Protein amyloid nanofibers provide a biocompatible platform for the development of functional nanomaterials. However, the functionalities generated up to date are still limited. Typical building ...blocks correspond to aggregation-prone proteins and peptides, which must be modified by complex and expensive reactions post-assembly. There is high interest in researching alternative strategies to tailor amyloid-based nanostructures’ functionality on demand. In the present study, the biotin-streptavidin system was exploited for this purpose. Prion-inspired heptapeptides (Ac-NYNYNYN-NH2, Ac-QYQYQYQ-NH2, and Ac-SYSYSYS-NH2) were doped with biotin-conjugated counterparts and assembled into amyloid-like fibers under mild conditions. The scaffolds’ versatile functionalization was demonstrated by decorating them with different streptavidin conjugates, including gold nanoparticles, quantum dots, and enzymes. In particular, they were functionalized with peroxidase or phosphatase activities using streptavidin conjugated with horseradish peroxidase and alkaline phosphatase, respectively. Modification of amyloid-like nanostructures has generally been restricted to the addition of a single protein moiety. We functionalized the fibrils simultaneously with glucose oxidase and horseradish peroxidase, coupling these activities to build up a nanostructured glucose biosensor. Overall, we present a simple, modular, and multivalent approach for developing amyloid-based nanomaterials functionalized with any desired combination of chemical and biological moieties.
Melanoma treatment with the BRAF V600E inhibitor vemurafenib provides therapeutic benefits but the common emergence of drug resistance remains a challenge. We generated A375 melanoma cells resistant ...to vemurafenib with the goal of investigating changes in miRNA expression patterns that might contribute to resistance. Increased expression of miR-204-5p and miR-211-5p occurring in vemurafenib-resistant cells was determined to impact vemurafenib response. Their expression was rapidly affected by vemurafenib treatment through RNA stabilization. Similar effects were elicited by MEK and ERK inhibitors but not AKT or Rac inhibitors. Ectopic expression of both miRNA in drug-naïve human melanoma cells was sufficient to confer vemurafenib resistance and more robust tumor growth
Conversely, silencing their expression in resistant cells inhibited cell growth. Joint overexpression of miR-204-5p and miR-211-5p durably stimulated Ras and MAPK upregulation after vemurafenib exposure. Overall, our findings show how upregulation of miR-204-5p and miR-211-5p following vemurafenib treatment enables the emergence of resistance, with potential implications for mechanism-based strategies to improve vemurafenib responses.
Identification of miRNAs that enable resistance to BRAF inhibitors in melanoma suggests a mechanism-based strategy to limit resistance and improve clinical outcomes.
.
The effect of the catalyst properties, particularly matrix acidity and its properties, has been studied in the transformation of dimethyl ether (DME) to light olefins. The catalysts used were ...prepared by agglomerating HZSM-5 zeolite with a different SiO2/Al2O3 ratio (30, 80, and 280) with bentonite or boehmite as a binder and α-Al2O3 as inert filler. The experiments have been carried out in a fixed bed reactor, under the following reaction conditions: 350 and 400 °C; space-time, 0.4 gzeolite h molC –1; time on stream, 4 h. The lower content of H2O in the reaction medium compared to that of the methanol transformation explains the advancement on the reaction scheme (with the transformation of olefins in other hydrocarbons) and more rapid deactivation by coke, which advises the use of catalysts with lower acidity and shaping the catalyst particles with a porous structure that attenuates the blocking of acid sites. The acidic properties of the zeolite have a significant impact on the DME conversion, yield and selectivity of light olefins, and catalyst stability. A good compromise of these rates is obtained with a catalyst prepared with HZSM-5 zeolite of moderate acidity (SiO2/Al2O3 = 280) and using boehmite as binder. In the calcination of catalyst the boehmite is converted into γ-Al2O3, whose weak acidity and mesoporous structure contribute to increase activity and stability of the catalyst.
