bluuebunny/crossref_metadata_2025 huggingface dataset:
Teacher Mobility: What Is It, How Is It Measured and What Factors Determine It? A Scoping Review
Authors: Palma-Vasquez Claudia , Carrasco Diego , Tapia-Ladino Mónica
Published: February 2022

Teacher mobility represents a serious problem due to the instability of the teaching force that has persisted over time in many countries. Therefore, retaining qualified teachers represents a challenge given the difficulty of having the necessary workforce to face the educational challenges of each year. Our objective was trying to identify how mobility is understood and measured, that is, teacher turnover and attrition, and to identify the results of the related factors according to the different perspectives. The PRISMA-Scr protocol was used, which establishes the information that should be included in a systematic review. The following key phrases were used: “teacher rotation” or “teacher mobility” or “teacher desertion” or teacher leavers or teacher stayers. The databases used were Web of Science, Scielo Citation Index and Google Scholar, which yielded an initial total of 760 documents published between 2008 and 2018, that after identification, screening, eligibility, and inclusion processes, were reduced to 213. The selection of articles was carried out independently by two researchers using a structured and recursive hierarchical strategy. The existence of multiple ways of defining and measuring teacher mobility was identified and a definition based on two perspectives was proposed that summarizes the conceptual and operational findings, which are indirect and direct mobility. The first refers to the intention to leave and the second to leave. We have identified more evidence related to direct studies of a quantitative approach and focused on teachers with medium or short experience. The factors associated with mobility were identified based on the approaches used and a key element was identified when distinguishing teacher mobility, which is voluntary and involuntary mobility. We identified multiple factors associated with teacher mobility, among which the precarious working environment, poor organizational conditions such as lack of leadership and support among colleagues, excessive workload and low self-efficacy stand out. The limitations of this study are discussed. The findings of this study are highly relevant since they allow proposing medium or short-term policies, such as improving the organizational conditions of the school to promote the retention of the teaching workforce.
‘Who Else If Not We’. Medical Students’ Perception and Experiences with Volunteering during the COVID-19 Crisis in Poznan, Poland
Authors: Domaradzki Jan
Published: February 2022

Introduction: The first wave of the COVID-19 pandemic resulted in the closure of all Polish medical universities. Simultaneously, due to staff shortages and the Polish health-care system being seriously challenged, many students were eager to contribute to the fight against the outbreak. This study explores medial student volunteers’ (MSV) perspectives and their lived experiences during the COVID-19 pandemic in Poland. Material and Methods: Semi-structured interviews were conducted with twenty-one students. Results: A total of seven major themes emerged from the interviews: 1. students’ reactions to the COVID-19 pandemic, 2. students’ experiences of the outbreak, 3. motivations for volunteering, 4. students’ perceptions of the COVID-19 volunteering, 5. organization of students’ volunteering, 6. benefits and costs of volunteering during COVID-19, and 7. social perception of MSVs. Although students volunteering was an example of civic responsibility and created new learning opportunities, many students felt unprepared for the pandemic, lacked social skills and access to psychological support, and were the target of stigmatization and discrimination. Discussion: Because during the first wave of the COVID-19 pandemic medical universities were closed and classes were held online, students’ volunteering became an important part of service learning and created an opportunity for education. Consequently, while it benefited students, patients and the healthcare system, students’ involvement reinforced such important values of medical ethos as: altruism, public service, and (professional) solidarity. However, some systemic approach should be undertaken that would prepare students better for future crises.
Implementation of Breastfeeding Policies at Workplace in Mexico: Analysis of Context Using a Realist Approach
Authors: Hernández-Cordero Sonia , Vilar-Compte Mireya , Litwan Kathrin , Lara-Mejía Vania , Rovelo-Velázquez Natalia , Ancira-Moreno Mónica , Sachse-Aguilera Matthias , Cobo-Armijo Fernanda
Published: February 2022

Return to work is one of the most significant barriers to breastfeeding (BF). Family-friendly policies are critical to ensure that BF and maternal work are not mutually exclusive. This study aims to determine contextual factors and underlying mechanisms influencing the implementation of workplace policies in Mexico. Following a qualitative approach, the study was conducted in the following four cities in Mexico: Mérida, Chihuahua, Guadalajara, and Monterrey. Interviews were conducted in 14 workplaces, and included 49 (potential) beneficiaries, 41 male employees, and 21 managers and human resources personnel. The information collected was analyzed through a deductive thematic analysis and mapped against the Context-Mechanism-Outcome framework of Breastfeeding Interventions at the Workplace. Contextual factors influencing a BF-friendly environment in the workplace were as follows: work-schedule flexibility, provision of lactation services (i.e., BF counseling) other than a lactation room, women’s previous experience with BF and family-friendly environments in the workplace. The underlying mechanisms enabling/impeding a BF-friendly environment at the workplace were as follows: awareness of Mexican maternity protection legislation, usage of BF interventions in the workplace, culture, supervisor/co-worker support and BF-friendly physical space. To achieve a BF-friendly environment in the workplace, actions at the level of public policy and workplaces must accompany adherence to Mexican legislation.
Oral Hygiene Practices and Knowledge among Adolescents Aged between 15 and 17 Years Old during Fixed Orthodontic Treatment: Multicentre Study Conducted in France
Authors: Inquimbert Camille , Clement Celine , Couatarmanach Antoine , Tramini Paul , Bourgeois Denis , Carrouel Florence
Published: February 2022

