bluuebunny/crossref_metadata_2025 huggingface dataset:
PENINGKATAN KOMPETENSI PROFESIONAL GURU DALAM PENGEMBANGAN MEDIA PEMBELAJARAN BERBASIS ICT DI UPT SD NEGERI WONODADI 01 KECAMATAN WONODADI
Authors: Mahdisom  , Isna Nurul Inayati
Published: July 2023

The Covid-19 pandemic has changed the way people live. This includes the need for technology. This condition certainly needs special attention from schools. Especially in monitoring and improving teacher competence in using ICT-based learning media. The results of observations made at the UPT SD Negeri Wonodadi 01 are known that the majority of teachers do not use ICT-based learning media when teaching because they experience difficulties in developing media and they have the assumption that the development of ICT-based learning media is expensive. So to improve the teaching and learning process, school action research through the development of ICT-based learning media in schools needs to be carried out. This type of research is school action research, this research was carried out at SD Negeri Wonodadi 01 in November 2021 with the research subjects being all 10 teachers of SD Negeri Wonodadi 01. The technique of collecting data from this school action research is through qualitative data obtained from observations, interviews and document studies. This procedure includes the following stages: (1) planning, (2) implementation, (3) observation, and (4) reflection. The results showed that in general the quality of the implementation of the activities had increased and the impact of the activities had a positive effect on student well-being. It was concluded that the professional competence of teachers in the development of ICT-based learning media increased.
IMPROVING TEACHER COMPETENCY IN IMPLEMENTING LEARNING METHODS BASED ON ACTIVITY THROUGH PEER TUTORS AT UPT SD NEGERI JATEN, WONODADI DISTRICT, BLITAR DISTRICT
Authors: Wulandari  , Isna Nurul Inayati
Published: July 2023

The results of the Analysis of Quality Report Cards in SD Negeri Jaten show that one of the low educational standards is the process standard. This is reinforced by the results of observations which show that some teachers at these schools do not yet have the ability to properly prepare activity-based lesson plans. For this reason, it is necessary to increase teacher competency in the implementation of active learning through peer tutors. This type of research is school action research. This research was conducted at SD Negeri Jaten in November 2021 with the research subjects being all SD Negeri Jaten teachers. The techniqueof collecting data from this school action research is through qualitative data obtained from observation/observations, interviews and document studies. This procedure includes the following stages: (1) planning, (2) implementation, (3) observation, and (4) reflection. The results showed that in general the quality of the implementation of activities to increase teacher competence in preparing lesson plans using active learning methods had increased and the impact of these activities had quite a positive effect on student well-being.
IMPROVING TEACHER ABILITY IN DEVELOPING HOTS BASED RPP THROUGH WORKSHOP AT UPT SD NEGERI SUTOJAYAN 03
Authors: Endang Sujarwati  , Isna Nurul Inayati
Published: July 2023

The results of observations at SD Negeri Sutojayan 03 show that some teachers still do not have good skills in preparing HOTS-based learning implementation plans. To address this, the researchers plan to carry out school action research with the theme ofincreasing teachers' abilities in preparing HOTS-based lesson plans. This type of research is school action research. This research was conducted at SD Negeri Sutojayan 03 in November 2021 with the research subjects being all teachers at SD Negeri Resapombo. The technique of collecting data from this school action research is through qualitative data obtained from observation/observations, interviews and document studies. This procedure includes the following stages: (1) planning, (2)implementation, (3) observation, and (4) reflection. Based on the results of reflection, monitoring and evaluation that have been carried out, it can be concluded that cycle 1 and cycle 2 activities have increased so that all objectives of this school action research activity are declared successful.
SCHOOL IN USE AND DEVELOPMENT OF ICT-BASED LEARNING MEDIA AT PLUMBANGAN 01 STATE ELEMENTARY SCHOOL
Authors: Suwarno  , Isna Nurul Inayati
Published: July 2023

The results of the analysis of the 8 SNP standards contained in the School Self Evaluation (EDS) UPT SD Negeri Plummbang 01 researchers found weaknesses in process standards, especially teacher competence, which still needed to be improved in the process of using ICT-based learning media and development. The type of this research is school action research. This research was conducted at Plukangan 01 Public Elementary School in November 2021 with the research subjects being all teachers of Resapombo Public Elementary School. The technique of collecting data from this school action research is through qualitative data obtained from observation/observations, interviews and document studies. This procedure includes the following stages: (1) planning, (2) implementation, (3) observation, and (4) reflection. Based on the results of reflection, monitoring and evaluation that have been carried out, it can be concluded that cycle 1 and cycle 2 activities have increased so that all objectives of the school action research activities are declared successful. Teacher competence in using ICT-based learning media and development is said to have increased.
PENERAPAN METODE THINK PAIR SHARE DALAM UPAYA MENINGKATKAN HASIL BELAJAR SISWA
Authors: SUTRISNO TRI
Published: July 2023

Abstract

Mathematics material becomes a 'scourge' for some students. Monotonous learning adds to the boredom of children learning mathematics. Mathematics teachers are required to be a fun educator figure so that the material can be absorbed properly. Based on the results of initial observations at SDN Kalianget Barat 1, it was found that from the number of students as many as 16 students in grade 6, there were 10 students who did not complete theme 1, sub-theme 1, mathematics. The tendency is that they think negatively about mathematics. As if mathematics is a scary subject, difficult, complicated and full of counting numbers. Even though teaching mathematics is not only with numbers that make students bored and less attractive. Teaching mathematics in elementary school (SD) classes does require a special method to make it fun and challenging. The Think Pair Share method is tried to be a model to overcome such problems. This improvement uses classroom action research (CAR), with the hope that the Think Pair Share method can improve student learning outcomes. Based on the results of the study that the use of the Think Pair Share method with good implementation can improve learning outcomes, it is stated from the results of the presentation that in the first cycle the number of children who completed as many as 4 people or 25%, while in the second cycle, the number of students who completed as many as 12 people or 75%, meaning the increase is read as much as 50%. From these data it can be concluded that the implementation of the Think Pair Share learning method can improve learning outcomes.
Development of STEM-Based E-Modules on Colloid Material to Train Scientific Literacy Skills
Authors: Nanda Aria , Rahmah Siti
Published: July 2023

