bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and In Vitro Evaluation of Splice-Switching Oligonucleotides Bearing Locked Nucleic Acids, Amido-Bridged Nucleic Acids, and Guanidine-Bridged Nucleic Acids
Authors: Shimo Takenori , Nakatsuji Yusuke , Tachibana Keisuke , Obika Satoshi
Published: March 2021

Our group previously developed a series of bridged nucleic acids (BNAs), including locked nucleic acids (LNAs), amido-bridged nucleic acids (AmNAs), and guanidine-bridged nucleic acids (GuNAs), to impart specific characteristics to oligonucleotides such as high-affinity binding and enhanced enzymatic resistance. In this study, we designed a series of LNA-, AmNA-, and GuNA-modified splice-switching oligonucleotides (SSOs) with different lengths and content modifications. We measured the melting temperature (Tm) of each designed SSO to investigate its binding affinity for RNA strands. We also investigated whether the single-stranded SSOs formed secondary structures using UV melting analysis without complementary RNA. As a result, the AmNA-modified SSOs showed almost the same Tm values as the LNA-modified SSOs, with decreased secondary structure formation in the former. In contrast, the GuNA-modified SSOs showed slightly lower Tm values than the LNA-modified SSOs, with no inhibition of secondary structures. We also evaluated the exon skipping activities of the BNAs in vitro at both the mRNA and protein expression levels. We found that both AmNA-modified SSOs and GuNA-modified SSOs showed higher exon skipping activities than LNA-modified SSOs but each class must be appropriately designed in terms of length and modification content.
ABCG2 Is Overexpressed on Red Blood Cells in Ph-Negative Myeloproliferative Neoplasms and Potentiates Ruxolitinib-Induced Apoptosis
Authors: Buks Ralfs , Brusson Mégane , Cochet Sylvie , Galochkina Tatiana , Cassinat Bruno , Nemazanyy Ivan , Peyrard Thierry , Kiladjian Jean-Jacques , de Brevern Alexandre G. , Azouzi Slim , El Nemer Wassim
Published: March 2021

Myeloproliferative neoplasms (MPNs) are a group of disorders characterized by clonal expansion of abnormal hematopoietic stem cells leading to hyperproliferation of one or more myeloid lineages. The main complications in MPNs are high risk of thrombosis and progression to myelofibrosis and leukemia. MPN patients with high risk scores are treated by hydroxyurea (HU), interferon-α, or ruxolitinib, a tyrosine kinase inhibitor. Polycythemia vera (PV) is an MPN characterized by overproduction of red blood cells (RBCs). ABCG2 is a member of the ATP-binding cassette superfamily transporters known to play a crucial role in multidrug resistance development. Proteome analysis showed higher ABCG2 levels in PV RBCs compared to RBCs from healthy controls and an additional increase of these levels in PV patients treated with HU, suggesting that ABCG2 might play a role in multidrug resistance in MPNs. In this work, we explored the role of ABCG2 in the transport of ruxolitinib and HU using human cell lines, RBCs, and in vitro differentiated erythroid progenitors. Using stopped-flow analysis, we showed that HU is not a substrate for ABCG2. Using transfected K562 cells expressing three different levels of recombinant ABCG2, MPN RBCs, and cultured erythroblasts, we showed that ABCG2 potentiates ruxolitinib-induced cytotoxicity that was blocked by the ABCG2-specific inhibitor KO143 suggesting ruxolitinib intracellular import by ABCG2. In silico modeling analysis identified possible ruxolitinib-binding site locations within the cavities of ABCG2. Our study opens new perspectives in ruxolitinib efficacy research targeting cell types depending on ABCG2 expression and polymorphisms among patients.
Biological Evaluation and Transcriptomic Analysis of Corylin as an Inhibitor of Osteoclast Differentiation
Authors: Yu Anna Xiao-Dan , Xiao Jian , Zhao Shi-Zheng , Kong Xiang-Peng , Kwan Kenneth Kin-Leung , Zheng Brody Zhong-Yu , Wu Kevin Qi-Yun , Dong Tina Ting-Xia , Tsim Karl Wah-Keung
Published: March 2021

Corylin, a flavonoid isolated from the fruit of Psoralea corylifolia, has an osteogenic effect on osteoblasts in vitro and bone micromass ex vivo. However, the effect and mechanism of corylin in regulating osteoclastogenesis remain unknown. By using murine bone marrow macrophages as the osteoclast precursor, corylin was found to inhibit the receptor activator of nuclear factor (NF) κB ligand (RANKL)-induced osteoclast differentiation via down-regulating osteoclastic marker genes. In parallel, F-actin formation and osteoclast migration were diminished in corylin-treated cultured osteoclasts, and subsequently the expressions of osteoclastic proteins were suppressed: the suppression of protein expression was further illustrated by transcriptomic analysis. Furthermore, corylin inhibited the nuclear translocation of p65, giving rise to a restraint in osteoclastic differentiation through the attenuation of transcription factors nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor of activated T cells c1 (NFATc1). There was no obvious change in apoptosis when the RANKL-induce osteoclasts were cultured in the presence of corylin. The finding supports the potential development of corylin as an osteoclast inhibitor against osteoporosis.
Detecting Bacterial Cell Viability in Few µL Solutions from Impedance Measurements on Silicon-Based Biochips
Authors: Bhat Vinayak J. , Vegesna Sahitya V. , Kiani Mahdi , Zhao Xianyue , Blaschke Daniel , Du Nan , Vogel Manja , Kluge Sindy , Raff Johannes , Hübner Uwe , Skorupa Ilona , Rebohle Lars , Schmidt Heidemarie
Published: March 2021

