bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Exercise on Cardiac Function Outcomes in Women Receiving Anthracycline or Trastuzumab Treatment for Breast Cancer: A Systematic Review and Meta-Analysis
Authors: Antunes Pedro , Esteves Dulce , Nunes Célia , Amarelo Anabela , Fonseca-Moutinho José , Afreixo Vera , Costa Henrique , Alves Alberto , Joaquim Ana
Published: September 2021

Background: we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of exercise training on cardiac function and circulating biomarkers outcomes among women with breast cancer (BC) receiving anthracycline or trastuzumab-containing therapy. Methods: PubMed, EMBASE, Cochrane Library, Web of Science and Scopus were searched. The primary outcome was change on left ventricular ejection fraction (LVEF). Secondary outcomes included diastolic function, strain imaging and circulating biomarkers. Results: Four RCTs were included, of those three were conducted during anthracycline and one during trastuzumab, involving 161 patients. All trials provided absolute change in LVEF (%) after a short to medium-term of treatment exposure (≤6 months). Pooled data revealed no differences in LVEF in the exercise group versus control [mean difference (MD): 2.07%; 95% CI: −0.17 to 4.34]. Similar results were observed by pooling data from the three RCTs conducted during anthracycline. Data from trials that implemented interventions with ≥36 exercise sessions (n = 3) showed a significant effect in preventing LVEF decline favoring the exercise (MD: 3.25%; 95% CI: 1.20 to 5.31). No significant changes were observed on secondary outcomes. Conclusions: exercise appears to have a beneficial effect in mitigating LVEF decline and this effect was significant for interventions with ≥36 exercise sessions.
Role of Seasonality and Fire in Regulating the Enzymatic Activities in Soils Covered by Different Vegetation in a Mediterranean Area
Authors: Memoli Valeria , Santorufo Lucia , Santini Giorgia , Musella Paola , Barile Rossella , De Marco Anna , Di Natale Gabriella , Trifuoggi Marco , Maisto Giulia
Published: September 2021

As they quickly respond to environmental conditions, soil enzymes, involved in nutrient cycles, are considered good indicators of soil quality. The Mediterranean area is a peculiar environment for climatic conditions and for fire frequency. Therefore, the research aimed to evaluate the role of seasonality and fire on enzymatic activities (i.e., hydrolase, dehydrogenase, and β-glucosidase) in soils covered by herbs, black locust, pine, and holm oak. In addition, the main soil abiotic properties that drive the enzymatic activities were also investigated. In order to achieve the aims, surface soils were collected in unburnt and burnt areas and characterized for water and organic matter contents, pH, concentrations of C and N, and available fractions of Al, Ca, Cu, Fe, Mg, Mn, Na, and Pb. The results highlighted that the soil enzymatic activities were mainly affected by seasonality more than by fire; in unburnt soils, their main drivers were nutrient availabilities, whereas, in burnt soils they were pH, water and organic matter contents, C and N concentrations, and both nutrient and metal availabilities. Finally, holm oak, as compared with herbs, pine, and black locust, conferred higher stability to soils that were affected by seasonality and fire.
Effects of pH, Total Solids, Temperature and Storage Duration on Gas Emissions from Slurry Storage: A Systematic Review
Authors: Qu Qingbo , Zhang Keqiang
Published: September 2021

Gaseous emissions are the main loss pathways of nutrients during dairy slurry storage. In this study, we compiled published data on cumulative ammonia (NH3), nitrous oxide (N2O) and methane (CH4) emissions from dairy slurry storage and evaluated the integrated effects of slurry pH, total solids (TS), ambient temperature (T) and length of storage (LOS) on emissions using linear mixed effects models. Results showed that the average nitrogen (N) loss by NH3 volatilization from slurry storage was 12.5% of total nitrogen (TN), while the loss by N2O emissions only accounted for 0.05–0.39% of slurry TN. The NH3–N losses were highly related to slurry pH, lowering slurry pH leading to significant decrease of emissions. Temperature also affected NH3–N losses, with higher losses from slurry storage under warm conditions than cold conditions. No significant relationship was observed between NH3–N losses and slurry TS contents within a range from 21–169 g kg−1. The losses of N2O–N from dairy slurry storage were less affected by slurry pH, TS contents and temperature. The carbon (C) loss as CH4 emissions varied from 0.01–17.2% of total carbon (TC). Emissions of CH4–C presented a significant positive relationship with temperature, a negative relationship with slurry TS contents and no significant relationship with slurry pH ranging from 6.6–8.6. Length of storage (more than 30 days) had no significant influence on cumulative gas emissions from slurry storage. This study provides new emission factors of NH3, N2O and CH4 in the percentage of TN or TC from dairy slurry storage. Our results indicate the potential interactive effects of slurry characteristics and storage conditions on gaseous emissions from slurry storage. Farm-scale measurements are needed to accurately estimate nutrient losses from liquid manure storage.
Functional Characterization of the Wheat Macrophage Migration Inhibitory Factor TaMIF1 in Wheat-Stripe Rust (Puccinia striiformis) Interaction
Authors: Zhao Mengxin , Chang Qing , Liu Yueni , Sang Peng , Kang Zhensheng , Wang Xiaojie
Published: September 2021

