The mechanistic/mammalian target of rapamycin (mTOR), a protein discovered in 1991, integrates a complex pathway with a key role in maintaining cellular homeostasis. By comprising two functionally ...distinct complexes, mTOR complex 1 (mTORC1) and mTORC2, it is a central cellular hub that integrates intra- and extracellular signals of energy, nutrient, and hormone availability, modulating the molecular responses to acquire a homeostatic state through the regulation of anabolic and catabolic processes. Accordingly, dysregulation of mTOR pathway has been implicated in a variety of human diseases. While major advances have been made regarding the regulators and effectors of mTOR signaling pathway, insights into the regulation of mTOR gene expression are beginning to emerge. Here, we present the current available data regarding the mTOR expression regulation at the level of transcription, translation and mRNA stability and systematize the current knowledge about the fluctuations of mTOR expression observed in several diseases, both cancerous and non-cancerous. In addition, we discuss whether mTOR expression changes can be used as a biomarker for diagnosis, disease progression, prognosis and/or response to therapeutics. We believe that our study will contribute for the implementation of new disease biomarkers based on mTOR as it gives an exhaustive perspective about the regulation of mTOR gene expression in both normal and pathological conditions.
The μeV axion is a well-motivated extension to the standard model. The Axion Dark Matter eXperiment (ADMX) collaboration seeks to discover this particle by looking for the resonant conversion of ...dark-matter axions to microwave photons in a strong magnetic field. In this Letter, we report results from a pathfinder experiment, the ADMX "Sidecar," which is designed to pave the way for future, higher mass, searches. This testbed experiment lives inside of and operates in tandem with the main ADMX experiment. The Sidecar experiment excludes masses in three widely spaced frequency ranges (4202-4249, 5086-5799, and 7173-7203 MHz). In addition, Sidecar demonstrates the successful use of a piezoelectric actuator for cavity tuning. Finally, this publication is the first to report data measured using both the TM_{010} and TM_{020} modes.
This Letter reports on a cavity haloscope search for dark matter axions in the Galactic halo in the mass range 2.81-3.31 μeV. This search utilizes the combination of a low-noise Josephson parametric ...amplifier and a large-cavity haloscope to achieve unprecedented sensitivity across this mass range. This search excludes the full range of axion-photon coupling values predicted in benchmark models of the invisible axion that solve the strong CP problem of quantum chromodynamics.
RNA interference has had major advances as a developing tool for pest management. In laboratory experiments, double-stranded RNA (dsRNA) is often administered to the insect by genetic modification of ...the crop, or synthesized in vitro and topically applied to the crop. Here, we engineered genetically modified yeast that express dsRNA targeting y-Tubulin in Drosophila suzukii. Our design takes advantage of the symbiotic interactions between Drosophila, yeast, and fruit crops. Yeast is naturally found growing on the surface of fruit crops, constitutes a major component of the Drosophila microbiome, and is highly attractive to Drosophila. Thus, this naturally attractive yeast biopesticide can deliver dsRNA to an insect pest without the need for genetic crop modification. We demonstrate that this biopesticide decreases larval survivorship, and reduces locomotor activity and reproductive fitness in adults, which are indicative of general health decline. To our knowledge, this is the first study to show that yeast can be used to deliver dsRNA to an insect pest.
We report the results from a haloscope search for axion dark matter in the 3.3-4.2 μeV mass range. This search excludes the axion-photon coupling predicted by one of the benchmark models of ..."invisible" axion dark matter, the Kim-Shifman-Vainshtein-Zakharov model. This sensitivity is achieved using a large-volume cavity, a superconducting magnet, an ultra low noise Josephson parametric amplifier, and sub-Kelvin temperatures. The validity of our detection procedure is ensured by injecting and detecting blind synthetic axion signals.
