bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomics Data Analysis for the Identification of Proteins and Derived Proteotypic Peptides of Potential Use as Putative Drought Tolerance Markers for Quercus ilex
Authors: San-Eufrasio Bonoso , Bigatton Ezequiel Darío , Guerrero-Sánchez Victor M. , Chaturvedi Palak , Jorrín-Novo Jesús V. , Rey María-Dolores , Castillejo María Ángeles
Published: March 2021

Drought is one of the main causes of mortality in holm oak (Quercus ilex) seedlings used in reforestation programs. Although this species shows high adaptability to the extreme climate conditions prevailing in Southern Spain, its intrinsic genetic variability may play a role in the differential response of some populations and individuals. The aim of this work was to identify proteins and derived proteotypic peptides potentially useful as putative markers for drought tolerance in holm oak by using a targeted post-acquisition proteomics approach. For this purpose, we used a set of proteins identified by shotgun (LC-MSMS) analysis in a drought experiment on Q. ilex seedlings from four different provenances (viz. the Andalusian provinces Granada, Huelva, Cadiz and Seville). A double strategy involving the quantification of proteins and target peptides by shotgun analysis and post-acquisition data analysis based on proteotypic peptides was used. To this end, an initial list of proteotypic peptides from proteins highly represented under drought conditions was compiled that was used in combination with the raw files from the shotgun experiment to quantify the relative abundance of the fragment’s ion peaks with the software Skyline. The most abundant peptides under drought conditions in at least two populations were selected as putative markers of drought tolerance. A total of 30 proteins and 46 derived peptides belonging to the redox, stress-related, synthesis,-folding and degradation, and primary and secondary metabolism functional groups were thus identified. Two proteins (viz., subtilisin and chaperone GrpE protein) were found at increased levels in three populations, which make them especially interesting for validation drought tolerance markers in subsequent experiments.
Direct Metal-Free Transformation of Alkynes to Nitriles: Computational Evidence for the Precise Reaction Mechanism
Authors: Hok Lucija , Vianello Robert
Published: March 2021

Density functional theory calculations elucidated the precise reaction mechanism for the conversion of diphenylacetylenes into benzonitriles involving the cleavage of the triple C≡C bond, with N-iodosuccinimide (NIS) as an oxidant and trimethylsilyl azide (TMSN3) as a nitrogen donor. The reaction requires six steps with the activation barrier ΔG‡ = 33.5 kcal mol−1 and a highly exergonic reaction free-energy ΔGR = −191.9 kcal mol−1 in MeCN. Reaction profiles agree with several experimental observations, offering evidence for the formation of molecular I2, interpreting the necessity to increase the temperature to finalize the reaction, and revealing thermodynamic aspects allowing higher yields for alkynes with para-electron-donating groups. In addition, the proposed mechanism indicates usefulness of this concept for both internal and terminal alkynes, eliminates the option to replace NIS by its Cl- or Br-analogues, and strongly promotes NaN3 as an alternative to TMSN3. Lastly, our results advise increasing the solvent polarity as another route to advance this metal-free strategy towards more efficient processes.
Pleiotropic Roles of ABC Transporters in Breast Cancer
Authors: He Ji , Fortunati Erika , Liu Dong-Xu , Li Yan
Published: March 2021

Chemotherapeutics are the mainstay treatment for metastatic breast cancers. However, the chemotherapeutic failure caused by multidrug resistance (MDR) remains a pivotal obstacle to effective chemotherapies of breast cancer. Although in vitro evidence suggests that the overexpression of ATP-Binding Cassette (ABC) transporters confers resistance to cytotoxic and molecularly targeted chemotherapies by reducing the intracellular accumulation of active moieties, the clinical trials that target ABCB1 to reverse drug resistance have been disappointing. Nevertheless, studies indicate that ABC transporters may contribute to breast cancer development and metastasis independent of their efflux function. A broader and more clarified understanding of the functions and roles of ABC transporters in breast cancer biology will potentially contribute to stratifying patients for precision regimens and promote the development of novel therapies. Herein, we summarise the current knowledge relating to the mechanisms, functions and regulations of ABC transporters, with a focus on the roles of ABC transporters in breast cancer chemoresistance, progression and metastasis.
SIRT1 Expression and Regulation in the Primate Testis
Authors: Wahab Fazal , Rodriguez Polo Ignacio , Behr Rüdiger
Published: March 2021

The epigenetic mechanisms controlling germ cell development and differentiation are still not well understood. Sirtuin-1 (SIRT1) is a nicotinamide adenosine dinucleotide (NAD)-dependent histone deacetylase and belongs to the sirtuin family of deacetylases. It catalyzes the removal of acetyl groups from a number of protein substrates. Some studies reported a role of SIRT1 in the central and peripheral regulation of reproduction in various non-primate species. However, testicular SIRT1 expression and its possible role in the testis have not been analyzed in primates. Here, we document expression of SIRT1 in testes of different primates and some non-primate species. SIRT1 is expressed mainly in the cells of seminiferous tubules, particularly in germ cells. The majority of SIRT1-positive germ cells were in the meiotic and postmeiotic phase of differentiation. However, SIRT1 expression was also observed in selected premeiotic germ cells, i.e., spermatogonia. SIRT1 co-localized in spermatogonia with irisin, an endocrine factor specifically expressed in primate spermatogonia. In marmoset testicular explant cultures, SIRT1 transcript levels are upregulated by the addition of irisin as compared to untreated controls explants. Rhesus macaques are seasonal breeders with high testicular activity in winter and low testicular activity in summer. Of note, SIRT1 mRNA and SIRT1 protein expression are changed between nonbreeding (low spermatogenesis) and breeding (high spermatogenesis) season. Our data suggest that SIRT1 is a relevant factor for the regulation of spermatogenesis in primates. Further mechanistic studies are required to better understand the role of SIRT1 during spermatogenesis.
Mitochondria and Pharmacologic Cardiac Conditioning—At the Heart of Ischemic Injury
Authors: Lotz Christopher , Herrmann Johannes , Notz Quirin , Meybohm Patrick , Kehl Franz
Published: March 2021

