Positional variations among heterogeneous nucleosome maps give dynamical information on chromatin

Although nucleosome remodeling is essential to transcriptional regulation in eukaryotes, little is known about its genome-wide behavior. Since a number of nucleosome positioning maps in vivo have been recently determined, we examined if their comparisons might be used for obtaining a genome-wide profile of nucleosome remodeling. Using seven yeast maps, the local variability of nucleosomes, measured by the entropy, was significantly higher in a set of reported unstable nucleosomes. The binding sites of four transcription factors, known as the remodeling factors, were distinctively high both in entropy and linker ratio, whereas those of Yhp1, their potential inhibitor, showed the lowest values in both of them. Taken together, our map shows the general information of nucleosome dynamics reasonably well. The “nucleosome dynamics” map provides the new significant correlation with the degree of expression variety instead of their intensity. Furthermore, the associations with gene function and histone modification were also discussed here

High cell density increases glioblastoma cell viability under glucose deprivation via degradation of the cystine/glutamate transporter xCT (SLC7A11)

The cystine/glutamate transporter system x c − consists of the light-chain subunit xCT (SLC7A11) and the heavy-chain subunit CD98 (4F2hc or SLC3A2) and exchanges extracellular cystine for intracellular glutamate at the plasma membrane. The imported cystine is reduced to cysteine and used for synthesis of GSH, one of the most important antioxidants in cancer cells. Because cancer cells have increased levels of reactive oxygen species, xCT, responsible for cystine–glutamate exchange, is overexpressed in many cancers, including glioblastoma. However, under glucose-limited conditions, xCT overexpression induces reactive oxygen species accumulation and cell death. Here we report that cell survival under glucose deprivation depends on cell density. We found that high cell density (HD) down-regulates xCT levels and increases cell viability under glucose deprivation. We also found that growth of glioblastoma cells at HD inactivates mTOR and that treatment of cells grown at low density with the mTOR inhibitor Torin 1 down-regulates xCT and inhibits glucose deprivation-induced cell death. The lysosome inhibitor bafilomycin A1 suppressed xCT down-regulation in HD-cultured glioblastoma cells and in Torin 1–treated cells grown at low density. Additionally, bafilomycin A1 exposure or ectopic xCT expression restored glucose deprivation–induced cell death at HD. These results suggest that HD inactivates mTOR and promotes lysosomal degradation of xCT, leading to improved glioblastoma cell viability under glucose-limited conditions. Our findings provide evidence that control of xCT protein expression via lysosomal degradation is an important mechanism for metabolic adaptation in glioblastoma cells

High-rate OVPE-GaN crystal growth at a very high temperature of 1300 °C

Abstract Polycrystal formation is an issue to be resolved to grow thick GaN crystals by the oxide vapor phase epitaxy (OVPE) method. Since the high-temperature growth at 1250 °C was effective in suppressing the polycrystal formation in our previous study, we attempt further high-temperature OVPE-GaN crystal growth at 1300 °C. However, the GaN surface decomposition becomes severe at 1300 °C. The pre-growth epitaxy was employed to avoid surface decomposition and enable high-temperature growth. Nearly polycrystal-free growth of GaN crystal was achieved, and we obtained a 478 μm thick OVPE-GaN layer at 1300 °C with a further high growth rate of about 200 μm h−1.</jats:p

Alteration of a Shiga toxin-encoding phage associated with a change in toxin production level and disease severity in Escherichia coli

Among the nine clades of Shiga toxin (Stx)-producing Escherichia coli O157:H7, clade 8 is thought to be highly pathogenic, as it causes severe disease more often than other clades. Two subclades have been proposed, but there are conflicting reports on intersubclade differences in Stx2 levels, although Stx2 production is a risk factor for severe disease development. The global population structure of clade 8 has also yet to be fully elucidated. Here, we present genome analyses of a global clade 8 strain set (n=510), including 147 Japanese strains sequenced in this study. The complete genome sequences of 18 of the 147 strains were determined to perform detailed clade-wide genome analyses together with 17 publicly available closed genomes. Intraclade variations in Stx2 production level and disease severity were also re-evaluated within the phylogenetic context. Based on phylogenomic analysis, clade 8 was divided into four lineages corresponding to the previously proposed SNP genotypes (SGs): SG8_30, SG8_31A, SG8_31B and SG8_32. SG8_30 and the common ancestor of the other SGs were first separated, with SG8_31A and SG8_31B emerging from the latter and SG8_32 emerging from SG8_31B. Comparison of 35 closed genomes revealed the overall structure of chromosomes and pO157 virulence plasmids and the prophage contents to be well conserved. However, Stx2a phages exhibit notable genomic diversity, even though all are integrated into the argW locus, indicating that subtype changes in Stx2a phage occurred from the γ subtype to its variant (γ_v1) in SG8_31A and from γ to δ in SG8_31B and SG8_32 via replacement of parts or almost entire phage genomes, respectively. We further show that SG8_30 strains (all carrying γ Stx2a phages) produce significantly higher levels of Stx2 and cause severe disease more frequently than SG8_32 strains (all carrying δ Stx2a phages). Clear conclusions on SG8_31A and SG8_31B cannot be made due to the small number of strains available, but as SG8_31A (carrying γ_v1 Stx2a phages) contains strains that produce much more Stx2 than SG8_30 strains, attention should also be paid to this SG.</jats:p

