bluuebunny/crossref_metadata_2025 huggingface dataset:
Adlî olgularda mesiodistal ve bukkolingual diş boyutlarından cinsiyet tespitinin geçerliliğinin saptanması
Authors: DOĞAN Yeşim , AKA Sema
Published: May 2021

Ölümle sonuçlanan bir olayda araştırmanın ilk aşaması kimliklendirmedir. Adlî olgularda kimliklendirme çoğunlukla görsel yöntemlerle gerçekleştirilse de cesedin tanımlanamaz olduğu durumda, bu mümkün olmaz. Özellikle vücut bütünlüğünün bozulduğu, ileri derecede çürümenin gerçekleştiği ya da sadece iskeletin ele geçirilebildiği durumlarda kimliklendirme farklı disiplinlerin bir arada çalışmasını gerektirir. Kimliklendirmenin ilk aşaması cinsiyetin saptanmasıdır. Tüm iskelet elimizde olduğunda belirgin seksüel farklılıklar içeren kemiklerin varlığında rahatlıkla gerçekleştirilen cinsiyet tayini, özellikle pelvis ve kafatası parçalarının yokluğunda zorlu bir süreç haline gelir. Dişler dirençli yapıları gereği patlama, yangın ve benzeri zorlu koşulların olduğu olaylarda elimizde kalan tek delil olma özelliği taşımaktadır. Diş örneklerinden cinsiyet tayini, odontometri ve DNA analizleri ile gerçekleştirilir. Odontometri ile doğru sonuç alma oranı toplumda diş boyutlarında gözlenen seksüel dimorfizm oranı ile ilişkili olup, değişik toplumlarda farklılıklar göstermektedir. Bu çalışmada amaç Türkiye’de diş boyutlarında tespit edilmiş seksüel dimorfizm oranının adlî vakalarda uygulanabilirliğini DNA analizleri ile test etmektir. Ankara Hastanesi, 75. Yıl Ağız ve Diş Sağlığı Merkezi’nde çekilmiş 110 diş örneği kullanılarak gerçekleştirilen odontometrik analiz sonuçları, Türk toplumu verileri ile kıyaslanmış ve cinsiyetin belirlenmesinde mesiodistal (MD) boyutun erkeklerde %40, kadınlarda %71,67 ve bukkolingual (BL) boyutun da erkeklerde %42, kadınlarda %78,33 başarı oranı tespit edilmiştir. Sonuç olarak yaşları, cinsiyet ve sağlık durumları bilinmeyen insanlardan çekilen dişlerde cinsiyet belirlemede odontometrik yöntemin başarı oranının, adlî bilimlerde bu yöntemin kullanılmasına olanak vermeyecek ölçüde düşük olduğu belirlenmiştir.
New Mathematical Model for the Russian Population Projections
Authors: Nosova M.
Published: May 2021

In this article, a new original mathematical model for the Russian population projections as an autonomous non-Markov queuing system with an unlimited number of servers and two types of customers is built. The research of this system was carried out a virtual phase method and a modified method of asymptotic analysis and was proofed that the asymptotic distribution of applications served in the system at time t is Gaussian. Such a queuing system sufficiently and adequately simulates the process of changing the age structure of the population and can be used to analyze demographic situations in a single country and around the world. The mathematical model has been applied to the analysis of the population growth in Russia. We have built optimistic scenario for population projections to answer the question of how the Russian population will grow without immigration.
The Effect of Project Exhibition Event on Physics Success and Prospective Teachers’ Opinions about Projects
Authors:   Department of Science Education, Gazi University, Gazi Faculty of Education, Ankara, Turkey, Yıldırım Ezgi Güven , Köklükaya Ayşe Nesibe ,   Department of Science Education, Gazi University, Gazi Faculty of Education, Ankara, Turkey
Published: May 2021

The purposes of this study were first to investigate the effects of the project-based learning (PBL) method and project exhibition event on the success of physics teacher candidates, and second, to reveal the experiment group students’ views toward this learning method and project exhibition. The research model called explanatory mixed method, in which both quantitative and qualitative research methods were used. The findings obtained from the research show that there was a significant difference in favor of the experiment group among the point averages of the achievement post-test of the groups. When the findings regarding the questions posed to prospective teachers were examined, it was seen that while they stated that there were a few disadvantages of PBL and project exhibition event, there were many advantages. The results obtained from the quantitative and qualitative data of the research showed that PBL contributed positively to the teaching process and learning characteristics in many aspects.
Biology Students’ Cognitive Structures about Basic Components of Living Organisms
Authors:   Department of Biology, Ministry of National Education, Kocaeli, Turkey, Özarslan Murat , Çetin Gülcan ,   Department of Mathematics and Science Education, Biology Education, Necatibey Faculty of Education, Balıkesir University, Balıkesir, Turkey
Published: May 2021

The aim of this study was to investigate 9th grade biology students’ cognitive structures about the basic components of the living organisms and association between the concepts forming these basic components. Participants consisted of 50 9th grade biology students in two secondary schools in the northwest of Turkey. Data were collected by the word association test (WAT) and the questionnaire of writing sentence (QWS). The WAT is comprised 16 key concepts related to Biology: Inorganic compounds, organic compounds, acid, base, salt, water, mineral, carbohydrate, fat, protein, enzyme, vitamin, nucleic acid, DNA, RNA, and ATP. For the analysis of the WAT, the frequencies of the number of words and the number of word varieties about each key concept in the WAT were counted. Mind maps were then drawn with the help of the technique of breakpoint according to represent the WAT data. The QWS was analyzed by content analysis method. The study results showed that the existing conceptual relationships in the mind maps of the students were actively used in the sentences in the students’ written QWS. The experiences of the students such as life, laboratory studies, and the sharing of teachers in lessons on healthy diet were effective in the cognitive structures of the students. However, the existence of significant deficiencies and some non-scientific relationships in the students’ cognitive structures on basic components of living organisms were detected.
Editorial
Authors:   College of Education, The University of Otago, Sexton Steven
Published: May 2021