The causes of low literacy in Indonesia are influenced by several factors including teaching materials that are not under the development of students, teacher-centered learning, and low levels of reading ability. This research was conducted to determine the differences in teaching materials used in schools and STEM-based e-modules that were developed and to see the level of feasibility and practicality of STEM-based e-modules. This research used to research and development (R&D) methods by adopting the borg and gall model consisting of over seven stages namely, research and data collection, planning, development, product validation, product revision, field trial, and final product. based on the results of STEM-based e-module validation on colloidal material, the percentage of media and material experts was 89.6% and 90.6%. The practicality of the teacher obtained a percentage of 89%. Based on the validation results of media experts, material experts, and teacher practicality, it was found that STEM-based e-modules were declared feasible and practical to use in the learning process. Based on the results of an analysis of differences in teaching materials in schools and the developed e-modules, it was stated that they were different both in terms of the format and the learning model used.
Stretchable Energy Harvesting Device based on Thermoelectric Composite Films
Authors: Kim Cheol Min , Park Kwi-Il
Published: July 2023

Thermoelectric energy harvesting has attracted a lot of attention for powering self-powered devices because of the potential to generate energy anywhere with a temperature difference. In particular, a stretchable thermoelectric generator (S-TEG) can be applied to the repetitively moving parts of a machine and even a human body. Herein, we suggested a S-TEG using thermoelectric composite films made by dispersing n-type Bi2Te2.7Se0.3 powders into the polyvinylidene fluoride elastomer. The prepared n-type thermoelectric composite film with 75 wt% of Bi2Te2.7Se0.3 powders showed a power factor of 1.81 mW m−1 K−2 at room temperature. Next, we fabricated S-TEG by encapsulating thermoelectric powders-based composite films, and Ag-coated textile electrodes with an Eco-flex matrix. The fabricated stretchable energy harvester generated a maximum output power of 2.35 nW at a temperature difference (ΔT) of 25 K. By repeatedly introducing ΔT=5K, our S-TEG converted the output voltage of 3.4 mV and current signals of 0.25 mA. Moreover, a finite element analysis with multiphysics COMSOL simulation software was conducted to compare the experimental and theoretical thermoelectric output performance of the fabricated S-TEG. Finally, we demonstrated energy harvesting by converting human body heat into electrical energy for potential utilization of our energy harvester. This study led to the development of a S-TEG design using thermoelectric film with a simple and low-cost fabrication procedure, providing a potential approach for use as a next-generation wearable device power source.
Pengujian Kelayaksan Material Gunung Bente Desa Madampi Kecamatan Lawa Kabupaten Muna Barat Sebagai Lapis Pondasi Kelas A
Authors: Nasrul Muhamad , Adityawan Muhamad Handy Dwi , Mustika Wayan
Published: July 2023

"This research aims to determine the feasibility of Mount Bente Material in Madampi Village as a Class Foundation Layer. From the results of research in the laboratory that based on existing tests, the characteristics of the material for Mount Bente in Madampi Village are not suitable for use as a class A road pavement layer because they do not meet the General Highways 2018 specifications (Devision 5). In testing the aggregate sieving analysis of Mount Bente in Madampi Village does not meet General Specifications for Bina Marga 2018 Revision 2 (Division 5) on sieve numbers 1”, 40, and 200 For Class A foundation layer, For laboratory CBR testing of class A aggregates, Mount Bente material, Madampi Village, Lawa District, Muna Barat Regency, 66% also do not meet the Standards specifications implied is 90%.”“Penelitian ini bertujuan untuk mengetahui kelayakan Material Gunung Bente Desa Madampi Sebagai Lapis Pondasi Kelas. Dari hasil penelitian dilaboratorium bahwa berdasarkan pengujian yang ada, karakteristik dari material Gunung Bente Desa Madampi tidak layak digunakan sebagai lapis perkerasan jalan kelas A karena tidak memenuhi spesifikasi Umum Bina Marga 2018 (Devisi 5).Pada pengujian analisa saringan agregat Gunung Bente Desa Madampi tidak memenuhi Spesifikasi Umum Bina Marga 2018 Revisi 2 (Divisi 5) pada saringan nomor 1”, 40, dan 200 Untuk lapis Pondasi Kelas A, Untuk pengujian CBR laboratorium agregat kelas A material Gunung Bente Desa Madampi Kecamtan Lawa Kabupaten Muna Barat 66 % juga tidak memenuhi Standar spesisifikasi yang diisyaratkan yaitu 90%.”
Tinjauan Kebutuhan Alat Berat Pada Proyek Peningkatan Jalan Ambaipua - Motaha
Authors: Resaldi La Ode , Nasrul Nasrul , Fitriah Firiah
Published: July 2023

