bluuebunny/crossref_metadata_2025 huggingface dataset:
Procedural Factors Influencing Forest Certification Audits: An Empirical Study in Romania
Authors: Hălălișan Aureliu-Florin , Popa Bogdan , Heras-Saizarbitoria Iñaki , Boiral Olivier , Arana-Landín Germán , Nicorescu Adelin-Ionuț , Abrudan Ioan Vasile
Published: February 2021

In the recent decades, forest certification based on third-party external audits has gained momentum. This type of certification has been developed as a monitoring tool aimed at improving governance in corporate environmental management and differentiating products in the increasing environmentally sensitive markets. Although the scholarly literature has extensively analyzed the adoption and dissemination of forest certification, the findings of the external audits and certification practices remain under researched. On the basis of the analysis of 105 audit reports issued by accredited third-party certification bodies in Romania, this article sheds light on procedural factors that have significant influence on the characteristics of non-conformities (NCs) identified by Forest Stewardship Council (FSC) third party audits. Our research offers empirical evidence that certain procedural factors such as the type of assessment, auditing days, number of auditors, or the presence of foreign members in an audit team have a significant influence on the auditing process outcomes: number and grade of non-conformities, standard references, or methods of NC detection. The study opens interesting new lines of research—the influence of procedural or other types of contextual factors on certification outcomes—and provides indications on the effectiveness of the certification procedures and guidelines in certification process quality assurance.
Prospects of Using Tree-Ring Earlywood and Latewood Width for Reconstruction of Crops Yield on Example of South Siberia
Authors: Babushkina Elena , Zhirnova Dina , Belokopytova Liliana , Mehrotra Nivedita , Shah Santosh , Keler Viktoria , Vaganov Eugene
Published: February 2021

Improvement of dendrochronological crops yield reconstruction by separate application of earlywood and latewood width chronologies succeeded in rain-fed semiarid region. (1) Background: Tree-ring width chronologies have been successfully applied for crops yield reconstruction models. We propose application of separated earlywood and latewood width chronologies as possible predictors improving the fitness of reconstruction models. (2) Methods: The generalized yield series of main crops (spring wheat, spring barley, oats) were investigated in rain-fed and irrigated areas in semiarid steppes of South Siberia. Chronologies of earlywood, latewood, and total ring width of Siberian larch (Larix sibirica Ledeb.) growing in forest-steppe in the middle of the study area were tested as predictors of yield reconstruction models. (3) Results: In the rain-fed territory, separation of earlywood and latewood allowed increasing variation of yield explained by reconstruction model from 17.4 to 20.5%, whereas total climatic-driven component of variation was 41.5%. However, both tree-ring based models explained only 7.7% of yield variation in the irrigated territory (climate inclusion increased it to 34.8%). Low temperature sensitivity of larch growth was the main limitation of the model. A 240-year (1780–2019) history of crop failures and yield variation dynamics were estimated from the actual data and the best reconstruction model. (4) Conclusions: Presently in the study region, breeding of the environment-resistant crops varieties compensates the increase of temperature in the yield dynamics, preventing severe harvest losses. Tree-ring based reconstructions may help to understand and forecast response of the crops to the climatic variability, and also the probability of crop failures, particularly in the rain-fed territories.
Functional Exploitation of Carob, Oat Flour, and Whey Permeate as Substrates for a Novel Kefir-Like Fermented Beverage: An Optimized Formulation
Authors: M’hir Sana , Filannino Pasquale , Mejri Asma , Tlais Ali Zein Alabiden , Di Cagno Raffaella , Ayed Lamia
Published: February 2021

This study investigated the fortification of a carob-based kefir-like beverage (KLB) with whey permeate (WP) and oat flour (OF). The response surface method was used to show the effect of WP and OF concentrations on lactic acid bacteria and yeast cell densities, pH, total titratable acidity (TTA), total phenolics content (TCP), DPPH radical scavenging activity, and overall acceptability (OA) in KLB. The statistical design provided thirteen formulations where OF concentration varied from 3% to 5% and WP from 10% to 15%. The enrichment of carob pods decoction with WP and OF had a positive effect on biomass production. Overall fermentation was shown to increase TPC of KLB. Furthermore, OF supplementation led to the higher levels of TPC and antiradical activity. WP negatively affected OA at linear and quadratic levels, whereas no effect of OF was observed at the linear level. The optimum point was found by using WP at 11.51% and OF at 4.77%. Optimized KLB resulted in an enrichment of bioavailable phenolics derivatives and highly digestible proteins.
Risk of Bacillus cereus in Relation to Rice and Derivatives
Authors: Rodrigo Dolores , Rosell Cristina M. , Martinez Antonio
Published: February 2021

Rice is a very popular food throughout the world and the basis of the diet of the citizens of many countries. It is used as a raw material for the preparation of many complex dishes in which different ingredients are involved. Rice, as a consequence of their cultivation, harvesting, and handling, is often contaminated with spores of Bacillus cereus, a ubiquitous microorganism found mainly in the soil. B. cereus can multiply under temperature conditions as low as 4 °C in foods that contain rice and have been cooked or subjected to treatments that do not produce commercial sterility. B. cereus produces diarrhoeal or emetic foodborne toxin when the consumer eats food in which a sufficient number of cells have grown. These circumstances mean that every year many outbreaks of intoxication or intestinal problems related to this microorganism are reported. This work is a review from the perspective of risk assessment of the risk posed by B. cereus to the health of consumers and of some control measures that can be used to mitigate such a risk.
Why Don’t We Tube Feed Hip Fracture Patients? Findings from the Implementation of an Enteral Tube Feeding Decision Support Tool
Authors: Barrimore Sally , Davey Madeleine , Pulle Ranjeev Chrysanth , Crouch Alisa , Bell Jack J.
Published: February 2021

