bluuebunny/crossref_metadata_2025 huggingface dataset:
Probing the Energetic Metabolism of Resting Cysts under Different Conditions from Molecular and Physiological Perspectives in the Harmful Algal Blooms-Forming Dinoflagellate Scrippsiella trochoidea
Authors: Li Fengting , Yang Aoao , Hu Zhangxi , Lin Siheng , Deng Yunyan , Tang Ying Zhong
Published: July 2021

Energetic metabolism is essential in maintaining the viability of all organisms. Resting cysts play important roles in the ecology of dinoflagellates, particularly for harmful algal blooms (HABs)-causative species. However, the energetic metabolism underlying the germination potency maintenance of resting cysts of dinoflagellate have been extremely scarce in studies from physiological and, particularly, molecular perspectives. Therefore, we used the cosmopolitan Scrippsiella trochoidea as a representative of HABs-forming and cyst-producing dinoflagellates in this work to obtain novel insights into the molecular mechanisms, regulating the energetic metabolism in dinoflagellate resting cysts, under different physical condition. As the starting step, we established a cDNA subtractive library via suppression subtractive hybridization (SSH) technology, from which we screened an incomplete sequence for the β subunit of ATP synthase gene (β-F1-ATPase), a key indicator for the status of cell’s energetic metabolism. The full-length cDNA of β-F1-ATPase gene from S.trochoidea (Stβ-F1-ATPase) was then obtained via rapid amplification of cDNA ends (RACE) (Accession: MZ343333). Our real-time qPCR detections, in vegetative cells and resting cysts treated with different physical conditions, revealed that (1) the expression of Stβ-F1-ATPase in resting cysts was generally much lower than that in vegetative cells, and (2) the Stβ-F1-ATPase expressions in the resting cysts under darkness, lowered temperature, and anoxia, and during an extended duration of dormancy, were significantly lower than that in cysts under the condition normally used for culture-maintaining (a 12 h light:12 h dark cycle, 21 °C, aerobic, and newly harvested). Our detections of the viability (via Neutral Red staining) and cellular ATP content of resting cysts, at the conditions corresponding to the abovementioned treatments, showed that both the viability and ATP content decreased rapidly within 12 h and then maintained at low levels within the 4-day experimentation under all the three conditions applied (4 °C, darkness, and anoxia), which are well in accordance with the measurements of the transcription of Stβ-F1-ATPase. These results demonstrated that the energy consumption of resting cysts reaches a low, but somehow stable, level within a short time period and is lower at low temperature, darkness, and anoxia than that at ambient temperature. Our work provides an important basis for explaining that resting cysts survive long-term darkness and low temperature in marine sediments from molecular and physiological levels.
Tumor Cell-Specific 2′-Fluoro RNA Aptamer Conjugated with Closo-Dodecaborate as A Potential Agent for Boron Neutron Capture Therapy
Authors: Vorobyeva Mariya A. , Dymova Maya A. , Novopashina Darya S. , Kuligina Elena V. , Timoshenko Valentina V. , Kolesnikov Iaroslav A. , Taskaev Sergey Yu. , Richter Vladimir A. , Venyaminova Alya G.
Published: July 2021

Boron neutron capture therapy (BNCT) is a binary radiotherapeutic approach to the treatment of malignant tumors, especially glioblastoma, the most frequent and incurable brain tumor. For successful BNCT, a boron-containing therapeutic agent should provide selective and effective accumulation of 10B isotope inside target cells, which are then destroyed after neutron irradiation. Nucleic acid aptamers look like very prospective candidates for carrying 10B to the tumor cells. This study represents the first example of using 2′-F-RNA aptamer GL44 specific to the human glioblastoma U-87 MG cells as a boron delivery agent for BNCT. The closo-dodecaborate residue was attached to the 5′-end of the aptamer, which was also labeled by the fluorophore at the 3′-end. The resulting bifunctional conjugate showed effective and specific internalization into U-87 MG cells and low toxicity. After incubation with the conjugate, the cells were irradiated by epithermal neutrons on the Budker Institute of Nuclear Physics neutron source. Evaluation of the cell proliferation by real-time cell monitoring and the clonogenic test revealed that boron-loaded aptamer decreased specifically the viability of U-87 MG cells to the extent comparable to that of 10B-boronophenylalanine taken as a control. Therefore, we have demonstrated a proof of principle of employing aptamers for targeted delivery of boron-10 isotope in BNCT. Considering their specificity, ease of synthesis, and large toolkit of chemical approaches for high boron-loading, aptamers provide a promising basis for engineering novel BNCT agents.
High-Throughput Screen Detects Calcium Signaling Dysfunction in Hutchinson-Gilford Progeria Syndrome
Authors: Fafián-Labora Juan A. , Morente-López Miriam , de Toro Fco. Javier , Arufe María C.
Published: July 2021

