Anti-HER2 IgY antibody-functionalized single-walled carbon nanotubes for detection and selective destruction of breast cancer cells

BACKGROUND: Nanocarrier-based antibody targeting is a promising modality in therapeutic and diagnostic oncology. Single-walled carbon nanotubes (SWNTs) exhibit two unique optical properties that can be exploited for these applications, strong Raman signal for cancer cell detection and near-infrared (NIR) absorbance for selective photothermal ablation of tumors. In the present study, we constructed a HER2 IgY-SWNT complex and demonstrated its dual functionality for both detection and selective destruction of cancer cells in an in vitro model consisting of HER2-expressing SK-BR-3 cells and HER2-negative MCF-7 cells. METHODS: The complex was constructed by covalently conjugating carboxylated SWNTs with anti-HER2 chicken IgY antibody, which is more specific and sensitive than mammalian IgGs. Raman signals were recorded on Raman spectrometers with a laser excitation at 785 nm. NIR irradiation was performed using a diode laser system, and cells with or without nanotube treatment were irradiated by 808 nm laser at 5 W/cm(2 )for 2 min. Cell viability was examined by the calcein AM/ethidium homodimer-1 (EthD-1) staining. RESULTS: Using a Raman optical microscope, we found the Raman signal collected at single-cell level from the complex-treated SK-BR-3 cells was significantly greater than that from various control cells. NIR irradiation selectively destroyed the complex-targeted breast cancer cells without harming receptor-free cells. The cell death was effectuated without the need of internalization of SWNTs by the cancer cells, a finding that has not been reported previously. CONCLUSION: We have demonstrated that the HER2 IgY-SWNT complex specifically targeted HER2-expressing SK-BR-3 cells but not receptor-negative MCF-7 cells. The complex can be potentially used for both detection and selective photothermal ablation of receptor-positive breast cancer cells without the need of internalization by the cells. Thus, the unique intrinsic properties of SWNTs combined with high specificity and sensitivity of IgY antibodies can lead to new strategies for cancer detection and therapy

Exploring the nature and synchronicity of early cluster formation in the Large Magellanic Cloud - IV. Evidence for multiple populations in Hodge 11 and NGC 2210

We present a multiple population search in two old Large Magellanic Cloud (LMC) Globular clusters, Hodge 11 and NGC 2210. This work uses data from the Advanced Camera for Surveys and Wide Field Camera 3 on the Hubble Space Telescope from programme GO- 14164 in Cycle 23. Both of these clusters exhibit a broadened main sequence with the second population representing (20±~5) per cent forNGC2210 and (30±~5) per cent forHodge 11. In both clusters, the smaller population is redder than the primary population, suggesting CNO variations. Hodge 11 also displays a bluer second population in the horizontal branch, which is evidence for helium enhancement. However, even though NGC 2210 shows similarities to Hodge 11 in the main sequence, there does not appear to be a second population on NGC 2210's horizontal branch. This is the first photometric evidence that ancient LMC Globular clusters exhibit multiple stellar populations.Fil: Gilligan, Christina K.. Dartmouth College; Estados UnidosFil: Chaboyer, Brian. Dartmouth College; Estados UnidosFil: Cummings, Jeffrey D.. University Johns Hopkins; Estados UnidosFil: Mackey, Dougal. Australian National University. Research School of Astronomy & Astrophysics; AustraliaFil: Cohen, Roger E.. Space Telescope Science Institute; Estados UnidosFil: Geisler, Douglas. Universidad de La Serena; ChileFil: Grocholski, Aaron J.. University of Washington; Estados UnidosFil: Parisi, Maria Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; ArgentinaFil: Sarajedini, Ata. University of Florida; Estados UnidosFil: Ventura, Paolo. Osservatorio Astronomico Di Roma; ItaliaFil: Villanova, Sandro. Universidad de Concepción; ChileFil: Yang, Soung-Chul. Korea Astronomy And Space Science Institute; Corea del SurFil: Wagner-Kaiser, Rachel. University of Florida; Estados Unido

Exploring the nature and synchronicity of early cluster formation in the Large Magellanic Cloud - V. Multiple populations in ancient globular clusters

