bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross-Predicting Essential Genes between Two Model Eukaryotic Species Using Machine Learning
Authors: Campos Tulio L. , Korhonen Pasi K. , Young Neil D.
Published: May 2021

Experimental studies of Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular and cellular processes in metazoans at large. Since the publication of their genomes, functional genomic investigations have identified genes that are essential or non-essential for survival in each species. Recently, a range of features linked to gene essentiality have been inferred using a machine learning (ML)-based approach, allowing essentiality predictions within a species. Nevertheless, predictions between species are still elusive. Here, we undertake a comprehensive study using ML to discover and validate features of essential genes common to both C. elegans and D. melanogaster. We demonstrate that the cross-species prediction of gene essentiality is possible using a subset of features linked to nucleotide/protein sequences, protein orthology and subcellular localisation, single-cell RNA-seq, and histone methylation markers. Complementary analyses showed that essential genes are enriched for transcription and translation functions and are preferentially located away from heterochromatin regions of C. elegans and D. melanogaster chromosomes. The present work should enable the cross-prediction of essential genes between model and non-model metazoans.
Analysis of Circulating miRNA Profile in Plasma Samples of Glioblastoma Patients
Authors: Géczi Dóra , Nagy Bálint , Szilágyi Melinda , Penyige András , Klekner Álmos , Jenei Adrienn , Virga József , Birkó Zsuzsanna
Published: May 2021

(1) Background: Glioblastoma multiforme (GBM) is among the most aggressive cancers with a poor prognosis. Treatment options are limited, clinicians lack efficient prognostic and predictive markers. Circulating miRNAs—besides being important regulators of cancer development—may have potential as diagnostic biomarkers of GBM. (2) Methods: In this study, profiling of 798 human miRNAs was performed on blood plasma samples from 6 healthy individuals and 6 patients with GBM, using a NanoString nCounter Analysis System. To validate our results, five miRNAs (hsa-miR-433-3p, hsa-miR-362-3p, hsa-miR-195-5p, hsa-miR-133a-3p, and hsa-miR-29a-3p) were randomly chosen for RT-qPCR detection. (3) Results: In all, 53 miRNAs were significantly differentially expressed in plasma samples of GBM patients when data were filtered for FC 1 and FDR 0.1. Target genes of the top 39 differentially expressed miRNAs were identified, and we carried out functional annotation and pathway enrichment analysis of target genes via GO and KEGG-based tools. General and cortex-specific protein–protein interaction networks were constructed from the target genes of top miRNAs to assess their functional connections. (4) Conclusions: We demonstrated that plasma microRNA profiles are promising diagnostic and prognostic molecular biomarkers that may find an actual application in the clinical practice of GBM, although more studies are needed to validate our results.
MIT-001 Restores Human Placenta-Derived Mesenchymal Stem Cells by Enhancing Mitochondrial Quiescence and Cytoskeletal Organization
Authors: Yu Won Dong , Kim Yu Jin , Cho Min Jeong , Kim Gi Jin , Kim Soon Ha , Kim Myung Joo , Ko Jung Jae , Lee Jae Ho
Published: May 2021

Inflammation is a major cause of several chronic diseases and is reported to be recovered by the immuno-modulation of mesenchymal stem cells (MSCs). While most studies have focussed on the anti-inflammatory roles of MSCs in stem cell therapy, the impaired features of MSCs, such as the loss of homeostasis by systemic aging or pathologic conditions, remain incompletely understood. In this study, we investigated whether the altered phenotypes of human placenta-derived MSCs (hPD-MSCs) exposed to inflammatory cytokines, including TNF-α and IFN-γ, could be protected by MIT-001, a small anti-inflammatory and anti-necrotic molecule. MIT-001 promoted the spindle-like shape and cytoskeletal organization extending across the long cell axis, whereas hPD-MSCs exposed to TNF-α/IFN-γ exhibited increased morphological heterogeneity with an abnormal cell shape and cytoskeletal disorganization. Importantly, MIT-001 improved mitochondrial distribution across the cytoplasm. MIT-001 significantly reduced basal respiration, ATP production, and cellular ROS levels and augmented the spare respiratory capacity compared to TNF-α/IFN-γ-exposed hPD-MSCs, indicating enhanced mitochondrial quiescence and homeostasis. In conclusion, while TNF-α/IFN-γ-exposed MSCs lost homeostasis and mitochondrial quiescence by becoming over-activated in response to inflammatory cytokines, MIT-001 was able to rescue mitochondrial features and cellular phenotypes. Therefore, MIT-001 has therapeutic potential for clinical applications to treat mitochondrion-related inflammatory diseases.
Diclofenac N-Derivatives as Therapeutic Agents with Anti-Inflammatory and Anti-Cancer Effect
Authors: Galisteo Alberto , Jannus Fatin , García-García Amalia , Aheget Houssam , Rojas Sara , Lupiañez José A. , Rodríguez-Diéguez Antonio , Reyes-Zurita Fernando J. , Quílez del Moral José F.
Published: May 2021