The aims of this study were to assess oral health knowledge, attitudes, and practices among orthodontic patients between the ages of 15 and 17 years old compared to adolescents without orthodontic treatment. This cross-sectional study included 392 adolescents drawn from various French teaching hospitals. A closed-ended questionnaire was used to collect data. Adolescents undergoing orthodontic treatment had a higher knowledge of oral health than adolescents without orthodontic treatment. The majority of adolescents for both groups (69%) claimed to brush their teeth twice a day. Regarding complimentary dental material, 81.9% of adolescents without orthodontic treatment never used an interdental brush and 78.8% never used dental floss. For those undergoing orthodontic treatment, 48.5% never used an interdental brush. Only 4% of adolescents without and 3% of adolescents with orthodontic treatment never consumed fizzy drinks, 4.9% and 3% never consumed sweets, and 4% and 8.4% never ate fast-food. Adolescents without treatment consumed more sodas (p = 0.048) and more fast food (p = 0.029). Adolescents had insufficient knowledge of oral health. Health education programmes should be implemented to improve adolescents’ knowledge and individual oral prophylaxis with interdental brushes.
Exploring the Multiscale Relationship between the Built Environment and the Metro-Oriented Dockless Bike-Sharing Usage
Authors: Li Zhitao , Shang Yuzhen , Zhao Guanwei , Yang Muzhuang
Published: February 2022

Dockless bike-sharing systems have become one of the important transport methods for urban residents as they can effectively expand the metro’s service area. We applied the ordinary least square (OLS) model, the geographically weighted regression (GWR) model and the multiscale geographically weighted regression (MGWR) model to capture the spatial relationship between the urban built environment and the usage of bike-sharing connected to the metro. A case study in Beijing, China, was conducted. The empirical result demonstrates that the MGWR model can explain the varieties of spatial relationship more precisely than the OLS model and the GWR model. The result also shows that, among the proposed built environment factors, the integrated usage of bike-sharing and metro is mainly affected by the distance to central business district (CBD), the Hotels-Residences points of interest (POI) density, and the road density. It is noteworthy that the effect of population density on dockless bike-sharing usage is only significant at weekends. In addition, the effects of the built environment variables on dockless bike-sharing usage also vary across space. A common feature is that most of the built environment factors have a more obvious impact on the metro-oriented dockless bike-sharing usage in the eastern part of the study area. This finding can provide support for governments and urban planners to efficiently develop a bike-sharing-friendly built environment that promotes the integration of bike-sharing and metro.
Antimicrobial Photodynamic Coatings Reduce the Microbial Burden on Environmental Surfaces in Public Transportation—A Field Study in Buses
Authors: Kalb Larissa , Bäßler Pauline , Schneider-Brachert Wulf , Eckl Daniel Bernhard
Published: February 2022

Millions of people use public transportation daily worldwide and frequently touch surfaces, thereby producing a reservoir of microorganisms on surfaces increasing the risk of transmission. Constant occupation makes sufficient cleaning difficult to achieve. Thus, an autonomous, permanent, antimicrobial coating (AMC) could keep down the microbial burden on such surfaces. A photodynamic AMC was applied to frequently touched surfaces in buses. The microbial burden (colony forming units, cfu) was determined weekly and compared to equivalent surfaces in buses without AMC (references). The microbial burden ranged from 0–209 cfu/cm2 on references and from 0–54 cfu/cm2 on AMC. The means were 13.4 ± 29.6 cfu/cm2 on references and 4.5 ± 8.4 cfu/cm2 on AMC (p < 0.001). The difference in microbial burden on AMC and references was almost constant throughout the study. Considering a hygiene benchmark of 5 cfu/cm2, the data yield an absolute risk reduction of 22.6% and a relative risk reduction of 50.7%. In conclusion, photodynamic AMC kept down the microbial burden, reducing the risk of transmission of microorganisms. AMC permanently and autonomously contributes to hygienic conditions on surfaces in public transportation. Photodynamic AMC therefore are suitable for reducing the microbial load and closing hygiene gaps in public transportation.
Modified Industrial Three-Dimensional Polylactic Acid Scaffold Cell Chip Promotes the Proliferation and Differentiation of Human Neural Stem Cells
Authors: Kim Gyeong-Ji , Lee Kwon-Jai , Choi Jeong-Woo , An Jeung Hee
Published: February 2022

In this study, we fabricated a three-dimensional (3D) scaffold using industrial polylactic acid (PLA), which promoted the proliferation and differentiation of human neural stem cells. An industrial PLA 3D scaffold (IPTS) cell chip with a square-shaped pattern was fabricated via computer-aided design and printed using a fused deposition modeling technique. To improve cell adhesion and cell differentiation, we coated the IPTS cell chip with gold nanoparticles (Au-NPs), nerve growth factor (NGF) protein, an NGF peptide fragment, and sonic hedgehog (SHH) protein. The proliferation of F3.Olig2 neural stem cells was increased in the IPTS cell chips coated with Au-NPs and NGF peptide fragments when compared with that of the cells cultured on non-coated IPTS cell chips. Cells cultured on the IPTS-SHH cell chip also showed high expression of motor neuron cell-specific markers, such as HB9 and TUJ-1. Therefore, we suggest that the newly engineered industrial PLA scaffold is an innovative tool for cell proliferation and motor neuron differentiation.
An Essential Role for Alzheimer’s-Linked Amyloid Beta Oligomers in Neurodevelopment: Transient Expression of Multiple Proteoforms during Retina Histogenesis
Authors: Bartley Samuel C. , Proctor Madison T. , Xia Hongjie , Ho Evelyn , Kang Dong S. , Schuster Kristen , Bicca Maíra A. , Seckler Henrique S. , Viola Kirsten L. , Patrie Steven M. , Kelleher Neil L. , De Mello Fernando G. , Klein William L.
Published: February 2022

