Large‐area Si‐doped graphene (SiG) is controllably synthesized for the first time. A much‐enhanced molecular‐sensing performance is achieved when SiG is used as a probing surface. This will open up ...opportunities for developing high‐performance sensors that are able to detect trace amounts of organic and fluorescent molecules. Furthermore, many fascinating properties predicted by theoretical calculations can be tested based on the as‐synthesized SiG.
Screening of a GSK-proprietary library against intracellular Mycobacterium tuberculosis identified 1, a thioalkylbenzoxazole hit. Biological profiling and mutant analysis revealed that this compound ...is a prodrug that is bioactivated by the mycobacterial enzyme MymA. A hit-expansion program including design, synthesis, and profiling of a defined set of analogues with optimized drug-like properties led to the identification of an emerging lead compound, displaying potency against intracellular bacteria in the low micromolar range, high in vitro solubility and permeability, and excellent microsomal stability.
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•Several enzymes were immobilized on octyl-glyoxyl supports.•4M sodium phosphate readily inactivated the enzymes while the enzymes kept the activity in 6M NaCl.•6M NaCl has positive ...or negative effects on thermostability depending on the enzyme.•100mM sodium phosphate presented moderate destabilizing effects in immobilized enzymes but not on all free enzymes.•Fluorescence spectrum suggested a massive structural change produced by sodium phosphate.
We have analyzed the effects of the buffer nature on the stability of immobilized lipases. Commercial phospholipase Lecitase Ultra (LU), lipase B from Candida antarctica (CALB) and lipase from Thermomyces lanuginosus (TLL) have been immobilized on octyl-glyoxyl agarose beads. The enzymes were readily inactivated using 4M sodium phosphate but 6M NaCl did not inactivate them. Using 2M of sodium phosphate, the inactivation of the 3 immobilized enzymes still was very significant even at 25°C but at lower rate than with higher phosphate concentration. Thermal stress inactivations of the immobilized enzymes revealed that even 100mM sodium phosphate produced a significant decrease in enzyme stability; this effect was less pronounced for Lecitase but dramatic for CALB. While 6M NaCl presented slightly positive (LU) or negative (TLL) effects on their thermal stabilities of, CALB was thermally stabilized under the same conditions. Results were very different using free enymes. Fluorescence spectroscopy revealed dramatic structural rearrangements of the immobilized enzymes in the presence of high phosphate concentration. From these results, the use of sodium phosphate does not seem to be recommended for studies on thermal stability of lipases, although this should be verified for each enzyme and immobilized preparation.
Pulmonary cavitation is vital to the persistence and spread of Mycobacterium tuberculosis (MTb), but mechanisms underlying this lung destruction are poorly understood. Fibrillar type I collagen ...provides the lung's tensile strength, and only matrix metalloproteinases (MMPs) can degrade it at neutral pH. We investigated MTb-infected lung tissue and found that airway epithelial cells adjacent to tuberculosis (Tb) granulomas expressed a high level of MMP-1 (interstitial collagenase). Conditioned media from MTb-infected monocytes (CoMTb) up-regulated epithelial cell MMP-1 promoter activity, gene expression, and secretion, whereas direct MTb infection did not. CoMTb concurrently suppressed tissue inhibitor of metalloprotease-1 (TIMP-1) secretion, further promoting matrix degradation, and in Tb patients very low TIMP-1 expression was detected. MMP-1 up-regulation required synergy between TNF-alpha and G protein-coupled receptor signaling pathways. CoMTb stimulated p38 MAPK phosphorylation, and this is the point of TNF-alpha synergy with G protein-coupled receptor activation. Furthermore, p38 phosphorylation was the switch up-regulating MMP-1 activity and decreasing TIMP-1 secretion. Activated p38 localized to MMP-1-secreting airway epithelial cells in Tb patients. These data reveal a monocyte-epithelial cell network whereby MTb may drive tissue destruction, and they demonstrate that p38 phosphorylation is a key regulatory point in the generation of a matrix-degrading phenotype.
Cassava, Manihot esculenta Crantz, is one of the most important crops world-wide representing the staple security for more than one billion of people. The development of dense genetic and physical ...maps, as the basis for implementing genetic and molecular approaches to accelerate the rate of genetic gains in breeding program represents a significant challenge. A reference genome sequence for cassava has been made recently available and community efforts are underway for improving its quality. Cassava is threatened by several pathogens, but the mechanisms of defense are far from being understood. Besides, there has been a lack of information about the number of genes related to immunity as well as their distribution and genomic organization in the cassava genome.
A high dense genetic map of cassava containing 2,141 SNPs has been constructed. Eighteen linkage groups were resolved with an overall size of 2,571 cM and an average distance of 1.26 cM between markers. More than half of mapped SNPs (57.4%) are located in coding sequences. Physical mapping of scaffolds of cassava whole genome sequence draft using the mapped markers as anchors resulted in the orientation of 687 scaffolds covering 45.6% of the genome. One hundred eighty nine new scaffolds are anchored to the genetic cassava map leading to an extension of the present cassava physical map with 30.7 Mb. Comparative analysis using anchor markers showed strong co-linearity to previously reported cassava genetic and physical maps. In silico based searching for conserved domains allowed the annotation of a repertory of 1,061 cassava genes coding for immunity-related proteins (IRPs). Based on physical map of the corresponding sequencing scaffolds, unambiguous genetic localization was possible for 569 IRPs.