A series of diclofenac N-derivatives (2, 4, 6, 8c, 9c, 10a-c) were synthesized in order to test their anti-cancer and anti-inflammatory effects. The anticarcinogen activity has been assayed against three cancer cell lines: HT29, human colon cancer cells; Hep-G2, human hepatic cells; and B16-F10, murine melanoma cells. First, we determined the cytotoxicity of the different compounds, finding that the most effective compound was compound 8c against all cell lines and both compounds 4 and 6 in human Hep-G2 and HT29 cell lines. Compounds 4 and 8c were selected for the percentage of apoptosis determination, cell cycle distribution, and mitochondrial membrane potential measure because these products presented the lowest IC50 values in two of the three cancer cell lines assayed (B16-F10 and HepG2), and were two of the three products with lowest IC50 in HT29 cell line. Moreover, the percentages of apoptosis induction were determined for compounds 4 and 8c, showing that the highest values were between 30 to 60%. Next, the effects of these two compounds were observed on the cellular cycle, resulting in an increase in the cell population in G2/M cell cycle phase after treatment with product 8c, whereas compound 4 increased the cells in phase G0/G1, by possible differentiation process induction. Finally, to determine the possible apoptosis mechanism triggered by these compounds, mitochondrial potential was evaluated, indicating the possible activation of extrinsic apoptotic mechanism. On the other hand, we studied the anti-inflammatory effects of these diclofenac (DCF) derivatives on lipopolysaccharide (LPS) activated RAW 264.7 macrophages-monocytes murine cells by inhibition of nitric oxide (NO) production. As a first step, we determined the cytotoxicity of the synthesized compounds, as well as DCF, against these cells. Then, sub-cytotoxic concentrations were used to determine NO release at different incubation times. The greatest anti-inflammatory effect was observed for products 2, 4, 8c, 10a, 10b, and 9c at 20 µg·mL−1 concentration after 48 h of treatment, with inhibition of produced NO between 60 to 75%, and a concentration that reduces to the 50% the production of NO (IC50 NO) between 2.5 to 25 times lower than that of DCF. In this work, we synthesized and determined for the first time the anti-cancer and anti-inflammatory potential of eight diclofenac N-derivatives. In agreement with the recent evidences suggesting that inflammation may contribute to all states of tumorigenesis, the development of these new derivatives capable of inducing apoptosis and anti-inflammatory effects at very low concentrations represent new effective therapeutic strategies against these diseases.
Implication of a Key Region of Six Bacillus cereus Genes Involved in Siroheme Synthesis, Nitrite Reductase Production and Iron Cluster Repair in the Bacterial Response to Nitric Oxide Stress
Authors: Porrini Constance , Guérin Cyprien , Tran Seav-Ly , Dervyn Rozenn , Nicolas Pierre , Ramarao Nalini
Published: May 2021

Bacterial response to nitric oxide (NO) is of major importance for bacterial survival. NO stress is a main actor of the eukaryotic immune response and several pathogenic bacteria have developed means for detoxification and repair of the damages caused by NO. However, bacterial mechanisms of NO resistance by Gram-positive bacteria are poorly described. In the opportunistic foodborne pathogen Bacillus cereus, genome sequence analyses did not identify homologs to known NO reductases and transcriptional regulators, such as NsrR, which orchestrate the response to NO of other pathogenic or non-pathogenic bacteria. Using a transcriptomic approach, we investigated the adaptation of B. cereus to NO stress. A cluster of 6 genes was identified to be strongly up-regulated in the early phase of the response. This cluster contains an iron-sulfur cluster repair enzyme, a nitrite reductase and three enzymes involved in siroheme biosynthesis. The expression pattern and close genetic localization suggest a functional link between these genes, which may play a pivotal role in the resistance of B. cereus to NO stress during infection.
Dual Reproductive Cell-Specific Promoter-Mediated Split-Cre/LoxP System Suitable for Exogenous Gene Deletion in Hybrid Progeny of Transgenic Arabidopsis
Authors: Yang Chen , Ge Jia , Fu Xiaokang , Luo Keming , Xu Changzheng
Published: May 2021

Genetically modified (GM) crops possess some superior characteristics, such as high yield and insect resistance, but their biosafety has aroused broad public concern. Some genetic engineering technologies have recently been proposed to remove exogenous genes from GM crops. Few approaches have been applied to maintain advantageous traits, but excising exogenous genes in seeds or fruits from these hybrid crops has led to the generation of harvested food without exogenous genes. In a previous study, split-Cre mediated by split intein could recombine its structure and restore recombination activity in hybrid plants. In the current study, the recombination efficiency of split-Cre under the control of ovule-specific or pollen-specific promoters was validated by hybridization of transgenic Arabidopsis containing the improved expression vectors. In these vectors, all exogenous genes were flanked by two loxP sites, including promoters, resistance genes, reporter genes, and split-Cre genes linked to the reporter genes via LP4/2A. A gene deletion system was designed in which NCre was driven by proDD45, and CCre was driven by proACA9 and proDLL. Transgenic lines containing NCre were used as paternal lines to hybridize with transgenic lines containing CCre. Because this hybridization method results in no co-expression of the NCre and CCre genes controlled by reproduction-specific promoters in the F1 progeny, the desirable characteristics could be retained. After self-crossing in F1 progeny, the expression level and protein activity of reporter genes were detected, and confirmed that recombination of split-Cre had occurred and the exogenous genes were partially deleted. The gene deletion efficiency represented by the quantitative measurements of GUS enzyme activity was over 59%, with the highest efficiency of 73% among variable hybrid combinations. Thus, in the present study a novel dual reproductive cell-specific promoter-mediated gene deletion system was developed that has the potential to take advantage of the merits of GM crops while alleviating biosafety concerns.
The Role of GSK-3β in the Regulation of Protein Turnover, Myosin Phenotype, and Oxidative Capacity in Skeletal Muscle under Disuse Conditions
Authors: Mirzoev Timur M. , Sharlo Kristina A. , Shenkman Boris S.
Published: May 2021