Editorial volume 29, issue 2
How Does The “Flipped Classroom Model” Impact On Student Motivation And Academic Achievement In A Chemistry Classroom?
Authors:   School of Education, Faculty of Humanities and Education, The University of the West Indies, Trinidad and Tobago, Sookoo-Singh Nicole , Boisselle Laila N ,   Division of Education, Higher Colleges of Technology, Ras al Khaimah Women’s Campus, United Arab Emirates
Published: May 2021

This action research was completed as a module on an in-service teacher education program and addressed form four (year 10, students aged 14–15 years old) students’ demotivation to study chemistry on the Caribbean island of Trinidad. My students often find chemistry challenging, and I suspect that teacher-centered methods probably contribute to their experience. The flipped classroom model was selected based on a review of the literature which identified it as a student-centered method with potential to impact both motivation and academic achievement. The research considered the flipped classroom’s impact on students’ motivation, academic performance, and perceptions of the intervention itself. The study was conducted over 4 weeks, and lessons were delivered asynchronously through the use of various Information Communication Technology resources such as email, websites, powerpoint presentations, and videos. Both qualitative and quantitative data were collected. Within the limitations of this study, academic achievement was not significantly impacted; student motivation was positively and significantly affected; and most students’ perception of the intervention was favorable though some indicated a preference for in-class lectures. Findings suggest further research into the utility of a blended method of synchronous and asynchronous lectures.
Characterization of Bradyrhizobium spp. Nodulating Lupinus cosentinii and L. luteus Microsymbionts in Morocco
Authors: Missbah El Idrissi Mustapha , Bouhnik Omar , ElFaik Salma , Alami Soufiane , Lamin Hanane , Bedmar Eulogio J. , Abdelmoumen Hanaa
Published: May 2021

In this work, we analyzed the diversity of the nodule-forming bacteria associated with Lupinus luteus and Lupinus cosentinii grown in the Maamora Cork oak forest acidic soils in Morocco. The phenotypic analysis showed the high diversity of the strains nodulating the two lupine's species. The strains were not tolerant to acidity or high alkalinity. They do not tolerate salinity or high temperatures either. The strains isolated from L. luteus were more tolerant to antibiotics and salinity than those isolated from L. cosentinii. The plant growth promoting (PGP) activities of our strains are modest, as among the 28 tested isolates, only six produced auxins, six produced siderophores, whereas three solubilized phosphates. Only two strains possess the three activities. The rrs gene sequences from eight representative strains selected following ARDRA and REP-PCR results revealed that they were members of the genus Bradyrhizobium. Six strains were then retained for further molecular analysis. The glnII, recA, gyrB, dnaK, and rpoB housekeeping gene sequence phylogeny showed that some strains were close to B. lupini LMG28514T whereas others may constitute new genospecies in the genus Bradyrhizobium. The strains were unable to nodulate Glycine max and Phaseolus vulgaris and effectively nodulated L. luteus, L. cosentinii, L. angustifolius, Chamaecytisus albidus, and Retama monosperma. The nodC and nodA symbiotic gene phylogenies showed that the strains are members of the genistearum symbiovar.
Functional Parameters of Prestin Are Not Correlated With the Best Hearing Frequency
Authors: Wang Zhongying , Ma Qingping , Lu Jiawen , Cui Xiaochen , Chen Haifeng , Wu Hao , Huang Zhiwu
Published: May 2021

Among the vertebrate lineages with different hearing frequency ranges, humans lie between the low-frequency hearing (1 kHz) of fish and amphibians and the high-frequency hearing (100 kHz) of bats and dolphins. Little is known about the mechanism underlying such a striking difference in the limits of hearing frequency. Prestin, responsible for cochlear amplification and frequency selectivity in mammals, seems to be the only candidate to date. Mammalian prestin is densely expressed in the lateral plasma membrane of the outer hair cells (OHCs) and functions as a voltage-dependent motor protein. To explore the molecular basis for the contribution of prestin in hearing frequency detection, we collected audiogram data from humans, dogs, gerbils, bats, and dolphins because their average hearing frequency rises in steps. We generated stable cell lines transfected with human, dog, gerbil, bat, and dolphin prestins (hPres, dPres, gPres, bPres, and nPres, respectively). The non-linear capacitance (NLC) of different prestins was measured using a whole-cell patch clamp. We found that the Qmax/Clin of bPres and nPres was significantly higher than that of humans. The V1/2 of hPres was more hyperpolarized than that of nPres. The z values of hPres and bPres were higher than that of nPres. We further analyzed the relationship between the high-frequency hearing limit (Fmax) and the functional parameters (V1/2, z, and Qmax/Clin) of NLC among five prestins. Interestingly, no significant correlation was found between the functional parameters and Fmax. Additionally, a comparative study showed that the amino acid sequences and tertiary structures of five prestins were quite similar. There might be a common fundamental mechanism driving the function of prestins. These findings call for a reconsideration of the leading role of prestin in hearing frequency perception. Other intriguing kinetics underlying the hearing frequency response of auditory organs might exist.
Hsa-miR-100-3p Controls the Proliferation, DNA Synthesis, and Apoptosis of Human Sertoli Cells by Binding to SGK3
Authors: Liu Bang , Cui Yinghong , Chen Wei , Du Li , Li Chunyun , Wan Cailin , He Zuping
Published: May 2021