Background: This study aimed to report (i) the prevalence of enteral tube feeding (ETF), (ii) investigate whether implementing a decision support tool influenced ETF rates, and (iii) understand reasons influencing decisions to offer ETF. Methods: A pre/post evaluation included consecutive patients admitted to a hip fracture unit. Following baseline data collection, a published ETF Decision Support Tool was implemented by the multidisciplinary team to determine the necessity and influencing reasons for offering ETF. Results: Pre-post groups (n = 90,86) were well matched for age (83 vs. 84.5 years; p = 0.304) and gender (females 57 vs. 57; p = 0.683). ETF rates remained low across groups (pre/post n = 4,2; p = 0.683) despite high malnutrition prevalence (41.6% vs. 50.6%; p = 0.238). Diverse and conflicting reasons were identified regarding decisions to offer ETF. Conclusion: A complex interplay of factors influences the team decision-making process to offer ETF to nutritionally vulnerable patients. These demands are individualised, rather than algorithmic, involving shared decision-making and informed consent processes.
A Deep Learning Approach for TUG and SPPB Score Prediction of (Pre-) Frail Older Adults on Real-Life IMU Data
Authors: Friedrich Björn , Lau Sandra , Elgert Lena , Bauer Jürgen M. , Hein Andreas
Published: February 2021

Since older adults are prone to functional decline, using Inertial-Measurement-Units (IMU) for mobility assessment score prediction gives valuable information to physicians to diagnose changes in mobility and physical performance at an early stage and increases the chances of rehabilitation. This research introduces an approach for predicting the score of the Timed Up & Go test and Short-Physical-Performance-Battery assessment using IMU data and deep neural networks. The approach is validated on real-world data of a cohort of 20 frail or (pre-) frail older adults of an average of 84.7 years. The deep neural networks achieve an accuracy of about 95% for both tests for participants known by the network.
Environmental Regulation and Exports: Evidence from the Comprehensive Air Pollution Policy in China
Authors: Chen Hong , Xu Yang
Published: February 2021

The impact of environmental regulation has been an important topic. Based on the Chinese Custom Database and China City Statistical Yearbook, this paper investigates the effect of environmental regulation on export values and explores potential mechanisms and heterogeneous effects. Taking advantage of China’s first comprehensive air pollution prevention and control plan, the Air Pollution Control in Key Zones policy, as a quasi-natural experiment, we employ the difference-in-differences method to examine the causal relationship between environmental regulation and exports. We find the statistically significant and negative effect of environmental regulation on exports at the city level. Moreover, we find that the potential mechanism is the change in export values caused by firm entry and exit, especially by exiters, rather than the change in the number of exporting firms in the city caused by firm entry and exit. In addition, we find the heterogeneous effects of environmental regulation based on the differences of environmental policy across cities and the Broad Economic Categories classification.
Factor XIII-A in Diseases: Role Beyond Blood Coagulation
Authors: Dull Katalin , Fazekas Fruzsina , Törőcsik Dániel
Published: February 2021

Multidisciplinary research from the last few decades has revealed that Factor XIII subunit A (FXIII-A) is not only involved in blood coagulation, but may have roles in various diseases. Here, we aim to summarize data from studies involving patients with mutations in the F13A1 gene, performed in FXIII-A knock-out mice models, clinical and histological studies assessing correlations between diseases severity and FXIII-A levels, as well as from in vitro experiments. By providing a complex overview on its possible role in wound healing, chronic inflammatory bowel diseases, athe-rosclerosis, rheumatoid arthritis, chronic inflammatory lung diseases, chronic rhinosinusitis, solid tumors, hematological malignancies, and obesity, we also demonstrate how the field evolved from using FXIII-A as a marker to accept and understand its active role in inflammatory and malignant diseases.
Diazotroph Paenibacillus triticisoli BJ-18 Drives the Variation in Bacterial, Diazotrophic and Fungal Communities in the Rhizosphere and Root/Shoot Endosphere of Maize
Authors: Li Yongbin , Li Qin , Chen Sanfeng
Published: February 2021

Application of diazotrophs (N2-fixing microorganisms) can decrease the overuse of nitrogen (N) fertilizer. Until now, there are few studies on the effects of diazotroph application on microbial communities of major crops. In this study, the diazotrophic and endospore-forming Paenibacillus triticisoli BJ-18 was inoculated into maize soils containing different N levels. The effects of inoculation on the composition and abundance of the bacterial, diazotrophic and fungal communities in the rhizosphere and root/shoot endosphere of maize were evaluated by sequencing the 16S rRNA, nifH gene and ITS (Inter Transcribed Spacer) region. P. triticisoli BJ-18 survived and propagated in all the compartments of the maize rhizosphere, root and shoot. The abundances and diversities of the bacterial and diazotrophic communities in the rhizosphere were significantly higher than in both root and shoot endospheres. Each compartment of the rhizosphere, root and shoot had its specific bacterial and diazotrophic communities. Our results showed that inoculation reshaped the structures of the bacterial, diazotrophic and fungal communities in the maize rhizosphere and endosphere. Inoculation reduced the interactions of the bacteria and diazotrophs in the rhizosphere and endosphere, while it increased the fungal interactions. After inoculation, the abundances of Pseudomonas, Bacillus and Paenibacillus in all three compartments, Klebsiella in the rhizosphere and Paenibacillus in the root and shoot were significantly increased, while the abundances of Fusarium and Giberella were greatly reduced. Paenibacillus was significantly correlated with plant dry weight, nitrogenase, N2-fixing rate, P solubilization and other properties of the soil and plant.
Ordered Clusters of the Complete Oxidative Phosphorylation System in Cardiac Mitochondria
Authors: Nesterov Semen , Chesnokov Yury , Kamyshinsky Roman , Panteleeva Alisa , Lyamzaev Konstantin , Vasilov Raif , Yaguzhinsky Lev
Published: February 2021