Hutchinson–Gilford progeria syndrome (HGPS) is a deadly childhood disorder, which is considered a very rare disease. It is caused by an autosomal dominant mutation on the LMNA gene, and it is characterized by accelerated aging. Human cell lines from HGPS patients and healthy parental controls were studied in parallel using next-generation sequencing (NGS) to unravel new non-previously altered molecular pathways. Nine hundred and eleven transcripts were differentially expressed when comparing healthy versus HGPS cell lines from a total of 21,872 transcripts; ITPR1, ITPR3, CACNA2D1, and CAMK2N1 stood out among them due to their links with calcium signaling, and these were validated by Western blot analysis. It was observed that the basal concentration of intracellular Ca2+ was statistically higher in HGPS cell lines compared to healthy ones. The relationship between genes involved in Ca2+ signaling and mitochondria-associated membranes (MAM) was demonstrated through cytosolic calcium handling by means of an automated fluorescent plate reading system (FlexStation 3, Molecular Devices), and apoptosis and mitochondrial ROS production were examined by means of flow cytometry analysis. Altogether, our data suggest that the Ca2+ signaling pathway is altered in HGPS at least in part due to the overproduction of reactive oxygen species (ROS). Our results unravel a new therapeutic window for the treatment of this rare disease and open new strategies to study pathologies involving both accelerated and healthy aging.
Glycoproteins Presenting Galactose and N-Acetylgalactosamine in Human Seminal Plasma as Potential Players Involved in Immune Modulation in the Fertilization Process
Authors: Szczykutowicz Justyna , Tkaczuk-Włach Joanna , Ferens-Sieczkowska Mirosława
Published: July 2021

In light of recent research, there is increasing evidence showing that extracellular semen components have a significant impact on the immune reaction of the female partner, leading to the tolerogenic response enabling the embryo development and implantation as well as further progress of healthy pregnancy. Seminal plasma glycoproteins are rich in the unique immunomodulatory glycoepitopes that may serve as ligands for endogenous lectins that decorate the surface of immune cells. Such interaction may be involved in modulation of the maternal immune response. Among immunomodulatory glycans, Lewis type antigens have been of interest for at least two decades, while the importance of T/Tn antigens and related structures is still far from understanding. In the current work, we applied two plant lectins capable of distinguishing glycoepitopes with terminal GalNAc and Gal to identify glycoproteins that are their efficient carriers. By means of lectin blotting and lectin affinity chromatography followed by LC-MS, we identified lactotransferrin, prolactin inducible protein as well as fibronectin and semenogelins 1 and 2 as lectin-reactive. Net-O-glycosylation analysis results indicated that the latter three may actually carry T and/or Tn antigens, while in the case of prolactin inducible protein and lactotransferrin LacdiNAc and lactosamine glycoepitopes were more probable. STRING bioinformatics analysis linked the identified glycoproteins in the close network, indicating their involvement in immune (partially innate) processes. Overall, our research revealed potential seminal plasma ligands for endogenous Gal/GalNAc specific lectins with a possible role in modulation of maternal immune response during fertilization.
Tissue Regeneration: The Dark Side of Opioids
Authors: Berthézène Cécile , Rabiller Lise , Jourdan Géraldine , Cousin Béatrice , Pénicaud Luc , Casteilla Louis , Lorsignol Anne
Published: July 2021

Opioids are regarded as among the most effective analgesic drugs and their use for the management of pain is considered standard of care. Despite their systematic administration in the peri-operative period, their impact on tissue repair has been studied mainly in the context of scar healing and is only beginning to be documented in the context of true tissue regeneration. Indeed, in mammals, growing evidence shows that opioids direct tissue repair towards scar healing, with a loss of tissue function, instead of the regenerative process that allows for recovery of both the morphology and function of tissue. Here, we review recent studies that highlight how opioids may prevent a regenerative process by silencing nociceptive nerve activity and a powerful anti-inflammatory effect. These data open up new perspectives for inducing tissue regeneration and argue for opioid-restricted strategies for managing pain associated with tissue injury.
Exciton Origin of Color-Tuning in Ca2+-Binding Photosynthetic Bacteria
Authors: Timpmann Kõu , Rätsep Margus , Kangur Liina , Lehtmets Alexandra , Wang-Otomo Zheng-Yu , Freiberg Arvi
Published: July 2021

Flexible color adaptation to available ecological niches is vital for the photosynthetic organisms to thrive. Hence, most purple bacteria living in the shade of green plants and algae apply bacteriochlorophyll a pigments to harvest near infra-red light around 850–875 nm. Exceptions are some Ca2+-containing species fit to utilize much redder quanta. The physical basis of such anomalous absorbance shift equivalent to ~5.5 kT at ambient temperature remains unsettled so far. Here, by applying several sophisticated spectroscopic techniques, we show that the Ca2+ ions bound to the structure of LH1 core light-harvesting pigment–protein complex significantly increase the couplings between the bacteriochlorophyll pigments. We thus establish the Ca-facilitated enhancement of exciton couplings as the main mechanism of the record spectral red-shift. The changes in specific interactions such as pigment–protein hydrogen bonding, although present, turned out to be secondary in this regard. Apart from solving the two-decade-old conundrum, these results complement the list of physical principles applicable for efficient spectral tuning of photo-sensitive molecular nano-systems, native or synthetic.
Stress-Related Dysfunction of Adult Hippocampal Neurogenesis—An Attempt for Understanding Resilience?
Authors: Leschik Julia , Lutz Beat , Gentile Antonietta
Published: July 2021