Clinical Investigation Of Use Of Episil® Oral Solution In Oral Mucositis During Radiotherapy For Head And Neck Cancer

Abstract Objective: Episil® is a bioadhesive barrier-forming oral liquid gel that has been used in recent years to relieve pain at the onset of oral mucositis (OM) associated with radiotherapy (RT) or chemoradiotherapy (CRT) in patients with head and neck cancer (HNC). We retrospectively analyzed the clinical effect of Episil® on OM in patients with HNC who underwent RT or CRT. Patients and Methods: A total of 65 patients with HNC were treated with RT or CRT at our hospital between June 2018 and May 2020. Among the 65 tumors, 64 were histologically confirmed as squamous cell carcinomas, and one malignant lymphoma. Results: The median total RT dose was 50 Gy (range, 30–70 Gy) and the completion rate of RT was 63/65 (97%). The median time to OM resolution was 47 (6–90) days and was significantly longer (53 [27–90] days) when the total RT dose was ³51 Gy (p&lt;0.001). Episil® was used in 26 patients; among them, 10 of whom discontinued its use due to several factors including ineffective pain relief, usage difficulties, and taste intolerance. The median duration of use was 30 (1–52) days and was significantly longer (34.5 [10–52] days) (p&lt;0.001) when patients experienced pain relief at treatment initiation. Conclusion: Although Episil® has been shown to be effective in improving the pain of OM caused by RT of HNC patients. Episil® needs to be improved, and medical professionals are required to give careful attention to each individual patient.</jats:p

Relationship between the frequency of electrocautery of Hunner lesions and changes in bladder capacity in patients with Hunner type interstitial cystitis

AbstractElectrocautery is a promising treatment option for patients with Hunner type interstitial cystitis (HIC), but frequently requires multiple sessions due to recurrence of the lesions. In the present study, we assessed the relationship between the frequency of electrocautery of Hunner lesions and changes in maximum bladder capacity (MBC) at hydrodistension in a large cohort of 118 HIC patients. Three mixed-effect linear regression analyses were conducted for MBC against (1) the number of sessions; (2) the number of sessions and the time between each session and the first session; and (3) other relevant clinical parameters in addition to the Model (2). The mean number of sessions was 2.8 times. MBC decreased approximately 50 mL for each additional electrocautery session, but this loss was offset by 10 mL for each year the subsequent session was postponed. MBC of &lt; 400 mL at the first session was a significant risk factor for MBC loss with further sessions. No other clinical parameters were associated with MBC over time. This study demonstrates a significant relationship between the frequency of electrocautery of Hunner lesions and MBC changes in HIC patients. Low MBC at the first session is a poor prognostic marker for MBC loss over multiple sessions.</jats:p

Global population structure of the Serratia marcescens complex and identification of hospital-adapted lineages in the complex

International audienceSerratia marcescens is an important nosocomial pathogen causing various opportunistic infections, such as urinary tract infections, bacteremia and sometimes even hospital outbreaks. The recent emergence and spread of multidrug-resistant (MDR) strains further pose serious threats to global public health. This bacterium is also ubiquitously found in natural environments, but the genomic differences between clinical and environmental isolates are not clear, including those between S. marcescens and its close relatives. In this study, we performed a large-scale genome analysis of S. marcescens and closely related species (referred to as the ‘ S. marcescens complex’), including more than 200 clinical and environmental strains newly sequenced here. Our analysis revealed their phylogenetic relationships and complex global population structure, comprising 14 clades, which were defined based on whole-genome average nucleotide identity. Clades 10, 11, 12 and 13 corresponded to S. nematodiphila , S. marcescens sensu stricto , S. ureilytica and S. surfactantfaciens , respectively. Several clades exhibited distinct genome sizes and GC contents and a negative correlation of these genomic parameters was observed in each clade, which was associated with the acquisition of mobile genetic elements (MGEs), but different types of MGEs, plasmids or prophages (and other integrative elements), were found to contribute to the generation of these genomic variations. Importantly, clades 1 and 2 mostly comprised clinical or hospital environment isolates and accumulated a wide range of antimicrobial resistance genes, including various extended-spectrum β-lactamase and carbapenemase genes, and fluoroquinolone target site mutations, leading to a high proportion of MDR strains. This finding suggests that clades 1 and 2 represent hospital-adapted lineages in the S. marcescens complex although their potential virulence is currently unknown. These data provide an important genomic basis for reconsidering the classification of this group of bacteria and reveal novel insights into their evolution, biology and differential importance in clinical settings