Skeletal muscles, being one of the most abundant tissues in the body, are involved in many vital processes, such as locomotion, posture maintenance, respiration, glucose homeostasis, etc. Hence, the maintenance of skeletal muscle mass is crucial for overall health, prevention of various diseases, and contributes to an individual’s quality of life. Prolonged muscle inactivity/disuse (due to limb immobilization, mechanical ventilation, bedrest, spaceflight) represents one of the typical causes, leading to the loss of muscle mass and function. This disuse-induced muscle loss primarily results from repressed protein synthesis and increased proteolysis. Further, prolonged disuse results in slow-to-fast fiber-type transition, mitochondrial dysfunction and reduced oxidative capacity. Glycogen synthase kinase 3β (GSK-3β) is a key enzyme standing at the crossroads of various signaling pathways regulating a wide range of cellular processes. This review discusses various important roles of GSK-3β in the regulation of protein turnover, myosin phenotype, and oxidative capacity in skeletal muscles under disuse/unloading conditions and subsequent recovery. According to its vital functions, GSK-3β may represent a perspective therapeutic target in the treatment of muscle wasting induced by chronic disuse, aging, and a number of diseases.
Conditional Loss of the Exocyst Component Exoc5 in Retinal Pigment Epithelium (RPE) Results in RPE Dysfunction, Photoreceptor Cell Degeneration, and Decreased Visual Function
Authors: Rohrer Bärbel , Biswal Manas R. , Obert Elisabeth , Dang Yujing , Su Yanhui , Zuo Xiaofeng , Fogelgren Ben , Kondkar Altaf A. , Lobo Glenn P. , Lipschutz Joshua H.
Published: May 2021

To characterize the mechanisms by which the highly conserved exocyst trafficking complex regulates eye physiology in zebrafish and mice, we focused on Exoc5 (also known as sec10), a central exocyst component. We analyzed both exoc5 zebrafish mutants and retinal pigmented epithelium (RPE)-specific Exoc5 knockout mice. Exoc5 is present in both the non-pigmented epithelium of the ciliary body and in the RPE. In this study, we set out to establish an animal model to study the mechanisms underlying the ocular phenotype and to establish if loss of visual function is induced by postnatal RPE Exoc5-deficiency. Exoc5−/− zebrafish had smaller eyes, with decreased number of melanocytes in the RPE and shorter photoreceptor outer segments. At 3.5 days post-fertilization, loss of rod and cone opsins were observed in zebrafish exoc5 mutants. Mice with postnatal RPE-specific loss of Exoc5 showed retinal thinning associated with compromised visual function and loss of visual photoreceptor pigments. Abnormal levels of RPE65 together with a reduced c-wave amplitude indicate a dysfunctional RPE. The retinal phenotype in Exoc5−/− mice was present at 20 weeks, but was more pronounced at 27 weeks, indicating progressive disease phenotype. We previously showed that the exocyst is necessary for photoreceptor ciliogenesis and retinal development. Here, we report that exoc5 mutant zebrafish and mice with RPE-specific genetic ablation of Exoc5 develop abnormal RPE pigmentation, resulting in retinal cell dystrophy and loss of visual pigments associated with compromised vision. Together, these data suggest that exocyst-mediated signaling in the RPE is required for RPE structure and function, indirectly leading to photoreceptor degeneration.
Initiation of Pancreatic Cancer: The Interplay of Hyperglycemia and Macrophages Promotes the Acquisition of Malignancy-Associated Properties in Pancreatic Ductal Epithelial Cells
Authors: Otto Lilli , Rahn Sascha , Daunke Tina , Walter Frederik , Winter Elsa , Möller Julia Luisa , Rose-John Stefan , Wesch Daniela , Schäfer Heiner , Sebens Susanne
Published: May 2021

Pancreatic ductal adenocarcinoma (PDAC) is still one of the most aggressive solid malignancies with a poor prognosis. Obesity and type 2 diabetes mellitus (T2DM) are two major risk factors linked to the development and progression of PDAC, both often characterized by high blood glucose levels. Macrophages represent the main immune cell population in PDAC contributing to PDAC development. It has already been shown that pancreatic ductal epithelial cells (PDEC) undergo epithelial–mesenchymal transition (EMT) when exposed to hyperglycemia or macrophages. Thus, this study aimed to investigate whether concomitant exposure to hyperglycemia and macrophages aggravates EMT-associated alterations in PDEC. Exposure to macrophages and elevated glucose levels (25 mM glucose) impacted gene expression of EMT inducers such as IL-6 and TNF-α as well as EMT transcription factors in benign (H6c7-pBp) and premalignant (H6c7-kras) PDEC. Most strikingly, exposure to hyperglycemic coculture with macrophages promoted downregulation of the epithelial marker E-cadherin, which was associated with an elevated migratory potential of PDEC. While blocking IL-6 activity by tocilizumab only partially reverted the EMT phenotype in H6c7-kras cells, neutralization of TNF-α by etanercept was able to clearly impair EMT-associated properties in premalignant PDEC. Altogether, the current study attributes a role to a T2DM-related hyperglycemic, inflammatory micromilieu in the acquisition of malignancy-associated alterations in premalignant PDEC, thus providing new insights on how metabolic diseases might promote PDAC initiation.
Intracameral Bevacizumab Versus Sub-Tenon’s Mitomycin C as Adjuncts to Trabeculectomy: 3-Year Results of a Prospective Randomized Study
Authors: Kopsinis Gerasimos , Tsoukanas Dimitrios , Kopsini Dimitra , Filippopoulos Theodoros
Published: May 2021

