) for 14 days was suppressed by dietary DHA and EPA. Surprisingly, a similar trend was seen in IL-10 gene knock-out (IL-10(–/–)) mice fed dietary n-3 PUFA. IL-10R cell surface expression was also significantly down-regulated on CD4(+) T cells from both the C57BL/6 and IL-10(–/–) mice fed dietary n-3 PUFA after 72 h of in vitro stimulation with αCD3/CD28. Enzyme-linked immunosorbent assay (ELISA) measurements revealed that C57BL/6 mice fed DHA had significantly reduced interferon (IFN)-γ and IL-10 levels 48 h post-activation. However, CD4(+) T cells from IL-10(–/–) mice fed dietary n-3 PUFA produced significantly greater levels of IFN-γ than the CO-fed group. Our data suggest that in the absence of IL-10, CD4(+) T cells from n-3 PUFA-fed mice may up-regulate IFN-γ. Suppressed CD4(+) T cells from n-3 PUFA-fed C57BL/6 mice may use mechanisms other than IL-10 to down-regulate T cell function