Harveyshort5357

Neuroblastoma, an embryonic tumor arising from neuronal crest progenitor cells, has been shown to contain a population of undifferentiated stem cells responsible for the malignant state and the unfavorable prognosis. Although many previous studies have analyzed neuroblastoma stem cells and their therapeutic targeting, this topic appears still open to novel investigations. Here we found that neurospheres derived from neuroblastoma stem-like cells showed a homogeneous staining for several key nucleolar proteins, such as Nucleolin, Nucleophosmin-1, Glypican-2 and PES-1. We investigated the effects of Roniciclib (BAY 1000394), an anticancer stem cells agent, on neurospheres and on an orthotopic neuroblastoma mouse model, discovering an impressive inhibition of tumor growth and indicating good chances for the use of Roniciclib in vivo. We demonstrated that Roniciclib is not only a Wnt/β-catenin signaling inhibitor, but also a nucleolar stress inducer, revealing a possible novel mechanism underlying Roniciclib-mediated repression of cell proliferation. Furthermore, we found that high expression of Nucleophosmin-1 correlates with patients' short survival. The co-expression of several stem cell surface antigens such as CD44v6 and CD114, together with the nucleolar markers here described, extends new possibilities to isolate undifferentiated subpopulations from neuroblastoma and identify new targets for the treatment of this childhood malignancy.The cornea provides the largest refractive power for the human visual system. Its stiffness, along with intraocular pressure (IOP), are linked to several pathologies, including keratoconus and glaucoma. Although mechanical tests can quantify corneal elasticity ex vivo, they cannot be used clinically. Dynamic optical coherence elastography (OCE), which launches and tracks shear waves to estimate stiffness, provides an attractive non-contact probe of corneal elasticity. To date, however, OCE studies report corneal moduli around tens of kPa, orders-of-magnitude less than those (few MPa) obtained by tensile/inflation testing. This large discrepancy impedes OCE's clinical adoption. Based on corneal microstructure, we introduce and fully characterize a nearly-incompressible transversely isotropic (NITI) model depicting corneal biomechanics. We show that the cornea must be described by at least two shear moduli, contrary to current single-modulus models, decoupling tensile and shear responses. We measure both as a function of IOP in ex vivo porcine cornea, obtaining values consistent with both tensile and shear tests. At pressures above 30 mmHg, the model begins to fail, consistent with non-linear changes in cornea at high IOP.During Leishmania transmission sand flies inoculate parasites and saliva into the skin of vertebrates. Saliva has anti-haemostatic and anti-inflammatory activities that evolved to facilitate bloodfeeding, but also modulate the host's immune responses. Sand fly salivary proteins have been extensively studied, but the nature and biological roles of protein-linked glycans remain overlooked. Here, we characterised the profile of N-glycans from the salivary glycoproteins of Lutzomyia longipalpis, vector of visceral leishmaniasis in the Americas. In silico predictions suggest half of Lu. longipalpis salivary proteins may be N-glycosylated. SDS-PAGE coupled to LC-MS analysis of sand fly saliva, before and after enzymatic deglycosylation, revealed several candidate glycoproteins. To determine the diversity of N-glycan structures in sand fly saliva, enzymatically released sugars were fluorescently tagged and analysed by HPLC, combined with highly sensitive LC-MS/MS, MALDI-TOF-MS, and exoglycosidase treatments. We found that the N-glycan composition of Lu. longipalpis saliva mostly consists of oligomannose sugars, with Man5GlcNAc2 being the most abundant, and a few hybrid-type species. Interestingly, some glycans appear modified with a group of 144 Da, whose identity has yet to be confirmed. Our work presents the first detailed structural analysis of sand fly salivary glycans.Predicting the risk of end-stage renal disease (ESRD) progression facilitates appropriate nephrology care of patients with chronic kidney disease (CKD). Previously, the kidney failure risk equations (KFREs) were developed and validated in several cohorts. The purpose of this study is to validate the KFREs in a Korean population and to recalibrate the equations. A total of 38,905 adult patients, including 13,244 patients with CKD stages G3-G5, who were referred to nephrology were recruited. Using the original KFREs (4-, 6- and 8-variable equations) and recalibration equations, we predicted the risk of 2- and 5-year ESRD progression. All analyses were conducted in CKD stages G3-G5 patients as well as the total population. In CKD stages G3-G5 patients, All the original 4-, 6- and 8-variable equations showed excellent areas under the receiver operating characteristic curve of 0.87 and 0.83 for the 2- and 5-year risk of ESRD, respectively. The results of net reclassification improvement, integrated discrimination index and Brier score showed that recalibration improved the prediction models in some cases. The original KFREs showed high discrimination in both CKD stages G3-G5 patients and the total population referred to nephrology in this large Korean cohort. selleck chemical KFREs can be implemented in Korean health systems and can guide nephrology referrals and other CKD-related treatment decisions.We examined the physical and mechanical properties of wood in Siberian larch (Larix sibirica) trees that grow naturally in five Mongolian provenances (Khentii, Arkhangai, Zavkhan, Khuvsgul, and Selenge) and the geographic variations between them. Five trees with stem diameters of 20 to 30 cm at 1.3 m above ground were collected from each provenance. The mean values of the modulus of elasticity (MOE), modulus of rupture (MOR), compressive strength parallel to