AbstrakAlat berat yang diteliti dalam Tugas Akhir ini adalah Wheel Loader, Dump Truck, Motor Grader, Vibrator Roller dan Water Tank Truck.Metode perhitungan yang digunakan adalah analisis data, perhitungan volume, perhitungan produktivitas mesin, jumlah mesin, waktu yang dibutuhkan dan analisis biaya mesin.Hasil penelitian lapis pondasi agregat kelas A dengan volume 1.022,25 m3, produktivitas untuk 1 unit wheel loader dapat mencapai 31,74 m3 / jam selama 4,6 hari, dengan harga sewa Rp. 23.464.393 per/hari, 5 unit dump truck dapat 3,87 m3 / jam selama 7,54 hari dengan harga sewa Rp. 296.106.862,66 per/hari, 1 unit motor grader dapat 25,94 m3 / jam selama 5,62 hari dengan harga sewa Rp. 34.998.305,67 per/hari, 1 unit Vibrator Roller bisa 37,35 m3/jam selama 3,90 hari dengan harga sewa Rp. 15.840.537,12 per/hari, Dan didapatkan 1 unit water tangker sebesar 71,14 m3 / jam selama 2 hari dengan harga sewa Rp. 7.823.036,3. AbstrakAlat berat yang di teliti pada Tugas Akhir ini yaitu Wheel Loader, Dump Truck, Motor Grader, Vibrator Roller dan Water Tank Truck .Metode perhitungan yang digunakan yaitu analisa data, perhitungan volume, perhitungan produktivitas alat berat, jumlah alat berat, waktu yang dibutuhkan dan analisa biaya alat berat.Hasil penelitian Lapis gitar agregat kelas A dengan volume 1.022,25 m3 maka produktivitas Untuk 1 unit wheel loader di dapat sebesar 31,74 m 3 /jam selama 4,6 hari, dengan harga sewa Rp. 23.464.393 per/hari, 5 unit dump truck di dapat sebesar 3,87 m 3 /jam selama 7,54 hari dengan harga sewa Rp. 296.106.862,66 per/hari, 1 unit motor grader dapat sebesar 25,94 m 3 /jam selama 5,62 hari dengan harga sewa Rp. 34.998.305,67 per/hari, 1 unit Vibrator Roller dapat sebesar 37,35 m 3 /jam selama 3,90 hari dengan harga sewa Rp. 15.840.537,12 per/hari, Dan 1 unit water tangker yang di dapatkan sebesar 71,14 m3 /jam selama 2 hari dengan harga sewa Rp. 7.823.036,3.
Photoinduced self-assembly of nanocrystals inside Al2O3-Lu2O3 glass
Authors: Okuno Tatsuya , Shimotsuma Yasuhiko , Shimizu Masahiro , Miura Kiyotaka
Published: July 2023

The femtosecond laser direct writing technique can allow spatially selective crystallization with suppression of thermal conduction effects. In the case of Al2O3-R2O3 (R = Y, Dy) glass, the polarization-dependent periodic nanostructure with crystallization is self-assembled, however, the formation mechanism of self-assembled nanocrystals in glass remains to be clarified. We focused on Al2O3-Lu2O3 glass prepared by a containerless laser melting method and demonstrated the formation of a nanograting with crystallization by femtosecond laser irradiation. Polarized luminescence measurements of the crystallized region by the pulse bursts with a controllable number of pulses reveal that luminescence anisotropy increased at more than 50 pulses in a burst, suggesting the formation of the nanograting. We have also followed the time variation of birefringence by polarized light imaging to evaluate the time scale for the formation of nanogratings with crystallization.
Characterization of human stem cell-derived hepatic stellate cells and liver sinusoidal endothelial cells during extended in vitro culture
Authors: Wilhelmsen Ingrid , Amirola Martinez Mikel , Stokowiec Justyna , Wang Chencheng , Aizenshtadt Aleksandra , Krauss Stefan
Published: July 2023

Background: There is a significant need for predictive and stable in vitro human liver representations for disease modeling and drug testing. Hepatic stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs) are important non-parenchymal cell components of the liver and are hence of relevance in a variety of disease models, including hepatic fibrosis. Pluripotent stem cell- (PSC-) derived HSCs (scHSCs) and LSECs (scLSECs) offer an attractive alternative to primary human material; yet, the suitability of scHSCs and scLSECs for extended in vitro modeling has not been characterized.

Methods: In this study, we describe the phenotypic and functional development of scHSCs and scLSECs during 14 days of 2D in vitro culture. Cell-specific phenotypes were evaluated by cell morphology, immunofluorescence, and gene- and protein expression. Functionality was assessed in scHSCs by their capacity for intracellular storage of vitamin A and response to pro-fibrotic stimuli induced by TGF-β. scLSECs were evaluated by nitric oxide- and factor VIII secretion as well as endocytic uptake of bioparticles and acetylated low-density lipoprotein. Notch pathway inhibition and co-culturing scHSCs and scLSECs were separately tested as options for enhancing long-term stability and maturation of the cells.

Results and Conclusion: Both scHSCs and scLSECs exhibited a post-differentiation cell type-specific phenotype and functionality but deteriorated during extended culture with PSC line-dependent variability. Therefore, the choice of PSC line and experimental timeframe is crucial when designing in vitro platforms involving scHSCs and scLSECs. Notch inhibition modestly improved long-term monoculture in a cell line-dependent manner, while co-culturing scHSCs and scLSECs provides a strategy to enhance phenotypic and functional stability.
Inhibition of Hepatitis B Virus (HBV) replication and antigen expression by Brucea javanica (L.) Merr. oil emulsion
Authors: Qin Bo , Shen Shu , Lai Juan , Yang Wei , Feng Lili , Ding Jiefeng
Published: July 2023

Introduction

The seeds of Brucea javanica (L.) Merr. (BJ) have been traditionally used to treat various types of cancers for many years in China. In this study, we systematically investigated a BJ oil emulsion (BJOE) produced from BJ seeds with the purpose of evaluating its antiviral effect against hepatitis B virus (HBV).