Conjunctival wound healing determines success after filtration surgery and the quest for better antifibrotic agents remains active. This study compares intracameral bevacizumab to sub-Tenon’s mitomycin C (MMC) in trabeculectomy. Primary open-angle or exfoliative glaucoma patients were randomized to either bevacizumab (n = 50 eyes) or MMC (n = 50 eyes). The primary outcome measure was complete success, defined as Intraocular Pressure (IOP) > 5 mmHg and ≤21 mmHg with a minimum 20% reduction from baseline without medications. Average IOP and glaucoma medications decreased significantly in both groups at all follow-up points compared to baseline (p < 0.001), without significant difference between groups at 3 years (IOP: bevacizumab group from 29 ± 9.4 to 15 ± 3.4 mmHg, MMC group from 28.3 ± 8.7 to 15.4 ± 3.8 mmHg, p = 0.60; Medications: bevacizumab group from 3.5 ± 0.9 to 0.5 ± 1, MMC group from 3.6 ± 0.7 to 0.6 ± 1.1, p = 0.70). Complete success, although similar between groups at 3 years (66% vs. 64%), was significantly higher for bevacizumab at months 6 and 12 (96% vs. 82%, p = 0.03; 88% vs. 72%, p = 0.04, respectively) with fewer patients requiring medications at months 6, 9 and 12 (4% vs. 18%, p = 0.03; 6% vs. 20%, p = 0.04; 8% vs. 24%, p = 0.03, respectively). Complication rates were similar between groups. In conclusion, intracameral bevacizumab appears to provide similar long-term efficacy and safety results as sub-Tenon’s MMC after trabeculectomy.
Long-Term Results (up to 20 Years) of 19 mm or Smaller Prostheses in the Aortic Position. Does Size Matter? A Propensity-Matched Survival Analysis
Authors: Feier Horea , Grigorescu Andrei , Falnita Lucian , Rachita Oana , Gaspar Marian , Luca Constantin T.
Published: May 2021

Background: The long-term performance of prostheses in the small aortic root is still unclear. Methods: Patients who received a 21 mm or smaller aortic valve between 2000–2018 were retrospectively analyzed. Propensity matching was used in order to account for baseline differences in 19 mm vs. 21 mm valve subgroups. Results: Survival at 10 years was 55.87 ± 5.54% for 19 mm valves vs. 57.17 ± 2.82% for 21 mm ones in the original cohort (p = 0.37), and 58.69 ± 5.61% in 19 mm valve recipients vs. 53.60 ± 5.66% for 21 mm valve subgroups in the matched cohort (p = 0.55). Smaller valves exhibited significantly more patient–prothesis mismatch (PPM) than larger ones (87.30% vs. 57.94%, p < 0.01). All-cause mortality was affected by PPM at 10 years (52.66 ± 3.28% vs. 64.38 ± 3.87%, p = 0.04) in the unmatched population. This difference disappeared, however, after matching: survival at 10 years was 51.82 ± 5.26% in patients with PPM and 63.12 ± 6.43% in patients without PPM. (p = 0.14) Conclusions: There is no survival penalty in using 19 mm prostheses in the small aortic root in the current era. Although PPM is more prevalent in smaller sized valve recipients, this does not translate into reduced survival at 10 years of follow-up.
Characteristics of Critically Ill Patients with COVID-19 Compared to Patients with Influenza—A Single Center Experience
Authors: Herbstreit Frank , Overbeck Marvin , Berger Marc Moritz , Skarabis Annabell , Brenner Thorsten , Schmidt Karsten
Published: May 2021

Infections with SARS-CoV-2 spread worldwide early in 2020. In previous winters, we had been treating patients with seasonal influenza. While creating a larger impact on the health care systems, comparisons regarding the intensive care unit (ICU) courses of both diseases are lacking. We compared patients with influenza and SARS-CoV-2 infections treated at a tertiary care facility offering treatment for acute respiratory distress syndrome (ARDS) and being a high-volume facility for extracorporeal membrane oxygenation (ECMO). Patients with COVID-19 during the first wave of the pandemic (n = 64) were compared to 64 patients with severe influenza from 2016 to 2020 at our ICU. All patients were treated using a standardized protocol. ECMO was used in cases of severe ARDS. Both groups had similar comorbidities. Time in ICU and mortality were not significantly different, yet mortality with ECMO was high amongst COVID-19 patients with approximately two-thirds not surviving. This is in contrast to a mortality of less than 40% in influenza patients with ECMO. Mortality was higher than estimated by SAPSII score on admission in both groups. Patients with COVID-19 were more likely to be male and non-smokers than those with influenza. The outcomes for patients with severe disease were similar. The study helps to understand similarities and differences between patients treated for severe influenza infections and COVID-19.
Modular Hardware Architecture for the Development of Underwater Vehicles Based on Systems Engineering
Authors: Aristizábal Luis M. , Zuluaga Carlos A. , Rúa Santiago , Vásquez Rafael E.
Published: May 2021

