Conducting polymer-based multilayer films for instructive biomaterial coatings

Aim: To demonstrate the design, fabrication and testing of conformable conducting biomaterials that encourage cell alignment. Materials & methods: Thin conducting composite biomaterials based on multilayer films of poly (3,4-ethylenedioxythiophene) derivatives, chitosan and gelatin were prepared in a layer-by-layer fashion. Fibroblasts were observed with fluorescence microscopy and their alignment (relative to the dipping direction and direction of electrical current passed through the films) was determined using ImageJ. Results: Fibroblasts adhered to and proliferated on the films. Fibroblasts aligned with the dipping direction used during film preparation and this was enhanced by a DC current. Conclusion: We report the preparation of conducting polymer-based films that enhance the alignment of fibroblasts on their surface which is an important feature of a variety of tissues. Lay abstract: Cells inhabit environments known as the extracellular matrix (ECM) which consists of a mixture of different biomolecules, and the precise composition and topographical properties are different in different tissues (e.g., bone, brain, muscle, skin). Cells interact intimately with the ECM, not only constructing the biomolecules, but assist its organization in 3D space, and its degradation (which is important for tissue remodeling); reciprocally, cells respond to the ECM (e.g., by modifying their size, shape, etc). Cellular alignment is observed in organs and tissues such as bones, muscles and skin, and this alignment is important for the healthy functioning of the organ/tissue. Here, we present a novel method of aligning cells on biomaterials, simply by applying an electrical current through the biomaterial

TLR9 ligation in pancreatic stellate cells promotes tumorigenesis

Modulation of Toll-like receptor (TLR) signaling can have protective or protumorigenic effects on oncogenesis depending on the cancer subtype and on specific inflammatory elements within the tumor milieu. We found that TLR9 is widely expressed early during the course of pancreatic transformation and that TLR9 ligands are ubiquitous within the tumor microenvironment. TLR9 ligation markedly accelerates oncogenesis, whereas TLR9 deletion is protective. We show that TLR9 activation has distinct effects on the epithelial, inflammatory, and fibrogenic cellular subsets in pancreatic carcinoma and plays a central role in cross talk between these compartments. Specifically, TLR9 activation can induce proinflammatory signaling in transformed epithelial cells, but does not elicit oncogene expression or cancer cell proliferation. Conversely, TLR9 ligation induces pancreatic stellate cells (PSCs) to become fibrogenic and secrete chemokines that promote epithelial cell proliferation. TLR9-activated PSCs mediate their protumorigenic effects on the epithelial compartment via CCL11. Additionally, TLR9 has immune-suppressive effects in the tumor microenvironment (TME) via induction of regulatory T cell recruitment and myeloid-derived suppressor cell proliferation. Collectively, our work shows that TLR9 has protumorigenic effects in pancreatic carcinoma which are distinct from its influence in extrapancreatic malignancies and from the mechanistic effects of other TLRs on pancreatic oncogenesis

Lifestyles and discomfort in a sample of young Romanian students

Introduction. The 40.3% of the Romanian youth population is at risk of poverty or social exclusion, and, in addition, the abuse of substances increases. It was interesting to evaluate the attitudes shared by pupils as well as their knowledge of these substances with a view to analyzing causes and types of risky behaviour in young people. Methods. This is an observational study on the harassment influence in the lifestyle of a sample of Craiova high-school students The Fagerstr\uf6m Test was applied to evaluate the degree of nicotine dependence, and the data processed to assess the Odds Ratio. Results. The sample was composed by 1,980 students with an average age of 17, of which 1,727 correctly responded to the questionnaire. The 37.4% of students admit to smoke, and the 67% to drink alcohol. The Fagerstr\uf6m test showed that the 68.2% of respondents are not highly addicted to smoke while the 31.8% was associated with a middle-to-high addiction level. A worrying weekly consumption of beer has been registered in the students. Regarding psychological distress caused by harassment a high Odds Ratio was recorded between the smokers and the drug users. Conclusions. More than half of students did not know about the health consequences of smoking, and the same result was recorded about the consumption of alcohol. A special attention should be done to the understanding of harassment problem in the young people. In fact, almost all the respondents declared to have suffered abuse and admits to use drug and cigarettes

On the evaluation of strain energy release rate of cement-bone bonded joints under mode II loading

Bone cements based on poly(methylmethacrylate) (PMMA) are primarily used in joint replacement surgeries. In the fixation of joint replacement, the self-curing cement fills constitutes a very important interface. To understand and improve the interaction between cortical bone and bone cement it is essential to characterize the mechanical properties of cement-bone bonded joints in full detail. In this study, the end-notched flexure test was used in the context of pure mode II fracture characterisation of cement-bone bonded joints. A data reduction scheme based on crack equivalent concept was employed to overcome the difficulties inherent to crack length monitoring during damage propagation. A finite element method combined with a cohesive zone model was first used to validate numerically the adopted method. The procedure was subsequently applied to experimental results to determine the fracture toughness of cement-bone bonded joints under pure mode II loading. The consistency of the obtained results leads to the conclusion that the adopted procedure is adequate to carry out fracture characterisation of these joints under pure mode II loading. The innovative aspect of the present work lies in the application of cohesive zone modelling approach to PMMA-based cement-bone bonded joints