Using two different types of impedance biochips (PS5 and BS5) with ring top electrodes, a distinct change of measured impedance has been detected after adding 1–5 µL (with dead or live Gram-positive Lysinibacillus sphaericus JG-A12 cells to 20 µL DI water inside the ring top electrode. We relate observed change of measured impedance to change of membrane potential of L. sphaericus JG-A12 cells. In contrast to impedance measurements, optical density (OD) measurements cannot be used to distinguish between dead and live cells. Dead L. sphaericus JG-A12 cells have been obtained by adding 0.02 mg/mL of the antibiotics tetracycline and 0.1 mg/mL chloramphenicol to a batch with OD0.5 and by incubation for 24 h, 30 °C, 120 rpm in the dark. For impedance measurements, we have used batches with a cell density of 25.5 × 108 cells/mL (OD8.5) and 270.0 × 108 cells/mL (OD90.0). The impedance biochip PS5 can be used to detect the more resistive and less capacitive live L. sphaericus JG-A12 cells. Also, the impedance biochip BS5 can be used to detect the less resistive and more capacitive dead L. sphaericus JG-A12 cells. An outlook on the application of the impedance biochips for high-throughput drug screening, e.g., against multi-drug-resistant Gram-positive bacteria, is given.
Bioactivities of Pseudocereal Fractionated Seed Proteins and Derived Peptides Relevant for Maintaining Human Well-Being
Authors: Capraro Jessica , Benedetti Stefano , Heinzl Giuditta , Scarafoni Alessio , Magni Chiara
Published: March 2021

Food proteins and peptides are able to exert a variety of well-known bioactivities, some of which are related to well-being and disease prevention in humans and animals. Currently, an active trend in research focuses on chronic inflammation and oxidative stress, delineating their major pathogenetic role in age-related diseases and in some forms of cancer. The present study aims to investigate the potential effects of pseudocereal proteins and their derived peptides on chronic inflammation and oxidative stress. After purification and attribution to protein classes according to classic Osborne’s classification, the immune-modulating, antioxidant, and trypsin inhibitor activities of proteins from quinoa (Chenopodium quinoa Willd.), amaranth (Amaranthus retroflexus L.), and buckwheat (Fagopyrum esculentum Moench) seeds have been assessed in vitro. The peptides generated by simulated gastro-intestinal digestion of each fraction have been also investigated for the selected bioactivities. None of the proteins or peptides elicited inflammation in Caco-2 cells; furthermore, all protein fractions showed different degrees of protection of cells from IL-1β-induced inflammation. Immune-modulating and antioxidant activities were, in general, higher for the albumin fraction. Overall, seed proteins can express these bioactivities mainly after hydrolysis. On the contrary, higher trypsin inhibitor activity was expressed by globulins in their intact form. These findings lay the foundations for the exploitation of these pseudocereal seeds as source of anti-inflammatory molecules.
Distinct Age-Specific miRegulome Profiling of Isolated Small and Large Intestinal Epithelial Cells in Mice
Authors: Lee Juneyoung , Mohsen Attayeb , Banerjee Anik , McCullough Louise D. , Mizuguchi Kenji , Shimaoka Motomu , Kiyono Hiroshi , Park Eun Jeong
Published: March 2021

The intestinal epithelium serves as a dynamic barrier to protect the host tissue from exposure to a myriad of inflammatory stimuli in the luminal environment. Intestinal epithelial cells (IECs) encompass differentiated and specialized cell types that are equipped with regulatory genes, which allow for sensing of the luminal environment. Potential inflammatory cues can instruct IECs to undergo a diverse set of phenotypic alterations. Aging is a primary risk factor for a variety of diseases; it is now well-documented that aging itself reduces the barrier function and turnover of the intestinal epithelium, resulting in pathogen translocation and immune priming with increased systemic inflammation. In this study, we aimed to provide an effective epigenetic and regulatory outlook that examines age-associated alterations in the intestines through the profiling of microRNAs (miRNAs) on isolated mouse IECs. Our microarray analysis revealed that with aging, there is dysregulation of distinct clusters of miRNAs that was present to a greater degree in small IECs (22 miRNAs) compared to large IECs (three miRNAs). Further, miRNA–mRNA interaction network and pathway analyses indicated that aging differentially regulates key pathways between small IECs (e.g., toll-like receptor-related cascades) and large IECs (e.g., cell cycle, Notch signaling and small ubiquitin-related modifier pathway). Taken together, current findings suggest novel gene regulation pathways by epithelial miRNAs in aging within the gastrointestinal tissues.
Advances and Perspectives in Dental Pulp Stem Cell Based Neuroregeneration Therapies
Authors: Luzuriaga Jon , Polo Yurena , Pastor-Alonso Oier , Pardo-Rodríguez Beatriz , Larrañaga Aitor , Unda Fernando , Sarasua Jose-Ramon , Pineda Jose Ramon , Ibarretxe Gaskon
Published: March 2021

