bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrafast Photoconversion Dynamics of the Knotless Phytochrome SynCph2
Authors: Fischer Tobias , van Wilderen Luuk J. G. W. , Gnau Petra , Bredenbeck Jens , Essen Lars-Oliver , Wachtveitl Josef , Slavov Chavdar
Published: October 2021

The family of phytochrome photoreceptors contains proteins with different domain architectures and spectral properties. Knotless phytochromes are one of the three main subgroups classified by their distinct lack of the PAS domain in their photosensory core module, which is in contrast to the canonical PAS-GAF-PHY array. Despite intensive research on the ultrafast photodynamics of phytochromes, little is known about the primary kinetics in knotless phytochromes. Here, we present the ultrafast Pr ⇆ Pfr photodynamics of SynCph2, the best-known knotless phytochrome. Our results show that the excited state lifetime of Pr* (~200 ps) is similar to bacteriophytochromes, but much longer than in most canonical phytochromes. We assign the slow Pr* kinetics to relaxation processes of the chromophore-binding pocket that controls the bilin chromophore’s isomerization step. The Pfr photoconversion dynamics starts with a faster excited state relaxation than in canonical phytochromes, but, despite the differences in the respective domain architectures, proceeds via similar ground state intermediate steps up to Meta-F. Based on our observations, we propose that the kinetic features and overall dynamics of the ultrafast photoreaction are determined to a great extent by the geometrical context (i.e., available space and flexibility) within the binding pocket, while the general reaction steps following the photoexcitation are most likely conserved among the red/far-red phytochromes.
Charting the N-Terminal Acetylome: A Comprehensive Map of Human NatA Substrates
Authors: Van Damme Petra
Published: October 2021

N-terminal acetylation (Nt-acetylation) catalyzed by conserved N-terminal acetyltransferases or NATs embodies a modification with one of the highest stoichiometries reported for eukaryotic protein modifications to date. Comprising the catalytic N-alpha acetyltransferase (NAA) subunit NAA10 plus the ribosome anchoring regulatory subunit NAA15, NatA represents the major acetyltransferase complex with up to 50% of all mammalian proteins representing potential substrates. Largely in consequence of the essential nature of NatA and its high enzymatic activity, its experimentally confirmed mammalian substrate repertoire remained poorly charted. In this study, human NatA knockdown conditions achieving near complete depletion of NAA10 and NAA15 expression resulted in lowered Nt-acetylation of over 25% out of all putative NatA targets identified, representing an up to 10-fold increase in the reported number of substrate N-termini affected upon human NatA perturbation. Besides pointing to less efficient NatA substrates being prime targets, several putative NatE substrates were shown to be affected upon human NatA knockdown. Intriguingly, next to a lowered expression of ribosomal proteins and proteins constituting the eukaryotic 48S preinitiation complex, steady-state levels of protein N-termini additionally point to NatA Nt-acetylation deficiency directly impacting protein stability of knockdown affected targets.
Tomatidine and Patchouli Alcohol as Inhibitors of SARS-CoV-2 Enzymes (3CLpro, PLpro and NSP15) by Molecular Docking and Molecular Dynamics Simulations
Authors: Zrieq Rafat , Ahmad Iqrar , Snoussi Mejdi , Noumi Emira , Iriti Marcello , Algahtani Fahad D. , Patel Harun , Saeed Mohd , Tasleem Munazzah , Sulaiman Shadi , Aouadi Kaïss , Kadri Adel
Published: October 2021

Considering the current dramatic and fatal situation due to the high spreading of SARS-CoV-2 infection, there is an urgent unmet medical need to identify novel and effective approaches for prevention and treatment of Coronavirus disease (COVID 19) by re-evaluating and repurposing of known drugs. For this, tomatidine and patchouli alcohol have been selected as potential drugs for combating the virus. The hit compounds were subsequently docked into the active site and molecular docking analyses revealed that both drugs can bind the active site of SARS-CoV-2 3CLpro, PLpro, NSP15, COX-2 and PLA2 targets with a number of important binding interactions. To further validate the interactions of promising compound tomatidine, Molecular dynamics study of 100 ns was carried out towards 3CLpro, NSP15 and COX-2. This indicated that the protein-ligand complex was stable throughout the simulation period, and minimal backbone fluctuations have ensued in the system. Post dynamic MM-GBSA analysis of molecular dynamics data showed promising mean binding free energy 47.4633 ± 9.28, 51.8064 ± 8.91 and 54.8918 ± 7.55 kcal/mol, respectively. Likewise, in silico ADMET studies of the selected ligands showed excellent pharmacokinetic properties with good absorption, bioavailability and devoid of toxicity. Therefore, patchouli alcohol and especially, tomatidine may provide prospect treatment options against SARS-CoV-2 infection by potentially inhibiting virus duplication though more research is guaranteed and secured.
Fucose Ameliorates Tritrichomonas sp.-Associated Illness in Antibiotic-Treated Muc2−/− Mice
Authors: Achasova Kseniya M. , Kozhevnikova Elena N. , Borisova Mariya A. , Litvinova Ekaterina A.
Published: October 2021

