bluuebunny/crossref_metadata_2025 huggingface dataset:
The Genetic and Molecular Analyses of RAD51C and RAD51D Identifies Rare Variants Implicated in Hereditary Ovarian Cancer from a Genetically Unique Population
Authors: Alenezi Wejdan M. , Milano Larissa , Fierheller Caitlin T. , Serruya Corinne , Revil Timothée , Oros Kathleen K. , Behl Supriya , Arcand Suzanna L. , Nayar Porangana , Spiegelman Dan , Gravel Simon , Mes-Masson Anne-Marie , Provencher Diane , Foulkes William D. , El Haffaf Zaki , Rouleau Guy , Bouchard Luigi , Greenwood Celia M. T. , Masson Jean-Yves , Ragoussis Jiannis , Tonin Patricia N.
Published: April 2022

To identify candidate variants in RAD51C and RAD51D ovarian cancer (OC) predisposing genes by investigating French Canadians (FC) exhibiting unique genetic architecture. Candidates were identified by whole exome sequencing analysis of 17 OC families and 53 early-onset OC cases. Carrier frequencies were determined by the genetic analysis of 100 OC or HBOC families, 438 sporadic OC cases and 1025 controls. Variants of unknown function were assayed for their biological impact and/or cellular sensitivity to olaparib. RAD51C c.414G>C;p.Leu138Phe and c.705G>T;p.Lys235Asn and RAD51D c.137C>G;p.Ser46Cys, c.620C>T;p.Ser207Leu and c.694C>T;p.Arg232Ter were identified in 17.6% of families and 11.3% of early-onset cases. The highest carrier frequency was observed in OC families (1/44, 2.3%) and sporadic cases (15/438, 3.4%) harbouring RAD51D c.620C>T versus controls (1/1025, 0.1%). Carriers of c.620C>T (n = 7), c.705G>T (n = 2) and c.137C>G (n = 1) were identified in another 538 FC OC cases. RAD51C c.705G>T affected splicing by skipping exon four, while RAD51D p.Ser46Cys affected protein stability and conferred olaparib sensitivity. Genetic and functional assays implicate RAD51C c.705G>T and RAD51D c.137C>G as likely pathogenic variants in OC. The high carrier frequency of RAD51D c.620C>T in FC OC cases validates previous findings. Our findings further support the role of RAD51C and RAD51D in hereditary OC.
The Autophagy Protein Pacer Positively Regulates the Therapeutic Potential of Mesenchymal Stem Cells in a Mouse Model of DSS-Induced Colitis
Authors: Bergmann Cristian A. , Beltran Sebastian , Vega-Letter Ana Maria , Murgas Paola , Hernandez Maria Fernanda , Gomez Laura , Labrador Luis , Cortés Bastián I. , Poblete Cristian , Quijada Cristobal , Carrion Flavio , Woehlbier Ute , Manque Patricio A.
Published: April 2022

Mesenchymal stem cells (MSC) have emerged as a promising tool to treat inflammatory diseases, such as inflammatory bowel disease (IBD), due to their immunoregulatory properties. Frequently, IBD is modeled in mice by using dextran sulfate sodium (DSS)-induced colitis. Recently, the modulation of autophagy in MSC has been suggested as a novel strategy to improve MSC-based immunotherapy. Hence, we investigated a possible role of Pacer, a novel autophagy enhancer, in regulating the immunosuppressive function of MSC in the context of DSS-induced colitis. We found that Pacer is upregulated upon stimulation with the pro-inflammatory cytokine TNFα, the main cytokine released in the inflammatory environment of IBD. By modulating Pacer expression in MSC, we found that Pacer plays an important role in regulating the autophagy pathway in this cell type in response to TNFα stimulation, as well as in regulating the immunosuppressive ability of MSC toward T-cell proliferation. Furthermore, increased expression of Pacer in MSC enhanced their ability to ameliorate the symptoms of DSS-induced colitis in mice. Our results support previous findings that autophagy regulates the therapeutic potential of MSC and suggest that the augmentation of autophagic capacity in MSC by increasing Pacer levels may have therapeutic implications for IBD.
Green Hydrogen in the UK: Progress and Prospects
Authors: Kendall Kevin
Published: April 2022

Green hydrogen has been known in the UK since Robert Boyle described flammable air in 1671. This paper describes how green hydrogen has become a new priority for the UK in 2021, beginning to replace fossil hydrogen production exceeding 1 Mte in 2021 when the British Government started to inject significant funding into green hydrogen sources, though much less than the USA, Germany, Japan and China. Recent progress in the UK was initiated in 2008 when the first UK green hydrogen station opened in Birmingham University, refuelling 5 hydrogen fuel cell battery electric vehicles (HFCBEVs) for the 50 PhD chemical engineering students that arrived in 2009. Only 10 kg/day were required, in contrast to the first large, green ITM power station delivering almost 600 kg/day of green hydrogen that opened in the UK, in Tyseley, in July 2021. The first question asked in this paper is: ‘What do you mean, Green?’. Then, the Clean Air Zone (CAZ) in Birmingham is described, with the key innovations defined. Progress in UK green hydrogen and fuel cell introduction is then recounted. The remarks of Elon Musk about this ‘Fool Cell; Mind bogglingly stupid’ technology are analysed to show that he is incorrect. The immediate deployment of green hydrogen stations around the UK has been planned. Another century may be needed to make green hydrogen dominant across the country, yet we will be on the correct path, once a profitable supply chain is established in 2022.
High Conservation Value of an Urban Population of a State-Endangered Turtle
Authors: Durkin Brian P. , Richards-Dimitrie Teal M. , Anderson Kaite P. , Howell Hunter J. , Seigel Richard A.
Published: April 2022