Human amyloid beta peptide (Aβ) is a brain catabolite that at nanomolar concentrations can form neurotoxic oligomers (AβOs), which are known to accumulate in Alzheimer’s disease. Because a predisposition to form neurotoxins seems surprising, we have investigated whether circumstances might exist where AβO accumulation may in fact be beneficial. Our investigation focused on the embryonic chick retina, which expresses the same Aβ as humans. Using conformation-selective antibodies, immunoblots, mass spectrometry, and fluorescence microscopy, we discovered that AβOs are indeed present in the developing retina, where multiple proteoforms are expressed in a highly regulated cell-specific manner. The expression of the AβO proteoforms was selectively associated with transiently expressed phosphorylated Tau (pTau) proteoforms that, like AβOs, are linked to Alzheimer’s disease (AD). To test whether the AβOs were functional in development, embryos were cultured ex ovo and then injected intravitreally with either a beta-site APP-cleaving enzyme 1 (BACE-1) inhibitor or an AβO-selective antibody to prematurely lower the levels of AβOs. The consequence was disrupted histogenesis resulting in dysplasia resembling that seen in various retina pathologies. We suggest the hypothesis that embryonic AβOs are a new type of short-lived peptidergic hormone with a role in neural development. Such a role could help explain why a peptide that manifests deleterious gain-of-function activity when it oligomerizes in the aging brain has been evolutionarily conserved.
New Insights in the Control of Fat Homeostasis: The Role of Neurotensin
Authors: Barchetta Ilaria , Baroni Marco Giorgio , Melander Olle , Cavallo Maria Gisella
Published: February 2022

Neurotensin (NT) is a small peptide with pleiotropic functions, exerting its primary actions by controlling food intake and energy balance. The first evidence of an involvement of NT in metabolism came from studies on the central nervous system and brain circuits, where NT acts as a neurotransmitter, producing different effects in relation to the specific region involved. Moreover, newer interesting chapters on peripheral NT and metabolism have emerged since the first studies on the NT-mediated regulation of gut lipid absorption and fat homeostasis. Intriguingly, NT enhances fat absorption from the gut lumen in the presence of food with a high fat content, and this action may explain the strong association between high circulating levels of pro-NT, the NT stable precursor, and the increased incidence of metabolic disorders, cardiovascular diseases, and cancer observed in large population studies. This review aims to provide a synthetic overview of the main regulatory effects of NT on several biological pathways, particularly those involving energy balance, and will focus on new evidence on the role of NT in controlling fat homeostasis, thus influencing the risk of unfavorable cardio–metabolic outcomes and overall mortality in humans.
Potential Role of Selenium in the Treatment of Cancer and Viral Infections
Authors: Rataan Aseel O. , Geary Sean M. , Zakharia Yousef , Rustum Youcef M. , Salem Aliasger K.
Published: February 2022

Selenium has been extensively evaluated clinically as a chemopreventive agent with variable results depending on the type and dose of selenium used. Selenium species are now being therapeutically evaluated as modulators of drug responses rather than as directly cytotoxic agents. In addition, recent data suggest an association between selenium base-line levels in blood and survival of patients with COVID-19. The major focus of this mini review was to summarize: the pathways of selenium metabolism; the results of selenium-based chemopreventive clinical trials; the potential for using selenium metabolites as therapeutic modulators of drug responses in cancer (clear-cell renal-cell carcinoma (ccRCC) in particular); and selenium usage alone or in combination with vaccines in the treatment of patients with COVID-19. Critical therapeutic targets and the potential role of different selenium species, doses, and schedules are discussed.
Breeding and Genomics Interventions for Developing Ascochyta Blight Resistant Grain Legumes
Authors: Jha Uday C. , Sharma Kamal Dev , Nayyar Harsh , Parida Swarup K. , Siddique Kadambot H. M.
Published: February 2022

Grain legumes are a key food source for ensuring global food security and sustaining agriculture. However, grain legume production is challenged by growing disease incidence due to global climate change. Ascochyta blight (AB) is a major disease, causing substantial yield losses in grain legumes worldwide. Harnessing the untapped reserve of global grain legume germplasm, landraces, and crop wild relatives (CWRs) could help minimize yield losses caused by AB infection in grain legumes. Several genetic determinants controlling AB resistance in various grain legumes have been identified following classical genetic and conventional breeding approaches. However, the advent of molecular markers, biparental quantitative trait loci (QTL) mapping, genome-wide association studies, genomic resources developed from various genome sequence assemblies, and whole-genome resequencing of global germplasm has revealed AB-resistant gene(s)/QTL/genomic regions/haplotypes on various linkage groups. These genomics resources allow plant breeders to embrace genomics-assisted selection for developing/transferring AB-resistant genomic regions to elite cultivars with great precision. Likewise, advances in functional genomics, especially transcriptomics and proteomics, have assisted in discovering possible candidate gene(s) and proteins and the underlying molecular mechanisms of AB resistance in various grain legumes. We discuss how emerging cutting-edge next-generation breeding tools, such as rapid generation advancement, field-based high-throughput phenotyping tools, genomic selection, and CRISPR/Cas9, could be used for fast-tracking AB-resistant grain legumes to meet the increasing demand for grain legume-based protein diets and thus ensuring global food security.
GLIS1 in Cancer-Associated Fibroblasts Regulates the Migration and Invasion of Ovarian Cancer Cells
Authors: Kim Mi Joung , Jung Daun , Park Joo Youn , Lee Seung Min , An Hee Jung
Published: February 2022