The mucus layer in the intestine plays a critical role in regulation of host–microbe interactions and maintaining homeostasis. Disruptions of the mucus layer due to genetic, environmental, or immune factors may lead to inflammatory bowel diseases (IBD). IBD frequently are accompanied with infections, and therefore are treated with antibiotics. Hence, it is important to evaluate risks of antibiotic treatment in individuals with vulnerable gut barrier and chronic inflammation. Mice with a knockout of the Muc2 gene, encoding the main glycoprotein component of the mucus, demonstrate a close contact of the microbes with the gut epithelium which leads to chronic inflammation resembling IBD. Here we demonstrate that the Muc2−/− mice harboring a gut protozoan infection Tritrichomonas sp. are susceptible to an antibiotic-induced depletion of the bacterial microbiota. Suppression of the protozoan infection with efficient metronidazole dosage or L-fucose administration resulted in amelioration of an illness observed in antibiotic-treated Muc2−/− mice. Fucose is a monosaccharide presented abundantly in gut glycoproteins, including Mucin2, and is known to be involved in host–microbe interactions, in particular in microbe adhesion. We suppose that further investigation of the role of fucose in protozoan adhesion to host cells may be of great value.
Members of the GADD45 Protein Family Show Distinct Propensities to form Toxic Amyloid-Like Aggregates in Physiological Conditions
Authors: Smaldone Giovanni , Caruso Daniela , Sandomenico Annamaria , Iaccarino Emanuela , Focà Annalia , Ruggiero Alessia , Ruvo Menotti , Vitagliano Luigi
Published: October 2021

The three members (GADD45α, GADD45β, and GADD45γ) of the growth arrest and DNA damage-inducible 45 (GADD45) protein family are involved in a myriad of diversified cellular functions. With the aim of unravelling analogies and differences, we performed comparative biochemical and biophysical analyses on the three proteins. The characterization and quantification of their binding to the MKK7 kinase, a validated functional partner of GADD45β, indicate that GADD45α and GADD45γ are strong interactors of the kinase. Despite their remarkable sequence similarity, the three proteins present rather distinct biophysical properties. Indeed, while GADD45β and GADD45γ are marginally stable at physiological temperatures, GADD45α presents the Tm value expected for a protein isolated from a mesophilic organism. Surprisingly, GADD45α and GADD45β, when heated, form high-molecular weight species that exhibit features (ThT binding and intrinsic label-free UV/visible fluorescence) proper of amyloid-like aggregates. Cell viability studies demonstrate that they are endowed with a remarkable toxicity against SHSY-5Y and HepG2 cells. The very uncommon property of GADD45β to form cytotoxic species in near-physiological conditions represents a puzzling finding with potential functional implications. Finally, the low stability and/or the propensity to form toxic species of GADD45 proteins constitute important features that should be considered in interpreting their many functions.
Simulated Microgravity Inhibits Rodent Dermal Fibroblastic Differentiation of Mesenchymal Stem Cells by Suppressing ERK/β-Catenin Signaling Pathway
Authors: Cheng Yansiwei , Zhou Yuhao , Lv Wenjun , Luo Qing , Song Guanbin
Published: October 2021

Studies have shown that bone marrow-derived mesenchymal stem cells (BMSCs) can differentiate into dermal fibroblasts to participate in skin-repairing. However, at present, little is known about how microgravity affects dermal fibroblastic differentiation of BMSCs in space. The aim of this study was to investigate the effect of simulated microgravity (SMG) on the differentiation of BMSCs into dermal fibroblasts and the related molecular mechanism. Here, using a 2D-clinostat device to simulate microgravity, we found that SMG inhibited the differentiation and suppressed the Wnt/β-catenin signaling and phosphorylation of extracellular regulated protein kinases 1/2 (ERK1/2). After upregulating the Wnt/β-catenin signaling with lithium chloride (LiCl) treatment, we found that the effect of the differentiation was restored. Moreover, the Wnt/β-catenin signaling was upregulated when phosphorylation of ERK1/2 was activated with tert-Butylhydroquinone (tBHQ) treatment. Taken together, our findings suggest that SMG inhibits dermal fibroblastic differentiation of BMSCs by suppressing ERK/β-catenin signaling pathway, inferring that ERK/β-catenin signaling pathway may act as a potential intervention target for repairing skin injury under microgravity conditions.
Expression/Activation of PAR-1 in Airway Epithelial Cells of COPD Patients: Ex Vivo/In Vitro Study
Authors: Montalbano Angela Marina , Chiappara Giuseppina , Albano Giusy Daniela , Ferraro Maria , Di Sano Caterina , Vitulo Patrizio , Pipitone Loredana , Ricciardolo Fabio Luigi Massimo , Anzalone Giulia , Profita Mirella
Published: October 2021

The role of PAR-1 expression and activation was described in epithelial cells from the central and distal airways of COPD patients using an ex vivo/in vitro model. PAR-1 immunoreactivity was studied in epithelial cells from surgical specimens of the central and distal airways of COPD patients and healthy control (HC). Furthermore, PAR-1 expression and activation were measured in both the human bronchial epithelial cell line (16HBE) and normal human bronchial epithelial cells (NHBEs) exposed to cigarette smoke extract (CSE) (10%) or thrombin. Finally, cell proliferation, apoptosis, and IL-8 release were detected in stimulated NHBEs. We identified higher levels of PAR-1 expression/activation in epithelial cells from the central airways of COPD patients than in HC. Active PAR-1 increased in epithelial cells from central and distal airways of COPD, with higher levels in COPD smokers (correlated with pack-years) than in COPD ex-smokers. 16HBE and NHBEs exposed to CSE or thrombin showed increased levels of active PAR-1 (localized in the cytoplasm) than baseline conditions, while NHBEs treated with thrombin or CSE showed increased levels of IL-8 proteins, with an additional effect when used in combination. Smoking habits generate the upregulation of PAR-1 expression/activation in airway epithelial cells, and promoting IL-8 release might affect the recruitment of infiltrating cells in the airways of COPD patients.
Many Drugs of Abuse May Be Acutely Transformed to Dopamine, Norepinephrine and Epinephrine In Vivo
Authors: Fitzgerald Paul J.
Published: October 2021

