Clustered PHD domains in KMT2/MLL proteins are attracted by H3K4me3 and H3 acetylation-rich active promoters and enhancers.

Histone lysine-specific methyltransferase 2 (KMT2A-D) proteins, alternatively called mixed lineage leukemia (MLL1-4) proteins, mediate positive transcriptional memory. Acting as the catalytic subunits of human COMPASS-like complexes, KMT2A-D methylate H3K4 at promoters and enhancers. KMT2A-D contain understudied highly conserved triplets and a quartet of plant homeodomains (PHDs). Here, we show that all clustered (multiple) PHDs localize to the well-defined loci of H3K4me3 and H3 acetylation-rich active promoters and enhancers. Surprisingly, we observe little difference in binding pattern between PHDs from promoter-specific KMT2A-B and enhancer-specific KMT2C-D. Fusion of the KMT2A CXXC domain to the PHDs drastically enhances their preference for promoters over enhancers. Hence, the presence of CXXC domains in KMT2A-B, but not KMT2C-D, may explain the promoter/enhancer preferences of the full-length proteins. Importantly, targets of PHDs overlap with KMT2A targets and are enriched in genes involved in the cancer pathways. We also observe that PHDs of KMT2A-D are mutated in cancer, especially within conserved folding motifs (Cys4HisCys2Cys/His). The mutations cause a domain loss-of-function. Taken together, our data suggest that PHDs of KMT2A-D guide the full-length proteins to active promoters and enhancers, and thus play a role in positive transcriptional memory.

The Short-Term Efficacy of a Three-Week Pulmonary Rehabilitation Program among Patients with Obstructive Lung Diseases.

Introduction: The recommended duration for pulmonary rehabilitation stands at a minimum of six weeks; however, this stipulation may pose constraints in various countries due to financial limitations imposed by insurance companies and/or national health funds, as is the case in Poland. Consequently, our study endeavors to analyze the short-term outcomes stemming from a condensed three-week PR regimen administered to patients diagnosed with chronic obstructive pulmonary disease (COPD), asthma, and the concomitance of these conditions (COPD-A)-this is an approach that is standard in the rehabilitation protocols endorsed by our national health fund. Methods: Patients diagnosed with COPD, asthma, and COPD-A, referred to the PR program, underwent retrospective analysis to evaluate the short-term efficacy of a three-week PR program. Patients underwent comprehensive assessment by respiratory physicians and rehabilitation consultants, leading to individualized PR programs. Clinical evaluations occurred at program onset and completion. Results: 125 patients participated: 37 COPD, 61 asthma, and 27 COPD-A. Significant improvements were observed in the COPD Assessment Test (CAT), the consensus-based GINA symptom control tool (GINA-SCT), the Modified Medical Research Council (mMRC) scale, forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and the 6-min walk test (6 MWT) distance, as well as in the St. George's Respiratory Questionnaire (SGRQ) scores. All groups experienced reduced dyspnea severity and improved exercise tolerance. FEV1 and FVC improved in asthma and COPD-A, but not significantly in COPD. Multivariable logistic regression identified predictive factors for PR response. Conclusions: The study supports the short-term efficacy of the three-week PR program in improving clinical outcomes, exercise tolerance, and quality of life in COPD and asthma patients. Tailoring interventions based on predictors of PR response can optimize outcomes. Further research, particularly of the COPD-A group, is needed for individualized approaches. Larger sample sizes are necessary to confirm our findings.

The Influence of Measurement Conditions on the Electrocaloric Effect in Ferroelectric Ceramics of Modified Barium Titanate.

In this work, the electrocaloric effect (ECE) and electrocaloric strength (ΔT/E) were measured and thermal and dielectric studies were performed on Pb-modified BaTiO3 (BPT). The saturated hysteresis loops and normal ferroelectric behavior of the ferroelectric ceramics allow the utilization of the indirect method to estimate the electrocaloric properties. The electrocaloric measurements were performed under high (18 kV/cm) versus low (8 kV/cm) electric field conditions. These conditions were chosen to notice and then eliminate an artificial negative electrocaloric effect in the tested ceramics. At the same time, relatively high values of positive electrocaloric temperature change ΔT (~ 2.19 K) and electrocaloric strength ΔT/E (~0.27-0.11 K·cm/kV) were obtained.

Composition-Related Dielectric, Ferroelectric and Electrocaloric Properties of Pb5Ge3O11 Single Crystals Modified by Ba Ions.