Human dental pulp stem cells (hDPSCs) are some of the most promising stem cell types for regenerative therapies given their ability to grow in the absence of serum and their realistic possibility to be used in autologous grafts. In this review, we describe the particular advantages of hDPSCs for neuroregenerative cell therapies. We thoroughly discuss the knowledge about their embryonic origin and characteristics of their postnatal niche, as well as the current status of cell culture protocols to maximize their multilineage differentiation potential, highlighting some common issues when assessing neuronal differentiation fates of hDPSCs. We also review the recent progress on neuroprotective and immunomodulatory capacity of hDPSCs and their secreted extracellular vesicles, as well as their combination with scaffold materials to improve their functional integration on the injured central nervous system (CNS) and peripheral nervous system (PNS). Finally, we offer some perspectives on the current and possible future applications of hDPSCs in neuroregenerative cell therapies.
Flies Do Not Jump to Conclusions: Estimation of the Minimum Post-Mortem Interval for a Partly Skeletonized Body Based on Larvae of Phormia regina (Diptera: Calliphoridae)
Authors: Niederegger Senta , Mall Gita
Published: March 2021

Skeletonization is often perceived as an indicator of long post-mortem intervals. The finding of feeding larvae of first colonizers, on the other hand, indicates days. We present a case in which both findings were present. Larvae of Phormia regina, aged 9 days, and skeletonization of the head and part of the thorax were both found on an unidentified female body. Identification of dentures eventually led to resolution of the case and a confession, which settled the seeming contradiction in favor of forensic entomology.
Rationale, Design, and Feasibility of a Prospective Multicenter Registry Study of Anthracycline-Induced Cardiotoxicity (AIC Registry)
Authors: Inoue Keiko , Iida Noriko , Tajiri Kazuko , Bando Hiroko , Chiba Shigeru , Tasaka Nobutaka , Nagashio Kenji , Sasamura Rumi , Naito Hiroyuki , Murata Momoko , Li Siqi , Ishizu Tomoko , Nakazawa Yoko , Sekine Ikuo , Ieda Masaki
Published: March 2021

As the number of cancer survivors increases, cardiac management in anthracycline-treated patients has become more important. We planned to conduct a prospective multicenter registry study for comprehensive echocardiographic and biomarker data collection and an evaluation of the current practice in terms of diagnosis and management of anthracycline-induced cardiotoxicity (AIC registry). To examine the feasibility of this registry study, we analyzed the 1-year follow-up data of 97 patients registered during the first year of this registry. The AIC registry was launched in July 2016. Data on echocardiographic parameters (e.g., two-and three-dimensional [(2- and 3-D) left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS)) and biomarkers (e.g., troponin T and brain natriuretic peptide) were collected before anthracycline treatment, every 3 months during the first year after starting anthracycline, and every 6 months during the second year. Eighty-three patients (86%) completed a 1-year follow-up. The measurable rates of 2D LVEF, 3D LVEF, and GLS on each visit were nearly optimal (100%, 86–93%, and 84–94%, respectively). During the 1-year follow-up, 5 patients (6.0%) developed cardiotoxicity (a reduction in LVEF ≥ 10 percentage points from baseline and <55%). The AIC registry study is feasible and will be the first study to collect sizable echocardiographic and biomarker data on cardiotoxicity in Japanese patients treated with anthracycline in a real-world setting.
Physicochemical Properties of Lipoproteins Assessed by Nuclear Magnetic Resonance as a Predictor of Premature Cardiovascular Disease. PRESARV-SEA Study
Authors: Fernández-Cidón Bárbara , Candás-Estébanez Beatriz , Gil-Serret Miriam , Amigó Núria , Corbella Emili , Rodríguez-Sánchez M. Ángeles , Padró-Miquel Ariadna , Brotons Carlos , Hernández-Mijares Antonio , Calmarza Pilar , Jarauta Estibaliz , Brea Angel J. , Mauri Marta , Guijarro Carlos , Vila Àlex , Valdivielso Pedro , Corbella Xavier , Pintó Xavier
Published: March 2021

Some lipoprotein disorders related to the residual risk of premature cardiovascular disease (PCVD) are not detected by the conventional lipid profile. In this case-control study, the predictive power of PCVD of serum sdLDL-C, measured using a lipoprotein precipitation method, and of the physicochemical properties of serum lipoproteins, analyzed by nuclear magnetic resonance (NMR) techniques, were evaluated. We studied a group of patients with a first PCVD event (n = 125) and a group of control subjects (n = 190). Conventional lipid profile, the size and number of Very Low Density Lipoproteins (VLDL), Low Density Lipoproteins (LDL), High Density Lipoproteins (HDL) particles, and the number of particles of their subclasses (large, medium, and small) were measured. Compared to controls, PCVD patients had lower concentrations of all LDL particles, and smaller and larger diameter of LDL and HDL particles, respectively. PCVD patients also showed higher concentrations of small dense LDL-cholesterol (sdLDL), and triglycerides (Tg) in LDL and HDL particles (HDL-Tg), and higher concentrations of large VLDL particles. Multivariate logistic regression showed that sdLDL-C, HDL-Tg, and large concentrations of LDL particles were the most powerful predictors of PCVD. A strong relationship was observed between increased HDL-Tg concentrations and PCVD. This study demonstrates that beyond the conventional lipid profile, PCVD patients have other atherogenic lipoprotein alterations that are detected by magnetic resonance imaging (MRI) analysis.
Development of a Digital Research Assistant for the Management of Patients’ Enrollment in Oncology Clinical Trials within a Research Hospital
Authors: Cesario Alfredo , Simone Irene , Paris Ida , Boldrini Luca , Orlandi Armando , Franceschini Gianluca , Lococo Filippo , Bria Emilio , Magno Stefano , Mulè Antonino , Santoro Angela , Damiani Andrea , Bianchi Daniele , Picchi Daniele , Rasi Guido , Daniele Gennaro , Fabi Alessandra , Sergi Paolo , Tortora Giampaolo , Masetti Riccardo , Valentini Vincenzo , D’Oria Marika , Scambia Giovanni
Published: March 2021