Pharmacologic cardiac conditioning increases the intrinsic resistance against ischemia and reperfusion (I/R) injury. The cardiac conditioning response is mediated via complex signaling networks. These networks have been an intriguing research field for decades, largely advancing our knowledge on cardiac signaling beyond the conditioning response. The centerpieces of this system are the mitochondria, a dynamic organelle, almost acting as a cell within the cell. Mitochondria comprise a plethora of functions at the crossroads of cell death or survival. These include the maintenance of aerobic ATP production and redox signaling, closely entwined with mitochondrial calcium handling and mitochondrial permeability transition. Moreover, mitochondria host pathways of programmed cell death impact the inflammatory response and contain their own mechanisms of fusion and fission (division). These act as quality control mechanisms in cellular ageing, release of pro-apoptotic factors and mitophagy. Furthermore, recently identified mechanisms of mitochondrial regeneration can increase the capacity for oxidative phosphorylation, decrease oxidative stress and might help to beneficially impact myocardial remodeling, as well as invigorate the heart against subsequent ischemic insults. The current review highlights different pathways and unresolved questions surrounding mitochondria in myocardial I/R injury and pharmacological cardiac conditioning.
Mechanisms of Proteolytic Enzymes and Their Inhibition in QM/MM Studies
Authors: Elsässer Brigitta , Goettig Peter
Published: March 2021

Experimental evidence for enzymatic mechanisms is often scarce, and in many cases inadvertently biased by the employed methods. Thus, apparently contradictory model mechanisms can result in decade long discussions about the correct interpretation of data and the true theory behind it. However, often such opposing views turn out to be special cases of a more comprehensive and superior concept. Molecular dynamics (MD) and the more advanced molecular mechanical and quantum mechanical approach (QM/MM) provide a relatively consistent framework to treat enzymatic mechanisms, in particular, the activity of proteolytic enzymes. In line with this, computational chemistry based on experimental structures came up with studies on all major protease classes in recent years; examples of aspartic, metallo-, cysteine, serine, and threonine protease mechanisms are well founded on corresponding standards. In addition, experimental evidence from enzyme kinetics, structural research, and various other methods supports the described calculated mechanisms. One step beyond is the application of this information to the design of new and powerful inhibitors of disease-related enzymes, such as the HIV protease. In this overview, a few examples demonstrate the high potential of the QM/MM approach for sophisticated pharmaceutical compound design and supporting functions in the analysis of biomolecular structures.
Murine Esophagus Expresses Glial-Derived Central Nervous System Antigens
Authors: Kapitza Christopher , Chunder Rittika , Scheller Anja , Given Katherine S. , Macklin Wendy B. , Enders Michael , Kuerten Stefanie , Neuhuber Winfried L. , Wörl Jürgen
Published: March 2021

Multiple sclerosis (MS) has been considered to specifically affect the central nervous system (CNS) for a long time. As autonomic dysfunction including dysphagia can occur as accompanying phenomena in patients, the enteric nervous system has been attracting increasing attention over the past years. The aim of this study was to identify glial and myelin markers as potential target structures for autoimmune processes in the esophagus. RT-PCR analysis revealed glial fibrillary acidic protein (GFAP), proteolipid protein (PLP), and myelin basic protein (MBP) expression, but an absence of myelin oligodendrocyte glycoprotein (MOG) in the murine esophagus. Selected immunohistochemistry for GFAP, PLP, and MBP including transgenic mice with cell-type specific expression of PLP and GFAP supported these results by detection of (1) GFAP, PLP, and MBP in Schwann cells in skeletal muscle and esophagus; (2) GFAP, PLP, but no MBP in perisynaptic Schwann cells of skeletal and esophageal motor endplates; (3) GFAP and PLP, but no MBP in glial cells surrounding esophageal myenteric neurons; and (4) PLP, but no GFAP and MBP in enteric glial cells forming a network in the esophagus. Our results pave the way for further investigations regarding the involvement of esophageal glial cells in the pathogenesis of dysphagia in MS.
Base-Pair Opening Dynamics Study of Fluoride Riboswitch in the Bacillus cereus CrcB Gene
Authors: Lee Juhyun , Sung Si-Eun , Lee Janghyun , Kang Jin Young , Lee Joon-Hwa , Choi Byong-Seok
Published: March 2021

