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5,6‑diiodo‑1H‑benzotriazole: new TBBt analogue that minutely affects mitochondrial activity
Get PDF4,5,6,7‑Tetrabromo‑1H‑benzotriazole is widely used as the eference ATP‑competitive inhibitor of protein kinase CK2. Herein, we study its new analogs: 5,6‑diiodo‑ and ,6‑diiodo‑4,7‑dibromo‑1H‑ benzotriazole. We used biophysical (MST, ITC) and biochemical (enzymatic assay) methods to describe the interactions of halogenated benzotriazoles with the catalytic subunit of human protein kinase CK2 (hCK2α). To trace the biological activity, we measured their ytotoxicity against four reference cancer cell lines and the effect on the mitochondrial inner membrane potential. The results obtained lead to the conclusion that iodinated compounds are an attractive alternative to brominated ones. One of them retains the cytotoxicity against selected cancer cell lines of the reference TBBt with a smaller side effect on mitochondrial activity. Both iodinated compounds are andidate leaders in the further development of CK2 inhibitors
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
Get PDFIn 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct auto
phagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field
The Codon Usage in the Minimal Natural Cell
Get PDFA statistical analysis of the variation in contents with the size of the current known small�est genomes, N. deltocephalinicola, C. ruddii, N. equitans, and M. genitalium, enabled the
indication of a minimal set of codons capable of naturally building a modern-type free�living unicellular organism in an early stage of evolution. Using a linear regression model,
the potential codon distribution in the minimal natural cell was predicted and compared to
the composition of the smallest synthetic, JCVI-Syn3.0. The distribution of the molecular
weight of potentially coded amino acids was also calculated. The main diferences in the
features of the minimal natural cell and H. Sapiens genome were analyzed. In this regard,
the content percentage of respective amino acids and their polarization charge proper�ties were reported and compared. The fractions of occurring nucleotides were calculated,
too. Then, the estimated numbers of codons in a minimal natural cell were related to the
expected numbers for random distribution. Shown increase, or decrease in the contents,
relative to the calculated random flling was related to the evolutionary preferences, vary�ing with the subsequent eras of the evolution of genetic code
Expression of versican mRNA transcript to predict cardiac remodelling after myocardial infarction
Get PDFBackground: Adverse left-ventricular remodelling (LVR) is defined as an increase in end-diastolic left-ventricular volume by 20% 6 months after acute myocardial infarction (AMI). LVR is associated with cardiac dysfunction, therefore deteriorating the prognosis.
Aims: We aimed to compare the concentrations of messenger RNA transcripts in the peripheral blood of patients with and without LVR at 6 months.
Methods: The study included 75 patients with first ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention. Whole blood concentrations of 6 transcripts were determined 24 hours after AMI using droplet digital polymerase chain reaction. The correlations between mRNA transcript expression and left ventricular ejection fraction (LVEF) and N-terminal-pro B type natriuretic peptide (NT-proBNP) concentration were evaluated.
Results: Among 75 patients, 4 were lost to follow-up and 71 were included in the analysis. Seventeen (24%) patients developed LVR at 6 months. Versican (VCAN) mRNA expression was lower in patients who developed LVR, compared to those who did not (P = 0.02), and discriminated between these patients (area under the ROC curve 67%; P = 0.04). Expression of VCAN transcript < 75.3 normalized units predicted LVR with 71% sensitivity and 67% specificity. In a multivariable regression analysis, VCAN expression remained the only independent predictor of LVR (OR 3.475; 95% CI, 1.000-12.075; P = 0.04).
Conclusions: Dysregulation of VCAN expression in the acute phase of AMI may contribute to LVR at 6 months. Whether decreased expression of VCAN might be a useful tool to predict LVR in clinical practice remains to be established
Dynamics of dark fermentation microbial communities in the light of lactate and butyrate production.