A cancer-associated fibroblasts (CAFs) are the most important players that modulate tumor aggressiveness. In this study, we aimed to identify CAF-related genes in ovarian serous carcinomas (OSC) that account for the high incidence and mortality of ovarian cancers (OCs) and to develop therapeutic targets for tumor microenvironment modulation. Here, we performed a microarray analysis of CAFs isolated from three metastatic and three nonmetastatic OSC tissues and compared their gene expression profiles. Among the genes increased in metastatic CAFs (mCAFs), GLIS1 (Glis Family Zinc Finger 1) showed a significant increase in both the gene mRNA and protein expression levels. Knockdown of GLIS1 in mCAFs significantly inhibited migration, invasion, and wound healing ability of OC cells. In addition, an in vivo study demonstrated that knockdown of GLIS1 in CAFs reduced peritoneal metastasis. Taken together, these results suggest that CAFs support migration and metastasis of OC cells by GLIS1 overexpression. It also indicates GLIS1 in CAFs might be a potential therapeutic target to inhibit OC metastasis.
A Splicing Mutation in Slc4a5 Results in Retinal Detachment and Retinal Pigment Epithelium Dysfunction
Authors: Collin Gayle B. , Shi Lanying , Yu Minzhong , Akturk Nurten , Charette Jeremy R. , Hyde Lillian F. , Weatherly Sonia M. , Pera Martin F. , Naggert Jürgen K. , Peachey Neal S. , Nishina Patsy M. , Krebs Mark P.
Published: February 2022

Fluid and solute transporters of the retinal pigment epithelium (RPE) are core components of the outer blood–retinal barrier. Characterizing these transporters and their role in retinal homeostasis may provide insights into ocular function and disease. Here, we describe RPE defects in tvrm77 mice, which exhibit hypopigmented patches in the central retina. Mapping and nucleotide sequencing of tvrm77 mice revealed a disrupted 5’ splice donor sequence in Slc4a5, a sodium bicarbonate cotransporter gene. Slc4a5 expression was reduced 19.7-fold in tvrm77 RPE relative to controls, and alternative splice variants were detected. SLC4A5 was localized to the Golgi apparatus of cultured human RPE cells and in apical and basal membranes. Fundus imaging, optical coherence tomography, microscopy, and electroretinography (ERG) of tvrm77 mice revealed retinal detachment, hypopigmented patches corresponding to neovascular lesions, and retinal folds. Detachment worsened and outer nuclear layer thickness decreased with age. ERG a- and b-wave response amplitudes were initially normal but declined in older mice. The direct current ERG fast oscillation and light peak were reduced in amplitude at all ages, whereas other RPE-associated responses were unaffected. These results link a new Slc4a5 mutation to subretinal fluid accumulation and altered light-evoked RPE electrophysiological responses, suggesting that SLC4A5 functions at the outer blood–retinal barrier.
Veratridine Can Bind to a Site at the Mouth of the Channel Pore at Human Cardiac Sodium Channel NaV1.5
Authors: Gulsevin Alican , Glazer Andrew M. , Shields Tiffany , Kroncke Brett M. , Roden Dan M. , Meiler Jens
Published: February 2022

The cardiac sodium ion channel (NaV1.5) is a protein with four domains (DI-DIV), each with six transmembrane segments. Its opening and subsequent inactivation results in the brief rapid influx of Na+ ions resulting in the depolarization of cardiomyocytes. The neurotoxin veratridine (VTD) inhibits NaV1.5 inactivation resulting in longer channel opening times, and potentially fatal action potential prolongation. VTD is predicted to bind at the channel pore, but alternative binding sites have not been ruled out. To determine the binding site of VTD on NaV1.5, we perform docking calculations and high-throughput electrophysiology experiments in the present study. The docking calculations identified two distinct binding regions. The first site was in the pore, close to the binding site of NaV1.4 and NaV1.5 blocking drugs in experimental structures. The second site was at the “mouth” of the pore at the cytosolic side, partly solvent-exposed. Mutations at this site (L409, E417, and I1466) had large effects on VTD binding, while residues deeper in the pore had no effect, consistent with VTD binding at the mouth site. Overall, our results suggest a VTD binding site close to the cytoplasmic mouth of the channel pore. Binding at this alternative site might indicate an allosteric inactivation mechanism for VTD at NaV1.5.
Neuropsychopharmacology of Emerging Drugs of Abuse: meta- and para-Halogen-Ring-Substituted α-PVP (“flakka”) Derivatives
Authors: Nadal-Gratacós Núria , Lleixà Esther , Gibert-Serramià Mónica , Estrada-Tejedor Roger , Berzosa Xavier , Batllori Xavier , Pubill David , Camarasa Jordi , Escubedo Elena , López-Arnau Raúl
Published: February 2022