This is the first study reported so far of an integrated high density genetic map using SNPs with integrated genetic and physical localization of newly annotated immunity related genes in cassava. These data build a solid basis for future studies to map and associate markers with single loci or quantitative trait loci for agronomical important traits. The enrichment of the physical map with novel scaffolds is in line with the efforts of the cassava genome sequencing consortium.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The management of chronic diseases (CD) includes physical activity (PA). It is necessary to determine the effects of COVID-19 restrictions in CD. The aim was to review the research related to PA ...levels before and during the COVID-19 pandemic in people with CD. This review was designed according to PRISMA guidelines and registered in PROSPERO: CRD42020218825. The search was performed in CINAHL, Medline, Scopus, and Web of Science up to January 2021. The PICOS recommendations were applied. The search was conducted by two reviewers, who completed the data extraction of included articles. Methodological quality was assessed using the STROBE checklist, and a meta-analysis was conducted. The literature search strategy identified 227 articles. Five studies remained and were included. Only three studies were included in the meta-analysis. Two articles used accelerometers to objectively compare PA levels before and during the pandemic. Three studies made this comparison using an online survey. All articles showed a decrease in PA levels during the COVID-19 pandemic. The meta-analysis showed a significant reduction in PA levels during pandemic. PA levels during the COVID-19 pandemic have been reduced with respect to previous levels of PA in patients with CD.
Mutations in genes of the RAS-BRAF-MAPK-ERK pathway have not been fully explored in patients with chronic lymphocytic leukemia. We, therefore, analyzed the clinical and biological characteristics of ...chronic lymphocytic leukemia patients with mutations in this pathway and investigated the
response of primary cells to BRAF and ERK inhibitors. Putative damaging mutations were found in 25 of 452 patients (5.5%). Among these,
was mutated in nine patients (2.0%), genes upstream of
(
,
,
,
,
and
) were mutated in 12 patients (2.6%), and genes downstream of
(
,
, and
) were mutated in five patients (1.1%). The most frequent mutations were missense, subclonal and mutually exclusive. Patients with these mutations more frequently had increased lactate dehydrogenase levels, high expression of ZAP-70, CD49d, CD38, trisomy 12 and unmutated immunoglobulin heavy-chain variable region genes and had a worse 5-year time to first treatment (hazard ratio 1.8,
=0.025). Gene expression analysis showed upregulation of genes of the MAPK pathway in the group carrying RAS-BRAF-MAPK-ERK pathway mutations. The BRAF inhibitors vemurafenib and dabrafenib were not able to inhibit phosphorylation of ERK, the downstream effector of the pathway, in primary cells. In contrast, ulixertinib, a pan-ERK inhibitor, decreased phospho-ERK levels. In conclusion, although larger series of patients are needed to corroborate these findings, our results suggest that the RAS-BRAF-MAPK-ERK pathway is one of the core cellular processes affected by novel mutations in chronic lymphocytic leukemia, is associated with adverse clinical features and could be pharmacologically inhibited.
4-Nitrophenol is a widely used emerging pollutant in various industries, including the production of agrochemicals, drugs, and synthetic dyes. Due to its potential environmental harmful effects, ...there is a need to study its reuse and removal from wastewater. This study used electrodialysis technology to separate 4-nitrophenol ions using a four-compartment stack. The effects of supporting electrolyte concentration, pH, voltages, and current density on the performance of electrodialysis for separating 4-nitrophenol were investigated. A high extraction percentage of 77% was achieved with low energy consumption (107 kWh kg
−1
) when high 4-nitrophenol flows and transport numbers were reached.
Atomically thin 2D materials provide an opportunity to investigate the atomic-scale details of defects introduced by particle irradiation. Once the atomic configuration of defects and their spatial ...distribution are revealed, the details of the mesoscopic phenomena can be unveiled. In this work, we created atomically small defects by controlled irradiation of gallium ions with doses ranging from 4.94 × 1012 to 4.00 × 1014 ions/cm2 on monolayer molybdenum disulfide (MoS2) crystals. The optical signatures of defects, such as the evolution of defect-activated LA-bands and a broadening of the first-order (E′ and A′1) modes, can be studied by Raman spectroscopy. High-resolution scanning transmission electron microscopy (HR-STEM) analysis revealed that most defects are vacancies of few-molybdenum atoms with surrounding sulfur atoms (V xMo+yS) at a low ion dose. When increasing the ion dose, the atomic vacancies merge and form nanometer-sized holes. Utilizing HR-STEM and image analysis, we propose the estimation of the finite crystal length (L fc) via the careful quantification of 0D defects in 2D systems through the formula L fc = 4.41/ η ion , where ηion corresponds to the ion dose. Combining HR-STEM and Raman spectroscopy, the formula to calculate L fc from Raman features, I(LA)/I(A′1) = 5.09/L fc 2, is obtained. We have also demonstrated an effective route to healing the ion irradiation-induced atomic vacancies by annealing defective MoS2 in a hydrogen disulfide (H2S) atmosphere. The H2S annealing improved the crystal quality of MoS2 with L fc greater than the calculated size of the A exciton wave function, which leads to a partial recovery of the photoluminescence signal after its quenching by ion irradiation.
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