Macrophage migration inhibitory factor (MIF), named for its role in inhibiting macrophage/monocyte migration, has multiple functions in modulation of inflammation, cell proliferation, angiogenesis, and tumorigenesis in vertebrates. Although homologs of this gene can be found in plants, the function of MIF in plants remains obscure. Here, we characterized TaMIF1 in Triticum aestivum resembling the MIF secreted from Homo sapiens. Transcript analysis revealed that TaMIF1 responded to stripe rust infection of wheat and was upregulated during the infection stage. TaMIF1 was localized to both the cytosol and nuclei in wheat mesophyll protoplast. Additionally, TaMIF1 possessed significant tautomerase activity, indicating conservation of MIFs across kingdoms. Agrobacterium tumefaciens infiltration assay demonstrated that TaMIF1 was capable of suppressing programmed cell death hinting its role in plant immunity. Heterologous expression of TaMIF1 increased fission yeast sensitivity to oxidative stress. Silencing TaMIF1 decreased the susceptibility of wheat to Pst seemingly through increasing reactive oxygen species accumulation. In conclusion, functions of the TaMIF1 were investigated in this study, which provides significant insight into understanding the role of MIFs across kingdoms.
Multiple Introductions of Rabbit Hemorrhagic Disease Virus Lagovirus europaeus/GI.2 in Africa
Authors: Ben Chehida Faten , Lopes Ana M. , Côrte-Real João V. , Sghaier Soufien , Aouini Rim , Messadi Lilia , Abrantes Joana
Published: September 2021

Rabbit hemorrhagic disease (RHD) causes high mortality and morbidity in European rabbits (Oryctolagus cuniculus). In Africa, the presence of the causative agent, the rabbit hemorrhagic disease virus (RHDV), was first confirmed in 1992 (genotype Lagovirus europaeus/GI.1). In 2015, the new genotype Lagovirus europaeus/GI.2 (RHDV2/b) was detected in Tunisia. Currently, GI.2 strains are present in several North and Sub-Saharan African countries. Considerable economic losses have been observed in industrial and traditional African rabbitries due to RHDV. Like other RNA viruses, this virus presents high recombination rates, with the emergence of GI.2 being associated with a recombinant strain. Recombination events have been detected with both pathogenic (GI.1b and GII.1) and benign (GI.3 and GI.4) strains. We obtained complete genome sequences of Tunisian GI.2 strains collected between 2018 and 2020 and carried out phylogenetic analyses. The results revealed that Tunisian strains are GI.3P-GI.2 strains that were most likely introduced from Europe. In addition, the results support the occurrence of multiple introductions of GI.2 into Africa, stressing the need for characterizing complete genome sequences of the circulating lagoviruses to uncover their origin. Continued monitoring and control of rabbit trade will grant a better containment of the disease and reduce the disease-associated economic losses.
Bitter Taste Disrupts Spatial Discrimination of Piperine-Evoked Burning Sensations: A Pilot Study
Authors: Liu David T. , Besser Gerold , Bayer Karina , Prem Bernhard , Mueller Christian A. , Renner Bertold
Published: September 2021

This study aimed to investigate the perceptual similarity between piperine-induced burning sensations and bitter taste using piperine-impregnated taste strips (PTS). This pilot study included 42 healthy participants. PTS of six ascending concentrations (1 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg piperine/dL 96% ethanol) were presented at the anterior tongue, and participants rated perceived intensity and duration. Then, participants performed a spatial discrimination task in which they had to report which of the two strips presented to the anterior tongue contained an irritating stimulus when one strip was always a PTS while the other strip was impregnated with either a single taste quality (sweet or bitter) or a blank strip. Repeated measures one-way ANOVA revealed that burning sensations of higher concentrated PTS were perceived more intense and more prolonged compared to lower concentrated PTS. McNemar’s test showed that PTS were identified correctly significantly less often when presented with bitter strips compared to when presented with blank (p = 0.002) or sweet strips (p = 0.017). Our results showed that bitter taste disrupts the spatial discrimination of piperine-evoked burning sensations. PTS might serve as a basis for further studies on disease-specific patterns in chemosensory disorders.
Novel Approaches to an Integrated Route for Trisomy 21 Evaluation
Authors: Buczyńska Angelika , Sidorkiewicz Iwona , Trochimiuk Anna , Ławicki Sławomir , Krętowski Adam Jacek , Zbucka-Krętowska Monika
Published: September 2021

Trisomy 21 (T21) is one of the most commonly occurring genetic disorders, caused by the partial or complete triplication of chromosome 21. Despite the significant progress in the diagnostic tools applied for prenatal screening, commonly used methods are still imprecise and involve invasive diagnostic procedures that are related to a maternal risk of miscarriage. In this case, novel prenatal biomarkers are still being evaluated using highly specialized techniques, which could increase the diagnostic usefulness of biochemical prenatal screening for T21. From the other hand, the T21′s pathogenesis, caused by the improper division of genetic material, disrupting many metabolic pathways, could be further evaluated with the use of omics methods, which could result in bringing relevant insights for the evaluation of potential medical targets. Accordingly, a literature search was undertaken to collect novel information about prenatal screening for Down syndrome with the use of advanced technology, with a particular emphasis on the evaluation of novel screening biomarkers and the discovery of potential medical targets. These meta-analyses are focused on novel approaches designed with the use of omics techniques, representing the most rapidly developing and promising field in research today. Considering the limitations and progress of these methods, the use of omics techniques in evaluating T21 pathogenesis could bring beneficial results in prenatal screening, simultaneously uncovering novel potential medical targets.
Eradication of Mature Bacterial Biofilms with Concurrent Improvement in Chronic Wound Healing Using Silver Nanoparticle Hydrogel Treatment
Authors: Haidari Hanif , Bright Richard , Garg Sanjay , Vasilev Krasimir , Cowin Allison J. , Kopecki Zlatko
Published: September 2021