Clinical trials in cancer treatment are imperative in enhancing patients’ survival and quality of life outcomes. The lack of communication among professionals may produce a non-optimization of patients’ accrual in clinical trials. We developed a specific platform, called “Digital Research Assistant” (DRA), to report real-time every available clinical trial and support clinician. Healthcare professionals involved in breast cancer working group agreed nine minimal fields of interest to preliminarily classify the characteristics of patients’ records (including omic data, such as genomic mutations). A progressive web app (PWA) was developed to implement a cross-platform software that was scalable on several electronic devices to share the patients’ records and clinical trials. A specialist is able to use and populate the platform. An AI algorithm helps in the matchmaking between patient’s data and clinical trial’s inclusion criteria to personalize patient enrollment. At the same time, an easy configuration allows the application of the DRA in different oncology working groups (from breast cancer to lung cancer). The DRA might represent a valid research tool supporting clinicians and scientists, in order to optimize the enrollment of patients in clinical trials. User Experience and Technology The acceptance of participants using the DRA is topic of a future analysis.
Germline Mutations in Other Homologous Recombination Repair-Related Genes Than BRCA1/2: Predictive or Prognostic Factors?
Authors: Cortesi Laura , Piombino Claudia , Toss Angela
Published: March 2021

The homologous recombination repair (HRR) pathway repairs double-strand DNA breaks, mostly by BRCA1 and BRCA2, although other proteins such as ATM, CHEK2, and PALB2 are also involved. BRCA1/2 germline mutations are targeted by PARP inhibitors. The aim of this commentary is to explore whether germline mutations in HRR-related genes other than BRCA1/2 have to be considered as prognostic factors or predictive to therapies by discussing the results of two articles published in December 2020. The TBCRC 048 trial published by Tung et al. showed an impressive objective response rate to olaparib in metastatic breast cancer patients with germline PALB2 mutation compared to germline ATM and CHEK2 mutation carriers. Additionally, Yadav et al. observed a significantly longer overall survival in pancreatic adenocarcinoma patients with germline HRR mutations compared to non-carriers. In our opinion, assuming that PALB2 is a high-penetrant gene with a key role in the HRR system, PALB2 mutations are predictive factors for response to treatment. Moreover, germline mutations in the ATM gene provide a better outcome in pancreatic adenocarcinoma, being more often associated to wild-type KRAS. In conclusion, sequencing of HRR-related genes other than BRCA1/2 should be routinely offered as part of a biological characterization of pancreatic and breast cancers.
QoS Enabled Heterogeneous BLE Mesh Networks
Authors: Basu Subho Shankar , Baert Mathias , Hoebeke Jeroen
Published: March 2021

Bluetooth Low Energy (BLE) is a widely known short-range wireless technology used for various Internet of Things (IoT) applications. Recently, with the introduction of BLE mesh networks, this short-range barrier of BLE has been overcome. However, the added advantage of an extended range can come at the cost of a lower performance of these networks in terms of latency, throughput and reliability, as the core operation of BLE mesh is based on advertising and packet flooding. Hence, efficient management of the system is required to achieve a good performance of these networks and a smoother functioning in dense scenarios. As the number of configuration points in a standard mesh network is limited, this paper describes a novel set of standard compliant Quality of Service (QoS) extensions for BLE mesh networks. The resulting QoS features enable better traffic management in the mesh network, providing sufficient redundancy to achieve reliability whilst avoiding unnecessary packet flooding to reduce collisions, as well as the prioritization of certain traffic flows and the ability to control end-to-end latencies. The QoS-based system has been implemented and validated in a small-scale BLE mesh network and compared against a setup without any QoS support. The assessment in a small-scale test setup confirms that applying our QoS features can enhance these types of non-scheduled and random access networks in a significant way.
The Role and Importance of a Footbridge Suspended over a Highway in the Opinion of Its Users—Trabzon (Turkey)
Authors: Hełdak Maria , Kurt Konakoglu Sultan Sevinc , Kurdoglu Banu Cicek , Goksal Hande , Przybyła Bogdan , Kazak Jan K.
Published: March 2021

In the urban landscape, footbridges appeared along with the development of urbanization through the implementation of more complex spatial structures. The introduction of transport transit to cities or sometimes urban gravity towards the important communication routes imposed their construction in order to ensure pedestrians’ safety and smooth flow of traffic. The aim of the study is to determine how an overpass in the city of Trabzon is used by people of different ages, the security and motivation problem, the possibility of a footbridge, and how an overpass is perceived as a crossing over a highway. The study addresses the problem of safety and motivation related to the use of an overpass by people of different ages and is focused on the perception of an overpass as a crossing over a highway. The overpass connects the northern part of the city with the parking lot and the seaside boulevards in Trabzon. It has been constructed over the road no. D010, also known as the Black Sea Coastal Highway. In total, 124 members of the urban population who used the overpass participated in a questionnaire, which included multiple-choice and open-ended questions. The ‘Semantic Differential Scale’ was also used to evaluate the results. The research revealed that the respondents who chose the road through the overpass for safety in most cases used it relatively rarely (59%). People who used the footbridge every day or frequently marked safety as the reason in 39% of cases only. This means that as pedestrians use the overpass more often, they begin to notice other functional features of the footbridge. The results of the study showed that the overpass was most frequently used for the purpose of going down to the coast (76.0%), although 51.2% reported rarely using the overpass, which showed it was used very little by pedestrians.
Growth and Antifungal Resistance of the Pathogenic Yeast, Candida Albicans, in the Microgravity Environment of the International Space Station: An Aggregate of Multiple Flight Experiences
Authors: Nielsen Sheila , White Kenna , Preiss Kyle , Peart Dakota , Gianoulias Kathryn , Juel Rachel , Sutton James , McKinney James , Bender Jaclyn , Pinc Gabrielle , Bergren Kela , Gans Wendy , Kelley Jessica , McQuaid Millard
Published: March 2021

