Noise underlies switching behavior of the bacterial flagellum

We report the switching behavior of the full bacterial flagellum system that includes the filament and the motor in wild-type Escherichia coli cells. In sorting the motor behavior by the clockwise bias, we find that the distributions of the clockwise (CW) and counterclockwise (CCW) intervals are either exponential or nonexponential with long tails. At low bias, CW intervals are exponentially distributed and CCW intervals exhibit long tails. At intermediate CW bias (0.5) both CW and CCW intervals are mainly exponentially distributed. A simple model suggests that these two distinct switching behaviors are governed by the presence of signaling noise within the chemotaxis network. Low noise yields exponentially distributed intervals, whereas large noise yields nonexponential behavior with long tails. These drastically different motor statistics may play a role in optimizing bacterial behavior for a wide range of environmental conditions.     

Efficient synthesis of exomethylene- and keto-exomethylene-d-glucopyranosyl nucleoside analogs as potential cytotoxic agents

A novel series of exomethylene- and keto-exomethylene-d-glucopyranonucleosides with thymine, uracil, and 5-fluorouracil as heterocyclic bases have been designed and synthesized. Wittig condensation of the 3-keto glucoside 1 gave the corresponding 1,2:5,6-di-O-isopropylidene-3-deoxy-3-methylene-d-glucofuranose (2), which after hydrolysis and acetylation led to the precursor 1,2,4,6-tetra-O-acetyl-3-deoxy-3-methylene-d-glucopyranose (4).Compound 4 was condensed with silylated thymine, uracil, and 5-fluorouracil, respectively, deacetylated and acetalated to afford 1-(3′-deoxy-4′,6′-O-isopropylidene-3′-methylene-β-d-glucopyranosyl)pyrimidines 7a–c. Oxidation of the free hydroxyl group in the 2′-position of the sugar moiety led to the formation of the labile 1-(3′-deoxy-4′,6′-O-isopropylidene-3′-methylene-β-d-glucopyranosyl-2′-ulose)pyrimidines 8a–c. Finally, deisopropylidenation of the resulted derivatives 8a–c afforded the diol nucleosides 9a–c. The target keto-exomethylene analogs 9a–c were more cytostatic against a variety of tumor cell lines than the corresponding saturated-hydroxy-exomethylene derivatives 6. In particular, the 5-fluorouracil derivative 9c was highly cytostatic at an IC₅₀ (50% inhibitory concentration) ranging between 0.56 and 9.4 μg/mL, which was comparable to the free parental 5-fluorouracil base.     

Optical method for monitoring of photodynamic inactivation of bacteria

Photodynamic inactivation is a new promising approach to treat bacterial infections. Usually, the evaluation of the efficacy of this method is done through time-consuming and labor-intensive microbiological test methods. This paper describes the development and implementation of an optical method to evaluate the photodynamic inactivation of bacteria based on non-invasive diffuse reflectance measurements. Five Staphylococcus aureus cultures and 15 mice have been used in this study. A skin lesion was created on the back of all animals, and it was contaminated with S. aureus (5.16 ± 0.013 log CFU/ml). Toluidine Blue O (c = 8.67 × 10 ^− 3 M) has been used as a photosensitiser agent. The bacterial cultures and animals were exposed to laser radiation (λ = 635 nm, P = 15 mW, DE = 8.654 J/cm²) for 20 min. The photodynamic inactivation of bacteria was monitored by acquiring the wounds’ reflection spectra at different time points and by microbiological exams on the bioptical material. The good correlation between the diffuse reflectance and colony-forming units demonstrates the value of this optical method based on diffuse reflectance measurements as a rapid technique to monitor photodynamic bacterial inactivation.     

Age and Visual Experience-dependent Expression of NMDAR1 Splice Variants in Rat Retina

The N-methyl-D-aspartate receptor (NMDAR) is a key molecule mediating brain plasticity related processes. Knowing that alternative splicing of the NMDAR1 (NR1) subunit offers molecular diversity to NMDAR, controls the forward trafficking of the NR1 protein and is important for placing NMDA receptors at synapses, we investigated herein the postnatal developmental expression and the influence of visual deprivation on NR1 subunit splice variants in rat retina. Real-time PCR was performed using oligonucleotide primers specific for N- terminal (NR1a, NR1b) and C-terminal splice variants (NR1-1, NR1-2, NR1-3, NR1-4). The developmental profiles of mRNA expression levels of all NR1 isoforms peaked at the end of the third week. Dark rearing led to reductions in both N- and C-terminal NR1 variants in several developmental ages and a significant interaction between age and visual experience was observed for NR1a, NR1-2 and NR1-4 expression. Our results have demonstrated a developmental and visual experience-dependent regulation of NR1 splicing in rat retina.     

Drosophila oogenesis as a bio-marker responding to EMF sources

The model biological organisms Drosophila melanogaster and Drosophila virilis have been utilized to assess effects on apoptotic cell death of follicles during oogenesis and reproductive capacity (fecundity) decline. A total of 280 different experiments were performed using newly emerged flies exposed for short time daily for 3–7?d to various EMF sources including: GSM 900/1800?MHz mobile phone, 1880–1900?MHz DECT wireless base, DECT wireless handset, mobile phone-DECT handset combination, 2.44?GHz wireless network (Wi-Fi), 2.44?GHz blue tooth, 92.8?MHz FM generator, 27.15?MHz baby monitor, 900?MHz CW RF generator and microwave oven’s 2.44?GHz RF and magnetic field components. Mobile phone was used as a reference exposure system for evaluating factors considered very important in dosimetry extending our published work with D. melanogaster to the insect D. virilis. Distance from the emitting source, the exposure duration and the repeatability were examined. All EMF sources used created statistically significant effects regarding fecundity and cell death-apoptosis induction, even at very low intensity levels (0.3?V/m blue tooth radiation), well below ICNIRP’s guidelines, suggesting that Drosophila oogenesis system is suitable to be used as a biomarker for exploring potential EMF bioactivity. Also, there is no linear cumulative effect when increasing the duration of exposure or using one EMF source after the other (i.e. mobile phone and DECT handset) at the specific conditions used. The role of the average versus the peak E-field values as measured by spectrum analyzers on the final effects is discussed.     

Non-coding RNAs and ferroptosis: potential implications for cancer therapy

Ferroptosis is a recently defined form of regulated cell death, which is biochemically and morphologically distinct from traditional forms of programmed cell death such as apoptosis or necrosis. It is driven by iron, reactive oxygen species, and phospholipids that are oxidatively damaged, ultimately resulting in mitochondrial damage and breakdown of membrane integrity. Numerous cellular signaling pathways and molecules are involved in the regulation of ferroptosis, including enzymes that control the cellular redox status. Alterations in the ferroptosis-regulating network can contribute to the development of various diseases, including cancer. Evidence suggests that ferroptosis is commonly suppressed in cancer cells, allowing them to survive and progress. However, cancer cells which are resistant to common chemotherapeutic drugs seem to be highly susceptible to ferroptosis inducers, highlighting the great potential of pharmacologic modulation of ferroptosis for cancer treatment. Non-coding RNAs (ncRNAs) are considered master regulators of various cellular processes, particularly in cancer where they have been implicated in all hallmarks of cancer. Recent work also demonstrated their involvement in the molecular control of ferroptosis. Hence, ncRNA-based therapeutics represent an exciting alternative to modulate ferroptosis for cancer therapy. This review summarizes the ncRNAs implicated in the regulation of ferroptosis in cancer and highlights their underlying molecular mechanisms in the light of potential therapeutic applications.Subject terms: Tumour biomarkers, Oncogenes