Fine features of optical potential well induced by nonlinearity

Particles trapped by optical tweezers, behaving as mechanical oscillators in an optomechanical system, have found tremendous applications in various disciplines and are still arousing research interest in frontier and fundamental physics. These optically trapped oscillators provide compact particle confinement and strong oscillator stiffness. But these features are limited by the size of the focused light spot of a laser beam, which is typically restricted by the optical diffraction limit. Here, we propose to build an optical potential well with fine features assisted by the nonlinearity of the particle material, which is independent of the optical diffraction limit. We show that the potential well shape can have super-oscillation-like features and a Fano-resonance-like phenomenon, and the width of the optical trap is far below the diffraction limit. A particle with nonlinearity trapped by an ordinary optical beam provides a new platform with a sub-diffraction potential well and can have applications in high-accuracy optical manipulation and high-precision metrology.Comment: 4 pages, 5 figure

Complete Sequence of a F33:A-:B- Conjugative Plasmid Carrying the oqxAB, fosA3, and blaCTX-M-55 Elements from a Foodborne Escherichia coli Strain

This study reports the complete sequence of pE80, a conjugative IncFII plasmid recovered from an Escherichia coli strain isolated from chicken meat. This plasmid harbors multiple resistance determinants including oqxAB, fosA3, blaCTX-M-55, and blaTEM-1, and is a close variant of the recently reported p42-2 element, which was recovered from E. coli of veterinary source. Recovery of pE80 constitutes evidence that evolution or genetic re-arrangement of IncFII type plasmids residing in animal-borne organisms is an active event, which involves acquisition and integration of foreign resistance elements into the plasmid backbone. Dissemination of these plasmids may further compromise the effectiveness of current antimicrobial strategies.Department of Applied Biology and Chemical Technolog

The role of EGFR double minutes in modulating the response of malignant gliomas to radiotherapy.

EGFR amplification in cells having double minute chromosomes (DM) is commonly found in glioblastoma multiforme (GBM); however, how much it contributes to the current failure to treat GBM successfully is unknown. We studied two syngeneic primary cultures derived from a GBM with and without cells carrying DM, for their differential molecular and metabolic profiles, in vivo growth patterns, and responses to irradiation (IR). Each cell line has a distinct molecular profile consistent with an invasive "go" (with DM) or angiogenic "grow" phenotype (without DM) demonstrated in vitro and in intracranial xenograft models. Cells with DM were relatively radio-resistant and used higher glycolytic respiration and lower oxidative phosphorylation in comparison to cells without them. The DM-containing cell was able to restore tumor heterogeneity by mis-segregation of the DM-chromosomes, giving rise to cell subpopulations without them. As a response to IR, DM-containing cells switched their respiration from glycolic metabolism to oxidative phosphorylation and shifted molecular profiles towards that of cells without DM. Irradiated cells with DM showed the capacity to alter their extracellular microenvironment to not only promote invasiveness of the surrounding cells, regardless of DM status, but also to create a pro-angiogenic tumor microenvironment. IR of cells without DM was found primarily to increase extracellular MMP2 activity. Overall, our data suggest that the DM-containing cells of GBM are responsible for tumor recurrence due to their high invasiveness and radio-resistance and the mis-segregation of their DM chromosomes, to give rise to fast-growing cells lacking DM chromosomes

PAX6 suppression of glioma angiogenesis and the expression of vascular endothelial growth factor A

We reported that PAX6 suppresses glioblastoma cell growth in vivo and anchorage-independent growth without significant alteration of cell proliferation in vitro, suggesting that PAX6 may alter the tumor microenvironment. Because we found that PAX6 downregulates expression of the gene encoding vascular endothelial growth factor A (VEGFA) in glioma cells, we used a subcutaneous xenograft model to verify PAX6 suppression of VEGFA-induced angiogenesis based on CD31-immunostaining of endothelial cells. The results showed a significant reduction of VEGFA at the transcription level in PAX6-transfected cells in xenografts and PAX6 has a suppressive effect on the microvascular amplification typically seen in glioblastoma. We showed that PAX6 suppression of VEGFA expression requires its DNA binding-domain. The C-terminal truncation mutant of PAX6, however, did not show the dominant negative function in regulating VEGFA expression that it showed previously in regulating MMP2 expression. In the glioma cell line U251HF, we further determined that blocking the PI3K/Akt signaling pathway with either adenoviral-mediated PTEN expression or LY294002 enhanced PAX6-mediated suppression of VEGFA in an additive manner; thus, PAX6-mediated suppression of VEGFA is not via the canonical pathway through HIF1A. These two VEGFA-regulatory pathways can also be similarly modulated in another malignant glioma cell line, U87, but not in LN229 where the basal VEGFA level is low and PTEN is wild-type. PAX6 suppression of VEGFA appears to be blocked in LN229. In conclusion, our data showed that PAX6 can initiate in glioma cells a new signaling pathway independent of PI3K/Akt-HIF1A signaling to suppress VEGFA expression