The existence of a complete oxidative phosphorylation system (OXPHOS) supercomplex including both electron transport system and ATP synthases has long been assumed based on functional evidence. However, no structural confirmation of the docking between ATP synthase and proton pumps has been obtained. In this study, cryo-electron tomography was used to reveal the supramolecular architecture of the rat heart mitochondria cristae during ATP synthesis. Respirasome and ATP synthase structure in situ were determined using subtomogram averaging. The obtained reconstructions of the inner mitochondrial membrane demonstrated that rows of respiratory chain supercomplexes can dock with rows of ATP synthases forming oligomeric ordered clusters. These ordered clusters indicate a new type of OXPHOS structural organization. It should ensure the quickness, efficiency, and damage resistance of OXPHOS, providing a direct proton transfer from pumps to ATP synthase along the lateral pH gradient without energy dissipation.
CD44 and Tumor-Derived Extracellular Vesicles (TEVs). Possible Gateway to Cancer Metastasis
Authors: Szatanek Rafał , Baj-Krzyworzeka Monika
Published: February 2021

Cancer metastasis, the final stage of tumor progression, is a complex process governed by the interplay of multiple types of cells and the tumor microenvironment. One of the aspects of this interplay involves the release of various factors by the tumor cells alone or by forcing other cells to do so. As a consequence of these actions, tumor cells are prepared in favorable conditions for their dissemination and spread to other sites/organs, which guarantees their escape from immunosurveillance and further progression. Tumor-derived extracellular vesicles (TEVs) represent a heterogeneous population of membrane-bound vesicles that are being actively released by different tumors. The array of proteins (i.e., receptors, cytokines, chemokines, etc.) and nucleic acids (i.e., mRNA, miR, etc.) that TEVs can transfer to other cells is often considered beneficial for the tumor’s survival and proliferation. One of the proteins that is associated with many different tumors as well as their TEVs is a cluster of differentiation 44 in its standard (CD44s) and variant (CD44v) form. This review covers the present information regarding the TEVs-mediated CD44s/CD44v transfer/interaction in the context of cancer metastasis. The content and the impact of the transferred cargo by this type of TEVs also are discussed with regards to tumor cell dissemination.
Sexual Dimorphisms, Anti-Hormonal Therapy and Cardiac Arrhythmias
Authors: Grouthier Virginie , Moey Melissa Y. Y. , Gandjbakhch Estelle , Waintraub Xavier , Funck-Brentano Christian , Bachelot Anne , Salem Joe-Elie
Published: February 2021

Significant variations from the normal QT interval range of 350 to 450 milliseconds (ms) in men and 360 to 460 ms in women increase the risk for ventricular arrhythmias. This difference in the QT interval between men and women has led to the understanding of the influence of sex hormones on the role of gender-specific channelopathies and development of ventricular arrhythmias. The QT interval, which represents the duration of ventricular repolarization of the heart, can be affected by androgen levels, resulting in a sex-specific predilection for acquired and inherited channelopathies such as acquired long QT syndrome in women and Brugada syndrome and early repolarization syndrome in men. Manipulation of the homeostasis of these sex hormones as either hormonal therapy for certain cancers, recreational therapy or family planning and in transgender treatment has also been shown to affect QT interval duration and increase the risk for ventricular arrhythmias. In this review, we highlight the effects of endogenous and exogenous sex hormones in the physiological and pathological states on QTc variation and predisposition to gender-specific pro-arrhythmias.
Priming with a Seaweed Extract Strongly Improves Drought Tolerance in Arabidopsis
Authors: Rasul Fiaz , Gupta Saurabh , Olas Justyna Jadwiga , Gechev Tsanko , Sujeeth Neerakkal , Mueller-Roeber Bernd
Published: February 2021