Biofilm-associated infections are a major cause of impaired wound healing. Despite the broad spectrum of anti-bacterial benefits provided by silver nanoparticles (AgNPs), these materials still cause controversy due to cytotoxicity and a lack of efficacy against mature biofilms. Herein, highly potent ultrasmall AgNPs were combined with a biocompatible hydrogel with integrated synergistic functionalities to facilitate elimination of clinically relevant mature biofilms in-vivo combined with improved wound healing capacity. The delivery platform showed a superior release mechanism, reflected by high biocompatibility, hemocompatibility, and extended antibacterial efficacy. In vivo studies using the S. aureus wound biofilm model showed that the AgNP hydrogel (200 µg/g) was highly effective in eliminating biofilm infection and promoting wound repair compared to the controls, including silver sulfadiazine (Ag SD). Treatment of infected wounds with the AgNP hydrogel resulted in faster wound closure (46% closure compared to 20% for Ag SD) and accelerated wound re-epithelization (60% for AgNP), as well as improved early collagen deposition. The AgNP hydrogel did not show any toxicity to tissue and/or organs. These findings suggest that the developed AgNP hydrogel has the potential to be a safe wound treatment capable of eliminating infection and providing a safe yet effective strategy for the treatment of infected wounds.
Voltammetric Electrochemical Sensor for Phylogenetic Study in Acer Linn.
Authors: Zhou Qingwei , Liu Kewei , Li Xiaolong , Gu Yonghua , Zheng Yuhong , Fan Boyuan , Wu Weihong
Published: September 2021

Acer Linn. is a highly divergent species morphology in the maple family (Aceraceae). It is one of the genera facing a very difficult taxonomic situation. The phylogeny of the genus and the taxonomic system under the genus remain unclear. The use of electrochemical fingerprints for plant phylogenetic study is an emerging application in biosensors. In this work, leaves of 18 species of Acer Linn. with an exo-taxa were selected for electrochemical fingerprint recording. Two different conditions were used for improving the data abundance. The fingerprint of all species showed a series of oxidation peaks. These peaks can be ascribed to the oxidation of flavonols, phenolic acids, procyanidins, alkaloids, and pigments in plant tissue. These electrochemical fingerprints can be used for the identification of plant species. We also performed a phylogenetic study with data from electrochemical fingerprinting. The phylogenetic tree of Acer is divided into three main clades. The result is in full agreement with A. shangszeense var. anfuense, A. pictum subsp. mono, A. amplum, A. truncatum, and A. miaotaiense, belonging to the subsection Platanoidea. A. nikoense and A. griseum were clustered together in the dendrogram. Another group that fits the traditional classification results is in the subsection Integrifolia.
Binding Analysis of Functionalized Multimode Optical-Fiber Sandwich-like Structure with Organic Polymer and Its Sensing Application for Humidity and Breath Monitoring
Authors: Jauregui-Vazquez Daniel , Lozano-Sotomayor Paulina , Mejía-Benavides Jorge Emmanuel , Díaz-Cervantes Erik
Published: September 2021

In recent years, the chemical modification of optical fibers (OFs) has facilitated the manufacture of sensors because OFs can identify several analytes present in aqueous solutions or gas phases. Nevertheless, it is imperative better to understand the chemical interactions in this molecular system to generate low-cost and efficient sensors. This work presents a theoretical and experimental study of organic polymeric functionalized OF structures and proposes a cost-effective alternative to monitor breathing and humidity. The device is based on silicon optical fibers functionalized with (3-Aminopropyl) triethoxysilane (APTES) and alginate. The theoretical analysis is carried out to validate the activation of the silicon dioxide fiber surface; moreover, the APTES–alginate layer is discussed. The computational simulation suggests that water can be absorbed by alginate, specifically by the calcium atom linked to the carboxylic acid group of the alginate. The analysis also demonstrates a higher electrostatic interaction between the water and the OF–APTES–alginate system; this interaction alters the optical fiber activated surface’s refractive index, resulting in transmission power variation. The humidity analysis shows a sensitivity of 3.1288 mV/RH, a time response close to 25 s, and a recovery time around 8 s. These results were achieved in the range of 50 to 95% RH. Moreover, the recovery and response time allow the human breath to be studied. The proposed mechanism or device is competitive with prior works, and the components involved made this sensor a cost-effective alternative for medical applications.
Prediction of Shear Strength of Reinforced Recycled Aggregate Concrete Beams without Stirrups
Authors: Setkit Monthian , Leelatanon Satjapan , Imjai Thanongsak , Garcia Reyes , Limkatanyu Suchart
Published: September 2021

