bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological Profiling of Semisynthetic C19-Functionalized Ferruginol and Sugiol Analogues
Authors: González-Cardenete Miguel A. , Rivas Fatima , Basset Rachel , Stadler Marco , Hering Steffen , Padrón José M. , Zaragozá Ramón J. , Dea-Ayuela María Auxiliadora
Published: February 2021

The abietane-type diterpenoids are significant bioactive compounds exhibiting a varied range of pharmacological properties. In this study, the first synthesis and biological investigation of the new abietane-diterpenoid (+)-4-epi-liquiditerpenoid acid (8a) together with several of its analogs are reported. The compounds were generated from the readily available methyl callitrisate (7), which was obtained from callitrisic acid present in Moroccan Sandarac resin. A biological evaluation was conducted to determine the effects of the different functional groups present in these molecules, providing basic structure–activity relationship (SAR) elements. In particular, the ferruginol and sugiol analogs compounds 10–16 were characterized by the presence of a phenol moiety, higher oxidization states at C-7 (ketone), and the hydroxyl, methyl ester or free carboxylic acid at C19. The biological profiling of these compounds was investigated against a panel of six human solid tumor cell lines (HBL-100, A549, HeLa, T-47D, SW1573 and WiDr), four parasitic Leishmania species (L. donovani, L. infantum, L. guyanensis and L. amazonensis) and two malaria strains (3D7 and K1). Furthermore, the capacity of the compounds to modulate gamma-aminobutyric acid type A (GABAA) receptors (α1β2γ2s) is also described. A comparison of the biological results with those previously reported of the corresponding C18-functionalized analogs was conducted.
Optimization of Computer Numerical Control Interpolation Parameters Using a Backpropagation Neural Network and Genetic Algorithm with Consideration of Corner Vibrations
Authors: Tseng Hsiang-Chun , Tsai Meng-Shiun , Cheng Chih-Chun , Li Chen-Jung
Published: February 2021

This paper presents an optimization algorithm for tuning the interpolation parameters of computer numerical control (CNC) controllers; it operates by considering multiple objective functions, namely, contour errors, the machining time (MT), and vibrations. The position commands, position errors, and vibration signals from 1024 experiments were considered in the designed trajectory. The experimental data—the maximum contour error (MCoE), MT, and corner vibration (CVib)—were analyzed to compute the performance index. A backpropagation neural network (BPNN) with 20 hidden layers was applied to predict the performance index. The correlation coefficients for the predicted values and experimental results for the MCoE, MT, and CVib based on the validation data were 0.9984, 0.9998, and 0.9354, respectively. The high correlation coefficients highlight the accuracy of the model for designing the interpolation parameter. After the BPNN model was developed, a genetic algorithm (GA) was adopted to determine the optimized parameters of the interpolation under different weighting of the performance index. A weighted sum approach involving the objective function was employed to determine the optimized interpolation parameters in the GA. Thus, operators can judge the feasibility of the interpolation parameter for various weighting settings. Finally, a mixed path was selected to verify the proposed algorithm.
A Multi-Channel Uncertainty-Aware Multi-Resolution Network for MR to CT Synthesis
Authors: Klaser Kerstin , Borges Pedro , Shaw Richard , Ranzini Marta , Modat Marc , Atkinson David , Thielemans Kris , Hutton Brian , Goh Vicky , Cook Gary , Cardoso Jorge , Ourselin Sebastien
Published: February 2021

Synthesising computed tomography (CT) images from magnetic resonance images (MRI) plays an important role in the field of medical image analysis, both for quantification and diagnostic purposes. Convolutional neural networks (CNNs) have achieved state-of-the-art results in image-to-image translation for brain applications. However, synthesising whole-body images remains largely uncharted territory, involving many challenges, including large image size and limited field of view, complex spatial context, and anatomical differences between images acquired at different times. We propose the use of an uncertainty-aware multi-channel multi-resolution 3D cascade network specifically aiming for whole-body MR to CT synthesis. The Mean Absolute Error on the synthetic CT generated with the MultiResunc network (73.90 HU) is compared to multiple baseline CNNs like 3D U-Net (92.89 HU), HighRes3DNet (89.05 HU) and deep boosted regression (77.58 HU) and shows superior synthesis performance. We ultimately exploit the extrapolation properties of the MultiRes networks on sub-regions of the body.
An Experimental Study for the Improvement of the Stain Resistance for Exterior Wall Paints in a Western City in China
Authors: Huang Xiao , Wang Caixia , Zhu Dengling
Published: February 2021

In recent years, with the rapid development of the building industry in western cities during the period of “Western Development” in China, the paints industry has developed rapidly and become more mature. In addition, waterborne inorganic exterior wall paints have been a great choice in the building industry because of their reduced volatile organic compounds (VOCs) and less toxicity and odor. However, the problem of stain resistance for exterior wall paints in western cities has not been solved, which has become a major obstacle to the application and promotion of exterior wall paints in western cities in China. Therefore, effective measures should eventually be carried out for improving the stain resistance of exterior wall paints in western cities in China. In this paper, an experimental study on improving stain resistance for exterior wall paints in a typical western city in China, Chongqing, is reported. In the three defined designs, the effects of the paint structure type, the pigment volume concentration (PVC), thickeners, cosolvents and wetting and dispersing agents on the stain resistance of exterior wall paints in a typical western city in China, Chongqing, were examined. The experimental results suggest that the stain resistance of silicone–acrylic paint was the most suitable among the three kinds of tested paints (silicone–acrylic paint, styrene–acrylic paint and pure acrylic paint). In addition, the PVC had a great influence on the stain resistance of the exterior wall paints. The compactness, water absorption and stain resistance of the paint’s film were the most suitable when the PVCs of the paints reached 45%. Furthermore, the tested wetting and dispersing agents made the same contributions to the paints’ stain resistance, as their decline rates for reflectivity were similar. The reflectivity of the film significantly decreased when the ratio of associating thickener to non-associating thickener reached 4:1, and also significantly declined when the content of propylene glycol reached 5%.
Multicenter Evaluation of the Cepheid Xpert® HBV Viral Load Test
Authors: Marcuccilli Fabbio , Chevaliez Stephane , Muller Thomas , Colagrossi Luna , Abbondanza Giulia , Beyser Kurt , Wlassow Mélanie , Ortonne Valérie , Perno Carlo Federico , Ciotti Marco
Published: February 2021

