Superswelling Microneedle Arrays for Dermal Interstitial Fluid (Prote)Omics

The noninvasive sampling of dermal interstitial fluid (ISF) for the monitoring of clinical biomarkers is a greatly appealing area of research. The identification of molecular biomarkers in biological fluids has been accelerated with -omics analyses but remains limited in ISF because of its time-consuming and complex extraction process. Here, the generation of microneedle (MN) patches made of superabsorbent acrylate-based hydrogels for the rapid sampling of dermal ISF is described to explore its proteome. In depth, iterative optimization allows the identification of novel acrylate-based compositions with the required chemical, mechanical, and biocompatibility properties allowing proteomic analysis of the extracted ISF for the first time after sampling with swelling MNs. The generated MN arrays show no cytotoxic effect, successfully cross the stratum corneum, and can collect up to 6 µL of dermal ISF in 10 min in vivo. Proteomics lead to the detection of 176 clinically relevant biomarkers in the collected samples validating the use of ISF as a relevant bodily fluid for disease monitoring and diagnostic. Importantly, it is discovered that extraction fingerprint is strongly dependent on the MNs chemistry, and thus specific biomarkers could be selectively extracted by tuning the composition of the patch, making the system versatile and specific.     

Quantitative Proteomic Approach Reveals Altered Metabolic Pathways in Response to the Inhibition of Lysine Deacetylases in A549 Cells under Normoxia and Hypoxia

Growing evidence is showing that acetylation plays an essential role in cancer, but studies on the impact of KDAC inhibition (KDACi) on the metabolic profile are still in their infancy. Here, we analyzed, by using an iTRAQ-based quantitative proteomics approach, the changes in the proteome of KRAS-mutated non-small cell lung cancer (NSCLC) A549 cells in response to trichostatin-A (TSA) and nicotinamide (NAM) under normoxia and hypoxia. Part of this response was further validated by molecular and biochemical analyses and correlated with the proliferation rates, apoptotic cell death, and activation of ROS scavenging mechanisms in opposition to the ROS production. Despite the differences among the KDAC inhibitors, up-regulation of glycolysis, TCA cycle, oxidative phosphorylation and fatty acid synthesis emerged as a common metabolic response underlying KDACi. We also observed that some of the KDACi effects at metabolic levels are enhanced under hypoxia. Furthermore, we used a drug repositioning machine learning approach to list candidate metabolic therapeutic agents for KRAS mutated NSCLC. Together, these results allow us to better understand the metabolic regulations underlying KDACi in NSCLC, taking into account the microenvironment of tumors related to hypoxia, and bring new insights for the future rational design of new therapies.     

A simple model for the semicontinuous heterophase polymerization: Ethyl methacrylate as a case example

A simple but comprehensive model considering homogeneous and micellar nucleation, coagulation, entry of radicals to particles and to micelles and radicals' exit from particles, is presented. The model is validated, in a starved semicontinuous heterophase polymerization of ethyl methacrylate, at three monomer addition rates. The model accurately describes the overall and instantaneous conversion, the average particle density and diameter, and the number and weight average molar masses evolutions over time. It is found that even though the average number of radicals is much smaller than 0.5, the system is not 0-1. An empirical function was used to describe the gel effect. The homogeneous nucleation was the prevailing mechanism for particle formation and large exit rates of radicals were observed. POLYM. ENG. SCI., 60: 223–232, 2019. © 2019 Society of Plastics Engineers     

Intraseptal scopolamine has differential effects on Pavlovian eye blink and heart rate conditioning.

Evaluated the effects of intraseptal scopolamine hydrobromide (40 μg) injections on Pavlovian (classical) conditioning, with tones used as the CS and a periorbital electric shock train as the UCS, using New Zealand albino rabbits. Eyeblink (EB) and heart rate (HTR) CRs were concomitantly recorded. Although injections of scopolamine into the medial septum impaired the acquisition of the Pavlovian conditioned eyelid reflex, these injections enhanced the magnitude of accompanying Pavlovian conditioned HTR decelerations. However, scopolamine applied to the lateral septal area had no effect on EB conditioning, relative to the vehicle; like medial injections, scopolamine also enhanced the magnitude of the accompanying HTR decelerations. Results are compatible with those of previous investigations indicating that medial septal dysfunction impairs somatomotor conditioning but leaves autonomic conditioning intact and that septal dysfunction produces a parasympathetic bias of the cardiovascular system. (49 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissipation in Mesoscopic Superconductors with Ac Magnetic Fields

The response of mesoscopic superconductors to an ac magnetic field is investigated both experimentally and with numerical simulations. We study small square samples with dimensions of the order of the penetration depth. We obtain the ac susceptibitity χ=χ′+iχ″ at microwave frequencies as a function of the dc magnetic field H _dc. We find that the dissipation, given by x″, has a non monotonous behavior in mesoscopic samples. In the numerical simulations we obtain that the dissipation increases before the penetration of vortices and then it decreases abruptly after vortices have entered, the sample. This is verified experimentally, where we find that χ″ has strong oscillations as a function of H _dc in small squares of Pb.     

Fueguian cranial morphology: the adaptation to a cold, harsh environment

Craniometric data from the three extinct tribes that inhabited Tierra del Fuego (Selk'nam, Yámana, and Kawéskar) were gathered following Howell's measurement technique. We studied 180 skulls preserved at thirteen different institutions. Analysis of variance (ANOVA) between groups showed that morphological similarities among Fueguian groups are far more important than some differences between marine (Yámana and Kawéskar) and terrestrial (Selk'nam) groups. A principal component analysis (PCA) generated from the correlation matrix shows that Fueguians fall as outliers with respect to the typical Mongoloid morphology. In addition, a UPGMA tree generated from a squared Euclidean distance matrix indicates that Fueguian groups have a morphological pattern that is very distinct from that of other present-day Amerindian groups, with the exception of the Eskimos. One of the variables that contributes substantially to the differentiation of Eskimos and Fueguians is the nasal height. This suggests that nasal morphology in both groups could be a response to adaptive pressures related to the cold environment. However, other morphological particularities of Fueguian skulls, such as craniofacial robustness and variables of craniofacial width, can be attributed to a large masticatory stress. As a whole, the morphological features of Fueguian groups can be regarded as a general adaptive response to a very harsh environment, along with the retention of some plesiomorphic features. Assuming that the initial entry in Tierra de Fuego took place around 10,000 years BP, before the disappearance of the last land bridges in the Magellan Straits, then this adaptation might have arisen in a relatively short period, hastened by the extreme environmental conditions.