Methods

HepG2.215 (a wild-type HBV cell line), HepG2, and Huh7, transfected with wildtype (WT) or lamivudine-resistance mutant (LMV-MT) HBV replicon plasmids, were treated with different doses of BJOE and then used for pharmacodynamic evaluation. Cell viability was determined using CCK8 assay. The levels of HBsAg/HBeAg in cell cultured supernatant, HBcAg in cell lysis solution, and HBV DNA in both were evaluated.

Results

BJOE at ≤5 mg/ml was nontoxic to carcinoma cell lines, but could significantly inhibit WT/LMV-MT HBV replication and HBs/e/c antigen expression in a dose-dependent manner by upregulating interleukin-6 (IL-6), demonstrating that it possesses moderate anti-HBV activity. As one of the major components of BJOE, bruceine B was found to play a dominant role in IL-6 induction and HBV inhibition.

Discussion

Our results demonstrated that BJOE suppressed HBV replication by stimulating IL-6, indicating that it has promising clinical therapeutic potential for both WT and LMV-MT HBV.
The role of Mycobacterium tuberculosis acetyltransferase and protein acetylation modifications in tuberculosis
Authors: Huang Yinxia , Zhu Chuanzhi , Pan Liping , Zhang Zongde
Published: July 2023

Tuberculosis (TB) is a widespread infectious disease caused by Mycobacterium tuberculosis (M. tb), which has been a significant burden for a long time. Post-translational modifications (PTMs) are essential for protein function in both eukaryotic and prokaryotic cells. This review focuses on the contribution of protein acetylation to the function of M. tb and its infected macrophages. The acetylation of M. tb proteins plays a critical role in virulence, drug resistance, regulation of metabolism, and host anti-TB immune response. Similarly, the PTMs of host proteins induced by M. tb are crucial for the development, treatment, and prevention of diseases. Host protein acetylation induced by M. tb is significant in regulating host immunity against TB, which substantially affects the disease’s development. The review summarizes the functions and mechanisms of M. tb acetyltransferase in virulence and drug resistance. It also discusses the role and mechanism of M. tb in regulating host protein acetylation and immune response regulation. Furthermore, the current scenario of isoniazid usage in M. tb therapy treatment is examined. Overall, this review provides valuable information that can serve as a preliminary basis for studying pathogenic research, developing new drugs, exploring in-depth drug resistance mechanisms, and providing precise treatment for TB.
Effect of ubiquinol on cardiorespiratory fitness during high-altitude acclimatization and de-acclimatization in healthy adults: the Shigatse CARdiorespiratory fitness study design
Authors: Yang Jie , Ye Xiaowei , Liu Zhen , Sun Mengjia , Yu Shiyong , Lv Hailin , Wu Boji , Zhang Chen , Gu Wenzhu , He Jingyu , Wang Xuhong , Huang Lan
Published: July 2023

Cardiorespiratory function influences exercise capacity and is an important determinant of high-altitude adaptation. Some studies have investigated the characteristics of changes in cardiorespiratory fitness during high-altitude acclimatization. However, studies on changes in cardiorespiratory fitness during high-altitude de-acclimatization are still lacking and have not yet been elucidated. Furthermore, few drugs have been studied to improve cardiorespiratory function during both processes. The Shigatse CARdiorespiratory Fitness (SCARF) study is a single-center, randomized, double-blind, placebo-control clinical trial to explore the effects of ubiquinol on cardiorespiratory fitness during high-altitude acclimatization and de-acclimatization in healthy adults. Participants will be randomly assigned 1:1 to ubiquinol 200 mg daily or a placebo for 14 days before departure until the end of data collection after return in 7 days. Cardiorespiratory fitness is the primary outcome, while acute mountain sickness and high-altitude de-acclimatization symptoms are secondary endpoints. In addition, laboratory measurements, including routine blood tests and serological measurements, will be performed. To the best of our knowledge, the SCARF study will be the first to reveal the changes in the cardiorespiratory fitness characteristics during high-altitude acclimatization and de-acclimatization. Furthermore, the results of this study will contribute to exploring whether ubiquinol supplementation could be beneficial for endurance exercise capacity at different altitudes and help improve adaptation to acute hypoxia and de-acclimatization.

Clinical Trial Registration: This study has been registered in the Chinese Clinical Trial Register (www.chictr.org.cn) as ChiCTR2200059900 and ChiCTR2200066328.
The importance of good practices and false hits for QSAR-driven virtual screening real application: a SARS-CoV-2 main protease (Mpro) case study
Authors: Serafim Mateus Sá Magalhães , Pantaleão Simone Queiroz , da Silva Elany Barbosa , McKerrow James H. , O’Donoghue Anthony J. , Mota Bruno Eduardo Fernandes , Honorio Kathia Maria , Maltarollo Vinícius Gonçalves
Published: July 2023