Get PDFAbstract
Background: This study focuses on the processes occurring during the acidogenic step of anaerobic digestion,
especially resulting from nutritional interactions between dark fermentation (DF) bacteria and lactic acid bacteria
(LAB). Previously, we have confirmed that DF microbial communities (MCs) that fed on molasses are able to convert
lactate and acetate to butyrate. The aims of the study were to recognize the biodiversity of DF-MCs able and
unable to convert lactate and acetate to butyrate and to define the conditions for the transformation.
Results: MCs sampled from a DF bioreactor were grown anaerobically in mesophilic conditions on different media
containing molasses or sucrose and/or lactate and acetate in five independent static batch experiments. The
taxonomic composition (based on 16S_rRNA profiling) of each experimental MC was analysed in reference to its
metabolites and pH of the digestive liquids. In the samples where the fermented media contained carbohydrates,
the two main tendencies were observed: (i) a low pH (pH ≤ 4), lactate and ethanol as the main fermentation
products, MCs dominated with Lactobacillus, Bifidobacterium, Leuconostoc and Fructobacillus was characterized by
low biodiversity; (ii) pH in the range 5.0–6.0, butyrate dominated among the fermentation products, the MCs
composed mainly of Clostridium (especially Clostridium_sensu_stricto_12), Lactobacillus, Bifidobacterium and
Prevotella. The biodiversity increased with the ability to convert acetate and lactate to butyrate. The MC processing
exclusively lactate and acetate showed the highest biodiversity and was dominated by Clostridium (especially
Clostridium_sensu_stricto_12). LAB were reduced; other genera such as Terrisporobacter, Lachnoclostridium,
Paraclostridium or Sutterella were found. Butyrate was the main metabolite and pH was 7. Shotgun metagenomic
analysis of the selected butyrate-producing MCs independently on the substrate revealed C.tyrobutyricum as the
dominant Clostridium species. Functional analysis confirmed the presence of genes encoding key enzymes of the
fermentation routes.
Conclusions: Batch tests revealed the dynamics of metabolic activity and composition of DF-MCs dependent on
fermentation conditions. The balance between LAB and the butyrate producers and the pH values were shown to
be the most relevant for the process of lactate and acetate conversion to butyrate. To close the knowledge gaps is
to find signalling factors responsible for the metabolic shift of the DF-MCs towards lactate fermentation
Funkcje białek Rab w roślinach – na poziomie komórki i organizmu
Get PDFBiałka Rab są niezbędne w procesach fuzji i pączkowania błon i w związku z tym są kluczowe dla regulacji transportu wewnątrzkomórkowego w komórkach eukariotycznych.
Białka Rab mają też wpływ na wiele innych aspektów funkcjonowania komórek, takich jak rearanżacje cytoszkieletu, wyznaczenie polarności komórki czy przekazywanie sygnałów.
Białka Rab oddziałują tu zarówno pośrednio, poprzez swój wpływ na dostarczanie odpowiednich białek i polisacharydów do ich miejsc docelowych w komórce, jak i bezpośrednio,
poprzez białka efektorowe. Konsekwencje zaburzeń w funkcjonowaniu białek Rab można obserwować na wszystkich poziomach działania organizmu - od komórek przez tkanki i organy aż po cały organizm. U roślin procesy zależne od białek Rab są istotne dla architektury komórki, jej różnicowania, reakcji na stres biotyczny i abiotyczny, a także dla wydajności produkcji rolniczej
Development of a Continuous System for 2-Phenylethanol Bioproduction by Yeast on Whey Permeate-Based Medium
Get PDF2-Phenylethanol (2-PE) is an alcohol with a rosy scent and antimicrobial activity, and therefore, it is widely used in the food and cosmetic industries as an aroma and preservative. This work was aimed to draw up a technology for 2-PE bioproduction on whey permeate, which is waste produced by the dairy industry, rich in lactase and proteins. Its composition makes it a harmful waste to dispose of; however, with a properly selected microorganism, it could be converted to a value-added product. Herein, two yeast Kluyveromyces marxianus strains and one Kluyveromyces lactis, isolated from dairy products, were tested for 2-PE production, firstly on standard media and then on whey permeate based media in batch cultures. Thereafter, the 2-PE bioproduction in a continuous system in a 4.8 L bioreactor was developed, and subsequently, the final product was recovered from culture broth. The results showed that the yield of 2-PE production increased by 60% in the continuous culture compared to batch culture. Together with a notable reduction of chemical oxygen demand for whey permeate, the present study reports a complete, effective, and environmentally friendly strategy for 2-PE bioproduction with a space-time yield of 57.5 mg L−1 h−1