Although reports of urban populations of amphibians and reptiles are increasingly common, the viability of such populations and information on threats to their continued existence remain less well known. From 2010–2018, we studied the nesting ecology of the imperiled Northern Map Turtle (Graptemys geographica) in an urbanized area in northeastern Maryland, USA. Mark-recapture data showed an estimated population size of 32 females with an annual survival of 89%. Females nested in highly altered areas such as flower gardens, along railroad rights-of-way, and along fence lines, but nest survival was much higher than in nearby natural areas, mainly due to very low predation rates from Raccoons. However, nesting females were subject to considerable disturbance from vehicle and foot traffic while nesting. To alleviate disturbance, we partnered with the town to construct a wildlife exclusion fence designed to isolate nesting Map Turtles from human disturbance. Due to the high annual survival of nests, this urban population may be important in the overall viability of Northern Map Turtles in this area.
Use of 6 Nucleotide Length Words to Study the Complexity of Gene Sequences from Different Organisms
Authors: Korotkov Eugene , Zaytsev Konstantin , Fedorov Alexey
Published: April 2022

In this paper, we attempted to find a relation between bacteria living conditions and their genome algorithmic complexity. We developed a probabilistic mathematical method for the evaluation of k-words (6 bases length) occurrence irregularity in bacterial gene coding sequences. For this, the coding sequences from different bacterial genomes were analyzed and as an index of k-words occurrence irregularity, we used W, which has a distribution similar to normal. The research results for bacterial genomes show that they can be divided into two uneven groups. First, the smaller one has W in the interval from 170 to 475, while for the second it is from 475 to 875. Plants, metazoan and virus genomes also have W in the same interval as the first bacterial group. We suggested that second bacterial group coding sequences are much less susceptible to evolutionary changes than the first group ones. It is also discussed to use the W index as a biological stress value.
Grand Canonical Ensembles of Sparse Networks and Bayesian Inference
Authors: Bianconi Ginestra
Published: April 2022

Maximum entropy network ensembles have been very successful in modelling sparse network topologies and in solving challenging inference problems. However the sparse maximum entropy network models proposed so far have fixed number of nodes and are typically not exchangeable. Here we consider hierarchical models for exchangeable networks in the sparse limit, i.e., with the total number of links scaling linearly with the total number of nodes. The approach is grand canonical, i.e., the number of nodes of the network is not fixed a priori: it is finite but can be arbitrarily large. In this way the grand canonical network ensembles circumvent the difficulties in treating infinite sparse exchangeable networks which according to the Aldous-Hoover theorem must vanish. The approach can treat networks with given degree distribution or networks with given distribution of latent variables. When only a subgraph induced by a subset of nodes is known, this model allows a Bayesian estimation of the network size and the degree sequence (or the sequence of latent variables) of the entire network which can be used for network reconstruction.
Analysis on Optimal Error Exponents of Binary Classification for Source with Multiple Subclasses
Authors: Kuramata Hiroto , Yagi Hideki
Published: April 2022

We consider a binary classification problem for a test sequence to determine from which source the sequence is generated. The system classifies the test sequence based on empirically observed (training) sequences obtained from unknown sources P1 and P2. We analyze the asymptotic fundamental limits of statistical classification for sources with multiple subclasses. We investigate the first- and second-order maximum error exponents under the constraint that the type-I error probability for all pairs of distributions decays exponentially fast and the type-II error probability is upper bounded by a small constant. In this paper, we first give a classifier which achieves the asymptotically maximum error exponent in the class of deterministic classifiers for sources with multiple subclasses, and then provide a characterization of the first-order error exponent. We next provide a characterization of the second-order error exponent in the case where only P2 has multiple subclasses but P1 does not. We generalize our results to classification in the case that P1 and P2 are a stationary and memoryless source and a mixed memoryless source with general mixture, respectively.
Transfer Learning Improving Predictive Mortality Models for Patients in End-Stage Renal Disease
Authors: Macias Edwar , Lopez Vicario Jose , Serrano Javier , Ibeas Jose , Morell Antoni
Published: April 2022

Deep learning is becoming a fundamental piece in the paradigm shift from evidence-based to data-based medicine. However, its learning capacity is rarely exploited when working with small data sets. Through transfer learning (TL), information from a source domain is transferred to a target one to enhance a learning task in such domain. The proposed TL mechanisms are based on sample and feature space augmentation. Thus, deep autoencoders extract complex representations for the data in the TL approach. Their latent representations, the so-called codes, are handled to transfer information among domains. The transfer of samples is carried out by computing a latent space mapping matrix that links codes from both domains for later reconstruction. The feature space augmentation is based on the computation of the average of the most similar codes from one domain. Such an average augments the features in a target domain. The proposed framework is evaluated in the prediction of mortality in patients in end-stage renal disease, transferring information related to the mortality of patients with acute kidney injury from the massive database MIMIC-III. Compared to other TL mechanisms, the proposed approach improves 6–11% in previous mortality predictive models. The integration of TL approaches into learning tasks in pathologies with data volume issues could encourage the use of data-based medicine in a clinical setting.
Experimental Investigation on Solar–Thermal Conversion and Migration Characteristics of Nanofluids
Authors: Sun Haoyang , Lin Guiping , Jin Haichuan , Zhou Ying , Ma Kuiyuan
Published: April 2022