This report was designed to compare spaceflight-induced cellular and physiological adaptations of Candida albicans cultured in microgravity on the International Space Station across several payloads. C. albicans is a common opportunistic fungal pathogen responsible for a variety of superficial infections as well as systemic and more severe infections in humans. Cumulatively, the propensity of this organism to be widespread through the population, the ability to produce disease in immunocompromised individuals, and the tendency to respond to environmental stress with characteristics associated with increased virulence, require a better understanding of the yeast response to microgravity for spaceflight crew safety. As such, the responses of this yeast cultivated during several missions using two in-flight culture bioreactors were analyzed and compared herein. In general, C. albicans had a slightly shorter generation time and higher growth propensity in microgravity as compared to terrestrial controls. Rates of cell filamentation differed between bioreactors, but were low and not significantly different between flight and terrestrial controls. Viable cells were retrieved and cultured, resulting in a colony morphology that was similar between cells cultivated in flight and in terrestrial control conditions, and in contrast to that previously observed in a ground-based microgravity analog system. Of importance, yeast demonstrated an increased resistance when challenged during spaceflight with the antifungal agent, amphotericin B. Similar levels of resistance were not observed when challenged with the functionally disparate antifungal drug caspofungin. In aggregate, yeast cells cultivated in microgravity demonstrated a subset of characteristics associated with virulence. In addition, and beyond the value of the specific responses of C. albicans to microgravity, this report includes an analysis of biological reproducibility across flight opportunities, compares two spaceflight hardware systems, and includes a summary of general flight and payload timelines.
Effect of Various Types of Muscle Contraction with Different Running Conditions on Mouse Humerus Morphology
Authors: Ozone Kaichi , Oka Yuichiro , Minegishi Yuki , Kano Takuma , Kokubun Takanori , Murata Kenji , Kanemura Naohiko
Published: March 2021

How various types of muscle contraction during exercises affect bone formation remains unclear. This study aimed to determine how exercises with different muscle contraction types affect bone morphology. In total, 20 mice were used and divided into four groups: Control, Level, Down Slow, and Down. Different types of muscle contraction were induced by changing the running angle of the treadmill. After the intervention, micro-computed tomography (Micro-CT), tartrate-resistant acid phosphatase/alkaline phosphatase (ALP) staining, and immunohistochemical staining were used to analyze the humerus head, tendon-to-bone attachment, and humerus diaphyseal region. Micro-CT found that the volume ratio of the humeral head, the volume of the tendon-to-bone attachment region, and the area of the humeral diaphyseal region increased in the Down group. However, no difference was detected in bone morphology between the Level and Down Slow groups. In addition, histology showed activation of ALP in the subarticular subchondral region in the Down Slow and Down groups and the fibrocartilage region in the tendon-to-bone attachment. Moreover, Osterix increased predominantly in the Down Slow and Down groups.Overall bone morphological changes in the humerus occur only when overuse is added to EC-dominant activity. Furthermore, different type of muscle contractile activities might promote bone formation in a site-specific manner.
Rice Transcriptome Analysis Reveals Nitrogen Starvation Modulates Differential Alternative Splicing and Transcript Usage in Various Metabolism-Related Genes
Authors: Chaudhary Saurabh , Kalkal Meenu
Published: March 2021

Nitrogen (N) is crucial for plant growth and development; however, excessive use of N fertilizers cause many problems including environmental damage, degradation of soil fertility, and high cost to the farmers. Therefore, immediate implementation is required to develop N efficient crop varieties. Rice being low nitrogen use efficiency (NUE) and a high demand staple food across the world has become a favorite crop to study the NUE trait. In the current study, we used the publicly available transcriptome data generated from the root and shoot tissues of two rice genotypes IR-64 and Nagina-22 (N-22) under optimum N supply (N+) and chronic N-starvation (N−). A stringent pipeline was applied to detect differentially expressed genes (DEGs), alternatively spliced (DAS) genes, differentially expressed transcripts (DETs) and differential transcript usage (DTU) transcripts in both the varieties and tissues under N+ and N− conditions. The DAS genes and DTU transcripts identified in the study were found to be involved in several metabolic and biosynthesis processes. We suggest alternative splicing (AS) plays an important role in fine-tuning the regulation of metabolic pathways related genes in genotype, tissue, and condition-dependent manner. The current study will help in understanding the transcriptional dynamics of NUE traits in the future.
Improvement of Platelet Respiration by Cell–Permeable Succinate in Diabetic Patients Treated with Statins
Authors: Avram Vlad Florian , Bîna Anca Mihaela , Sima Alexandra , Aburel Oana Maria , Sturza Adrian , Burlacu Ovidiu , Timar Romulus Zorin , Muntean Danina Mirela , Elmér Eskil , Crețu Octavian Marius
Published: March 2021

