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Rhodococcus sp. strain RHA1, a potent polychlorinated-biphenyl (PCB)-degrading strain, contains three linear plasmids ranging in size from 330 to 1,100 kb. As part of a genome sequencing project, we report here the complete sequence and characterization of the smallest and least-well-characterized of the RHA1 plasmids, pRHL3. The plasmid is an actinomycete invertron, containing large terminal inverted repeats with a tightly associated protein and a predicted open reading frame (ORF) that is similar to that of a mycobacterial rep gene. The pRHL3 plasmid has 300 putative genes, almost 21% of which are predicted to have a catabolic function. Most of these are organized into three clusters. One of the catabolic clusters was predicted to include limonene degradation genes. Consistent with this prediction, RHA1 grew on limonene, carveol, or carvone as the sole carbon source. The plasmid carries three cytochrome P450-encoding (CYP) genes, a finding consistent with the high number of CYP genes found in other actinomycetes. Two of the CYP genes appear to belong to novel families; the third belongs to CYP family 116 but appears to belong to a novel class based on the predicted domain structure of its reductase. Analyses indicate that pRHL3 also contains four putative 'genomic islands' (likely to have been acquired by horizontal transfer), insertion sequence elements, 19 transposase genes, and a duplication that spans two ORFs. One of the genomic islands appears to encode resistance to heavy metals. The plasmid does not appear to contain any housekeeping genes. However, each of the three catabolic clusters contains related genes that appear to be involved in glucose metabolism.

Mouse pancreatic development is critically dependent on epithelial-mesenchymal interactions. The pancreas differs from other epithelial-mesenchymal organs in that the epithelium gives rise to both epithelial exocrine cells and non-epithelial endocrine cells. We studied the nature of the interactions between the epithelium and mesenchyme with respect to the decision between exocrine and endocrine lineages. We show here a tripartite influence of mesenchyme on the developing epithelium. First, close proximity or contact of mesenchyme with the epithelium induces exocrine differentiation. Second, this mesenchymal proximity to the epithelium suppresses endocrine differentiation. Third, mesenchyme has an overall enhancing effect on the degree of insulin differentiation, suggesting a pro-endocrine effect in those epithelial cells at a distance from the mesenchyme. Proximity or contact between the mesenchyme and epithelium appeared to be necessary for the pro-exocrine effects of mesenchyme. We found that, in a co-culture system, NIH3T3 cells were able to substitute for mesenchyme in exocrine induction as well as in both the endocrine induction and endocrine inhibition, implying that the responsible molecules are not unique to pancreatic mesenchyme. Laminin appears to be a key molecule mediating the epithelial-mesenchymal interactions that lead to exocrine differentiation, since inhibition of laminin expression resulted in blockage of the pro-exocrine induction of mesenchyme. Keywords: Epithelial-mesenchymal interactions; Pancreas; Epithelium culture; Endocrine and exocrine differentiation; Laminin; Morpholino antisense oligos; Insulin

Thermal atomic layer etching (ALE) for SiO2 films with self-limiting behavior on the surface modification step was developed using sequential exposure to HF and NH3 gases followed by infrared (IR) annealing. X-ray photoelectron spectroscopy analysis showed that an (NH4)2SiF6-based surface-modified layer was formed on the SiO2 surface after gas exposures and that this layer was removed using IR annealing. The etch per cycle (EPC) of the ALE process saturated at 0.9 nm/cycle as the gas exposure times increased. With this self-limiting behavior, SiO2 was etched with high selectivity to poly-Si and Si3N4. The dependence of the EPC on the partial pressures of HF and NH3 was found to be in good agreement with the Langmuir adsorption model. This indicated that the HF and NH-3 molecules were in equilibrium between adsorption and desorption during the exposure, which resulted in the self-limiting formation of the modified layer. In addition to the process with an HF gas flow, it was demonstrated that an H2/SF6 plasma can replace the HF gas exposure step to supply the SiO2 surfaces with HF molecules. The EPC saturated at 2.7 nm/cycle, while no measurable thickness change was observed for poly-Si and Si3N4 films. [ABSTRACT FROM AUTHOR]

Background: The association between salt intake and clinical outcomes in hemodialysis patients has been controversial. This study aimed to clarify the association between salt intake and mortality in hemodialysis patients. Method: The present study included patients who underwent hemodialysis from June 1st 2016 to May 31st 2020. Corrected salt intake by ideal body weight was the main predictor of outcomes. Ideal body weight was calculated assuming that the ideal body mass index is 22 kg/m2 for the Japanese population. The multivariate Cox proportional hazards model was used to determine the association between corrected salt intake and mortality, adjusting for potential confounders. The outcomes considered were all-cause mortality and cumulative incidence of cardiovascular events at year 4. Result: A total of 492 adult patients were enrolled in the study. The mean daily salt intake and corrected salt intake at baseline were 9.5 g/day and 0.17 g/kg/day, respectively. The low corrected salt intake group (< 0.13 g/kg/day) demonstrated the highest 4-year all-cause mortality. No association was observed between corrected salt intake and the cumulative incidence of cardiovascular events. In multivariate Cox proportional hazards analysis, only the group with corrected salt intake of 0.16–0.20 g/kg/day was associated with a decreased hazard risk for all-cause death compared with the low corrected salt intake group. Conclusion: The present study found that a low salt intake was associated with high all-cause mortality in hemodialysis patients. Reduced long-term survival may be attributed to malnutrition resulting from excessive salt restriction. [ABSTRACT FROM AUTHOR]

INTELLANCE‐J was a phase 1/2 study of a potent antibody‐drug conjugate targeting epidermal growth factor receptor (EGFR), depatuxizumab mafodotin (Depatux‐M), as a second‐ or first‐line therapy, alone or combined with chemotherapy or chemoradiotherapy in 53 Japanese patients with World Health Organization (WHO) grade III/IV glioma. In second‐line arms, patients with EGFR‐amplified recurrent WHO grade III/IV glioma received Depatux‐M plus chemotherapy (temozolomide) or Depatux‐M alone regardless of EGFR status. In first‐line arms, patients with newly diagnosed WHO grade III/IV glioma received Depatux‐M plus chemoradiotherapy. The study was halted following lack of survival benefit with first‐line Depatux‐M in the global trial INTELLANCE‐1. The primary endpoint was 6‐month progression‐free survival (PFS) in patients with EGFR‐amplified tumors receiving second‐line Depatux‐M plus chemotherapy. Common nonocular treatment‐emergent adverse events (TEAEs) with both second‐line and first‐line Depatux‐M included lymphopenia (42%, 33%, respectively), thrombocytopenia (39%, 47%), alanine aminotransferase increase (29%, 47%), and aspartate aminotransferase increase (24%, 60%); incidence of grade ≥3 TEAEs was 66% and 53%, respectively. Ocular side effects (OSEs) occurred in 93% of patients receiving second‐line Depatux‐M plus chemotherapy and all patients receiving second‐line Depatux‐M alone or first‐line Depatux‐M plus chemoradiotherapy. Most OSEs were manageable with dose modifications and concomitant medications. The 6‐month PFS estimate was 25.6% (95% confidence interval [CI] 11.4‒42.6), and median PFS was 2.1 months (95% CI 1.9‒3.9) with second‐line Depatux‐M plus chemotherapy in the EGFR‐amplified subgroup. This study showed acceptable safety profile of Depatux‐M alone or plus chemotherapy/chemoradiotherapy in Japanese patients with WHO grade III/IV glioma. The study was registered at ClinicalTrials.gov (NCT02590263). [ABSTRACT FROM AUTHOR]