For decades, recycled coarse aggregate (RCA) has been used to make recycled aggregate concrete (RAC). Numerous studies have compared the mechanical properties and durability of recycled aggregate concrete (RAC) to those of natural aggregate concrete (NAC). However, test results on the shear strength of reinforced recycled aggregate concrete beams are still limited and sometimes contradictory. Shear failure is generally brittle and must be prevented. This article studies experimentally and analytically the shear strength of reinforced RAC beams without stirrups. Eight RAC beams and two controlled NAC beams were tested under the four-point flexural test with the shear span-to-effective depth ratio (a/d) of 3.10. The main parameters investigated were the replacement percentage of RCA (0%, 25%, 50%, 75%, and 100%) and longitudinal reinforcement ratio (ρw) of 1.16% and 1.81%. It was found that the normalized shear stresses of RAC beams with ρw = 1.81% at all levels of replacement percentage were quite similar to those of the NAC counterparts. Moreover, the normalized shear stress of the beam with 100% RCA and ρw = 1.16% was only 6% lower than that of the NAC beam. A database of 128 RAC beams without shear reinforcement from literature was analyzed to evaluate the accuracy of the ACI 318-19 shear provisions in predicting the shear strength of the beams. For an RCA replacement ratio of between 50% and 100%, it was proposed to apply a reduction factor of 0.75 to the current ACI code equation to account for the physical variations of RCA, such as replacement percentage, RCA source and quality, density, amount of residual mortar, and physical irregularity.
Musings from the Tribbles Research and Innovation Network
Authors: Ruiz-Cantos Miriam , Hutchison Claire E. , Shoulders Carol C.
Published: September 2021

This commentary integrates historical and modern findings that underpin our understanding of the cell-specific functions of the Tribbles (TRIB) proteins that bear on tumorigenesis. We touch on the initial discovery of roles played by mammalian TRIB proteins in a diverse range of cell-types and pathologies, for example, TRIB1 in regulatory T-cells, TRIB2 in acute myeloid leukaemia and TRIB3 in gliomas; the origins and diversity of TRIB1 transcripts; microRNA-mediated (miRNA) regulation of TRIB1 transcript decay and translation; the substantial conformational changes that ensue on binding of TRIB1 to the transcription factor C/EBPα; and the unique pocket formed by TRIB1 to sequester its C-terminal motif bearing a binding site for the E3 ubiquitin ligase COP1. Unashamedly, the narrative is relayed through the perspective of the Tribbles Research and Innovation Network, and its establishment, progress and future ambitions: the growth of TRIB and COP1 research to hasten discovery of their cell-specific contributions to health and obesity-related cancers.
Protein Ligands in the Secretome of CD36+ Fibroblasts Induce Growth Suppression in a Subset of Breast Cancer Cell Lines
Authors: Jabbari Kosar , Winkelmaier Garrett , Andersen Cody , Yaswen Paul , Quilici David , Furuta Saori , Cheng Qingsu , Parvin Bahram
Published: September 2021

Reprogramming the tumor stroma is an emerging approach to circumventing the challenges of conventional cancer therapies. This strategy, however, is hampered by the lack of a specific molecular target. We previously reported that stromal fibroblasts (FBs) with high expression of CD36 could be utilized for this purpose. These studies are now expanded to identify the secreted factors responsible for tumor suppression. Methodologies included 3D colonies, fluorescent microscopy coupled with quantitative techniques, proteomics profiling, and bioinformatics analysis. The results indicated that the conditioned medium (CM) of the CD36+ FBs caused growth suppression via apoptosis in the triple-negative cell lines of MDA-MB-231, BT549, and Hs578T, but not in the ERBB2+ SKBR3. Following the proteomics and bioinformatic analysis of the CM of CD36+ versus CD36− FBs, we determined KLF10 as one of the transcription factors responsible for growth suppression. We also identified FBLN1, SLIT3, and PENK as active ligands, where their minimum effective concentrations were determined. Finally, in MDA-MB-231, we showed that a mixture of FBLN1, SLIT3, and PENK could induce an amount of growth suppression similar to the CM of CD36+ FBs. In conclusion, our findings suggest that these ligands, secreted by CD36+ FBs, can be targeted for breast cancer treatment.
Optimal Sequencing and Predictive Biomarkers in Patients with Advanced Prostate Cancer
Authors: Cattrini Carlo , España Rodrigo , Mennitto Alessia , Bersanelli Melissa , Castro Elena , Olmos David , Lorente David , Gennari Alessandra
Published: September 2021

The treatment landscape of advanced prostate cancer has completely changed during the last decades. Chemotherapy (docetaxel, cabazitaxel), androgen-receptor signaling inhibitors (ARSi) (abiraterone acetate, enzalutamide), and radium-223 have revolutionized the management of metastatic castration-resistant prostate cancer (mCRPC). Lutetium-177–PSMA-617 is also going to become another treatment option for these patients. In addition, docetaxel, abiraterone acetate, apalutamide, enzalutamide, and radiotherapy to primary tumor have demonstrated the ability to significantly prolong the survival of patients with metastatic hormone-sensitive prostate cancer (mHSPC). Finally, apalutamide, enzalutamide, and darolutamide have recently provided impactful data in patients with nonmetastatic castration-resistant disease (nmCRPC). However, which is the best treatment sequence for patients with advanced prostate cancer? This comprehensive review aims at discussing the available literature data to identify the optimal sequencing approaches in patients with prostate cancer at different disease stages. Our work also highlights the potential impact of predictive biomarkers in treatment sequencing and exploring the role of specific agents (i.e., olaparib, rucaparib, talazoparib, niraparib, and ipatasertib) in biomarker-selected populations of patients with prostate cancer (i.e., those harboring alterations in DNA damage and response genes or PTEN).
Recent Advances of Pd/C-Catalyzed Reactions
Authors: Mao Zhenjun , Gu Haorui , Lin Xufeng
Published: September 2021

