The influence of depressive symptoms on experimental smoking and intention to smoke in a diverse youth sample.

Numerous studies have shown associations between smoking and depression, but the generalizability of the relationship across ethnic groups remains unknown. The present study assessed the association between depression and smoking intention and experimentation among adolescents from four ethnic groups in the Los Angeles area-Chinese/Chinese American, Latino/Hispanic, Persian/Iranian, and White. Over 800 7th graders in the Los Angeles area completed measures of depressive symptoms, experimentation with smoking, intention to smoke, and sociodemographic covariates. Chinese/Chinese American students had the lowest levels of depressive symptoms, whereas Latinos/Hispanics had the highest levels. Latinos/Hispanics also were the most likely to intend to smoke in the next year and were the most likely to have started experimenting with cigarette smoking. Depressive symptoms were significantly associated with intention to smoke even after controlling for language use acculturation, socioeconomic status, gender, and ethnicity. The association between depressive symptoms and intention to smoke did not vary significantly across ethnic groups. These results indicate that the association between depressive symptoms and adolescent smoking generalizes across diverse ethnic groups.     

Rheological assessment of the sol-gel transition for self-assembling low molecular weight gelators

The complexity of the transition from solution to gel for low molecular weight gelators in apolar solvents makes it incredibly difficult to assess the gel point. Since both nucleation and crystal growth occurs prior to the formation of a continuous three dimensional network numerous techniques, such as calorimetry and inflection point of the complex modulus, are invalid when probing the gel point. However, monitoring the frequency dependence of G′ and G″ illustrates the transition from a dilute solution to a weak gel which may be differentiated from the gel point observed by the decreasing value of the complex viscosity as a function of frequency. For 3% 12-hydroxystearic acid in mineral oil once the gelator nucleates the material behaves as a dilute solution, upon crystal growth (67 °C) we observe the true cross over point which is independent of frequency and finally a strong gel is formed at 64 °C where G′ and G″ are independent of frequency.     

Biophysical Modulation of Mesenchymal Stem Cell Differentiation in the Context of Skeletal Repair

A prominent feature of the skeleton is its ability to remodel in response to biophysical stimuli and to repair under varied biophysical conditions. This allows the skeleton considerable adaptation to meet its physiological roles of stability and movement. Skeletal cells and their mesenchymal precursors exist in a native environment rich with biophysical signals, and they sense and respond to those signals to meet organismal demands of the skeleton. While mechanical strain is the most recognized of the skeletal biophysical stimuli, signaling phenomena also include fluid flow, hydrostatic pressure, shear stress, and ion-movement-related electrokinetic phenomena including, prominently, streaming potentials. Because of the complex interactions of these electromechanical signals, it is difficult to isolate the significance of each. The application of external electrical and electromagnetic fields allows an exploration of the effects of these stimuli on cell differentiation and extra-cellular matrix formation in the absence of mechanical strain. This review takes a distinctly translational approach to mechanistic and preclinical studies of differentiation and skeletal lineage commitment of mesenchymal cells under biophysical stimulation. In vitro studies facilitate the examination of isolated cellular responses while in vivo studies permit the observation of cell differentiation and extracellular matrix synthesis.     

SOAT1: A Suitable Target for Therapy in High-Grade Astrocytic Glioma?

Targeting molecular alterations as an effective treatment for isocitrate dehydrogenase-wildtype glioblastoma (GBM) patients has not yet been established. Sterol-O-Acyl Transferase 1 (SOAT1), a key enzyme in the conversion of endoplasmic reticulum cholesterol to esters for storage in lipid droplets (LD), serves as a target for the orphan drug mitotane to treat adrenocortical carcinoma. Inhibition of SOAT1 also suppresses GBM growth. Here, we refined SOAT1-expression in GBM and IDH-mutant astrocytoma, CNS WHO grade 4 (HGA), and assessed the distribution of LD in these tumors. Twenty-seven GBM and three HGA specimens were evaluated by multiple GFAP, Iba1, IDH1 R132H, and SOAT1 immunofluorescence labeling as well as Oil Red O staining. To a small extent SOAT1 was expressed by tumor cells in both tumor entities. In contrast, strong expression was observed in glioma-associated macrophages. Triple immunofluorescence labeling revealed, for the first time, evidence for SOAT1 colocalization with Iba1 and IDH1 R132H, respectively. Furthermore, a notable difference in the amount of LD between GBM and HGA was observed. Therefore, SOAT1 suppression might be a therapeutic option to target GBM and HGA growth and invasiveness. In addition, the high expression in cells related to neuroinflammation could be beneficial for a concomitant suppression of protumoral microglia/macrophages.     