Solar–thermal conversion and migration characteristics of nanofluids have attracted intensive attention recently. Due to the strong absorption of solar energy, solar collectors with nanofluids have wide applications in many areas including desalination and power generation. Researchers have mainly focused on the macroscopic performance of nanofluids in solar collectors, but the nanoparticles’ migration characteristics with vapor during phase transformation have not been further investigated. Therefore, an experimental investigation on solar–thermal conversion characteristics of nanofluids and migration characteristics with vapor during phase transformation was conducted in this work, in order to verify the enhancement effect of nanoparticles on solar energy absorption and explore the nanoparticles’ migration behavior with vapor. It was found that part of Ag nanoparticles migrate out of the nanofluids with generated vapor by boiling nanofluids, and most of the nanoparticles remained in the nanofluids. In addition, more Ag nanoparticles migrated with vapor with the increased heating power. The concentration of migrated nanofluids was 20.58 ppm with a power of 16.2 W and 31.39 ppm with a power of 20 W. The investigation pointed out the potential danger of nanofluids in the process of utility and provided a reference for the standardized application of nanofluids.
Review of Transparent and Semi-Transparent Building-Integrated Photovoltaics for Fenestration Application Modeling in Building Simulations
Authors: Romaní Joaquim , Ramos Alba , Salom Jaume
Published: April 2022

Building-integrated photovoltaics (BIPV) have attracted interest due to their capacity to feasibly supply buildings with renewable power generation, helping to achieve net-zero or net-positive energy goals. BIPV systems include many different solutions depending on the application, the PV technology, and the envelope material they substitute. Among BIPV systems, the last two decades have seen a rising interest in transparent and semi-transparent BIPV (T- and ST-BIPV), which add features such as daylighting and solar radiation control. T- and ST-BIPV mainly consist of opaque PV cells embedded in fenestration systems (PV cladding), while most recent research considers semi-transparent PV cells (homogeneous PV glazing) with improved optical properties. The evaluation of T- and ST-BIPV systems in building performance is complex, as it needs to combine optical, thermal, electrical, and daylighting calculations. Therefore, adequate modeling tools are key to the development of these technologies. A literature review is presented on T- and ST-BIPV. First, the types of T- and ST-BIPV technologies present in the literature are summarized, highlighting the current trends. Then, the most common optical, thermal, and electrical models are described, finishing with a summary of the T-and ST-BIPV modeling capabilities of the most common building simulation tools. Regardless of the implemented modeling tools, the main challenges to be considered are the optical model, the inclusion of the PV output in the window energy balance, and the calculation of the cell temperature for the correct assessment of cell efficiency. Modeling research mostly considers conventional PV (Si-based PV and thin-film) technologies, and research studies rarely address the cost evaluation of these T- and ST-BIPV systems.
Accelerated Stress Tests for Solid Oxide Cells via Artificial Aging of the Fuel Electrode
Authors: Vladikova Daria , Burdin Blagoy , Sheikh Asrar , Piccardo Paolo , Krapchanska Milena , Montinaro Dario , Spotorno Roberto
Published: April 2022

Solid Oxide Cells (SOCs) are under intensive development due to their great potential to meet the 2030 targets for decarbonization. One of their advantages is that they can work in reversible mode. However, in respect to durability, there are still some technical challenges. Although the quick development of experimental and modeling approaches gives insight into degradation mechanisms, an obligatory step that cannot be avoided is the performance of long-term tests. Taking into account the target for a commercial lifetime is 80,000 h, experiments lasting years are not acceptable for market needs. This work aims to develop accelerated stress tests (ASTs) for SOCs by the artificial aging of the fuel electrode via redox cycling, which follows the degradation processes of calendar aging (Ni coarsening and migration). However, it can cause irreversible damage by the formation of cracks at the interface anode/electrolyte. The advantages of the developed procedure are that it offers a mild level of oxidation, which can be governed and regulated by the direct impedance monitoring of the Ni network resistance changes during oxidation/reduction on a bare anode sample. Once the redox cycling conditions are fixed and the anode/electrolyte sample is checked for cracks, the procedure is introduced for the AST in full-cell configuration. The developed methodology is evaluated by a comparative analysis of current voltage and impedance measurements of pristine, artificially aged, and calendar-aged button cells, combined with microstructural characterization of their anodes. It can be applied in both fuel cell and electrolyzer mode. The results obtained in this study from the electrochemical tests show that the artificially aged experimental cell corresponds to at least 3500 h of nominal operation. The number of hours is much bigger in respect to the microstructural aging of the anode. Taking into consideration that the duration of the performed 20 redox cycles is about 50 to 60 working hours, the acceleration factor in respect to experimental timing is estimated to be higher than 60, without any damaging of the sample. This result shows that the selected approach is very promising for a large decrease in testing times for SOCs.
Review of Photovoltaic Power and Aquaculture in Desert
Authors: Vo Thi Thu Em , Je Seung-Mo , Jung Se-Hoon , Choi Jaehyeon , Huh Jun-Ho , Ko Han-Jong
Published: April 2022

