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Sphingolipids (SLs) are essential components of all eukaryotic cellular membranes. In fungi, plants and many protozoa, the primary SL is inositol-phosphorylceramide (IPC). Trypanosoma cruzi is a protozoan parasite that causes Chagas disease (CD), a chronic illness for which no vaccines or effective treatments are available. IPC synthase (IPCS) has been considered an ideal target enzyme for drug development because phosphoinositol-containing SL is absent in mammalian cells and the enzyme activity has been described in all parasite forms of T . cruzi . Furthermore, IPCS is an integral membrane protein conserved amongst other kinetoplastids, including Leishmania major , for which specific inhibitors have been identified. Using a CRISPR-Cas9 protocol, we generated T . cruzi knockout (KO) mutants in which both alleles of the IPCS gene were disrupted. We demonstrated that the lack of IPCS activity does not affect epimastigote proliferation or its susceptibility to compounds that have been identified as inhibitors of the L . major IPCS. However, disruption of the T . cruzi IPCS gene negatively affected epimastigote differentiation into metacyclic trypomastigotes as well as proliferation of intracellular amastigotes and differentiation of amastigotes into tissue culture-derived trypomastigotes. In accordance with previous studies suggesting that IPC is a membrane component essential for parasite survival in the mammalian host, we showed that T . cruzi IPCS null mutants are unable to establish an infection in vivo , even in immune deficient mice.

Background Mosquito borne viruses, such as dengue, Zika, yellow fever and Chikungunya, cause millions of infections every year. These viruses are mostly transmitted by two urban-adapted mosquito species, Aedes aegypti and Aedes albopictus . Although mechanistic understanding remains largely unknown, Aedes mosquitoes may have unique adaptations that lower the impact of viral infection. Recently, we reported the identification of an Aedes specific double-stranded RNA binding protein (dsRBP), named Loqs2, that is involved in the control of infection by dengue and Zika viruses in mosquitoes. Preliminary analyses suggested that the loqs2 gene is a paralog of loquacious ( loqs ) and r2d2 , two co-factors of the RNA interference (RNAi) pathway, a major antiviral mechanism in insects. Results Here we analyzed the origin and evolution of loqs2 . Our data suggest that loqs2 originated from two independent duplications of the first double-stranded RNA binding domain of loqs that occurred before the origin of the Aedes Stegomyia subgenus, around 31 million years ago . We show that the loqs2 gene is evolving under relaxed purifying selection at a faster pace than loqs , with evidence of neofunctionalization driven by positive selection. Accordingly, we observed that Loqs2 is localized mainly in the nucleus, different from R2D2 and both isoforms of Loqs that are cytoplasmic. In contrast to r2d2 and loqs , loqs2 expression is stage- and tissue-specific, restricted mostly to reproductive tissues in adult Ae. aegypti and Ae. albopictus . Transgenic mosquitoes engineered to express loqs2 ubiquitously undergo developmental arrest at larval stages that correlates with massive dysregulation of gene expression without major effects on microRNAs or other endogenous small RNAs, classically associated with RNA interference. Conclusions Our results uncover the peculiar origin and neofunctionalization of loqs2 driven by positive selection. This study shows an example of unique adaptations in Aedes mosquitoes that could ultimately help explain their effectiveness as virus vectors.

RNA interference (RNAi) mediated by the small interfering RNA (siRNA) pathway is a major antiviral mechanism in insects. This pathway is triggered when double-stranded RNA (dsRNA) produced during virus replication is recognized by Dicer-2, leading to the formation of virus-derived siRNA duplexes. These siRNAs are loaded onto the programmable nuclease Argonaute-2 (AGO2), with one strand serving as a guide to target and cleave fully complementary sequences of viral RNAs. While siRNAs are generated from viral dsRNA, the specific viral RNA species targeted for silencing during RNA virus replication remains unclear. In this study, we characterized the primary viral RNA targets of the Drosophila siRNA pathway during infections caused by negative and positive RNA viruses, namely Vesicular stomatitis virus (VSV) and Sindbis virus (SINV). Our findings reveal that polyadenylated transcripts of VSV and SINV are the major targets of silencing by the siRNA pathway during infection, likely when they are poised for translation. Consistent with earlier findings, we show that AGO2 is associated with ribosomes in control and virus infected cells. Therefore, we propose that the inhibition of the replication of RNA viruses in Drosophila results from the silencing of incoming viral transcripts, facilitated by the association of AGO2 with ribosomes.