It is well established that a wide range of drugs of abuse acutely boost the signaling of the sympathetic nervous system and the hypothalamic–pituitary–adrenal (HPA) axis, where norepinephrine and epinephrine are major output molecules. This stimulatory effect is accompanied by such symptoms as elevated heart rate and blood pressure, more rapid breathing, increased body temperature and sweating, and pupillary dilation, as well as the intoxicating or euphoric subjective properties of the drug. While many drugs of abuse are thought to achieve their intoxicating effects by modulating the monoaminergic neurotransmitter systems (i.e., serotonin, norepinephrine, dopamine) by binding to these receptors or otherwise affecting their synaptic signaling, this paper puts forth the hypothesis that many of these drugs are actually acutely converted to catecholamines (dopamine, norepinephrine, epinephrine) in vivo, in addition to transformation to their known metabolites. In this manner, a range of stimulants, opioids, and psychedelics (as well as alcohol) may partially achieve their intoxicating properties, as well as side effects, due to this putative transformation to catecholamines. If this hypothesis is correct, it would alter our understanding of the basic biosynthetic pathways for generating these important signaling molecules, while also modifying our view of the neural substrates underlying substance abuse and dependence, including psychological stress-induced relapse. Importantly, there is a direct way to test the overarching hypothesis: administer (either centrally or peripherally) stable isotope versions of these drugs to model organisms such as rodents (or even to humans) and then use liquid chromatography-mass spectrometry to determine if the labeled drug is converted to labeled catecholamines in brain, blood plasma, or urine samples.
Electron Spin Resonance Evaluation of Buccal Membrane Fluidity Alterations by Sodium Caprylate and L-Menthol
Authors: Chede Laxmi Shanthi , Wagner Brett A. , Buettner Garry R. , Donovan Maureen D.
Published: October 2021

The ability of sodium caprylate and l-menthol to fluidize phospholipid bilayers composed of lipids simulating the buccal epithelium was investigated using electron spin resonance (ESR) to evaluate the action of these agents as permeation enhancers. 5-Doxyl stearic acid (5-DSA) and 16-doxyl stearic acid (16-DSA) were used as spin labels to identify alterations in membrane fluidity near the polar head groups or inner acyl regions of the lipid bilayer, respectively. The molecular motion of both 5-DSA and 16-DSA showed increased disorder near the polar and inner hydrophobic regions of the bilayer in the presence of sodium caprylate suggesting fluidization in both the regions, which contributes to its permeation enhancing effects. L-menthol decreased the order parameter for 16-DSA, showing membrane fluidization only in the inner acyl regions of the bilayer, which also corresponded to its weaker permeation enhancing effects. The rapid evaluation of changes in fluidity of the bilayer in the presence of potential permeation enhancers using ESR enables improved selection of effective permeation enhancers and enhancer combinations based on their effect on membrane fluidization.
Pachymic Acid Attenuated Doxorubicin-Induced Heart Failure by Suppressing miR-24 and Preserving Cardiac Junctophilin-2 in Rats
Authors: Younis Nahla N. , Salama Alaa , Shaheen Mohamed A. , Eissa Rana G.
Published: October 2021

Defects in cardiac contractility and heart failure (HF) are common following doxorubicin (DOX) administration. Different miRs play a role in HF, and their targeting was suggested as a promising therapy. We aimed to target miR-24, a suppressor upstream of junctophilin-2 (JP-2), which is required to affix the sarcoplasmic reticulum to T-tubules, and hence the release of Ca2+ in excitation–contraction coupling using pachymic acid (PA) and/or losartan (LN). HF was induced with DOX (3.5 mg/kg, i.p., six doses, twice weekly) in 24 rats. PA and LN (10 mg/kg, daily) were administered orally for four weeks starting the next day of the last DOX dose. Echocardiography, left ventricle (LV) biochemical and histological assessment and electron microscopy were conducted. DOX increased serum BNP, HW/TL, HW/BW, mitochondrial number/size and LV expression of miR-24 but decreased EF, cardiomyocyte fiber diameter, LV content of JP-2 and ryanodine receptors-2 (RyR2). Treatment with either PA or LN reversed these changes. Combined PA + LN attained better results than monotherapies. In conclusion, HF progression following DOX administration can be prevented or even delayed by targeting miR-24 and its downstream JP-2. Our results, therefore, suggest the possibility of using PA alone or as an adjuvant therapy with LN to attain better management of HF patients, especially those who developed tolerance toward LN.
Proteolytic Cleavage of Bioactive Peptides and Protease-Activated Receptors in Acute and Post-Colitis
Authors: De bruyn Michelle , Ceuleers Hannah , Hanning Nikita , Berg Maya , De Man Joris G. , Hulpiau Paco , Hermans Cedric , Stenman Ulf-Håkan , Koistinen Hannu , Lambeir Anne-Marie , De Winter Benedicte Y. , De Meester Ingrid
Published: October 2021