Newborn neurons in the adult hippocampus are regulated by many intrinsic and extrinsic cues. It is well accepted that elevated glucocorticoid levels lead to downregulation of adult neurogenesis, which this review discusses as one reason why psychiatric diseases, such as major depression, develop after long-term stress exposure. In reverse, adult neurogenesis has been suggested to protect against stress-induced major depression, and hence, could serve as a resilience mechanism. In this review, we will summarize current knowledge about the functional relation of adult neurogenesis and stress in health and disease. A special focus will lie on the mechanisms underlying the cascades of events from prolonged high glucocorticoid concentrations to reduced numbers of newborn neurons. In addition to neurotransmitter and neurotrophic factor dysregulation, these mechanisms include immunomodulatory pathways, as well as microbiota changes influencing the gut-brain axis. Finally, we discuss recent findings delineating the role of adult neurogenesis in stress resilience.
Gene Transcription as a Therapeutic Target in Leukemia
Authors: Khamidullina Alvina I. , Varlamova Ekaterina A. , Hammoud Nour Alhuda , Yastrebova Margarita A. , Bruter Alexandra V.
Published: July 2021

Blood malignancies often arise from undifferentiated hematopoietic stem cells or partially differentiated stem-like cells. A tight balance of multipotency and differentiation, cell division, and quiescence underlying normal hematopoiesis requires a special program governed by the transcriptional machinery. Acquisition of drug resistance by tumor cells also involves reprogramming of their transcriptional landscape. Limiting tumor cell plasticity by disabling reprogramming of the gene transcription is a promising strategy for improvement of treatment outcomes. Herein, we review the molecular mechanisms of action of transcription-targeted drugs in hematological malignancies (largely in leukemia) with particular respect to the results of clinical trials.
Molecular Responses to Cadmium Exposure in Two Contrasting Durum Wheat Genotypes
Authors: Sabella Erika , Luvisi Andrea , Genga Alessandra , De Bellis Luigi , Aprile Alessio
Published: July 2021

Cadmium is a heavy metal that can be easily accumulated in durum wheat kernels and enter the human food chain. Two near-isogenic lines (NILs) with contrasting cadmium accumulation in grains, High-Cd or Low-Cd (H-Cd NIL and L-Cd NIL, respectively), were used to understand the Cd accumulation and transport mechanisms in durum wheat roots. Plants were cultivated in hydroponic solution, and cadmium concentrations in roots, shoots and grains were quantified. To evaluate the molecular mechanism activated in the two NILs, the transcriptomes of roots were analyzed. The observed response is complex and involves many genes and molecular mechanisms. We found that the gene sequences of two basic helix–loop–helix (bHLH) transcription factors (bHLH29 and bHLH38) differ between the two genotypes. In addition, the transporter Heavy Metal Tolerance 1 (HMT-1) is expressed only in the low-Cd genotype and many peroxidase genes are up-regulated only in the L-Cd NIL, suggesting ROS scavenging and root lignification as active responses to cadmium presence. Finally, we hypothesize that some aquaporins could enhance the Cd translocation from roots to shoots. The response to cadmium in durum wheat is therefore extremely complex and involves transcription factors, chelators, heavy metal transporters, peroxidases and aquaporins. All these new findings could help to elucidate the cadmium tolerance in wheat and address future breeding programs.
How to Obtain a Mega-Intestine with Normal Morphology: In Silico Modelling of Postnatal Intestinal Growth in a Cd97-Transgenic Mouse
Authors: Hofmann Felix , Thalheim Torsten , Rother Karen , Quaas Marianne , Kerner Christiane , Przybilla Jens , Aust Gabriela , Galle Joerg
Published: July 2021

Intestinal cylindrical growth peaks in mice a few weeks after birth, simultaneously with crypt fission activity. It nearly stops after weaning and cannot be reactivated later. Transgenic mice expressing Cd97/Adgre5 in the intestinal epithelium develop a mega-intestine with normal microscopic morphology in adult mice. Here, we demonstrate premature intestinal differentiation in Cd97/Adgre5 transgenic mice at both the cellular and molecular levels until postnatal day 14. Subsequently, the growth of the intestinal epithelium becomes activated and its maturation suppressed. These changes are paralleled by postnatal regulation of growth factors and by an increased expression of secretory cell markers, suggesting growth activation of non-epithelial tissue layers as the origin of enforced tissue growth. To understand postnatal intestinal growth mechanistically, we study epithelial fate decisions during this period with the use of a 3D individual cell-based computer model. In the model, the expansion of the intestinal stem cell (SC) population, a prerequisite for crypt fission, is largely independent of the tissue growth rate and is therefore not spontaneously adaptive. Accordingly, the model suggests that, besides the growth activation of non-epithelial tissue layers, the formation of a mega-intestine requires a released growth control in the epithelium, enabling accelerated SC expansion. The similar intestinal morphology in Cd97/Adgre5 transgenic and wild type mice indicates a synchronization of tissue growth and SC expansion, likely by a crypt density-controlled contact inhibition of growth of intestinal SC proliferation. The formation of a mega-intestine with normal microscopic morphology turns out to originate in changes of autonomous and conditional specification of the intestinal cell fate induced by the activation of Cd97/Adgre5.
Recent Progress in the Molecular Imaging of Nonalcoholic Fatty Liver Disease
Authors: Wegrzyniak Olivia , Rosestedt Maria , Eriksson Olof
Published: July 2021

Pathological fibrosis of the liver is a landmark feature in chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Diagnosis and assessment of progress or treatment efficacy today requires biopsy of the liver, which is a challenge in, e.g., longitudinal interventional studies. Molecular imaging techniques such as positron emission tomography (PET) have the potential to enable minimally invasive assessment of liver fibrosis. This review will summarize and discuss the current status of the development of innovative imaging markers for processes relevant for fibrogenesis in liver, e.g., certain immune cells, activated fibroblasts, and collagen depositions.
Skeletal Muscle Mitochondria Dysfunction in Genetic Neuromuscular Disorders with Cardiac Phenotype
Authors: Ignatieva Elena , Smolina Natalia , Kostareva Anna , Dmitrieva Renata
Published: July 2021