Bathymetry (seafloor depth), is a critical parameter providing the geospatial context for a multitude of marine scientific studies. Since 1997, the International Bathymetric Chart of the Arctic Ocean (IBCAO) has been the authoritative source of bathymetry for the Arctic Ocean. IBCAO has merged its efforts with the Nippon Foundation-GEBCO-Seabed 2030 Project, with the goal of mapping all of the oceans by 2030. Here we present the latest version (IBCAO Ver. 4.0), with more than twice the resolution (200 × 200 m versus 500 × 500 m) and with individual depth soundings constraining three times more area of the Arctic Ocean (∼19.8% versus 6.7%), than the previous IBCAO Ver. 3.0 released in 2012. Modern multibeam bathymetry comprises ∼14.3% in Ver. 4.0 compared to ∼5.4% in Ver. 3.0. Thus, the new IBCAO Ver. 4.0 has substantially more seafloor morphological information that offers new insights into a range of submarine features and processes; for example, the improved portrayal of Greenland fjords better serves predictive modelling of the fate of the Greenland Ice Sheet.Measurement(s)depthTechnology Type(s)digital curationFactor Type(s)geographic locationSample Characteristic - Environmentocean floorSample Characteristic - LocationArctic OceanMachine-accessible metadata file describing the reported data: 10.6084/m9.figshare.12369314

Cellulose nanocrystals (CNCs) are a very versatile material, and optimizing the reaction conditions to obtain them is vital for cost savings, purity, selectivity, or performance. In this study, the reaction conditions of the CNCs were tested, as well as their application as binders for the fabrication of electrodes of a symmetric capacitor (based on activated carbon). The resulting CNCs were physicochemically characterized using Fourier transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction, atomic force microscopy, and its capacitive properties using cyclic voltammetry (CV). It was found that the best reaction conditions were at 45°C, 30 and 45 minutes, and 64 wt%. The CNCs were used as a binder, as they conferred stability to the electrodes and prevented the crumbling of the activated carbon electrodes. The CV measurements showed a capacitor behavior; CNCs can be used in energy storage applications.

Hydroxyethylcellulose (HEC) is a biodegradable, biocompatible polymer which is responsive to the temperature and pH values that can be reached by the human body. Polyacrylamide (PAAm) is a biocompatible and absorbent material which is highly used as a Drug Delivery System (DDS) due to its swelling capacity. In this work, a composite of HEC and PAAm was synthesized at a ratio of 25/75 wt% in order to evaluate its use as a transdermal DDS for acetaminophen. Drug release tests were performed in a phosphate buffer solution (PBS) at 35, 37, and 39 °C. The Korsmeyer-Peppas model was presented as a mathematical optimization problem and solved by Differential Evolution (DE) algorithm. Additionally, drug release data was modelled by Multigene Symbolic Regression (MSR) based on Genetic Programming (GP) algorithm. A drug release mathematical model was generated by MSR. The model is capable to reliably describe the kinetics of acetaminophen release from HEC/PAAm and to predict the concentrations of drug that is released in times beyond the experiment runtime.

There is continuing interest in the growing family of nanocellulosic materials prepared from plant cell wall material. While most of the research on cellulose nanocrystals has focused on the product of sulfuric acid hydrolysis stabilized by surface sulfate half-esters, cellulose nanocrystals with surface carboxyl groups have also been prepared by oxidation of lignocellulosic materials with ammonium persulfate. The major difference is that the persulfate oxidation leads to nanocrystals stabilized by surface carboxyl groups. Some properties of cellulose nanocrystals from cotton and wood, prepared by persulfate oxidation, are compared with those observed for nanocrystals prepared by sulfuric acid hydrolysis. Evidence from polarized light microscopy showed that the nanocrystal suspensions prepared by persulfate oxidation also form chiral nematic ordered phases in water.