We examine four ancient LargeMagellanic Cloud (LMC) globular clusters (GCs) for evidence of multiple stellar populations using the Advanced Camera for Surveys andWide Field Camera 3 on the Hubble Space Telescope Programme GO-14164. NGC 1466, NGC 1841, and NGC 2257 all show evidence for a redder, secondary population along themain sequence. Reticulum does not showevidence for the presence of a redder population, but thisGChas the least number of stars and Monte Carlo simulations indicate that the sample of main-sequence stars is too small to robustly infer whether a redder population exists in this cluster. The second, redder, population of the other three clusters constitutes ∼ 30 - 40 per cent of the total population along the main sequence. This brings the total number of ancient LMC GCs with known split or broadened main sequences to five. However, unlike for Hodge 11 and NGC 2210 (see Gilligan et al. (2019)), none of the clusters shows evidence for multiple populations in the horizontal branch. We also do not find evidence of a second population along the red giant branch.Fil: Gilligan, Christina K.. Dartmouth College; Estados UnidosFil: Chaboyer, Brian. Dartmouth College; Estados UnidosFil: Cummings, Jeffrey D.. University Johns Hopkins; Estados UnidosFil: Mackey, Dougal. Australian National University; AustraliaFil: Cohen, Roger E.. Space Telescope Science Institute; Estados UnidosFil: Geisler, Douglas. Universidad de Concepción; ChileFil: Grocholski, Aaron J.. University of Florida; Estados UnidosFil: Parisi, Maria Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Astronomía Teórica y Experimental. Universidad Nacional de Córdoba. Observatorio Astronómico de Córdoba. Instituto de Astronomía Teórica y Experimental; ArgentinaFil: Sarajedini, Ata. University of Florida; Estados UnidosFil: Ventura, Paolo. Osservatorio Astronomico Di Roma; ItaliaFil: Villanova, Sandro. Universidad de Concepción; ChileFil: Yang, Soung-Chul. Korea Astronomy And Space Science Institute; Corea del SurFil: Wagner-Kaiser, Rachel. University of Florida; Estados Unido

High-resolution fMRI of content-sensitive subsequent memory responses in human medial temporal lobe

Abstract & The essential role of the medial temporal lobe (MTL) in long-term memory for individual events is well established, yet important questions remain regarding the mnemonic functions of the component structures that constitute the region. Within the hippocampus, recent functional neuroimaging findings suggest that formation of new memories depends on the dentate gyrus and the CA 3 field, whereas the contribution of the subiculum may be limited to retrieval. During encoding, it has been further hypothesized that structures within MTL cortex contribute to encoding in a content-sensitive manner, whereas hippocampal structures may contribute to encoding in a more domain-general manner. In the current experiment, highresolution fMRI techniques were utilized to assess novelty and subsequent memory effects in MTL subregions for two classes of stimuli-faces and scenes. During scanning, participants performed an incidental encoding (target detection) task with novel and repeated faces and scenes. Subsequent recognition memory was indexed for the novel stimuli encountered during scanning. Analyses revealed voxels sensitive to both novel faces and novel scenes in all MTL regions. However, similar percentages of voxels were sensitive to novel faces and scenes in perirhinal cortex, entorhinal cortex, and a combined region comprising the dentate gyrus, CA 2 , and CA 3 , whereas parahippocampal cortex, CA 1 , and subiculum demonstrated greater sensitivity to novel scene stimuli. Paralleling these findings, subsequent memory effects in perirhinal cortex were observed for both faces and scenes, with the magnitude of encoding activation being related to later memory strength, as indexed by a graded response tracking recognition confidence, whereas subsequent memory effects were scene-selective in parahippocampal cortex. Within the hippocampus, encoding activation in the subiculum correlated with subsequent memory for both stimulus classes, with the magnitude of encoding activation varying in a graded manner with later memory strength. Collectively, these findings suggest a gradient of content sensitivity from posterior (parahippocampal) to anterior (perirhinal) MTL cortex, with MTL cortical regions differentially contributing to successful encoding based on event content. In contrast to recent suggestions, the present data further indicate that the subiculum may contribute to successful encoding irrespective of event content. &amp

Achieving sustainable aquaculture: Historical and current perspectives and future needs and challenges

Important operational changes that have gradually been assimilated and new approaches that are developing as part of the movement toward sustainable intensive aquaculture production systems are presented via historical, current, and future perspectives. Improved environmental and economic sustainability based on increased efficiency of production continues to be realized. As a result, aquaculture continues to reduce its carbon footprint through reduced greenhouse gas emissions. Reduced use of freshwater and land resources per unit of production, improved feed management practices as well as increased knowledge of nutrient requirements, effective feed ingredients and additives, domestication of species, and new farming practices are now being applied or evaluated. Successful expansion into culture of marine species, both off and on shore, offers the potential of substantial increases in sustainable intensive aquaculture production combined with integrative efforts to increase efficiency will principally contribute to satisfying the increasing global demand for protein and food security needs