EFEMP1 suppresses malignant glioma growth and exerts its action within the tumor extracellular compartment

<p>Abstract</p> <p>Purpose</p> <p>There are conflicting reports regarding the function of EFEMP1 in different cancer types. In this study, we sought to evaluate the role of EFEMP1 in malignant glioma biology.</p> <p>Experimental Design</p> <p>Real-time qRT-PCR was used to quantify <it>EFEMP1 </it>expression in 95 glioblastoma multiforme (GBM). Human high-grade glioma cell lines and primary cultures were engineered to express ectopic EFEMP1, a small hairpin RNA of EFEMP1, or treated with exogenous recombinant EFEMP1 protein. Following treatment, growth was assayed both <it>in vitro </it>and <it>in vivo </it>(subcutaneous (s.c.) and intracranial (i.c.) xenograft model systems).</p> <p>Results</p> <p>Cox regression revealed that EFEMP1 is a favorable prognostic marker for patients with GBM. Over-expression of EFEMP1 eliminated tumor development and suppressed angiogenesis, cell proliferation, and VEGFA expression, while the converse was true with knock-down of endogenous EFEMP1 expression. The EFEMP1 suppression of tumor onset time was nearly restored by ectopic VEGFA expression; however, overall tumor growth rate remained suppressed. This suggested that inhibition of angiogenesis was only partly responsible for EFEMP1's impact on glioma development. In glioma cells that were treated by exogenous EFEMP1 protein or over-expressed endogenous EFEMP1, the EGFR level was reduced and AKT signaling activity attenuated. Mixing of EFEMP1 protein with cells prior to s.c. and i.c. implantations or injection of the protein around the established s.c. xenografts, both significantly suppressed tumorigenicity.</p> <p>Conclusions</p> <p>Overall, our data reveals that EEFEMP1 suppresses glioma growth <it>in vivo</it>, both by modulating the tumor extracellular microenvironment and by altering critical intracellular oncogenic signaling pathways.</p

Association of gestational age at birth with subsequent suspected Developmental Coordination Disorder in early childhood

Importance. It remains unknown whether children born at different degrees of prematurity, early-term and post-term might have a higher risk of developing Developmental Coordination Disorder (DCD) compared to completely full-term children (39-40 gestational weeks). Objective. To differentiate between suspected DCD in children with different gestational ages based on a national representative sample in China. DESIGN, SETTING, AND PARTICIPANTS We conducted a retrospective cohort study in China from 2018 to 2019. A total of 152,433 children from 2,403 public kindergartens in 551 cities of China aged 3-5 years old were included in the final analysis. The association between gestational age and motor performance was investigated. A multi-level regression model was developed to determine the strength of association for different gestational ages associated with suspected DCD when considering kindergartens as clusters. Main outcomes and measures. Children’s motor performance was assessed using the Little Developmental Coordination Disorder Questionnaire (LDCDQ), completed by parents. Gestational age was determined according to the mother’s medical records. Results. Of the 152,433 children aged 3-5 years old, 80,370 (52.7%) were male, and 72,063 (47.3%) were female. There were 45,052 children aged 3 years old (29.6%), 59,796 aged 4 years old(39.2%), and 47,585 children aged 5 years old (31.2%). The LDCDQ total scores for very-preterm (β=-1.74, 95%CI: -1.98, 1.50; p<0.001), moderately-preterm (β=-1.24, 95%CI: -1.60, -0.89; p<0.001), late-preterm (β=-0.92, 95%CI: -1.08, -0.76; p<0.001), early-term (β=-0.36, 95%CI: -0.46, -0.25; p<0.001) and post-term children (β=-0.47, 95%CI: -0.67, -0.26; p<0.001) were significantly lower than full-term children when adjusting for child, family and maternal health characteristics. The very-preterm (OR=1.35, 95%CI: 1.23,1.48; p<0.001), moderately-preterm (OR=1.18, 95%CI: 1.02, 1.36; p<0.001), late-preterm (OR =1.24, 95%CI: 1.16,1.32; p<0.001), early-term (OR =1.11, 95%CI: 1.06,1.16; p<0.001) and post-term children (OR =1.167, 95%CI: 1.07, 1.27; p<0.001) were more likely to fall in the suspected Developmental Coordination Disorder (DCD) category on the LDCDQ compared with completely full-term children after adjusting for the same characteristics. The associations between different gestational ages and suspected DCD were stronger in boys and older (5 year old) children (each p<0.05). Conclusions and relevance. We found significant associations between every degree of prematurity at birth, early-term and post-term birth with suspected DCD when compared with full-term birth. Our findings have important implications for understanding motor development in children born at different gestational ages. Long-term follow-up and rehabilitation interventions should be considered for early- and post-term born children