PV (photovoltaic) capacity is steadily increasing every year, and the rate of increase is also increasing. A desert area with a large equipment installation area and abundant solar radiation is a good candidate. PV power plants installed in the desert have advantages in themselves, but when combined with desert aquacultures, additional benefits can be obtained while compensating for the shortcomings of the aquaculture industry. The importance of the aquaculture industry is increasing, with aquaculture products approaching half of the total supply of marine products due to sea environmental pollution and reduced resources. Moreover, in deserts, where marine products are difficult to obtain, aquaculture is a good way to save marine products. However, one of the many problems that complicate the introduction of aquaculture in the desert is that it is difficult to supply and demand electricity because the site is not near a viable electric grid. However, combination with PV can solve this problem. This paper investigates the solar power and aquaculture industry in the desert and explains the limitations and challenges of the solar power and aquaculture industry in the desert. Based on this, we hope to increase interest in the solar power and aquaculture industry in the desert and help with future research.
Subfossil Scots Pine (Pinus sylvestris L.) Wood from Northern Finland—Physical, Mechanical, and Chemical Properties and Suitability for Specialty Products
Authors: Möttönen Veikko , Helama Samuli , Pranovich Andrey , Korotkova Ekaterina , Xu Chunlin , Herva Hannu , Heräjärvi Henrik , Mäkinen Harri , Nöjd Pekka , Jyske Tuula
Published: April 2022

The physical, mechanical, and chemical properties of both stem wood and knot wood were investigated from two subfossil Scots pine (Pinus sylvestris L.) trunks retrieved from a lake in Finnish Lapland, dated to 404–486 CE and to 1318–1444 CE. Both the stem wood and the knot wood of the younger trunk had higher moisture content, lower density, and lower strength properties in comparison to the older trunk. The ash content of the stem wood of the younger trunk was lower, but the ash content of the knot wood was higher than that of the older trunk. Due to the degradation that occurred over time, all the values of physical and mechanical properties were lower compared to typical values of recently grown Scots pine wood. The chemical composition of both stem wood samples was close to the composition of the recently grown wood, and the only exception was the small decrease of the cellulose and hemicellulose in the subfossil samples. The bulk extractives were well-preserved, but terpenes and fatty acids underwent transformation, resulting in more stable compounds. The SWOT analysis (strengths, weaknesses, opportunities, and threats) showed pros and cons for the productization of subfossil wood, with the branding value of an ancient material being the potential enabler in developing commercial niche uses.
Simulation Models of the Dynamics of Forest Ecosystems
Authors: Larocque Guy R.
Published: April 2022

The development of simulation models of the dynamics of forest ecosystems has been an active area of research [...]
Coastal Monitoring Using Unmanned Aerial Vehicles (UAVs) for the Management of the Spanish Mediterranean Coast: The Case of Almenara-Sagunto
Authors: Chapapría Vicent Esteban , Peris José Serra , González-Escrivá José A.
Published: April 2022

The concentration of the world’s population in coastal areas means an increase in pressure on the environment and coastal ecosystems. The impacts of climate change affect natural biophysical and ecological systems and human health. Research has been developed to create coastal monitoring with Unmanned Aerial Vehicles (UAVs) that allow data to be obtained and methodologies that integrate computer vision algorithms for 3D and image processing techniques for analysis, combined with maritime information. The Valencian oval is located on the Spanish Mediterranean coast and registers significant coastal erosion. It is a densely populated area, with high economic relevance and tourist activity. The main goals of the developed research in this coastal area include creating a methodology of data collection that identifies environmental indicators significant to community health and uses in the coastal areas, to test progression of interventions and to assess coastal erosion detection and monitoring. The final objective is to aid in decision-making and coastal management. Sediment characterization was obtained, and continuous maritime information was collected. The dynamic evolution of coastal areas was researched by using UAVs on the Spanish Mediterranean coast. This technique is suitable for measuring medium to small coastal changes. Flight planning was carried out using the grid mode and adapted to areas in order to obtain a homogeneous pixel size and precision. This monitoring program takes advantage of technological development with very low economic costs and is a good tool for making decisions that must be based on scientific information. With the monitoring work, an annual erosion between 12 and 6 m was detected. The monitoring program has evidenced the shoreline trend as a result of the impact of rigid structures, mainly ports and groins, in promoting down-drift erosion processes in the area.
Nonverbal Oro-Motor Exercises: Do They Really Work for Phonoarticulatory Difficulties?
Authors: Parra-López Pablo , Olmos-Soria Marina , Valero-García Ana V.
Published: April 2022

Articulation disorders are deficiencies in the realization of speech sounds unrelated to organic or neurological disorders. Over the last decade, there has been a debate on the efficiency of non-verbal oro-motor exercises, which are orofacial movements programmed and organized in an intentional and coordinated way to control lips, tongue, and soft palate muscles. Of the 122 children evaluated, 52 presented articulatory difficulties. An intervention with nonverbal oro-motor exercises was applied, and children were again assessed following treatment. The results showed no differences between the experimental and control groups, either in the number of sounds that improved after this period or in the severity of difficulties (we categorized those with articulation difficulties in two to six sounds as ‘medium’ and those with difficulties in articulating more than seven sounds as ‘severe’). These results indicated that nonverbal oro-motor exercises alone are not efficient for intervention in difficulties in the realization of sounds in 4-year-old children.
Impact of High-Intensity Circuit Resistance Exercise on Physical Fitness, Inflammation, and Immune Cells in Female Breast Cancer Survivors: A Randomized Control Trial
Authors: Lee Kwang-Jin , An Keun-Ok
Published: April 2022