Composition and function of the C1b/C1f region in the ciliary central apparatus
Get PDFMotile cilia are ultrastructurally complex cell organelles with the ability to actively move. The highly conserved central apparatus of motile 9 × 2 + 2 cilia is composed of two microtubules and several large microtubule-bound projections, including the C1b/C1f supercomplex. The composition and function of C1b/C1f subunits has only recently started to emerge. We show that in the model ciliate Tetrahymena thermophila, C1b/C1f contains several evolutionarily conserved proteins: Spef2A, Cfap69, Cfap246/LRGUK, Adgb/androglobin, and a ciliate-specific protein Tt170/TTHERM_00205170. Deletion of genes encoding either Spef2A or Cfap69 led to a loss of the entire C1b projection and resulted in an abnormal vortex motion of cilia. Loss of either Cfap246 or Adgb caused only minor alterations in ciliary motility. Comparative analyses of wild-type and C1b-deficient mutant ciliomes revealed that the levels of subunits forming the adjacent C2b projection but not C1d projection are greatly reduced, indicating that C1b stabilizes C2b. Moreover, the levels of several IFT and BBS proteins, HSP70, and enzymes that catalyze the final steps of the glycolytic pathway: enolase ENO1 and pyruvate kinase PYK1, are also reduced in the C1b-less mutants
Endogenous Polyamines and Ethylene Biosynthesis in Relation to Germination of Osmoprimed Brassica napus Seeds under Salt Stress
Get PDFCurrently, seed priming is reported as an efficient and low-cost approach to increase crop yield, which could not only promote seed germination and improve plant growth state but also increase abiotic stress tolerance. Salinity represents one of the most significant abiotic stresses that alters multiple processes in plants. The accumulation of polyamines (PAs) in response to salt stress is one of the most remarkable plant metabolic responses. This paper examined the effect of osmopriming on endogenous polyamine metabolism at the germination and early seedling development of Brassica napus in relation to salinity tolerance. Free, conjugated and bound polyamines were analyzed, and changes in their accumulation were discussed with literature data. The most remarkable differences between the corresponding osmoprimed and unprimed seeds were visible in the free (spermine) and conjugated (putrescine, spermidine) fractions. The arginine decarboxylase pathway seems to be responsible for the accumulation of PAs in primed seeds. The obvious impact of seed priming on tyramine accumulation was also demonstrated. Moreover, the level of ethylene increased considerably in seedlings issued from primed seeds exposed to salt stress. It can be concluded that the polyamines are involved in creating the beneficial effect of osmopriming on germination and early growth of Brassica napus seedlings under saline conditions through moderate changes in their biosynthesis and accumulation
Cyclic Dipeptides: The Biological and Structural Landscape with Special Focus on the Anti-Cancer Proline-Based Scaffold
Get PDFCyclic dipeptides, also know as diketopiperazines (DKP), the simplest cyclic forms of peptides widespread in nature, are unsurpassed in their structural and bio-functional diversity. DKPs, especially those containing proline, due to their unique features such as, inter alia, extra-rigid conformation, high resistance to enzyme degradation, increased cell permeability, and expandable ability to bind a diverse of targets with better affinity, have emerged in the last years as biologically pre-validated platforms for the drug discovery. Recent advances have revealed their enormous potential in the development of next-generation theranostics, smart delivery systems, and biomaterials. Here, we present an updated review on the biological and structural profile of these appealing biomolecules, with a particular emphasis on those with anticancer properties, since cancers are the main cause of death all over the world. Additionally, we provide a consideration on supramolecular structuring and synthons, based on the proline-based DKP privileged scaffold, for inspiration in the design of compound libraries in search of ideal ligands, innovative self-assembled nanomaterials, and bio-functional architectures