The protease activity in inflammatory bowel disease (IBD) and irritable bowel syndrome has been studied extensively using synthetic fluorogenic substrates targeting specific sets of proteases. We explored activities in colonic tissue from a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis rat model by investigating the cleavage of bioactive peptides. Pure trypsin- and elastase-like proteases on the one hand and colonic tissue from rats with TNBS-induced colitis in the acute or post-inflammatory phase on the other, were incubated with relevant peptides to identify their cleavage pattern by mass spectrometry. An increased cleavage of several peptides was observed in the colon from acute colitis rats. The tethered ligand (TL) sequences of peptides mimicking the N-terminus of protease-activated receptors (PAR) 1 and 4 were significantly unmasked by acute colitis samples and these cleavages were positively correlated with thrombin activity. Increased cleavage of β-endorphin and disarming of the TL-sequence of the PAR3-based peptide were observed in acute colitis and linked to chymotrypsin-like activity. Increased processing of the enkephalins points to the involvement of proteases with specificities different from trypsin- or chymotrypsin-like enzymes. In conclusion, our results suggest thrombin, chymotrypsin-like proteases and a set of proteases with different specificities as potential therapeutic targets in IBD.
The Impact of Selenium Deficiency on Cardiovascular Function
Authors: Shimada Briana K. , Alfulaij Naghum , Seale Lucia A.
Published: October 2021

Selenium (Se) is an essential trace element that is necessary for various metabolic processes, including protection against oxidative stress, and proper cardiovascular function. The role of Se in cardiovascular health is generally agreed upon to be essential yet not much has been defined in terms of specific functions. Se deficiency was first associated with Keshan’s Disease, an endemic disease characterized by cardiomyopathy and heart failure. Since then, Se deficiency has been associated with multiple cardiovascular diseases, including myocardial infarction, heart failure, coronary heart disease, and atherosclerosis. Se, through its incorporation into selenoproteins, is vital to maintain optimal cardiovascular health, as selenoproteins are involved in numerous crucial processes, including oxidative stress, redox regulation, thyroid hormone metabolism, and calcium flux, and inadequate Se may disrupt these processes. The present review aims to highlight the importance of Se in cardiovascular health, provide updated information on specific selenoproteins that are prominent for proper cardiovascular function, including how these proteins interact with microRNAs, and discuss the possibility of Se as a potential complemental therapy for prevention or treatment of cardiovascular disease.
Electrical Signaling of Plants under Abiotic Stressors: Transmission of Stimulus-Specific Information
Authors: Mudrilov Maxim , Ladeynova Maria , Grinberg Marina , Balalaeva Irina , Vodeneev Vladimir
Published: October 2021

Plants have developed complex systems of perception and signaling to adapt to changing environmental conditions. Electrical signaling is one of the most promising candidates for the regulatory mechanisms of the systemic functional response under the local action of various stimuli. Long-distance electrical signals of plants, such as action potential (AP), variation potential (VP), and systemic potential (SP), show specificities to types of inducing stimuli. The systemic response induced by a long-distance electrical signal, representing a change in the activity of a complex of molecular-physiological processes, includes a nonspecific component and a stimulus-specific component. This review discusses possible mechanisms for transmitting information about the nature of the stimulus and the formation of a specific systemic response with the participation of electrical signals induced by various abiotic factors.
A New Perspective on Adsorbent Materials Based Impregnated MgSiO3 with Crown Ethers for Palladium Recovery
Authors: Ciopec Mihaela , Grad Oana , Negrea Adina , Duteanu Narcis , Negrea Petru , Paul Cristina , Ianăși Catalin , Mosoarca Giannin , Vancea Cosmin
Published: October 2021

The study of new useful, efficient and selective structures for the palladium ions’ recovery has led to the development of a new series of macromolecules. Thus, this study presents a comparative behavior of two crown benzene ethers that modify the magnesium silicate surface used as adsorbent for palladium. These crown ethers are dibenzo18-crown-6 (DB18C6) and dibenzo 30-crown-10 (DB30C10). The obtained materials were characterized by scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDX) and Fourier-transform infrared spectroscopy (FT-IR). The specific surface area (BET) and point of zero charge (PZC) of the two materials were determined. The palladium ions’ recovery from synthetic aqueous solutions studies aimed to establish the adsorption mechanism. For this desideratum, the kinetic, equilibrium and thermodynamic studies show that MgSiO3-DB30C10 have a higher adsorption capacity (35.68 mg g−1) compared to MgSiO3-DB18C6 (21.65 mg g−1). Thermodynamic studies highlight that the adsorption of Pd(II) on the two studied materials are spontaneous and endothermic processes. The positive values of the entropy (ΔS0) suggest that the studied adsorption processes show a higher disorder at the liquid/solid interface. Desorption studies were also performed, and it was found that the degree of desorption was 98.3%.
The NLRP3 Inflammasome: Relevance in Solid Organ Transplantation
Authors: Burke Ryan M. , Dale Bethany L. , Dholakia Shamik
Published: October 2021

The NOD, LRR, and pyrin domain-containing 3 (NLRP3) protein has been established as a central component of the inflammasome and regulates the inflammatory response to a myriad of environmental, microbial, and endogenous danger stimuli. Assembly of the NLRP3 inflammasome results in the cleavage and activation of caspase-1, in turn causing release of the pro-inflammatory interleukins 1-beta and 18. This activation response, while crucial to coordinated innate immune defense, can be aberrantly activated by the likes of cell-free DNA, and cause significant autoimmune pathology. Complications of autoimmunity induced by aberrant NLRP3 inflammasome activation have a great degree of mechanistic crossover with alloimmune injury in solid organ transplant, and stratagems to neutralize NLRP3 inflammasome activation may prove beneficial in solid organ transplant management. This article reviews NLRP3 inflammasome biology and the pathology associated with its hyperactivation, as well as the connections between NLRP3 inflammasome activation and allograft homeostasis.
Genome-Wide Identification and Characterization of Polygalacturonase Gene Family in Maize (Zea mays L.)
Authors: Lu Lu , Hou Quancan , Wang Linlin , Zhang Tianye , Zhao Wei , Yan Tingwei , Zhao Lina , Li Jinping , Wan Xiangyuan
Published: October 2021