Accurate measurement of the hepatitis B virus (HBV) DNA is important for the management of patients with chronic HBV infection. Here, the performance of the Xpert® HBV Viral Load test (Xpert HBV Viral Load) versus the Roche COBAS® Ampliprep/COBAS® TaqMan® system (CAP/CTM HBV) HBV test v2.0 was evaluated. From September 2017 to December 2017, a total of 876 prospectively collected or archived serum or EDTA plasma specimens from subjects chronically infected with HBV were tested using the Xpert HBV Viral Load and the CAP/CTM HBV v2.0 assays. Of the 876 specimens tested, 560 were within the quantitative range of both assays. The agreement between the two methods was 90.0%. No difference in plasma or serum samples was observed. Deming regression analysis showed a good correlation of the Xpert HBV Viral Load assay with the CAP/CTM HBV v2.0 assay. The Bland–Altman analysis showed a good agreement between the results of the Xpert HBV Viral Load assay and the CAP/CTM HBV assay, with a mean difference (±1.96 standard deviation) of 0.0091 ± 0.3852 Log IU/mL. Comparing the two assays, only nineteen specimens (2.1%) had a difference greater than 1.96 times the standard deviation. The Xpert® HBV Viral Load test is suitable for monitoring patients with HBV infection and is useful in diagnostic settings.
Beneficial Anti-Platelet and Anti-Inflammatory Properties of Irish Apple Juice and Cider Bioactives
Authors: Tsoupras Alexandros , Moran Donal , Pleskach Hayley , Durkin Maria , Traas Con , Zabetakis Ioannis
Published: February 2021

Several bioactives from fruit juices and beverages like phenolics, nucleotides and polar lipids (PL) have exhibited anti-platelet cardio-protective properties. However, apple juice and cider lipid bioactives have not been evaluated so far. The aim of this study was to investigate the anti-platelet and anti-inflammatory effects and structure activity relationships of Irish apple juice and Real Irish cider lipid bioactives against the platelet-activating factor (PAF)- and adenosine diphosphate (ADP)-related thrombotic and inflammatory manifestations in human platelets. Total Lipids (TL) were extracted from low, moderate and high in tannins apple juices and from their derived-through-fermentation cider products, as well as from commercial apple juice and cider. These were separated into neutral lipids (NL) and PL, while all lipid extracts were further assessed for their ability to inhibit aggregation of human platelets induced by PAF and ADP. In all cases, PL exhibited the strongest anti-platelet bioactivities and were further separated by high-performance liquid chromatography (HPLC) analysis into PL subclasses/fractions that were also assessed for their antiplatelet potency. The PL from low in tannins apple juice exhibited the strongest antiplatelet effects against PAF and ADP, while PL from its fermented cider product were less active. Moreover, the phosphatidylcholines (PC) in apple juices and the phosphatidylethanolamines (PE) in apple ciders were the most bioactive HPLC-derived PL subclasses against PAF-induced platelet aggregation. Structural elucidation of the fatty acid composition by gas chromatography mass spectra (GCMS) analysis showed that PL from all samples are rich in beneficial monounsaturated fatty acids (MUFA) and omega 3 (n-3) polyunsaturated fatty acids (PUFA), providing a possible explanation for their strong anti-platelet properties, while the favorable low levels of their omega-6/omega-3 (n-6/n-3) PUFA ratio, especially for the bioactive PC and PE subclasses, further support an anti-inflammatory cardio-protective potency for these apple products. In conclusion, Irish apple juice and Real Irish cider were found to possess bioactive PL compounds with strong antiplatelet and anti-inflammatory properties, while fermentation seems to be an important modulating factor on their lipid content, structures and bioactivities. However, further studies are needed to evaluate these effects.
“Stay-at-Home” Lifestyle Effect on Weight Gain during the COVID-19 Outbreak Confinement in China
Authors: Zhu Qi , Li Min , Ji Yu , Shi Youpeng , Zhou Jie , Li Qianyue , Qin Ruoyu , Zhuang Xun
Published: February 2021