Drought represents a major threat to plants in natural ecosystems and agricultural settings. The biostimulant Super Fifty (SF), produced from the brown alga Ascophyllum nodosum, enables ecologically friendly stress mitigation. We investigated the physiological and whole-genome transcriptome responses of Arabidopsis thaliana to drought stress after a treatment with SF. SF strongly decreased drought-induced damage. Accumulation of reactive oxygen species (ROS), which typically stifle plant growth during drought, was reduced in SF-primed plants. Relative water content remained high in SF-treated plants, whilst ion leakage, a measure of cell damage, was reduced compared to controls. Plant growth requires a functional shoot apical meristem (SAM). Expression of a stress-responsive negative growth regulator, RESPONSIVE TO DESICCATION 26 (RD26), was repressed by SF treatment at the SAM, consistent with the model that SF priming maintains the function of the SAM during drought stress. Accordingly, expression of the cell cycle marker gene HISTONE H4 (HIS4) was maintained at the SAMs of SF-primed plants, revealing active cell cycle progression after SF priming during drought. In accordance with this, CYCP2;1, which promotes meristem cell division, was repressed by drought but enhanced by SF. SF also positively affected stomatal behavior to support the tolerance to drought stress. Collectively, our data show that SF priming mitigates multiple cellular processes that otherwise impair plant growth under drought stress, thereby providing a knowledge basis for future research on crops.
ERK-Directed Phosphorylation of mGlu5 Gates Methamphetamine Reward and Reinforcement in Mouse
Authors: Fultz Elissa K. , Quadir Sema G. , Martin Douglas , Flaherty Daniel M. , Worley Paul F. , Kippin Tod E. , Szumlinski Karen K.
Published: February 2021

Methamphetamine (MA) is a highly addictive psychomotor stimulant drug. In recent years, MA use has increased exponentially on a global scale, with the number of MA-involved deaths reaching epidemic proportions. There is no approved pharmacotherapy for treating MA use disorder, and we know relatively little regarding the neurobiological determinants of vulnerability to this disease. Extracellular signal-regulated kinase (ERK) is an important signaling molecule implicated in the long-lasting neuroadaptations purported to underlie the development of substance use disorders, but the role for this kinase in the propensity to develop addiction, particularly MA use disorder, is uncharacterized. In a previous MA-induced place-conditioning study of C57BL/6J mice, we characterized mice as MA-preferring, -neutral, or -avoiding and collected tissue from the medial prefrontal cortex (mPFC). Using immunoblotting, we determined that elevated phosphorylated ERK expression within the medial prefrontal cortex (mPFC) is a biochemical correlate of the affective valence of MA in a population of C57BL/6J mice. We confirmed the functional relevance for mPFC ERK activation for MA-induced place-preference via site-directed infusion of the MEK inhibitor U0126. By contrast, ERK inhibition did not have any effect upon MA-induced locomotion or its sensitization upon repeated MA treatment. Through studies of transgenic mice with alanine point mutations on T1123/S1126 of mGlu5 that disrupt ERK-dependent phosphorylation of the receptor, we discovered that ERK-dependent mGlu5 phosphorylation normally suppresses MA-induced conditioned place-preference (MA-CPP), but is necessary for this drug’s reinforcing properties. If relevant to humans, the present results implicate individual differences in the capacity of MA-associated cues/contexts to hyper-activate ERK signaling within mPFC in MA Use Disorder vulnerability and pose mGlu5 as one ERK-directed target contributing to the propensity to seek out and take MA.
Analysis of m6A RNA Methylation-Related Genes in Liver Hepatocellular Carcinoma and Their Correlation with Survival
Authors: Li Yong , Qi Dandan , Zhu Baoli , Ye Xin
Published: February 2021

N6-methyladenosine (m6A) modification on RNA plays an important role in tumorigenesis and metastasis, which could change gene expression and even function at multiple levels such as RNA splicing, stability, translocation, and translation. In this study, we aim to conduct a comprehensive analysis on m6A RNA methylation-related genes, including m6A RNA methylation regulators and m6A RNA methylation-modified genes, in liver hepatocellular carcinoma, and their relationship with survival and clinical features. Data, which consist of the expression of widely reported m6A RNA methylation-related genes in liver hepatocellular carcinoma from The Cancer Genome Atlas (TCGA), were analyzed by one-way ANOVA, Univariate Cox regression, a protein–protein interaction network, gene enrichment analysis, feature screening, a risk prognostic model, correlation analysis, and consensus clustering analysis. In total, 405 of the m6A RNA methylation-related genes were found based on one-way ANOVA. Among them, DNA topoisomerase 2-alpha (TOP2A), exodeoxyribonuclease 1 (EXO1), ser-ine/threonine-protein kinase Nek2 (NEK2), baculoviral IAP repeat-containing protein 5 (BIRC5), hyaluronan mediated motility receptor (HMMR), structural maintenance of chromosomes protein 4 (SMC4), bloom syndrome protein (BLM), ca-sein kinase I isoform epsilon (CSNK1E), cytoskeleton-associated protein 5 (CKAP5), and inner centromere protein (INCENP), which were m6A RNA methylation-modified genes, were recognized as the hub genes based on the protein–protein interaction analysis. The risk prognostic model showed that gender, AJCC stage, grade, T, and N were significantly different between the subgroup with the high and low risk groups. The AUC, the evaluation parameter of the prediction model which was built by RandomForest, was 0.7. Furthermore, two subgroups were divided by consensus clustering analysis, in which stage, grade, and T differed. We identified the important genes expressed significantly among two clusters, including uridine-cytidine kinase 2 (UCK2), filensin (BFSP1), tubulin-specific chaperone D (TBCD), histone-lysine N-methyltransferase PRDM16 (PRDM16), phosphorylase b ki-nase regulatory subunit alpha (PHKA2), serine/threonine-protein kinase BRSK2 (BRSK2), Arf-GAP with coiled-coil (ACAP3), general transcription factor 3C polypep-tide 2 (GTF3C2), and guanine nucleotide exchange factor MSS4 (RABIF). In our study, the m6A RNA methylation-related genes in liver hepatocellular carcinoma were analyzed systematically, including the expression, interaction, function, and prognostic values, which provided an important theoretical basis for m6A RNA methylation in liver cancer. The nine important m6A-related genes could be prognostic markers in the survival time of patients.
Novel Transcript Discovery Expands the Repertoire of Pathologically-Associated, Long Non-Coding RNAs in Vascular Smooth Muscle Cells
Authors: Bennett Matthew , Ulitsky Igor , Alloza Iraide , Vandenbroeck Koen , Miscianinov Vladislav , Mahmoud Amira , Ballantyne Margaret , Rodor Julie , Baker Andrew
Published: February 2021