Nature provides copious examples of self-assembling supramolecular nanofibers. Among them, amyloid structures have found amazing applications as advanced materials in fields such as biomedicine and ...nanotechnology. Prions are a singular subset of proteins able to switch between a soluble conformation and an amyloid state. The ability to transit between these two conformations is encoded in the so-called prion domains (PrDs), which are long and disordered regions of low complexity, enriched in polar and uncharged amino acids such as Gln, Asn, Tyr, Ser, and Gly. The polar nature of PrDs results in slow amyloid formation, which allows kinetic control of fiber assembly. This approach has been exploited for fabrication of multifunctional materials because in contrast to most amyloids, PrDs lack hydrophobic stretches that can nucleate their aggregation, their assembly depends on the establishment of a large number of weak interactions along the complete domain. The length and low complexity of PrDs make their chemical synthesis for applied purposed hardly affordable. Here, we designed four minimalist polar binary patterned peptides inspired in PrDs, which include the Q/N/G/S-Y-Q/N/G/S motif frequently observed in these domains: NYNYNYN, QYQYQYQ, SYSYSYS, and GYGYGYG. Despite their small size, they all recapitulate the properties of full-length PrDs, self-assembling into nontoxic amyloids under physiological conditions. Thus, they constitute small building blocks for the construction of tailored prion-inspired nanostructures. We exploited Tyr residues in these peptides to generate highly stable dityrosine cross-linked assemblies for the immobilization of metal nanoparticles in the fibrils surface and to develop an electrocatalytic amyloid scaffold. Moreover, we show that the shorter and more polar NYNNYN, QYQQYQ, and SYSSYS hexapeptides also self-assemble into amyloid-like structures, consistent with the presence of these tandem motifs in human prion-like proteins.
Gas chromatography coupled to mass spectrometry (GC/MS) has been a long-standing approach used for identifying small molecules due to the highly reproducible ionization process of electron impact ...ionization (EI). However, the use of GC-EI MS in untargeted metabolomics produces large and complex data sets characterized by coeluting compounds and extensive fragmentation of molecular ions caused by the hard electron ionization. In order to identify and extract quantitative information on metabolites across multiple biological samples, integrated computational workflows for data processing are needed. Here we introduce eRah, a free computational tool written in the open language R composed of five core functions: (i) noise filtering and baseline removal of GC/MS chromatograms, (ii) an innovative compound deconvolution process using multivariate analysis techniques based on compound match by local covariance (CMLC) and orthogonal signal deconvolution (OSD), (iii) alignment of mass spectra across samples, (iv) missing compound recovery, and (v) identification of metabolites by spectral library matching using publicly available mass spectra. eRah outputs a table with compound names, matching scores and the integrated area of compounds for each sample. The automated capabilities of eRah are demonstrated by the analysis of GC-time-of-flight (TOF) MS data from plasma samples of adolescents with hyperinsulinaemic androgen excess and healthy controls. The quantitative results of eRah are compared to centWave, the peak-picking algorithm implemented in the widely used XCMS package, MetAlign, and ChromaTOF software. Significantly dysregulated metabolites are further validated using pure standards and targeted analysis by GC-triple quadrupole (QqQ) MS, LC-QqQ, and NMR. eRah is freely available at http://CRAN.R-project.org/package=erah.
The early epidemiology of the 2022 monkeypox epidemic in non-endemic countries differs substantially from the epidemiology previously reported from endemic countries. We aimed to describe the ...epidemiological and clinical characteristics among individuals with confirmed cases of monkeypox infection.
We descriptively analysed data for patients with confirmed monkeypox who were included in the GeoSentinel global clinical-care-based surveillance system between May 1 and July 1 2022, across 71 clinical sites in 29 countries. Data collected included demographics, travel history including mass gathering attendance, smallpox vaccination history, social history, sexual history, monkeypox exposure history, medical history, clinical presentation, physical examination, testing results, treatment, and outcomes. We did descriptive analyses of epidemiology and subanalyses of patients with and without HIV, patients with CD4 counts of less than 500 cells per mm3 or 500 cells per mm3 and higher, patients with one sexual partner or ten or more sexual partners, and patients with or without a previous smallpox vaccination.
226 cases were reported at 18 sites in 15 countries. Of 211 men for whom data were available, 208 (99%) were gay, bisexual, or men who have sex with men (MSM) with a median age of 37 years (range 18–68; IQR 32–43). Of 209 patients for whom HIV status was known, 92 (44%) men had HIV infection with a median CD4 count of 713 cells per mm3 (range 36–1659; IQR 500–885). Of 219 patients for whom data were available, 216 (99%) reported sexual or close intimate contact in the 21 days before symptom onset; MSM reported a median of three partners (IQR 1–8). Of 195 patients for whom data were available, 78 (40%) reported close contact with someone who had confirmed monkeypox. Overall, 30 (13%) of 226 patients were admitted to hospital; 16 (53%) of whom had severe illness, defined as hospital admission for clinical care rather than infection control. No deaths were reported. Compared with patients without HIV, patients with HIV were more likely to have diarrhoea (p=0·002), perianal rash or lesions (p=0·03), and a higher rash burden (median rash burden score 9 IQR 6–21 for patients with HIV vs median rash burden score 6 IQR 3–14 for patients without HIV; p<0·0001), but no differences were identified in the proportion of men who had severe illness by HIV status.
Clinical manifestations of monkeypox infection differed by HIV status. Recommendations should be expanded to include pre-exposure monkeypox vaccination of groups at high risk of infection who plan to engage in sexual or close intimate contact.