Human Sertoli cell is required for completing normal spermatogenesis, and significantly, it has important applications in reproduction and regenerative medicine because of its great plasticity. Nevertheless, the molecular mechanisms underlying the fate decisions of human Sertoli cells remain to be clarified. Here, we have demonstrated the expression, function, and mechanism of Homo sapiens-microRNA (hsa-miR)-100-3p in human Sertoli cells. We revealed that miR-100-3p was expressed at a higher level in human Sertoli cells by 10% fetal bovine serum (FBS) than 0.5% FBS. MiR-100-3p mimics enhanced the DNA synthesis and the proliferation of human Sertoli cells, as indicated by 5-ethynyl-2′-deoxyuridine (EdU) and Cell Counting Kit-8 (CCK-8) assays. Flow cytometry showed that miR-100-3p mimics reduced the apoptosis of human Sertoli cells, and notably, we predicted and further identified serum/glucocorticoid regulated kinase family member 3 (SGK3) as a direct target of MiR-100-3p. SGK3 silencing increased the proliferation and decreased the apoptosis of human Sertoli cells, while SGK3 siRNA 3 assumed a similar role to miR-100-3p mimics in human Sertoli cells. Collectively, our study indicates that miR-100-3p regulates the fate decisions of human Sertoli cells by binding to SGK3. This study is of great significance, since it provides the novel epigenetic regulator for the proliferation and apoptosis of human Sertoli cells and it may offer a new clue for gene therapy of male infertility.
Long Non-coding RNA RUNDC3A-AS1 Promotes Lung Metastasis of Thyroid Cancer via Targeting the miR-182-5p/ADAM9
Authors: Ma Dawei , Zhu Yan , Zhang Xiao , Zhang Jia , Chen Wei , Chen Xinyuan , Qian Yichun , Zhao Yanbin , Hu Tingting , Yao Zhangyu , Zhao Wei , Zhang Yuan , Liu Fangzhou
Published: May 2021

Long non-coding RNAs (lncRNAs) have been identified as influential indicators in variety of malignancies. Among which, LncRNA RUNDC3A-AS1 is reported to upregulate in thyroid cancer. However, the expression pattern and the pathological function of lncRNA RUNDC3A-AS1 in thyroid cancer is unclear. In this study, we examined the expression levels of lncRNA RUNDC3A-AS1 in the thyroid cancer tissues and cell lines via RT-qPCR analysis. The effects of RUNDC3A-AS1 on thyroid cancer cell metastasis were detected by transwell chamber assay, scratch assay in vitro and lung metastasis model in vivo. The results indicated that RUNDC3A-AS1 was highly expressed in the thyroid cancer tissues and cell lines. Functionally, knockdown of RUNDC3A-AS1 could repress the migration and invasion of thyroid cancer cells in vitro, and inhibit thyroid cancer metastasis to lung in vivo. Mechanistically, RUNDC3A-AS1 served as an inhibitor of miR-182-5p in tumor tissues and cell lines. RUNDC3A-AS1 inhibited the expression of miR-182-5p to increase the expression level of ADAM9, thus further aggravating the malignancy of thyroid cancer. Therefore, the RUNDC3A-AS1/miR-182-5p/ADAM9 axis may be a potential therapeutic target for the treatment of thyroid cancer metastasis.
Glial Cells Promote Myelin Formation and Elimination
Authors: Hughes Alexandria N.
Published: May 2021

Building a functional nervous system requires the coordinated actions of many glial cells. In the vertebrate central nervous system (CNS), oligodendrocytes myelinate neuronal axons to increase conduction velocity and provide trophic support. Myelination can be modified by local signaling at the axon-myelin interface, potentially adapting sheaths to support the metabolic needs and physiology of individual neurons. However, neurons and oligodendrocytes are not wholly responsible for crafting the myelination patterns seen in vivo. Other cell types of the CNS, including microglia and astrocytes, modify myelination. In this review, I cover the contributions of non-neuronal, non-oligodendroglial cells to the formation, maintenance, and pruning of myelin sheaths. I address ways that these cell types interact with the oligodendrocyte lineage throughout development to modify myelination. Additionally, I discuss mechanisms by which these cells may indirectly tune myelination by regulating neuronal activity. Understanding how glial-glial interactions regulate myelination is essential for understanding how the brain functions as a whole and for developing strategies to repair myelin in disease.
Plasma Extracellular Vesicle Size and Concentration Are Altered in Alzheimer’s Disease, Dementia With Lewy Bodies, and Frontotemporal Dementia
Authors: Longobardi Antonio , Benussi Luisa , Nicsanu Roland , Bellini Sonia , Ferrari Clarissa , Saraceno Claudia , Zanardini Roberta , Catania Marcella , Di Fede Giuseppe , Squitti Rosanna , Binetti Giuliano , Ghidoni Roberta
Published: May 2021