Vascular smooth muscle cells (VSMCs) provide vital contractile force within blood vessel walls, yet can also propagate cardiovascular pathologies through proliferative and pro-inflammatory activities. Such phenotypes are driven, in part, by the diverse effects of long non-coding RNAs (lncRNAs) on gene expression. However, lncRNA characterisation in VSMCs in pathological states is hampered by incomplete lncRNA representation in reference annotation. We aimed to improve lncRNA representation in such contexts by assembling non-reference transcripts in RNA sequencing datasets describing VSMCs stimulated in vitro with cytokines, growth factors, or mechanical stress, as well as those isolated from atherosclerotic plaques. All transcripts were then subjected to a rigorous lncRNA prediction pipeline. We substantially improved coverage of lncRNAs responding to pro-mitogenic stimuli, with non-reference lncRNAs contributing 21–32% for each dataset. We also demonstrate non-reference lncRNAs were biased towards enriched expression within VSMCs, and transcription from enhancer sites, suggesting particular relevance to VSMC processes, and the regulation of neighbouring protein-coding genes. Both VSMC-enriched and enhancer-transcribed lncRNAs were large components of lncRNAs responding to pathological stimuli, yet without novel transcript discovery 33–46% of these lncRNAs would remain hidden. Our comprehensive VSMC lncRNA repertoire allows proper prioritisation of candidates for characterisation and exemplifies a strategy to broaden our knowledge of lncRNA across a range of disease states.
Estrogen Receptors Alpha and Beta Mediate Synaptic Transmission in the PFC and Hippocampus of Mice
Authors: Zhang Mingyue , Weiland Hannah , Schöfbänker Michael , Zhang Weiqi
Published: February 2021

Distinct from ovarian estradiol, the steroid hormone 17ß-estradiol (E2) is produced in the brain and is involved in numerous functions, particularly acting as a neurosteroid. However, the physiological role of E2 and the mechanism of its effects are not well known. In hippocampal slices, 17ß-estradiol has been found to cause a modest increase in fast glutamatergic transmission; because some of these effects are rapid and acute, they might be mediated by membrane-associated receptors via nongenomic action. Moreover, activation of membrane estrogen receptors can rapidly modulate neuron function in a sex-specific manner. To further investigate the neurological role of E2, we examined the effect of E2, as an estrogen receptor (ER) agonist, on synaptic transmission in slices of the prefrontal cortex (PFC) and hippocampus in both male and female mice. Whole-cell recordings of spontaneous excitatory postsynaptic currents (sEPSC) in the PFC showed that E2 acts as a neuromodulator in glutamatergic transmission in the PFC in both sexes, but often in a cell-specific manner. The sEPSC amplitude and/or frequency responded to E2 in three ways, namely by significantly increasing, decreasing or having no response. Additional experiments using an agonist selective for ERß, diarylpropionitrile (DPN) showed that in males the sEPSC and spontaneous inhibitory postsynaptic currents sIPSC responses were similar to their E2 responses, but in females the estrogen receptor ß (ERß) agonist DPN did not influence excitatory transmission in the PFC. In contrast, in the hippocampus of both sexes E2 potentiated the gluatmatergic synaptic transmission in a subset of hippocampal cells. These data indicate that activation of E2 targeting probably a estrogen subtypes or different downstream signaling affect synaptic transmission in the brain PFC and hippocampus between males versus females mice.
MC38 Tumors Induce Musculoskeletal Defects in Colorectal Cancer
Authors: Huot Joshua R. , Pin Fabrizio , Essex Alyson L. , Bonetto Andrea
Published: February 2021

Colorectal cancer (CRC) is a leading cause of cancer-related death, and the prevalence of CRC in young adults is on the rise, making this a largescale clinical concern. Advanced CRC patients often present with liver metastases (LM) and an increased incidence of cachexia, i.e., musculoskeletal wasting. Despite its high incidence in CRC patients, cachexia remains an unresolved issue, and animal models for the study of CRC cachexia, in particular, metastatic CRC cachexia, remain limited; therefore, we aimed to establish a new model of metastatic CRC cachexia. C57BL/6 male mice (8 weeks old) were subcutaneously (MC38) or intrasplenically injected (mMC38) with MC38 murine CRC cells to disseminate LM, while experimental controls received saline (n = 5–8/group). The growth of subcutaneous MC38 tumors was accompanied by a reduction in skeletal muscle mass (−16%; quadriceps muscle), plantarflexion force (−22%) and extensor digitorum longus (EDL) contractility (−20%) compared to experimental controls. Meanwhile, the formation of MC38 LM (mMC38) led to heighted reductions in skeletal muscle mass (−30%; quadriceps), plantarflexion force (−28%) and EDL contractility (−35%) compared to sham-operated controls, suggesting exacerbated cachexia associated with LM. Moreover, both MC38 and mMC38 tumor hosts demonstrated a marked loss of bone indicated by reductions in trabecular (Tb.BV/TV: −49% in MC38, and −46% in mMC38) and cortical (C.BV/TV: −12% in MC38, and −8% in mMC38) bone. Cell culture experiments revealed that MC38 tumor-derived factors directly promote myotube wasting (−18%) and STAT3 phosphorylation (+5-fold), while the pharmacologic blockade of STAT3 signaling was sufficient to preserve myotube atrophy in the presence of MC38 cells (+21%). Overall, these results reinforce the notion that the formation of LM heightens cachexia in an experimental model of CRC.
The Role of Lipids in Legionella-Host Interaction
Authors: Kowalczyk Bozena , Chmiel Elzbieta , Palusinska-Szysz Marta
Published: February 2021