In February 2020, a novel coronavirus (SARS-COV2) broke out in Wuhan city of China. The Chinese government decisively imposed nationwide confinement. This study comprised a structured, online questionnaire, based on 40 items inquiring about socio-demographic information and anthropometric data (reporting weight and height), as well as changes in food intake, physical activity, and sleep during the COVID-19 outbreak. Questionnaires were distributed to residents of Jiangsu and other provinces from 29 March to 5 April. A total of 889 respondents were included, aged between 16 and 70 years (61% females). There was a significant increase in total food intake by 9.8% and a slight increase by 29.2% of respondents, and a significant decrease in physical activity by 31.5% and a slight decrease by 23.4% of respondents, especially in snacks and drinks, and outdoor activities. The rate of weight gain in the total population was 30.6% and the average weight gain was 0.5 ± 2.8 kg. The main factors contributing to weight gain were increased food intake and reduced physical activity. Additionally, normal-weight people were more likely to gain weight than people with overweight/obesity during the COVID-19 confinement. This study provided a good warning and educational reference value on lifestyle changes during the COVID-19 confinement.
Trajectory Shifts in Interdisciplinary Research of the Aryl Hydrocarbon Receptor—A Personal Perspective on Thymus and Skin
Authors: Esser Charlotte
Published: February 2021

Identifying historical trajectories is a useful exercise in research, as it helps clarify important, perhaps even “paradigmatic”, shifts in thinking and moving forward in science. In this review, the development of research regarding the role of the transcription factor “aryl hydrocarbon receptor” (AHR) as a mediator of the toxicity of environmental pollution towards a link between the environment and a healthy adaptive response of the immune system and the skin is discussed. From this fascinating development, the opportunities for targeting the AHR in the therapy of many diseases become clear.
Analysis of the Conditions That Affect the Selective Processing of Endogenous Notch1 by ADAM10 and ADAM17
Authors: Alabi Rolake O. , Lora Jose , Celen Arda B. , Maretzky Thorsten , Blobel Carl P.
Published: February 2021

Notch signaling is critical for controlling a variety of cell fate decisions during metazoan development and homeostasis. This unique, highly conserved signaling pathway relies on cell-to-cell contact, which triggers the proteolytic release of the cytoplasmic domain of the membrane-anchored transcription factor Notch from the membrane. A disintegrin and metalloproteinase (ADAM) proteins are crucial for Notch activation by processing its S2 site. While ADAM10 cleaves Notch1 under physiological, ligand-dependent conditions, ADAM17 mainly cleaves Notch1 under ligand-independent conditions. However, the mechanism(s) that regulate the distinct contributions of these ADAMs in Notch processing remain unclear. Using cell-based assays in mouse embryonic fibroblasts (mEFs) lacking ADAM10 and/or ADAM17, we aimed to clarify what determines the relative contributions of ADAM10 and ADAM17 to ligand-dependent or ligand-independent Notch processing. We found that EDTA-stimulated ADAM17-dependent Notch1 processing is rapid and requires the ADAM17-regulators iRhom1 and iRhom2, whereas the Delta-like 4-induced ligand-dependent Notch1 processing is slower and requires ADAM10. The selectivity of ADAM17 for EDTA-induced Notch1 processing can most likely be explained by a preference for ADAM17 over ADAM10 for the Notch1 cleavage site and by the stronger inhibition of ADAM10 by EDTA. The physiological ADAM10-dependent processing of Notch1 cannot be compensated for by ADAM17 in Adam10-/- mEFs, or by other ADAMs shown here to be able to cleave the Notch1 cleavage site, such as ADAMs9, 12, and 19. Collectively, these results provide new insights into the mechanisms underlying the substrate selectivity of ADAM10 and ADAM17 towards Notch1.
Platelet Lysate Nebulization Protocol for the Treatment of COVID-19 and Its Sequels: Proof of Concept and Scientific Rationale
Authors: Beitia Maider , Delgado Diego , Sánchez Pello , Vallejo de la Cueva Ana , Cugat José Ramón , Sánchez Mikel
Published: February 2021

One of the most severe effects of coronavirus disease 2019 (COVID-19) is lung disorders such as acute respiratory distress syndrome. In the absence of effective treatments, it is necessary to search for new therapies and therapeutic targets. Platelets play a fundamental role in respiratory disorders resulting from viral infections, being the first line of defense against viruses and essential in maintaining lung function. The direct application of platelet lysate (PL) obtained from the platelet-rich plasma of healthy donors could help in the improvement of the patient due its anti-inflammatory, immunomodulatory, antifibrotic, and repairing effects. This work evaluates PL nebulization by analyzing its levels of growth factors and its biological activity on lung fibroblast cell cultures, besides describing a scientific basis for its use in this kind of pathology. The data of the work suggest that the molecular levels and biological activity of the PL are maintained after nebulization. Airway administration would allow acting directly on the lung tissue modulating inflammation and stimulating reparative processes on key structures such as the alveolocapillary barrier, improving the disease and sequels. The protocol developed in this work is a first step for the study of nebulized PL both in animal experimentation and in clinical trials.
Promotion and Inhibition of Amyloid-β Peptide Aggregation: Molecular Dynamics Studies
Authors: Itoh Satoru , Okumura Hisashi
Published: February 2021