Changes in the molecular structure of synthetic cathinones has led to an increase in the number of novel emerging drugs in the illicit drug market at an unprecedented rate. Unfortunately, little is known about the neuropsychopharmacology of recently emerged halogen-substituted α-PVP derivatives. Thus, the aim of this study was to investigate the role of para- and meta-halogen (F-, Cl-, and Br-) substitutions on the in vitro, in silico, and in vivo effects of α-pyrrolidinopentiophenone (α-PVP) derivatives. HEK293 cells expressing the human dopamine or serotonin transporter (hDAT and hSERT) were used for the uptake inhibition and transporter affinity assays. Molecular docking was used to model the interaction mechanism against DAT. Swiss CD-1 mice were used for the horizontal locomotor activity, open field test, and conditioned place preference paradigm. All compounds demonstrated potent DA uptake inhibition and higher DAT selectivity than cocaine. Meta-substituted cathinones showed higher DAT/SERT ratios than their para- analogs, which correlates with an increased psychostimulant effect in vivo and with different meta- and para-in silico interactions at DAT. Moreover, all compounds induced rewarding and acute anxiogenic effects in mice. In conclusion, the present study demonstrates the role of meta- and para-halogen substitutions in the mechanism of action and provides the first evidence of the rewarding and anxiety-like properties of halogenated α-PVP derivatives.
In Vivo Metabolic Responses to Different Formulations of Amino Acid Mixtures for the Treatment of Phenylketonuria (PKU)
Authors: Giarratana Nadia , Giardino Luciana , Bighinati Andrea , Reiner Giorgio , Rocha Júlio César
Published: February 2022

Phenylketonuria (PKU) is a rare autosomal recessive inborn error of metabolism where the mainstay of treatment is a Phe restricted diet consisting of a combination of limited amounts of natural protein with supplementation of Phe-free or low-Phe protein substitutes and special low protein foods. Suboptimal outcomes may be related to the different absorption kinetics of free AAs, which have lower biological efficacy than natural proteins. Physiomimic TechnologyTM is a technology engineered to prolong AA (AA-PT) release allowing physiological absorption and masking the odor and taste of free AAs. The aim of these studies was to assess the impact of AA-PT formulation on selected functional and metabolic parameters both in acute and long-term experimental studies. Adult rats in fasting conditions were randomized in different groups and treated by oral gavage. Acute AA-PT administration resulted in significantly lower BUN at 90 min versus baseline. Both BUN and glycemia were modulated in the same direction as intact casein protein. Long-term treatment with AA-PT significantly reduces the protein expression of the muscle degradation marker Bnip3L (−46%) while significantly increasing the proliferation of market myostatin (+58%). Animals dosed for 15 days with AA-PT had significantly stronger grip strength (+30%) versus baseline. In conclusion, the results suggest that the AA-PT formulation may have beneficial effects on both AA oxidation and catabolism with a direct impact on muscle as well as on other metabolic pathways.
Salicylic Acid in Root Growth and Development
Authors: Bagautdinova Zulfira Z. , Omelyanchuk Nadya , Tyapkin Aleksandr V. , Kovrizhnykh Vasilina V. , Lavrekha Viktoriya V. , Zemlyanskaya Elena V.
Published: February 2022

In plants, salicylic acid (SA) is a hormone that mediates a plant’s defense against pathogens. SA also takes an active role in a plant’s response to various abiotic stresses, including chilling, drought, salinity, and heavy metals. In addition, in recent years, numerous studies have confirmed the important role of SA in plant morphogenesis. In this review, we summarize data on changes in root morphology following SA treatments under both normal and stress conditions. Finally, we provide evidence for the role of SA in maintaining the balance between stress responses and morphogenesis in plant development, and also for the presence of SA crosstalk with other plant hormones during this process.
High Mobility Group A1 Regulates Transcription Levels of Oligodendrocyte Marker Genes in Cultured Oligodendrocyte Precursor Cells
Authors: Egawa Naohiro , Hamanaka Gen , Chung Kelly K. , Ishikawa Hidehiro , Shindo Akihiro , Maki Takakuni , Takahashi Ryosuke , Inoue Haruhisa , Lo Eng H. , Arai Ken
Published: February 2022

Oligodendrocyte precursor cells (OPCs) serve as progenitor cells of terminally differentiated oligodendrocytes. Past studies have confirmed the importance of epigenetic system in OPC differentiation to oligodendrocytes. High mobility group A1 (HMGA1) is a small non-histone nuclear protein that binds DNA and modifies the chromatin conformational state. However, it is still completely unknown about the roles of HMGA1 in the process of OPC differentiation. In this study, we prepared primary OPC cultures from the neonatal rat cortex and examined whether the loss- and gain-of-function of HMGA1 would change the mRNA levels of oligodendrocyte markers, such as Cnp, Mbp, Myrf and Plp during the process of OPC differentiation. In our system, the mRNA levels of Cnp, Mbp, Myrf and Plp increased depending on the oligodendrocyte maturation step, but the level of Hmga1 mRNA decreased. When HMGA1 was knocked down by a siRNA approach, the mRNA levels of Cnp, Mbp, Myrf and Plp were smaller in OPCs with Hmga1 siRNA compared to the ones in the control OPCs. On the contrary, when HMGA1 expression was increased by transfection of the Hmga1 plasmid, the mRNA levels of Cnp, Mbp, Myrf and Plp were slightly larger compared to the ones in the control OPCs. These data may suggest that HMGA1 participates in the process of OPC differentiation by regulating the mRNA expression level of myelin-related genes.
Mathematical Description of the Increase in Selectivity of an Anion-Exchange Membrane Due to Its Modification with a Perfluorosulfonated Ionomer
Authors: Kozmai Anton , Pismenskaya Natalia , Nikonenko Victor
Published: February 2022

