bluuebunny/crossref_metadata_2025 huggingface dataset:
An Empirical Investigation on Evolutionary Algorithm Evolving Developmental Timings
Authors: Ohnishi Kei , Hamano Kouta , Koeppen Mario
Published: November 2020

Recently, evolutionary algorithms that can efficiently solve decomposable binary optimization problems have been developed. They are so-called model-based evolutionary algorithms, which build a model for generating solution candidates by applying a machine learning technique to a population. Their central procedure is linkage detection that reveals a problem structure, that is, how the entire problem consists of sub-problems. However, the model-based evolutionary algorithms have been shown to be ineffective for problems that do not have relevant structures or those whose structures are hard to identify. Therefore, evolutionary algorithms that can solve both types of problems quickly, reliably, and accurately are required. The objective of the paper is to investigate whether the evolutionary algorithm evolving developmental timings (EDT) that we previously proposed can be the desired one. The EDT makes some variables values more quickly converge than the remains for any problems, and then, decides values of the remains to obtain a higher fitness value under the fixation of the variables values. In addition, factors to decide which variable values converge more quickly, that is, developmental timings are evolution targets. Simulation results reveal that the EDT has worse performance than the linkage tree genetic algorithm (LTGA), which is one of the state-of-the-art model-based evolutionary algorithms, for decomposable problems and also that the difference in the performance between them becomes smaller for problems with overlaps among linkages and also that the EDT has better performance than the LTGA for problems whose structures are hard to identify. Those results suggest that an appropriate search strategy is different between decomposable problems and those hard to decompose.
Synthesis of Magnetic Metal-Organic Frame Material and Its Application in Food Sample Preparation
Authors: Yang Jingying , Wang Yabin , Pan Mingfei , Xie Xiaoqian , Liu Kaixin , Hong Liping , Wang Shuo
Published: November 2020

A variety of contaminants in food is an important aspect affecting food safety. Due to the presence of its trace amounts and the complexity of food matrix, it is very difficult to effectively separate and accurately detect them. The magnetic metal-organic framework (MMOF) composites with different structures and functions provide a new choice for the purification of food matrix and enrichment of trace targets, thus providing a new direction for the development of new technologies in food safety detection with high sensitivity and efficiency. The MOF materials composed of inorganic subunits and organic ligands have the advantages of regular pore structure, large specific surface area and good stability, which have been thoroughly studied in the pretreatment of complex food samples. MMOF materials combined different MOF materials with various magnetic nanoparticles, adding magnetic characteristics to the advantages of MOF materials, which are in terms of material selectivity, biocompatibility, easy operation and repeatability. Combined with solid phase extraction (SPE) technique, MMOF materials have been widely used in the food pretreatment. This article introduced the new preparation strategies of different MMOF materials, systematically summarizes their applications as SPE adsorbents in the pretreatment of food contaminants and analyzes and prospects their future application prospects and development directions.
Characterization of the Aromatic and Phenolic Profile of Five Different Wood Chips Used for Ageing Spirits and Wines
Authors: Guerrero-Chanivet María , Valcárcel-Muñoz Manuel J. , García-Moreno M. Valme , Guillén-Sánchez Dominico A.
Published: November 2020

Wooden barrels and wood chips are usually used in the ageing of spirits and wines to improve their sensorial profile. Oak wood is the most popular material used in cooperage, but there are other interesting woods, such as cherry or chestnut, that could be considered for this purpose. In this study, a novel method for the determination of the aromatic profile of wood powder by Direct Thermal Desorption-Gas Chromatography-Mass Spectrometry (DTD-GC-MS) was optimized by experimental design. The volatile composition of five different types of wood chips was determined by direct analysis of wood powder by DTD-GC-MS method developed. Thirty-one compounds from wood were identified through this analysis, allowing the differentiation between woods. The aromatic and phenolic compound profile of the 50% hydroalcoholic extract of each type of wood studied was analyzed by Stir-bar Sorptive Extraction-Gas Chromatography-Mass Spectrometry (SBSE-GC-MS) and Ultra-High-Performance Liquid Chromatography (UHPLC) to determine which wood compounds are transferred to spirits and wine after ageing. Different phenolic profiles were found by UHPLC in each wood extract, allowing their differentiation. However, results obtained by SBSE-GC-MS did not allow distinguishing between wood extracts. The analysis of wood in solid state, without any type of previous treatment except grinding, by DTD-GC-MS does not imply any loss of information of the aromatic compounds present in wood as other techniques. This is a potential method to identify aromas in wood that, in addition, allows different types of wood to be differentiated.
Membrane-Anchored Hairless Protein Restrains Notch Signaling Activity
Authors: Maier Dieter
Published: November 2020

The Notch signaling pathway governs cell-to-cell communication in higher eukaryotes. In Drosophila, after cleavage of the transmembrane receptor Notch, the intracellular domain of Notch (ICN) binds to the transducer Suppressor of Hairless (Su(H)) and shuttles into the nucleus to activate Notch target genes. Similarly, the Notch antagonist Hairless transfers Su(H) into the nucleus to repress Notch target genes. With the aim to prevent Su(H) nuclear translocation, Hairless was fused to a transmembrane domain to anchor the protein at membranes. Indeed, endogenous Su(H) co-localized with membrane-anchored Hairless, demonstrating their binding in the cytoplasm. Moreover, adult phenotypes uncovered a loss of Notch activity, in support of membrane-anchored Hairless sequestering Su(H) in the cytosol. A combined overexpression of membrane-anchored Hairless with Su(H) lead to tissue proliferation, which is in contrast to the observed apoptosis after ectopic co-overexpression of the wild-type genes, indicating a shift to a gain of Notch activity. A mixed response, general de-repression of Notch signaling output, plus inhibition at places of highest Notch activity, perhaps reflects Su(H)’s role as activator and repressor, supported by results obtained with the Hairless-binding deficient Su(H)LLL mutant, inducing activation only. Overall, the results strengthen the idea of Su(H) and Hairless complex formation within the cytosolic compartment.
Finding MEMO—Emerging Evidence for MEMO1′s Function in Development and Disease
Authors: Schotanus Michaela D. , Van Otterloo Eric
Published: November 2020

