Preparation and characterization of stable aqueous suspensions of up-converting Er3+/Yb3+-doped LiNbO3 nanocrystals

The preparation of LiNbO3:Er3+/Yb3+ nanocrystals and their up-conversion properties have been studied. It is demonstrated that polyethyleneimine- (PEI) assisted dispersion procedures allow obtaining stable aqueous LiNbO3:Er3+/Yb3+ powder suspensions, with average size particles well below the micron range (100–200 nm) and the isoelectric point of the suspension reaching values well above pH 7. After excitation of Yb3+ ions at a wavelength of 980 nm, the suspensions exhibit efficient, and stable, IR-to-visible (green and red) up-conversion properties, easily observed by the naked eye, very similar to those of the starting crystalline bulk material

Export of nutrient rich Northern Component Water preceded early Oligocene Antarctic glaciation

The onset of the North Atlantic Deep Water formation is thought to have coincided with Antarctic ice-sheet growth about 34 million years ago (Ma). However, this timing is debated, in part due to questions over the geochemical signature of the ancient Northern Component Water (NCW) formed in the deep North Atlantic. Here we present detailed geochemical records from North Atlantic sediment cores located close to sites of deep-water formation. We find that prior to 36 Ma, the northwestern Atlantic was stratified, with nutrient-rich, low-salinity bottom waters. This restricted basin transitioned into a conduit for NCW that began flowing southwards approximately one million years before the initial Antarctic glaciation. The probable trigger was tectonic adjustments in subarctic seas that enabled an increased exchange across the Greenland–Scotland Ridge. The increasing surface salinity and density strengthened the production of NCW. The late Eocene deep-water mass differed in its carbon isotopic signature from modern values as a result of the leakage of fossil carbon from the Arctic Ocean. Export of this nutrient-laden water provided a transient pulse of CO2 to the Earth system, which perhaps caused short-term warming, whereas the long-term effect of enhanced NCW formation was a greater northward heat transport that cooled Antarctica

A European Perspective on Auditory Processing Disorder-Current Knowledge and Future Research Focus

Current notions of “hearing impairment,” as reflected in clinical audiological practice, do not acknowledge the needs of individuals who have normal hearing pure tone sensitivity but who experience auditory processing difficulties in everyday life that are indexed by reduced performance in other more sophisticated audiometric tests such as speech audiometry in noise or complex non-speech sound perception. This disorder, defined as “Auditory Processing Disorder” (APD) or “Central Auditory Processing Disorder” is classified in the current tenth version of the International Classification of diseases as H93.25 and in the forthcoming beta eleventh version. APDs may have detrimental effects on the affected individual, with low esteem, anxiety, and depression, and symptoms may remain into adulthood. These disorders may interfere with learning per se and with communication, social, emotional, and academic-work aspects of life. The objective of the present paper is to define a baseline European APD consensus formulated by experienced clinicians and researchers in this specific field of human auditory science. A secondary aim is to identify issues that future research needs to address in order to further clarify the nature of APD and thus assist in optimum diagnosis and evidence-based management. This European consensus presents the main symptoms, conditions, and specific medical history elements that should lead to auditory processing evaluation. Consensus on definition of the disorder, optimum diagnostic pathway, and appropriate management are highlighted alongside a perspective on future research focus

Imidazoacridinone-dependent lysosomal photodestruction: a pharmacological Trojan horse approach to eradicate multidrug-resistant cancers

Multidrug resistance (MDR) remains a primary hindrance to curative cancer therapy. Thus, introduction of novel strategies to overcome MDR is of paramount therapeutic significance. Sequestration of chemotherapeutics in lysosomes is an established mechanism of drug resistance. Here, we show that MDR cells display a marked increase in lysosome number. We further demonstrate that imidazoacridinones (IAs), which are cytotoxic fluorochromes, undergo a dramatic compartmentalization in lysosomes because of their hydrophobic weak base nature. We hence developed a novel photoactivation-based pharmacological Trojan horse approach to target and eradicate MDR cancer cells based on photo-rupture of IA-loaded lysosomes and tumor cell lysis via formation of reactive oxygen species. Illumination of IA-loaded cells resulted in lysosomal photodestruction and restoration of parental cell drug sensitivity. Lysosomal photodestruction of MDR cells overexpressing the key MDR efflux transporters ABCG2, ABCB1 or ABCC1 resulted in 10- to 52-fold lower IC(50) values of various IAs, thereby restoring parental cell sensitivity. Finally, in vivo application of this photodynamic therapy strategy after i.v. injection of IAs in human ovarian tumor xenografts in the chorioallantoic membrane model revealed selective destruction of tumors and their associated vasculature. These findings identify lysosomal sequestration of IAs as an Achilles heel of MDR cells that can be harnessed to eradicate MDR tumor cells via lysosomal photodestruction