Alzheimer’s disease (AD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB) are the three major neurodegenerative dementias. In this study, we provide evidence that an alteration in extracellular vesicles (EVs) release is common across the three most common neurodegenerative dementias, AD, DLB, and FTD. Specifically, we analyzed plasma EVs in three groups of patients affected by AD, DLB, and FTD, and we found a significant reduction in EVs concentration and larger EVs size in all patient groups. We then investigated whether the loss of neurotrophic factors is also a common pathogenic mechanism among FTD, DLB, and AD, and if levels of neurotrophic factors might affect EVs release. Plasma levels of progranulin and cystatin C (CysC) were partially altered; however, taking together all variables significantly associated with the diagnostic groups only EVs size and concentration were able to distinguish patients from controls. The diagnostic performance of these two EVs parameters together (ratio) was high, with a sensitivity of 83.3% and a specificity of 86.7%, able to distinguish patients from controls but not to differentiate the different forms of dementias. Among the candidate neurotrophic factors, only CysC levels were associated with EVs concentration. Our study suggests that an alteration in the intercellular communication mediated by EVs might be a common molecular pathway underlying neurodegenerative dementias. The identification of shared disease mechanisms is of pivotal importance to develop treatments to delay disease progression. To this aim, further studies investigating plasma EVs size and concentration as early biomarkers of dementia are required.
Navigating the Crossroads of Cell Therapy and Natural Heart Regeneration
Authors: Elde Stefan , Wang Hanjay , Woo Y. Joseph
Published: May 2021

Cardiovascular disease remains the leading cause of death worldwide despite significant advances in our understanding of the disease and its treatment. Consequently, the therapeutic potential of cell therapy and induction of natural myocardial regeneration have stimulated a recent surge of research and clinical trials aimed at addressing this challenge. Recent developments in the field have shed new light on the intricate relationship between inflammation and natural regeneration, an intersection that warrants further investigation.
Native Chemical Computation. A Generic Application of Oscillating Chemistry Illustrated With the Belousov-Zhabotinsky Reaction. A Review
Authors: Dueñas-Díez Marta , Pérez-Mercader Juan
Published: May 2021

Computing with molecules is at the center of complex natural phenomena, where the information contained in ordered sequences of molecules is used to implement functionalities of synthesized materials or to interpret the environment, as in Biology. This uses large macromolecules and the hindsight of billions of years of natural evolution. But, can one implement computation with small molecules? If so, at what levels in the hierarchy of computing complexity? We review here recent work in this area establishing that all physically realizable computing automata, from Finite Automata (FA) (such as logic gates) to the Linearly Bound Automaton (LBA, a Turing Machine with a finite tape) can be represented/assembled/built in the laboratory using oscillatory chemical reactions. We examine and discuss in depth the fundamental issues involved in this form of computation exclusively done by molecules. We illustrate their implementation with the example of a programmable finite tape Turing machine which using the Belousov-Zhabotinsky oscillatory chemistry is capable of recognizing words in a Context Sensitive Language and rejecting words outside the language. We offer a new interpretation of the recognition of a sequence of chemicals representing words in the machine's language as an illustration of the “Maximum Entropy Production Principle” and concluding that word recognition by the Belousov-Zhabotinsky Turing machine is equivalent to extremal entropy production by the automaton. We end by offering some suggestions to apply the above to problems in computing, polymerization chemistry, and other fields of science.
Computational Characterization of Astrophysical Species: The Case of Noble Gas Hydride Cations
Authors: Montes de Oca-Estévez María Judit , Prosmiti Rita
Published: May 2021

Theoretical–computational studies together with recent astronomical observations have shown that under extreme conditions in the interstellar medium (ISM), complexes of noble gases may be formed. Such observations have generated a wide range of possibilities. In order to identify new species containing such atoms, the present study gathers spectroscopic data for noble gas hydride cations, NgH+ (Ng = He, Ne, Ar) from high-level ab initio quantum chemistry computations, aiming to contribute in understanding the chemical bonding and electron sharing in these systems. The interaction potentials are obtained from CCSD(T)/CBS and MRCI+Q calculations using large basis sets, and then employed to compute vibrational levels and molecular spectroscopic constants for all known stable isotopologues of ground state NgH+ cations. Comparisons with previously reported values available are discussed, indicating that the present data could serve as a benchmark for future studies on these systems and on higher-order cationic noble gas hydrides of astrophysical interest.
Identification of 2-(thiophen-2-yl)acetic Acid-Based Lead Compound for mPGES-1 Inhibition
Authors: Di Micco Simone , Terracciano Stefania , Ruggiero Dafne , Potenza Marianna , Vaccaro Maria C. , Fischer Katrin , Werz Oliver , Bruno Ines , Bifulco Giuseppe
Published: May 2021

We report the implementation of our in silico/synthesis pipeline by targeting the glutathione-dependent enzyme mPGES-1, a valuable macromolecular target in both cancer therapy and inflammation therapy. Specifically, by using a virtual fragment screening approach of aromatic bromides, straightforwardly modifiable by the Suzuki-Miyaura reaction, we identified 3-phenylpropanoic acid and 2-(thiophen-2-yl)acetic acid to be suitable chemical platforms to develop tighter mPGES-1 inhibitors. Among these, compounds 1c and 2c showed selective inhibitory activity against mPGES-1 in the low micromolar range in accordance with molecular modeling calculations. Moreover, 1c and 2c exhibited interesting IC50 values on A549 cell lines compared to CAY10526, selected as reference compound. The most promising compound 2c induced the cycle arrest in the G0/G1 phase at 24 h of exposure, whereas at 48 and 72 h, it caused an increase of subG0/G1 fraction, suggesting an apoptosis/necrosis effect.
AMPK: Potential Therapeutic Target for Vascular Calcification
Authors: Lu Yi , Yuan Tan , Min Xinjia , Yuan Zhen , Cai Zhejun
Published: May 2021