Riboswitches are segments of noncoding RNA that bind with metabolites, resulting in a change in gene expression. To understand the molecular mechanism of gene regulation in a fluoride riboswitch, a base-pair opening dynamics study was performed with and without ligands using the Bacillus cereus fluoride riboswitch. We demonstrate that the structural stability of the fluoride riboswitch is caused by two steps depending on ligands. Upon binding of a magnesium ion, significant changes in a conformation of the riboswitch occur, resulting in the greatest increase in their stability and changes in dynamics by a fluoride ion. Examining hydrogen exchange dynamics through NMR spectroscopy, we reveal that the stabilization of the U45·A37 base-pair due to the binding of the fluoride ion, by changing the dynamics while maintaining the structure, results in transcription regulation. Our results demonstrate that the opening dynamics and stabilities of a fluoride riboswitch in different ion states are essential for the genetic switching mechanism.
Formation of Autoimmune Lesions Is Independent of Antibiotic Treatment in NOD Mice
Authors: Sato Mami , Arakaki Rieko , Tawara Hiroaki , Tsunematsu Takaaki , Ishimaru Naozumi
Published: March 2021

The relationship between autoimmunity and changes in intestinal microbiota is not yet fully understood. In this study, the role of intestinal microbiota in the onset and progression of autoimmune lesions in non-obese diabetic (NOD) mice was evaluated by administering antibiotics to alter their intestinal microenvironment. Flow cytometric analysis of spleen cells showed that antibiotic administration did not change the proportion or number of T and B cells in NOD mice, and pathological analysis demonstrated that autoimmune lesions in the salivary glands and in the pancreas were also not affected by antibiotic administration. These results suggest that the onset and progression of autoimmunity may be independent of enteral microbiota changes. Our findings may be useful for determining the appropriate use of antibiotics in patients with autoimmune diseases who are prescribed drugs to maintain systemic immune function.
Analysis of HPV Integrations in Mexican Pre-Tumoral Cervical Lesions Reveal Centromere-Enriched Breakpoints and Abundant Unspecific HPV Regions
Authors: Garza-Rodríguez María Lourdes , Oyervides-Muñoz Mariel Araceli , Pérez-Maya Antonio Alí , Sánchez-Domínguez Celia Nohemí , Berlanga-Garza Anais , Antonio-Macedo Mauro , Valdés-Chapa Lezmes Dionicio , Vidal-Torres Diego , Vidal-Gutiérrez Oscar , Pérez-Ibave Diana Cristina , Treviño Víctor
Published: March 2021

Human papillomavirus (HPV) DNA integration is a crucial event in cervical carcinogenesis. However, scarce studies have focused on studying HPV integration (HPVint) in early-stage cervical lesions. Using HPV capture followed by sequencing, we investigated HPVint in pre-tumor cervical lesions. Employing a novel pipeline, we analyzed reads containing direct evidence of the integration breakpoint. We observed multiple HPV infections in most of the samples (92%) with a median integration rate of 0.06% relative to HPV mapped reads corresponding to two or more sequence breakages. Unlike cancer studies, most integrations events were unique (supported by one read), consistent with the lack of clonal selection. Congruent to other studies, we found that breakpoints could occur, practically, in any part of the viral genome. We noted that L1 had a higher frequency of rupture integration (25%). Based on host genome integration frequencies, we found previously reported integration sites in cancer for genes like FHIT, CSMD1, and LRP1B and putatively many new ones such as those exemplified in CSMD3, ROBO2, and SETD3. Similar host integrations regions and genes were observed in diverse HPV types within many genes and even equivalent integration positions in different samples and HPV types. Interestingly, we noted an enrichment of integrations in most centromeres, suggesting a possible mechanism where HPV exploits this structural machinery to facilitate integration. Supported by previous findings, overall, our analysis provides novel information and insights about HPVint.
A Voluntary Statewide Newborn Screening Pilot for Spinal Muscular Atrophy: Results from Early Check
Authors: Kucera Katerina , Taylor Jennifer , Robles Veronica , Clinard Kristin , Migliore Brooke , Boyea Beth , Okoniewski Katherine , Duparc Martin , Rehder Catherine , Shone Scott , Fan Zheng , Raspa Melissa , Peay Holly , Wheeler Anne , Powell Cynthia , Bailey Donald , Gehtland Lisa
Published: March 2021

Prior to statewide newborn screening (NBS) for spinal muscular atrophy (SMA) in North Carolina, U.S.A., we offered voluntary screening through the Early Check (EC) research study. Here, we describe the EC experience from October 2018 through December 2020. We enrolled a total of 12,065 newborns and identified one newborn with 0 copies of SMN1 and two copies of SMN2, consistent with severe early onset of SMA. We also detected one false positive result, likely stemming from an unrelated blood disorder associated with a low white blood cell count. We evaluated the timing of NBS for babies enrolled prenatally (n = 932) and postnatally (n = 11,133) and reasons for delays in screening and reporting. Although prenatal enrollment led to faster return of results (median = 13 days after birth), results for babies enrolled postnatally were still available within a timeframe (median = 21 days after birth) that allowed the opportunity to receive essential treatment early in life. We evaluated an SMA q-PCR screening method at two separate time points, confirming the robustness of the assay. The pilot project provided important information about SMA screening in anticipation of forthcoming statewide expansion as part of regular NBS.
An Ontological Framework to Facilitate Early Detection of ‘Radicalization’ (OFEDR)—A Three World Perspective
Authors: Wendelberg Linda
Published: March 2021