Questions remain about whether resistance exercise has a positive effect on immune and inflammatory cells. The purpose of this study was to evaluate the effect of 12 weeks of high-intensity circuit resistance exercise (HCRE) on inflammation and immune cells, and physical fitness, of female breast cancer survivors (FBCSs). Thirty FBCSs were randomly assigned to the HCRE (n = 15) and control (n = 15) groups. HRCE was administered for 50 min a day, 2–3 times a week, for 12 weeks. The control group only performed activities of daily living during the study period. Baseline and post-intervention measures included body composition, muscular strength, muscular endurance, flexibility, reaction time, balance, inflammation, and immune cell measurements. The results showed that HCRE improved body mass index, body fat, muscle mass, grip strength, back muscle strength, sit-up, whole-body reaction, standing on one leg with eyes closed, Y-balance test, and NKCA in FBCSs. The improvement of physical strength and immune cells of FBCSs was achieved using the 12-week HRCE program. Future studies must analyze various exercise intensities and types, and should be conducted on other cancer survivors. In addition, strategies should be developed to allow FBCSs to participate in resistance training.
Activities for Residents of Dutch Nursing Homes during the COVID-19 Pandemic: A Qualitative Study
Authors: Smeitink Marlon M. P. , Smaling Hanneke J. A. , van Tol Lisa S. , Haaksma Miriam L. , Caljouw Monique A. A. , Achterberg Wilco P.
Published: April 2022

To protect nursing home residents from getting infected with COVID-19, several measures have been imposed. The aim of this study was to describe the impact of these measures on activities for Dutch nursing home residents, the conditions under which the activities could take place, and the considerations when making decisions about the (dis)continuation of activities. The study consisted of the data of the qualitative MINUTES-study. Textual units derived from documentation of an outbreak team (OT) meetings on activities, well-being, informal caregivers, and volunteers from 39 long-term care organizations were re-analyzed using a content analysis. The results shows that OTs more often discussed restarting and continuing activities than stopping activities during the COVID-19 pandemic. There were differences between time periods, but activities never completely stopped according to the minutes. Activities were offered in an adapted way, often under certain conditions, such as organizing activities at other locations (e.g., outside), with limited group size, and following specific guidelines. The main focus of the considerations made were the ability to adhere to the guidelines, the well-being of residents, ensuring safety, and balancing benefits versus risks given vaccination availability and coverage. Overall, the study showed that organizing activities for nursing home residents despite COVID-19 measures is possible.
Socioeconomic Status and Nutritional Status as Predictors of Food Insecurity in Older Adults: A Case Study from Southern Ecuador
Authors: Encalada-Torres Janneth , Abril-Ulloa Victoria , Wong Sara , Alvarado-Romero Samantha , Bedoya-Ortega Maria , Encalada-Torres Lorena
Published: April 2022

While life expectancy is increasing due to scientific advancement, quality of life in aging depends, among other factors, on the nutritional status and socioeconomic status of older adults. To determine socioeconomic status and its association with nutritional status as a predictor of food insecurity among older adults in southern Ecuador, a cross-sectional study of 188 older adults in urban areas and 212 in rural areas was conducted. Nutritional status, food insecurity, and socioeconomic status were measured. Data were analyzed using SPSS v 15.0 for descriptive statistics and bivariate analysis. Of the older participants, 59% had malnutrition, the majority women, and 24.7% were in poverty. Underweight was associated with low socioeconomic status for adults between 65 and 74 years old (OR = 7.710; CI 95% = 1.691–35.147), while obesity was associated with low socioeconomic status and non-manual labor (OR = 3.048; CI 95% = 1.268–7.326). Over 80% of older adults living in homes without children younger than 18 and at low socioeconomic status had food insecurity. The prevalence of underweight, overweight, and obesity points to widespread nutritional problems, especially in rural areas, that are significantly associated with low socioeconomic status. This demonstrates the need for multidisciplinary programs and government policies that can contribute to reducing food insecurity among the highly vulnerable older population.
Prepregnancy Polycystic Ovary Syndrome as a Risk Factor of Subsequent Preterm Labor: A National Population-Based Cohort Study
Authors: Pan Mei-Lien , Chen Li-Ru , Chen Kuo-Hu
Published: April 2022

Background: Preterm labor and the following preterm births, which account for most of the perinatal deaths, are an important issue in public health. The study aims to assess the risk of subsequent preterm labor in pregnant females who have prepregnancy polycystic ovary syndrome (PCOS). Methods: This study has enrolled 1,000,000 randomly sampled females retrieved from the Taiwan National Health Insurance Research Database (NHIRD) during 1998–2012. The study excluded prepregnancy PCOS females who were initially diagnosed at age <15 or >45, and those who had inconsistent diagnoses. Moreover, the medical records of blood hormone tests, gynecologic ultrasonography, pelvic examinations, and tocometers were verified to confirm the accuracy of both diagnoses of PCOS and preterm labor. Among the prepregnancy PCOS females who became pregnant (the case group), each was age-matched to four females without prepregnancy PCOS (the control group). Results: Pregnant females in the case group (n = 1959) had a higher incidence of preterm labor than those in the control group (n = 7836) (42.98% vs. 21.99%, p < 0.0001). Analyzed by using logistic regression, the risk of preterm labor was significantly higher in the case group compared with the control group (crude OR: 2.674; 95% CI: 2.410–2.968, p < 0.0001). After adjustment with covariates, further analysis revealed a similar trend (adjusted OR: 2.405; 95% CI: 2.158–2.680, p < 0.0001). Among 1959 PCOS females in the case group, 196 had undergone metformin treatment. Compared with females without metformin treatment (the non-metformin subgroup), the metformin users (metformin subgroup) presented a reduced risk for preterm labor (adjusted OR: 2.238; 95% CI: 1.657–3.023). The risk of subsequent preterm labor was reduced by about 10% for the metformin subgroup compared with the non-metformin subgroup. Conclusions: Prepregnancy PCOS is an independent and significant risk factor of subsequent preterm labor. Among prepregnancy PCOS females, the risk of preterm labor is lowered by about 10% in metformin users compared with non-metformin females.
Generation of Inducible BCL11B Knockout in TAL1/LMO1 Transgenic Mouse T Cell Leukemia/Lymphoma Model
Authors: Przybylski Grzegorz K. , Korsak Dorota , Iżykowska Katarzyna , Nowicka Karina , Zalewski Tomasz , Tubacka Małgorzata , Mosor Maria , Januszkiewicz-Lewandowska Danuta , Frydrychowicz Magdalena , Boruczkowski Maciej , Dworacki Grzegorz , van den Brandt Jens , Grabarczyk Piotr , Schmidt Christian A. , Zeng Chengwu , Li Yangqiu
Published: April 2022

