Bladder cancer (BC) is a frequently diagnosed malignancy affecting predominantly adult and elderly populations. It is expected that due to the longer life time, BC will become even more frequent in the future; thus in consequence, it will represent serious health problem of older society part. The treatment of advanced BC is mostly ineffective due to its very aggressive behavior. So far, no effective targeted therapy is used for BC treatment. Here, we found that BC is characterized by lower protein levels of BRM, INI1, and BAF155 main subunits of SWI/SNF chromatin remodeling complex (CRC) which is involved in global control of gene expression and influences various important cellular processes like: cell cycle control, apoptosis, DNA repair, etc. Moreover, the expression of SMARCA2, a BRM encoding gene, strongly correlated with BC metastasis and expression of such metabolic genes as PKM2 and PRKAA1. Furthermore, the analysis of T24 and 5637 commonly used BC cell lines revealed different expression levels of metabolic genes including FBP1 gene encoding Frutose-1,6-Bisphosphatase, an enzyme controlling glycolysis flux and gluconeogenesis. The tested BC cell lines exhibited various molecular and metabolic alterations as well as differential glucose uptake, growth rate, and migration potential. We have shown that BRM subunit is involved in the transcriptional control of genes encoding metabolic enzymes.Moreover, we found that the FBP1 expression level and the SWI/SNF CRCs may serve as markers of molecular subtypes of BC. Collectively, this study may provide a new knowledge about the molecular and metabolic BC subtypes which likely will be of high importance for the clinic in the future.

Growing tumors avoid recognition and destruction by the immune system. During continuous stimulation of tumor-infiltrating lymphocytes (TILs) by tumors, TILs become functionally exhausted; thus, they become unable to kill tumor cells and to produce certain cytokines and lose their ability to proliferate. This collectively results in the immune escape of cancer cells. Here, we show that breast cancer cells expressing PD-L1 can accelerate exhaustion of persistently activated human effector CD4+ T cells, manifesting in high PD-1 and PD-L1 expression level son T cell surfaces, decreased glucose metabolism genes, strong downregulation of SWI/SNF chromatin remodeling complex subunits, and p21 cell cycle inhibitor upregulation. This results in inhibition of T cell proliferation and reduction of T cell numbers. The RNAseq analysis on exhausted CD4+ T cells indicated strong overexpression of IDO1 and genes encoding pro-inflammatory cytokines and chemokines. Some interleukins were also detected in media from CD4+ T cells co-cultured with cancer cells. The PD-L1 overexpression was also observed in CD4+ T cells after co-cultivation with other cell lines overexpressing PD-L1, which suggested the existence of a general mechanism of CD4+ T cell exhaustion induced by cancer cells. The ChIP analysis on the PD-L1 promoter region indicated that the BRM recruitment in control CD4+ T cells was replaced by BRG1 and EZH2 in CD4+ T cells strongly exhausted by cancer cells. These findings suggest that epi-drugs such as EZH2 inhibitors may be used as immunomodulators in cancer treatment.

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We estimated the usefulness of spore-crystals preparations of the two B. thuringiensis isolates, MPU B9 and MPU B54, for reducing the number of pests. The potential insecticidal toxicities of B. thuringiensis isolates were assessed by the analysis of the genes coding for crystalline proteins. The activities of spore-crystals preparations were determined against Dendrolimus pini L. (Lepidoptera: Lasiocampidae) and compared with the toxicity of spores and crystals of B. thuringiensis subsp. kurstaki HD-1 from commercial biopesticide Foray. Although the analysis of crystalline toxin gene profiles indicated potentially higher activities of MPU B9 and MPU B54 crystals against the pests than that of HD-1, the toxicities of isolate and HD-1 preparations against D. pini caterpillars were similar. The LC50 amounted to 3.42×104 spores and crystals for HD-1, 3.36×104 for MPU B9 and 3.5×104 for MPU B54. Additionally, the toxicity of the MPU B54 preparation was evaluated against Spodoptera exigua (Hubner) (Lepidoptera: Noctuidae). The LC50 was 4.5×105 spores and crystals of MPU B54, and 2.69×106 spores and crystals of HD-1. The LC50 of the MPU B54 preparation against S. exigua was approximately six-fold higher than that of HD-1. However, due to the very wide fiducidal limits for LC50 values, which for both preparations overlap to a large extent, the toxicity of the preparations should be considered the same. The varied profiles of crystalline toxin genes and important toxicity of spore-crystal mixtures of isolates against S. exigua and D. pini indicate the effectiveness of the mixtures against pests and make the strains an alternative for HD-1 for reducing the number of insects.