In this paper, we studied some ferroelectric properties of archetypal oxide uniaxial ferroelectric single crystals of Pb5Ge3O11 modified by Ba ions. They include dielectric, DSC, ferroelectric polarization, and electrocaloric effect (ECE) measurements. The measurements show that increasing Ba doping considerably influences all the measured parameters, mainly by lowering the Curie temperature, gradually diffusing the phase transition, and decreasing values of polarization as well as the coercive field. The decrease in overall ECE is influenced by decreasing polarization. Compared with the pure PGO single crystals, this decrease is from 1.2 K to 0.2 K. However, the effect of diffusing the phase transition increases the range of its occurrence (up to 30 K), which might be beneficial in applications.

Special Issue: Emerging Dielectric, Piezoelectric, and Ferroelectric Ceramic and Crystalline Materials and Their Applications.

Materials Physics: Emerging Dielectric, Piezoelectric, and Ferroelectric Ceramic and Crystalline Materials and their Applications is an open Special Issue of Materials, which aims to publish original and review papers on new scientific and applied research and make great contributions to the identification and understanding of ceramic and crystalline materials which today enable applications that were previously virtually unimaginable [...].

An Overview of Some Nonpiezoelectric Properties of BaTiO3 Ceramics Doped by Eu Ions.

Ferroelectric ceramics BaTiO3:x%Eu (x = 0, 0.1, 1, 2, 3) were synthesized by a conventional method. Structural investigation confirmed that all ceramics possessed tetragonal (P4mm) symmetries at room temperature for the undoped ceramics as well as for the doped ceramics. Furthermore, a slight downshifting of the Curie temperature (TC) with an increasing Eu3+ doping amount has been noted. The Raman spectra unveiled the existence of new modes for higher-doped BaTiO3:x%Eu (BTEx) which are related to local disorders and defects. The ferroelectric properties were found to depend on both doping and the microstructure. The electrocaloric effect was also studied for those ceramics. It was observed that ΔT decreases with doping; however, the temperature range of its occurrence widens considerably.

Effectiveness of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease after lobectomy due to non-small cell lung cancer - a single-center retrospective study.

INTRODUCTION: The procedure of lung parenchyma resection may result in impairment of physical capacity and quality of life. In patients with operable non-small cell lung cancer (NSCLC), lobectomy is an elective procedure. Chronic obstructive pulmonary disease (COPD) is a common coexisting condition in patients with NSCLC. Effectiveness of post-operative pulmonary rehabilitation (PR) in patients who underwent lobectomy due to NSCLC and suffering from COPD as compared to individuals without COPD has not been determined yet. The aim of the study was to compare effectiveness of post-operative PR in patients with COPD after lobectomy due to NSCLC (COPD[+] L [+]) with individuals with COPD without lung parenchyma resection (COPD(+) L(-)) and those who underwent lobectomy due to NSCLC and not suffering from COPD (COPD[-] L[+]). MATERIAL AND METHODS: Thirty-seven patients with non-small cell lung cancer (21 patients with and 16 patients without COPD) who underwent lobectomy and 29 subjects with COPD referred to the Lung Diseases Treatment and Rehabilitation Centre in Lodz in 2018-2019 were included in this retrospective analysis. The patients participated in a 3-week inpatient pulmonary rehabilitation (PR) program which included breathing exercises, physical workout, relaxation exercises, education, psychological support and nutrition consulting. The evaluation included lung function measurements, six-minute walking test (6MWT) and the St. George's Respiratory Questionnaire (SGRQ) score. The results obtained before the rehabilitation were compared to those achieved after the 3-week PR program and compared between the study groups. RESULTS: A significant increase in the distance covered during 6MWT was observed in all the three groups studied: COPD(+) L(+) (Δ = 62.52 ± 14.58 m); COPD(-) L(+) (Δ = 73.67 ± 11.58 m); and COPD(+) L(-) (Δ = 59.93 ± 10.02 m) (p < 0.001 for all). Similarly, a statistically and clinically significant improvement in the total SGRQ score was recorded: COPD(+) L(+) ∆ = -12.05 ± 3.96 points; p < 0.05 and COPD(-) L(+) ∆ = -12.30 ± 4.85 points; p < 0.01 and COPD(+) (L-) ∆= -14.07 ± 3.36 points (p < 0.001). No significant differences in the outcome improvement between the study groups were identified. CONCLUSIONS: The results of the study show that COPD(+) L(+) patients gained benefits from post-operative PR comparable to COPD(+) L(-) and COPD(-) L(+) subjects by improving their physical capacity and quality of life.