Computer-Aided Drug Design (CADD) approaches, such as those employing quantitative structure-activity relationship (QSAR) methods, are known for their ability to uncover novel data from large databases. These approaches can help alleviate the lack of biological and chemical data, but some predictions do not generate sufficient positive information to be useful for biological screenings. QSAR models are often employed to explain biological data of chemicals and to design new chemicals based on their predictions. In this review, we discuss the importance of data set size with a focus on false hits for QSAR approaches. We assess the challenges and reliability of an initial in silico strategy for the virtual screening of bioactive molecules. Lastly, we present a case study reporting a combination approach of hologram-based quantitative structure-activity relationship (HQSAR) models and random forest-based QSAR (RF-QSAR), based on the 3D structures of 25 synthetic SARS-CoV-2 Mpro inhibitors, to virtually screen new compounds for potential inhibitors of enzyme activity. In this study, optimal models were selected and employed to predict Mpro inhibitors from the database Brazilian Compound Library (BraCoLi). Twenty-four compounds were then assessed against SARS-CoV-2 Mpro at 10 µM. At the time of this study (March 2021), the availability of varied and different Mpro inhibitors that were reported definitely affected the reliability of our work. Since no hits were obtained, the data set size, parameters employed, external validations, as well as the applicability domain (AD) could be considered regarding false hits data contribution, aiming to enhance the design and discovery of new bioactive molecules.
Eye movements are stable predictors of word reading ability in young readers
Authors: Strandberg Andrea , Nilsson Mattias , Östberg Per , Seimyr Gustaf Öqvist
Published: July 2023

During the first years of formal instruction in reading, there are developmental changes to the characteristics of children’s eye movements that correspond to their progress. Generally, these changes are driven by improved text processing and a shift from reliance on sub-lexical to lexical processes. Currently, however, little is known about to what extent early eye movements during reading in ecological contexts account for variations in later word reading ability. In this paper we investigate this association in 164 children in first grade and 206 children in second grade. We recorded their eye movements during normal text passage reading in an unrestricted eye tracking set-up. We analyzed to what extent they account for variation in word reading ability 1 year post-recording, and make comparisons to concurrent predictions. Regression analysis revealed that eye movements accounted for approximately 60% of the variance in concurrent word reading ability and approximately 48% 1 year later. Mean fixation duration explained unique variance in reading ability and largely drives the correlation. Proportion of regressions was not a significant longitudinal predictor among the youngest readers. The difference between the concurrent and longitudinal predictions was greatest in the younger children, which was in line with our expectation. Findings are discussed in relation to current models of word reading. Our results suggest that eye movements are stable predictors of word reading ability. Ultimately, knowledge of what can be gleaned from early readers’ natural eye movements about later word reading ability could help inform assessments of reading development in the educational setting, where the presence of digital assessment tools is growing.
Agentic playful pre-service teachers: positionings from teacher-initiated playful teacher to community-shared playful teacher
Authors: Melasalmi Anitta , Siklander Signe , Kangas Marjaana , Hurme Tarja-Riitta
Published: July 2023

Play and playfulness are understood as basic and vital elements of early childhood education (ECE), and together with playful pedagogies, they perform a central role in Finnish ECE. In multidisciplinary research, children’s learning is generally understood through the inquiring process of play. However, playfulness, as opposed to play, has received relatively little scholarly attention, and educators’ use of playfulness has received even less. Playfulness is a vital part of life for both adults and children. At the same time, teachers’ behavior can influence the playfulness of a child; moreover, teachers’ own playfulness is critical for establishing warm and secure relationships with children. As such, the aim of this research was to explore pre-service teachers’ (PsTs’) understanding of agentic playfulness, particularly in the ECE context. Study participants included 159 PsTs; study data were gathered from PsTs’ written reflections regarding the use of playfulness in their future work. The results of qualitative analyses showed that the PsTs’ agentic playfulness mirrored a relational and tensious space consisting of three domains: teacher-initiated agentic playfulness, child-centered agentic playfulness, and community-shared agentic playfulness. Each domain revealed dimensions of the nature of PsTs’ orientation of their agentic playfulness. The results are discussed in relation to pedagogization of play, relational pedagogy community of learners, and teacher education supporting and developing future ECE teachers’ agentic playfulness.
Organochlorine pesticides and epigenetic alterations in thyroid tumors
Authors: Salimi Fouzieh , Asadikaram Gholamreza , Ashrafi Mohammad Reza , Zeynali Nejad Hamid , Abolhassani Moslem , Abbasi-Jorjandi Mojtaba , Sanjari Mojgan
Published: July 2023

Purpose

Cancer incidence depends on various factors e.g., pesticide exposures which cause epigenetic alterations. The present research aimed to investigate the organochlorine pesticides (OCPs) impacts on promoter methylation of three tumor-suppressor genes and four histone modifications in thyroid nodules in 61 Papillary thyroid carcinoma (PTC) and 70 benign thyroid nodules (BTN) patients.

Methods

OCPs were measured by Gas chromatography. To identify promoter methylation of TSHR, ATM, and P16 genes, the nested-methylation-specific PCR (MSP) was utilized, and histone lysine acetylation (H3K9, H4K16, and H3K18) and lysine methylation (H4K20) were detected by performing western blot analysis.

Results

Further TSHR methylation and less P16 methylation were observed in PTC than in BTN. No substantial difference was detected for ATM methylation between PTC and BTN groups. Also, OCP dramatically increased the odds ratio of TSHR (OR=3.98, P=0.001) and P16 (OR=5.65, P<0.001) methylation while confounding variables reduced the chances of ATM methylation arising from 2,4-DDE and 4,4-DDT influence. Hypomethylation of H4K20 and hypo-acetylation of H3K9, H4K16, and H3K18 (P<0.001) were observed in PTC samples than BTN. Furthermore, OCPs substantially decreased the odds ratio of H3K9 (OR=3.68, P<0.001) and H4K16 (OR=6.03, P<0.001) acetylation.

