Vapor nanobubble is the more reliable photothermal mechanism for inducing endosomal escape of siRNA without disturbing cell homeostasis

Strategies for controlled delivery of therapeutic siRNA into living cells are in high demand as endosomal escape remains the most prominent bottleneck at the intracellular level. Photothermal properties of gold nanoparticles (AuNP) can be used to overcome the endosomal membrane barrier upon laser irradiation by two mechanisms: endosomal rupture by mechanical energy from water vapor nanobubbles (VNBs), or permeabilization of the endosomal membrane by heat diffusion. Here we evaluated how both mechanisms influence cargo release, transfection efficiency, acute cytotoxicity and cell homeostasis. Using a siRNA/AuNP drug delivery system we found that the in vitro release of siRNA from the AuNP carrier occurs equally efficiently by VNB formation or heat generation. Heat-mediated endosomal escape happened more efficiently in cells that had more particles per endosome, resulting in variable siRNA-induced downregulation (20-50%). VNB-mediated endosomal escape did not dependent on the number of AuNP per endosome, yielding high downregulations (50-60%) independent of the cell type. Effects on cell homeostasis by whole transcriptome analysis, showed a quick recover after 24 h or 48 h for either of both photothermal mechanisms. We conclude that VNBs are more consistent to induce efficient endosomal escape and gene silencing independent of the cell type without long lasting effects on cell homeostasis

Hypoglycemic Activity of Okra (Abelmoschus esculentus) in Participants with Impaired Fasting Glucose

Impaired fasting glucose (IFG) is characterized by a blood glucose level higher than normalbut lower than that of diabetes level. Abelmoschus esculentus (okra) is an alternativehypoglycemic and antidiabetic plant due to its phytochemical constituents that regulateintestinal glucose absorption and prevents insulin resistance. This study determined thehypoglycemic activity of okra among IFG participants. Subjects were random subjects withimpaired fasting glucose results upon screening. Quasi-experimental pre-test post-test wasused where a standard glucose load was consumed in the control phase and powdered okraseed-peel mixed with the glucose load was consumed during the experimental phase. The bloodsugar concentration was measured again every hour until three hours after consumption of thestandard glucose load. In the experimental phase, the same group of participants was asked toconsume 75 grams of glucose load with powdered okra peel that depends on their body weight(200 mg/kg of body mass). Fasting, 1 -hour, 2-hour and 3-hour glucose concentration weremeasured the same way it was done during the control phase. Statistical analysis revealed thatAbelmoschus esculentus has its hypoglycemic effect only during the first hour while dataresults for the 2nd and 3 rd hour are considered insignificant. The results proved that okra’smechanism in lowering glucose levels is immediate yet of short duration. Based on the datagathered, the researchers conclude that the powdered peel of Abelmoschus esculentus (okra) iseffective in lowering the blood glucose levels of IFG individuals only during the first hour afterthe administration of oral glucose load. Abelmoschus esculentus may not be effective inlowering the blood glucose after the next hours due to the fact that its mechanism of action isimmediate but of short duration. The researchers recommend future researches on the study ofAbelmoschus esculentus using increased dosage of each participant and that the experimentshould be performed at the same month

Silicone optical elements for cost-effective freeform solar concentration

The use of silicone optical elements is demonstrated for a concentrated photovoltaic system. These components show over 96% transmission through most of the solar spectrum and excellent temperature stability. Unique moldability enables the use of complex freeform designs. A light, compact, and cost-effective concentrated photovoltaic system based on silicone optics is proposed. In this system, air-plasma treatment is utilized to overcome the mechanical properties of silicone and difficulties with coating to reduce Fresnel loss. Lens arrays and waveguides are fabricated by injection molding following freeform optical design by LightTools. First-order characterizations are also performed. (c) 2019 Optical Society of America under the terms of the OSA Open Access Publishing AgreementAdvanced Research Projects Agency-Energy (ARPA-E) MOSAIC program [DE-AR0000839]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Achieving global malaria eradication in changing landscapes.

Land use and land cover changes, such as deforestation, agricultural expansion and urbanization, are one of the largest anthropogenic environmental changes globally. Recent initiatives to evaluate the feasibility of malaria eradication have highlighted impacts of landscape changes on malaria transmission and the potential of these changes to undermine malaria control and elimination efforts. Multisectoral approaches are needed to detect and minimize negative impacts of land use and land cover changes on malaria transmission while supporting development aiding malaria control, elimination and ultimately eradication. Pathways through which land use and land cover changes disrupt social and ecological systems to increase or decrease malaria risks are outlined, identifying priorities and opportunities for a global malaria eradication campaign. The impacts of land use and land cover changes on malaria transmission are complex and highly context-specific, with effects changing over time and space. Landscape changes are only one element of a complex development process with wider economic and social dimensions affecting human health and wellbeing. While deforestation and other landscape changes threaten to undermine malaria control efforts and have driven the emergence of zoonotic malaria, most of the malaria elimination successes have been underpinned by agricultural development and land management. Malaria eradication is not feasible without addressing these changing risks while, conversely, consideration of malaria impacts in land management decisions has the potential to significantly accelerate progress towards eradication. Multisectoral cooperation and approaches to linking malaria control and environmental science, such as conducting locally relevant ecological monitoring, integrating landscape data into malaria surveillance systems and designing environmental management strategies to reduce malaria burdens, are essential to achieve malaria eradication