Although conserved throughout animal kingdoms, the protein encoded by the gene Mediator of ERBB2 Driven Cell Motility 1 or MEMO1, has only recently come into focus. True to its namesake, MEMO1 first emerged from a proteomic screen of molecules bound to the ERBB2 receptor and was found to be necessary for efficient cell migration upon receptor activation. While initially placed within the context of breast cancer metastasis—a pathological state that has provided tremendous insight into MEMO1′s cellular roles—MEMO1′s function has since expanded to encompass additional cancer cell types, developmental processes during embryogenesis and homeostatic regulation of adult organ systems. Owing to MEMO1′s deep conservation, a variety of model organisms have been amenable to uncovering biological facets of this multipurpose protein; facets ranging from the cellular (e.g., receptor signaling, cytoskeletal regulation, redox flux) to the organismal (e.g., mineralization and mineral homeostasis, neuro/gliogenesis, vasculogenesis) level. Although these facets emerge at the intersection of numerous biological and human disease processes, how and if they are interconnected remains to be resolved. Here, we review our current understanding of this ‘enigmatic’ molecule, its role in development and disease and open questions emerging from these previous studies.
B Chromosomes and Cytogenetic Characteristics of the Common Nase Chondrostoma nasus (Linnaeus, 1758)
Authors: Boroń Alicja , Grabowska Anna , Spóz Aneta , Przybył Anna
Published: November 2020

Supernumerary B chromosomes (Bs) are very promising structures, among others, in that they are an additional genomic compartment for evolution. In this study, we tested the presence and frequency of B chromosomes and performed the first cytogenetic examination of the common nase (Chondrostoma nasus). We investigated the individuals from two populations in the Vistula River basin, in Poland, according to the chromosomal distribution of the C-bands and silver nucleolar organizer regions (Ag-NORs), using sequential staining with AgNO3 and chromomycin A3 (CMA3). Furthermore, we analyzed the chromosomal localization of two rDNA families (45S and 5S rDNA) using fluorescence in situ hybridization (FISH) with rDNA probes. Chondrostoma nasus individuals showed a standard (A) chromosome set consisting of 2n = 50: 12 metacentric, 32 submetacentric, and 6 acrocentric chromosomes (NF = 94). Fourteen out of the 20 analyzed individuals showed 1–2 mitotically unstable submetacentric B chromosomes of different sizes. Six of them, in 14.1% of the analyzed metaphase plates, had a single, medium-sized submetacentric B (Bsm) chromosome (2n = 51) with a heterochromatic block located in its pericentromeric region. The other seven individuals possessed a Bsm (2n = 51) in 19.4% of the analyzed metaphase plates, and a second Bsm chromosome (2n = 52), the smallest in the set, in 15.5% of metaphase plates, whereas one female was characterized by both Bsm chromosomes (2n = 52) in 14.3% of the analyzed metaphase plates. AgNORs, GC-rich DNA sites, and 28S rDNA hybridization sites were observed in the short arms of two submetacentric chromosome pairs of A set. The constitutive heterochromatin was visible as C bands in the centromeric regions of almost all Chondrostoma nasus chromosomes and in the pericentromeric region of several chromosome pairs. Two 5S rDNA hybridization sites in the pericentromeric position of the largest acrocentric chromosome pair were observed, whereas two other such sites in co-localization on a smaller pair of NOR chromosomes indicate a species-specific character. The results herein broaden our knowledge in the field of B chromosome distribution and molecular cytogenetics of Chondrostoma nasus: a freshwater species from the Leuciscidae family.
ENSO and Light-Absorbing Impurities and Their Impact on Snow Albedo in the Sierra Nevada de Santa Marta, Colombia
Authors: Bolaño-Ortiz Tomás R. , Diaz-Gutiérrez Viverlys L. , Camargo-Caicedo Yiniva
Published: November 2020

Snow albedo is an important variable in the coupled atmosphere-earth system at the global level. Moreover, studying its behavior allows us to know the state of the cryosphere. The Sierra Nevada de Santa Marta (SNSM) is a glacier area and the northernmost tropical (10.82° N, 73.75° W) region in South America. It has a height of up to 5775 m.a.sl., which is the second highest mountain in the world near the marine coast. We analyzed variations in snow albedo related to snow cover, snowfall, temperature, light-absorbing impurities such as blank carbon (BC), organic carbon (OC) and dust, and El Niño—Southern Oscillation (ENSO) phenomenon through 20 years (2000–2020). We mainly use daily data from the Moderate Resolution Imaging Spectroradiometer (MODIS) onboard the Terra and Aqua NASA satellites. Results showed through correlations that snow albedo has decreased due to Land Surface Temperature (55%, p < 0.001), a positive phase of ENSO (42%, p < 0.001) and dust (37%, p < 0.01) in the SNSM. Additionally, a dust negative effect was more evident on the southern side (up to 49%, p < 0.001) of the SNSM. Backward trajectories by the NOAA HYSPLIT model suggest that dust sources would be soil erosion in the surrounding region. Results can help recognize the influence of ENSO and dust in the glacier decrease of the SNSM.
Evaluation of the Geo-Mechanical Properties Property Recovery in Time of Conditioned Soil for EPB-TBM Tunneling
Authors: Carigi Andrea , Todaro Carmine , Martinelli Daniele , Amoroso Cristina , Peila Daniele
Published: November 2020

