Quantum dots (QD) are inorganic nanocrystals with outstanding optical properties, specially suited for biological imaging applications. Their attachment to biomolecules in mild aqueous conditions for the design of bioconjugates is therefore highly desirable. 1,3-dipolar [3 + 2] cycloaddition between azides and terminal alkynes ("click chemistry") could represent an attractive QD functionalization method. Unfortunately, the use of the popular Cu(I)-catalyzed version of this reaction is not applicable for achieving this goal, since the presence of copper dramatically alters the luminescence properties of QD dispersions. We demonstrate here that copper-free click chemistry, between strained cyclooctyne functionalized QD and azido-biomolecules, leads to highly luminescent conjugates. In addition, we show that QD-cyclooctyne can be used at previously unreported low concentration (250 nM) for imaging the incorporation of azido-modified sialic acid in cell membrane glycoproteins.

Fluorescence is a very promising radioactive-free technique for functional imaging in small animals and, in the future, in humans. However, most commercial near-infrared dyes display poor optical properties, such as low fluorescence quantum yields and short fluorescence lifetimes. In this paper, we explore whether the encapsulation of infrared cyanine dyes within the core of lipid nanoparticles (LNPs) could improve their optical properties. Lipophilic dialkylcarbocyanines DiD and DiR are loaded very efficiently in 30-35-nm-diam lipid droplets stabilized in water by surfactants. No significant fluorescence autoquenching is observed up to 53 dyes per particle. Encapsulated in LNP, which are stable for more than one year at room temperature in HBS buffer (HEPES 0.02 M, EDTA 0.01 M, pH 5.5), DiD and DiR display far improved fluorescence quantum yields Phi (respectively, 0.38 and 0.25) and longer fluorescence lifetimes tau (respectively, 1.8 and 1.1 ns) in comparison to their hydrophilic counterparts Cy5 (Phi=0.28, tau=1.0 ns) and Cy7 (Phi=0.13, tau=0.57 ns). Moreover, dye-loaded LNPs are able to accumulate passively in various subcutaneous tumors in mice, thanks to the enhanced permeability and retention effect. These new fluorescent nanoparticles therefore appear as very promising labels for in vivo fluorescence imaging.

Fundamental selectivity limits of quantum control are pushed by introducing laser driven optimal dynamic discrimination to create distinguishing excitations on two nearly identical flavin molecules. Even with modest spectral resources, significant specificity is achieved with optimal pulse shapes, which amplify small molecular differences to create distinct, identifying signals. Rather than being a hindrance, system complexity appears to aid the control process and augments control field capability, which bodes well for implementation of quantum control in a variety of demanding applications.

Rationale: Although many familial cases of pulmonary arterial hypertension (PAH) exhibit an autosomal dominant mode of inheritance with the majority having mutations in essential constituents of the bone morphogenetic protein (BMP) signaling, the specific contribution of the long-term loss of signal transduction triggered by the type 2 BMP receptor (BMPR2) remains poorly characterized. Objective: To investigate the role of BMP9, the main ligand of ALK1/BMPR2 heterocomplexes, in pulmonary hypertension (PH). Method and Results: The absence of BMP9 in Bmp9-/-mice and its inhibition in C57BL/6 mice using neutralizing anti-BMP9 antibodies substantially prevent against chronic hypoxia induced PH judged by right ventricular systolic pressure (RVSP) measurement, right ventricular hypertrophy, and pulmonary distal arterial muscularization. In agreement with these observations, we found that the BMP9/BMP10 ligand trap ALK1ECD administered in monocrotaline (MCT) or Sugen/hypoxia (SuHx) rats substantially attenuate proliferation of pulmonary vascular cells, inflammatory cell infiltration and regresses established PH in rats. Our data obtained in human pulmonary endothelial cells derived from controls and PAH patients indicate that BMP9 can affect the balance between endothelin-1, apelin and adrenomedullin. We reproduced these in vitro observations in mice chronically exposed to hypoxia, with Bmp9-/-mice exhibiting lower mRNA levels of the vasoconstrictor peptide endothelin (ET)-1 and higher levels of the two potent vasodilator factors apelin and adrenomedullin (ADM) compared with Bmp9 +/+ littermates. Conclusion: Taken together, our data indicate that the loss of BMP9, by deletion or inhibition, has beneficial effects against PH onset and progression.