Legionella are Gram-stain-negative rods associated with water environments: either natural or man-made systems. The inhalation of aerosols containing Legionella bacteria leads to the development of a severe pneumonia termed Legionnaires’ disease. To establish an infection, these bacteria adapt to growth in the hostile environment of the host through the unusual structures of macromolecules that build the cell surface. The outer membrane of the cell envelope is a lipid bilayer with an asymmetric composition mostly of phospholipids in the inner leaflet and lipopolysaccharides (LPS) in the outer leaflet. The major membrane-forming phospholipid of Legionella spp. is phosphatidylcholine (PC)—a typical eukaryotic glycerophospholipid. PC synthesis in Legionella cells occurs via two independent pathways: the N-methylation (Pmt) pathway and the Pcs pathway. The utilisation of exogenous choline by Legionella spp. leads to changes in the composition of lipids and proteins, which influences the physicochemical properties of the cell surface. This phenotypic plasticity of the Legionella cell envelope determines the mode of interaction with the macrophages, which results in a decrease in the production of proinflammatory cytokines and modulates the interaction with antimicrobial peptides and proteins. The surface-exposed O-chain of Legionella pneumophila sg1 LPS consisting of a homopolymer of 5-acetamidino-7-acetamido-8-O-acetyl-3,5,7,9-tetradeoxy-l-glycero-d-galacto-non-2-ulosonic acid is probably the first component in contact with the host cell that anchors the bacteria in the host membrane. Unusual in terms of the structure and function of individual LPS regions, it makes an important contribution to the antigenicity and pathogenicity of Legionella bacteria.
N-palmitoyl-D-glucosamine, A Natural Monosaccharide-Based Glycolipid, Inhibits TLR4 and Prevents LPS-Induced Inflammation and Neuropathic Pain in Mice
Authors: Iannotta Monica , Belardo Carmela , Trotta Maria Consiglia , Iannotti Fabio Arturo , Vitale Rosa Maria , Maisto Rosa , Boccella Serena , Infantino Rosmara , Ricciardi Flavia , Mirto Benito Fabio , Ferraraccio Franca , Panarese Iacopo , Amodeo Pietro , Tunisi Lea , Cristino Luigia , D’Amico Michele , di Marzo Vincenzo , Luongo Livio , Maione Sabatino , Guida Francesca
Published: February 2021

Toll-like receptors (TLRs) are key receptors through which infectious and non-infectious challenges act with consequent activation of the inflammatory cascade that plays a critical function in various acute and chronic diseases, behaving as amplification and chronicization factors of the inflammatory response. Previous studies have shown that synthetic analogues of lipid A based on glucosamine with few chains of unsaturated and saturated fatty acids, bind MD-2 and inhibit TLR4 receptors. These synthetic compounds showed antagonistic activity against TLR4 activation in vitro by LPS, but little or no activity in vivo. This study aimed to show the potential use of N-palmitoyl-D-glucosamine (PGA), a bacterial molecule with structural similarity to the lipid A component of LPS, which could be useful for preventing LPS-induced tissue damage or even peripheral neuropathies. Molecular docking and molecular dynamics simulations showed that PGA stably binds MD-2 with a MD-2/(PGA)3 stoichiometry. Treatment with PGA resulted in the following effects: (i) it prevented the NF-kB activation in LPS stimulated RAW264.7 cells; (ii) it decreased LPS-induced keratitis and corneal pro-inflammatory cytokines, whilst increasing anti-inflammatory cytokines; (iii) it normalized LPS-induced miR-20a-5p and miR-106a-5p upregulation and increased miR-27a-3p levels in the inflamed corneas; (iv) it decreased allodynia in peripheral neuropathy induced by oxaliplatin or formalin, but not following spared nerve injury of the sciatic nerve (SNI); (v) it prevented the formalin- or oxaliplatin-induced myelino-axonal degeneration of sciatic nerve. SIGNIFICANCE STATEMENT We report that PGA acts as a TLR4 antagonist and this may be the basis of its potent anti-inflammatory activity. Being unique because of its potency and stability, as compared to other similar congeners, PGA can represent a tool for the optimization of new TLR4 modulating drugs directed against the cytokine storm and the chronization of inflammation.
Integrated Metabolome and Transcriptome Analysis Unveils Novel Pathway Involved in the Formation of Yellow Peel in Cucumber
Authors: Chen Chen , Zhou Geng , Chen Juan , Liu Xiaohong , Lu Xiangyang , Chen Huiming , Tian Yun
Published: February 2021