Polygalacturonase (PG, EC 3.2.1.15) is a crucial enzyme for pectin degradation and is involved in various developmental processes such as fruit ripening, pollen development, cell expansion, and organ abscission. However, information on the PG gene family in the maize (Zea mays L.) genome and the specific members involved in maize anther development are still lacking. In this study, we identified 55 PG family genes from the maize genome and further characterized their evolutionary relationship and expression patterns. Phylogenetic analysis revealed that ZmPGs are grouped into six Clades, and gene structures of the same Clade are highly conserved, suggesting their functional conservation. The ZmPGs are randomly distributed across maize chromosomes, and collinearity analysis showed that many ZmPGs might be derived from tandem duplications and segmental duplications, and these genes are under purifying selection. Furthermore, gene expression analysis provided insights into possible functional divergence among ZmPGs. Based on the RNA-seq data analysis, we found that many ZmPGs are expressed in various tissues while 18 ZmPGs are highly expressed in maize anther, and their detailed expression profiles in different anther developmental stages were further investigated by using RT-qPCR analysis. These results provide valuable information for further functional characterization and application of the ZmPGs in maize.
Anti-Inflammatory Activity of N-Docosahexaenoylethanolamine and N-Eicosapentaenoylethanolamine in a Mouse Model of Lipopolysaccharide-Induced Neuroinflammation
Authors: Tyrtyshnaia Anna , Konovalova Sophia , Bondar Anatoly , Ermolenko Ekaterina , Sultanov Ruslan , Manzhulo Igor
Published: October 2021

The search for methods of cognitive impairment treatment and prevention in neurological and neurodegenerative diseases is an urgent task of modern neurobiology. It is now known that various diseases, accompanied by dementia, exhibit a pronounced neuroinflammation. Considering the significant docosahexaenoic and eicosapentaenoic polyunsaturated fatty acids’ therapeutic potential, we decided to investigate and compare anti-inflammatory activity of their N-acylethanolamine derivatives. As a result, we found that both N-docosahexaenoylethanolamine (synaptamide) and N-eicosapentaenoylethanolamine (EPEA) prevents an LPS-mediated increase in the proinflammatory cytokines TNF-α and IL-6 production in the SIM-A9 microglia culture. In an in vivo experiment, synaptamide reversed an increase in LPS-mediated hippocampal TNF-α and IL-1β, but EPEA did not. However, both compounds contributed to the microglia polarization towards the M2-phenotype. Synaptamide, rather than EPEA, inhibited the Iba-1-positive microglia staining area increase. However, both synaptamide and EPEA prevented the LPS-mediated astrogliosis. A study of BDNF immunoreactivity showed that synaptamide, but not EPEA, reversed an LPS-mediated decrease in BDNF production. Despite the more pronounced anti-inflammatory activity of synaptamide, both compounds were effective in maintaining a normal level of hippocampal long-term potentiation in neuroinflammation. The results indicate a high therapeutic potential for both compounds. However, some tests have shown higher activity of synaptamide compared to EPEA.
Hyperglycemia Altered DNA Methylation Status and Impaired Pancreatic Differentiation from Embryonic Stem Cells
Authors: Chen Andy Chun Hang , Huang Wen , Fong Sze Wan , Chan Chris , Lee Kai Chuen , Yeung William Shu Biu , Lee Yin Lau
Published: October 2021

The prevalence of type 2 diabetes (T2D) is rapidly increasing across the globe. Fetal exposure to maternal diabetes was correlated with higher prevalence of impaired glucose tolerance and T2D later in life. Previous studies showed aberrant DNA methylation patterns in pancreas of T2D patients. However, the underlying mechanisms remained largely unknown. We utilized human embryonic stem cells (hESC) as the in vitro model for studying the effects of hyperglycemia on DNA methylome and early pancreatic differentiation. Culture in hyperglycemic conditions disturbed the pancreatic lineage potential of hESC, leading to the downregulation of expression of pancreatic markers PDX1, NKX6−1 and NKX6−2 after in vitro differentiation. Genome-wide DNA methylome profiling revealed over 2000 differentially methylated CpG sites in hESC cultured in hyperglycemic condition when compared with those in control glucose condition. Gene ontology analysis also revealed that the hypermethylated genes were enriched in cell fate commitment. Among them, NKX6−2 was validated and its hypermethylation status was maintained upon differentiation into pancreatic progenitor cells. We also established mouse ESC lines at both physiological glucose level (PG-mESC) and conventional hyperglycemia glucose level (HG-mESC). Concordantly, DNA methylome analysis revealed the enrichment of hypermethylated genes related to cell differentiation in HG-mESC, including Nkx6−1. Our results suggested that hyperglycemia dysregulated the epigenome at early fetal development, possibly leading to impaired pancreatic development.
The Natural Pigment Violacein Potentially Suppresses the Proliferation and Stemness of Hepatocellular Carcinoma Cells In Vitro
Authors: Kim Yu Jin , Yuk Nayeong , Shin Hee Jeong , Jung Hye Jin
Published: October 2021