Vascular calcification (VC) is an urgent worldwide health issue with no available medical treatment. It is an active cell-driven process by osteogenic differentiation of vascular cells with complex mechanisms. The AMP-activated protein kinase (AMPK) serves as the master sensor of cellular energy status. Accumulating evidence reveals the vital role of AMPK in VC progression. AMPK is involved in VC in various ways, including inhibiting runt-related transcription factor 2 signaling pathways, triggering autophagy, attenuating endoplasmic reticulum stress and dynamic-related protein 1-mediated mitochondrial fission, and activating endothelial nitric oxide synthase. AMPK activators, like metformin, are associated with reduced calcification deposits in certain groups of patients, indicating that AMPK is a potential therapeutic target for VC.
Best Practice for Measuring Permafrost Temperature in Boreholes Based on the Experience in the Swiss Alps
Authors: Noetzli Jeannette , Arenson Lukas U. , Bast Alexander , Beutel Jan , Delaloye Reynald , Farinotti Daniel , Gruber Stephan , Gubler Hansueli , Haeberli Wilfried , Hasler Andreas , Hauck Christian , Hiller Martin , Hoelzle Martin , Lambiel Christophe , Pellet Cécile , Springman Sarah M. , Vonder Muehll Daniel , Phillips Marcia
Published: May 2021

Temperature measurements in boreholes are the most common method allowing the quantitative and direct observation of permafrost evolution in the context of climate change. Existing boreholes and monitoring networks often emerged in a scientific context targeting different objectives and with different setups. A standardized, well-planned and robust instrumentation of boreholes for long-term operation is crucial to deliver comparable, high-quality data for scientific analyses and assessments. However, only a limited number of guidelines are available, particularly for mountain regions. In this paper, we discuss challenges and devise best practice recommendations for permafrost temperature measurements at single sites as well as in a network, based on two decades of experience gained in the framework of the Swiss Permafrost Monitoring Network PERMOS. These recommendations apply to permafrost observations in mountain regions, although many aspects also apply to polar lowlands. The main recommendations are (1) to thoroughly consider criteria for site selection based on the objective of the measurements as well as on preliminary studies and available data, (2) to define the sampling strategy during planification, (3) to engage experienced drilling teams who can cope with inhomogeneous and potentially unstable subsurface material, (4) to select standardized and robust instrumentation with high accuracy temperature sensors and excellent long-term stability when calibrated at 0°C, ideally with double sensors at key depths for validation and substitution of questionable data, (5) to apply standardized maintenance procedures allowing maximum comparability and minimum data processing, (6) to implement regular data control procedures, and (7) to ensure remote data access allowing for rapid trouble shooting and timely reporting. Data gaps can be avoided by timely planning of replacement boreholes. Recommendations for standardized procedures regarding data quality documentation, processing and final publication will follow later.
Albanian Preschool Personnel’s Perceived Obstacles to Implementing Effective Inclusive Education
Authors: Hyseni Duraku Zamira , Jahiu Genta , Likaj Shllaku Eglantina , Boci Loreta , Shtylla Hysnie
Published: May 2021

Access to high-quality early education promotes the academic success of children with disabilities; however, they are often overlooked in mainstream programs that lack essential support services. This study aimed to examine the obstacles to supporting inclusion and providing effective early education programs for children with disabilities in Albania as perceived by the preschool personnel. Preschool personnel (n= 107) working with children (3–6 years old) in the municipality of Tirana, in Albania, completed the survey. The obstacles to supporting children with disabilities were identified as lack of knowledge, supportive techniques, specific working tools, suitable facilities, and support staff, insufficient cooperation with parents, and inadequate educational programs for children with disabilities. The contextual factors and practical implications of the study, as well as future directions for research, are discussed in this article.
Pre-Service Special Educators’ Understandings of Relational Competence
Authors: Aspelin Jonas , Östlund Daniel , Jönsson Anders
Published: May 2021

Research demonstrates that the teacher-student relationship is essential for students with special educational needs. This article investigates how pre-service special educators (n = 74) perceive teachers’ relational competence, as manifested in their relations with students exhibiting behavioral difficulties. The data comprises educators’ written analyses of teacher-student interactions simulated through digital video, both before and after being provided with explicit criteria on teachers’ relational competence. The findings reveal a change in the educators’ perceptions as they shift from a focus on teaching strategies and the learning environment toward an awareness of teacher-student interaction, and from the teacher’s management of problematic student behavior toward an acknowledgment of the communicative and socio-emotional challenges in contexts involving students with different needs.
Thyroid Function Changes and Pubertal Progress in Females: A Longitudinal Study in Iodine-Sufficient Areas of East China
Authors: Wang Yingying , He Dandan , Fu Chaowei , Dong Xiaolian , Jiang Feng , Su Meifang , Xu Qian , Huang Peixin , Wang Na , Chen Yue , Jiang Qingwu
Published: May 2021

Background

The onset of puberty is influenced by thyroid function, and thyroid hormones (THs) fluctuate substantially during the period of pubertal development. However, it needs to be further clarified how THs change at specific puberty stages and how it influences pubertal development in girls. So far, longitudinal data from China are scarce.