This paper addresses the development of a modular hardware architecture for the design/construction/operation of a remotely operated vehicle (ROV), based on systems engineering. The Vee model is first presented as a sequential process that emphasizes the validation processes with stakeholders and verification plans in the development and production stages of the ROV’s life cycle. The conceptual design process starts with the mapping of user requirements to engineering specifications, using the House of Quality (HoQ), a quality function deployment tool that allows executing a functional-division-based hardware design process that facilitates the integration of components and subsystems, as desired for modular architectures. Then, the functional division and hardware architectures are described, and their connection is made through the proposed system architecture that sets the foundation for the definition of a physical architecture, as it involves flows that connect abstract functions with a real context. Development and production stages are exemplified through the design, construction, and integration of some hardware components needed for the remotely operated vehicle Pionero500, and the operational stage briefly describes the first sea trials conducted for the ROV. Systems engineering has shown to be a very useful tool for the development of marine vehicles and marine engineering projects that require modular architectures.
Education Is Entertainment? Zoo Science Communication on YouTube
Authors: Llewellyn Thomas , Rose Paul E.
Published: May 2021

YouTube is the dominant online video-sharing platform and offers zoos an opportunity to engage a vast audience with conservation content. As there is limited research evaluating how zoos currently utilize YouTube, we cataloged and evaluated the content of 20 zoological organizations (focusing on the top 1000 most viewed videos from each channel) from 2006 to 2019. Separately, educational content in a subsample of the most viewed and recently produced videos from three zoo-YouTube channels was catalogued and evaluated for the period 2016 to 2019. We found that channels are becoming more focused on producing entertainment, rather than education-based content and not reflecting the taxonomic diversity of their animals. Videos containing conservation content may not be the most popular with the YouTube audience (making up only 3% of the most viewed videos), but there is evidence that outputs are becoming more conservation orientated, with more conservation-focused videos being produced over time. Zoos may be engaging with large audiences via YouTube, but should carefully consider how they represent different taxonomic classes and how they can create educational material in interesting and accessible forms.
Exploring the Release of Toxic Oligomers from α-Synuclein Fibrils with Antibodies and STED Microscopy
Authors: Bigi Alessandra , Ermini Emilio , Chen Serene W. , Cascella Roberta , Cecchi Cristina
Published: May 2021

α-Synuclein (αS) is an intrinsically disordered and highly dynamic protein involved in dopamine release at presynaptic terminals. The abnormal aggregation of αS as mature fibrils into intraneuronal inclusion bodies is directly linked to Parkinson’s disease. Increasing experimental evidence suggests that soluble oligomers formed early during the aggregation process are the most cytotoxic forms of αS. This study investigated the uptake by neuronal cells of pathologically relevant αS oligomers and fibrils exploiting a range of conformation-sensitive antibodies, and the super-resolution stimulated emission depletion (STED) microscopy. We found that prefibrillar oligomers promptly penetrate neuronal membranes, thus resulting in cell dysfunction. By contrast, fibril docking to the phospholipid bilayer is accompanied by αS conformational changes with a progressive release of A11-reactive oligomers, which can enter into the neurons and trigger cell impairment. Our data provide important evidence on the role of αS fibrils as a source of harmful oligomers, which resemble the intermediate conformers formed de novo during aggregation, underling the dynamic and reversible nature of protein aggregates responsible for α-synucleinopathies.
PDK2: An Underappreciated Regulator of Liver Metabolism
Authors: Woolbright Benjamin L. , Harris Robert A.
Published: May 2021

Pyruvate metabolism is critical for all mammalian cells. The pyruvate dehydrogenase complex couples the pyruvate formed as the primary product of glycolysis to the formation of acetyl-CoA required as the primary substrate of the citric acid cycle. Dysregulation of this coupling contributes to alterations in metabolic flexibility in obesity, diabetes, cancer, and more. The pyruvate dehydrogenase kinase family of isozymes phosphorylate and inactive the pyruvate dehydrogenase complex in the mitochondria. This function makes them critical mediators of mitochondrial metabolism and drug targets in a number of disease states. The liver expresses multiple PDKs, predominantly PDK1 and PDK2 in the fed state and PDK1, PDK2, and PDK4 in the starved and diabetic states. PDK4 undergoes substantial transcriptional regulation in response to a diverse array of stimuli in most tissues. PDK2 has received less attention than PDK4 potentially due to the dramatic changes in transcriptional gene regulation. However, PDK2 is more responsive than the other PDKs to feedforward and feedback regulation by substrates and products of the pyruvate dehydrogenase complex. Although underappreciated, this makes PDK2 particularly important for the minute-to-minute fine control of the pyruvate dehydrogenase complex and a major contributor to metabolic flexibility. The purpose of this review is to characterize the underappreciated role of PDK2 in liver metabolism. We will focus on known biological actions and physiological roles as well as what roles PDK2 may play in disease states. We will also define current inhibitors and address their potential as therapeutic agents in the future.
Low-Frequency Dielectric Relaxation in Structures Based on Macroporous Silicon with Meso-Macroporous Skin-Layer
Authors: Castro Rene , Spivak Yulia , Shevchenko Sergey , Moshnikov Vyacheslav
Published: May 2021

