Interferometric imaging of the type IIIb and U radio bursts observed with LOFAR on 22 August 2017

Context. The Sun is the source of different types of radio bursts that are associated with solar flares, for example. Among the most frequently observed phenomena are type III solar bursts. Their radio images at low frequencies (below 100 MHz) are relatively poorly studied due to the limitations of legacy radio telescopes.Aims. We study the general characteristics of types IIIb and U with stria structure solar radio bursts in the frequency range of 20-80 MHz, in particular the source size and evolution in different altitudes, as well as the velocity and energy of electron beams responsible for their generation.Methods. In this work types IIIb and U with stria structure radio bursts are analyzed using data from the LOFAR telescope including dynamic spectra and imaging observations, as well as data taken in the X-ray range (GOES and RHESSI satellites) and in the extreme ultraviolet (SDO satellite).Results. In this study we determined the source size limited by the actual shape of the contour at particular frequencies of type IIIb and U solar bursts in a relatively wide frequency band from 20 to 80 MHz. Two of the bursts seem to appear at roughly the same place in the studied active region and their source sizes are similar. It is different in the case of another burst, which seems to be related to another part of the magnetic field structure in this active region. The velocities of the electron beams responsible for the generation of the three bursts studied here were also found to be different.Peer reviewe

SYK inhibition targets acute myeloid leukemia stem cells by blocking their oxidative metabolism

Spleen tyrosine kinase (SYK) is an important oncogene and signaling mediator activated by cell surface receptors crucial for acute myeloid leukemia (AML) maintenance and progression. Genetic or pharmacologic inhibition of SYK in AML cells leads to increased differentiation, reduced proliferation, and cellular apoptosis. Herein, we addressed the consequences of SYK inhibition to leukemia stem-cell (LSC) function and assessed SYK-associated pathways in AML cell biology. Using gain-of-function MEK kinase mutant and constitutively active STAT5A, we demonstrate that R406, the active metabolite of a small-molecule SYK inhibitor fostamatinib, induces differentiation and blocks clonogenic potential of AML cells through the MEK/ERK1/2 pathway and STAT5A transcription factor, respectively. Pharmacological inhibition of SYK with R406 reduced LSC compartment defined as CD34+CD38-CD123+ and CD34+CD38-CD25+ in vitro, and decreased viability of LSCs identified by a low abundance of reactive oxygen species. Primary leukemic blasts treated ex vivo with R406 exhibited lower engraftment potential when xenotransplanted to immunodeficient NSG/J mice. Mechanistically, these effects are mediated by disturbed mitochondrial biogenesis and suppression of oxidative metabolism (OXPHOS) in LSCs. These mechanisms appear to be partially dependent on inhibition of STAT5 and its target gene MYC, a well-defined inducer of mitochondrial biogenesis. In addition, inhibition of SYK increases the sensitivity of LSCs to cytarabine (AraC), a standard of AML induction therapy. Taken together, our findings indicate that SYK fosters OXPHOS and participates in metabolic reprogramming of AML LSCs in a mechanism that at least partially involves STAT5, and that SYK inhibition targets LSCs in AML. Since active SYK is expressed in a majority of AML patients and confers inferior prognosis, the combination of SYK inhibitors with standard chemotherapeutics such as AraC constitutes a new therapeutic modality that should be evaluated in future clinical trials

Diarrheal-associated gut dysbiosis in cancer and inflammatory bowel disease patients is exacerbated by Clostridioides difficile infection