Mitochondrial dysfunction is considered the major contributor to skeletal muscle wasting in different conditions. Genetically determined neuromuscular disorders occur as a result of mutations in the structural proteins of striated muscle cells and therefore are often combined with cardiac phenotype, which most often manifests as a cardiomyopathy. The specific roles played by mitochondria and mitochondrial energetic metabolism in skeletal muscle under muscle-wasting conditions in cardiomyopathies have not yet been investigated in detail, and this aspect of genetic muscle diseases remains poorly characterized. This review will highlight dysregulation of mitochondrial representation and bioenergetics in specific skeletal muscle disorders caused by mutations that disrupt the structural and functional integrity of muscle cells.
Epigenetic Regulation of microRNAs in Cancer: Shortening the Distance from Bench to Bedside
Authors: Pajares María J. , Alemany-Cosme Ester , Goñi Saioa , Bandres Eva , Palanca-Ballester Cora , Sandoval Juan
Published: July 2021

Cancer is a complex disease involving alterations of multiple processes, with both genetic and epigenetic features contributing as core factors to the disease. In recent years, it has become evident that non-coding RNAs (ncRNAs), an epigenetic factor, play a key role in the initiation and progression of cancer. MicroRNAs, the most studied non-coding RNAs subtype, are key controllers in a myriad of cellular processes, including proliferation, differentiation, and apoptosis. Furthermore, the expression of miRNAs is controlled, concomitantly, by other epigenetic factors, such as DNA methylation and histone modifications, resulting in aberrant patterns of expression upon the occurrence of cancer. In this sense, aberrant miRNA landscape evaluation has emerged as a promising strategy for cancer management. In this review, we have focused on the regulation (biogenesis, processing, and dysregulation) of miRNAs and their role as modulators of the epigenetic machinery. We have also highlighted their potential clinical value, such as validated diagnostic and prognostic biomarkers, and their relevant role as chromatin modifiers in cancer therapy.
Platelet and Erythrocyte Extravasation across Inflamed Corneal Venules Depend on CD18, Neutrophils, and Mast Cell Degranulation
Authors: De La Cruz Angie , Hargrave Aubrey , Magadi Sri , Courson Justin A. , Landry Paul T. , Zhang Wanyu , Lam Fong W. , Bray Monica A. , Smith C. Wayne , Burns Alan R. , Rumbaut Rolando E.
Published: July 2021

Platelet extravasation during inflammation is under-appreciated. In wild-type (WT) mice, a central corneal epithelial abrasion initiates neutrophil (PMN) and platelet extravasation from peripheral limbal venules. The same injury in mice expressing low levels of the β2-integrin, CD18 (CD18hypo mice) shows reduced platelet extravasation with PMN extravasation apparently unaffected. To better define the role of CD18 on platelet extravasation, we focused on two relevant cell types expressing CD18: PMNs and mast cells. Following corneal abrasion in WT mice, we observed not only extravasated PMNs and platelets but also extravasated erythrocytes (RBCs). Ultrastructural observations of engorged limbal venules showed platelets and RBCs passing through endothelial pores. In contrast, injured CD18hypo mice showed significantly less venule engorgement and markedly reduced platelet and RBC extravasation; mast cell degranulation was also reduced compared to WT mice. Corneal abrasion in mast cell-deficient (KitW-sh/W-sh) mice showed less venule engorgement, delayed PMN extravasation, reduced platelet and RBC extravasation and delayed wound healing compared to WT mice. Finally, antibody-induced depletion of circulating PMNs prior to corneal abrasion reduced mast cell degranulation, venule engorgement, and extravasation of PMNs, platelets, and RBCs. In summary, in the injured cornea, platelet and RBC extravasation depends on CD18, PMNs, and mast cell degranulation.
Engineering of Bio-Adhesive Ligand Containing Recombinant RGD and PHSRN Fibronectin Cell-Binding Domains in Fusion with a Colored Multi Affinity Tag: Simple Approach for Fragment Study from Expression to Adsorption
Authors: Ben Abla Amina , Boeuf Guilhem , Elmarjou Ahmed , Dridi Cyrine , Poirier Florence , Changotade Sylvie , Lutomski Didier , Elm’selmi Abdellatif
Published: July 2021

Engineering of biomimetic motives have emerged as promising approaches to improving cells’ binding properties of biomaterials for tissue engineering and regenerative medicine. In this study, a bio-adhesive ligand including cell-binding domains of human fibronectin (FN) was engineered using recombinant protein technology, a major extracellular matrix (ECM) protein that interacts with a variety of integrins cell-surface’s receptors and other ECM proteins through specific binding domains. 9th and 10th fibronectin type III repeat containing Arginine-Glycine-Aspartic acid (RGD) and Pro-His-Ser-Arg-Asn (PHSRN) synergic site (FNIII9-10) were expressed in fusion with a Colored Multi Affinity Tag (CMAT) to develop a simplified production and characterization process. A recombinant fragment was produced in the bacterial system using E. coli with high yield purified protein by double affinity chromatography. Bio-adhesive surfaces were developed by passive coating of produced fragment onto non adhesive surfaces model. The recombinant fusion protein (CMAT-FNIII9/10) demonstrated an accurate monitoring capability during expression purification and adsorption assay. Finally, biological activity of recombinant FNIII9/10 was validated by cellular adhesion assay. Binding to α5β1 integrins were successfully validated using a produced fragment as a ligand. These results are robust supports to the rational development of bioactivation strategies for biomedical and biotechnological applications.
Norepinephrine May Oppose Other Neuromodulators to Impact Alzheimer’s Disease
Authors: Fitzgerald Paul J.
Published: July 2021