This paper presents an ontology that involves using information from various sources from different disciplines and combining it in order to predict whether a given person is in a radicalization process. The purpose of the ontology is to improve the early detection of radicalization in persons, thereby contributing to increasing the extent to which the unwanted escalation of radicalization processes can be prevented. The ontology combines findings related to existential anxiety that are related to political radicalization with well-known criminal profiles or radicalization findings. The software Protégé, delivered by the technical field at Stanford University, including the SPARQL tab, is used to develop and test the ontology. The testing, which involved five models, showed that the ontology could detect individuals according to “risk profiles” for subjects based on existential anxiety. SPARQL queries showed an average detection probability of 5% including only a risk population and 2% on a whole test population. Testing by using machine learning algorithms proved that inclusion of less than four variables in each model produced unreliable results. This suggest that the Ontology Framework to Facilitate Early Detection of ‘Radicalization’ (OFEDR) ontology risk model should consist of at least four variables to reach a certain level of reliability. Analysis shows that use of a probability based on an estimated risk of terrorism may produce a gap between the number of subjects who actually have early signs of radicalization and those found by using probability estimates for extremely rare events. It is reasoned that an ontology exists as a world three object in the real world.
The Influence of Port Tugs on Improving the Navigational Safety of the Port
Authors: Paulauskas Vytautas , Simutis Martynas , Plačiene Birute , Barzdžiukas Raimondas , Jonkus Martynas , Paulauskas Donatas
Published: March 2021

Port tugs are an important element in port activity and navigational safety issues. Port tugs ensure the safety of big ships while they are entering, manoeuvring, mooring and unmooring, and are of huge importance during other port operations. At the same time, optimizing the number of port tugs and tug bollard pull is also important from a port navigational safety and economic point of view. Calculation and evaluation methods of the optimal request for tugs bollard pull, in particular, port operations, are very important in order to guarantee the navigational safety of the port and ships during the main ship operations in the port. This article provides the number of requested port tugs and bollard pull calculation and evaluation methods on the basis of forces and moments acting on ships. On the basis of real ship voyages and manoeuvring at ports data as well as high accuracy simulators, theoretical methods were used, which were followed by our conclusions and recommendations, which can be used by port harbour masters and tug companies. Modern tugs have become an important element and integral part of modern port navigational safety. Such modern port tugs are also used for navigational safety and other important port functions and activities, such as fire protection and search and rescue operations. The optimal number and capacity evaluation of port tugs depending on port capacity and conditions are studied in this article.
Candidate Core Designs for the Transformational Challenge Reactor
Authors: Ade Brian J. , Betzler Benjamin R. , Wysocki Aaron J. , Greenwood Michael S. , Chesser Phillip C. , Terrani Kurt A. , Jain Prashant K. , Burns Joseph R. , Hiscox Briana D. , Rader Jordan D. , Heineman Jesse J. W. , Heidet Florent , Bergeron Aurelien , Sterbentz James W. , Holschuh Tommy V. , Brown Nicholas R. , Kile Robert F.
Published: March 2021

Early cycle activities under the Transformational Challenge Reactor (TCR) program focused on analyzing and maturing four reactor core design concepts: two fast-spectrum systems and two thermal-spectrum systems. A rapid, iterative approach has been implemented through which designs can be modified and analyzed and subcomponents can be manufactured in parallel over time frames of weeks rather than months or years. To meet key program initiatives (e.g., timeline, material use), several constraints—including fissile material availability (less than 250 kg of HALEU), component availabilities, materials compatibility, and additive manufacturing capabilities—were factored into the design effort, yielding small (less than one cubic meter in volume) cores with near-term viability. The fast-spectrum designs did not meet the fissile material constraint, so the thermal-spectrum systems became the primary design focus. Since significant progress has been made on advanced moderator materials (YHx) under the TCR program, gas-cooled thermal-spectrum systems using less than 250 kg of HALEU that occupy less than 1 m3 are now feasible. The designs for two of these systems have been evolved and matured. In both thermal-spectrum design concepts, bidirectional coolant flow is used. Coolant flows down through YHx moderator elements and is reversed in a bottom manifold and core support structure, and then flows up though or around the fuel elements. The main difference between the two thermal-spectrum design concepts is the fuel elements—one uses traditional UO2 ceramic fuel, and the other uses UN-bearing TRISO fuel particles embedded inside a SiC matrix. Core neutronics and thermal performance for these systems are assessed and summarized herein.
The Effect of the Flux Separability Approximation on Multigroup Neutron Transport
Authors: Nelson Adam G. , Boyd William , Romano Paul K.
Published: March 2021

The angular dependence of flux-weighted multigroup cross sections is commonly neglected when generating multigroup libraries. The error of this flux separability approximation is typically not isolated from other error sources due to a lack of availability of library generation and corresponding solvers that cannot relax this approximation. These errors can now be isolated and quantified with the availability of a multigroup Monte Carlo transport and multigroup library-generation capability in the OpenMC Monte Carlo transport code. This work will discuss relevant details of the OpenMC implementation, provide an example case useful for detailing the type of errors one can expect from making the flux separability approximation, and end with more realistic problems which show the impact of the approximation and highlight how it can strongly arise from an energy-dependent resonance absorption effect. Since the angle-dependence is intrinsically linked to the energy group structure, these examples also show that relaxing the flux separability approximation with angle-dependent cross sections could be used to reduce either the fine-tuning required to set a multigroup energy structure for a specific reactor type or the number of energy groups required to obtain a desired level of accuracy for a given problem. This trade-off could increase the costs of generating multigroup cross sections, and has the potential to require more memory for storing the multigroup library during the transport calculations, but it can significantly reduce the computational time required since the runtime of a discrete ordinates or method of characteristics neutron transport solver scales roughly linearly with the number of groups.
Evaluation of 11 DNA Automated Extraction Protocols for the Detection of the 5 Mains Candida Species from Artificially Spiked Blood
Authors: Menu Estelle , Landier Jordi , Prudent Elsa , Ranque Stéphane , L’Ollivier Coralie
Published: March 2021