The spectra of dielectric relaxation of macroporous silicon with a mesoporous skin layer in the frequency range 1–106 Hz during cooling (up to 293–173 K) and heating (293–333 K) are presented. Macroporous silicon (pore diameter ≈ 2.2–2.7 μm) with a meso-macroporous skin layer was obtained by the method of electrochemical anodic dissolution of monocrystalline silicon in a Unno-Imai cell. A mesoporous skin layer with a thickness of about 100–200 nm in the form of cone-shaped nanostructures with pore diameters near 13–25 nm and sizes of skeletal part about 35–40 nm by ion-electron microscopy was observed. The temperature dependence of the relaxation of the most probable relaxation time is characterized by two linear sections with different slope values; the change in the slope character is observed at T ≈ 250 K. The features of the distribution of relaxation times in meso-macroporous silicon at temperatures of 223, 273, and 293 K are revealed. The Havriliak-Negami approach was used for approximation of the relaxation curves ε″ = f(ν). The existence of a symmetric distribution of relaxers for all temperatures was found (Cole-Cole model). A discussion of results is provided, taking into account the structure of the studied object.
Correlation between the Compressive Strength and Ultrasonic Pulse Velocity of Cement Mortars Blended with Silica Fume: An Analysis of Microstructure and Hydration Kinetics
Authors: Hong Geuntae , Oh Sangwoo , Choi Seongcheol , Chin Won-Jong , Kim Young-Jin , Song Chiwon
Published: May 2021

The effect of the replacement rate of silica fume (SF) on the correlation between the compressive strength and ultrasonic pulse velocity (UPV) of cement mortar was experimentally analyzed. Specimens were fabricated with different replacement rates of SF, the compressive strength and UPV were measured, and isothermal calorimetry and mercury intrusion porosimetry tests were conducted to analyze the effects of replacement on the hydration kinetics and microstructures on these properties. Field emission scanning electron microscopy analysis was performed to observe SF particles and microstructure. The substitution of SF changed the cement mortar’s hydration kinetics and microstructures, resulting in different strengths and UPVs depending on the replacement rate. The compressive strength and UPV for cement mortars blended with SF also showed a different exponential relationship depending on the SF replacement rate.
Studies on Carbon Materials Produced from Salts with Anions Containing Carbon Atoms for Carbon Paste Electrode
Authors: Skrzypczyńska Katarzyna , Świątkowski Andrzej , Diduszko Ryszard , Dąbek Lidia
Published: May 2021

In the presented work, the properties of carbon materials obtained in the reaction of sodium bicarbonate (C-SB) and ammonium oxalate (C-AO) with magnesium by combustion synthesis were investigated. For the materials obtained in this way, the influence of the type of precursor on their properties was analyzed, including: Degree of crystallinity, porous structure, surface topography, and electrochemical properties. It has been shown that the products obtained in magnesiothermic process were found to contain largely the turbostratic carbon forming a petal-like graphene material. Both materials were used as modifiers of carbon paste electrodes, which were then used to determine the concentration of chlorophenol solutions by voltammetric method. It was shown that the peak current determined from the registered differential pulse voltammograms was mainly influenced by the volume of mesopores and the adsorption capacity of 4-chlorophenol for both obtained carbons.
Directional Shift-Stable Functions
Authors: Mesiar Radko , Stupňanová Andrea
Published: May 2021

Recently, some new types of monotonicity—in particular, weak monotonicity and directional monotonicity of an n-ary real function—were introduced and successfully applied. Inspired by these generalizations of monotonicity, we introduce a new notion for n-ary functions acting on [0,1]n, namely, the directional shift stability. This new property extends the standard shift invariantness (difference scale invariantness), which can be seen as a particular directional shift stability. The newly proposed property can also be seen as a particular kind of local linearity. Several examples and a complete characterization for the case of n=2 of directionally shift-stable aggregation and pre-aggregation functions are also given.
Minimax Estimation in Regression under Sample Conformity Constraints
Authors: Borisov Andrey
Published: May 2021

The paper is devoted to the guaranteeing estimation of parameters in the uncertain stochastic nonlinear regression. The loss function is the conditional mean square of the estimation error given the available observations. The distribution of regression parameters is partially unknown, and the uncertainty is described by a subset of probability distributions with a known compact domain. The essential feature is the usage of some additional constraints describing the conformity of the uncertain distribution to the realized observation sample. The paper contains various examples of the conformity indices. The estimation task is formulated as the minimax optimization problem, which, in turn, is solved in terms of saddle points. The paper presents the characterization of both the optimal estimator and the set of least favorable distributions. The saddle points are found via the solution to a dual finite-dimensional optimization problem, which is simpler than the initial minimax problem. The paper proposes a numerical mesh procedure of the solution to the dual optimization problem. The interconnection between the least favorable distributions under the conformity constraint, and their Pareto efficiency in the sense of a vector criterion is also indicated. The influence of various conformity constraints on the estimation performance is demonstrated by the illustrative numerical examples.
A Low-Protein High-Fat Diet Leads to Loss of Body Weight and White Adipose Tissue Weight via Enhancing Energy Expenditure in Mice
Authors: Rang Yifeng , Ma Sihui , Yang Jiao , Liu Huan , Suzuki Katsuhiko , Liu Chunhong
Published: May 2021