While much of biomedical research since the middle of the twentieth century has focused on molecular pathways inside the cell, there is increasing evidence that extracellular signaling pathways are also critically important in health and disease. The neuromodulators norepinephrine (NE), serotonin (5-hydroxytryptamine, 5HT), dopamine (DA), acetylcholine (ACH), and melatonin (MT) are extracellular signaling molecules that are distributed throughout the brain and modulate many disease processes. The effects of these five neuromodulators on Alzheimer’s disease (AD) are briefly examined in this paper, and it is hypothesized that each of the five molecules has a u-shaped (or Janus-faced) dose-response curve, wherein too little or too much signaling is pathological in AD and possibly other diseases. In particular it is suggested that NE is largely functionally opposed to 5HT, ACH, MT, and possibly DA in AD. In this scenario, physiological “balance” between the noradrenergic tone and that of the other three or four modulators is most healthy. If NE is largely functionally opposed to other prominent neuromodulators in AD, this may suggest novel combinations of pharmacological agents to counteract this disease. It is also suggested that the majority of cases of AD and possibly other diseases involve an excess of noradrenergic tone and a collective deficit of the other four modulators.
Thermodynamics and Intermolecular Interactions of Nicotinamide in Neat and Binary Solutions: Experimental Measurements and COSMO-RS Concentration Dependent Reactions Investigations
Authors: Cysewski Piotr , Przybyłek Maciej , Kowalska Anna , Tymorek Natalia
Published: July 2021

In this study, the temperature-dependent solubility of nicotinamide (niacin) was measured in six neat solvents and five aqueous-organic binary mixtures (methanol, 1,4-dioxane, acetonitrile, DMSO and DMF). It was discovered that the selected set of organic solvents offer all sorts of solvent effects, including co-solvent, synergistic, and anti-solvent features, enabling flexible tuning of niacin solubility. In addition, differential scanning calorimetry was used to characterize the fusion thermodynamics of nicotinamide. In particular, the heat capacity change upon melting was measured. The experimental data were interpreted by means of COSMO-RS-DARE (conductor-like screening model for realistic solvation–dimerization, aggregation, and reaction extension) for concentration dependent reactions. The solute–solute and solute–solvent intermolecular interactions were found to be significant in all of the studied systems, which was proven by the computed mutual affinity of the components at the saturated conditions. The values of the Gibbs free energies of pair formation were derived at an advanced level of theory (MP2), including corrections for electron correlation and zero point vibrational energy (ZPE). In all of the studied systems the self-association of nicotinamide was found to be a predominant intermolecular complex, irrespective of the temperature and composition of the binary system. The application of the COSMO-RS-DARE approach led to a perfect match between the computed and measured solubility data, by optimizing the parameter of intermolecular interactions.
Allosteric Modulation of GSK-3β as a New Therapeutic Approach in Limb Girdle Muscular Dystrophy R1 Calpain 3-Related
Authors: Rico Anabel , Guembelzu Garazi , Palomo Valle , Martínez Ana , Aiastui Ana , Casas-Fraile Leire , Valls Andrea , López de Munain Adolfo , Sáenz Amets
Published: July 2021

Limb-girdle muscular dystrophy R1 calpain 3-related (LGMDR1) is an autosomal recessive muscular dystrophy produced by mutations in the CAPN3 gene. It is a rare disease and there is no cure or treatment for the disease while the pathophysiological mechanism by which the absence of calpain 3 provokes the dystrophy in muscles is not clear. However, key proteins implicated in Wnt and mTOR signaling pathways, which regulate muscle homeostasis, showed a considerable reduction in their expression and in their phosphorylation in LGMDR1 patients’ muscles. Finally, the administration of tideglusib and VP0.7, ATP non-competitive inhibitors of glycogen synthase kinase 3β (GSK-3β), restore the expression and phosphorylation of these proteins in LGMDR1 cells, opening the possibility of their use as therapeutic options.
Modelling the Condensation Phenomena within the Radial Turbine of a Fuel Cell Turbocharger
Authors: Wittmann Tim , Lück Sebastian , Bode Christoph , Friedrichs Jens
Published: July 2021

Radial turbines used in automotive fuel cell turbochargers operate with humid air. The gas expansion in the turbine causes droplets to form, which then grow through condensation. The associated release of latent heat and decrease in the gaseous mass flow strongly influence the thermodynamics of the turbine. This study aims to investigate these phenomena. For this purpose, the classical nucleation theory and Young’s growth law are integrated into a Euler–Lagrange approach. The main advantages of this approach are the calculation of individual droplet trajectories and a full resolution of the droplet spectrum. The results indicate an onset of nucleation at the blade tip and in the tip gap, followed by nucleation over the entire blade span, depending on the humidity at the turbine inlet. With a saturated turbine inflow, condensation causes the outlet temperature to rise to almost the same level as at the inlet. In addition, condensation losses reduce the efficiency and the latent heat released by condensation leads to significant thermal throttling.
Hyperparasitism of Acroclisoides sinicus (Huang and Liao) (Hymenoptera: Pteromalidae) on Two Biological Control Agents of Halyomorpha halys
Authors: Mele Alberto , Scaccini Davide , Pozzebon Alberto
Published: July 2021