The Pd/C-catalyzed reactions, including reduction reactions and cross-coupling reactions, play an irreplaceable role in modern organic synthesis. Compared to the homogeneous palladium catalyst system, the heterogeneous Pd/C catalyst system offers an alternative protocol that has particular advantages and applications. Herein, a review on Pd/C-catalyzed reactions is presented. Both the advances in Pd/C-catalyzed methodologies and the application of Pd/C-catalysis in total synthesis are covered in this review.
Promotion Effect of Palladium on BiVO4 Sensing Material for Epinephrine Detection
Authors: Luk Hsiang-Ning , Chou Tsong-Yung , Huang Bai-Hao , Lin Yu-Syuan , Li Hui , Wu Ren-Jang
Published: September 2021

In this study, the Pd/BiVO4 composite was prepared by hydrothermal method as an electrochemical sensing material for epinephrine. X-ray diffraction, scanning electron microscopy, and a transmission electron microscope were used to characterize the samples. In the electrochemical detection system, cyclic voltammetry and differential pulse voltammetry were applied to measure the concentration of the epinephrine solution (0.9–27.5 µM) with the Pd/BiVO4-coated glassy carbon electrode. As a result, the oxidation peak current of Pd/BiVO4/GCE demonstrated good linearity with the epinephrine concentration. The detection limit of the epinephrine concentration by cyclic voltammetry and differential pulse voltammetry were 0.262 µM and 0.154 µM, respectively. Additionally, the proposed sensing material exhibited good reproducibility, stability, and selectivity. A plausible sensing mechanism was proposed.
D-2-Hydroxyglutarate in Glioma Biology
Authors: Chou Fu-Ju , Liu Yang , Lang Fengchao , Yang Chunzhang
Published: September 2021

Isocitrate dehydrogenase (IDH) mutations are common genetic abnormalities in glioma, which result in the accumulation of an “oncometabolite”, D-2-hydroxyglutarate (D-2-HG). Abnormally elevated D-2-HG levels result in a distinctive pattern in cancer biology, through competitively inhibiting α-ketoglutarate (α-KG)/Fe(II)-dependent dioxgenases (α-KGDDs). Recent studies have revealed that D-2-HG affects DNA/histone methylation, hypoxia signaling, DNA repair, and redox homeostasis, which impacts the oncogenesis of IDH-mutated cancers. In this review, we will discuss the current understanding of D-2-HG in cancer biology, as well as the emerging opportunities in therapeutics in IDH-mutated glioma.
Strategic Development of an Immunotoxin for the Treatment of Glioblastoma and Other Tumours Expressing the Calcitonin Receptor
Authors: Gupta Pragya , Hare David L. , Wookey Peter J.
Published: September 2021

New strategies aimed at treatment of glioblastoma are frequently proposed to overcome poor prognosis. Recently, research has focused on glioma stem cells (GSCs), some quiescent, which drive expansion of glioblastoma and provide the complexity and heterogeneity of the tumour hierarchy. Targeting quiescent GSCs is beyond the capability of conventional drugs such as temozolomide. Here, we discuss the proposal that the calcitonin receptor (CT Receptor), expressed in 76–86% of patient biopsies, is expressed by both malignant glioma cells and GSCs. Forty-two percent (42%) of high-grade glioma (HGG; representative of GSCs) cell lines available from one source express CT Receptor protein in cell culture. The pharmacological calcitonin (CT)-response profiles of four of the HGG cell lines were reported, suggesting mutational/splicing inactivation. Alternative splicing, commonly associated with cancer cells, could result in the predominant expression of the insert-positive isoform and explain the atypical pharmacology exhibited by CT non-responders. A role for the CT Receptor as a putative tumour suppressor and/or oncoprotein is discussed. Both CT responders and non-responders were sensitive to immunotoxins based on an anti-CT Receptor antibody conjugated to ribosomal-inactivating proteins. Sensitivity was increased by several logs with the triterpene glycoside SO1861, an endosomal escape enhancer. Under these conditions, the immunotoxins were 250–300 times more potent than an equivalent antibody conjugated with monomethyl auristatin E. Further refinements for improving the penetration of solid tumours are discussed. With this knowledge, a potential strategy for effective targeting of CSCs expressing this receptor is proposed for the treatment of GBM.
Perturbed Brain Glucose Metabolism Caused by Absent SIRT3 Activity
Authors: Kristian Tibor , Karimi Arman J. , Fearnow Adam , Waddell Jaylyn , McKenna Mary C.
Published: September 2021

Acetylation is a post-translational modification that regulates the activity of enzymes fundamentally involved in cellular and mitochondrial bioenergetic metabolism. NAD+ dependent deacetylase sirtuin 3 (SIRT3) is localized to mitochondria where it plays a key role in regulating acetylation of TCA cycle enzymes and the mitochondrial respiratory complexes. Although the SIRT3 target proteins in mitochondria have been identified, the effect of SIRT3 activity on mitochondrial glucose metabolism in the brain remains elusive. The impact of abolished SIRT3 activity on glucose metabolism was determined in SIRT3 knockout (KO) and wild type (WT) mice injected with [1,6-13C]glucose using ex vivo 13C-NMR spectroscopy. The 1H-NMR spectra and amino acid analysis showed no differences in the concentration of lactate, glutamate, alanine, succinate, or aspartate between SIRT3 KO and WT mice. However, glutamine, total creatine (Cr), and GABA were lower in SIRT3 KO brain. Incorporation of label from [1,6-13C]glucose metabolism into lactate or alanine was not affected in SIRT3 KO brain. However, the incorporation of the label into all isotopomers of glutamate, glutamine, GABA and aspartate was lower in SIRT3 KO brain, reflecting decreased activity of mitochondrial and TCA cycle metabolism in both neurons and astrocytes. This is most likely due to hyperacetylation of mitochondrial enzymes due to suppressed SIRT3 activity in the brain of SIRT3 KO mice. Thus, the absence of Sirt3 results in impaired mitochondrial oxidative energy metabolism and neurotransmitter synthesis in the brain. Since the SIRT3 activity is NAD+ dependent, these results might parallel changes in glucose metabolism under pathologic reduction in mitochondrial NAD+ pools.
Compositional Features of Distinct Microbiota Base on Serum Extracellular Vesicle Metagenomics Analysis in Moderate to Severe Psoriasis Patients
Authors: Chang Chih-Jung , Zhang Jing , Tsai Yu-Ling , Chen Chun-Bing , Lu Chun-Wei , Huo Yu-Ping , Liou Huey-Ming , Ji Chao , Chung Wen-Hung
Published: September 2021