grain (CS), and shearing strength (SS) ranged from 7.03 to 9.51 GPa, 79.8 to 103.9 MPa, 46.3 to 51.1 MPa, and 10.4 to 13.0 MPa, respectively. Significant differences were found in radial and tangential shrinkage, MOE, MOR, and SS in wood among the five provenances. In addition, juvenile wood had inferior physical and mechanical properties in comparison to mature wood within and among provenances. Furthermore, there were significant differences in all examined properties, except for CS, in mature wood among the five provenances. Higher correlation coefficients were also obtained in mature wood among all mechanical properties, except for SS.The generation of few-cycle laser pulses proved to be a key enabling technology in strong-field physics and ultrafast science. The question naturally arises whether one can induce few-cycle localized plasmon oscillations in optical near-fields. Here, we perform a comparative study of different plasmonic nanoresonators illuminated by few-cycle pulses. We analyze the number of cycles (NOC) of the plasmonic field, the near-field enhancement (NFE) as well as the figure of merit NFE/NOC. The pulse length dependence of these quantities is also investigated. Throughout the inspected pulse-length interval silica-gold and silica-silver core-shell monomers have the potential to preserve the NOC of the incoming pulse, silver bow-ties result in the highest NFE, whereas gold core-shell dimers have the highest NFE/NOC. Based on the analysis, silver bow-ties, gold core-shell and silver nanorod dimers proved to be the most suitable for few-cycle near-field amplification.The Atg12-Atg5/Atg16L1 complex is recruited by WIPI2b to the site of autophagosome formation. Atg16L1 is an effector of the Golgi resident GTPase Rab33B. Here we identified a minimal stable complex of murine Rab33B(30-202) Q92L and Atg16L1(153-210). Atg16L1(153-210) comprises the C-terminal part of the Atg16L1 coiled-coil domain. We have determined the crystal structure of the Rab33B Q92L/Atg16L1(153-210) effector complex at 3.47 Å resolution. This structure reveals that two Rab33B molecules bind to the diverging α-helices of the dimeric Atg16L1 coiled-coil domain. We mutated Atg16L1 and Rab33B interface residues and found that they disrupt complex formation in pull-down assays and cellular co-localization studies. The Rab33B binding site of Atg16L1 comprises 20 residues and immediately precedes the WIPI2b binding site. Rab33B mutations that abolish Atg16L binding also abrogate Rab33B association with the Golgi stacks. Atg16L1 mutants that are defective in Rab33B binding still co-localize with WIPI2b in vivo. The close proximity of the Rab33B and WIPI2b binding sites might facilitate the recruitment of Rab33B containing vesicles to provide a source of lipids during autophagosome biogenesis.Delay discounting describes the phenomenon whereby the subjective value of a reward declines as the time until its receipt increases. Individuals differ in the subjective value that they assign to future rewards, yet, the components feeding into this appraisal of value remain unclear. We examined whether temporal psychological distance, i.e. the closeness one feels to the past and future, is one such component. English speakers in the USA and Mandarin speakers in China completed a delay discounting task and organized past and future world events on a canvas according to their representation of the event's temporal position relative to themselves. Previous work has identified linguistic and cultural differences in time conception between these populations, thus, we hypothesized that this sample would display the variability necessary to probe whether temporal psychological distance plays a role in reward valuation. We found that English speakers employed horizontal, linear representations of world events, while Mandarin speakers used more two-dimensional, circular representations. Across cultures, individuals who represented the future as more distant discounted future rewards more strongly. Distance representations of past events, however, were associated with discounting behaviors selectively in Mandarin speakers. This suggests that temporal psychological distance plays a fundamental role in farsighted decision-making.Aedes aegypti is the main vector of dengue, Zika, chikungunya, and yellow fever viruses. Controlling populations of vector mosquito species in urban environments is a major challenge and being able to determine what aquatic habitats should be prioritized for controlling Ae. aegypti populations is key to the development of more effective mosquito control strategies. Therefore, our objective was to leverage on the Miami-Dade County, Florida immature mosquito surveillance system based on requested by citizen complaints through 311 calls to determine what are the most important aquatic habitats in the proliferation of Ae. aegypti in Miami. We used a tobit model for Ae. aegypti larvae and pupae count data, type and count of aquatic habitats, and daily rainfall. Our results revealed that storm drains had 45% lower percentage of Ae. aegypti larvae over the total of larvae and pupae adjusted for daily rainfall when compared to tires, followed by bromeliads with 33% and garbage cans with 17%. These results are indicating that storm drains, bromeliads and garbage cans had significantly more pupae in relation to larvae when compared to tires, traditionally know as productive aquatic habitats for Ae. aegypti. Ultimately, the methodology and results from this study can be used by mosquito control agencies to identify habitats that should be prioritized in mosquito management and control actions, as well as to guide and improve policies and increase community awareness and engagement. Moreover, by targeting the most productive aquatic habitats this approach will allow the development of critical emergency outbreak responses by directing the control response efforts to the most productive aquatic habitats.