The soil conditioning is a process of fundamental importance during the excavation of tunnels with Earth Pressure Balance full face machine. The soil conditioning is achieved through the addition of foam at the excavation face and in the bulk chamber that modifies the natural soil properties from solid-like to fluid-like with a pulpy behavior. Clearly, a material with a pulpy or fluid-like consistency is not suitable for the construction of embankments of landfill or for other civil purposes. It is therefore important to have a procedure able to identify how long it is necessary before the conditioned soil recovers its geo-mechanical properties, since this knowledge is needed at the design stages from a logistic point of view. The paper proposes and discusses a procedure to find out whether and when the conditioned soil gets back to its original properties. The procedure foresees direct shear tests, vane tests, Proctor tests, and rotational mixer tests at different time schedules from the production of the conditioned soil in the laboratory. The conditioned soil samples have been cured in a controlled environment up to 60 days from the conditioning. Thanks to these tests, it is possible to assess if and when the soil recovers its natural behavior or if a permanent alteration is induced. The proposed procedure has been applied to a standard alluvial soil showing that most of the original properties of the soil are recovered already after seven days from the conditioning. The carried-out tests have shown that the procedure is feasible and easy to apply.
Discovery of Ancient Volcanoes in the Okhotsk Sea (Russia): New Constraints on the Opening History of the Kurile Back Arc Basin
Authors: Werner Reinhard , Baranov Boris , Hoernle Kaj , Bogaard Paul van den , Hauff Folkmar , Tararin Igor
Published: November 2020

Here we present the first radiometric age and geochemical (major and trace element and isotope) data for samples from the Hydrographer Ridge, a back arc volcano of the Kurile Island Arc, and a newly discovered chain of volcanoes (“Sonne Volcanoes”) on the northwestern continental slope of the Kurile Basin on the opposite side of the arc. The 40Ar/39Ar age and geochemical data show that Hydrographer Ridge (3.2–3.3 Ma) and the “Sonne Volcanoes” (25.3–25.9 Ma) have very similar trace element and isotope characteristics to those of the Kurile Island Arc, indicating derivation from a common magma source. We conclude that the age of the “Sonne Volcanoes” marks the time of opening of the Kurile Basin, implying slow back arc spreading rates of 1.3–1.8 cm/y. Combined with published data from the Kurile fore arc, our data suggest that the processes of subduction, Kurile Basin opening and frontal arc extension occurred synchronously and that extension in the rear part and in the frontal part of the Kurile Island Arc must have been triggered by the same mechanism.
Effects of the Cardiac and Comorbid Conditions Heart Failure (3C-HF) Score at Admission on Life Space at Three Months after Hospital Discharge in Elderly Patients with Heart Failure: A Short Report
Authors: Naito Koichi , Kamo Miyuki
Published: November 2020

We assessed 22 elderly patients with heart failure, 3 months after hospital discharge. We examined and compared factors that predict small life space after discharge with the same factors before discharge. Life-Space Assessment was used to classify the participants as either having “small living spaces” or “large living spaces”. We collected data regarding characteristics, Cardiac and Comorbid Conditions Heart Failure Score (3C-HF score), and evaluated motor function. We also collected data on the patients’ lifestyle habits. We investigated spreading life space at 3 months after discharge by mailing a questionnaire to the subjects. Using multiple logistic regression analysis, we were able to predict the patients having a small life space at 3 months after discharge by the Cardiac and Comorbid Conditions Heart Failure (3C-HF) score (odds ratio, 1.19; 95% confidence interval, 1.01–1.39; p = 0.038) at admission. Overall, the 3C-HF score at admission may be associated with the size of life space at 3 months after hospital discharge in elderly patients with heart failure. Future multicenter studies should be conducted to validate the results of this study by measuring post-discharge activity with a more objective index.
Medication Risk Management in Routine Dispensing in Community Pharmacies
Authors: Kallio Sonja , Eskola Tiina , Pohjanoksa-Mäntylä Marika , Airaksinen Marja
Published: November 2020

Community pharmacists have a duty to contribute to medication risk management in outpatient care. This study aimed to investigate the actions taken by pharmacists in routine dispensing to manage medication risks. The study was conducted as a national cross-sectional online survey targeted at all community pharmacies in Finland (n = 576) in October 2015. One pharmacist from each pharmacy was recommended to be the spokesperson for the outlet to describe their practices. Responses were received from 169 pharmacies (response rate of 29%). Pharmacists were oriented to solving poor adherence and technical problems in prescriptions, whereas responsibility for therapeutic risks was transferred to the patient to resolve them with the physician. Pharmacists have access to a wide range of electronic medication risk management tools, but they are rarely utilized in daily dispensing. Attention was paid to drug–drug interactions and the frequency of dispensing with regard to high-risk medicines. Pharmacies rarely had local agreements with other healthcare providers to solve medication-related risks. In routine dispensing, more attention needs to be given to the identification and solving of therapeutic risks in medications, especially those of older adults. Better participation of community pharmacists in medication risk management requires stronger integration and an explicit mandate to solve the therapeutic risks.
Nicotine Dependence and Loss of Autonomy among Greek Adolescent Smokers: A Countrywide Cross-Sectional Study
Authors: Soteriades Soteris , Basagiannis Athanasios , Soteriades Elpidoforos S. , Barbouni Anastasia , Mouchtouri Varvara , Rachiotis George , Hadjichristodoulou Christos
Published: November 2020