Hepatocellular carcinoma (HCC) is a malignant type of primary liver cancer with high incidence and mortality, worldwide. A major challenge in the treatment of HCC is chemotherapeutic resistance. It is therefore necessary to develop novel anticancer drugs for suppressing the growth of HCC cells and overcoming drug resistance for improving the treatment of HCC. Violacein is a deep violet-colored indole derivative that is produced by several bacterial strains, including Chromobacterium violaceum, and it possesses numerous pharmacological properties, including antitumor activity. However, the therapeutic effects of violacein and the mechanism underlying its antitumor effect against HCC remain to be elucidated. This study is the first to demonstrate that violacein inhibits the proliferation and stemness of Huh7 and Hep3B HCC cells. The antiproliferative effect of violacein was attributed to cell cycle arrest at the sub-G1 phase and the induction of apoptotic cell death. Violacein induced nuclear condensation, dissipated mitochondrial membrane potential (MMP), increased generation of reactive oxygen species (ROS), activated the caspase cascade, and upregulated p53 and p21. The anticancer effect of violacein on HCC cells was also associated with the downregulation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK)1/2 signaling. Violacein not only suppressed the proliferation and formation of tumorspheres of Huh7 and Hep3B cancer stem-like cells but also reduced the expression of key markers of cancer stemness, including CD133, Sox2, Oct4, and Nanog, by inhibiting the signal transducer and activator of transcription 3 (STAT3)/AKT/ERK pathways. These results suggest the therapeutic potential of violacein in effectively suppressing HCC by targeting the proliferation and stemness of HCC cells.
Changes in Maternal Platelet Physiology during Gestation and Their Interaction with Trophoblasts
Authors: Forstner Désirée , Guettler Jacqueline , Gauster Martin
Published: October 2021

Upon activation, maternal platelets provide a source of proinflammatory mediators in the intervillous space of the placenta. Therefore, platelet-derived factors may interfere with different trophoblast subtypes of the developing human placenta and might cause altered hormone secretion and placental dysfunction later on in pregnancy. Increased platelet activation, and the subsequent occurrence of placental fibrinoid deposition, are linked to placenta pathologies such as preeclampsia. The composition and release of platelet-derived factors change over gestation and provide a potential source of predicting biomarkers for the developing fetus and the mother. This review indicates possible mechanisms of platelet-trophoblast interactions and discusses the effect of increased platelet activation on placenta development.
Aggregation Properties of Albumin in Interacting with Magnetic Fluids
Authors: Velichko Elena N. , Nepomnyashchaya Elina K. , Baranov Maksim A. , Skvortsov Alexey N. , Pleshakov Ivan V. , Dong Ge
Published: October 2021

In this study, interactions of Fe3O4 magnetic nanoparticles with serum albumin biomolecules in aqueous solutions were considered. The studies were conducted with the laser correlation spectroscopy and optical analysis of dehydrated films. It was shown that the addition of magnetite to an albumin solution at low concentrations of up to 10−6 g/L led to the formation of aggregates with sizes of up to 300 nm in the liquid phase and an increase in the number of spiral structures in the dehydrated films, which indicated an increase in their stability. With a further increase in the magnetite concentration in the solution (from 10−4 g/L), the magnetic particles stuck together and to albumin, thus forming aggregates with sizes larger than 1000 nm. At the same time, the formation of morphological structures in molecular films was disturbed, and a characteristic decrease in their stability occurred. Most stable films were formed at low concentrations of magnetic nanoparticles (less than 10−4 g/L) when small albumin–magnetic nanoparticle aggregates were formed. These results are important for characterizing the interaction processes of biomolecules with magnetic nanoparticles and can be useful for predicting the stability of biomolecular films with the inclusion of magnetite particles.
Deletion of Neuronal CuZnSOD Accelerates Age-Associated Muscle Mitochondria and Calcium Handling Dysfunction That Is Independent of Denervation and Precedes Sarcopenia
Authors: Su Yu , Claflin Dennis R. , Huang Meixiang , Davis Carol S. , Macpherson Peter C. D. , Richardson Arlan , Van Remmen Holly , Brooks Susan V.
Published: October 2021

Skeletal muscle suffers atrophy and weakness with aging. Denervation, oxidative stress, and mitochondrial dysfunction are all proposed as contributors to age-associated muscle loss, but connections between these factors have not been established. We examined contractility, mitochondrial function, and intracellular calcium transients (ICTs) in muscles of mice throughout the life span to define their sequential relationships. We performed these same measures and analyzed neuromuscular junction (NMJ) morphology in mice with postnatal deletion of neuronal Sod1 (i-mn-Sod1-/- mice), previously shown to display accelerated age-associated muscle loss and exacerbation of denervation in old age, to test relationships between neuronal redox homeostasis, NMJ degeneration and mitochondrial function. In control mice, the amount and rate of the decrease in mitochondrial NADH during contraction was greater in middle than young age although force was not reduced, suggesting decreased efficiency of NADH utilization prior to the onset of weakness. Declines in both the peak of the ICT and force were observed in old age. Muscles of i-mn-Sod1-/- mice showed degeneration of mitochondrial and calcium handling functions in middle-age and a decline in force generation to a level not different from the old control mice, with maintenance of NMJ morphology. Together, the findings support the conclusion that muscle mitochondrial function decreases during aging and in response to altered neuronal redox status prior to NMJ deterioration or loss of mass and force suggesting mitochondrial defects contribute to sarcopenia independent of denervation.
A Novel Cre/lox-Based Genetic Tool for Repeated, Targeted and Markerless Gene Integration in Yarrowia lipolytica
Authors: Zhou Qinghua , Jiao Liangcheng , Li Wenjuan , Hu Zhiming , Li Yunchong , Zhang Houjin , Yang Min , Xu Li , Yan Yunjun
Published: October 2021