Conclusion

The current research indicated that OCPs could contribute to PTC progression by TSHR promoter hypermethylation and decreased acetylation of H3K9 and H4K16. In addition, in PTC patients, assessing TSHR promoter methylation and acetylation of H3K9 and H4K16 could have predictive values.
Chronic-binge ethanol feeding aggravates systemic dyslipidemia in Ldlr-/- mice, thereby accelerating hepatic fibrosis
Authors: Hoebinger Constanze , Rajcic Dragana , Silva Beatriz , Hendrikx Tim
Published: July 2023

Objective

Chronic ethanol consumption is known to cause alcohol-associated liver disease, which poses a global health concern as almost a quarter of heavy drinkers develop severe liver damage. Alcohol-induced liver disease ranges from a mild, reversible steatotic liver to alcoholic steatohepatitis and irreversible liver fibrosis and cirrhosis, ultimately requiring liver transplantation. While ethanol consumption is associated with dysregulated lipid metabolism and altered cholesterol homeostasis, the impact of dyslipidemia and pre-existing hypercholesterolemia on the development of alcohol-associated liver disease remains to be elucidated.

Design

To address the influence of systemic dyslipidemia on ethanol-induced liver disease, chronic-binge ethanol feeding was applied to female C57BL/6J (wild type) mice and mice deficient for the low-density lipoprotein receptor (Ldlr-/-), which display a human-like lipoprotein profile with elevated cholesterol and triglyceride levels in circulation. Respective control groups were pair-fed an isocaloric diet.

Results

Chronic-binge ethanol feeding did not alter systemic lipid levels in wild type mice. While increased systemic cholesterol levels in Ldlr-/- mice were not affected by ethanol feeding, chronic-binge ethanol diet aggravated elevated plasma triglyceride levels in Ldlr-/- mice. Despite higher circulatory triglyceride levels in Ldlr-/- mice, hepatic lipid levels and the development of hepatic steatosis were not different from wild type mice after ethanol diet, while hepatic expression of genes related to lipid metabolism (Lpl) and transport (Cd36) showed minor changes. Immunohistochemical assessment indicated a lower induction of infiltrating neutrophils in the livers of ethanol-fed Ldlr-/- mice compared to wild type mice. In line, hepatic mRNA levels of the pro-inflammatory genes Ly6g, Cd11b, Ccr2, Cxcl1 and F4/80 were reduced, indicating less inflammation in the livers of Ldlr-/- mice which was associated with reduced Tlr9 induction. While systemic ALT and hepatic MDA levels were not different, Ldlr-deficient mice showed accelerated liver fibrosis development after chronic-binge ethanol diet than wild type mice, as indicated by increased levels of Sirius Red staining and higher expression of pro-fibrotic genes Tgfb, Col1a1 and Col3a1. Ldlr-/- and wild type mice had similar plasma ethanol levels and did not show differences in the hepatic mRNA levels of Adh1 and Cyp2e1, important for ethanol metabolism.

Conclusion

Our results highlight that chronic-binge ethanol feeding enhances systemic dyslipidemia in Ldlr-/- mice which might accelerate the development of hepatic fibrosis, independent of hepatic lipid levels.
Short-chain fatty acids, secondary bile acids and indoles: gut microbial metabolites with effects on enteroendocrine cell function and their potential as therapies for metabolic disease
Authors: Masse Karly E. , Lu Van B.
Published: July 2023

The gastrointestinal tract hosts the largest ecosystem of microorganisms in the body. The metabolism of ingested nutrients by gut bacteria produces novel chemical mediators that can influence chemosensory cells lining the gastrointestinal tract. Specifically, hormone-releasing enteroendocrine cells which express a host of receptors activated by these bacterial metabolites. This review will focus on the activation mechanisms of glucagon-like peptide-1 releasing enteroendocrine cells by the three main bacterial metabolites produced in the gut: short-chain fatty acids, secondary bile acids and indoles. Given the importance of enteroendocrine cells in regulating glucose homeostasis and food intake, we will also discuss therapies based on these bacterial metabolites used in the treatment of metabolic diseases such as diabetes and obesity. Elucidating the mechanisms gut bacteria can influence cellular function in the host will advance our understanding of this fundamental symbiotic relationship and unlock the potential of harnessing these pathways to improve human health.
Optical genome mapping in an atypical Pelizaeus-Merzbacher prenatal challenge
Authors: Rogac Mihael , Kovanda Anja , Lovrečić Luca , Peterlin Borut
Published: July 2023

Pathogenic genetic variants represent a challenge in prenatal counseling, especially when clinical presentation in familial carriers is atypical. We describe a prenatal case involving a microarray-detected duplication of PLP1 which causes X-linked Pelizaeus-Merzbacher disease, a progressive hypomyelinating leukodystrophy. Because of atypical clinical presentation in an older male child, the duplication was examined using a novel technology, optical genome mapping, and was found to be an inverted duplication, which has not been previously described. Simultaneously, segregation analysis identified another healthy adult male carrier of this unique structural rearrangement. The novel PLP1 structural variant was reclassified, and a healthy boy was delivered. In conclusion, we suggest that examining structural variants with novel methods is warranted especially in cases with atypical clinical presentation and may in these cases lead to improved prenatal and postnatal genetic counseling.
Identification of the novel FOXP3-dependent Treg cell transcription factor MEOX1 by high-dimensional analysis of human CD4+ T cells
Authors: Baßler Kevin , Schmidleithner Lisa , Shakiba Mehrnoush Hadaddzadeh , Elmzzahi Tarek , Köhne Maren , Floess Stefan , Scholz Rebekka , Ohkura Naganari , Sadlon Timothy , Klee Kathrin , Neubauer Anna , Sakaguchi Shimon , Barry Simon C. , Huehn Jochen , Bonaguro Lorenzo , Ulas Thomas , Beyer Marc
Published: July 2023