Aggregates of amyloid-β (Aβ) peptides are known to be related to Alzheimer’s disease. Their aggregation is enhanced at hydrophilic–hydrophobic interfaces, such as a cell membrane surface and air-water interface, and is inhibited by polyphenols, such as myricetin and rosmarinic acid. We review molecular dynamics (MD) simulation approaches of a full-length Aβ peptide, Aβ40, and Aβ(16–22) fragments in these environments. Since these peptides have both hydrophilic and hydrophobic amino acid residues, they tend to exist at the interfaces. The high concentration of the peptides accelerates the aggregation there. In addition, Aβ40 forms a β-hairpin structure, and this structure accelerates the aggregation. We also describe the inhibition mechanism of the Aβ(16–22) aggregation by polyphenols. The aggregation of Aβ(16–22) fragments is caused mainly by the electrostatic attraction between charged amino acid residues known as Lys16 and Glu22. Since polyphenols form hydrogen bonds between their hydroxy and carboxyl groups and these charged amino acid residues, they inhibit the aggregation.
Guideline Adherence and Registry Recruitment of Congenital Primary Hypothyroidism: Data from the German Registry for Congenital Hypothyroidism (HypoDok)
Authors: Thomann Julia , Tittel Sascha R. , Voss Egbert , Oeverink Rudolf , Palm Katja , Fricke-Otto Susanne , Kapelari Klaus , Holl Reinhard W. , Woelfle Joachim , Bettendorf Markus
Published: February 2021

Neonatal screening for congenital primary hypothyroidism (CH) is mandatory in Germany but medical care thereafter remains inconsistent. Therefore, the registry HypoDok of the German Society of Pediatric Endocrinology and Diabetology (DGKED) was analyzed to evaluate the implementation of evidence-based guidelines and to assess the number of included patients. Inclusion criteria were (i) date of birth between 10/2001 and 05/2020 and (ii) increased thyroid-stimulating hormone (TSH) at screening and/or confirmation. The cohort was divided into before (A) and after (B) guideline publication in 02/2011, to assess the guideline’s influence on medical care. A total of 659 patients were analyzed as group A (n = 327) and group B (n = 332) representing 17.5% and 10.3% of CH patients identified in the German and Austrian neonatal screening program during the respective time period. Treatment start and thyroxine doses were similar in both groups and consistent with recommendations. Regular follow-ups were documented. In the first three years of life, less than half of the patients underwent audiometry; developmental assessment was performed in 49.3% (A) and 24.8% (B) (p < 0.01). Documentation of CH patient care by pediatric endocrinologists seemed to be established, however, it reflected only a minority of the affected patients. Therefore, comprehensive documentation as an important instrument of quality assurance and evidence-based medicine should be legally enforced and officially funded in order to record, comprehend, and optimize care and outcome in patients with rare diseases such as CH.
Electrophysiological and Behavioral Responses of Holotrichia parallela to Volatiles from Peanut
Authors: Zhang Mengmeng , Cui Zhihao , Zhang Nuo , Xie Guanglin , Wang Wenkai , Chen Li
Published: February 2021

Holotrichia parallela (Coleoptera: Scarabaeidae: Melolonthinae) is a notorious pest of many crops, especially peanuts. In this study, volatiles from peanut plants were analyzed using both gas chromatographic-electroantennographic detection (GC-EAD) and gas chromatography/mass spectrometry (GC/MS) techniques, and tested for adult attraction with field trapping bioassays in Hebei Province, China. GC-EAD analyses indicated that H. parallela antennae strongly responded to twelve GC peaks, including eight identified compounds, (Z)-β-ocimene, hexanal, 6-methyl-5-hepten-2-one, nonanal, dihydromyrcenol, linalool, β-caryophyllene, methyl salicylate, and four unidentified compounds. When tested individually in field conditions from 24 to 31 July, 2020, β-caryophyllene and hexanal significantly attracted both sexes of H. parallela, whereas all other compounds were unattractive. A blend of β-caryophyllene and hexanal at a ratio of 2:1, close to the natural ratio of these two compounds from the intact peanut plant, was most attractive to the beetles. The remaining identified compounds, (Z)-β-ocimene, 6-methyl-5-hepten-2-one, nonanal, dihydromyrcenol, linalool, and methyl salicylate had no synergistic effects on H. parallela attraction when tested in combination with the blend of β-caryophyllene and hexanal. These results demonstrated that β-caryophyllene and hexanal in the volatiles from peanut plants have strong attraction to H. parallela. These two compounds have the potential to be used for monitoring H. parallela and its management programs.
A Propensity Score-Matched Analysis to Assess the Outcomes in Pre- and Post-Fast-Track Hip and Knee Elective Prosthesis Patients
Authors: Romano Luigi U. , Rigoni Marta , Torri Emanuele , Nella Marilena , Morandi Monica , Casetti Piergiorgio , Nollo Giandomenico
Published: February 2021

Fast-track surgery is a multimodal evidence-based approach to perioperative care aimed at reducing complications and recovery time. We compared a fast-track protocol to standard care in the setting of a small Italian general hospital. Propensity score estimation before and after the study was performed to compare pre-fast-track (pre-FT; January 2013–March 2014) and fast-track (FT; January 2016–December 2016) patients undergoing elective hip and knee replacement surgery with a three-year follow-up (up to January 2020). The primary endpoints were the mean hemoglobin drop, mean predischarge hemoglobin, transfusion and reinfusion rates, pain, ambulation day, hospital length of stay (LOS), and discharge to home/outpatient care or rehabilitation hospital center. The secondary endpoints were the adherence measures to the FT protocol, namely, tourniquet and surgical times, use of drains and catheters, type of anesthesia administered, and complications within three years. The risk difference (RD) and the adjusted odds ratio (aOR) were calculated for each outcome. After the propensity score estimation, we analyzed 59 patients in the pre-FT and 122 in the FT categories. The FT patients, with respect to the pre-FT patients, ameliorated their mean hemoglobin drop from 3.7 to 3.1 g/dl (p < 0.01) and improved their predischarge mean hemoglobin (10.5 g/dL versus 11.0 g/dL; p = 0.01). Furthermore, the aOR of being transfused was reduced by 81% (p < 0,01); the RD of being reinfused was reduced by 63% (p < 0.01); the aOR of having low pain on the first day was increased by more than six times (p < 0.01); the RD of ambulating the first day increased by 91% (p < 0.01); the aOR of admission to a rehabilitation hospital center was reduced by 98% (p < 0.01); the aOR of home discharge increased by 42 times (p < 0.01); the median LOS, tourniquet and surgical times, and use of catheters and drains significantly decreased. Patients with complications at 1 month were 43.1% and 38.2%, respectively, of pre-FT and FT patients (p = 0.63). Complications at 6, 12, 24, and 36 months were significantly lower for the FT patients. This study showed that the uptake of enhanced recovery practices was successful and resulted in the improvement of clinical and organizational outcomes. The fast-track concept and related programs may optimize perioperative care and streamline surgical and rehabilitation care paths.
Implantation of autologous Expanded Mesenchymal Stromal Cells in Hip Osteonecrosis through Percutaneous Forage: Evaluation of the Operative Technique
Authors: Gómez-Barrena Enrique , Padilla-Eguiluz Norma , Consortium REBORNE
Published: February 2021