The unconventional yeast Yarrowia lipolytica is extensively applied in bioproduction fields owing to its excellent metabolite and protein production ability. Nonetheless, utilization of this promising host is still restricted by the limited availability of precise and effective gene integration tools. In this study, a novel and efficient genetic tool was developed for targeted, repeated, and markerless gene integration based on Cre/lox site-specific recombination system. The developed tool required only a single selection marker and could completely excise the unnecessary sequences. A total of three plasmids were created and seven rounds of marker-free gene integration were examined in Y. lipolytica. All the integration efficiencies remained above 90%, and analysis of the protein production and growth characteristics of the engineered strains confirmed that genome modification via the novel genetic tool was feasible. Further work also confirmed that the genetic tool was effective for the integration of other genes, loci, and strains. Thus, this study significantly promotes the application of the Cre/lox system and presents a powerful tool for genome engineering in Y. lipolytica.
ANÁLISIS TÉRMICO, HIDROFORMILACIÓN DE CANFENO E HIDROGENACIÓN DE LIMONENO CON COMPLEJOS TRIFENILFOSFINA-RUTENIO(II) CONTENIENDO LIGANDOS N-HETEROCÍCLICOS
Authors: Cuenú-Cabezas Fernando , Duque María Cristina , Bolaños-Rivera Alberto
Published: October 2021

En este trabajo reportamos los estudios térmicos de termogravimetría (TGA) y la actividad catalítica en la hidroformilación en fase homogénea de canfeno utilizando complejos del tipo [RuCl (PPh ) (N-het)], donde los N-heterocíclicos son: 2-acetilpiridina 2 3 2 (2-acpy); 3- acetilpiridina (3-acpy), 4- acetilpiridina (4-acpy), 2-aminopiridina (2-ampy); 3 aminopiridina (3-ampy) y 4- aminopiridina (4-ampy). Los estudios de TGA muestran  que los complejos presentan pérdidas de masa que fueron asignadas a la disociación de ligandos, la mayoría de los complejos disocian un ligando trifenilfosfina y un N-heterocíclico en la primera descomposición, para luego sufrir la descomposición total del complejo o la disociación de otro ligando. En la hidroformilación de canfeno La posición de los sustituyentes en el anillo de la piridina ejercen una notable influencia en la selectividad y actividad del catalizador, los sustituyentes donores de densidad de carga en el anillo piridínico y que se encuentran ubicados en posiciones orto inducen a que el complejo sea menos activo que cuando el complejo presenta sustituyentes piridínicos en posición para. El mismo fenómeno se observa con complejos en donde el anillo de la piridina se encuentra sustituido por grupos atractores de densidad de carga.
EVALUACIÓN DE TRES MÉTODOS DE ESCARIFICACIÓN EN SEMILLAS DE ALGARROBO
Authors: Orozco-Cardona Andrés Felipe , Franco-Herrera Natalia , Taborda-Beltrán Laura Andrea
Published: October 2021

Se realizó un estudio con el fin de evaluar la efectividad de tres métodos de escarificación: mecánico, físico y químico sobre la germinación de semillas de algarrobo (Hymenaea courbaril L.). Se tomaron 20 semillas por cada tratamiento, siendo 10 de ellas la réplica (200 semillas en total). Una vez aplicados los respectivos tratamientos en cada uno de los métodos evaluados, las semillas fueron puestas en recipientes plásticos con tierra y llevadas posteriormente al invernadero de la Universidad del Quindío. Un mes después se tomaron datos de porcentajes de semillas germinadas, no germinadas y muertas, encontrando que dentro de los métodos empleados, el químico mostró mejores resultados, y dentro de los tratamientos el más eficaz fue el de H SO .2 4
DESIGUALDAD Y PERSONAS MAYORES DE 60 AÑOS EN LA CIUDAD DE ARMENIA, QUINDÍO
Authors: Giraldo-Navia Néstor Raúl , Fernández-Gallego Álvaro Alfonso , DelaRosa-Bobadilla John Jaime
Published: October 2021

Por las características exploratorias y focalizadas de la investigación “Condiciones de vida de los adultos mayores de la ciudad de Armenia”, la desigualdad será medida a partir del ingreso, los aportes económicos de las personas mayores al hogar y los cambios en los consumos, como variables de aproximación a ella, incluso con las limitaciones que impone. En correspondencia con trabajos de la Comisión Económica para América Latina (CEPAL), el aporte de las personas mayores de 60 años para el sostenimiento y reproducción económica de los hogares es considerable, desde un casi 50% en adelante y de modo absoluto para los hogares situados en las franjas de Pobreza y Pobreza Extrema. El aporte, en la medida en que es mayor el ingreso del hogar, disminuye el aporte alto de los cabezas de hogar mayores, pero tiende a aumentar el aporte medio de manera importante. Esto configura unos arreglos familiares de corresponsabilidades económicas directas entre los miembros mayores y los menores de 60 años. En cuanto a los consumos, leídos a través de los ingresos, resulta mucho más sensible para entender el comportamiento económico de los hogares, desde el que es dable observar, independiente de las tres categorías de No Pobre, Pobre y Pobreza Extrema, ya analizadas (Giraldo, Fernández y De la Rosa, 2008), y que han arrojado resultados consistentes, pero en este caso específico no tan precisos como ahora.
EL MUNDO POSIBLE DE LOS HÉROES MEDIÁTICOS (Aparte del libro: Los héroes mediáticos)
Authors: Leal-Larrarte Sandra
Published: October 2021