Methods

A cohort study was conducted among girls during puberty in iodine-sufficient regions of East China between 2017 to 2019. Serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were determined for each participant. Thyroid homeostasis structure parameters (THSPs), including the ratio of FT4 to FT3 (FT4/FT3), Jostel’s TSH index (TSHI), and thyroid feedback quantile-based index (TFQI), were calculated. Puberty category scores (PCS), calculated based on the Puberty Development Scale (PDS), was used to assess the stage of puberty. Girls were grouped into three categories according to PCS changes (△PCS) and six categories according puberty stage (BPFP: pre-pubertal at both baseline and follow-up; BPFL: pre-pubertal at baseline and late-pubertal at follow-up, respectively; BPFT: pre-pubertal at baseline and post-pubertal at follow-up, respectively; BLFL: late-pubertal at both baseline and follow-up; BLFT: late-pubertal at baseline and post-pubertal at follow-up, respectively; BTFT: post-pubertal at both baseline and follow-up). Multiple linear regression analyses were used to evaluate the associations of THs changes with pubertal progress.

Results

The levels of serum TSH and FT3 decreased while serum FT4 increased during the study period (P<0.001). In multiple linear regression analyses, after adjustment for covariables, FT3 decreased by an additional 0.24 pmol/L (95% CI: -0.47 to -0.01) in the higher △PCS group than the lower △PCS group. Compared with the BLFL group, the BPFT group showed an additional decline in FT3 (β= -0.39 pmol/L, 95%CI: -0.73 to -0.04), the BTFT group showed a lower decline in TSH (β=0.50 mU/L, 95% CI: 0.21 to 0.80) and a lower decline in TSHI (β=0.24, 95%CI: 0.06 to 0.41), respectively. There was no association of △FT4 or △TFQI with △PCS or the puberty pattern.

Conclusions

Serum TSH and FT3 decreased while serum FT4 increased among girls during puberty. Both the initial stage and the velocity of pubertal development were related to thyroid hormone fluctuations.
Spatiotemporal Changes of Near-Surface Ozone Concentration From 2015 to 2018 in Beijing
Authors: Xie Junfei , Shi Shengwei , Wu Lingyun , Zhang Xin
Published: May 2021

In this study, we investigated the spatiotemporal changes of near-surface O3 concentration based on 33 automatic air quality monitoring stations in Beijing in 2015 and 2018. Here we show that the diurnal variations for O3 concentration at 33 monitoring stations exhibited a single-peak mode with a minimum concentration from 06:00 to 07:00 and a maximum value from 14:00 to 15:00. We find that the O3 concentration was significantly positively correlated with the air temperature, solar total radiation, and wind speed, while it was negatively correlated with the relative humidity. Among those factors, the air temperature played the most important role in influencing O3 concentration (relative contribution is greater than 88% in the boosted regression trees model). We also present that the annual variation of O3 concentration at all stations tended to be a “bell-shaped” curve distribution with a peak in summer and the lowest value in winter. The annual averaged O3 concentration at 33 stations in Beijing was 57.5 ± 9.8 μg⋅m−3 in 2015 and 60.3 ± 9.0 μg⋅m−3 in 2018. In addition, we detect that the annual averaged value of the O3 concentration was lower in the central and southern Beijing, and higher in the northern Beijing both in 2015 and 2018. The spatial difference of the O3 concentration could be explained by the traffic pollution, vegetation coverage, atmospheric regional transmission, and atmospheric particulate matter concentration.
MPRAdecoder: Processing of the Raw MPRA Data With a priori Unknown Sequences of the Region of Interest and Associated Barcodes
Authors: Letiagina Anna E. , Omelina Evgeniya S. , Ivankin Anton V. , Pindyurin Alexey V.
Published: May 2021

Massively parallel reporter assays (MPRAs) enable high-throughput functional evaluation of numerous DNA regulatory elements and/or their mutant variants. The assays are based on the construction of reporter plasmid libraries containing two variable parts, a region of interest (ROI) and a barcode (BC), located outside and within the transcription unit, respectively. Importantly, each plasmid molecule in a such a highly diverse library is characterized by a unique BC–ROI association. The reporter constructs are delivered to target cells and expression of BCs at the transcript level is assayed by RT-PCR followed by next-generation sequencing (NGS). The obtained values are normalized to the abundance of BCs in the plasmid DNA sample. Altogether, this allows evaluating the regulatory potential of the associated ROI sequences. However, depending on the MPRA library construction design, the BC and ROI sequences as well as their associations can be a priori unknown. In such a case, the BC and ROI sequences, their possible mutant variants, and unambiguous BC–ROI associations have to be identified, whereas all uncertain cases have to be excluded from the analysis. Besides the preparation of additional “mapping” samples for NGS, this also requires specific bioinformatics tools. Here, we present a pipeline for processing raw MPRA data obtained by NGS for reporter construct libraries with a priori unknown sequences of BCs and ROIs. The pipeline robustly identifies unambiguous (so-called genuine) BCs and ROIs associated with them, calculates the normalized expression level for each BC and the averaged values for each ROI, and provides a graphical visualization of the processed data.
Pneumolysin Is Responsible for Differential Gene Expression and Modifications in the Epigenetic Landscape of Primary Monocyte Derived Macrophages
Authors: Cole Joby , Angyal Adrienn , Emes Richard D. , Mitchell Tim John , Dickman Mark J. , Dockrell David H.
Published: May 2021