Obesity has become a worldwide health problem over the past three decades. During obesity, metabolic dysfunction of white adipose tissue (WAT) is a key factor increasing the risk of type 2 diabetes. A variety of diet approaches have been proposed for the prevention and treatment of obesity. The low-protein high-fat diet (LPHF) is a special kind of high-fat diet, characterized by the intake of a low amount of protein, while compared to typical high-fat diet, may induce weight loss and browning of WAT. Physical activity is another effective intervention to treat obesity by reducing WAT mass, inducing browning of WAT. In order to determine whether an LPHF, along with exercise enhanced body weight loss and body fat loss as well as the synergistic effect of an LPHF and exercise on energy expenditure in a mice model, we combined a 10-week LPHF with an 8-week forced treadmill training. Meanwhile, a traditional high-fat diet (HPHF) containing the same fat and relatively more protein was introduced as a comparison. In the current study, we further analyzed energy metabolism-related gene expression, plasma biomarkers, and related physiological changes. When comparing to HPHF, which induced a dramatic increase in body weight and WAT weight, the LPHF led to considerable loss of body weight and WAT, without muscle mass and strength decline, while it exhibited a risk of liver and pancreas damage. The mechanism underlying the LPHF-induced loss of body weight and WAT may be attributed to the synergistically upregulated expression of Ucp1 in WAT and Fgf21 in the liver, which may enhance energy expenditure. The 8-week training did not further enhance weight loss and increased plasma biomarkers of muscle damage when combined with LPHF. Furthermore, LPHF reduced the expression of fatty acid oxidation-related genes in adipose tissues, muscle tissues, and liver. Our results indicated that an LPHF has potential for obesity treatment, while the physiological condition should be monitored during application.
Microbiomes in Suspended Soils of Vascular Epiphytes Differ from Terrestrial Soil Microbiomes and from Each Other
Authors: Eskov Alen K. , Zverev Alexei O. , Abakumov Evgeny V.
Published: May 2021

Microbial biodiversity parameters for tropical rainforests remain poorly understood. Whilst the soil microbiome accounts up to 95% of the total diversity of microorganisms in terrestrial ecosystems, the microbiome of suspended soils formed by vascular epiphytes remains completely unexplored. Samples of ground and suspended soils were collected in Cat Tien National Park, southern Vietnam. DNA extraction and sequencing were performed, and libraries of 16s rDNA gene sequences were analyzed. Alpha diversity indices of the microorganisms were the highest in the forest ground soil. In general, the microbiological diversity of all the soil types was found to be similar at the phylum level. Taxonomic composition of the bacterial communities in the suspended soils of plants from the same species are not closer than the taxonomic compositions of the communities in the suspended soils of different plant species. However, the beta diversity analysis revealed significant differences in the movement of mineral elements in terrestrial versus suspended soils. Our data showed that the suspended soils associated with vascular epiphytes were a depository of unique microbiological biodiversity. A contributing factor was the presence of large amounts of organic matter in the suspended soils—deposits collected by the epiphytes—which would have been degraded by termites if it had reached the ground. Further, the nutrient content of the suspended soils was prime for soil respiration activity and taxonomic microbial community biodiversity.
A Machine Learning Approach to Study Glycosidase Activities from Bifidobacterium
Authors: Sabater Carlos , Ruiz Lorena , Margolles Abelardo
Published: May 2021

This study aimed to recover metagenome-assembled genomes (MAGs) from human fecal samples to characterize the glycosidase profiles of Bifidobacterium species exposed to different prebiotic oligosaccharides (galacto-oligosaccharides, fructo-oligosaccharides and human milk oligosaccharides, HMOs) as well as high-fiber diets. A total of 1806 MAGs were recovered from 487 infant and adult metagenomes. Unsupervised and supervised classification of glycosidases codified in MAGs using machine-learning algorithms allowed establishing characteristic hydrolytic profiles for B. adolescentis, B. bifidum, B. breve, B. longum and B. pseudocatenulatum, yielding classification rates above 90%. Glycosidase families GH5 44, GH32, and GH110 were characteristic of B. bifidum. The presence or absence of GH1, GH2, GH5 and GH20 was characteristic of B. adolescentis, B. breve and B. pseudocatenulatum, while families GH1 and GH30 were relevant in MAGs from B. longum. These characteristic profiles allowed discriminating bifidobacteria regardless of prebiotic exposure. Correlation analysis of glycosidase activities suggests strong associations between glycosidase families comprising HMOs-degrading enzymes, which are often found in MAGs from the same species. Mathematical models here proposed may contribute to a better understanding of the carbohydrate metabolism of some common bifidobacteria species and could be extrapolated to other microorganisms of interest in future studies.
Beyond Lockdown: The Potential Side Effects of the SARS-CoV-2 Pandemic on Public Health
Authors: Paltrinieri Sara , Bressi Barbara , Costi Stefania , Mazzini Elisa , Cavuto Silvio , Ottone Marta , De Panfilis Ludovica , Fugazzaro Stefania , Rondini Ermanno , Giorgi Rossi Paolo
Published: May 2021

Lockdowns to contain the spread of the SARS-CoV-2 have disrupted routines and behaviors, which could lead to a worsening of lifestyle and an increase in the burden of non-communicable diseases. This study aimed to describe the changes in physical activity, diet, alcohol drinking, and cigarette smoking during lockdown. A self-administered online survey addressing adults living in a province in northern Italy was advertised through websites and social media. Citizens could access the survey in anonymity from 4 May until 15 June 2020. A total of 1826 adults completed the survey, with a worsening of physical activity (35.1%), diet (17.6%), alcohol drinking (12.5%), and cigarette smoking (7.7%) reported. In contrast, 33.5% reported an improvement in diet, 12.6% in alcohol drinking, 5.3% in physical activity and 4.1% in cigarette smoking. Female sex, young adult age, suspension of work activity, and symptoms of psychological distress were the factors associated with a greater likelihood of change, which was frequently for the worse. Lockdown had an impact on lifestyle, with some net beneficial effects on diet and mostly negative effects on physical activity. Public health measures should be implemented to avoid long-term negative effects of the lockdown, supporting individuals more prone to change for the worse.
Review on the Regional Effects of Gastrointestinal Luminal Stimulation on Appetite and Energy Intake: (Pre)clinical Observations
Authors: Wilbrink Jennifer , Masclee Gwen , Klaassen Tim , van Avesaat Mark , Keszthelyi Daniel , Masclee Adrian
Published: May 2021