Yellow peel will adversely affect the appearance quality of cucumber fruit, but the metabolites and the molecular mechanism of pigment accumulation in cucumber peel remain unclear. Flavonoid metabolome and transcriptome analyses were carried out on the young peel and old peel of the color mutant L19 and the near-isogenic line L14. The results showed that there were 165 differential flavonoid metabolites in the old peel between L14 and L19. The total content of representative flavonoid metabolites in the old peel of L14 was 95 times that of L19, and 35 times that of young peel of L14, respectively. This might explain the difference of pigment accumulation in yellow peel. Furthermore, transcriptome analysis showed that there were 3396 and 1115 differentially expressed genes in the yellow color difference group (Young L14 vs. Old L14 and Old L14 vs. Old L19), respectively. These differentially expressed genes were significantly enriched in the MAPK signaling pathway–plant, plant–pathogen interaction, flavonoid biosynthesis and cutin, suberine and wax biosynthesis pathways. By analyzing the correlation between differential metabolites and differentially expressed genes, six candidate genes related to the synthesis of glycitein, kaempferol and homoeriodictyol are potentially important. In addition, four key transcription factors that belong to R2R3-MYB, bHLH51 and WRKY23 might be the major drivers of transcriptional changes in the peel between L14 and L19. Then, the expression patterns of these important genes were confirmed by qRT-PCR. These results suggested that the biosynthesis pathway of homoeriodictyol was a novel way to affect the yellowing of cucumber peel. Together, the results of this study provide a research basis for the biosynthesis and regulation of flavonoids in cucumber peel and form a significant step towards identifying the molecular mechanism of cucumber peel yellowing.
Distinct Effects of Escherichia coli,Pseudomonas aeruginosa and Staphylococcus aureus Cell Wall Component-Induced Inflammation on the Iron Metabolism of THP-1 Cells
Authors: Pandur Edina , Tamási Kitti , Pap Ramóna , Jánosa Gergely , Sipos Katalin
Published: February 2021

Macrophages are essential immune cells of the innate immune system. They participate in the development and regulation of inflammation. Macrophages play a fundamental role in fighting against bacterial infections by phagocytosis of bacteria, and they also have a specific role in immunomodulation by secreting pro-inflammatory cytokines. In bacterial infection, macrophages decrease the serum iron concentration by removing iron from the blood, acting as one of the most important regulatory cells of iron homeostasis. We examined whether the Gram-positive and Gram-negative cell wall components from various bacterial strains affect the cytokine production and iron transport, storage and utilization of THP-1 monocytes in different ways. We found that S. aureus lipoteichoic acid (LTA) was less effective in activating pro-inflammatory cytokine expression that may related to its effect on fractalkine production. LTA-treated cells increased iron uptake through divalent metal transporter-1, but did not elevate the expression of cytosolic and mitochondrial iron storage proteins, suggesting that the cells maintained iron efflux via the ferroportin iron exporter. E. coli and P. aeruginosa lipopolysaccharides (LPSs) acted similarly on THP-1 cells, but the rates of the alterations of the examined proteins were different. E. coli LPS was more effective in increasing the pro-inflammatory cytokine production, meanwhile it caused less dramatic alterations in iron metabolism. P. aeruginosa LPS-treated cells produced a smaller amount of pro-inflammatory cytokines, but caused remarkable elevation of both cytosolic and mitochondrial iron storage proteins and intracellular iron content compared to E. coli LPS. These results prove that LPS molecules from different bacterial sources alter diverse molecular mechanisms in macrophages that prepossess the outcome of the bacterial infection.
Mitochondrial Homeostasis Mediates Lipotoxicity in the Failing Myocardium
Authors: Kretzschmar Tom , Wu Jasmine M. F. , Schulze P. Christian
Published: February 2021

Heart failure remains the most common cause of death in the industrialized world. In spite of new therapeutic interventions that are constantly being developed, it is still not possible to completely protect against heart failure development and progression. This shows how much more research is necessary to understand the underlying mechanisms of this process. In this review, we give a detailed overview of the contribution of impaired mitochondrial dynamics and energy homeostasis during heart failure progression. In particular, we focus on the regulation of fatty acid metabolism and the effects of fatty acid accumulation on mitochondrial structural and functional homeostasis.
Bioelectrical Impedance Analysis in Patients Undergoing Major Head and Neck Surgery: A Prospective Observational Pilot Study
Authors: Tzelnick Sharon , Singer Pierre , Shopen Yoni , Moshkovitz Limor , Fireman Shlomo , Shpitzer Thomas , Mizrachi Aviram , Bachar Gideon
Published: February 2021