IntroductionLow diversity gut dysbiosis can take different forms depending on the disease context. In this study, we used shotgun metagenomic sequencing and gas chromatography–mass spectrometry (GC-MS) to compared the metagenomic and metabolomic profiles of Clostridioides (Clostridium) difficile diarrheal cancer and inflammatory bowel disease (IBD) patients and defined the additive effect of C. difficile infection (CDI) on intestinal dysbiosis.ResultsThe study cohort consisted of 138 case-mix cancer patients, 43 IBD patients, and 45 healthy control individuals. Thirty-three patients were also infected with C. difficile. In the control group, three well-known enterotypes were identified, while the other groups presented with an additional Escherichia-driven enterotype. Bacterial diversity was significantly lower in all groups than in healthy controls, while the highest level of bacterial species richness was observed in cancer patients. Fifty-six bacterial species had abundance levels that differentiated diarrheal patient groups from the control group. Of these species, 52 and 4 (Bacteroides fragilis, Escherichia coli, Klebsiella pneumoniae, and Ruminococcus gnavus) were under-represented and over-represented, respectively, in all diarrheal patient groups. The relative abundances of propionate and butyrate were significantly lower in fecal samples from IBD and CDI patients than in control samples. Isobutyrate, propanate, and butyrate concentrations were lower in cancer, IBD, and CDI samples, respectively. Glycine and valine amino acids were over- represented in diarrheal patients.ConclusionOur data indicate that different external and internal factors drive comparable profiles of low diversity dysbiosis. While diarrheal-related low diversity dysbiosis may be a consequence of systemic cancer therapy, a similar phenotype is observed in cases of moderate to severe IBD, and in both cases, dysbiosis is exacerbated by incidence of CDI

Characteristics of the gut microbiome in esports players compared with those in physical education students and professional athletes

IntroductionEsports is a category of competitive video games that, in many aspects, may be similar to traditional sports; however, the gut microbiota composition of players has not been yet studied.Materials and methodsHere, we investigated the composition and function of the gut microbiota, as well as short chain fatty acids (SCFAs), and amino acids, in a group of 109 well-characterized Polish male esports players. The results were compared with two reference groups: 25 endurance athletes and 36 healthy students of physical education. DNA and metabolites isolated from fecal samples were analyzed using shotgun metagenomic sequencing and mass spectrometry, respectively. Physical activity and nutritional measures were evaluated by questionnaire.ResultsAlthough anthropometric, physical activity and nutritional measures differentiated esports players from students, there were no differences in bacterial diversity, the Bacteroidetes/Firmicutes ratio, the composition of enterotype clusters, metagenome functional content, or SCFA concentrations. However, there were significant differences between esports players and students with respect to nine bacterial species and nine amino acids. By contrast, all of the above-mentioned measures differentiated professional athletes from esports players and students, with 45 bacteria differentiating professional athletes from the former and 31 from the latter. The only species differentiating all three experimental groups was Parabacteroides distasonis, showing the lowest and highest abundance in esports players and athletes, respectively.ConclusionOur study confirms the marked impact of intense exercise training on gut microbial structure and function. Differences in lifestyle and dietary habits between esports players and physical education students appear to not have a major effect on the gut microbiota

Hydrogel Alginate Seed Coating as an Innovative Method for Delivering Nutrients at the Early Stages of Plant Growth

Seed coating containing fertilizer nutrients and plant growth biostimulants is an innovative technique for precision agriculture. Nutrient delivery can also be conducted through multilayer seed coating. For this purpose, sodium alginate with NPK, which was selected in a preliminary selection study, crosslinked with divalent ions (Cu(II), Mn(II), Zn(II)) as a source of fertilizer micronutrients, was used to produce seed coating. The seeds were additionally coated with a solution containing amino acids derived from high-protein material. Amino acids can be obtained by alkaline hydrolysis of mealworm larvae (Gly 71.2 ± 0.6 mM, Glu 55.8 ± 1.3 mM, Pro 48.8 ± 1.5 mM, Ser 31.4 ± 1.5 mM). The formulations were applied in different doses per 100 g of seeds: 35 mL, 70 mL, 105 mL, and 140 mL. SEM-EDX surface analysis showed that 70 mL of formulation/100 g of seeds formed a continuity of coatings but did not result in a uniform distribution of components on the surface. Extraction tests proved simultaneous low leaching of nutrients into water (max. 10%), showing a slow release pattern. There occurred high bioavailability of fertilizer nutrients (even up to 100%). Pot tests on cucumbers (Cornichon de Paris) confirmed the new method’s effectiveness, yielding a 50% higher fresh sprout weight and four times greater root length than uncoated seeds. Seed coating with hydrogel has a high potential for commercial application, stimulating the early growth of plants and thus leading to higher crop yields