Diabetes mellitus (DM) is the most severe metabolic disease that reached the level of a global pandemic and is associated with high cardiovascular morbidity. Statins are the first–line lipid–lowering therapy in diabetic patients with or without a history of atherosclerotic disease. Although well tolerated, chronic treatment may result in side effects that lead to treatment interruption. Mitochondrial dysfunction has emerged as a central pathomechanism in DM– and statin–induced side effects. Assessment of mitochondrial respiration in peripheral platelets has been increasingly used as a mirror of organ mitochondrial dysfunction. The present study aimed to assess the: (i) changes in mitochondrial respiration elicited by statins in patients with type 2 DM and (ii) the effects of cell–permeable succinate (NV118) on respiratory parameters in platelets harvested from these patients. No significant changes were found in global mitochondrial respiration of intact platelets isolated from diabetic patients treated with either atorvastatin or rosuvastatin. Similarly, no significant changes in mitochondrial respiration of permeabilized platelets were found between diabetic patients treated with atorvastatin and healthy controls. Acute ex vivo administration of NV118 significantly improved respiration in isolated platelets. These results prompt further research on the role of permeable succinate as a therapeutic alternative for improving mitochondrial function in metabolic pathologies and point to the role of peripheral platelets as a potential biomarker of treatment response.
Priming by High Temperature Stress Induces MicroRNA Regulated Heat Shock Modules Indicating Their Involvement in Thermopriming Response in Rice
Authors: Kushawaha Akhilesh Kumar , Khan Ambreen , Sopory Sudhir Kumar , Sanan-Mishra Neeti
Published: March 2021

Rice plants often encounter high temperature stress, but the associated coping strategies are poorly understood. It is known that a prior shorter exposure to high temperature, called thermo-priming, generally results in better adaptation of the plants to subsequent exposure to high temperature stress. High throughput sequencing of transcript and small RNA libraries of rice seedlings primed with short exposure to high temperature followed by high temperature stress and from plants exposed to high temperature without priming was performed. This identified a number of transcripts and microRNAs (miRs) that are induced or down regulated. Among them osa-miR531b, osa-miR5149, osa-miR168a-5p, osa-miR1846d-5p, osa-miR5077, osa-miR156b-3p, osa-miR167e-3p and their respective targets, coding for heat shock activators and repressors, showed differential expression between primed and non-primed plants. These findings were further validated by qRT-PCR. The results indicate that the miR-regulated heat shock proteins (HSPs)/heat shock transcription factors (HSFs) may serve as important regulatory nodes which are induced during thermo-priming for plant survival and development under high temperatures.
Green Microwave-Assisted Synthesis of CoFeRu-Based Electrocatalyst for the Oxygen Reduction Reaction
Authors: Sandoval Antonia , Borja Edgar , Magallón Lorena , Su Javier
Published: March 2021

A simple and rapid synthesis of a CoFeRu-based electrocatalyst by a microwave-assisted method (using water as the microwave absorbing solvent) is reported in this work. Agglomerates with different sizes and shapes are observed by scanning electron microscopy technique. The energy dispersive X-ray spectroscopy shows a low atomic percentage of Co and similar atomic percentage of Fe and Ru. However, the X-ray diffraction exhibits only the presence of metallic Ru and Fe2O3 (hematite) phases. The oxygen reduction without and with 2 mol L−1 methanol is studied using the rotating disk electrode technique. The electrochemical kinetic parameters obtained are compared to a similar electrocatalyst reported in the literature, which was synthesized using a mixture of an organic solvent with DI water as the microwave absorbing solvent. An improvement on the activity of the electrocatalyst synthesized is observed, where high Tafel slopes are not observed. The electrocatalyst also showed tolerance to the presence of methanol during the oxygen reduction reaction.
The Influence of Irrigation during the Finishing and Polishing of Composite Resin Restorations—A Systematic Review of In Vitro Studies
Authors: Silva João Paulo , Coelho Ana , Paula Anabela , Amaro Inês , Saraiva José , Ferreira Manuel Marques , Marto Carlos Miguel , Carrilho Eunice
Published: March 2021

The surface smoothness of composite restorations affects not only their esthetic appearance but also other properties. Thus, rough surfaces can lead to staining, plaque accumulation, gingival irritation, recurrent caries, abrasiveness, wear kinetics, and tactile perception by the patient. The aim of this study was to evaluate the influence of irrigation during the finishing and polishing of composite resin restorations. A systematic search of the PubMed, Cochrane Library, EMBASE, Web of Science, and Clinical Trials databases was conducted. Papers published up to 11 February 2021 were considered. The quality of each study was assessed using the modified Consolidated Standards of Reporting Trials checklist for reporting in vitro studies on dental materials. No clinical studies were identified. Six in vitro studies were included, reporting changes in physical and esthetic properties. After performing a methodological quality assessment of the studies, some limitations were identified, the main limitation being the heterogeneous methodology across studies. The evidence resulting from this systematic review did not favor either wet or dry finishing/polishing procedures. There is a clear need for well-designed studies focusing on the comparison of dry/wet finishing/polishing with standard protocols to evaluate the differences among different materials and methods.
Comparison of Flux-Switching and Interior Permanent Magnet Synchronous Generators for Direct-Driven Wind Applications Based on Nelder–Mead Optimal Designing
Authors: Prakht Vladimir , Dmitrievskii Vladimir , Kazakbaev Vadim , Andriushchenko Ekaterina
Published: March 2021