Three endo-β-mannanase genes expressed in the micropylar endosperm and in the radicle influence germination of Arabidopsis thaliana seeds

Mannans are hemicellulosic polysaccharides in the plant primary cell wall (CW). Mature seeds, specially their endosperm cells, have CWs rich in mannan-based polymers that confer a strong mechanical resistance for the radicle protrusion upon germination. The rupture of the seed coat and endosperm are two sequential events during the germination of Arabidopsis thaliana. Endo-β-mannanases (MAN; EC. 3.2.1.78) are hydrolytic enzymes that catalyze cleavage of β1 → 4 bonds in the mannan-polymer. In the genome of Arabidopsis, the endo-β-mannanase (MAN) family is represented by eight members. The expression of these eight MAN genes has been systematically explored in different organs of this plant and only four of them (AtMAN7, AtMAN6, AtMAN2 and AtMAN5) are expressed in the germinating seeds. Moreover, in situ hybridization analysis shows that their transcript accumulation is restricted to the micropylar endosperm and to the radicle and this expression disappears soon after radicle emergence. T-DNA insertion mutants in these genes (K.O. MAN7, K.O. MAN6, K.O. MAN5), except that corresponding to AtMAN2 (K.O. MAN2), germinate later than the wild type (Wt). K.O. MAN6 is the most affected in the germination time course with a t 50 almost double than that of the Wt. These data suggest that AtMAN7, AtMAN5 and specially AtMAN6 are important for the germination of A. thaliana seeds by facilitating the hydrolysis of the mannan-rich endosperm cell walls

Measuring the response to visually presented faces in the human lateral prefrontal cortex

Neuroimaging studies identify multiple face-selective areas in the human brain. In the current study, we compared the functional response of the face area in the lateral prefrontal cortex to that of other face-selective areas. In Experiment 1, participants (n = 32) were scanned viewing videos containing faces, bodies, scenes, objects, and scrambled objects. We identified a face-selective area in the right inferior frontal gyrus (rIFG). In Experiment 2, participants (n = 24) viewed the same videos or static images. Results showed that the rIFG, right posterior superior temporal sulcus (rpSTS), and right occipital face area (rOFA) exhibited a greater response to moving than static faces. In Experiment 3, participants (n = 18) viewed face videos in the contralateral and ipsilateral visual fields. Results showed that the rIFG and rpSTS showed no visual field bias, while the rOFA and right fusiform face area (rFFA) showed a contralateral bias. These experiments suggest two conclusions; firstly, in all three experiments, the face area in the IFG was not as reliably identified as face areas in the occipitotemporal cortex. Secondly, the similarity of the response profiles in the IFG and pSTS suggests the areas may perform similar cognitive functions, a conclusion consistent with prior neuroanatomical and functional connectivity evidence

Vascular regrowth following photodynamic therapy in the chicken embryo chorioallantoic membrane

Photodynamic therapy (PDT) induces damage to the endothelium, which can lead to increased vascular permeability and, under intensive PDT conditions, even to platelet aggregation, vasoconstriction, and blood flow stasis. Eventually, ischemia, hypoxia, and inflammation can occur, resulting in angiogenesis. We studied the sequence of the vascular events after Visudyne®-PDT in the chicken chorioallantoic membrane (CAM) at day 11 of development. Using epi-fluorescence microscopy, we monitored the regrowth of capillaries in the PDT treated area. Immediately after irradiation, the treatment resulted in blood flow arrest. And 24 h post PDT, sprouting of new blood vessels was observed at the edge of the PDT zone. Neovessels looping out from the edge of the PDT zone gave rise to specialized endothelial tip structures guiding the vessels towards the center of the treated area. At 48 h almost all of the treated area was repopulated with functional but morphologically altered vasculature. These observations also showed reperfusion of some of the vessels that had been closed by the PDT treatment. CAM samples were immunohistochemically stained for Ki-67 showing proliferation of endothelial cells in the PDT area. Also, several markers of immature and angiogenic blood vessels, such as αVβ3-integrin, vimentin and galectin-1, were found to be enhanced in the PDT area, while the endothelial maturation marker intercellular adhesion molecule (ICAM)-1 was found to be suppressed. These results demonstrate that the new vascular bed is formed by both neo-angiogenesis and reperfusion of existing vessels. Both the quantitative real-time RT–PCR profile and the response to pharmacological treatment with Avastin®, an inhibitor of angiogenesis, suggest that angiogenesis occurs after PDT. The observed molecular profiling results and the kinetics of gene regulation may enable optimizing combination therapies involving PDT for treatment of cancer and other diseases