Nicotine dependence is one of the main reasons for the continuation of smoking among adolescents. Loss of autonomy (LOA) is a measure of dependence. This study is the first to investigate LOA and its determinants among Greek adolescents. In 2013, 13-to-15-year-old middle-school students were selected by multi-stage clustered sampling. LOA was evaluated with the Hooked-on-Nicotine Checklist (HONC). Multiple univariate analysis was used to assess the association between adolescent demographics, smoking habits, and loss of autonomy. Three-hundred thirty-nine current smokers responded to the questionnaire (response rate: 82.3%). Of these respondents, 51.2% were male and 88.8% reported at least one LOA symptom. The mean HONC score was 4.13/10 (95% CI: 3.82–4.45). Higher scores were negatively associated with lower smoking frequency (cumulative odds ratio (cOR): 0.240, 95% CI: 0.144–0.400) and positively associated with lower age at first cigarette (cOR: 2.29, 95% CI: 1.38–3.82). Female gender was significantly associated with the prevalence but not the degree of LOA. Overall, the prevalence and the degree of nicotine dependence among adolescent smokers in Greece is similar to other countries. Frequent smoking and initiation of smoking at a younger age are linked to nicotine dependence, although it was not possible to make causal inferences. The relationship between nicotine dependence and gender remains unclear.
Significant Predictors of Sports Performance in Elite Men Judo Athletes Based on Multidimensional Regression Models
Authors: Kostrzewa Maciej , Laskowski Radosław , Wilk Michal , Błach Wiesław , Ignatjeva Angelina , Nitychoruk Magdalena
Published: November 2020

Background: This research aimed to identify the most significant predictors of sports level using regression modeling. Methods: This study examined 16 judokas (aged 23 (±2.5)) from four weight categories, with four athletes in each category (66 kg, 73 kg, 81 kg and 90 kg). Each athlete was a member of the Polish National Team, an international master class (IM) or national master class (M). The tests were carried out twice (every two weeks) during the pre-competitive season in the morning, after a 10-min warm-up. The tests were performed according to the following protocol: Explosive Strength Lower Limbs (ExSLL) [W], Strength Endurance Lower Limbs (SELL) [%], Explosive Strength Upper Limbs (ExSUL) [W], Strength Endurance Upper Limbs (SEUL) [%]. The relationships between the dependent variable (ranking score) and the other analyzed variables (predictors) were estimated using the one-factor ridge regression analysis. Results: There were significant intergroup and intragroup differences in the results of explosive strength and strength endurance of the lower and upper limbs. The best predictors were identified using regression modeling: ExSLL, SELL, and SEUL. Conclusions: Increasing the value of these predictors by a unit should significantly affect the scores in the ranking table. Correlation analysis showed that all variables that are strongly correlated with the Polish Judo Association (PJA) ranking table scores may have an effect on the sports performance.
The Association between Parental Psychological Control, Deviant Peer Affiliation, and Internet Gaming Disorder among Chinese Adolescents: A Two-Year Longitudinal Study
Authors: Lin Shuang , Yu Chengfu , Chen Jun , Sheng Jing , Hu Yousong , Zhong Lin
Published: November 2020

Abundant empirical research indicates a relationship between parental psychological control and adolescent Internet gaming disorder (IGD), but the direction and underlying mechanism of this association remain unclear. Using a two-year longitudinal design across three time points, the present study examined the reciprocal processes between parental psychological control and IGD and explored whether deviant peer affiliation explains this bidirectional association. The sample consisted of 908 participants (480 boys and 428 girls) who participated in three measurements and completed questionnaires assessing parental psychological control, deviant peer affiliation, and IGD. Autoregressive cross-lagged models indicated a direct reciprocal relationship between parental psychological control and IGD. Furthermore, the results showed that parental psychological control exerts an indirect effect on adolescent IGD via deviant peer affiliation, but the inverse indirect effect via deviant peer affiliation was non-significant. Knowledge regarding the direct and underlying mechanisms of the reciprocal relationship between parental psychological control and IGD has important implications for prevention and intervention of adolescent IGD.
Mindfulness and Psychological Distress in Kindergarten Teachers: The Mediating Role of Emotional Intelligence
Authors: Cheng Xiulan , Ma Ying , Li Jiaqi , Cai Yonghui , Li Ling , Zhang Jiao
Published: November 2020

Kindergarten teachers are often exposed to great stress. Considering that, mindfulness has been demonstrated to act as a critical role in the psychological well-being of kindergarten teachers. The present study assessed mindfulness in teaching (MT), psychological distress and emotional intelligence (EI) among 511 kindergarten teachers in mainland China and investigated the mediating role of EI to explore the association mechanism between kindergarten teachers’ MT and psychological distress. The major results suggested that kindergarten teachers’ MT was negatively related to their psychological distress (depression, anxiety, and stress). Results of path analyses indicated that the total score of EI and dimension of regulation of emotion (ROE) could serve as significant mediators. The findings suggest that mindfulness might be beneficial to relieve kindergarten teachers’ psychological distress through the mediating role of EI.
Single-Walled Carbon Nanotubes Attenuate Cytotoxic and Oxidative Stress Response of Pb in Human Lung Epithelial (A549) Cells
Authors: Ahamed Maqusood , Akhtar Mohd Javed , Khan M. A. Majeed
Published: November 2020