The permanent magnet flux-switching machine (PMFSM) is one of the most promising machines with magnets inserted into the stator. To determine in which applications the use of PMFSM is promising, it is essential to compare the PMFSM with machines of other types. This study provides a theoretical comparison of the PMFSM with a conventional interior permanent magnet synchronous machine (IPMSM) in the gearless generator of a low-power wind turbine (332 rpm, 51.4 Nm). To provide a fair comparison, both machines are optimized using the Nelder–Mead algorithm. The minimized optimization objectives are the required power of frequency converter, cost of active materials, torque ripple and losses of a generator averaged over the working profile of the wind turbine. In order to reduce the computational time, the substituting profile method is applied. Based on the results of the calculations, the advantages and disadvantages of the considered machines were revealed: the IPMSM has significantly lower losses and higher efficiency than the PMFSM, and the PMFSM requires much less rare-earth magnets and copper and is, therefore, cheaper in mass production.
Characterization of a New Biofunctional, Exolytic Alginate Lyase from Tamlana sp. s12 with High Catalytic Activity and Cold-Adapted Features
Authors: Yin Rui , Yi Yan-Jun , Chen Zhuo , Wang Bao-Xun , Li Xue-Han , Zhou Yan-Xia
Published: March 2021

Alginate, a major acidic polysaccharide in brown algae, has attracted great attention as a promising carbon source for biorefinery systems. Alginate lyases, especially exo-type alginate lyase, play a critical role in the biorefinery process. Although a large number of alginate lyases have been characterized, few can efficiently degrade alginate comprised of mannuronate (M) and guluronate (G) at low temperatures by means of an exolytic mode. In this study, the gene of a new exo-alginate lyase—Alys1—with high activity (1350 U/mg) was cloned from a marine strain, Tamlana sp. s12. When sodium alginate was used as a substrate, the recombinant enzyme showed optimal activity at 35 °C and pH 7.0–8.0. Noticeably, recombinant Alys1 was unstable at temperatures above 30 °C and had a low melting temperature of 56.0 °C. SDS and EDTA significantly inhibit its activity. These data indicate that Alys1 is a cold-adapted enzyme. Moreover, the enzyme can depolymerize alginates polyM and polyG, and produce a monosaccharide as the minimal alginate oligosaccharide. Primary substrate preference tests and identification of the final oligosaccharide products demonstrated that Alys1 is a bifunctional alginate lyase and prefers M to G. These properties make Alys1 a valuable candidate in both basic research and industrial applications.
Microstructural Stability of Extruded Mg-Mn-Ce Hollow Profiles with Weld Seams
Authors: Gensch Felix , Gall Sven , Lechner Stefan , Fahrenson Christoph , Mueller Soeren
Published: March 2021

Despite aluminum profiles, magnesium profiles have not been well developed due to the low formability. Furthermore, extruded magnesium profiles show a strong dependence on the mechanical properties, according to the loading direction. This is caused by a strong basal texture, which is directly dependent on the process parameters during the extrusion and the subsequent aging. Thus, the present paper focuses on the analysis of the microstructure and its evolution of extruded magnesium hollow profiles, which were subjected to a series of heat treatments at 475 °C up to one hour. The hollow profiles were extruded through a porthole die, thus, containing longitudinal weld seams. These were formed by material that underwent heavy shearing along the tool surface based on the friction conditions in the porthole die. Three extrusion ratios (ER = 8:1, ER = 16:1, ER = 30:1) were applied, resulting in three different wall thicknesses of the profiles. The microstructure of the profiles was analyzed using light-optical microscopy (LOM) and scanning electron microscopy (SEM) coupled with electron backscatter diffraction (EBSD). The analysis revealed no change of the microstructure of the profiles extruded at the two higher extrusion ratios within the time frame of the heat treatment. In contrast, the microstructure and, thus, the micro-texture of the profile with the lowest extrusion ratio (ER = 8:1) has been affected to a great extent. While only small changes in microstructure in the weld-free area were observed, the initial microstructure in the weld seam was transformed from fine recrystallized grains into a significantly bimodal microstructure mainly due to an abnormal grain growth (AGG). These changes were accompanied by a promotion of the rare-earth (RE) texture component for the weld-free material and a change of the overall texture from RE to a typical non-RE double fiber texture for the weld seam due to the intense AGG within the short-time heat treatments. In addition, the influence of the extrusion ratio on particle size and distribution as well as the character of the microstructure governing the behavior during heat treatments was analyzed and discussed.
Application of Low Melting Metals for Separation of Uranium and Zirconium in a “Fused Chloride—Liquid Alloy” System
Authors: Volkovich Vladimir A. , Maltsev Dmitry S. , Soldatova Mariya N. , Ryzhov Aleksandr A. , Ivanov Aleksandr B.
Published: March 2021

Closeness of electrochemical properties of uranium and zirconium makes separation of these metals in pyroelectrochemical reprocessing of spent nuclear fuels a challenging task. Varying electrode material can change metals’ deposition potentials. The study was aimed at assessing the effect of the cathode material on deposition potentials of zirconium and uranium from 3LiCl–2KCl based melts. Solid (tungsten) and liquid (gallium, zinc, Ga–Zn, Ga–Sn and Ga–In alloy) working electrodes were tested at 532–637 °C. Galvanostatic cathodic polarization was employed and the applied cathodic current varied from 0.0001 to 1 A. Gallium–zinc eutectic alloy demonstrated the largest difference of zirconium and uranium deposition potentials. Zirconium/uranium separation factors were experimentally determined in a “molten salt—liquid metal” system for gallium and Ga–Zn eutectic based alloys.
Hydrogen-Assisted Fatigue Propagation in Corner Cracks at Holes Located in Plates under Tensile Loading
Authors: Toribio Jesús , González Beatriz , Matos Juan-Carlos
Published: March 2021