Hydrogels are commonly used as Drug Delivery Systems (DDS) as patches due to its ability to store drug molecules within their structures. The release can be activated under certain stimuli, such as temperature and pH. In this paper, the mathematical modelling of acetaminophen release in hydroxypropyl cellulose with polyacrylamide (HPC/PAAm) is reported. The HPC/PAAm gel was synthesized in proportions of 25/75 wt% and was characterized by FTIR, DSC, optical microscopy, SEM, and TGA, with and without acetaminophen. The release tests were performed for hypothermic, normal, and febrile human body conditions, at 35, 37, and 39°C, respectively, on two release media: water and phosphate buffer solution. In order to describe the release of acetaminophen in HPC/PAAm gel, a genetic programming algorithm was used to accomplish Multigene Symbolic Regression (MSR). Characterization results showed that the drug was crystallized on the surface of the HPC/PAAm gel. Release test results showed that several simultaneous processes occurred in the acetaminophen diffusion phenomenon. A unique mathematical model was obtained by MSR. This model was able to describe the release of acetaminophen in HPC/PAAm gel with high values of R2 and adjusted R2 and to simulate the drug release at times beyond the end of the experiment. High values of R2 and low values of Coefficient of Variation (CV), Root-Mean-Square Error (RMSE), and Mean Absolute Error (MAE) were obtained from the comparison between the simulated and the experimental data. This allows to conclude that the mathematical model is reliable to represent and simulate the acetaminophen release in HPC/PAAm gel at 35, 37, and 39°C.

The use of organic materials in optics/photonics is highly attractive due to its promising applications in bioimaging, optoelectronic devices, photonic pigments, etc. However, the absence of π units in polysaccharides like cellulose or chitosan represents a disadvantage as these aromatic rings or double bonds are crucial to reduce non-radiative transitions in organic materials. To our knowledge, the mechanism to achieve photoluminescence (PL) in carbohydrate polymers without π units yet to be studied. Herein, we studied the effect of the drying of cellulose samples on PL, analyzing the effect of a thermal treatment by FTIR and UV-Vis. On one hand, the dominant wavelength of all PL spectra is at 520 nm, all samples show an increment in maximum intensity of PL between 29 and 49% and diffuse reflectance after the dehydration. A blueshift was found in the PL spectra, which was confirmed by chromaticity measurements. On the other hand, there is a relationship between the reduction of the adsorbed water and OH intermolecular stretching vibrations (FTIR) and the increment in PL, specifically in bands corresponding to the intermolecular H-bonds of O3-H···O5 and O2-H···O6. According to all data collected, an energy level diagram of cellulose samples was proposed indicating a phonon induced character of luminescence.

Mosquito borne viruses, such as dengue, Zika, yellow fever and Chikungunya, cause millions of infections every year. These viruses are mostly transmitted by two urban-adapted mosquito species, Aedes aegypti and Aedes albopictus. Although mechanistic understanding remains largely unknown, Aedes mosquitoes may have unique adaptations that lower the impact of viral infection. Recently, we reported the identification of an Aedes specific double-stranded RNA binding protein (dsRBP), named Loqs2, that is involved in the control of infection by dengue and Zika viruses in mosquitoes. Preliminary analyses suggested that the loqs2 gene is a paralog of loquacious (loqs) and r2d2, two co-factors of the RNA interference (RNAi) pathway, a major antiviral mechanism in insects. Here we analyzed the origin and evolution of loqs2. Our data suggest that loqs2 originated from two independent duplications of the first double-stranded RNA binding domain of loqs that occurred before the origin of the Aedes Stegomyia subgenus, around 31 million years ago. We show that the loqs2 gene is evolving under relaxed purifying selection at a faster pace than loqs, with evidence of neofunctionalization driven by positive selection. Accordingly, we observed that Loqs2 is localized mainly in the nucleus, different from R2D2 and both isoforms of Loqs that are cytoplasmic. In contrast to r2d2 and loqs, loqs2 expression is stage- and tissue-specific, restricted mostly to reproductive tissues in adult Ae. aegypti and Ae. albopictus. Transgenic mosquitoes engineered to express loqs2 ubiquitously undergo developmental arrest at larval stages that correlates with massive dysregulation of gene expression without major effects on microRNAs or other endogenous small RNAs, classically associated with RNA interference. Our results uncover the peculiar origin and neofunctionalization of loqs2 driven by positive selection. This study shows an example of unique adaptations in Aedes mosquitoes that could ultimately help explain their effectiveness as virus vectors.