The molecular detection of Candida plays an important role in the diagnosis of candidaemia, a major cause of morbidity and mortality. The sensitivity of this diagnosis is partly related to the efficiency of yeast DNA extraction. In this monocentric study, we investigated the suitability of 11 recent automated procedures for the extraction of low and high amounts of Candida DNA from spiked blood. The efficacy of the DNA extraction procedures to detect Candida spp. in blood samples ranged from 31.4% to 80.6%. The NucliSENSTM easyMAGTM procedure was the most efficient, for each species and each inoculum. It significantly outperformed the other procedures at the lower Candida inocula mimicking the clinical setting. This study highlighted a heterogeneity in DNA extraction efficacy between the five main Candida species (Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis and Candida krusei). Up to five automated procedures were appropriate for C. krusei DNA extraction, whereas only one method yielded an appropriate detection of low amount of C. tropicalis. In the era of the syndromic approach to bloodstream infection diagnosis, this evaluation of 11 automated DNA extraction methods for the PCR diagnosis of candidaemia, puts the choice of an appropriate method in routine diagnosis within the reach of laboratories.
Fungal-Induced Programmed Cell Death
Authors: Williams Thomas J. , Gonzales-Huerta Luis E. , Armstrong-James Darius
Published: March 2021

Fungal infections are a cause of morbidity in humans, and despite the availability of a range of antifungal treatments, the mortality rate remains unacceptably high. Although our knowledge of the interactions between pathogenic fungi and the host continues to grow, further research is still required to fully understand the mechanism underpinning fungal pathogenicity, which may provide new insights for the treatment of fungal disease. There is great interest regarding how microbes induce programmed cell death and what this means in terms of the immune response and resolution of infection as well as microbe-specific mechanisms that influence cell death pathways to aid in their survival and continued infection. Here, we discuss how programmed cell death is induced by fungi that commonly cause opportunistic infections, including Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans, the role of programmed cell death in fungal immunity, and how fungi manipulate these pathways.
Genetic Diversity and Pathogenicity of Rhizoctonia spp. Isolates Associated with Red Cabbage in Samsun (Turkey)
Authors: Erper Ismail , Ozer Goksel , Kalendar Ruslan , Avci Sirin , Yildirim Elif , Alkan Mehtap , Turkkan Muharrem
Published: March 2021

A total of 132 Rhizoctonia isolates were recovered from red cabbage plants with root rot and wirestem symptoms in the province of Samsun (Turkey) between 2018 and 2019. Based on the sequence analysis of the internal transcribed spacer (ITS) region located between the 18S and 28S ribosomal RNA genes and including nuclear staining, these 124 isolates were assigned to multinucleate Rhizoctonia solani, and eight were binucleate Rhizoctonia. The most prevalent anastomosis group (AG) was AG 4 (84%), which was subdivided into AG 4 HG-I (81%) and AG 4 HG-III (3%), followed by AG 5 (10%) and AG-A (6%), respectively. The unweighted pair group method phylogenetic tree resulting from the data of 68 isolates with the inter-PBS amplification DNA profiling method based on interspersed retrotransposon element sequences confirmed the differentiation of AGs with a higher resolution. In the greenhouse experiment with representative isolates (n = 24) from AGs on red cabbage (cv. Rondale), the disease severity index was between 3.33 and 4.0 for multinucleate AG isolates and ranged from 2.5 to 3.17 for AG-A isolates. In the pathogenicity assay of six red cabbage cultivars, one isolate for each AG was tested using a similar method, and all cultivars were susceptible to AG 4 HG-I and AG 4 HG-III isolates. Redriver and Remale were moderately susceptible, while Rescue, Travero, Integro, and Rondale were susceptible to the AG 5 isolate. The results indicate that the most prevalent and aggressive AGs of Rhizoctonia are devastating pathogens to red cabbage, which means that rotation with nonhost-crops for these AGs may be the most effective control strategy. This is the first comprehensive study of Rhizoctonia isolates in red cabbage using a molecular approach to assess genetic diversity using iPBS-amplified DNA profiling.
Genetic Correction of IL-10RB Deficiency Reconstitutes Anti-Inflammatory Regulation in iPSC-Derived Macrophages
Authors: Hoffmann Dirk , Sens Johanna , Brennig Sebastian , Brand Daniel , Philipp Friederike , Vollmer Barbosa Philippe , Kuehle Johannes , Steinemann Doris , Lenz Daniela , Buchegger Theresa , Morgan Michael , Falk Christine S. , Klein Christoph , Lachmann Nico , Schambach Axel
Published: March 2021