APOB CRISPR-Cas9 Engineering in Hypobetalipoproteinemia: A Promising Tool for Functional Studies of Novel Variants

Hypobetalipoproteinemia is characterized by LDL-cholesterol and apolipoprotein B (apoB) plasma levels below the fifth percentile for age and sex. Familial hypobetalipoproteinemia (FHBL) is mostly caused by premature termination codons in the APOB gene, a condition associated with fatty liver and steatohepatitis. Nevertheless, many families with a FHBL phenotype carry APOB missense variants of uncertain significance (VUS). We here aimed to develop a proof-of-principle experiment to assess the pathogenicity of VUS using the genome editing of human liver cells. We identified a novel heterozygous APOB-VUS (p.Leu351Arg), in a FHBL family. We generated APOB knock-out (KO) and APOB-p.Leu351Arg knock-in Huh7 cells using CRISPR-Cas9 technology and studied the APOB expression, synthesis and secretion by digital droplet PCR and ELISA quantification. The APOB expression was decreased by 70% in the heterozygous APOB-KO cells and almost abolished in the homozygous-KO cells, with a consistent decrease in apoB production and secretion. The APOB-p.Leu351Arg homozygous cells presented with a 40% decreased APOB expression and undetectable apoB levels in cellular extracts and supernatant. Thus, the p.Leu351Arg affected the apoB secretion, which led us to classify this new variant as likely pathogenic and to set up a hepatic follow-up in this family. Therefore, the functional assessment of APOB-missense variants, using gene-editing technologies, will lead to improvements in the molecular diagnosis of FHBL and the personalized follow-up of these patients.     

Chemorheology of Aqueous-Based Alumina-Poly(vinyl alcohol) Gelcasting Suspensions

A new gelcasting system based on aqueous-based alumina-poly(vinyl alcohol) (PVA) suspensions cross-linked by an organotitanate coupling agent has been developed. The chemorheological properties of this system exhibited a strong compositional dependence. A sol-gel phase diagram was established, which yielded the critical titanium concentration ([Ti]_c) required for gelation at a given PVA volume fraction as well as the minimum PVA volume fraction (φ^min_PVA= 0.0245) and titanium concentration ([Ti]_min= 9.984 × 10^-4 g of Ti/mL) below which gelation was not observed irrespective of solution composition. The gelation time of suspensions of constant PVA volume fraction (φ^soln_PVA) decreased with increased cross-linking agent concentration, temperature, and solids volume fraction. The steady-state viscosity and elastic modulus of polymer solutions (φ^soln_PVA= 0.05) of varying [Ti] were well described by the percolation model, giving scaling exponents of 0.84 and 1.79, respectively. The steady-state elastic modulus of gelcasting suspensions, which provided a measure of their handling strength in the as-gelled state, increased with increased solids volume fraction.     

Simple and Straightforward Synthesis of Porous Ionosilica for Efficient Chromate Adsorption

We report a very simple synthesis strategy for the formation of moderately porous ionosilica materials containing ammonium groups. We synthesized an ionosilica xerogel and an ionosilica aerogel, either via conventional or supercritical work‐up. The synthesis scheme of both precursor and ionosilica materials could easily be up‐scaled to a 100 g scale. All syntheses and work‐up procedures are sustainable as no additional agent and very low quantities of solvents were used, and no additional purifications steps were necessary. Although both materials show excellent anion exchange properties for chromate adsorption, noticeable differences were found regarding the thermodynamics of the exchange process. We attribute these differences to different surface chemistries of the materials, induced by the different work‐up procedures. Due to the easy availability of high quantities of material, ionosilicas can be implemented as functional ion exchange materials in larger scale processes, thus opening new fields of applications.