Towards in cellulo virus crystallography

Viruses are a significant threat to both human health and the economy, and there is an urgent need for novel anti-viral drugs and vaccines. High-resolution viral structures inform our understanding of the virosphere, and inspire novel therapies. Here we present a method of obtaining such structural information that avoids potentially disruptive handling, by collecting diffraction data from intact infected cells. We identify a suitable combination of cell type and virus to accumulate particles in the cells, establish a suitable time point where most cells contain virus condensates and use electron microscopy to demonstrate that these are ordered crystalline arrays of empty capsids. We then use an X-ray free electron laser to provide extremely bright illumination of sub-micron intracellular condensates of bacteriophage phiX174 inside living Escherichia coli at room temperature. We have been able to collect low resolution diffraction data. Despite the limited resolution and completeness of these initial data, due to a far from optimal experimental setup, we have used novel methodology to determine a putative space group, unit cell dimensions, particle packing and likely maturation state of the particles.Peer reviewe

Exploring the nature and synchronicity of early cluster formation in the Large Magellanic Cloud - III. Horizontal branch morphology

We leverage new high-quality data from Hubble Space Telescope program GO-14164 to explore the variation in horizontal branch morphology among globular clusters in the Large Magellanic Cloud (LMC). Our new observations lead to photometry with a precision commensurate with that available for the Galactic globular cluster population. Our analysis indicates that, once metallicity is accounted for, clusters in the LMC largely share similar horizontal branch morphologies regardless of their location within the system. Furthermore, the LMC clusters possess, on average, slightly redder morphologies than most of the inner halo Galactic population; we find, instead, that their characteristics tend to be more similar to those exhibited by clusters in the outer Galactic halo. Our results are consistent with previous studies, showing a correlation between horizontal branch morphology and age.DMis grateful for support from an Australian Research Council (ARC) Future Fellowship (FT160100206). DG gratefully acknowledges support from the Chilean BASAL Centro de Excelencia en Astrofisica y Tecnologıas Afines (CATA) grant PFB-06/2007

Assessment of ABT-263 activity across a cancer cell line collection leads to a potent combination therapy for small-cell lung cancer

BH3 mimetics such as ABT-263 induce apoptosis in a subset of cancer models. However, these drugs have shown limited clinical efficacy as single agents in small-cell lung cancer (SCLC) and other solid tumor malignancies, and rational combination strategies remain underexplored. To develop a novel therapeutic approach, we examined the efficacy of ABT-263 across >500 cancer cell lines, including 311 for which we had matched expression data for select genes. We found that high expression of the proapoptotic gene Bcl2-interacting mediator of cell death (BIM) predicts sensitivity to ABT-263. In particular, SCLC cell lines possessed greater BIM transcript levels than most other solid tumors and are among the most sensitive to ABT-263. However, a subset of relatively resistant SCLC cell lines has concomitant high expression of the antiapoptotic myeloid cell leukemia 1 (MCL-1). Whereas ABT-263 released BIM from complexes with BCL-2 and BCL-XL, high expression of MCL-1 sequestered BIM released from BCL-2 and BCL-XL, thereby abrogating apoptosis. We found that SCLCs were sensitized to ABT-263 via TORC1/2 inhibition, which led to reduced MCL-1 protein levels, thereby facilitating BIM-mediated apoptosis. AZD8055 and ABT-263 together induced marked apoptosis in vitro, as well as tumor regressions in multiple SCLC xenograft models. In a Tp53; Rb1 deletion genetically engineered mouse model of SCLC, the combination of ABT-263 and AZD8055 significantly repressed tumor growth and induced tumor regressions compared with either drug alone. Furthermore, in a SCLC patient-derived xenograft model that was resistant to ABT-263 alone, the addition of AZD8055 induced potent tumor regression. Therefore, addition of a TORC1/2 inhibitor offers a therapeutic strategy to markedly improve ABT-263 activity in SCLC.United States. Dept. of Defense (Grant W81-XWH-13-1-0323)National Cancer Institute (U.S.) (Cancer Center Support Grant P30-CA14051