Patient material from rare diseases such as very early-onset inflammatory bowel disease (VEO-IBD) is often limited. The use of patient-derived induced pluripotent stem cells (iPSCs) for disease modeling is a promising approach to investigate disease pathomechanisms and therapeutic strategies. We successfully developed VEO-IBD patient-derived iPSC lines harboring a mutation in the IL-10 receptor β-chain (IL-10RB) associated with defective IL-10 signaling. To characterize the disease phenotype, healthy control and VEO-IBD iPSCs were differentiated into macrophages. IL-10 stimulation induced characteristic signal transducer and activator of transcription 3 (STAT3) and suppressor of cytokine signaling 3 (SOCS3) downstream signaling and anti-inflammatory regulation of lipopolysaccharide (LPS)-mediated cytokine secretion in healthy control iPSC-derived macrophages. In contrast, IL-10 stimulation of macrophages derived from patient iPSCs did not result in STAT3 phosphorylation and subsequent SOCS3 expression, recapitulating the phenotype of cells from patients with IL-10RB deficiency. In line with this, LPS-induced cytokine secretion (e.g., IL-6 and tumor necrosis factor-α (TNF-α)) could not be downregulated by exogenous IL-10 stimulation in VEO-IBD iPSC-derived macrophages. Correction of the IL-10RB defect via lentiviral gene therapy or genome editing in the adeno-associated virus integration site 1 (AAVS1) safe harbor locus led to reconstitution of the anti-inflammatory response. Corrected cells showed IL-10RB expression, IL-10-inducible phosphorylation of STAT3, and subsequent SOCS3 expression. Furthermore, LPS-mediated TNF-α secretion could be modulated by IL-10 stimulation in gene-edited VEO-IBD iPSC-derived macrophages. Our established disease models provide the opportunity to identify and validate new curative molecular therapies and to investigate phenotypes and consequences of additional individual IL-10 signaling pathway-dependent VEO-IBD mutations.
Crisis and the Role of Money in the Real and Financial Economies—An Innovative Approach to Monetary Stimulus
Authors: Simmons Richard , Dini Paolo , Culkin Nigel , Littera Giuseppe
Published: March 2021

‘Financial crisis’ is sometimes regarded as synonymous with ‘economic crisis’, but this is an oversimplification and risks missing the feedback loops between the financial and real economies. In this paper, the role of money is revisited in the context of distinguishing the real economy from the financial economy. A theoretical framework is developed to explain how endogenous (bank credit) and central bank exogenous (quantitative easing, QE) money creation feed into the real and financial economies. It looks at how the velocity of monetary circulation varies between the two economies and across asset types within the financial economy. Monetary transmission mechanisms are set into a framework that helps explain how QE stimulus risks combining asset price bubbles with poor growth in the real economy. The real economy transmission mechanism of ‘helicopter money’ is given context, enabling an assessment of the efficacy of both the QE and helicopter money policy routes. Finally, we present a new type of monetary transmission, ‘Smart Helicopter Money’, to deliver monetary stimulus to innovators, SMEs and high-growth firms via both complementary currencies and a modified form of QE in order to achieve proportionally greater impact on the real economy.
Toxicity and Anti-Proliferative Properties of Anisomeles indica Ethanol Extract on Cervical Cancer HeLa Cells and Zebrafish Embryos
Authors: Bich-Loan Nguyen T. , Kien Kieu Trung , Thanh Nguyen Lai , Kim-Thanh Nguyen T. , Huy Nguyen Quang , The-Hai Pham , Muller Marc , Nachtergael Amandine , Duez Pierre , Thang Nguyen Dinh
Published: March 2021

In this study, we showed that crude extract of Anisomeles indica (AI-EtE) expressed its toxicity to HeLa cells with an IC50 dose of 38.8 µg/mL and to zebrafish embryos with malformations, lethality and hatching inhibition at 72-hpf at doses higher than 75 µg/mL. More interestingly, flow cytometry revealed that AI-EtE significantly promoted the number of cells entering apoptotic. Accordingly, the transcript levels of BAX, CASPASE-8, and CASPASE-3 in the cells treated with AI-EtE at IC50 dose were 1.55-, 1.62-, and 2.45-fold higher than those in the control cells, respectively. Moreover, treatment with AI-EtE caused cell cycle arrest at the G1 phase in a p53-independent manner. Particularly, percentages of AI-EtE-treated cells in G1, S, G2/M were, respectively 85%, 6.7% and 6.4%; while percentages of control cells in G1, S, G2/M were 64%, 15% and 19%, respectively. Consistent with cell cycle arrest, the expressions of CDKN1A and CDNK2A in AI-EtE-treated cells were up-regulated 1.9- and 1.64-fold, respectively. Significantly, treatment with AI-EtE also decreased anchorage-independent growth of HeLa cells. In conclusion, we suggest that Anisomeles indica can be considered as a medicinal plant with a possible use against cervical cancer cells; however, the used dose should be carefully monitored, especially when applying to pregnant women.
The Effect of Tocilizumab on Inflammatory Markers in Patients Hospitalized with Serious Infections. Case Series and Review of Literature
Authors: Berman Mark , Ben-Ami Ronen , Berliner Shlomo , Anouk Marina , Kaufman Ilana , Broyde Adi , Borok Sara , Elkayam Ori
Published: March 2021