In this paper, we simulate the changes in the structure and transport properties of an anion-exchange membrane (CJMA-7, Hefei Chemjoy Polymer Materials Co. Ltd., China) caused by its modification with a perfluorosulfonated ionomer (PFSI). The modification was made in several stages and included keeping the membrane at a low temperature, applying a PFSI solution on its surface, and, subsequently, drying it at an elevated temperature. We applied the known microheterogeneous model with some new amendments to simulate each stage of the membrane modification. It has been shown that the PFSI film formed on the membrane-substrate does not affect significantly its properties due to the small thickness of the film (≈4 µm) and similar properties of the film and substrate. The main effect is caused by the fact that PFSI material “clogs” the macropores of the CJMA-7 membrane, thereby, blocking the transport of coions through the membrane. In this case, the membrane microporous gel phase, which exhibits a high selectivity to counterions, remains the primary pathway for both counterions and coions. Due to the above modification of the CJMA-7 membrane, the coion (Na+) transport number in the membrane equilibrated with 1 M NaCl solution decreased from 0.11 to 0.03. Thus, the modified membrane became comparable in its transport characteristics with more expensive IEMs available on the market.
SMRT and Illumina RNA-Seq Identifies Potential Candidate Genes Related to the Double Flower Phenotype and Unveils SsAP2 as a Key Regulator of the Double-Flower Trait in Sagittaria sagittifolia
Authors: Gao Meiping , Jiang Wen , Lin Zhicheng , Lin Qian , Ye Qinghua , Wang Wei , Xie Qian , He Xinhua , Luo Cong , Chen Qingxi
Published: February 2022

Double flowers are one of the important objectives of ornamental plant breeding. Sagittaria sagittifolia is an aquatic herb in the Alismataceae family that is widely used as an ornamental plant in gardens. However, the reference genome has not been published, and the molecular regulatory mechanism of flower formation remains unclear. In this study, single molecule real-time (SMRT) sequencing technology combined with Illumina RNA-Seq was used to perform a more comprehensive analysis of S. sagittifolia for the first time. We obtained high-quality full-length transcripts, including 53,422 complete open reading frames, and identified 5980 transcription factors that belonged to 67 families, with many MADS-box genes involved in flower formation being obtained. The transcription factors regulated by plant hormone signals played an important role in the development of double flowers. We also identified an AP2 orthologous gene, SsAP2, with a deletion of the binding site for miR172, that overexpressed SsAP2 in S. sagittifolia and exhibited a delayed flowering time and an increased number of petals. This study is the first report of a full-length transcriptome of S. sagittifolia. These reference transcripts will be valuable resources for the analysis of gene structures and sequences, which provide a theoretical basis for the molecular regulatory mechanism governing the formation of double flowers.
Regulatory Roles of the N-Terminal Intrinsically Disordered Region of Modular Src
Authors: Kato Goro
Published: February 2022

Src, the prototype of Src family kinases (SFKs), is a modular protein consisting of SH4 (SH4) and unique (UD) domains in an N-terminal intrinsically disordered region (IDR), and SH3, SH2, and kinase (KD) folded domains conserved among SFKs. Src functions as a pleiotropic signaling hub in proliferating and post-mitotic cells, and it is related to cancer and neurological diseases. However, its regulatory mechanism is unclear because the existing canonical model is derived from crystallographic analyses of folded constructs lacking the IDR. This work reviews nuclear magnetic resonance analyses of partially structured lipid-binding segments in the flexible UD and the fuzzy intramolecular complex (FIMC) comprising IDR and SH3 domains, which interacts with lipid membranes and proteins. Furthermore, recently determined IDR-related Src characteristics are discussed, including dimerization, SH4/KD intramolecular fastener bundling of folded domains, and the sorting of adhesive structures. Finally, the modulatory roles of IDR phosphorylation in Src activities involving the FIMC are explored. The new regulatory roles of IDRs are integrated with the canonical model to elucidate the functions of full-length Src. This review presents new aspects of Src regulation, and provides a future direction for studies on the structure and function of Src, and their implications for pathological processes.
The Value of Whole-Genome Sequencing for Mitochondrial DNA Population Studies: Strategies and Criteria for Extracting High-Quality Mitogenome Haplotypes
Authors: Sturk-Andreaggi Kimberly , Ring Joseph D. , Ameur Adam , Gyllensten Ulf , Bodner Martin , Parson Walther , Marshall Charla , Allen Marie
Published: February 2022

Whole-genome sequencing (WGS) data present a readily available resource for mitochondrial genome (mitogenome) haplotypes that can be utilized for genetics research including population studies. However, the reconstruction of the mitogenome is complicated by nuclear mitochondrial DNA (mtDNA) segments (NUMTs) that co-align with the mtDNA sequences and mimic authentic heteroplasmy. Two minimum variant detection thresholds, 5% and 10%, were assessed for the ability to produce authentic mitogenome haplotypes from a previously generated WGS dataset. Variants associated with NUMTs were detected in the mtDNA alignments for 91 of 917 (~8%) Swedish samples when the 5% frequency threshold was applied. The 413 observed NUMT variants were predominantly detected in two regions (nps 12,612–13,105 and 16,390–16,527), which were consistent with previously documented NUMTs. The number of NUMT variants was reduced by ~97% (400) using a 10% frequency threshold. Furthermore, the 5% frequency data were inconsistent with a platinum-quality mitogenome dataset with respect to observed heteroplasmy. These analyses illustrate that a 10% variant detection threshold may be necessary to ensure the generation of reliable mitogenome haplotypes from WGS data resources.
Red Blood Cell Morphodynamics in Patients with Polycythemia Vera and Stroke
Authors: Kuznetsova Polina I. , Raskurazhev Anton A. , Shabalina Alla A. , Melikhyan Anait L. , Subortseva Irina N. , Tanashyan Marine M.
Published: February 2022