Epigenetic modifications regulate gene expression in the host response to a diverse range of pathogens. The extent and consequences of epigenetic modification during macrophage responses to Streptococcus pneumoniae, and the role of pneumolysin, a key Streptococcus pneumoniae virulence factor, in influencing these responses, are currently unknown. To investigate this, we infected human monocyte derived macrophages (MDMs) with Streptococcus pneumoniae and addressed whether pneumolysin altered the epigenetic landscape and the associated acute macrophage transcriptional response using a combined transcriptomic and proteomic approach. Transcriptomic analysis identified 503 genes that were differentially expressed in a pneumolysin-dependent manner in these samples. Pathway analysis highlighted the involvement of transcriptional responses to core innate responses to pneumococci including modules associated with metabolic pathways activated in response to infection, oxidative stress responses and NFκB, NOD-like receptor and TNF signalling pathways. Quantitative proteomic analysis confirmed pneumolysin-regulated protein expression, early after bacterial challenge, in representative transcriptional modules associated with innate immune responses. In parallel, quantitative mass spectrometry identified global changes in the relative abundance of histone post translational modifications (PTMs) upon pneumococcal challenge. We identified an increase in the relative abundance of H3K4me1, H4K16ac and a decrease in H3K9me2 and H3K79me2 in a PLY-dependent fashion. We confirmed that pneumolysin blunted early transcriptional responses involving TNF-α and IL-6 expression. Vorinostat, a histone deacetylase inhibitor, similarly downregulated TNF-α production, reprising the pattern observed with pneumolysin. In conclusion, widespread changes in the macrophage transcriptional response are regulated by pneumolysin and are associated with global changes in histone PTMs. Modulating histone PTMs can reverse pneumolysin-associated transcriptional changes influencing innate immune responses, suggesting that epigenetic modification by pneumolysin plays a role in dampening the innate responses to pneumococci.
Glucocorticoid-Induced Exacerbation of Mycobacterial Infection Is Associated With a Reduced Phagocytic Capacity of Macrophages
Authors: Xie Yufei , Xie Jiajun , Meijer Annemarie H. , Schaaf Marcel J. M.
Published: May 2021

Glucocorticoids are effective drugs for treating immune-related diseases, but prolonged therapy is associated with an increased risk of various infectious diseases, including tuberculosis. In this study, we have used a larval zebrafish model for tuberculosis, based onMycobacterium marinum(Mm) infection, to study the effect of glucocorticoids. Our results show that the synthetic glucocorticoid beclomethasone increases the bacterial burden and the dissemination of a systemicMminfection. The exacerbatedMminfection was associated with a decreased phagocytic activity of macrophages, higher percentages of extracellular bacteria, and a reduced rate of infected cell death, whereas the bactericidal capacity of the macrophages was not affected. The inhibited phagocytic capacity of macrophages was associated with suppression of the transcription of genes involved in phagocytosis in these cells. The decreased bacterial phagocytosis by macrophages was not specific forMm, since it was also observed upon infection withSalmonellaTyphimurium. In conclusion, our results show that glucocorticoids inhibit the phagocytic activity of macrophages, which may increase the severity of bacterial infections like tuberculosis.
Myeloid Arginase 1 Insufficiency Exacerbates Amyloid-β Associated Neurodegenerative Pathways and Glial Signatures in a Mouse Model of Alzheimer’s Disease: A Targeted Transcriptome Analysis
Authors: Ma Chao , Hunt Jerry B. , Kovalenko Andrii , Liang Huimin , Selenica Maj-Linda B. , Orr Michael B. , Zhang Bei , Gensel John C. , Feola David J. , Gordon Marcia N. , Morgan Dave , Bickford Paula C. , Lee Daniel C.
Published: May 2021

Brain myeloid cells, include infiltrating macrophages and resident microglia, play an essential role in responding to and inducing neurodegenerative diseases, such as Alzheimer’s disease (AD). Genome-wide association studies (GWAS) implicate many AD casual and risk genes enriched in brain myeloid cells. Coordinated arginine metabolism through arginase 1 (Arg1) is critical for brain myeloid cells to perform biological functions, whereas dysregulated arginine metabolism disrupts them. Altered arginine metabolism is proposed as a new biomarker pathway for AD. We previously reported Arg1 deficiency in myeloid biased cells using lysozyme M (LysM) promoter-driven deletion worsened amyloidosis-related neuropathology and behavioral impairment. However, it remains unclear how Arg1 deficiency in these cells impacts the whole brain to promote amyloidosis. Herein, we aim to determine how Arg1 deficiency driven by LysM restriction during amyloidosis affects fundamental neurodegenerative pathways at the transcriptome level. By applying several bioinformatic tools and analyses, we found that amyloid-β (Aβ) stimulated transcriptomic signatures in autophagy-related pathways and myeloid cells’ inflammatory response. At the same time, myeloid Arg1 deficiency during amyloidosis promoted gene signatures of lipid metabolism, myelination, and migration of myeloid cells. Focusing on Aβ associated glial transcriptomic signatures, we found myeloid Arg1 deficiency up-regulated glial gene transcripts that positively correlated with Aβ plaque burden. We also observed that Aβ preferentially activated disease-associated microglial signatures to increase phagocytic response, whereas myeloid Arg1 deficiency selectively promoted homeostatic microglial signature that is non-phagocytic. These transcriptomic findings suggest a critical role for proper Arg1 function during normal and pathological challenges associated with amyloidosis. Furthermore, understanding pathways that govern Arg1 metabolism may provide new therapeutic opportunities to rebalance immune function and improve microglia/macrophage fitness.
Combining a Universal Telomerase Based Cancer Vaccine With Ipilimumab in Patients With Metastatic Melanoma - Five-Year Follow Up of a Phase I/IIa Trial
Authors: Aamdal Elin , Inderberg Else Marit , Ellingsen Espen Basmo , Rasch Wenche , Brunsvig Paal Fredrik , Aamdal Steinar , Heintz Karen-Marie , Vodák Daniel , Nakken Sigve , Hovig Eivind , Nyakas Marta , Guren Tormod Kyrre , Gaudernack Gustav
Published: May 2021