En toda historia caben cientos de posibilidades, cada una constituye un mundo de acción. La pregunta es ¿a través de qué medios o porqué razones, los autores eligen determinada opción? Los héroes de cómic, que a pesar de sufrir críticas acerca de sus contenidos han contribuido en el engrandecimiento cultural de generaciones enteras, responden a las necesidades sociales y a los pareceres del contexto socioeconómico en el que están inscritos al momento de su ejecución. Igual pasa con nuestros héroes nacionales, productos de melodramas diversos muestran la historia del excluido y su capacidad e inteligencia para enfrentar con éxito esa exclusión de la que es víctima. Son dos tipos de héroes, para dos tipos de sociedad: una en la que ser fuerte es la clave y otra en la que no tener opciones es lo normal.
DISEÑO Y CREACION DE UN MATERIAL EDUCATIVO COMPUTARIZADO (YAKU 1.0) REFERENTE A LA TEMATICA DEL AGUA Y SU GESTIÓN INTEGRAL
Authors: Bustamante-Toro César Augusto , Álzate-Ríos Héctor Fabio
Published: October 2021

Mediante esta investigación se logró crear y diseñar un material educativo computarizado (MEC) denominado YAKU versión 1.0,  con el objeto de promover en los usuarios de diferentes comunidades educativas, espacios de reflexión, análisis y discusión con respecto a la conservación y uso eficiente del agua. YAKU 1.0 es un material didáctico multimedia en formato CD ROM, sobre la temática del agua y su gestión integral para la vida y el desarrollo sostenible; para ello se utilizaron las ventajas multimediales (texto, imágenes, animaciones y sonido) y empleo de Herramientas de desarrollo multimedia como: Neobook 5.5 como utilitario principal, Windows Movie Maker 5.1, Flash MX, editores fotográficos, entre otros.

Asimismo, en dicha investigación se logró desarrollar una metodología propia y dinámica, siendo consecuentes con el contexto socio-educativo y cultural. Se aplicaron los principales parámetros considerados para la creación y diseño de MECs teniendo en cuenta dos fases: Fase 1: Prediseño y condiciones pedagógicas del MEC, Fase 2: Procesamiento y condiciones técnicas del MEC. Todo lo anterior, con el propósito de generar un campo de acción que permita la conformación de grupos de desarrollo de MECs en diferentes áreas del conocimiento; igualmente, se pretende promover el uso del computador y las TIC como herramienta pedagógica fundamental en la interacción del conocimiento en el sector agua.
Again About a Unique Academic Study of Spatial Development of Post-Soviet Russia
Authors: Shvetsov Alexander Nikolaevich
Published: October 2021

The article summarizes the results of many years of fundamental interdisciplinary research on a wide range of socioeconomic problems of the spatial development of Russia in the post-Soviet period. An overview of the content and main results of four programs of the Presidium of the Russian Academy of Sciences, carried out on this topic in 2009–2020, is given. We are talking about an unprecedented megaproject for domestic and, apparently, for world science, which marks a new — interdisciplinary — type of research on a wide range of priority theoretical and applied issues for modern Russian reality, which form the supporting framework of the latest topical spatial problems. This is a large-scale, polythematic, complexly organized project that has been carried out for more than ten years. The article provides a characteristic of the theoretical and methodological approach, methodological tools and forms of organizing scientific research within the framework of the project, as well as an assessment of the results obtained in it.

The issue of scientific support for the development of state strategic decisions for the spatial development of the country is being discussed. It is proposed to use the results of scientific research obtained during the implementation of these programs as a scientific basis for strategic planning of spatial development.
Anti-crisis transformation of the financial strategy of the automotive company PJSC «KAMAZ»
Authors: Petrikova Elena Mikhailovna
Published: October 2021

The relevance of the chosen topic is the need to build a financial strategy of the company in the conditions of financial instability in the economy caused by the COVID-19 pandemic. The article compares the results of the effectiveness of the actual implementation of the strategy of PJSC «KAMAZ» in 2015–2019 and plans to achieve key performance indicators of the financial strategy in 2020–2025, taking into account the current unstable financial situation in the economy. Much attention is paid to the analysis of the situation on the product sales market, the need to adjust the financial strategy taking into account the complex of anti-crisis measures to diversify activities, optimize costs, increase productivity, increase profit and profitability. The main risks of the company that the company may face in the conditions of financial instability are identified, and proposals are presented for a set of measures that it is advisable to apply as part of the anti-crisis transformation of the financial strategy of the automotive company PJSC «KAMAZ».
Russia — Brazil: approval of the strategic partnership
Authors: Chirkin Sergey Alekseevich
Published: October 2021

The article examines the state and prospects for the development of trade and economic cooperation between Russia and Brazil. The investment component of bilateral economic relations and military-technical cooperation are considered. Quantitative indicators on the volumes and dynamics of bilateral foreign trade turnover, the structure of trade operations are given. The emphasis is placed on the strategic partnership and technological alliance of the two countries declared at the interstate level. The reasons hindering the development of bilateral cooperation are analyzed. The areas where cooperation would contribute to the creation of technological alliances are highlighted. The peculiarities of Brazil`s foreign trade policy are studied, including in relation to Russian products imported by the country. In comparative terms, the main economic indicators of the two countries are given. In conclusion, the views aimed at strengthening and expanding Russian-Brazilian economic relations are expressed. The relevance of the topic is due to the approved in 2018 the national project «International cooperation and Export», aimed at increasing Russian non-primary non-energy exports.