Polycythemia vera (PV) is a Ph-negative myeloproliferative neoplasm (MPN) which is characterized by erythrocytosis and a high incidence of thrombotic complications, including stroke. The study aimed to evaluate red blood cell (RBC) morphodynamic properties in PV patients and their possible association with stroke. We enrolled 48 patients with PV in this cross-sectional study, 13 of which have a history of ischemic stroke. The control group consisted of 90 healthy subjects. RBC deformability and aggregation analysis were performed using a laser-assisted optical rotational red cell analyzer. The following parameters were calculated: aggregation amplitude (Amp), RBC rouleaux formation time constant (Tf), time of formation of three-dimensional aggregates (Ts), aggregation index (AI), rate of complete disaggregation (y-dis), and the maximal elongation of RBC (EImax). Statistical analysis was performed with the R programming language. There were significant differences in RBCs morphodynamics features between patients with PV and the control group. Lower EImax (0.47 (0.44; 0.51) vs. 0.51 (0.47; 0.54), p < 0.001) and γ-dis (100 (100; 140) vs. 140 (106; 188) s−1, p < 0.001) along with higher amplitude (10.1 (8.6; 12.2) vs. 7.7 (6.6; 9.2), p < 0.001) was seen in patients with PV compared with control. A statistically significant difference between PV patients with and without stroke in aggregation amplitude was found (p = 0.03). A logistic regression model for stroke was built based on RBC morphodynamics which performed reasonably well (p = 0.01). RBC alterations may be associated with overt cerebrovascular disease in PV, suggesting a possible link between erythrocyte morphodynamics and increased risk of stroke.
The Multifaceted Roles of Mast Cells in Immune Homeostasis, Infections and Cancers
Authors: Sobiepanek Anna , Kuryk Łukasz , Garofalo Mariangela , Kumar Sandeep , Baran Joanna , Musolf Paulina , Siebenhaar Frank , Fluhr Joachim Wilhelm , Kobiela Tomasz , Plasenzotti Roberto , Kuchler Karl , Staniszewska Monika
Published: February 2022

Mast cells (MCs) play important roles in normal immune responses and pathological states. The location of MCs on the boundaries between tissues and the external environment, including gut mucosal surfaces, lungs, skin, and around blood vessels, suggests a multitude of immunological functions. Thus, MCs are pivotal for host defense against different antigens, including allergens and microbial pathogens. MCs can produce and respond to physiological mediators and chemokines to modulate inflammation. As long-lived, tissue-resident cells, MCs indeed mediate acute inflammatory responses such as those evident in allergic reactions. Furthermore, MCs participate in innate and adaptive immune responses to bacteria, viruses, fungi, and parasites. The control of MC activation or stabilization is a powerful tool in regulating tissue homeostasis and pathogen clearance. Moreover, MCs contribute to maintaining the homeostatic equilibrium between host and resident microbiota, and they engage in crosstalk between the resident and recruited hematopoietic cells. In this review, we provide a comprehensive overview of the functions of MCs in health and disease. Further, we discuss how mouse models of MC deficiency have become useful tools for establishing MCs as a potential cellular target for treating inflammatory disorders.
The Impact of Red Blood Cell Transfusion on Blood Lactate in Non-Bleeding Critically Ill Patients—A Retrospective Cohort Study
Authors: Czempik Piotr F. , Gierczak Dawid , Wilczek Dawid , Krzych Łukasz J.
Published: February 2022

Anemia should preferably be managed without red blood cell transfusion (RBCT); instead, therapy should be focused on causes of anemia along with efforts to minimize blood loss. Lactate could potentially be used as a physiologic RBCT trigger, although there are some limitations to its interpretation. The aim of our study was to analyze the impact of RBCT on blood lactate with consideration of factors known to increase its concentration and to assess the usefulness of blood lactate as a potential physiologic RBCT trigger. We performed a retrospective analysis of all RBCT episodes in non-bleeding critically ill patients. We retrieved demographic data, data on RBCT itself (duration, type of RBC, volume of RBC, age of RBC), laboratory parameters (lactate, hemoglobin, glucose, total bilirubin), and factors potentially increasing lactate. We analyzed 77 RBCTs with elevated pre-RBCT lactate. The median age of patients was 66 (IQR 57–73) years and the distribution of sexes was even. The named factors potentially influencing lactate had no impact on its concentration. The median pre-post RBCT lactate was 2.44 (IQR 2.08–3.27) and 2.13 (IQR 1.75–2.88) mmol/L, respectively (p < 0.01); the median decrease was 0.41 (IQR 0.07–0.92) mmol/L. We conclude that RBCT did not normalize mildly elevated lactate. Common causes of elevated lactate probably had no impact on its concentration. Therefore lactate may have a limited role as a physiologic RBCT trigger in non-bleeding severely anemic critically ill patients.
Management of Childhood Glaucoma Following Cataract Surgery
Authors: Simons Anne-Sophie , Casteels Ingele , Grigg John , Stalmans Ingeborg , Vandewalle Evelien , Lemmens Sophie
Published: February 2022