Bone forage to treat early osteonecrosis of the femoral head (ONFH) has evolved as the channel to percutaneously deliver cell therapy into the femoral head. However, its efficacy is variable and the drivers towards higher efficacy are currently unknown. The aim of this study was to evaluate the forage technique and correlate it with the efficacy to heal ONFH in a multicentric, multinational clinical trial to implant autologous mesenchymal stromal cells expanded from bone marrow (BM-hMSCs). Methods: In the context of EudraCT 2012-002010-39, patients with small and medium-sized (mean volume = 13.3%, range: 5.4 to 32.2) ONFH stage II (Ficat, ARCO, Steinberg) C1 and C2 (Japanese Investigation Committee (JIC)) were treated with percutaneous forage and implantation of 140 million BM-hMSCs in a standardized manner. Postoperative hip radiographs (AP—anteroposterior and lateral), and MRI sections (coronal and transverse) were retrospectively evaluated in 22 patients to assess the femoral head drilling orientation in both planes, and its relation to the necrotic area. Results: Treatment efficacy was similar in C1 and C2 (coronal plane) and in anterior to posterior (transverse plane) osteonecrotic lesions. The drill crossed the sclerotic rim in all cases. The forage was placed slightly valgus, at 139.3 ± 8.4 grades (range, 125.5–159.3) with higher dispersion (f = 2.6; p = 0.034) than the anatomical cervicodiaphyseal angle. Bonferroni’s correlation between both angles was 0.50 (p = 0.028). More failures were seen with a varus drill positioning, aiming at the central area of the femoral head, outside the weight-bearing area (WBA) (p = 0.049). In the transverse plane, the anterior positioning of the drill did not result in better outcomes (p = 0.477). Conclusion: The forage drilling to deliver cells should be positioned within the WBA in the coronal plane, avoiding varus positioning, and central to anterior in the transverse plane. The efficacy of delivered MSCs to regenerate bone in ONFH could be influenced by the drilling direction. Standardization of this surgical technique is desirable.
DOM Biological Lability in an Estuarine System in Two Contrasting Periods
Authors: Retelletti Brogi Simona , Casotti Raffaella , Misson Benjamin , Balestra Cecilia , Gonnelli Margherita , Vestri Stefano , Santinelli Chiara
Published: February 2021

Estuarine processes play a key role in determining the amount and quality of land-derived dissolved organic matter (DOM) reaching the oceans. Microbial-mediated reactions can affect the concentration, quality, and bioavailability of DOM within an estuary. In this study, we investigated biological DOM removal in a small estuary and its variability in two contrasting seasons (spring and autumn) characterized by natural differences in the concentration and quality of the riverine DOM. Two incubation experiments were carried out using natural DOM and heterotrophic prokaryotes community collected at the estuary in March and September. Dissolved organic carbon (DOC) concentration, DOM fluorescence, and the heterotrophic prokaryotes abundance (HPA) showed marked differences between the two seasons. These parameters were followed through time for up to two months. Despite the marked differences in the initial conditions, the DOC removal rates were surprisingly similar in the two periods (16 µM DOC month−1 in March and 18 µM DOC month−1 in September), with the biggest removal in the first 48 h. The trend of fluorescent DOM (FDOM) during the incubation showed marked differences between the two periods. In March, the net removal of all the FDOM components was observed consistently with the decrease in DOC; whereas, in September, the net production of humic-like substances was observed.
Performance Analysis of Ice-Relative Upward-Looking Doppler Navigation of Underwater Vehicles Beneath Moving Sea Ice
Authors: Barker Laughlin D. L. , Whitcomb Louis L.
Published: February 2021

This paper addresses the problem of ice-relative underwater robotic vehicle navigation relative to moving or stationary contiguous sea ice. A review of previously-reported under-ice navigation methods is given, as well as motivation for the use of under-ice robotic vehicles with precision navigation capabilities. We then describe our proposed approach, which employs two or more satellite navigation beacons atop the sea ice along with other precision vehicle and ship mounted navigation sensors to estimate vehicle, ice, and ship states by means of an Extended Kalman Filter. A performances sensitivity analysis for a simulated 7.7 km under ice survey is reported. The number and the location of ice deployed satellite beacons, rotational and translational ice velocity, and separation of ship-based acoustic range sensors are varied, and their effects on estimate error and uncertainty are examined. Results suggest that increasing the number and/or separation of ice-deployed satellite beacons reduces estimate uncertainty, whereas increasing separation of ship-based acoustic range sensors has little impact on estimate uncertainty. Decreasing ice velocity is also correlated with reduced estimate uncertainty. Our analysis suggests that the proposed method is feasible and can offer scientifically useful navigation accuracy over a range of operating conditions.
CDOM Spatiotemporal Variability in the Mediterranean Sea: A Modelling Study
Authors: Lazzari Paolo , Álvarez Eva , Terzić Elena , Cossarini Gianpiero , Chernov Ilya , D’Ortenzio Fabrizio , Organelli Emanuele
Published: February 2021