CD4+ T cells play a central role in the adaptive immune response through their capacity to activate, support and control other immune cells. Although these cells have become the focus of intense research, a comprehensive understanding of the underlying regulatory networks that orchestrate CD4+ T cell function and activation is still incomplete. Here, we analyzed a large transcriptomic dataset consisting of 48 different human CD4+ T cell conditions. By performing reverse network engineering, we identified six common denominators of CD4+ T cell functionality (CREB1, E2F3, AHR, STAT1, NFAT5 and NFATC3). Moreover, we also analyzed condition-specific genes which led us to the identification of the transcription factor MEOX1 in Treg cells. Expression of MEOX1 was comparable to FOXP3 in Treg cells and can be upregulated by IL-2. Epigenetic analyses revealed a permissive epigenetic landscape for MEOX1 solely in Treg cells. Knockdown of MEOX1 in Treg cells revealed a profound impact on downstream gene expression programs and Treg cell suppressive capacity. These findings in the context of CD4+ T cells contribute to a better understanding of the transcriptional networks and biological mechanisms controlling CD4+ T cell functionality, which opens new avenues for future therapeutic strategies.
Role of epithelial sodium channel-related inflammation in human diseases
Authors: Chen Yabin , Yu Xiao , Yan Zhiping , Zhang Shuijun , Zhang Jiacheng , Guo Wenzhi
Published: July 2023

The epithelial sodium channel (ENaC) is a heterotrimer and is widely distributed throughout the kidneys, blood vessels, lungs, colons, and many other organs. The basic role of the ENaC is to mediate the entry of Na+ into cells; the ENaC also has an important regulatory function in blood pressure, airway surface liquid (ASL), and endothelial cell function. Aldosterone, serum/glucocorticoid kinase 1 (SGK1), shear stress, and posttranslational modifications can regulate the activity of the ENaC; some ion channels also interact with the ENaC. In recent years, it has been found that the ENaC can lead to immune cell activation, endothelial cell dysfunction, aggravated inflammation involved in high salt-induced hypertension, cystic fibrosis, pseudohypoaldosteronism (PHA), and tumors; some inflammatory cytokines have been reported to have a regulatory role on the ENaC. The ENaC hyperfunction mediates the increase of intracellular Na+, and the elevated exchange of Na+ with Ca2+ leads to an intracellular calcium overload, which is an important mechanism for ENaC-related inflammation. Some of the research on the ENaC is controversial or unclear; we therefore reviewed the progress of studies on the role of ENaC-related inflammation in human diseases and their mechanisms.
Thymic epithelial cell fate and potency in early organogenesis assessed by single cell transcriptional and functional analysis
Authors: Farley Alison Mary , Chengrui An , Palmer Sam , Liu Dong , Kousa Anastasia I. , Rouse Paul , Major Viktoria , Sweetman Joanna , Morys Jan , Corsinotti Andrea , Nichols Jennifer , Ure Janice , McLay Renee , Boulter Luke , Chapman S. Jon , Tomlinson Simon R. , Blackburn C. Clare
Published: July 2023

During development, cortical (c) and medullary (m) thymic epithelial cells (TEC) arise from the third pharyngeal pouch endoderm. Current models suggest that within the thymic primordium most TEC exist in a bipotent/common thymic epithelial progenitor cell (TEPC) state able to generate both cTEC and mTEC, at least until embryonic day 12.5 (E12.5) in the mouse. This view, however, is challenged by recent transcriptomics and genetic evidence. We therefore set out to investigate the fate and potency of TEC in the early thymus. Here using single cell (sc) RNAseq we identify a candidate mTEC progenitor population at E12.5, consistent with recent reports. Via lineage-tracing we demonstrate this population as mTEC fate-restricted, validating our bioinformatics prediction. Using potency analyses we also establish that most E11.5 and E12.5 progenitor TEC are cTEC-fated. Finally we show that overnight culture causes most if not all E12.5 cTEC-fated TEPC to acquire functional bipotency, and provide a likely molecular mechanism for this changed differentiation potential. Collectively, our data overturn the widely held view that a common TEPC predominates in the E12.5 thymus, showing instead that sublineage-primed progenitors are present from the earliest stages of thymus organogenesis but that these early fetal TEPC exhibit cell-fate plasticity in response to extrinsic factors. Our data provide a significant advance in the understanding of fetal thymic epithelial development and thus have implications for thymus-related clinical research, in particular research focussed on generating TEC from pluripotent stem cells
Clonal composition and differentiation stage of human CD30+ B cells in reactive lymph nodes
Authors: Küppers Ralf , Budeus Bettina , Hartmann Sylvia , Hansmann Martin-Leo
Published: July 2023

Introduction

Normal CD30+ B cells represent a distinct B-cell differentiation stage with features of strong activation. We lack an in depth understanding of these cells, because they are not present in peripheral blood and are typically very rare in reactive lymphoid organs. CD30+ B cells have been discussed as a potential precursor population for the malignant CD30+ Hodgkin and Reed-Sternberg cells in classical Hodgkin lymphoma. As CD30+ B cells can be more numerous in some cases of reactive lymphadenitis, we aimed to characterize these CD30+ B cells in terms of their differentiation stage and clonal composition, also as a means to clarify whether such CD30+ B-cell populations may represent potential precursor lesions of Hodgkin lymphoma.

Methods

We microdissected single CD30+ B cells from tissue sections of eight reactive lymph nodes with substantial numbers of such cells and sequenced their rearranged immunoglobulin (Ig) heavy chain V region (IGHV) genes.