Glaucoma remains a frequent serious complication following cataract surgery in children. The optimal approach to management for ‘glaucoma following cataract surgery’ (GFCS), one of the paediatric glaucoma subtypes, is an ongoing debate. This review evaluates the various management options available and aims to propose a clinical management strategy for GFCS cases. A literature search was conducted in four large databases (Cochrane, PubMed, Embase, and Web of Science), from 1995 up to December 2021. Thirty-nine studies—presenting (1) eyes with GFCS; a disease entity as defined by the Childhood Glaucoma Research Network Classification, (2) data on treatment outcomes, and (3) follow-up data of at least 6 months—were included. Included papers report on GFCS treated with angle surgery, trabeculectomy, glaucoma drainage device implantation (GDD), and cyclodestructive procedures. Medical therapy is the first-line treatment in GFCS, possibly to bridge time to surgery. Multiple surgical procedures are often required to adequately control GFCS. Angle surgery (360 degree) may be considered before proceeding to GDD implantation, since this technique offers good results and is less invasive. Literature suggests that GDD implantation gives the best chance for long-term IOP control in childhood GFCS and some studies put this technique forward as a good choice for primary surgery. Cyclodestruction seems to be effective in some cases with uncontrolled IOP. Trabeculectomy should be avoided, especially in children under the age of one year and children that are left aphakic. The authors provide a flowchart to guide the management of individual GFCS cases.
Awakened Beta-Cell Function Decreases the Risk of Hypoglycemia in Pregnant Women with Type 1 Diabetes Mellitus
Authors: Delmis Josip , Ivanisevic Marina
Published: February 2022

Diabetes in pregnancy creates many problems for both the mother and child. Pregnant women with type 1 diabetes experience more frequent hypoglycemic and hyperglycemic episodes. This study aimed to determine the risk of clinically significant biochemical hypoglycemia (CSBH) by HbA1c, fasting C-peptide, mean plasma glucose (PG), and insulin dose in pregnant women type 1 diabetes mellitus according to each trimester of the pregnancy. Methods. We conducted a prospective observational study of 84 pregnant women with type 1 diabetes in an academic hospital. To present the hypoglycemia, we divided the participants into two groups: those who did not have clinically significant biochemical hypoglycemia (CSBH−; n = 30) and those who had clinically significant biochemical hypoglycemia (CSBH+; n = 54). Results. In the first, second, and third trimesters, the duration of T1DM, fasting C-peptide, and mean glucose concentration was inversely associated with CSBH. Conclusions. Insulin overdose is the most common risk factor for hypoglycemia. In pregnant women with type 1 diabetes with elevated fasting C-peptide levels, the insulin dose should be diminished to reduce the risk of hypoglycemia.
Endoscopic Ultrasound-Guided Fine-Needle Biopsy Using 22G Franseen Needles without Rapid On-Site Evaluation for Diagnosis of Intraabdominal Masses
Authors: Pausawasdi Nonthalee , Cheirsilpa Kunsuda , Chalermwai Wipapat , Asokan Ishan , Sriprayoon Tassanee , Charatcharoenwitthaya Phunchai
Published: February 2022

Background: The impact of rapid on-site cytologic evaluation (ROSE) on endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is widely debated. This study aims to assess the diagnostic performance of EUS-FNB in the absence of ROSE in abdominal masses. Methods: Patients with abdominal masses undergoing EUS-FNB using 22-gauge Franseen needles and the slow-pull technique were prospectively enrolled in this study. Macroscopic on-site evaluation (MOSE) was performed without ROSE. Results: 100 patients were recruited between 2018 and 2020. Seventy-eight patients had neoplasms, and twenty-two patients had benign diseases. Common diagnoses included pancreatic cancer (n = 27), mesenchymal tumors (n = 17), and metastatic tumors (n = 14). The mean mass size was 3.9 ± 2.6 cm. The median pass number was three. Eighty-nine percent had adequate specimens for histologic evaluation. Malignancy increased the odds of obtaining adequate tissue (OR 5.53, 95% CI, 1.36–22.5). For pancreatic cancer, FNB had a sensitivity of 92.3%, a specificity of 100%, a positive predictive value (PPV) of 100%, a negative predictive value (NPV) of 97%, and an AUROC of 0.96. The sensitivity, specificity, PPV, NPV, and AUROC for mesenchymal cell tumors were 100%, 95.9%, 84.2%, 100%, and 0.98, respectively. For metastatic tumors, FNB was 100% sensitive and specific, with an AUROC of 1.00. There were no procedure-related complications. Conclusions: 22-gauge Franseen needles with the slow-pull technique and MOSE without ROSE provide excellent diagnostic performances for malignant lesions. Thus, MOSE should be implemented in real-world practice, and ROSE can be obviated when EUS-FNB is employed.
Influence of Ipsilateral Graft Inflow to Arteriovenous Fistula for Hemodialysis in Coronary Bypass Surgery
Authors: Sohn Bongyeon , Chang Hyoung-Woo , Lee Jae-Hang , Kim Dongjung , Kim Junsung , Lim Cheong , Park Kay-Hyun
Published: February 2022

In coronary artery bypass grafting (CABG) for patients on hemodialysis, there has been concern about “coronary steal”. This study aims to evaluate the influence of using an in situ internal thoracic artery (ITA) ipsilateral to a preexisting arteriovenous fistula (AVF) in dialysis-dependent patients undergoing CABG. Between 2004 and 2018, dialysis-dependent patients with AVFs who underwent CABG were enrolled. According to the locational relationship of AVFs and in situ ITA grafts, the patients were divided into the ipsilateral group (n = 22) and the contralateral group (n = 21). Inverse probability weighting analysis was used to estimate and compare the late clinical outcomes. The late cardiac-related adverse events were not significantly different between the two groups: “major adverse cardiovascular and cerebrovascular events (MACCE)” (p = 0.090), “composite outcome of recurrent angina and coronary re-intervention” (p = 0.600). The in situ ITA graft of CABG on the ipsilateral side to AVF was not a significant risk factor for MACCE or the composite outcome of recurrent angina and coronary re-intervention. There was no statistically significant difference in the graft patency between the groups. Therefore, it might not be necessary to avoid using an in situ ITA on the ipsilateral side of an upper-arm AVF for optimal coronary artery bypass grafting in dialysis-dependent patients.