This study investigates the spatial and temporal variability of chromophoric-dissolved organic matter (CDOM) in the Mediterranean Sea. The analysis is carried out using a state-of-the-art 3D biogeochemical model. The model describes the plankton dynamics, the cycles of the most important limiting nutrients, and the particulate and dissolved pools of carbon. The source of CDOM is directly correlated to the dynamics of dissolved organic carbon (DOC) by a fixed production quota. Then CDOM degrades by photobleaching and remineralization. The main innovation of the system is the inclusion of a bio-optical radiative transfer model that computes surface upwelling irradiance, and therefore simulates remotely sensed reflectance (Rrs). Simulation results of three model configurations are evaluated using satellite Rrs, particularly at 412 nm, 443 nm, and 490 nm. All simulations show a winter minimum in Rrs for the considered bands. However, different parameterizations of DOC-release induce a different accumulation of CDOM, especially in the eastern Mediterranean, and a different Rrs signature: a more active microbial loop during summer implies a decrease of Rrs at 412 nm. We demonstrate how the usage of a bio-optical model allows us to corroborate hypotheses on CDOM-cycling based on blue–violet Rrs data, supporting the importance of this complementary data stream with respect to satellite-derived chlorophyll.
A Numerical Swallowing-Capacity Analysis of a Vacant, Cylindrical, Bi-Directional Tidal Turbine Duct in Aligned & Yawed Flow Conditions
Authors: Borg Mitchell G. , Xiao Qing , Allsop Steven , Incecik Atilla , Peyrard Christophe
Published: February 2021

Introducing a duct along the perimeter of a rotor has been acknowledged to augment turbine performance. The outcome causation due to a bi-directional, cylindrical shroud, however, is uncertain. This study analyses the hydrodynamic swallowing capacity of a true-scale, vacant duct for tidal turbine applications in aligned and yawed inlet flow conditions by utilising three-dimensional unsteady computational fluid dynamics. The performance is investigated within free-stream magnitudes of 1 to 7 m.s−1, and a bearing angular range of 0° to 45° with the duct axis. In proportion to the free-stream magnitude, the normalised axial velocity through the duct increases as a result of a diminishment in pressure drag. Within yawed flow, the maximum capacity falls at a bearing of 23.2°, resulting in a performance increase of 4.13% above that at aligned flow conditions. The analysis concludes that the augmentation at yawed flow occurs due to the duct cross-sectional profile lift variation with angle-of-attack. Towards nominal yaw angle, the internal static pressure reduces, permitting a higher mass-flow rate. Beyond the nominal angle-of-attack, flow separation occurs within the duct, increasing pressure drag, thereby reducing the swallowing capacity.
Cinnamon Oil Inhibits Penicillium expansum Growth by Disturbing the Carbohydrate Metabolic Process
Authors: Lai Tongfei , Sun Yangying , Liu Yaoyao , Li Ran , Chen Yuanzhi , Zhou Ting
Published: February 2021

Penicillium expansum is a major postharvest pathogen that mainly threatens the global pome fruit industry and causes great economic losses annually. In the present study, the antifungal effects and potential mechanism of cinnamon oil against P. expansum were investigated. Results indicated that 0.25 mg L−1 cinnamon oil could efficiently inhibit the spore germination, conidial production, mycelial accumulation, and expansion of P. expansum. In addition, it could effectively control blue mold rots induced by P. expansum in apples. Cinnamon oil could also reduce the expression of genes involved in patulin biosynthesis. Through a proteomic quantitative analysis, a total of 146 differentially expressed proteins (DEPs) involved in the carbohydrate metabolic process, most of which were down-regulated, were noticed for their large number and functional significance. Meanwhile, the expressions of 14 candidate genes corresponding to DEPs and the activities of six key regulatory enzymes (involving in cellulose hydrolyzation, Krebs circle, glycolysis, and pentose phosphate pathway) showed a similar trend in protein levels. In addition, extracellular carbohydrate consumption, intracellular carbohydrate accumulation, and ATP production of P. expansum under cinnamon oil stress were significantly decreased. Basing on the correlated and mutually authenticated results, we speculated that disturbing the fungal carbohydrate metabolic process would be partly responsible for the inhibitory effects of cinnamon oil on P. expansum growth. The findings would provide new insights into the antimicrobial mode of cinnamon oil.
Post-Translational Modifications Drive Success and Failure of Fungal–Host Interactions
Authors: Retanal Charmaine , Ball Brianna , Geddes-McAlister Jennifer
Published: February 2021