US Centers for Disease Control and Prevention, International Society of Travel Medicine.
Display omitted
•Effect of SiO2/Al2O3 ratio, temperature and pressure on coke amount & composition.•Two types of coke: soft (confined oligomers) and hard (olefinic & aromatic species).•Oligomer ...confinement (soft coke) main responsible for catalyst deactivation.•Catalyst regeneration procedure by soft coke sweeping and hard coke combustion.•Full recovery of catalyst initial activity by hard coke combustion at 500 °C.
The deactivation phenomenon of HZSM-5 catalysts (SiO2/Al2O3 ratio = 30–280) in the 1-butene oligomerization has been studied. Experiments were performed in a fixed-bed reactor at 175−325 °C; 1.5−40 bar; and, 2−6 g h molC−1. Used catalysts were analyzed by: temperature-programmed sweeping with N2 (TPS-N2), soluble coke analysis by gas chromatography/mass spectrometry (GC/MS); Fourier-transform infrared spectroscopy (FTIR); temperature-programmed oxidation (TPO), and; combined TPO/FTIR. The main deactivation cause is the oligomer (soft coke) confinement in the catalyst matrix, which depends on the reaction conditions (temperature and pressure). Soft coke is removed by TPS-N2 at 400 °C, whereas the remaining hard coke, by combustion. Two types of hard coke are distinguished, which are located in the catalyst matrix and in the zeolite micropores, being the second fraction more refractory to combustion. The low developed nature of soft coke facilitates catalyst regeneration, which is fully achieved by the combustion of hard coke at 500 °C.
Priming effects in soils across Europe Siles, José A.; Díaz‐López, Marta; Vera, Alfonso ...
Global change biology,
March 2022, 2022-03-00, 20220301, Letnik:
28, Številka:
6
Journal Article
Recenzirano
Land use is a key factor driving changes in soil carbon (C) cycle and contents worldwide. The priming effect (PE)—CO2 emissions from changed soil organic matter decomposition in response to fresh C ...inputs—is one of the most unpredictable phenomena associated with C cycling and related nutrient mobilization. Yet, we know very little about the influence of land use on soil PE across contrasting environments. Here, we conducted a continental‐scale study to (i) determine the PE induced by 13C‐glucose additions to 126 cropland and seminatural (forests and grasslands) soils from 22 European countries; (ii) compare PE magnitude in soils under various crop types (i.e., cereals, nonpermanent industrial crops, and orchards); and (iii) model the environmental factors influencing PE. On average, PEs were negative in seminatural (with values ranging between −60 and 26 µg C g−1 soil after 35 days of incubation; median = −11) and cropland (from −55 to 27 µC g−1 soil; median = −4.3) soils, meaning that microbial communities preferentially switched from soil organic C decomposition to glucose mineralization. PE was significantly less negative in croplands compared with seminatural ecosystems and not influenced by the crop type. PE was driven by soil basal respiration (reflecting microbial activity), microbial biomass C, and soil organic C, which were all higher in seminatural ecosystems compared with croplands. This cross European experimental and modeling study elucidated that PE intensity is dependent on land use and allowed to clarify the factors regulating this important C cycling process.
A continental‐scale study was performed to determine the priming effects in croplands and seminatural soils from Europe, and to model the environmental factors determining priming effects. Priming effects were driven by soil basal respiration, microbial biomass C, and soil organic C, which were all higher in seminatural ecosystems compared with croplands.
For this work, an integrated system composed of a polypropylene reactor and a palladium on silica monolithic catalyst was designed and manufactured by 3D‐printing. These devices are able to perform ...solution phase chemistry in a robotic orbital shaker. The capped reactor was obtained in its entirety by 3D‐printing, using polypropylene and fused deposition modeling. The monolithic catalyst was also obtained by 3D‐printing ‐robocasting‐ of a silica support, sintering and subsequent palladium deposition through the wet impregnation method. The catalytic efficiency in Sonogashira or Suzuki reactions as well as the recyclability of the entire system – catalyst+reactor – were studied. The strong electrostatic adsorption (SEA) of the palladium on sintered silica and the reduced mechanical stress produced by the convenient adjustment of the catalyst into the polypropylene reactor makes the catalytic system reusable without significant loss of catalytic activity.
3D‐printing technology was applied for the construction of an integrated polypropylene reactor+palladium on silica catalyst system. Impregnation of the silica monolith with palladium nanoparticles was performed efficiently by strong electrostatic adsorption. Suzuki and Sonogashira reactions were performed. The easy work up, the negligible leaching and the reusability of the entire reactor/catalyst system makes it useful for parallel synthesis in drug discovery.
PDF