The bacterial microbiota in the skin and intestine of patients with psoriasis were different compared with that of healthy individuals. However, the presence of a distinct blood microbiome in patients with psoriasis is yet to be investigated. In this study, we investigated the differences in bacterial communities in plasma-derived extracellular vesicles (EVs) between patients with moderate to severe psoriasis (PSOs) and healthy controls (HCs). The plasma EVs from the PSO (PASI > 10) (n = 20) and HC (n = 8) groups were obtained via a series of centrifugations, and patterns were examined and confirmed using transmission electron microscopy (TEM) and EV-specific markers. The taxonomic composition of the microbiota was determined by using full-length 16S ribosomal RNA gene sequencing. The PSO group had lower bacterial diversity and richness compared with HC group. Principal coordinate analysis (PCoA)-based clustering was used to assess diversity and validated dysbiosis for both groups. Differences at the level of amplicon sequence variant (ASV) were observed, suggesting alterations in specific ASVs according to health conditions. The HC group had higher levels of the phylum Firmicutes and Fusobacteria than in the PSO group. The order Lactobacillales, family Brucellaceae, genera Streptococcus, and species Kingella oralis and Aquabacterium parvum were highly abundant in the HC group compared with the PSO group. Conversely, the order Bacillales and the genera Staphylococcus and Sphihgomonas, as well as Ralstonia insidiosa, were more abundant in the PSO group. We further predicted the microbiota functional capacities, which revealed significant differences between the PSO and HC groups. In addition to previous studies on microbiome changes in the skin and gut, we demonstrated compositional differences in the microbe-derived EVs in the plasma of PSO patients. Plasma EVs could be an indicator for assessing the composition of the microbiome of PSO patients.
Impact of Microorganisms and Parasites on Neuronally Controlled Drosophila Behaviours
Authors: Montanari Martina , Royet Julien
Published: September 2021

Like all invertebrates, flies such as Drosophila lack an adaptive immune system and depend on their innate immune system to protect them against pathogenic microorganisms and parasites. In recent years, it appears that the nervous systems of eucaryotes not only control animal behavior but also cooperate and synergize very strongly with the animals’ immune systems to detect and fight potential pathogenic threats, and allow them to adapt their behavior to the presence of microorganisms and parasites that coexist with them. This review puts into perspective the latest progress made using the Drosophila model system, in this field of research, which remains in its infancy.
The Manifold Cellular Functions of von Willebrand Factor
Authors: Mojzisch Angelika , Brehm Maria A.
Published: September 2021

The plasma glycoprotein von Willebrand factor (VWF) is exclusively synthesized in endothelial cells (ECs) and megakaryocytes, the precursor cells of platelets. Its primary function lies in hemostasis. However, VWF is much more than just a “fishing hook” for platelets and a transporter for coagulation factor VIII. VWF is a true multitasker when it comes to its many roles in cellular processes. In ECs, VWF coordinates the formation of Weibel–Palade bodies and guides several cargo proteins to these storage organelles, which control the release of hemostatic, inflammatory and angiogenic factors. Leukocytes employ VWF to assist their rolling on, adhesion to and passage through the endothelium. Vascular smooth muscle cell proliferation is supported by VWF, and it regulates angiogenesis. The life cycle of platelets is accompanied by VWF from their budding from megakaryocytes to adhesion, activation and aggregation until the end in apoptosis. Some tumor cells acquire the ability to produce VWF to promote metastasis and hide in a shell of VWF and platelets, and even the maturation of osteoclasts is regulated by VWF. This review summarizes the current knowledge on VWF’s versatile cellular functions and the resulting pathophysiological consequences of their dysregulation.
Plectin in the Central Nervous System and a Putative Role in Brain Astrocytes
Authors: Potokar Maja , Jorgačevski Jernej
Published: September 2021

Plectin, a high-molecular-mass cytolinker, is abundantly expressed in the central nervous system (CNS). Currently, a limited amount of data about plectin in the CNS prevents us from seeing the complete picture of how plectin affects the functioning of the CNS as a whole. Yet, by analogy to its role in other tissues, it is anticipated that, in the CNS, plectin also functions as the key cytoskeleton interlinking molecule. Thus, it is likely involved in signalling processes, thereby affecting numerous fundamental functions in the brain and spinal cord. Versatile direct and indirect interactions of plectin with cytoskeletal filaments and enzymes in the cells of the CNS in normal physiological and in pathologic conditions remain to be fully addressed. Several pathologies of the CNS related to plectin have been discovered in patients with plectinopathies. However, in view of plectin as an integrator of a cohesive mesh of cellular proteins, it is important that the role of plectin is also considered in other CNS pathologies. This review summarizes the current knowledge of plectin in the CNS, focusing on plectin isoforms that have been detected in the CNS, along with its expression profile and distribution alongside diverse cytoskeleton filaments in CNS cell types. Considering that the bidirectional communication between neurons and glial cells, especially astrocytes, is crucial for proper functioning of the CNS, we place particular emphasis on the known roles of plectin in neurons, and we propose possible roles of plectin in astrocytes.
Store-Operated Calcium Entry in Skeletal Muscle: What Makes It Different?
Authors: Lilliu Elena , Koenig Stéphane , Koenig Xaver , Frieden Maud
Published: September 2021