Halyomorpha halys (Stål) is an invasive Asian pest that causes severe crop losses on various crops. Nowadays, management strategies against this pest mainly rely on pesticide use, but biological control with egg parasitoids is considered the most promising long-term and sustainable solution. Trissolcus japonicus (Ashmead) and Trissolcus mitsukurii (Ashmead) are Asian egg parasitoids already present in Europe and are the most effective biological control agents of H. halys. Therefore, these two species are considered for biological control programs in Europe and other parts of the world. Acroclisoides sinicus (Huang and Liao) is a pteromalid parasitoid wasp that frequently emerged from H. halys egg masses collected in northern Italy. This species has been hypothesized to be a hyperparasitoid of Trissolcus spp. parasitoids. This study was carried out under laboratory conditions where A. sinicus was tested in no-choice and two-choice experiments to assess the host preference between T. japonicus and T. mitsukurii. Olfactory responses of A. sinicus from volatiles emitted from different potential hosts were also tested. In all trials, A. sinicus showed a clear preference for parasitizing H. halys eggs previously parasitized by T. mitsukurii compared to T. japonicus. In no-choice experiments, the impact of the hyperparasitoid on T. japonicus was low, showing an exploitation rate of 4.0%, while up to a 96.2% exploitation rate was observed on T. mitsukurii. Acroclisoides sinicus was also attracted by volatiles emitted by egg masses parasitized by T. mitsukurii, while no response was observed to egg masses parasitized by T. japonicus or not parasitized. Therefore, according to the results obtained here, A. sinicus could limit the population development of T. mitsukurii, while lesser effects are expected on T. japonicus.
Genetic Screening to Identify Candidate Resistance Alleles to Cry1F Corn in Fall Armyworm Using Targeted Sequencing
Authors: Schlum Katrina , Lamour Kurt , Tandy Peter , Emrich Scott J. , de Bortoli Caroline Placidi , Rao Tejas , Viteri Dillon Diego M. , Linares-Ramirez Angela M. , Jurat-Fuentes Juan Luis
Published: July 2021

Evolution of practical resistance is the main threat to the sustainability of transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt crops). Monitoring of resistance to Cry and Vip3A proteins produced by Bt crops is critical to mitigate the development of resistance. Currently, Cry/Vip3A resistance allele monitoring is based on bioassays with larvae from inbreeding field-collected moths. As an alternative, DNA-based monitoring tools should increase sensitivity and reduce overall costs compared to bioassay-based screening methods. Here, we evaluated targeted sequencing as a method allowing detection of known and novel candidate resistance alleles to Cry proteins. As a model, we sequenced a Cry1F receptor gene (SfABCC2) in fall armyworm (Spodoptera frugiperda) moths from Puerto Rico, a location reporting continued practical field resistance to Cry1F-producing corn. Targeted sequencing detected a previously reported Cry1F resistance allele (SfABCC2mut), in addition to a resistance allele originally described in S. frugiperda populations from Brazil. Moreover, targeted sequencing detected mutations in SfABCC2 as novel candidate resistance alleles. These results support further development of targeted sequencing for monitoring resistance to Bt crops and provide unexpected evidence for common resistance alleles in S. frugiperda from Brazil and Puerto Rico.
Turkestan Cockroaches Avoid Entering a Static Electric Field upon Perceiving an Attractive Force Applied to Antennae Inserted into the Field
Authors: Matsuda Yoshinori , Nonomura Teruo , Toyoda Hideyoshi
Published: July 2021

This study analysed the mechanism of avoidance behaviour by adult Turkestan cockroaches (Shelfordella lateralis Walker) in response to a static electric field (S-EF) formed in the space between a negatively charged polyvinyl chloride-insulated iron plate (N-PIP) and a grounded metal net (G-MN). The negative surface charge supplied to the iron plate by a voltage generator caused the G-MN to polarise positively via electrostatic induction. In the S-EF, the negative charge of the N-PIP created a repulsive force that pushed free electrons in the field toward the ground via the G-MN. When insects released in the space surrounded by the S-EF inserted their antennae into the S-EF, they pulled them back reflexively and moved backward. The analysis indicated that an electric current flowed transiently toward the ground when an insect inserted its antennae into the S-EF. The insect became positively charged via this discharge and was attracted to the opposite pole (N-PIP). In response to this attractive force, the insect pulled its antennae back quickly. The positive electrification caused by the removal of free electrons from the antenna tip triggered the avoidance behaviour.
Is There an Association between Epicardial Adipose Tissue and Outcomes after Paroxysmal Atrial Fibrillation Catheter Ablation?
Authors: Hammache Néfissa , Pegorer-Sfes Hugo , Benali Karim , Magnin Poull Isabelle , Olivier Arnaud , Echivard Mathieu , Pace Nathalie , Minois Damien , Sadoul Nicolas , Mandry Damien , Sellal Jean Marc , de Chillou Christian
Published: July 2021