Transcription Factor Prospero Homeobox 1 (PROX1) as a Potential Angiogenic Regulator of Follicular Thyroid Cancer Dissemination

It is well known that Prospero homeobox 1 (PROX1) is a crucial regulator of lymphangiogenesis, that reprograms blood endothelial cells to lymphatic phenotype. However, the role of PROX1 in tumor progression, especially in angiogenesis remains controversial. Herein, we studied the role of PROX1 in angiogenesis in cell lines derived from follicular thyroid cancer (FTC: FTC-133) and squamous cell carcinoma of the thyroid gland (SCT: CGTH-W-1) upon PROX1 knockdown. The genes involved in angiogenesis were selected by RNA-seq, and the impact of PROX1 on vascularization potential was investigated using human umbilical vein endothelial cells (HUVECs) cultured in conditioned medium collected from FTC- or SCT-derived cancer cell lines after PROX1 silencing. The angiogenic phenotype was examined in connection with the analysis of focal adhesion and correlated with fibroblast growth factor 2 (FGF2) levels. Additionally, the expression of selected genes involved in angiogenesis was detected in human FTC tissues. As a result, we demonstrated that PROX1 knockdown resulted in upregulation of factors associated with vascularization, such as metalloproteinases (MMP1 and 3), FGF2, vascular endothelial growth factors C (VEGFC), BAI1 associated protein 2 (BAIAP2), nudix hydrolase 6 (NUDT6), angiopoietin 1 (ANGPT1), and vascular endothelial growth factor receptor 2 (KDR). The observed molecular changes resulted in the enhanced formation of capillary-like structures by HUVECs and upregulated focal adhesion in FTC-133 and CGTH-W-1 cells. The signature of selected angiogenic genes’ expression in a series of FTC specimens varied depending on the case. Interestingly, PROX1 and FGF2 showed opposing expression levels in FTC tissues and seven thyroid tumor-derived cell lines. In summary, our data revealed that PROX1 is involved in the spreading of thyroid cancer cells by regulation of angiogenesis

Molecular Signature of Prospero Homeobox 1 (PROX1) in Follicular Thyroid Carcinoma Cells

The prospero homeobox 1 (PROX1) transcription factor is a product of one of the lymphangiogenesis master genes. It has also been suggested to play a role in carcinogenesis, although its precise role in tumour development and metastasis remains unclear. The aim of this study was to gain more knowledge on the PROX1 function in thyroid tumorigenesis. Follicular thyroid cancer-derived cells—CGTH-W-1—were transfected with PROX1-siRNA (small interfering RNA) and their proliferation, cell cycle, apoptosis and motility were then analysed. The transcriptional signature of PROX1 depletion was determined using RNA-Sequencing (RNA-Seq) and the expression of relevant genes was further validated using reverse transcriptase quantitative PCR (RT-qPCR), Western blot and immunocytochemistry. PROX1 depletion resulted in a decreased cell motility, with both migratory and invasive potential being significantly reduced. The cell morphology was also affected, while the other studied cancer-related cell characteristics were not significantly altered. RNA-seq analysis revealed significant changes in the expression of transcripts encoding genes involved in both motility and cytoskeleton organization. Our transcriptional analysis of PROX1-depleted follicular thyroid carcinoma cells followed by functional and phenotypical analyses provide, for the first time, evidence that PROX1 plays an important role in the metastasis of thyroid cancer cells by regulating genes involved in focal adhesion and cytoskeleton organization in tumour cells