Post-translational modifications (PTMs) change the structure and function of proteins and regulate a diverse array of biological processes. Fungal pathogens rely on PTMs to modulate protein production and activity during infection, manipulate the host response, and ultimately, promote fungal survival. Given the high mortality rates of fungal infections on a global scale, along with the emergence of antifungal-resistant species, identifying new treatment options is critical. In this review, we focus on the role of PTMs (e.g., phosphorylation, acetylation, ubiquitination, glycosylation, and methylation) among the highly prevalent and medically relevant fungal pathogens, Candida spp., Aspergillus spp., and Cryptococcus spp. We explore the role of PTMs in fungal stress response and host adaptation, the use of PTMs to manipulate host cells and the immune system upon fungal invasion, and the importance of PTMs in conferring antifungal resistance. We also provide a critical view on the current knowledgebase, pose questions key to our understanding of the intricate roles of PTMs within fungal pathogens, and provide research opportunities to uncover new therapeutic strategies.
Targeted Delivery of Gene Silencing in Fungi Using Genetically Engineered Bacteria
Authors: Niño-Sánchez Jonatan , Chen Li-Hung , De Souza Jorge Teodoro , Mosquera Sandra , Stergiopoulos Ioannis
Published: February 2021

Exploiting RNA interference (RNAi) in disease control through non-transformative methods that overcome the hurdle of producing transgenic plants has attracted much attention over the last years. Here, we explored such a method and used non-pathogenic bacteria as a versatile system for delivering RNAi to fungi. Specifically, the RNaseIII-null mutant strain of Escherichia coli HT115(DE3) was transformed with two plasmid vectors that enabled the constitutive or IPTG-inducible production of double-stranded RNAs (dsRNAs) against genes involved in aflatoxins production in Aspergillus flavus (AflC) or virulence of Botrytis cinerea (BcSAS1). To facilitate the release of the dsRNAs, the bacterial cells were further genetically engineered to undergo a bacteriophage endolysin R-mediated autolysis, following a freeze-thaw cycle. Exposure under in vitro conditions of A. flavus or B. cinerea to living bacteria or their whole-cell autolysates induced silencing of AflC and BcSAS1 in a bacteria concentration-dependent manner, and instigated a reduction in aflatoxins production and mycelial growth, respectively. In planta applications of the living bacteria or their crude whole-cell autolysates produced similar results, thus creating a basis for translational research. These results demonstrate that bacteria can produce biologically active dsRNA against target genes in fungi and that bacteria-mediated RNAi can be used to control fungal pathogens.
Systematic Comparison of Cell Wall-Related Proteins of Different Yeasts
Authors: Lozančić Mateja , Žunar Bojan , Hrestak Dora , Lopandić Ksenija , Teparić Renata , Mrša Vladimir
Published: February 2021

Yeast cell walls have two major roles, to preserve physical integrity of the cell, and to ensure communication with surrounding molecules and cells. While the first function requires evolutionary conserved polysaccharide network synthesis, the second needs to be flexible and provide adaptability to different habitats and lifestyles. In this study, the comparative in silico analysis of proteins required for cell wall biosynthesis and functions containing 187 proteins of 92 different yeasts was performed in order to assess which proteins were broadly conserved among yeasts and which were more species specific. Proteins were divided into several groups according to their role and localization. As expected, many Saccharomyces cerevisiae proteins involved in protein glycosylation, glycosylphosphatidylinositol (GPI) synthesis and the synthesis of wall polysaccharides had orthologues in most other yeasts. Similarly, a group of GPI anchored proteins involved in cell wall biosynthesis (Gas proteins and Dfg5p/Dcw1p) and other non-GPI anchored cell wall proteins involved in the wall synthesis and remodeling were highly conserved. However, GPI anchored proteins involved in flocculation, aggregation, cell separation, and those of still unknown functions were not highly conserved. The proteins localized in the cell walls of various yeast species were also analyzed by protein biotinylation and blotting. Pronounced differences were found both in the patterns, as well as in the overall amounts of different groups of proteins. The amount of GPI-anchored proteins correlated with the mannan to glucan ratio of the wall. Changes of the wall proteome upon temperature shift to 42 °C were detected.
In Vitro and In Vivo Anti-Candida Activity and Structural Analysis of Killer Peptide (KP)-Derivatives
Authors: Ciociola Tecla , Pertinhez Thelma A. , De Simone Tiziano , Magliani Walter , Ferrari Elena , Belletti Silvana , D’Adda Tiziana , Conti Stefania , Giovati Laura
Published: February 2021

The previously described decapeptide AKVTMTCSAS (killer peptide, KP), derived from the variable region of a recombinant yeast killer toxin-like anti-idiotypic antibody, proved to exert a variety of antimicrobial, antiviral, and immunomodulatory activities. It also showed a peculiar self-assembly ability, likely responsible for the therapeutic effect in animal models of systemic and mucosal candidiasis. The present study analyzed the biological and structural properties of peptides derived from KP by substitution or deletion of the first residue, leaving unchanged the remaining amino acids. The investigated peptides proved to exert differential in vitro and/or in vivo anti-Candida activity without showing toxic effects on mammalian cells. The change of the first residue in KP amino acidic sequence affected the conformation of the resulting peptides in solution, as assessed by circular dichroism spectroscopy. KP-derivatives, except one, were able to induce apoptosis in yeast cells, like KP itself. ROS production and changes in mitochondrial transmembrane potential were also observed. Confocal and transmission electron microscopy studies allowed to establish that selected peptides could penetrate within C. albicans cells and cause gross morphological alterations. Overall, the physical and chemical properties of the first residue were found to be important for peptide conformation, candidacidal activity and possible mechanism of action. Small antimicrobial peptides could be exploited for the development of a new generation of antifungal drugs, given their relative low cost and ease of production as well as the possibility of devising novel delivery systems.
Summary of Guidelines for Managing Histoplasmosis among People Living with HIV
Authors: Perez Freddy , Caceres Diego , Ford Nathan , Ravasi Giovanni , Gomez Beatriz , Pasqualotto Alessandro , Hine Paul , Adenis Antoine , Nacher Mathieu , Chiller Tom , Baddley John ,   for the Guideline Development Group for diagnosing and managing disseminated histoplasmosis among people living with HIV
Published: February 2021