Background: Head and neck patients are prone to malnutrition. Perioperative fluids administration in this patient group may influence nutritional status. We aimed to investigate perioperative changes in patients undergoing major head and neck surgery and to examine the impact of perioperative fluid administration on body composition and metabolic changes using bioelectrical impedance. Furthermore, we sought to correlate these metabolic changes with postoperative complication rate. In this prospective observational pilot study, bioelectrical impedance analysis (BIA) was performed preoperatively and on postoperative days (POD) 2 and 10 on patients who underwent major head and neck surgeries. BIA was completed in 34/37 patients; mean total intraoperative and post-anesthesia fluid administration was 3682 ± 1910 mL and 1802 ± 1466 mL, respectively. Total perioperative fluid administration was associated with postoperative high extra-cellular water percentages (p = 0.038) and a low phase-angle score (p < 0.005), which indicates low nutritional status. Patients with phase angle below the 5th percentile at POD 2 had higher local complication rates (p = 0.035) and longer hospital length of stay (LOS) (p = 0.029). Multivariate analysis failed to demonstrate that high-volume fluid administration and phase angle are independent factors for postoperative complications. High-volume perioperative fluids administration impacts postoperative nutritional status with fluid shift toward the extra-cellular space and is associated with factors that increase the risk of postoperative complications and longer LOS. An adjusted, low-volume perioperative fluid regimen should be considered in patients with comorbidities in order to minimize postoperative morbidity.
Surgical Performance Is Not Negatively Impacted by Wearing a Commercial Full-Face Mask with Ad Hoc 3D-Printed Filter Connection as a Substitute for Personal Protective Equipment during the COVID-19 Pandemic: A Randomized Controlled Cross-Over Trial
Authors: Felinska Eleni Amelia , Chen Zi-Wei , Fuchs Thomas Ewald , Otto Benjamin , Kenngott Hannes Götz , Kowalewski Karl-Friedrich , Müller-Stich Beat Peter , Nickel Felix
Published: February 2021

(1) Background: During the COVID-19 pandemic, shortages in the supply of personal protective equipment (PPE) have become apparent. The idea of using commonly available full-face diving (FFD) masks as a temporary solution was quickly spread across social media. However, it was unknown whether an FFD mask would considerably impair complex surgical tasks. Thus, we aimed to assess laparoscopic surgical performance while wearing an FFD mask as PPE. (2) Methods: In a randomized-controlled cross-over trial, 40 laparoscopically naive medical students performed laparoscopic procedures while wearing an FFD mask with ad hoc 3D-printed connections to heat and moisture exchange (HME) filters vs. wearing a common surgical face mask. The performance was evaluated using global and specific Objective Structured Assessment of Technical Skills (OSATS) checklists for suturing and cholecystectomy. (3) Results: For the laparoscopic cholecystectomy, both global OSATS scores and specific OSATS scores for the quality of procedure were similar (Group 1: 25 ± 4.3 and 45.7 ± 12.9, p = 0.485, vs. Group 2: 24.1 ± 3.7 and 43.3 ± 7.6, p = 0.485). For the laparoscopic suturing task, the FFD mask group needed similar times to the surgical mask group (3009 ± 1694 s vs. 2443 ± 949 s; p = 0.200). Some participants reported impaired verbal communication while wearing the FFD mask, as it muffled the sound of speech, as well as discomfort in breathing. (4) Conclusions: FFD masks do not affect the quality of laparoscopic surgical performance, despite being uncomfortable, and may therefore be used as a substitute for conventional PPE in times of shortage—i.e., the global COVID-19 pandemic.
Tracking Down the Epigenetic Footprint of HCV-Induced Hepatocarcinogenesis
Authors: Domovitz Tom , Gal-Tanamy Meital
Published: February 2021

Hepatitis C virus (HCV) is a major cause of death and morbidity globally and is a leading cause of hepatocellular carcinoma (HCC). Incidence of HCV infections, as well as HCV-related liver diseases, are increasing. Although now, with new direct acting antivirals (DAAs) therapy available, HCV is a curable cancer-associated infectious agent, HCC prevalence is expected to continue to rise because HCC risk still persists after HCV cure. Understanding the factors that lead from HCV infection to HCC pre- and post-cure may open-up opportunities to novel strategies for HCC prevention. Herein, we provide an overview of the reported evidence for the induction of alterations in the transcriptome of host cells via epigenetic dysregulation by HCV infection and describe recent reports linking the residual risk for HCC post-cure with a persistent HCV-induced epigenetic signature. Specifically, we discuss the contribution of the epigenetic changes identified following HCV infection to HCC risk pre- and post-cure, the molecular pathways that are epigenetically altered, the downstream effects on expression of cancer-related genes, the identification of targets to prevent or revert this cancer-inducing epigenetic signature, and the potential contribution of these studies to early prognosis and prevention of HCC as an approach for reducing HCC-related mortality.
A Fuzzy Optimization Model for the Berth Allocation Problem and Quay Crane Allocation Problem (BAP + QCAP) with n Quays
Authors: Lujan Edwar , Vergara Edmundo , Rodriguez-Melquiades Jose , Jiménez-Carrión Miguel , Sabino-Escobar Carlos , Gutierrez Flabio
Published: February 2021

This work introduces a fuzzy optimization model, which solves in an integrated way the berth allocation problem (BAP) and the quay crane allocation problem (QCAP). The problem is solved for multiple quays, considering vessels’ imprecise arrival times. The model optimizes the use of the quays. The BAP + QCAP, is a NP-hard (Non-deterministic polynomial-time hardness) combinatorial optimization problem, where the decision to assign available quays for each vessel adds more complexity. The imprecise vessel arrival times and the decision variables—berth and departure times—are represented by triangular fuzzy numbers. The model obtains a robust berthing plan that supports early and late arrivals and also assigns cranes to each berth vessel. The model was implemented in the CPLEX solver (IBM ILOG CPLEX Optimization Studio); obtaining in a short time an optimal solution for very small instances. For medium instances, an undefined behavior was found, where a solution (optimal or not) may be found. For large instances, no solutions were found during the assigned processing time (60 min). Although the model was applied for n = 2 quays, it can be adapted to “n” quays. For medium and large instances, the model must be solved with metaheuristics.