Polyvinyl-Pyrrolidone-Coated Silver Nanoparticles—The Colloidal,Chemical, and Biological Consequences of Steric Stabilization under Biorelevant Conditions

(1) Background: Several properties of silver nanoparticles (AgNPs), such as cytotoxic, anticancer, and antimicrobial activities, have been subjects of intense research; however, important aspects such as nanoparticle aggregation are generally neglected, although a decline in colloidal stability leads to a loss of the desired biological activities. Colloidal stability is affected by pH, ionic strength, or a plethora of biomolecules that interact with AgNPs under biorelevant conditions. (2) Methods: As only a few studies have focused on the relationship between aggregation behavior and the biological properties of AgNPs, here, we have systematically evaluated this issue by completing a thorough analysis of sterically (via polyvinyl-pyrrolidone (PVP)) stabilized AgNPs that were subjected to different circumstances. We assessed ultraviolet–visible light absorption, dynamic light scattering, zeta potential measurements, in vitro cell viability, and microdilution assays to screen both colloidal stability as well as bioactivity. (3) Results: The results revealed that although PVP provided outstanding biorelevant colloidal stability, the chemical stability of AgNPs could not be maintained completely with this capping material. (4) Conclusion: These unexpected findings led to the realization that stabilizing materials have more profound importance in association with biorelevant applications of nanomaterials than just being simple colloidal stabilizers.     

Hydrodynamic constraints on prey-capture performance in forward-striking snakes

Some specialized aquatic snakes such as Natrix tessellata strike at fish by rapidly accelerating their head towards the prey with their mouth opened widely. This strategy is believed to be suboptimal as relatively high drag forces act on the open jaws and, therefore, probably limit strike speed. Moreover, the bow wave in front of the snake''s jaws could push prey away from the mouth, thus potentially explaining the relatively low capture success observed in these animals (<20%). Here, we used laser-scan based computational fluid dynamics to test these potential constraints on prey-capture performance for N. tessellata. Our simulations showed that drag force indeed increases drastically for striking at a high gape angle. However, we estimated the overall cost in slowing down strike speed to be less pronounced due to the instationary dynamics of the system. In contrast to the expectations, forward displacement of prey was relatively limited (<13% of head length), and forceful collisions between prey and the leading edge of the jaw regularly occurred. However, our models showed that precise aiming by the snake was needed to reduce the chance of deviating the prey to a path bypassing the mouth. Our study also indicated several hydrodynamic advantages for snakes to strike at relatively large prey.     

Modulation of Inflammatory Cytokine Production in Human Monocytes by cGMP and IRAK3

Interleukin-1 receptor-associated kinase-3 (IRAK3) is a critical checkpoint molecule of inflammatory responses in the innate immune system. The pseudokinase domain of IRAK3 contains a guanylate cyclase (GC) centre that generates small amounts of cyclic guanosine monophosphate (cGMP) associated with IRAK3 functions in inflammation. However, the mechanisms of IRAK3 actions are poorly understood. The effects of low cGMP levels on inflammation are unknown, therefore a dose–response effect of cGMP on inflammatory markers was assessed in THP-1 monocytes challenged with lipopolysaccharide (LPS). Sub-nanomolar concentrations of membrane permeable 8-Br-cGMP reduced LPS-induced NFκB activity, IL-6 and TNF-α cytokine levels. Pharmacologically upregulating cellular cGMP levels using a nitric oxide donor reduced cytokine secretion. Downregulating cellular cGMP using a soluble GC inhibitor increased cytokine levels. Knocking down IRAK3 in THP-1 cells revealed that unlike the wild type cells, 8-Br-cGMP did not suppress inflammatory responses. Complementation of IRAK3 knockdown cells with wild type IRAK3 suppressed cytokine production while complementation with an IRAK3 mutant at GC centre only partially restored this function. Together these findings indicate low levels of cGMP form a critical component in suppressing cytokine production and in mediating IRAK3 action, and this may be via a cGMP enriched nanodomain formed by IRAK3 itself.     

Cardiovascular Disease-Associated MicroRNAs as Novel Biomarkers of First-Trimester Screening for Gestational Diabetes Mellitus in the Absence of Other Pregnancy-Related Complications