In recent years, the development of new electrochemical cells for redox flow batteries (RFBs) has been of great interest. This paper presents the design and hydrodynamic evaluation of differing RFBs ...geometries, via computational tools, considering that experimental optimization is expensive and highly time consuming. A new geometry, similar to an electrochemical reactor that has a net-like spacer, is proposed as an alternative to conventional design. We applied a theoretical framework provided by the fluid dynamics equations of Navier–Stokes and Brinkman, considering a porous electrode in typical and modified cell geometries. The mass transport was evaluated via tracer molecule distribution at different time points after the tracer injection. The proposed geometry exhibited a more homogeneous flow distribution featuring an increased mean electrolyte velocity inside the electrode (six times higher than in a typical geometry featuring an interdigitated flow field). The increased velocity resulted in shorter retention times. Based on these results, the proposed geometry featuring a net-like spacer is a promising configuration for RFB applications. This work also provides a new approach for developing and characterizing RFBs.
Graphical abstract
Biofilms contain microbial cells which are protected by a self-produced matrix and they firmly attach themselves to many different food industry surfaces. Due to this protection, microorganisms ...within biofilms are much more difficult to eradicate and therefore to control than suspended cells. A bacterium that tends to produce these structures and persist in food processing plants is
. To this effect, many attempts have been made to develop control strategies to be applied in the food industry, although there seems to be no clear direction on how to manage the risk the bacteria poses. There is no standardized protocol that is applied equally to all food sectors, so the strategies for the control of this pathogen depend on the type of surface, the nature of the product, the conditions of the food industry environment, and indeed the budget. The food industry performs different preventive and corrective measures on possible
-contaminated surfaces. However, a critical evaluation of the sanitization methods applied must be performed to discern whether the treatment can be effective in the long-term. This review will focus on currently used strategies to eliminate biofilms and control their formation in processing facilities in different food sectors (i.e., dairy, meat, fish, chilled vegetables, and ready-to-eat products). The technologies employed for their control will be exemplified and discussed with the objective of understanding how
can be improved through food safety management systems.
Aim:To describe the different retinal morphological characteristics that can present on optical coherence topography (OCT) in a spectrum of uveitic diseases.Methods:We reviewed the literature and our ...own OCT image archive for characteristic features that may be suggestive of a particular disease process.Results:OCT demonstrates a variety of characteristic morphological changes, some that may point towards a specific disease process. We describe the various forms of macular oedema found in uveitis as well as OCT features typically found in multifocal choroiditis, serpiginous chorioretinitis, toxoplasma chorioretinitis, Vogt–Koyanagi–Harada, sympathetic ophthalmia and the vitreomacular traction syndrome.Conclusion:Ophthalmologists should be aware of the variety of retinal morphological characteristics that can present on OCT in uveitic disease. Recognition may aid in the diagnostic process, which is complementary to conventional fundal photography and fluorescein angiography. This can facilitate earlier diagnosis and, more importantly, the initiation of specific treatment.
Several epidemiological studies in diabetic patients have demonstrated a protective effect of metformin to the development of several types of cancer. The underlying mechanisms of such phenomenon is ...related to the effect of metformin on cell proliferation among which, mTOR, AMPK and other targets have been identified. However, little is known about the role that metformin treatment have on other cell types such as keratinocytes and whether exposure to metformin of these cells might have serious repercussions in wound healing delay and in the development of complications in diabetic patients with foot ulcers or in their exacerbation.
HaCaT Cells were exposed to various concentrations of metformin and cell viability was evaluated by a Resazurin assay; Proliferation was also evaluated with a colony formation assay and with CFSE dilution assay by flow cytometry. Cell cycle was also evaluated by flow cytometry by PI staining. An animal model of wound healing was used to evaluate the effect of metformin in wound closure. Also, an analysis of patients receiving metformin treatment was performed to determine the effect of metformin treatment on the outcome and wound area. Statistical analysis was performed on SPSS v. 18 and GraphPad software v.5.
Metformin treatment significantly reduces cell proliferation; colony formation and alterations of the cell cycle are observed also in the metformin treated cells, particularly in the S phase. There is a significant increase in the area of the wound of the metformin treated animals at different time points (P<0.05). There is also a significant increase in the size and wound area of the patients with diabetic foot ulcers at the time of hospitalization. A protective effect of metformin was observed for amputation, probably associated with the anti inflammatory effects reported of metformin.
Metformin treatment reduces cell proliferation and reduces wound healing in an animal model and affects clinical outcomes in diabetic foot ulcer patients. Chronic use of this drug should be further investigated to provide evidence of their security in association with DFU.
PDF