Current knowledge on store-operated Ca2+ entry (SOCE) regarding its localization, kinetics, and regulation is mostly derived from studies performed in non-excitable cells. After a long time of relative disinterest in skeletal muscle SOCE, this mechanism is now recognized as an essential contributor to muscle physiology, as highlighted by the muscle pathologies that are associated with mutations in the SOCE molecules STIM1 and Orai1. This review mainly focuses on the peculiar aspects of skeletal muscle SOCE that differentiate it from its counterpart found in non-excitable cells. This includes questions about SOCE localization and the movement of respective proteins in the highly organized skeletal muscle fibers, as well as the diversity of expressed STIM isoforms and their differential expression between muscle fiber types. The emerging evidence of a phasic SOCE, which is activated during EC coupling, and its physiological implication is described as well. The specific issues related to the use of SOCE modulators in skeletal muscles are discussed. This review highlights the complexity of SOCE activation and its regulation in skeletal muscle, with an emphasis on the most recent findings and the aim to reach a current picture of this mesmerizing phenomenon.
Towards Understanding the Pathogenicity of DROSHA Mutations in Oncohematology
Authors: Bug Dmitrii S. , Tishkov Artem V. , Moiseev Ivan S. , Porozov Yuri B. , Petukhova Natalia V.
Published: September 2021

Myelodysplastic syndrome (MDS) refers to a heterogeneous group of closely related clonal hematopoietic disorders, which are characterized by accumulation of somatic mutations. The acquired mutation burden is suggested to define the pathway and consequent phenotype of the pathology. Recent studies have called attention to the role of miRNA biogenesis genes in MDS progression; in particular, the mutational pressure of the DROSHA gene was determined. Therefore, this highlights the importance of studying the impact of all collected missense mutations found within the DROSHA gene in oncohematology that might affect the functionality of the protein. In this study, the selected mutations were extensively examined by computational screening, and the most deleterious were subjected to a further molecular dynamic simulation in order to uncover the molecular mechanism of the structural damage to the protein altering its biological function. The most significant effect was found for variants I625K, L1047S, and H1170D, presumably affecting the endonuclease activity of DROSHA. Such alterations arisen during MDS progression should be taken into consideration as evoking certain clinical traits in the malignifying clonal evolution.
Subgenome Discrimination in Brassica and Raphanus Allopolyploids Using Microsatellites
Authors: Campomayor Nicole Bon , Waminal Nomar Espinosa , Kang Byung Yong , Nguyen Thi Hong , Lee Soo-Seong , Huh Jin Hoe , Kim Hyun Hee
Published: September 2021

Intergeneric crosses between Brassica species and Raphanus sativus have produced crops with prominent shoot and root systems of Brassica and R. sativus, respectively. It is necessary to discriminate donor genomes when studying cytogenetic stability in distant crosses to identify homologous chromosome pairing, and microsatellite repeats have been used to discriminate subgenomes in allopolyploids. To identify genome-specific microsatellites, we explored the microsatellite content in three Brassica species (B. rapa, AA, B. oleracea, CC, and B. nigra, BB) and R. sativus (RR) genomes, and validated their genome specificity by fluorescence in situ hybridization. We identified three microsatellites showing A, C, and B/R genome specificity. ACBR_msat14 and ACBR_msat20 were detected in the A and C chromosomes, respectively, and ACBR_msat01 was detected in B and R genomes. However, we did not find a microsatellite that discriminated the B and R genomes. The localization of ACBR_msat20 in the 45S rDNA array in ×Brassicoraphanus 977 corroborated the association of the 45S rDNA array with genome rearrangement. Along with the rDNA and telomeric repeat probes, these microsatellites enabled the easy identification of homologous chromosomes. These data demonstrate the utility of microsatellites as probes in identifying subgenomes within closely related Brassica and Raphanus species for the analysis of genetic stability of new synthetic polyploids of these genomes.
Effects of High Dietary Carbohydrate and Lipid Intake on the Lifespan of C. elegans
Authors: Franco-Juárez Berenice , Gómez-Manzo Saúl , Hernández-Ochoa Beatriz , Cárdenas-Rodríguez Noemi , Arreguin-Espinosa Roberto , Pérez de la Cruz Verónica , Ortega-Cuellar Daniel
Published: September 2021

Health and lifespan are influenced by dietary nutrients, whose balance is dependent on the supply or demand of each organism. Many studies have shown that an increased carbohydrate–lipid intake plays a critical role in metabolic dysregulation, which impacts longevity. Caenorhabditis elegans has been successfully used as an in vivo model to study the effects of several factors, such as genetic, environmental, diet, and lifestyle factors, on the molecular mechanisms that have been linked to healthspan, lifespan, and the aging process. There is evidence showing the causative effects of high glucose on lifespan in different diabetic models; however, the precise biological mechanisms affected by dietary nutrients, specifically carbohydrates and lipids, as well as their links with lifespan and longevity, remain unknown. Here, we provide an overview of the deleterious effects caused by high-carbohydrate and high-lipid diets, as well as the molecular signals that affect the lifespan of C. elegans; thus, understanding the detailed molecular mechanisms of high-glucose- and lipid-induced changes in whole organisms would allow the targeting of key regulatory factors to ameliorate metabolic disorders and age-related diseases.
Chromatin Organization and Function in Drosophila
Authors: Llorens-Giralt Palmira , Camilleri-Robles Carlos , Corominas Montserrat , Climent-Cantó Paula
Published: September 2021