Histoplasmosis is a frequent fungal opportunistic infection in people living with HIV (PLHIV), associated every year to a total of 5% to 15% of AIDS-related deaths among this population. In 2020, the first global guidelines for diagnosing and managing disseminated histoplasmosis among PLHIV was published. This document recommends (1) detection of circulating Histoplasma antigens as the recommended laboratory assay to diagnose histoplasmosis among PLHIV; (2) the use of liposomal amphotericin for induction therapy in severe or moderately severe disease, followed by a maintenance therapy with itraconazole for 12 months; a shorter maintenance therapy could be considered if the patient is clinically stable and if immune status has improved; (3) antiretroviral therapy initiation as soon as possible among patients with histoplasmosis without involvement of central nervous system; and (4) that for the treatment of co-infection with histoplasmosis and tuberculosis (TB), treatment of TB should be initiated according to the World Health Organization treatment guidelines. Appropriate health education of providers, supportive supervision, and policy guidance for the care of PLHIV are required.
Hungry for Sex: Differential Roles for Ustilago maydisb Locus Components in Haploid Cells vis à vis Nutritional Availability
Authors: Wallen R. Margaret , Richardson Kirsten , Furnish Madison , Mendoza Hector , Dentinger Allison , Khanal Sunita , Perlin Michael H.
Published: February 2021

Mating-types allow single-celled eukaryotic organisms to distinguish self from non-self in preparation for sexual reproduction. The components of mating-type loci provide initial self/non-self-recognition through pheromone and receptor interactions that control early cell fusion events. However, they may also provide a second level of scrutiny that requires differences in alleles leading to production of a transcription factor required for successful downstream developmental pathways after initial cell fusion. Interestingly, the protein subunits of these transcription factors have not been thoroughly examined for their roles, if any, in the haploid cells themselves. In Ustilago maydis, the causative agent of galls in maize plants, the b locus, encoding bEast (bE) and bWest (bW), components of the eventual requisite transcription factor, has been extensively studied for its role in formation of the stable dikaryon after mating and subsequent pathogenic program. Little is known, however, about any roles for bE or bW in haploid cells. Since mating in fungi is often induced under conditions of nitrogen starvation, we have explored connections between the b locus and the nitrogen-sensing and response pathways in U. maydis. We previously identified a connection in haploid cells between the b locus and Ump2, the high-affinity transceptor, a protein that both transports ammonium and triggers filamentous growth as a response to nitrogen starvation. Deletion of the entire b locus abrogates the filamentous response to low ammonium, a phenotype that is rescued by overexpression of Ump2. Here we further investigated the individual roles of bE and bW in haploid cells. We show that bE and bW are expressed differentially in haploid cells starved for ammonium. Their respective deletion elicits different effects on transcription of mating and pathogenic-related genes and, importantly, on the degree of pathogenic development in host plants. This is the first demonstration of a role for these mating locus components on haploid development and the first to demonstrate a connection to the ammonium transceptors.
Different Weight Loss Intervention Approaches Reveal a Lack of a Common Pattern of Gut Microbiota Changes
Authors: Gutiérrez-Repiso Carolina , Molina-Vega María , Bernal-López M. Rosa , Garrido-Sánchez Lourdes , García-Almeida José M. , Sajoux Ignacio , Moreno-Indias Isabel , Tinahones Francisco J.
Published: February 2021

Options for treatment of obesity include dietary approaches and bariatric surgery. Previous studies have shown that weight loss interventions have an impact on gut microbiota. However, a pattern of gut microbiota changes associated with weight loss independently of the type of intervention has not been described yet. This study includes 61 individuals who followed different weight loss strategies in three different trials: 21 followed a hypocaloric Mediterranean diet (MedDiet), 18 followed a very-low-calorie ketogenic diet (VLCKD) and 22 patients underwent sleeve gastrectomy bariatric surgery (BS). Gut microbiota profile was assessed by next-generation sequencing. A common taxon that had significantly changed within the three weight loss interventions could not be find. At the family level, Clostiridiaceae significantly increased its abundance with MedDiet and VLCKD, whilst Porphyromonadacean and Rikenellaceae significantly increased with VLCKD and BS. At genus level, in VLCKD and BS, Parabacteroides and Alistipes significantly increased their abundance whilst Lactobacillus decreased. At the species level, BS and VLCKD produced an increase in Parabacteroidesdistasonis and a decrease in Eubactieriumventriosum and Lactobacillusrogosae, whilst Orodibactersplanchnicus increased its abundance after the BS and MedDiet. Predicted metagenome analysis suggested that most of the changes after VLCKD were focused on pathways related to biosynthesis and degradation/utilization/assimilation, while BS seems to decrease most of the biosynthesis pathways. MedDiet was enriched in several pathways related to fermentation to short-chain fatty acids. Our results show that weight loss is not associated with a specific pattern of gut microbiota changes independently of the strategy used. Indeed, gut microbiota changes according to type of weight loss intervention.