Macronutrients in the gastrointestinal (GI) lumen are able to activate “intestinal brakes”, feedback mechanisms on proximal GI motility and secretion including appetite and energy intake. In this review, we provide a detailed overview of the current evidence with respect to four questions: (1) are regional differences (duodenum, jejunum, ileum) present in the intestinal luminal nutrient modulation of appetite and energy intake? (2) is this “intestinal brake” effect macronutrient specific? (3) is this “intestinal brake” effect maintained during repetitive activation? (4) can the “intestinal brake” effect be activated via non-caloric tastants? Recent evidence indicates that: (1) regional differences exist in the intestinal modulation of appetite and energy intake with a proximal to distal gradient for inhibition of energy intake: ileum and jejunum > duodenum at low but not at high caloric infusion rates. (2) the “intestinal brake” effect on appetite and energy appears not to be macronutrient specific. At equi-caloric amounts, the inhibition on energy intake and appetite is in the same range for fat, protein and carbohydrate. (3) data on repetitive ileal brake activation are scarce because of the need for prolonged intestinal intubation. During repetitive activation of the ileal brake for up to 4 days, no adaptation was observed but overall the inhibitory effect on energy intake was small. (4) the concept of influencing energy intake by intra-intestinal delivery of non-caloric tastants is intriguing. Among tastants, the bitter compounds appear to be more effective in influencing energy intake. Energy intake decreases modestly after post-oral delivery of bitter tastants or a combination of tastants (bitter, sweet and umami). Intestinal brake activation provides an interesting concept for preventive and therapeutic approaches in weight management strategies.
Endothelial Dysfunction and SARS-CoV-2 Infection: Association and Therapeutic Strategies
Authors: Deng Hai , Tang Ting-Xuan , Chen Deng , Tang Liang-Sheng , Yang Xiang-Ping , Tang Zhao-Hui
Published: May 2021

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has been recently considered a systemic disorder leading to the procoagulant state. Preliminary studies have shown that SARS-CoV-2 can infect endothelial cells, and extensive evidence of inflammation and endothelial dysfunction has been found in advanced COVID-19. Endothelial cells play a critical role in many physiological processes, such as controlling blood fluidity, leukocyte activation, adhesion, platelet adhesion and aggregation, and transmigration. Therefore, it is reasonable to think that endothelial dysfunction leads to vascular dysfunction, immune thrombosis, and inflammation associated with COVID-19. This article summarizes the association of endothelial dysfunction and SARS-CoV-2 infection and its therapeutic strategies.
Dynamic Reactive Power Compensation in Power Systems through the Optimal Siting and Sizing of Photovoltaic Sources
Authors: Buitrago-Velandia Andrés Felipe , Montoya Oscar Danilo , Gil-González Walter
Published: May 2021

The problem of the optimal placement and sizing of photovoltaic power plants in electrical power systems from high- to medium-voltage levels is addressed in this research from the point of view of the exact mathematical optimization. To represent this problem, a mixed-integer nonlinear programming model considering the daily demand and solar radiation curves was developed. The main advantage of the proposed optimization model corresponds to the usage of the reactive power capabilities of the power electronic converter that interfaces the photovoltaic sources with the power systems, which can work with lagging or leading power factors. To model the dynamic reactive power compensation, the η-coefficient was used as a function of the nominal apparent power converter transference rate. The General Algebraic Modeling System software with the BONMIN optimization package was used as a computational tool to solve the proposed optimization model. Two simulation cases composed of 14 and 27 nodes in transmission and distribution levels were considered to validate the proposed optimization model, taking into account the possibility of installing from one to four photovoltaic sources in each system. The results show that energy losses are reduced between 13% and 56% as photovoltaic generators are added with direct effects on the voltage profile improvement.
Using Sentinel-1, Sentinel-2, and Planet Imagery to Map Crop Type of Smallholder Farms
Authors: Rao Preeti , Zhou Weiqi , Bhattarai Nishan , Srivastava Amit K. , Singh Balwinder , Poonia Shishpal , Lobell David B. , Jain Meha
Published: May 2021

Remote sensing offers a way to map crop types across large spatio-temporal scales at low costs. However, mapping crop types is challenging in heterogeneous, smallholder farming systems, such as those in India, where field sizes are often smaller than the resolution of historically available imagery. In this study, we examined the potential of relatively new, high-resolution imagery (Sentinel-1, Sentinel-2, and PlanetScope) to identify four major crop types (maize, mustard, tobacco, and wheat) in eastern India using support vector machine (SVM). We found that a trained SVM model that included all three sensors led to the highest classification accuracy (85%), and the inclusion of Planet data was particularly helpful for classifying crop types for the smallest farms (<600 m2). This was likely because its higher spatial resolution (3 m) could better account for field-level variations in smallholder systems. We also examined the impact of image timing on the classification accuracy, and we found that early-season images did little to improve our models. Overall, we found that readily available Sentinel-1, Sentinel-2, and Planet imagery were able to map crop types at the field-scale with high accuracy in Indian smallholder systems. The findings from this study have important implications for the identification of the most effective ways to map crop types in smallholder systems.