Eukaryotic genomes are packaged into high-order chromatin structures organized in discrete territories inside the cell nucleus, which is surrounded by the nuclear envelope acting as a barrier. This chromatin organization is complex and dynamic and, thus, determining the spatial and temporal distribution and folding of chromosomes within the nucleus is critical for understanding the role of chromatin topology in genome function. Primarily focusing on the regulation of gene expression, we review here how the genome of Drosophila melanogaster is organized into the cell nucleus, from small scale histone–DNA interactions to chromosome and lamina interactions in the nuclear space.
Biosensors for Detection and Monitoring of Joint Infections
Authors: Longo Umile Giuseppe , De Salvatore Sergio , Zompanti Alessandro , Di Naro Calogero , Grasso Simone , Casciaro Carlo , Sabatini Anna , Mazzola Alessandro , Pennazza Giorgio , Santonico Marco , Denaro Vincenzo
Published: September 2021

The aim of this review is to assess the use of biosensors in the diagnosis and monitoring of joint infection (JI). JI is worldwide considered a significant cause of morbidity and mortality in developed countries. Due to the progressive ageing of the global population, the request for joint replacement increases, with a significant rise in the risk of periprosthetic joint infection (PJI). Nowadays, the diagnosis of JI is based on clinical and radiological findings. Nuclear imaging studies are an option but are not cost-effective. Serum inflammatory markers and the analysis of the aspirated synovial fluid are required to confirm the diagnosis. However, a quick and accurate diagnosis of JI may remain elusive as no rapid and highly accurate diagnostic method was validated. A comprehensive search on Medline, EMBASE, Scopus, CINAH, CENTRAL, Google Scholar, and Web of Science was conducted from the inception to June 2021. The PRISMA guidelines were used to improve the reporting of the review. The MINORS was used for quality assessment. From a total of 155 studies identified, only four articles were eligible for this study. The main advantages of biosensors reported were accuracy and capability to detect bacteria also in negative culture cases. Otherwise, due to the few studies and the low level of evidence of the papers included, it was impossible to find significant results. Therefore, further high-quality studies are required.
Controlled Growth of WO3 Pyramidal Thin Film via Hot-Filament Chemical Vapor Deposition: Electrochemical Detection of Ethylenediamine
Authors: Imran Mohammad , Kim Eun-Bi , Kwak Dong-Heui , Akhtar Mohammad Shaheer , Ameen Sadia
Published: September 2021

In this work, the structural, optical, morphological, and sensing features of tungsten oxide (WO3) thin film deposited on a silicon substrate via hot-filament chemical vapor deposition (HFCVD) are described. The experimental characterization tools, such as X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), ultraviolet-visible (UV-Vis), and Fourier transform infra-red (FTIR) spectroscopies, etc., were used to determine the properties of WO3 NPys thin films. The grown WO3 thin film illustrated closely packed porous pyramidal nanostructures (NPys) of improved grain size properties. The diffraction analysis revealed (100) and (200) of WO3 phases, suggesting the classic monoclinic crystal WO3 structure. HFCVD grown WO3 NPys thin film was employed as electro-active electrode for detecting ethylenediamine in 10 mL of 0.1 M phosphate buffer solution (PBS) by varying the ethylenediamine concentrations from 10 μM to 200 μM at room temperature. With a detection of limit (LOD) of ~9.56 μM, and a quick reaction time (10 s), the constructed chemical sensor achieved a high sensitivity of ~161.33 μA μM−1 cm−2. The durability test displayed an excellent stability of electrochemical sensor by maintaining over 90% sensitivity after 4 weeks of operation. This work provides a strategy for a facile preparation of WO3 NPys thin film electrode for sensor applications.
Plasma Surface Engineering to Biofunctionalise Polymers for β-Cell Adhesion
Authors: Tran Clara , Hallahan Nicole , Kosobrodova Elena , Tong Jason , Thorn Peter , Bilek Marcela
Published: September 2021

Implant devices containing insulin-secreting β-cells hold great promise for the treatment of diabetes. Using in vitro cell culture, long-term function and viability are enhanced when β-cells are cultured with extracellular matrix (ECM) proteins. Here, our goal is to engineer a favorable environment within implant devices, where ECM proteins are stably immobilized on polymer scaffolds, to better support β-cell adhesion. Four different polymer candidates (low-density polyethylene (LDPE), polystyrene (PS), polyethersulfone (PES) and polysulfone (PSU)) were treated using plasma immersion ion implantation (PIII) to enable the covalent attachment of laminin on their surfaces. Surface characterisation analysis shows the increased hydrophilicity, polar groups and radical density on all polymers after the treatment. Among the four polymers, PIII-treated LDPE has the highest water contact angle and the lowest radical density which correlate well with the non-significant protein binding improvement observed after 2 months of storage. The study found that the radical density created by PIII treatment of aromatic polymers was higher than that created by the treatment of aliphatic polymers. The higher radical density significantly improves laminin attachment to aromatic polymers, making them better substrates for β-cell adhesion.