Background: In patients undergoing paroxysmal atrial fibrillation (PAF) ablation, pulmonary vein isolation (PVI) alone fails in maintaining sinus rhythm in up to one third of patients after a first catheter ablation. Epicardial adipose tissue (EAT), as an endocrine-active organ, could play a role in the recurrence of AF after catheter ablation. Objective: To evaluate the predictive value of clinical, echocardiographic, biological parameters and epicardial fat density measured by computed tomography scan (CT-scan) on AF recurrence in PAF patients who underwent a first pulmonary vein isolation procedure using radiofrequency (RF). Methods: This monocentric retrospective study included all patients undergoing first-time RF PAF ablation at the Nancy University Hospital between March 2015 and December 2018 with one-year follow-up. Results: 389 patients were included, of whom 128 (32.9%) had AF recurrence at one-year follow-up. Neither total-EAT volume (88.6 ± 37.2 cm3 vs. 91.4 ± 40.5 cm3, p = 0.519), nor total-EAT radiodensity (−98.8 ± 4.1 HU vs. −98.8 ± 3.8 HU, p = 0.892) and left atrium-EAT radiodensity (−93.7 ± 4.3 HU vs. −93.4 ± 6.0 HU, p = 0.556) were significantly associated with AF recurrence after PAF ablation. In multivariate analysis, previous cavo-tricuspid isthmus (CTI) ablation, ablation procedure duration, BNP and triglyceride levels remained independently associated with AF recurrence after catheter ablation at 12-months follow-up. Conclusion: Contrary to persistent AF, EAT parameters are not associated with AF recurrence after paroxysmal AF ablation. Thus, the role of the metabolic atrial substrate in PAF pathophysiology appears less obvious than in persistent AF.
Quality of Life in Female Patients Following Ileal Neobladder and Ileal Conduit: Where Are We?
Authors: Siracusano Salvatore , Zaka Agustina , Romantini Federico , Porcaro Antonio Benito , Vicentini Carlo , Lonardi Cristina
Published: July 2021

Women undergoing a radical cystectomy (RC) followed by a urinary diversion (UD) for bladder cancer (BC), experience a substantial reduction in health-related quality of life (HRQOL). At present, studies comparing long-term QOL outcomes for different UD methods in female patients are lacking. We summarize the current state of the QoL assessment in female patients after an RC.
The Effects of Temperature and Salinity Stressors on the Survival, Condition and Valve Closure of the Manila Clam, Venerupis philippinarum in a Holding Facility
Authors: Bae Hyeonmi , Im Jibin , Joo Soobin , Cho Boongho , Kim Taewon
Published: July 2021

We investigated the response of the Manila clam Venerupis philippinarum to possible temperature and salinity changes in a holding facility. First, clams were exposed to four temperatures for 15 days. Valve closure and survival of clams exposed to seawater at 18 °C were higher than that of those exposed to seawater at 24 °C. Second, clams were exposed to six salinities for 15 days. Survival of clams exposed to two salinity fluctuation conditions (24–30 and 27–24 psu) was lower than that of clams exposed to constant 30 psu conditions. Valve closures of clams exposed to constant low salinity conditions (24 psu) and two salinity fluctuation conditions (24–30 and 27–24 psu) were higher than those exposed to constant 30 psu conditions. Lastly, clams were exposed to two different temperatures and three different salinity conditions for 8 days. Valve closure and survival decreased significantly under the combination of 24 °C and 18 psu. These results suggest that an increase in temperature or a wider range of salinity fluctuations are detrimental to the survival of the Manila clam. The synergistic effect of temperature and salinity stressors may decrease the survival period of clams compared to the effect of a single stressor.
The Effect of Object Geometric Features on Frequency Inflection Point of Underwater Active Electrolocation System
Authors: Han Yuanjian , Wu Hailong , Peng Jiegang , Ou Bin
Published: July 2021

Biologists have discovered a kind of weakly electric fish that identifies its prey by using active electrolocation in virtual darkness. In this study, we built an underwater active electrolocation system platform designed to investigate the biological mechanism allowing these fish to distinguish objects and determine how the amplitude information-frequency characteristic (AIFC) response are affected by the geometric characteristics of target objects in the active electrolocation system. We used a single-frequency sinusoidal signal to scan metal objects in different orientations and observed the amplitude information response variation of the disturbed detection signal. The detection frequency dead zone (DFDZ) and the frequency inflection point (FIP) were used to characterize the variation. In addition, we repeated the experiments after replacing the metal objects with objects of different materials and geometric characteristics to summarize the general laws. Our results showed that the FIP value of the detection signal was lowest when the object was detected in the orientation of its corner and highest when the object was detected in the orientation of its surface. The geometrical characteristics of metal objects in different orientations have a certain influence on the amplitude of the detection signal. Article Highlights: (1) The general law between the shape of metal probed objects, and electric field detection signal was found and summarized. (2) We used a single-frequency sinusoidal signal to scan regular metal probed objects, and it was found that the frequency inflection point (FIP) of the metal probed objects edge was the highest, whereas that of the corner was the lowest. (3) The shape of a metal object can be recognized by scanning regular metal objects with an electric field signal.
Strategies to Integrate Genomic Medicine into Clinical Care: Evidence from the IGNITE Network
Authors: Sperber Nina R. , Dong Olivia M. , Roberts Megan C. , Dexter Paul , Elsey Amanda R. , Ginsburg Geoffrey S. , Horowitz Carol R. , Johnson Julie A. , Levy Kenneth D. , Ong Henry , Peterson Josh F. , Pollin Toni I. , Rakhra-Burris Tejinder , Ramos Michelle A. , Skaar Todd , Orlando Lori A.
Published: July 2021