The B-cell CLL/lymphoma 11B gene (BCL11B) plays a crucial role in T-cell development, but its role in T-cell malignancies is still unclear. To study its role in the development of T-cell neoplasms, we generated an inducible BCL11B knockout in a murine T cell leukemia/lymphoma model. Mice, bearing human oncogenes TAL BHLH Transcription Factor 1 (TAL1; SCL) or LIM Domain Only 1 (LMO1), responsible for T-cell acute lymphoblastic leukemia (T-ALL) development, were crossed with BCL11B floxed and with CRE-ER/lox mice. The mice with a single oncogene BCL11Bflox/floxCREtg/tgTAL1tg or BCL11Bflox/floxCREtg/tgLMO1tg were healthy, bred normally, and were used to maintain the mice in culture. When crossed with each other, >90% of the double transgenic mice BCL11Bflox/floxCREtg/tgTAL1tgLMO1tg, within 3 to 6 months after birth, spontaneously developed T-cell leukemia/lymphoma. Upon administration of synthetic estrogen (tamoxifen), which binds to the estrogen receptor and activates the Cre recombinase, the BCL11B gene was knocked out by excision of its fourth exon from the genome. The mouse model of inducible BCL11B knockout we generated can be used to study the role of this gene in cancer development and the potential therapeutic effect of BCL11B inhibition in T-cell leukemia and lymphoma.
Photoperiod-Dependent Expression of MicroRNA in Drosophila
Authors: Pegoraro Mirko , Fishman Bettina , Zonato Valeria , Zouganelis Georgios , Francis Amanda , Kyriacou Charalambos P. , Tauber Eran
Published: April 2022

Like many other insects in temperate regions, Drosophila melanogaster exploits the photoperiod shortening that occurs during the autumn as an important cue to trigger a seasonal response. Flies survive the winter by entering a state of reproductive arrest (diapause), which drives the relocation of resources from reproduction to survival. Here, we profiled the expression of microRNA (miRNA) in long and short photoperiods and identified seven differentially expressed miRNAs (dme-mir-2b, dme-mir-11, dme-mir-34, dme-mir-274, dme-mir-184, dme-mir-184*, and dme-mir-285). Misexpression of dme-mir-2b, dme-mir-184, and dme-mir-274 in pigment-dispersing, factor-expressing neurons largely disrupted the normal photoperiodic response, suggesting that these miRNAs play functional roles in photoperiodic timing. We also analyzed the targets of photoperiodic miRNA by both computational predication and by Argonaute-1-mediated immunoprecipitation of long- and short-day RNA samples. Together with global transcriptome profiling, our results expand existing data on other Drosophila species, identifying genes and pathways that are differentially regulated in different photoperiods and reproductive status. Our data suggest that post-transcriptional regulation by miRNA is an important facet of photoperiodic timing.
Nanoparticle-Based Radiosensitization
Authors: Kempson Ivan
Published: April 2022

Radiotherapy is a highly affordable treatment and provides many excellent outcomes [...]
Glucocorticoid Receptor β Isoform Predominates in the Human Dysplastic Brain Region and Is Modulated by Age, Sex, and Antiseizure Medication
Authors: Westcott Rosemary , Chung Natalie , Ghosh Arnab , Ferguson Lisa , Bingaman William , Najm Imad M. , Ghosh Chaitali
Published: April 2022

The glucocorticoid receptor (GR) at the blood–brain barrier (BBB) is involved in the pathogenesis of drug-resistant epilepsy with focal cortical dysplasia (FCD); however, the roles of GR isoforms GRα and GRβ in the dysplastic brain have not been revealed. We utilized dysplastic/epileptic and non-dysplastic brain tissue from patients who underwent resective epilepsy surgery to identify the GRα and GRβ levels, subcellular localization, and cellular specificity. BBB endothelial cells isolated from the dysplastic brain tissue (EPI-ECs) were used to decipher the key BBB proteins related to drug regulation and BBB integrity compared to control and transfected GRβ-overexpressed BBB endothelial cells. GRβ was upregulated in dysplastic compared to non-dysplastic tissues, and an imbalance of the GRα/GRβ ratio was significant in females vs. males and in patients > 45 years old. In EPI-ECs, the subcellular localization and expression patterns of GRβ, Hsp90, CYP3A4, and CYP2C9 were consistent with GRβ+ brain endothelial cells. Active matrix metalloproteinase levels and activity increased, whereas claudin-5 levels decreased in both EPI-ECs and GRβ+ endothelial cells. In conclusion, the GRβ has a major effect on dysplastic BBB functional proteins and is age and gender-dependent, suggesting a critical role of brain GRβ in dysplasia as a potential biomarker and therapeutic target in epilepsy.
Cell Model of Depression: Reduction of Cell Stress with Mirtazapine
Authors: Correia Ana Salomé , Fraga Sónia , Teixeira João Paulo , Vale Nuno
Published: April 2022