In this study, hydrogen-assisted fatigue propagation (a kind of corrosion fatigue phenomenon) in corner cracks at holes located in plates under tensile loading was studied, the results compared with those obtained for propagation by fatigue in air. To this end, numerical modeling was carried out for the case studied to evaluate the advance of the crack front based on the Paris equation and the stress intensity factors (SIFs) obtained by Raju and Newman. The results showed that the cracks tended toward a preferential propagation path in their growth, the effect of the presence of the stress concentrator on the preferential fatigue propagation path being more pronounced in the crack growth by fatigue in air than in the crack growth by corrosion fatigue.
Anisotropic Plasticity and Fracture of Three 6000-Series Aluminum Alloys
Authors: Thomesen Susanne , Hopperstad Odd Sture , Børvik Tore
Published: March 2021

The influence of microstructure on plasticity and fracture of three 6000-series aluminum alloys is studied with emphasis on the anisotropy caused by the extrusion process. Tension tests on smooth and notched specimens are performed in different directions with respect to the extrusion direction, where the stress and strain to fracture are based on local measurements inside the neck or notch. The microstructure of the alloys, i.e., grain structure, crystallographic texture and size distribution of constituent particles, is characterized and used to explain the experimental findings. The experiments show considerable differences in the directional variation of the yield stress, the plastic flow, the work hardening, and the failure strain between alloys exhibiting recrystallization texture and deformation texture. The alloys with recrystallized microstructure exhibited substantial anisotropic work hardening caused by texture evolution and a stronger notch sensitivity of the failure strain than the alloy with deformed, non-recrystallized microstructure. Comparisons are made with previous experiments on the same alloys in the cast and homogenized condition, and the effects of the microstructural changes caused by the extrusion process on the macroscopic response are discussed.
The Influence of Crystal Orientation on Subsurface Damage of Mono-Crystalline Silicon by Bound-Abrasive Grinding
Authors: Yang Wei , Li Yaguo
Published: March 2021

Subsurface damage (SSD) produced in a grinding process will affect the performance and operational duration of single-crystal silicon. In order to reduce the subsurface damage depth generated during the grinding process by adjusting the process parameters (added), experiments were designed to investigate the influence of machining factors on SSD. This included crystal orientation, diamond grit size in the grinding wheel, peripheral speed of the grinding wheel, and feeding with the intention to optimize the parameters affecting SSD. Compared with isotropic materials such as glass, we considered the impact of grinding along different crystal directions <100> and <110> on subsurface damage depth (added). The Magnetorheological Finishing (MRF) spot technique was used to detect the depth of SSD. The results showed that the depth of SSD in silicon increased with the size of diamond grit. SSD can be reduced by either increasing the peripheral speed of the grinding wheel or decreasing the feeding rate of the grinding wheel in the <100> crystal orientation, if the same size of diamond grit was employed. In addition, we proposed a modified model around surface roughness and subsurface crack depth, which considered plastic and brittle deformation mechanisms and material properties of different crystal orientations. When the surface roughness (RZ) exceeded the brittle-plastic transition’s critical value RZC (RZC<100> > 1.5 μm, RZC<110> > 0.8 μm), cracks appeared on the subsurface. The experimental results were consistent with the predicted model, which could be used to predict the subsurface cracks by measuring the surface roughness. However, the model only gives the approximate range of subsurface defects, such as dislocations. The morphology and precise depth of plastic deformation subsurface defects, such as dislocations generated in the fine grinding stage, needed to be inspected by transmission electron microscopy (TEM), which were further studied.
In Vitro Antioxidant Activity of Litsea martabanica Root Extract and Its Hepatoprotective Effect on Chlorpyrifos-Induced Toxicity in Rats
Authors: Kunnaja Phraepakaporn , Chansakaow Sunee , Wittayapraparat Absorn , Yusuk Pedcharada , Sireeratawong Seewaboon
Published: March 2021

In Thailand, people in the highland communities whose occupational exposure to pesticides used the root of Litsea martabanica as a detoxifying agent. However, the scientific data to support the traditional use of this plant are insufficient. This study aimed to evaluate the antioxidant activity and anti-pesticide potential of L. martabanica root extract. Antioxidant properties were investigated by 2,2′-diphenyl-1-picrylhydrazyl (DPPH) assay, superoxide radicals scavenging assay, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay, ferric reducing antioxidant power (FRAP), and total phenolic content determination. In all assays, L. martabanica extracts and their fractions exhibited high antioxidant activities differently. The water extract is traditionally used as a detoxifying agent. Therefore, it was chosen for in vivo experiments. The rats received the extract in a way that mimics the traditional methods of tribal communities followed by chlorpyrifos for 16 days. The results showed that acetylcholinesterase activity decreases in pesticide-exposed rats. Treatment with the extract caused increasing acetylcholinesterase activity in the rats. Therefore, L. martabanica extract may potentially be used as a detoxifying agent, especially for the chlorpyrifos pesticide. The antioxidant properties of L. martabanica may provide a beneficial effect by protecting liver cells from damage caused by free radicals. Histopathology results revealed no liver cell necrosis and showed the regeneration of liver cells in the treatment group. L. martabanica extract did not cause changes in behavior, liver weight, hematological and biochemical profiles of the rats.