Background: The human anti-IL-6 receptor antibody tocilizumab (TCZ) has been approved for the treatment of rheumatoid arthritis (RA) and giant cell arteritis (GCA). It is observed that CRP levels drop quickly after starting TCZ treatment. This may lead to misinterpretation of laboratory results when accessing the patient with infectious disease while on TCZ. We conducted this study to report cases treated with tocilizumab who developed serious infections with special reference to levels of CRP and to review the literature on the effect of tocilizumab on acute phase response (APR) during infections. Methods: The files of RA and GCA patients hospitalized in the Tel Aviv medical center between 2009–2019 were reviewed. Cases of patients with RA and GCA treated with tocilizumab who were hospitalized due to severe infections were reviewed with special emphasis on the duration of treatment, type of infection, and APR. Results: We identified nine admissions. Seven patients were treated with tocilizumab for RA, two for GCA. The diagnosis was pneumonia in three cases, osteomyelitis in one, cellulitis in one, endocarditis due to Whipple disease in one, abscess of cervix uteri in one, meningitis in one, and perforated diverticulitis in one. The mean CRP levels on admission were 4.75 mg/L (normal range, up to 5 mg/L). All cases were diagnosed correctly on admission. Conclusions: CRP levels may not correctly reflect the severity of infectious diseases during tocilizumab treatment. Increased awareness of the masking effect of tocilizumab on the APR during infection is needed in order to avoid a delay in the diagnosis.
Clinical Characteristics, Differential Diagnosis and Genetic Analysis of Concentric Retinitis Pigmentosa
Authors: Nakahara Mei , Oishi Akio , Miyata Manabu , Ikeda Hanako Ohashi , Hasegawa Tomoko , Numa Shogo , Otsuka Yuki , Oishi Maho , Matsuda Fumihiko , Tsujikawa Akitaka
Published: March 2021

Concentric retinitis pigmentosa (RP), in which retinal degeneration is limited in the periphery, is rare and little information exists to date on the subject. Herein, we describe the clinical and genetic characteristics of this atypical form of RP. We retrospectively reviewed our database and identified 14 patients with concentric RP. Additionally, 14 patients with age-matched typical RP were also included. Patients with concentric RP had better visual acuity (logarithm of minimum angle of resolution −0.04 vs. 0.32, p = 0.047) and preserved ellipsoid zones (7630 µm vs. 2646 µm, p < 0.001) compared to typical RP. The electroretinogram showed subnormal but recordable responses in patients with concentric RP. Genetic testing was done in nine patients with concentric RP and revealed causative mutations in the EYS gene in one patient and the RP9 gene in one patient. Two patients had myotonic dystrophy and the diagnosis was revised as myotonic dystrophy-associated retinopathy. Concentric RP is a rare, atypical form of RP with better visual function. There is some overlap in the causative genes in concentric and typical RP. Myotonic dystrophy-associated retinopathy is an important differential diagnosis.
Development of Toughened Flax Fiber Reinforced Composites. Modification of Poly(lactic acid)/Poly(butylene adipate-co-terephthalate) Blends by Reactive Extrusion Process
Authors: Andrzejewski Jacek , Nowakowski Michał
Published: March 2021

The presented study focuses on the development of flax fiber (FF) reinforced composites prepared with the use of poly(lactic acid)/poly(butylene adipate-co-terephthalate)—PLA/PBAT blend system. This type of modification was aimed to increase impact properties of PLA-based composites, which are usually characterized by high brittleness. The PLA/PBAT blends preparation was carried out using melt blending technique, while part of the samples was prepared by reactive extrusion process with the addition of chain extender (CE) in the form of epoxy-functionalized oligomer. The properties of unreinforced blends was evaluated using injection molded samples. The composite samples were prepared by compression molding technique, while flax fibers reinforcement was in the form of plain fabric. The properties of the laminated sheets were investigated during mechanical test measurements (tensile, flexural, impact). Differential scanning calorimetry (DSC) analysis was used to determine the thermal properties, while dynamic mechanical thermal analysis (DMTA) and heat deflection temperature (HDT) measurements were conducted in order to measure the thermomechanical properties. Research procedure was supplemented with structure evaluation using scanning electron microscopy (SEM) analysis. The comparative study reveals that the properties of PLA/PBAT-based composites were more favorable, especially in the context of impact resistance improvement. However, for CE modified samples also the modulus and strength was improved. Structural observations after the impact tests confirmed the presence of the plastic deformation of PLA/PBAT matrix, which confirmed the favorable properties of the developed materials. The use of PBAT phase as the impact modifier strongly reduced the PLA brittleness, while the reactive extrusion process improves the fiber-matrix interactions leading to higher stiffness and strength.
Influence of Cement Replacement with Fly Ash and Ground Sand with Different Fineness on Alkali-Silica Reaction of Mortar
Authors: Ramjan Suwat , Tangchirapat Weerachart , Jaturapitakkul Chai , Chee Ban Cheah , Jitsangiam Peerapong , Suwan Teewara
Published: March 2021

The alkali-silica reaction (ASR) is an important consideration in ensuring the long-term durability of concrete materials, especially for those containing reactive aggregates. Although fly ash (FA) has proven to be useful in preventing ASR expansion, the filler effect and the effect of FA fineness on ASR expansion are not well defined in the present literature. Hence, this study aimed to examine the effects of the filler and fineness of FA on ASR mortar expansion. FAs with two different finenesses were used to substitute ordinary Portland cement (OPC) at 20% by weight of binder. River sand (RS) with the same fineness as the FA was also used to replace OPC at the same rate as FA. The replacement of OPC with RS (an inert material) was carried out to observe the filler effect of FA on ASR. The results showed that FA and RS provided lower ASR expansions compared with the control mortar. Fine and coarse fly ashes in this study had almost the same effectiveness in mitigating the ASR expansion of the mortars. For the filler effect, smaller particles of RS had more influence on the ASR reduction than RS with coarser particles. A significant mitigation of the ASR expansion was obtained by decreasing the OPC content in the mortar mixture through its partial substitution with FA and RS.
Multifunctional Cotton Fabrics Obtained by Modification with Silanes Containing Esters of Phosphoric Acid as Substituents
Authors: Przybylak Marcin , Dutkiewicz Michał , Szubert Karol , Maciejewski Hieronim , Rojewski Szymon
Published: March 2021