Structural Invariants in Individuals Language Use: The "Ego Network" of Words

The cognitive constraints that humans exhibit in their social interactions have been extensively studied by anthropologists, who have highlighted their regularities across different types of social networks. We postulate that similar regularities can be found in other cognitive processes, such as those involving language production. In order to provide preliminary evidence for this claim, we analyse a dataset containing tweets of a heterogeneous group of Twitter users (regular users and professional writers). Leveraging a methodology similar to the one used to uncover the well-established social cognitive constraints, we find that a concentric layered structure (which we call ego network of words, in analogy to the ego network of social relationships) very well captures how individuals organise the words they use. The size of the layers in this structure regularly grows (approximately 2–3 times with respect to the previous one) when moving outwards, and the two penultimate external layers consistently account for approximately 60% and 30% of the used words (the outermost layer contains 100% of the words), irrespective of the number of the total number of layers of the user

Inhibiting ERK Activation with CI-1040 Leads to Compensatory Upregulation of Alternate MAPKs and Plasminogen Activator Inhibitor-1 following Subtotal Nephrectomy with No Impact on Kidney Fibrosis

Extracellular-signal regulated kinase (ERK) activation by MEK plays a key role in many of the cellular processes that underlie progressive kidney fibrosis including cell proliferation, apoptosis and transforming growth factor β1-mediated epithelial to mesenchymal transition. We therefore assessed the therapeutic impact of ERK1/2 inhibition using a MEK inhibitor in the rat 5/6 subtotal nephrectomy (SNx) model of kidney fibrosis. There was a twentyfold upregulation in phospho-ERK1/2 expression in the kidney after SNx in Male Wistar rats. Rats undergoing SNx became hypertensive, proteinuric and developed progressive kidney failure with reduced creatinine clearance. Treatment with the MEK inhibitor, CI-1040 abolished phospho- ERK1/2 expression in kidney tissue and prevented phospho-ERK1/2 expression in peripheral lymphocytes during the entire course of therapy. CI-1040 had no impact on creatinine clearance, proteinuria, glomerular and tubular fibrosis, and α-smooth muscle actin expression. However, inhibition of ERK1/2 activation led to significant compensatory upregulation of the MAP kinases, p38 and JNK in kidney tissue. CI-1040 also increased the expression of plasminogen activator inhibitor-1 (PAI-1), a key inhibitor of plasmin-dependent matrix metalloproteinases. Thus inhibition of ERK1/2 activation has no therapeutic effect on kidney fibrosis in SNx possibly due to increased compensatory activation of the p38 and JNK signalling pathways with subsequent upregulation of PAI-1

Development of a Real-Time Microchip PCR System for Portable Plant Disease Diagnosis

Rapid and accurate detection of plant pathogens in the field is crucial to prevent the proliferation of infected crops. Polymerase chain reaction (PCR) process is the most reliable and accepted method for plant pathogen diagnosis, however current conventional PCR machines are not portable and require additional post-processing steps to detect the amplified DNA (amplicon) of pathogens. Real-time PCR can directly quantify the amplicon during the DNA amplification without the need for post processing, thus more suitable for field operations, however still takes time and require large instruments that are costly and not portable. Microchip PCR systems have emerged in the past decade to miniaturize conventional PCR systems and to reduce operation time and cost. Real-time microchip PCR systems have also emerged, but unfortunately all reported portable real-time microchip PCR systems require various auxiliary instruments. Here we present a stand-alone real-time microchip PCR system composed of a PCR reaction chamber microchip with integrated thin-film heater, a compact fluorescence detector to detect amplified DNA, a microcontroller to control the entire thermocycling operation with data acquisition capability, and a battery. The entire system is 25 × 16 × 8 cm(3) in size and 843 g in weight. The disposable microchip requires only 8-µl sample volume and a single PCR run consumes 110 mAh of power. A DNA extraction protocol, notably without the use of liquid nitrogen, chemicals, and other large lab equipment, was developed for field operations. The developed real-time microchip PCR system and the DNA extraction protocol were used to successfully detect six different fungal and bacterial plant pathogens with 100% success rate to a detection limit of 5 ng/8 µl sample

Farmers' reasoning behind the uptake of agroforestry practices: evidence from multiple case-studies across Europe

Potential benefits and costs of agroforestry practices have been analysed by experts, but few studies have captured farmers’ perspectives on why agroforestry might be adopted on a European scale. This study provides answers to this question, through an analysis of 183 farmer interviews in 14 case study systems in eight European countries. The study systems included high natural and cultural value agroforestry systems, silvoarable systems, high value tree systems, and silvopasture systems, as well as systems where no agroforestry practices were occurring. A mixed method approach combining quantitative and qualitative approaches was taken throughout the interviews. Narrative thematic data analysis was performed. Data collection proceeded until no new themes emerged. Within a given case study, i.e. the different systems in different European regions, this sampling was performed both for farmers who practice agroforestry and farmers who did not. Results point to a great diversity of agroforestry practices, although many of the farmers are not aware of the term or concept of agroforestry, despite implementing the practice in their own farms. While only a few farmers mentioned eligibility for direct payments in the CAP as the main reason to remove trees from their land, to avoid the reduction of the funded area, the tradition in the family or the region, learning from others, and increasing the diversification of products play the most important role in adopting or not agroforestry systems