BACKGROUND: Chronic rhinosinusitis (CRS) is one of the most common health complaints affecting 15% of the world’s population. Recent reports confirm the participation of sensory organs in defense process against pathogenic microorganisms. The bitter taste receptor TAS2R38 is described to play a role in upper airway defence system . The purpose of this study was to assess the function of the bitter taste receptor in correlation with severity of CRS, sensory organ disorders and allergic reaction. MATERIAL AND METHODS: The study contained 100 patients undergoing nasal surgery, divided into two groups CRS with and without nasal polyps. The control group consisted of patients undergoing septoplasty after excluding rhinosinusitis. Sinus mucosa samples obtained during surgery were used to assess the TAS2R38 expression using immunohistochemistry method. IgE level was noticed in blood samples collected from patients. The Sniffin Sticks test was performed. RESULTS: CRS patients had higher expression of TAS2R38 receptor compared to controls (p = 0.0175). Statistically significant higher TAS2R38 H-score in nasal mucosa was found among patients with a higher inflammation process in CT scan (p = 0.001), higher IgE level (p=0,04) and abnormal result of the Sniffin Sticks test. CONCLUSIONS: Patients with CRS had significant TAS2R38 receptor overexpression correlating with the severity of inflammatory changes in CT scans, abnormal perception of smells and higher IgE level. The cumulative impact was found between the inflammatory changes, smell disfunction and the severity of subjective symptoms of CRS (according to EPOS) and the intensity of cell staining (index H-score).

The Arabidopsis ERECTA family (ERf) of leucine-rich repeat receptor-like kinases (LRR-RLKs) comprising ERECTA (ER), ERECTA-LIKE 1 (ERL1), and ERECTA-LIKE 2 (ERL2) controls epidermal patterning, inflorescence architecture, and stomata development and patterning. These proteins are reported to be plasma membrane associated. Here we show that the er/erl1/erl2 mutant exhibits impaired gibberellin (GA) biosynthesis and perception alongside broad transcriptional changes. The ERf kinase domains were found to localize to the nucleus where they interact with the SWI3B subunit of the SWI/SNF chromatin remodeling complex (CRCs). The er/erl1/erl2 mutant exhibits reduced SWI3B protein level and affected nucleosomal chromatin structure. Similar to swi3c and brm plants with inactivated subunits of SWI/SNF CRCs, it also does not accumulate DELLA RGA and GAI proteins. The ER kinase phosphorylates SWI3B in vitro, and the inactivation of all ERf proteins leads to the decreased phosphorylation of SWI3B protein in vivo. The identified correlation between DELLA overaccumulation and SWI3B proteasomal degradation, and the physical interaction of SWI3B with DELLA proteins indicate an important role of SWI3B-containing SWI/SNF CRCs in gibberellin signaling. Co-localization of ER and SWI3B on GID1 (GIBBERELLIN INSENSITIVE DWARF 1) DELLA target gene promoter regions and abolished SWI3B binding to GID1 promoters in er/erl1/erl2 plants supports the conclusion that ERf-SWI/SNF CRC interaction is important for transcriptional control of GA receptors. Thus, the involvement of ERf proteins in the transcriptional control of gene expression, and observed similar features for human HER2 (epidermal growth family receptor member), indicate an exciting target for further studies of evolutionarily conserved non-canonical functions of eukaryotic membrane receptors.

Male antler moths (Cerapteryx graminis) were attracted to traps baited with dispensers loaded with mixtures varying between 7.3 and 4.6 of Z11-16:Ald and ZI 1-16:Ac. The blends between 7-20% of Z11-16:Ac and 93-80% of Z11-16:Ald in its evaporated phase yielded the greatest catches in field trials. No variations in trap catches within these ratios were noticed. Additionally the emission rates of the attractive blend varying between 37 and 534 ng/h, trap catches decreased by 80% over the same period. The addition of Z11-16:OH had a strong inhibiting effect on the trap catches. Trap catches of different types of dispensers having evaporation area-to-volume between 1.2 mm-' and 1.8 mm-' were dependent on emission rates and ratios of Zl l-16:Ald and ZI 1-16:Ac in evaporated phase. Minifer type dispensers with evaporation area-to-volume 1.5 mm-' and higher evaporation rates are more economic and convenient to use. Attractant traps started to catch at earlier dates than light traps and were more attractive at lower insect densities.

This document has been produced with the financial assistance of the European Union (EU). It should not be reported as representing the official views of the EU, the OECD or its member countries, or of partners participating in the SIGMA Programme. The opinions expressed and arguments employed are those of the authors. This document, as well as any data and any map included herein, are without prejudice to the status of or sovereignty over any territory, to the delimitation of international frontiers and boundaries and to the name of any territory, city or area.