Combined exposure of single-walled carbon nanotubes (SWCNTs) and trace metal lead (Pb) in ambient air is unavoidable. Most of the previous studies on the toxicity of SWCNTs and Pb have been conducted individually. There is a scarcity of information on the combined toxicity of SWCNTs and Pb in human cells. This work was designed to explore the combined effects of SWCNTs and Pb in human lung epithelial (A549) cells. SWCNTs were prepared through the plasma-enhanced vapor deposition technique. Prepared SWCNTs were characterized by x-ray diffraction, x-ray photoelectron spectroscopy, scanning electron microscopy, and dynamic light scattering. We observed that SWCNTs up to a concentration of 100 µg/mL was safe, while Pb induced dose-dependent (5–100 µg/mL) cytotoxicity in A549 cells. Importantly, cytotoxicity, cell cycle arrest, mitochondrial membrane potential depletion, lipid peroxidation, and induction of caspase-3 and -9 enzymes following Pb exposure (50 µg/mL for 24 h) were efficiently attenuated by the co-exposure of SWCNTs (10 µg/mL for 24 h). Furthermore, generation of Pb-induced pro-oxidants (reactive oxygen species and hydrogen peroxide) and the reduction of antioxidants (antioxidant enzymes and glutathione) were also mitigated by the co-exposure of SWCNTs. Inductively coupled plasma-mass spectrometry results suggest that the adsorption of Pb on the surface of SWCNTs could attenuate the bioavailability and toxicity of Pb in A549 cells. Our data warrant further research on the combined effects of SWCNTs and Pb in animal models.
Transcription Factor PLAGL1 Is Associated with Angiogenic Gene Expression in the Placenta
Authors: Starks Rebekah R. , Abu Alhasan Rabab , Kaur Haninder , Pennington Kathleen A. , Schulz Laura C. , Tuteja Geetu
Published: November 2020

During pregnancy, the placenta is important for transporting nutrients and waste between the maternal and fetal blood supply, secreting hormones, and serving as a protective barrier. To better understand placental development, we must understand how placental gene expression is regulated. We used RNA-seq data and ChIP-seq data for the enhancer associated mark, H3k27ac, to study gene regulation in the mouse placenta at embryonic day (e) 9.5, when the placenta is developing a complex network of blood vessels. We identified several upregulated transcription factors with enriched binding sites in e9.5-specific enhancers. The most enriched transcription factor, PLAGL1 had a predicted motif in 233 regions that were significantly associated with vasculature development and response to insulin stimulus genes. We then performed several experiments using mouse placenta and a human trophoblast cell line to understand the role of PLAGL1 in placental development. In the mouse placenta, Plagl1 is expressed in endothelial cells of the labyrinth layer and is differentially expressed in placentas from mice with gestational diabetes compared to placentas from control mice in a sex-specific manner. In human trophoblast cells, siRNA knockdown significantly decreased expression of genes associated with placental vasculature development terms. In a tube assay, decreased PLAGL1 expression led to reduced cord formation. These results suggest that Plagl1 regulates overlapping gene networks in placental trophoblast and endothelial cells, and may play a critical role in placental development in normal and complicated pregnancies.
Hypoxic Regulation of Gene Transcription and Chromatin: Cause and Effect
Authors: Kindrick Jessica D. , Mole David R.
Published: November 2020

Cellular responses to low oxygen (hypoxia) are fundamental to normal physiology and to the pathology of many common diseases. Hypoxia-inducible factor (HIF) is central to this by enhancing the transcriptional activity of many hundreds of genes. The cellular response to HIF is cell-type-specific and is largely governed by the pre-existing epigenetic landscape. Prior to activation, HIF-binding sites and the promoters of HIF-target genes are already accessible, in contact with each other through chromatin looping and display markers of activity. However, hypoxia also modulates the epigenetic environment, both in parallel to and as a consequence of HIF activation. This occurs through a combination of oxygen-sensitive changes in enzyme activity, transcriptional activation of epigenetic modifiers, and localized recruitment to chromatin by HIF and activated RNApol2. These hypoxic changes in the chromatin environment may both contribute to and occur as a consequence of transcriptional regulation. Nevertheless, they have the capacity to both modulate and extend the transcriptional response to hypoxia.
Tn5 Transposase Applied in Genomics Research
Authors: Li Niannian , Jin Kairang , Bai Yanmin , Fu Haifeng , Liu Lin , Liu Bin
Published: November 2020

The development of high-throughput sequencing (next-generation sequencing technology (NGS)) and the continuous increase in experimental throughput require the upstream sample processing steps of NGS to be as simple as possible to improve the efficiency of the entire NGS process. The transposition system has fast “cut and paste” and “copy and paste” functions, and has been innovatively applied to the NGS field. For example, the Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-Seq) uses high-throughput sequencing to detect chromatin regions accessible by Tn5 transposase. Linear Amplification via Transposon Insertion (LIANTI) uses Tn5 transposase for linear amplification, haploid typing, and structural variation detection. Not only is it efficient and simple, it effectively shortens the time for NGS sample library construction, realizes large-scale and rapid sequencing, improves sequencing resolution, and can be flexibly modified for more technological innovation.
Intravital Assessment of Blood Platelet Function. A Review of the Methodological Approaches with Examples of Studies of Selected Aspects of Blood Platelet Function
Authors: Polak Dawid , Talar Marcin , Watala Cezary , Przygodzki Tomasz
Published: November 2020