The complexity of genomic medicine can be streamlined by implementing some form of clinical decision support (CDS) to guide clinicians in how to use and interpret personalized data; however, it is not yet clear which strategies are best suited for this purpose. In this study, we used implementation science to identify common strategies for applying provider-based CDS interventions across six genomic medicine clinical research projects funded by an NIH consortium. Each project’s strategies were elicited via a structured survey derived from a typology of implementation strategies, the Expert Recommendations for Implementing Change (ERIC), and follow-up interviews guided by both implementation strategy reporting criteria and a planning framework, RE-AIM, to obtain more detail about implementation strategies and desired outcomes. We found that, on average, the three pharmacogenomics implementation projects used more strategies than the disease-focused projects. Overall, projects had four implementation strategies in common; however, operationalization of each differed in accordance with each study’s implementation outcomes. These four common strategies may be important for precision medicine program implementation, and pharmacogenomics may require more integration into clinical care. Understanding how and why these strategies were successfully employed could be useful for others implementing genomic or precision medicine programs in different contexts.
Localization of METTL16 at the Nuclear Periphery and the Nucleolus Is Cell Cycle-Specific and METTL16 Interacts with Several Nucleolar Proteins
Authors: Stixová Lenka , Komůrková Denisa , Svobodová Kovaříková Alena , Fagherazzi Paolo , Bártová Eva
Published: July 2021

METTL16 methyltransferase is responsible for the methylation of N6-adenosine (m6A) in several RNAs. In mouse cells, we showed that the nuclear distribution of METTL16 is cell cycle-specific. In the G1/S phases, METTL16 accumulates to the nucleolus, while in the G2 phase, the level of METTL16 increases in the nucleoplasm. In metaphase and anaphase, there is a very low pool of the METTL16 protein, but in telophase, residual METTL16 appears to be associated with the newly formed nuclear lamina. In A-type lamin-depleted cells, we observed a reduction of METTL16 when compared with the wild-type counterpart. However, METTL16 does not interact with A-type and B-type lamins, but interacts with Lamin B Receptor (LBR) and Lap2α. Additionally, Lap2α depletion caused METTL16 downregulation in the nuclear pool. Furthermore, METTL16 interacted with DDB2, a key protein of the nucleotide excision repair (NER), and also with nucleolar proteins, including TCOF, NOLC1, and UBF1/2, but not fibrillarin. From this view, the METTL16 protein may also regulate the transcription of ribosomal genes because we observed that the high level of m6A in 18S rRNA appeared in cells with upregulated METTL16.
Experimental Study on Activated Carbon-MIL-101(Cr) Composites for Ethanol Vapor Adsorption
Authors: Liu Zhongbao , Gao Jiayang , Qi Xin , Zhao Zhi , Sun Han
Published: July 2021

In this study, the hydrothermal method was used to synthesize MIL-101(Cr), and activated carbon (AC) with different content was incorporated in to MIL-101(Cr), thereby obtaining AC-MIL-101(Cr) composite material with a huge specific surface area. The physical properties of MIL-101(Cr) and AC-MIL-101(Cr) were characterized by powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), nitrogen adsorption and desorption and specific surface area testing, and ethanol vapor adsorption performance testing. The results show that with the increase of activated carbon content, the thermal stability of AC-MIL-101(Cr) is improved. Compared with the pure sample, the BET specific surface area and pore volume of AC-MIL-101(Cr) have increased. In the relative pressure range of 0–0.4, the saturated adsorption capacity of AC-MIL-101(Cr) to ethanol vapor decreases slightly. It is lower than MIL-101(Cr), but its adsorption rate is improved. Therefore, AC-MIL-101(Cr)/ethanol vapor has a good application prospect in adsorption refrigeration systems. The exploration of AC-MIL-101(Cr) composite materials in this paper provides a reference for the future application of carbon-based/MOFS composite adsorbent/ethanol vapor working fluid in adsorption refrigeration.
Microstructure and Properties of TiB2 Composites Produced by Spark Plasma Sintering with the Addition of Ti5Si3
Authors: Twardowska Agnieszka , Podsiadło Marcin , Sulima Iwona , Bryła Krzysztof , Hyjek Paweł
Published: July 2021

Titanium diboride (TiB2) is a hard, refractory material, attractive for a number of applications, including wear-resistant machine parts and tools, but it is difficult to densify. The spark plasma sintering (SPS) method allows producing TiB2-based composites of high density with different sintering aids, among them titanium silicides. In this paper, Ti5Si3 is used as a sintering aid for the sintering of TiB2/10 wt % Ti5Si3 and TiB2/20 wt % Ti5Si3 composites at 1600 °C and 1700 °C for 10 min. The phase composition of the initial powders and produced composites was analyzed by the X-ray diffraction method using CuKα radiation. The microstructure was examined using scanning electron microscopy, accompanied by energy-dispersive spectroscopy (EDS). The hardness was determined using a diamond indenter of Vickers geometry loaded at 9.81 N. Friction–wear properties were tested in the dry sliding test in a ball-on-disc configuration, using WC as a counterpart material. The major phases present in the TiB2/Ti5Si3 composites were TiB2 and Ti5Si3. Traces of TiC were also identified. The hardness of the TiB2/Ti5Si3 composites was in the range of 1860–2056 HV1 and decreased with Ti5Si3 content, as well as the specific wear rate Wv. The coefficient of friction for the composites was in the range of 0.5–0.54, almost the same as for TiB2 sinters. The main mechanism of wear was abrasive.