Depression is a very prevalent and complex disease. This condition is associated with a high rate of relapse, making its treatment a challenge. Thus, an intensive investigation of this disease and its treatment is necessary. In this work, through cell viability assays (MTT and neutral red assays) and alkaline comet assays, we aimed to test the induction of stress in human SH-SY5Y cells through the application of hydrocortisone and hydrogen peroxide and to test the reversal or attenuation of this stress through the application of mirtazapine to the cells. Our results demonstrated that hydrogen peroxide, and not hydrocortisone, can induce cellular stress, as evidenced by DNA damage and a global cellular viability reduction, which were alleviated by the antidepressant mirtazapine. The establishment of a cellular model of depression through stress induction is important to study new possibilities of treatment of this disease using cell cultures.
Imbalance in Sirt1 Alternative Splicing in Response to Chronic Stress during the Adolescence Period in Female Mice
Authors: Shlomi Shir , Toledano Roni , Nitzan Keren , Shahaf Sigal Dror , Break Emanuela P. , Frenkel Dan , Doron Ravid
Published: April 2022

Stressful unpredictable life events have been implicated in numerous diseases. It is now becoming clear that some life periods are more vulnerable than others. As adolescence is a sensitive period in brain development, the long-term effects of stress during this period could be significant. We investigated the long-term effects of exposure to unpredictable chronic mild stress in adolescent mice on alternative splicing of Sirtuin 1. One-month-old mice were exposed to 4 weeks of UCMS and examined for anxiety and cognition at the age of 2, 4 and 6 months. We found a rise in anxious behavior immediately after the exposure to stress. Notably, there was a long-term impairment of performance in cognitive tasks and an imbalance in Sirtuin 1 and TrkB receptor alternative splicing in the stress-exposed mice compared with controls. To conclude, our results show that exposure to unpredictable chronic mild stress during adolescence affects cognition in adulthood. Understanding pathways affiliated with stress may help minimize the long-term emotional effects of an unpredictable, stressful event.
Comparative Analysis of the Metabolome and Transcriptome between the Green and Yellow-Green Regions of Variegated Leaves in a Mutant Variety of the Tree Species Pteroceltis tatarinowii
Authors: Qiao Qian , Wu Chong , Cheng Tian-Tian , Yan Yu , Zhang Lin , Wan Ying-Lin , Wang Jia-Wei , Liu Qing-Zhong , Feng Zhen , Liu Yan
Published: April 2022

In nature, many different factors cause plants to develop variegated leaves. To explore the mechanism of variegated leaf formation in Pteroceltis tatarinowii, a mutant variety (‘Jinyuyuan’), which was induced by ethylmethylsulfone, was selected, and its morphological structure, physiology, biochemistry, transcription and metabolism were analysed. According to differences in colour values, the colours were divided into two regions: a green region and a yellow-green region. The chlorophyll content of the two regions was significantly different. Moreover, the yellow-green regions of the leaves were significantly thinner than the green regions. The chloroplast ultrastructure in the yellow-green region revealed small chloroplasts, large vacuoles, small starch grains, obviously increased numbers of osmophilic grains, loose lamellae of the inner capsule and thin lamellae. Moreover, the yellow-green region was accompanied by oxidative stress, and the activity of the oxidative phosphorylation pathway related to oxidative activity in the transcriptome showed an upward trend. Vitamin B6 and proline contents also increased, indicating that the antioxidant activity of cells in the yellow-green region increased. Transcriptomic and metabolomic analysis showed that the differentially expressed genes (DEGs) related to chlorophyll synthesis and metabolism led to a decrease in the photosynthesis and then a decrease in the assimilation ability and contents of sucrose, starch and other assimilates. Amino acid synthesis and metabolism, lipid synthesis and the activity of metabolic pathways were obviously downregulated, and the contents of differentially accumulated metabolites associated with amino acids and lipids were also reduced. At the same time, 31 out of 32 DEGs involved in the flavonoid synthesis pathway were downregulated, which affected leaf colour. We hypothesized that the variegated leaves of P. tatarinowii ‘Jinyuyuan’ are caused by transcriptional and post-transcriptional regulation. Mutations in pigment and flavonoid synthesis pathway genes and transcription factor genes directly affect both pigment and flavonoid synthesis and degradation rate, which in turn affect carbon assimilation, carbon fixation, related protein synthesis and enzyme activity, lipid synthesis and degradation and the activity of other metabolic pathways, eventually leading to the formation of different colour regions.
Soluble Epoxide Hydrolase as a Therapeutic Target for Neuropsychiatric Disorders
Authors: Shan Jiajing , Hashimoto Kenji
Published: April 2022