Platelet biology owes to intravital studies not only a better understanding of platelets’ role in primary hemostasis but also findings that platelets are important factors in inflammation and atherosclerosis. Researchers who enter the field of intravital platelet studies may be confused by the heterogeneity of experimental protocols utilized. On the one hand, there are a variety of stimuli used to activate platelet response, and on the other hand there are several approaches to measure the outcome of the activation. A number of possible combinations of activation factors with measurement approaches result in the aforementioned heterogeneity. The aim of this review is to present the most often used protocols in a systematic way depending on the stimulus used to activate platelets. By providing examples of studies performed with each of the protocols, we attempt to explain why a particular combination of stimuli and measurement method was applied to study a given aspect of platelet biology.
Anti-Cancer Effect of Cordycepin on FGF9-Induced Testicular Tumorigenesis
Authors: Chang Ming-Min , Hong Siou-Ying , Yang Shang-Hsun , Wu Chia-Ching , Wang Chia-Yih , Huang Bu-Miin
Published: November 2020

Cordycepin, a bioactive constituent from the fungus Cordyceps sinensis, could inhibit cancer cell proliferation and promote cell death via induction of cell cycle arrest, apoptosis and autophagy. Our novel finding from microarray analysis of cordycepin-treated MA-10 mouse Leydig tumor cells is that cordycepin down-regulated the mRNA levels of FGF9, FGF18, FGFR2 and FGFR3 genes in MA-10 cells. Meanwhile, the IPA-MAP pathway prediction result showed that cordycepin inhibited MA-10 cell proliferation by suppressing FGFs/FGFRs pathways. The in vitro study further revealed that cordycepin decreased FGF9-induced MA-10 cell proliferation by inhibiting the expressions of p-ERK1/2, p-Rb and E2F1, and subsequently reducing the expressions of cyclins and CDKs. In addition, a mouse allograft model was performed by intratumoral injection of FGF9 and/or intraperitoneal injection of cordycepin to MA-10-tumor bearing C57BL/6J mice. Results showed that FGF9-induced tumor growth in cordycepin-treated mice was significantly smaller than that in a PBS-treated control group. Furthermore, cordycepin decreased FGF9-induced FGFR1-4 protein expressions in vitro and in vivo. In summary, cordycepin inhibited FGF9-induced testicular tumor growth by suppressing the ERK1/2, Rb/E2F1, cell cycle pathways, and the expressions of FGFR1-4 proteins, suggesting that cordycepin can be used as a novel anticancer drug for testicular cancers.
Meta-Analysis Suggests Differing Indirect Effects of Viral, Bacterial, and Fungal Plant Pathogens on the Natural Enemies of Insect Herbivores
Authors: Srisakrapikoop Ussawit , Pirie Tara J. , Fellowes Mark D. E.
Published: November 2020

Indirect effects are ubiquitous in nature, and have received much attention in terrestrial plant–insect herbivore–enemy systems. In such tritrophic systems, changes in plant quality can have consequential effects on the behavior and abundance of insect predators and parasitoids. Plant quality as perceived by insect herbivores may vary for a range of reasons, including because of infection by plant pathogens. However, plant diseases vary in their origin (viral, bacterial or fungal) and as a result may have differing effects on plant physiology. To investigate if the main groups of plant pathogens differ in their indirect effects on higher trophic levels, we performed a meta-analysis using 216 measured responses from 29 primary studies. There was no overall effect of plant pathogens on natural enemy traits as differences between pathogen types masked their effects. Infection by fungal plant pathogens showed indirect negative effects on the performance and preference of natural enemies via both chewing and piercing-sucking insect herbivore feeding guilds. Infection by bacterial plant pathogens had a positive effect on the natural enemies (parasitoids) of chewing herbivores. Infection by viral plant pathogens showed no clear effect, although parasitoid preference may be positively affected by their presence. It is important to note that given the limited volume of studies to date on such systems, this work should be considered exploratory. Plant pathogens are very common in nature, and tritrophic systems provide an elegant means to examine the consequences of indirect interactions in ecology. We suggest that further studies examining how plant pathogens affect higher trophic levels would be of considerable value.
The Role of Obesity in Early and Long-Term Outcomes after Surgical Excision of Lung Oligometastases from Colorectal Cancer
Authors: Londero Francesco , Parise Orlando , Grossi William , Morelli Angelo , Masullo Gianluca , Bartoletti Michele , Tetta Cecilia , Livi Ugolino , Maessen Jos G. , Gelsomino Sandro
Published: November 2020