Background

Ipilimumab improves survival for patients with metastatic malignant melanoma. Combining a therapeutic cancer vaccine with ipilimumab may increase efficacy by providing enhanced anti-tumor immune responses. UV1 consists of three synthetic long peptides from human telomerase reverse transcriptase (hTERT). These peptides comprise epitopes recognized by T cells from cancer patients experiencing long-term survival following treatment with a first-generation hTERT vaccine, and generate long-lasting immune responses in cancer patients when used as monotherapy. The objective of this trial was to investigate the safety and efficacy of combining UV1 with ipilimumab in metastatic melanoma.

Patients and Methods

In this phase I/IIa, single center trial [NCT02275416], patients with metastatic melanoma received repeated UV1 vaccinations, with GM-CSF as an adjuvant, in combination with ipilimumab. Patients were evaluated for safety, efficacy and immune response. Immune responses against vaccine peptides were monitored in peripheral blood by measuring antigen-specific proliferation and IFN-γ production.

Results

Twelve patients were recruited. Adverse events were mainly diarrhea, injection site reaction, pruritus, rash, nausea and fatigue. Ten patients showed a Th1 immune response to UV1 peptides, occurring early and after few vaccinations. Three patients obtained a partial response and one patient a complete response. Overall survival was 50% at 5 years.

Conclusion

Treatment was well tolerated. The rapid expansion of UV1-specific Th1 cells in the majority of patients indicates synergy between UV1 vaccine and CTLA-4 blockade. This may have translated into clinical benefit, encouraging the combination of UV1 vaccination with standard of care treatment regimes containing ipilimumab/CTLA-4 blocking antibodies.
Identification of Potentially Therapeutic Immunogenic Peptides From Paracoccidioides lutzii Species
Authors: Silva Leandro B. R. , Taira Cleison L. , Cleare Levi G. , Martins Michele , Junqueira Magno , Nosanchuk Joshua D. , Taborda Carlos P.
Published: May 2021

Paracoccidioidomycosis (PCM) is an endemic mycosis in Latin America caused by the thermodimorphic fungi of the genus Paracoccidioides spp. Paracoccidioides lutzii (PL) is one of the 5 species that constitute the Paracoccidioides genus. PL expresses low amounts of glycoprotein (Gp) 43 (PLGp43) and PLGp43 displays few epitopes in common with the P. brasiliensis (PB) immunodominant antigen PBGp43, which is commonly used for serological diagnosis of PCM. This difference in structure between the glycoproteins markedly reduces the efficiency of serological diagnosis in patients infected with PL. We previously demonstrated that peptide 10 (P10) from the PBGp43 induces protective immune responses in in vitro and in vivo models of PB PCM. Since, P10 has proven to be a promising therapeutic to combat PB, we sought to identify peptides in PL that could similarly be applied for the treatment of PCM. PL yeast cell proteins were isolated from PL: dendritic cell co-cultures and subjected to immunoproteomics. This approach identified 18 PL peptides that demonstrated in silico predictions for immunogenicity. Eight of the most promising peptides were synthesized and applied to lymphocytes obtained from peptide-immunized or PL-infected mice as well as to in vitro cultures with peptides or dendritic cells pulsed the peptides. The peptides LBR5, LBR6 and LBR8 efficiently promoted CD4+ and CD8+ T cell proliferation and dendritic cells pulsed with LBR1, LBR3, LBR7 or LBR8 stimulated CD4+ T cell proliferation. We observed increases of IFN-γ in the supernatants from primed T cells for the conditions with peptides without or with dendritic cells, although IL-2 levels only increased in response to LBR8. These novel immunogenic peptides derived from PL will be employed to develop new peptide vaccine approaches and the proteins from which they are derived can be used to develop new diagnostic assays for PL and possibly other Paracoccidioides spp. These findings identify and characterize new peptides with a promising therapeutic profile for future against this important neglected systemic mycosis.
Placenta-Derived Exosomes as a Modulator in Maternal Immune Tolerance During Pregnancy
Authors: Bai Kunfeng , Li Xintong , Zhong Jiangming , Ng Ernest H. Y. , Yeung William S.B. , Lee Cheuk-Lun , Chiu Philip C. N.
Published: May 2021

Exosomes are a subset of extracellular vesicles with an average diameter of ~100nm. Exosomes are released by all cells through an endosome-dependent pathway and carry nucleic acids, proteins, lipids, cytokines and metabolites, mirroring the state of the originating cells. The function of exosomes has been implicated in various reproduction processes, such as embryo development, implantation, decidualization and placentation. Placenta-derived exosomes (pEXO) can be detected in the maternal blood as early as 6 weeks after conception and their levels increase with gestational age. Importantly, alternations in the molecular signatures of pEXO are observed in pregnancy-related complications. Thus, these differentially expressed molecules could be the potential biomarkers for diagnosis of the pregnancy-associated diseases. Recent studies have demonstrated that pEXO play a key role in the establishment of maternal immune tolerance, which is critical for a successful pregnancy. To gain a better understanding of the underlying mechanism, we highlighted the advanced studies of pEXO on immune cells in pregnancy.