Functional consequences of postnatal interventions in a mouse model of Fragile X syndrome

BackgroundFragile X syndrome (FXS) is a leading genetic cause of autism and intellectual disability with cortical hyperexcitability and sensory hypersensitivity attributed to loss and hypofunction of inhibitory parvalbumin-expressing (PV) cells. Our studies provide novel insights into the role of excitatory neurons in abnormal development of PV cells during a postnatal period of inhibitory circuit refinement.MethodsTo achieve Fragile X mental retardation gene (Fmr1) deletion and re-expression in excitatory neurons during the postnatal day (P)14-P21 period, we generated CreCaMKIIa/Fmr1Flox/y (cOFF) and CreCaMKIIa/Fmr1FloxNeo/y (cON) mice, respectively. Cortical phenotypes were evaluated in adult mice using biochemical, cellular, clinically relevant electroencephalogram (EEG) and behavioral tests.ResultsWe found that similar to global Fmr1 KO mice, the density of PV-expressing cells, their activation, and sound-evoked gamma synchronization were impaired in cOFF mice, but the phenotypes were improved in cON mice. cOFF mice also showed enhanced cortical gelatinase activity and baseline EEG gamma power, which were reduced in cON mice. In addition, TrkB phosphorylation and PV levels were lower in cOFF mice, which also showed increased locomotor activity and anxiety-like behaviors. Remarkably, when FMRP levels were restored in only excitatory neurons during the P14-P21 period, TrkB phosphorylation and mouse behaviors were also improved.ConclusionsThese results indicate that postnatal deletion or re-expression of FMRP in excitatory neurons is sufficient to elicit or ameliorate structural and functional cortical deficits, and abnormal behaviors in mice, informing future studies about appropriate treatment windows and providing fundamental insights into the cellular mechanisms of cortical circuit dysfunction in FXS

Strong Constraints on Neutrino Nonstandard Interactions from TeV-Scale νμ_{μ} Disappearance at IceCube

We report a search for nonstandard neutrino interactions (NSI) using eight years of TeV-scale atmospheric muon neutrino data from the IceCube Neutrino Observatory. By reconstructing incident energies and zenith angles for atmospheric neutrino events, this analysis presents unified confidence intervals for the NSI parameter εμτ. The best-fit value is consistent with no NSI at a p value of 25.2%. With a 90% confidence interval of −0.0041≤εμτ≤0.0031 along the real axis and similar strength in the complex plane, this result is the strongest constraint on any NSI parameter from any oscillation channel to date

Searching for High-energy Neutrino Emission from Galaxy Clusters with IceCube

Galaxy clusters have the potential to accelerate cosmic rays (CRs) to ultrahigh energies via accretion shocks or embedded CR acceleration sites. The CRs with energies below the Hillas condition will be confined within the cluster and eventually interact with the intracluster medium gas to produce secondary neutrinos and gamma rays. Using 9.5 yr of muon neutrino track events from the IceCube Neutrino Observatory, we report the results of a stacking analysis of 1094 galaxy clusters with masses ≳10$^{14}$ M⊙ and redshifts between 0.01 and ∼1 detected by the Planck mission via the Sunyaev–Zel’dovich effect. We find no evidence for significant neutrino emission and report upper limits on the cumulative unresolved neutrino flux from massive galaxy clusters after accounting for the completeness of the catalog up to a redshift of 2, assuming three different weighting scenarios for the stacking and three different power-law spectra. Weighting the sources according to mass and distance, we set upper limits at a 90% confidence level that constrain the flux of neutrinos from massive galaxy clusters (≳10$^{14}$ M⊙) to be no more than 4.6% of the diffuse IceCube observations at 100 TeV, assuming an unbroken E−$^{2.5}$ power-law spectrum

Engaging the user community for advancing societal applications of the surface water ocean topography mission

Scheduled for launch in 2021, the Surface Water and Ocean Topography (SWOT) mission will be a truly unique mission that will provide high-temporal-frequency maps of surface water extents and elevation variations of global water bodies (lakes/reservoirs, rivers, estuaries, oceans, and sea ice) at higher spatial resolution than is available with current technologies (Biancamaria et al. 2016; Alsdorf et al. 2007). The primary instrument on SWOT is based on a Ka-band radar interferometer (KaRIN), which uses radar interferometery technology. The satellite will fly two radar antennas at either end of a 10-m (33 ft) mast, allowing it to measure the elevation of the surface along a 120-km (75 mi)-wide swath below. The availability of high-frequency and high-resolution maps of elevations and extents for surface water bodies and oceans will present unique opportunities to address numerous societally relevant challenges around the globe (Srinivasan et al. 2015). These opportunities may include such diverse and far-ranging applications as fisheries management, flood inundation mapping/risk mitigation/forecasting, wildlife conservation, global data assimilation for improving forecast of ocean tides and weather, reservoir management, climate change impacts and adaptation, and river discharge estimation, among others