Obesity correlates with better outcomes in many neoplastic conditions. The aim of this study was to assess its role in the prognosis and morbidity of patients submitted to resection of lung oligometastases from colorectal cancer. Seventy-six patients undergoing a first pulmonary metastasectomy were retrospectively included in the study. Seventeen (22.3%) were obese (body mass index (BMI) >30 kg/m2). Assessed outcomes were overall survival, time to recurrence, and incidence of post-operative complications. Median follow-up was 33 months (IQR 16–53). At follow-up, 37 patients (48.6%) died, whereas 39 (51.4%) were alive. A significant difference was found in the 3-year overall survival (obese 80% vs. non-obese 56.8%, p = 0.035). Competing risk analysis shows that the cumulative incidence of recurrence was not different between the two groups. Multivariate analysis reveals that the number of metastases (p = 0.028), post-operative pneumonia (p = 0.042), and DFS (p = 0.007) were significant predictors of death. Competing risk regression shows that no independent risk factor for recurrence has been identified. The complication rate was not different between the two groups (17.6% vs. 13.6%, p = 0.70). Obesity is a positive prognostic factor for survival after pulmonary metastasectomy for colorectal cancer. Overweight patients do not experience more post-operative complications. Our results need to be confirmed by large multicenter studies.
The Effect of the Dose of Isotonic Saline on the Correction of Serum Sodium in the Treatment of Hypovolemic Hyponatremia
Authors: Ruiz-Sánchez Jorge Gabriel , Meneses Diego , Álvarez-Escolá Cristina , Cuesta Martin , Calle-Pascual Alfonso Luis , Runkle Isabelle
Published: November 2020

Background: Overcorrection of serum sodium (SNa) during therapy of hyponatremia can result in osmotic demyelination syndrome. Our aim was to determine the relationship between the isotonic saline solution dose (ISSD) administered and the 24-h SNa increase (24SNa) in patients with hypovolemic hyponatremia (HH). Methods: Retrospective study of HH patients treated with ISS in a tertiary hospital of Madrid, Spain, between 1 January–30 May 2019. The 24-h ISSD received and corresponding 24SNa were calculated. The latter was classified as 3 groups: ≥8 mmol/L, ≥6 mmol/L, or <4 mmol/L. Multivariate regression analyses were performed and ROC curves calculated to study the relationship between ISSD and 24SNa. Results: Thirty patients were included, age 72 years (60–80), 50% were women. 24SNa was ≥8 mmol/L/24 h in 33%, ≥6 mmol/L/24 h in 50%, and <4 mmol/L/24 h in 30%. Median ISSD in each group was: 32 mL/kg/24 h (29–37), 31 mL/kg/24 h (25–33), and 20 mL/kg/24 h (14–22), respectively. An ISSD ≥ 30 mL/kg/24 h had an odds ratio (OR) of 16 (95% CI: 2.5–95.1; p = 0.004) for a 24SNa ≥8 mmol/L, with a sensitivity and specificity of 80%. Conclusions: The 24SNa depends on ISSD. An ISSD between 23–30 mL/kg/24 h seems to be safe and effective.
Current Challenges in the Post-Transplant Care of Liver Transplant Recipients in Germany
Authors: Herzer Kerstin , Sterneck Martina , Welker Martin-Walter , Nadalin Silvio , Kirchner Gabriele , Braun Felix , Malessa Christina , Herber Adam , Pratschke Johann , Weiss Karl Heinz , Jaeckel Elmar , Tacke Frank
Published: November 2020

Improving long-term patient and graft survival after liver transplantation (LT) remains a major challenge. Compared to the early phase after LT, long-term morbidity and mortality of the recipients not only depends on complications immediately related to the graft function, infections, or rejection, but also on medical factors such as de novo malignancies, metabolic disorders (e.g., new-onset diabetes, osteoporosis), psychiatric conditions (e.g., anxiety, depression), renal failure, and cardiovascular diseases. While a comprehensive post-transplant care at the LT center and the connected regional networks may improve outcome, there is currently no generally accepted standard to the post-transplant management of LT recipients in Germany. We therefore described the structure and standards of post-LT care by conducting a survey at 12 German LT centers including transplant hepatologists and surgeons. Aftercare structures and form of cost reimbursement considerably varied between LT centers across Germany. Further discussions and studies are required to define optimal structure and content of post-LT care systems, aiming at improving the long-term outcomes of LT recipients.
Potential Second-Hits in Hereditary Hemorrhagic Telangiectasia
Authors: Bernabeu Carmelo , Bayrak-Toydemir Pinar , McDonald Jamie , Letarte Michelle
Published: November 2020

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder that presents with telangiectases in skin and mucosae, and arteriovenous malformations (AVMs) in internal organs such as lungs, liver, and brain. Mutations in ENG (endoglin), ACVRL1 (ALK1), and MADH4 (Smad4) genes account for over 95% of HHT. Localized telangiectases and AVMs are present in different organs, with frequencies which differ among affected individuals. By itself, HHT gene heterozygosity does not account for the focal nature and varying presentation of the vascular lesions leading to the hypothesis of a “second-hit” that triggers the lesions. Accumulating research has identified a variety of triggers that may synergize with HHT gene heterozygosity to generate the vascular lesions. Among the postulated second-hits are: mechanical trauma, light, inflammation, vascular injury, angiogenic stimuli, shear stress, modifier genes, and somatic mutations in the wildtype HHT gene allele. The aim of this review is to summarize these triggers, as well as the functional mechanisms involved.
Lycium barbarum Polysaccharide Suppresses Expression of Fibrotic Proteins in Primary Human Corneal Fibroblasts
Authors: Kwok Sum Sum , Wong Francisca Siu-Yin , Shih Kendrick Co , Chan Yau-Kei , Bu Yashan , Chan Tommy Chung-Yan , Ng Alex Lap-Ki , Lo Amy Cheuk-Yin , Tong Louis , Yam Gary Hin-Fai , Jhanji Vishal
Published: November 2020