We assessed the diagnostic potential of cardiovascular disease-associated microRNAs for the early prediction of gestational diabetes mellitus (GDM) in singleton pregnancies of Caucasian descent in the absence of other pregnancy-related complications. Whole peripheral venous blood samples were collected within 10 to 13 weeks of gestation. This retrospective study involved all pregnancies diagnosed with only GDM (n = 121) and 80 normal term pregnancies selected with regard to equality of sample storage time. Gene expression of 29 microRNAs was assessed using real-time RT-PCR. Upregulation of 11 microRNAs (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-23a-3p, miR-100-5p, miR-125b-5p, miR-126-3p, miR-181a-5p, miR-195-5p, miR-499a-5p, and miR-574-3p) was observed in pregnancies destinated to develop GDM. Combined screening of all 11 dysregulated microRNAs showed the highest accuracy for the early identification of pregnancies destinated to develop GDM. This screening identified 47.93% of GDM pregnancies at a 10.0% false positive rate (FPR). The predictive model for GDM based on aberrant microRNA expression profile was further improved via the implementation of clinical characteristics (maternal age and BMI at early stages of gestation and an infertility treatment by assisted reproductive technology). Following this, 69.17% of GDM pregnancies were identified at a 10.0% FPR. The effective prediction model specifically for severe GDM requiring administration of therapy involved using a combination of these three clinical characteristics and three microRNA biomarkers (miR-20a-5p, miR-20b-5p, and miR-195-5p). This model identified 78.95% of cases at a 10.0% FPR. The effective prediction model for GDM managed by diet only required the involvement of these three clinical characteristics and eight microRNA biomarkers (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-100-5p, miR-125b-5p, miR-195-5p, miR-499a-5p, and miR-574-3p). With this, the model identified 50.50% of GDM pregnancies managed by diet only at a 10.0% FPR. When other clinical variables such as history of miscarriage, the presence of trombophilic gene mutations, positive first-trimester screening for preeclampsia and/or fetal growth restriction by the Fetal Medicine Foundation algorithm, and family history of diabetes mellitus in first-degree relatives were included in the GDM prediction model, the predictive power was further increased at a 10.0% FPR (72.50% GDM in total, 89.47% GDM requiring therapy, and 56.44% GDM managed by diet only). Cardiovascular disease-associated microRNAs represent promising early biomarkers to be implemented into routine first-trimester screening programs with a very good predictive potential for GDM.     

Running versus weight lifting in the treatment of depression.

We compared the effectiveness of an aerobic and nonaerobic exercise in the treatment of clinical depression in women. A total of 40 women, screened on the Research Diagnostic Criteria for major or minor depressive disorder, were randomly assigned to an 8-week running (aerobic), weight-lifting (nonaerobic), or wait-list control condition. Subjects were reassessed at mid- and posttreatment, and at 1-, 7-, and 12-month follow-ups. Depression was monitored by the Beck Depression Inventory, Lubin's Depression Adjective Check List, and the Hamilton Rating Scale for Depression; fitness level was assessed using submaximal treadmill testing. Results were remarkably consistent across measures, with both exercise conditions significantly reducing depression compared with the wait list control condition, and generally appearing indistinguishable from each other. No significant between-group fitness changes were noted. These findings indicate that both types of exercise conditions significantly reduce depression and that these results are not dependent on achieving an aerobic effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Extracellular Prolidase (PEPD) Induces Anabolic Processes through EGFR, β1-integrin,and IGF-1R Signaling Pathways in an Experimental Model of Wounded Fibroblasts

The role of prolidase (PEPD) as a ligand of the epidermal growth factor receptor (EGFR) was studied in an experimental model of wound healing in cultured fibroblasts. The cells were treated with PEPD (1–100 nM) and analysis of cell viability, proliferation, migration, collagen biosynthesis, PEPD activity, and the expressions of EGFR, insulin-like growth factor 1 (IGF-1), and β₁-integrin receptor including downstream signaling proteins were performed. It has been found that PEPD stimulated proliferation and migration of fibroblasts via activation of the EGFR-downstream PI3K/Akt/mTOR signaling pathway. Simultaneously, PEPD stimulated the expression of β₁-integrin and IGF-1 receptors and proteins downstream to these receptors such as FAK, Grb2, and ERK1/2. Collagen biosynthesis was increased in control and “wounded” fibroblasts under PEPD treatment. The data suggest that PEPD-induced EGFR signaling may serve as a new attempt to therapy wound healing.     

Modeling and performance improvement of folded coupled lines in miniaturized Quasi‐lumped directional couplers

An efficient modeling method for folded coupled inductors for application in quasi‐lumped directional couplers designed in both symmetric and asymmetric structures has been proposed. The presented model takes into account the deteriorative effects which occur when coupled inductors realized as electrically short coupled‐lines matched to the high impedance standard are folded into, for example, meander or spiral pattern. The deteriorative influence of coupled‐lines' folding on the performance of the resulting directional coupler has been modeled as additional lumped inductors and capacitors on the schematic diagram of a quasi‐lumped directional coupler's subsection. Moreover, it has been shown that this deteriorative influence can be substantially minimized when values of lumped elements constituting the directional coupler are appropriately changed. The proposed design procedure has been experimentally verified by measurements of two 3‐dB single‐section directional couplers designed in symmetric and asymmetric structures as quasi‐lumped couplers with folded coupled inductors. The measurement results show a good agreement with both circuit and electromagnetic analysis which proves the correctness and usefulness of the presented methods. © 2014 Wiley Periodicals, Inc. Int J RF and Microwave CAE 25:1–9, 2015.     

Expanding an Efficient,Electrically Driven and CNT‐Tagged P450 System into the Third Dimension: A Nanowired CNT‐Containing and Enzyme‐Stabilising 3 D Sol–Gel Electrode

Although electrochemically catalysed P450 reactions have been described, their efficiency and applicability remained limited. This is mostly due to low enzyme activity, laborious protein immobilisation and the small electrode surface. We established a novel protein immobilisation method for a determined orientation and electrical wiring of the enzyme without post‐expression modification. By genetic introduction of an anchor‐peptide our method is applicable for screening medium to large mutant libraries and detection by an electrode system. The system was expanded by using wired carbon nanotubes within a sol‐gel matrix to create a three dimensional electrode.