It has been found that soluble epoxide hydrolase (sEH; encoded by the EPHX2 gene) in the metabolism of polyunsaturated fatty acids (PUFAs) plays a key role in inflammation, which, in turn, plays a part in the pathogenesis of neuropsychiatric disorders. Meanwhile, epoxy fatty acids such as epoxyeicosatrienoic acids (EETs), epoxyeicosatetraenoic acids (EEQs), and epoxyeicosapentaenoic acids (EDPs) have been found to exert neuroprotective effects in animal models of neuropsychiatric disorders through potent anti-inflammatory actions. Soluble expoxide hydrolase, an enzyme present in all living organisms, metabolizes epoxy fatty acids into the corresponding dihydroxy fatty acids, which are less active than the precursors. In this regard, preclinical findings using sEH inhibitors or Ephx2 knock-out (KO) mice have indicated that the inhibition or deficiency of sEH can have beneficial effects in several models of neuropsychiatric disorders. Thus, this review discusses the current findings of the role of sEH in neuropsychiatric disorders, including depression, autism spectrum disorder (ASD), schizophrenia, Parkinson’s disease (PD), and stroke, as well as the potential mechanisms underlying the therapeutic effects of sEH inhibitors.
Local Insulin-Derived Amyloidosis Model Confronted with Silymarin: Histological Insights and Gene Expression of MMP, TNF-α, and IL-6
Authors: Azarfar Katia , Yaghmaei Parichehreh , Amoli Mahsa M. , Hayati-Roodbari Nasim , Ebrahim-Habibi Azadeh
Published: April 2022

Amyloidosis is a heterogeneous group of protein deposition diseases associated with the presence of amyloid fibrils in tissues. Analogs of insulin that are used for treating diabetic patients (including regular insulin) can form amyloid fibrils, both in vitro and in vivo as reported in patients. The main purpose of this study was the induction of localized insulin-generated amyloidosis and the observation of silymarin effects on this process. In order to obtain amyloid structures, regular insulin was incubated at 37 °C for 24 h. Congo red absorbance and transmission electron microscopy images validated the formation of amyloid fibrils. Those fibrils were then injected subcutaneously into rats once per day for 6, 12 or 18 consecutive days in the presence or absence of silymarin, and caused development of firm waxy masses. These masses were excised and stained with Hematoxylin and Eosin, Congo red and Thioflavin S. Histological examination showed adipose cells and connective tissue in which amyloid deposition was visible. Amyloids decreased in the presence of silymarin, and the same effect was observed when silymarin was added to normal insulin and injected subsequently. Furthermore, plasma concentrations of MMP2, TNF-α, and IL-6 inflammatory factors were measured, and their gene expression was locally assessed in the masses by immunohistochemistry. All three factors increased in the amyloidosis state, while silymarin had an attenuating effect on their plasma levels and gene expression. In conclusion, we believe that silymarin could be effective in counteracting insulin-generated local amyloidosis.
Novel Antibacterial Copolymers Based on Quaternary Ammonium Urethane-Dimethacrylate Analogues and Triethylene Glycol Dimethacrylate
Authors: Chrószcz Marta W. , Barszczewska-Rybarek Izabela M. , Kazek-Kęsik Alicja
Published: April 2022

The growing scale of secondary caries and occurrence of antibiotic-resistant bacterial strains require the development of antibacterial dental composites. It can be achieved by the chemical introduction of quaternary ammonium dimethacrylates into dental composites. In this study, physicochemical and antibacterial properties of six novel copolymers consisting of 60 wt. % quaternary ammonium urethane-dimethacrylate analogues (QAUDMA) and 40 wt. % triethylene glycol dimethacrylate (TEGDMA) were investigated. Uncured compositions had suitable refractive index (RI), density (dm), and glass transition temperature (Tgm). Copolymers had low polymerization shrinkage (S), high degree of conversion (DC) and high glass transition temperature (Tgp). They also showed high antibacterial effectiveness against S. aureus and E. coli bacterial strains. It was manifested by the reduction in cell proliferation, decrease in the number of bacteria adhered on their surfaces, and presence of growth inhibition zones. It can be concluded that the copolymerization of bioactive QAUDMAs with TEGDMA provided copolymers with high antibacterial activity and rewarding physicochemical properties.
Human Serine Racemase Weakly Binds the Third PDZ Domain of PSD-95
Authors: Giaccari Roberta , Marchesani Francesco , Compari Carlotta , Fisicaro Emilia , Mozzarelli Andrea , Campanini Barbara , Bettati Stefano , Bruno Stefano , Faggiano Serena
Published: April 2022

Human serine racemase (hSR) is a pyridoxal-5′-phosphate (PLP)-dependent dimer that catalyzes the formation of D-serine from L-serine, as well as the dehydration of both L- and D-serine to pyruvate and ammonia. As D-serine is a co-agonist of N-methyl-D-aspartate receptors (NMDARs), hSR is a key enzyme in glutamatergic neurotransmission. hSR activity is finely regulated by Mg2+, ATP, post-translational modifications, and the interaction with protein partners. In particular, the C-terminus of murine SR binds the third PDZ domain (PDZ3) of postsynaptic density protein 95 (PSD-95), a member of the membrane-associated guanylate kinase (MAGUK) family involved in the trafficking and localization of glutamate receptors. The structural details of the interaction and the stability of the complex have not been elucidated yet. We evaluated the binding of recombinant human PSD-95 PDZ3 to hSR by glutaraldehyde cross-linking, pull-down assays, isothermal titration calorimetry, nuclear magnetic resonance, and enzymatic assays. Overall, a weak interaction was observed, confirming the binding for the human orthologs but supporting the hypothesis that a third protein partner (i.e., stargazin) is required for the regulation of hSR activity by PSD-95 and to stabilize their interaction.