The development of novel flame retardants for cotton textiles that form a stable layer on textile fiber is of high economical and practical relevance. A novel flame retardant fluorinated phosphoric acid esters modified silicone resins for cotton modification were synthesized. The investigated phosphoric acid esters based compounds were substituted by a fluorinated chain or ring, and alkoxysilyl groups. The presence of alkoxysilyl groups allowed the formation of bonds with cellulose, while derivatives of phosphoric esters reduced the flammability of fabrics. Additionally, the presence of fluoride in their structures affected the hydrophobic properties. Cotton fabrics were modified in a simple one-step process by dip-coating method. The flame retardant properties of modified textiles were examined by performing microcalorimetric analysis, thermogravimetry analysis, and measuring oxygen index. The hydrophobicity was evaluated by measuring the water contact angle. The modified fabrics were characterized by SEM-EDS (Scanning Electron Microscopy with Energy Dispersive Spectroscopy) analysis and surface morphology. As a result of the tests, multifunctional fabrics were obtained.
Environment-Friendly Electrochemical Processes
Authors: Martínez-Huitle Carlos A.
Published: March 2021

The present water crisis is probable to grow worse in the coming decades, and this has motivated the scientific community to identify innovative, safe, and robust water treatment technologies at a lower cost and with less energy, diminishing the use of chemicals and impact on the environment [...]
SARS-CoV-2 Detection in Fecal Sample from a Patient with Typical Findings of COVID-19 Pneumonia on CT but Negative to Multiple SARS-CoV-2 RT-PCR Tests on Oropharyngeal and Nasopharyngeal Swab Samples
Authors: Brogna Barbara , Brogna Carlo , Petrillo Mauro , Conte Adriana Modestina , Benincasa Giulio , Montano Luigi , Piscopo Marina
Published: March 2021

Reverse transcriptase polymerase chain reaction (RT-PCR) negative results in the upper respiratory tract represent a major concern for the clinical management of coronavirus disease 2019 (COVID-19) patients. Herein, we report the case of a 43-years-old man with a strong clinical suspicion of COVID-19, who resulted in being negative to multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR tests performed on different oropharyngeal and nasopharyngeal swabs, despite serology having confirmed the presence of SARS-CoV-2 IgM. The patient underwent a chest computed tomography (CT) that showed typical imaging findings of COVID-19 pneumonia. The presence of viral SARS-CoV-2 was confirmed only by performing a SARS-CoV-2 RT-PCR test on stool. Performing of SARS-CoV-2 RT-PCR test on fecal samples can be a rapid and useful approach to confirm COVID-19 diagnosis in cases where there is an apparent discrepancy between COVID-19 clinical symptoms coupled with chest CT and SARS-CoV-2 RT-PCR tests’ results on samples from the upper respiratory tract.
The Pulmonary Venous Return from Normal to Pathological—Clinical Correlations and Review of Literature
Authors: Tarniceriu Cristina Claudia , Hurjui Loredana Liliana , Tanase Daniela Maria , Nedelcu Alin Horatiu , Gradinaru Irina , Ursaru Manuela , Stefan Rudeanu Alexandra , Delianu Carmen , Lozneanu Ludmila
Published: March 2021

Pulmonary veins carry oxygenated blood from lungs to the left atrium of the heart. The anatomy of the pulmonary veins is variable with some anatomic variants. In clinical practice the difference between the normal anatomy of pulmonary veins with its variants and abnormal anatomy is very important for clinicians. Variants of pulmonary veins may occur in number, diameter and normal venous return. We present a case report and a review of the literature with the pulmonary venous return that deviates from the usual anatomical configuration and ranges from normal variant drainage to anomalous pulmonary—systemic communication. Initially, it was considered as an anatomical variant of the pulmonary venous return associated with the persistence of the left superior vena cava. Upon detailed exploration it was established that it was an anomaly of the pulmonary venous return which led in time to the installation of its complications. Diagnosis can be difficult, sometimes missed, or only made late in adulthood when complications were installed. Knowledge of variant anatomy and anomalous pulmonary venous return play a crucial role in the diagnostically challenging patient.
QT Interval Prolongation in Patients with Systemic Sclerosis—Are the Holter ECG Recordings a Better Option for QT Interval Evaluation?
Authors: Saramet Elena E. , Cojocaru Doina-Clementina , Ungurianu Sorin , Negru Robert D. , Ancuta Codrina
Published: March 2021

Background and Objectives: Cardiac involvement in systemic sclerosis has important consequences on patient survival. Myocardial fibrosis and microcirculation involvement can generate arrhythmic complications, which can be associated with a higher death risk. QT interval prolongation is considered as a risk factor for ectopic ventricular events and can be evaluated using standard short ECG recordings or 24-h Holter ECG recordings. Materials and Methods: 39 patients with systemic sclerosis were submitted to a standard ECG recording at admission and 24-h Holter ECG monitoring. Results: QT interval values resulted from Holter ECG monitoring are higher than the values generated by the short-term ECG recordings. Holter ECG monitoring permits the detection of ventricular ectopy in patients with no events on standard ECG. Conclusions: In patients with systemic sclerosis, 24-h Holter ECG recordings can realize a more precise evaluation of the extent of QTc interval prolongation and ventricular ectopic events associated with myocardial involvement.