Results

The CD30+ B cells were polyclonal B cells in all instances, and they not only encompass post-germinal center (GC) B cells with mutated IGHV genes, but also include a substantial fraction of pre-germinal center B cells with unmutated IGHV genes. In five of the lymph nodes, mostly small clonal expansions were detected among the CD30+ B cells. Most of the expanded clones carried somatically mutated IGHV genes and about half of the mutated clones showed intraclonal diversity.

Discussion

We conclude that in human reactive lymph nodes with relatively many CD30+ B cells, these cells are a heterogenous population of polyclonal B cells encompassing activated pre-GC B cells as well as GC and post-GC B cells, with some clonal expansions. Because of their polyclonality and frequent pre-GC differentiation stage, there is no indication that such cell-rich CD30+ B-cell populations represent precursor lesions of Hodgkin lymphoma.
Cell type-specific roles of NLRP3, inflammasome-dependent and -independent, in host defense, sterile necroinflammation, tissue repair, and fibrosis
Authors: Honda Tamisa Seeko Bandeira , Ku John , Anders Hans-Joachim
Published: July 2023

The NLRP3 inflammasome transforms a wide variety of infectious and non-infectious danger signals that activate pro-inflammatory caspases, which promote the secretion of IL-1β and IL-18, and pyroptosis, a pro-inflammatory form of cell necrosis. Most published evidence documents the presence and importance of the NLRP3 inflammasome in monocytes, macrophages, and neutrophils during host defense and sterile forms of inflammation. In contrast, in numerous unbiased data sets, NLRP3 inflammasome-related transcripts are absent in non-immune cells. However, an increasing number of studies report the presence and functionality of the NLRP3 inflammasome in almost every cell type. Here, we take a closer look at the reported cell type-specific expression of the NLRP3 inflammasome components, review the reported inflammasome-dependent and -independent functions, and discuss possible explanations for this discrepancy.
A luminescence-based method to assess antigen presentation and antigen-specific T cell responses for in vitro screening of immunomodulatory checkpoints and therapeutics
Authors: Álvarez Freile Jimena , Qi Yuzhu , Jacob Lisa , Lobo Maria Franceskin , Lourens Harm Jan , Huls Gerwin , Bremer Edwin
Published: July 2023

Investigations into the strength of antigen-specific responses in vitro is becoming increasingly relevant for decision making in early-phase research of novel immunotherapeutic approaches, including adoptive cell but also immune checkpoint inhibitor (ICI)-based therapies. In the latter, antigen-specific rapid and high throughput tools to investigate MHC/antigen-specific T cell receptor (TCR) activation haven’t been implemented yet. Here, we present a simple and rapid luminescence-based approach using the human papillomavirus 16 (HPV16) E711-20 peptide as model antigen and E7-TCR transgenic Jurkat.NFAT-luciferase reporter cells. Upon E7 peptide pulsing of HLA-A2+ cell lines and macrophages, an effector to target ratio dependent increase in luminescence compared to non-pulsed cells was observed after co-incubation with E7-TCR expressing Jurkat, but not with parental cells. Analogous experiments with cells expressing full-length HPV16 identified that E7-specific activation of Jurkat cells enabled detection of endogenous antigen processing and MHC-I presentation. As proof of concept, overexpression of established checkpoints/inhibitory molecules (e.g., PD-L1 or HLA-G) significantly reduced the E7-specific TCR-induced luminescence, an effect that could be restored after treatment with corresponding targeting antagonistic antibodies. Altogether, the luminescence-based method described here represents an alternative approach for the rapid evaluation of MHC-dependent antigen-specific T cell responses in vitro. It can be used as a rapid tool to evaluate the impact of the immunosuppressive tumor microenvironment or novel ICI in triggering effective T cell responses, as well as speeding up the development of novel therapeutics within the immune-oncology field.
The cold-water coral province of the eastern Ligurian Sea (NW Mediterranean Sea): historical and novel evidences
Authors: Bo Marzia , Enrichetti Francesco , Betti Federico , Gay Guido , Quarta Gianluca , Calcagnile Lucio , Bavestrello Giorgio
Published: July 2023

Several bathyal cold-water coral provinces, characterized by a lush growth of habitat-forming scleractinians, have been recognized in the Mediterranean Sea. However, the search for this biogenic habitat only marginally targeted the Italian coast of the Ligurian Sea (NW Mediterranean basin) despite historical and a few recent local studies in the region reporting the presence of corals. This study used bathymetry maps, side-scan sonar profiles, historical charts, and trawling routes to identify sites that could potentially host coral habitats in the eastern sector of the Ligurian Sea. Remotely operated vehicle video footage from various projects (2015-2021, 20 dives) was then used to characterize four sub-areas (Genoa Plateau, Portofino, Deiva Marina, and Monterosso) where corals were detected between 450 m and 750 m depth. Radiocarbon dating was used to trace back the geological history of the coral structures. A small coral mound, impacted by trawling activities, was found on the Genoa Plateau, while four massive coral structures were found in the other sub-areas, mainly located in a morphologically complex and highly energetic canyon region. High levels of megafaunal biodiversity, including rarely reported alcyonaceans as Placogorgia coronata, were observed together with moderate fishing impact. Overall, the identified coral areas potentially account for 9 km2 of both subfossil mounds (as old as 13300 years BP), dominated by Desmophyllum pertusum, and living reefs, dominated by Madrepora oculata, the latter representing up to 23% of the substrate coverage. The few living colonies of D. pertusum in the area represent the first documented records for the Ligurian Sea. These data support the presence of a distinct eastern Ligurian cold-water coral province.