(1) Objective: To study the anti-fibrotic effects of Lycium barbarum polysaccharides (LBP) on corneal stromal fibroblasts and assess LBP’s effect on cell viability. (2) Methods: Primary human corneal keratocytes of passage 3 to 6 were used for all experiments. Cells are pretreated with LBP solution for 24 h and then transforming growth factor beta 1 (TGFβ1) for 48 h and collected for experiments. Fibrotic protein analysis was performed using immunofluorescence and Western blot. The effect of LBP on cell viability was assessed using the MTS assay. (3) Results: LBP significantly reduced the expression of fibrotic proteins, including α-SMA and extracellular matrix proteins (collagen type I and III). LBP significantly decreased the viability of myofibroblasts but not the fibroblasts. Conclusions: In this study, LBP was effective in the prevention of fibrosis gene expression. Further studies to assess the underlying mechanism and pharmacological properties will facilitate the formation of a topical LBP solution for in vivo studies.
Is Routine Prophylaxis Against Pneumocystis jirovecii Needed in Liver Transplantation? A Retrospective Single-Centre Experience and Current Prophylaxis Strategies in Spain
Authors: Fortea José Ignacio , Cuadrado Antonio , Puente Ángela , Álvarez Fernández Paloma , Huelin Patricia , Álvarez Tato Carmen , García Carrera Inés , Cobreros Marina , Cagigal Cobo María Luisa , Calvo Montes Jorge , Ruiz de Alegría Puig Carlos , Rodríguez SanJuán Juan Carlos , Castillo Suescun Federico José , Fernández Santiago Roberto , Echeverri Cifuentes Juan Andrés , Casafont Fernando , Crespo Javier , Fábrega Emilio
Published: November 2020

In liver transplant (LT) recipients, Pneumocystis jirovecii pneumonia (PJP) is most frequently reported before 1992 when immunosuppressive regimens were more intense. It is uncertain whether universal PJP prophylaxis is still applicable in the contemporary LT setting. We aimed to examine the incidence of PJP in LT recipients followed at our institution where routine prophylaxis has never been practiced and to define the prophylaxis strategies currently employed among LT units in Spain. All LT performed from 1990 to October 2019 were retrospectively reviewed and Spanish LT units were queried via email to specify their current prophylaxis strategy. During the study period, 662 LT procedures were carried out on 610 patients. Five cases of PJP were identified, with only one occurring within the first 6 months. The cumulative incidence and incidence rate were 0.82% and 0.99 cases per 1000 person transplant years. All LT units responded, the majority of which provide prophylaxis (80%). Duration of prophylaxis, however, varied significantly. The low incidence of PJP in our unprophylaxed cohort, with most cases occurring beyond the usual recommended period of prophylaxis, questions a one-size-fits-all approach to PJP prophylaxis. A significant heterogeneity in prophylaxis strategies exists among Spanish LT centres.
In Vivo Confocal Microscopy of the Corneal-Conjunctival Transition in the Evaluation of Epithelial Renewal after SLET
Authors: Pedrotti Emilio , Chierego Chiara , Cozzini Tiziano , Merz Tommaso , Lagali Neil , De Gregorio Alessandra , Fasolo Adriano , Bonacci Erika , Bonetto Jacopo , Marchini Giorgio
Published: November 2020

Examination of the corneal surface by in vivo confocal microscopy (IVCM) allows for objective identification of corneal and conjunctival cell phenotypes to evaluate different epithelialization patterns. Detection of a corneal-conjunctival epithelial transition could be considered as a sign of restored epithelial function following simple limbal epithelial transplantation (SLET). This is a prospective, interventional case series. We assessed patients with limbal stem cell deficiency (LSCD) by IVCM, preoperatively and at monthly intervals following SLET. Sectors in the central and peripheral cornea were scanned. Immediately upon detection of multi-layered cells with the epithelial phenotype in the central cornea and confirmation of epithelial transition in all corneal sectors, the decision for keratoplasty was taken. Ten patients were enrolled. After SLET, epithelial phenotype in the central cornea and an epithelial transition were identified within six and nine months in seven and one patients, respectively. One patient was a partial success and one failed. Five patients underwent keratoplasty, with stable results up to 12 months. Identification of the epithelial transition zone by IVCM permits assessment of the efficacy of SLET, enabling subsequent planning of keratoplasty for visual rehabilitation. The stability of the corneal surface following keratoplasty confirms that the renewal of the corneal epithelium was effectively retained.
Pathogenesis of Human Immunodeficiency Virus-Mycobacterium tuberculosis Co-Infection
Authors: Wong Kevin , Nguyen James , Blair Lillie , Banjanin Marina , Grewal Bunraj , Bowman Shane , Boyd Hailey , Gerstner Grant , Cho Hyun Jun , Panfilov David , Tam Cho Ki , Aguilar Delaney , Venketaraman Vishwanath
Published: November 2020

Given that infection with Mycobacterium tuberculosis (Mtb) is the leading cause of death amongst individuals living with HIV, understanding the complex mechanisms by which Mtb exacerbates HIV infection may lead to improved treatment options or adjuvant therapies. While it is well-understood how HIV compromises the immune system and leaves the host vulnerable to opportunistic infections such as Mtb, less is known about the interplay of disease once active Mtb is established. This review explores how glutathione (GSH) depletion, T cell exhaustion, granuloma formation, and TNF-α upregulation, as a result of Mtb infection, leads to an increase in HIV disease severity. This review also examines the difficulties of treating coinfected patients and suggests further research on the clinical use of GSH supplementation.