Bacterial samples ͑Escherichia coli and Bacillus subtilis͒ have been analyzed by laser-induced breakdown spectroscopy ͑LIBS͒ using femtosecond pulses. We compare the obtained spectra with those resulting from the classical nanosecond LIBS. Specific features of femtosecond LIBS have been demonstrated, very attractive for analyzing biological sample: ͑i͒ a lower plasma temperature leading to negligible nitrogen and oxygen emissions from excited ambient air and a better contrast in detection of trace mineral species; and ͑ii͒ a specific ablation regime that favors intramolecular bonds emission with respect to atomic emission. A precise kinetic study of molecular band head intensities allows distinguishing the contribution of native CN bonds released by the sample from that due to carbon recombination with atmospheric nitrogen. Furthermore a sensitive detection of trace mineral elements provide specific spectral signature of different bacteria. An example is given for the Gram test provided by different magnesium emissions from Escherichia coli and Bacillus subtilis. An entire spectrum consists of hundred resolved lines belonging to 13 atomic or molecular species, which provides an ensemble of valuable data to identify different bacteria.

International audienceA sample of Escherichia coli has been analyzed by laser-induced breakdown spectroscopy (LIBS) using femtosecond pulses. The spectrum shows strong CN molecular bands due to the direct ablation of native CN molecular bonds from the bacteria in contrast with weak atomic lines from carbon. The native nature of the observed CN bonds is supported by the kinetic behavior of the CN band head which rapidly decays with a time constant of 94 ns, while for a pure graphite sample the CN band head increases with a delay of 450 ns due to recombination with the ambient air. Moreover, about hundred resolved lines belonging to 12 atomic or molecular species are recorded, providing a valuable spectral signature to identify the bacterium

Breast cancer stem cells (bCSCs) have been implicated in tumor progression and therapeutic resistance; however, the molecular mechanisms that define this state are unclear. We have performed two microRNA (miRNA) gain- and loss-of-function screens to identify miRNAs that regulate the choice between bCSC self-renewal and differentiation. We find that micro-RNA (miR)-600 silencing results in bCSC expansion, while its overexpression reduces bCSC self-renewal, leading to decreased in vivo tumorigenicity. miR-600 targets stearoyl desaturase 1 (SCD1), an enzyme required to produce active, lipid-modified WNT proteins. In the absence of miR-600, WNT signaling is active and promotes self-renewal, whereas overexpression of miR-600 inhibits the production of active WNT and promotes bCSC differentiation. In a series of 120 breast tumors, we found that a low level of miR-600 is correlated with active WNT signaling and a poor prognosis. These findings highlight a miR-600-centered signaling network that governs bCSC-fate decisions and influences tumor progression.

The discovery of microRNAs (miRNAs) in 1993 has challenged the dogma of gene expression regulation. MiRNAs affect most of cellular processes from metabolism, through cell proliferation and differentiation, to cell death. In cancer, deregulated miRNA expression leads to tumor development and progression by promoting acquisition of cancer hallmark traits. The multi-target action of miRNAs, which enable regulation of entire signaling networks, makes them attractive tools for the development of anti-cancer therapies. Hence, supplementing downregulated miRNA by synthetic oligonucleotides or silencing overexpressed miRNAs through artificial antagonists became a common strategy in cancer research. However, the ultimate success of miRNA therapeutics will depend on solving pharmacokinetic and targeted delivery issues. The development of a number of nanocarrier-based platforms holds significant promises to enhance the cell specific controlled delivery and safety profile of miRNA-based therapies. In this review, we provide among the most comprehensive assessments to date of promising nanomedicine platforms that have been tested preclinically, pertaining to the treatment of selected solid tumors including lung, liver, breast, and glioblastoma tumors as well as endocrine malignancies. The future challenges and potential applications in clinical oncology are discussed.