bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical Study of Large-Scale Fire in Makkah’s King Abdulaziz Road Tunnel
Authors: Guedri Kamel , Abdoon Abdullah A. , Bagabar Omar S. , Oreijah Mowffaq , Bouzid Abdessattar , Munshi Shadi M.
Published: December 2021

Tunnel fires are one of the most dangerous catastrophic events that endanger human life. They cause damage to infrastructure because of the limited space in the tunnel, lack of escape facilities, and difficulty that intervention forces have in reaching the fire position, especially in highly crowded areas, such as Makkah in the Hajj season. Unfortunately, performing experimental tests on tunnel fire safety is particularly challenging because of the prohibitive cost, limited possibilities, and losses that these tests can cause. Therefore, large-scale modeling, using fire dynamic simulation, is one of the best techniques used to limit these costs and losses. In the present work, a fire scenario in the Makkah’s King Abdulaziz Road tunnel was analyzed using the Fire Dynamics Simulator (FDS). The effects of the heat released per unit area, soot yield, and CO yield on the gas temperature, radiation, concentrations of the oxygen and combustion products CO and CO2, and air velocity were examined. The results showed that the radiation increased with the heat released per unit area and the soot yield affected all parameters, except the oxygen concentration and air velocity. The CO yield significantly affects CO concentration, and its influence on the other studied parameters is negligible. Moreover, based on the validation part, the results proved that FDS have limitations in tunnel fires, which impact the smoke layer calculation at the upstream zone of the fire. Therefore, the users or researchers should carefully be concerned about these weaknesses when using FDS to simulate tunnel fires. Further comprehensive research is crucial, as tunnel fires have severe impacts on various aspects of people’s lives.
The Use of Potassium Chloride and Tapioca Starch to Enhance the Flavour and Texture of Phosphate- and Sodium-Reduced Low Fat Breakfast Sausages Manufactured Using High Pressure-Treated Meat
Authors: Cruz-Romero Malco C. , O’Flynn Claire C. , Troy Declan , Mullen Anne M. , Kerry Joe P.
Published: December 2021

The objective of this study was to investigate the use of potassium chloride (KCl) and tapioca starch (TS) to reduce salt levels below 1.5% in sausages manufactured using previously high pressure (HP) processed pork (150 MPa). A 3 × 2 × 1 factorial design was used to formulate breakfast sausages with three salt levels (0.5%, 1.0%, and 1.5%), two ingredient levels (no added ingredient or added as a combination of KCl\TS), and one pressure level (150 MPa). Partial replacement of NaCl with KCl and addition of TS had beneficial effects on the water binding abilities of sausage batters by decreasing (p < 0.05) total expressible fluid (%) and increasing water holding capacity (%). Overall, results indicated that the use of KCl\TS imparted some beneficial effects to salt-reduced low fat breakfast sausages and has the potential to reduce salt levels in the breakfast sausages to 1.0% while still maintaining the organoleptic and functional properties traditionally associated with these meat products.
Organic Acid-Catalyzed Subcritical Water Hydrolysis of Immature Citrus unshiu Pomace
Authors: Lim Sang-Bin
Published: December 2021

Immature Citrus unshiu pomace (ICUP) was hydrolyzed under organic acid-catalyzed, subcritical water (SW) conditions to produce flavonoid monoglucosides (hesperetin-7-O-glycoside and prunin) and aglycons (hesperetin and naringenin) with high biological activities. The results of single-factor experiments showed that with 8 h of hydrolysis and an increasing citric acid concentration, the yield of flavonoid monoglucosides (hesperetin-7-O-glycoside and prunin) increased from 0 to 7% citric acid. Afterward, the hesperetin-7-O-glycoside yield remained constant (from 7 to 19% citric acid) while the pruning yield decreased with 19% of citric acid, whereas the aglycon yield increased continuously. In response surface methodology analysis, a citric acid concentration and hydrolysis duration of 13.34% and 7.94 h were predicted to produce the highest monoglucoside yield of 15.41 mg/g, while 18.48% citric acid and a 9.65 h hydrolysis duration produced the highest aglycon yield of 10.00 mg/g. The inhibitory activities of the SW hydrolysates against pancreatic lipase (PL) and xanthine oxidase (XO) were greatly affected by citric acid concentration and hydrolysis duration, respectively. PL and α-glucosidase inhibition rates of 88.2% and 62.7%, respectively, were achieved with 18.48% citric acid and an 8 h hydrolysis duration, compared to 72.8% for XO with 16% citric acid and 12 h of hydrolysis. This study confirms the potential of citric acid-catalyzed SW hydrolysis of ICUP for producing flavonoid monoglucosides and aglycons with enhanced enzyme inhibitory activities.
Drug-Induced Phase Separation in Polyelectrolyte Microgels
Authors: Al-Tikriti Yassir , Hansson Per
Published: December 2021

Polyelectrolyte microgels may undergo volume phase transition upon loading and the release of amphiphilic molecules, a process important in drug delivery. The new phase is “born” in the outermost gel layers, whereby it grows inward as a shell with a sharp boundary to the “mother” phase (core). The swelling and collapse transitions have previously been studied with microgels in large solution volumes, where they go to completion. Our hypothesis is that the boundary between core and shell is stabilized by thermodynamic factors, and thus that collapsed and swollen phases should be able to also coexist at equilibrium. We investigated the interaction between sodium polyacrylate (PA) microgel networks (diameter: 400–850 µm) and the amphiphilic drug amitriptyline hydrochloride (AMT) in the presence of NaCl/phosphate buffer of ionic strength (I) 10 and 155 mM. We used a specially constructed microscopy cell and micromanipulators to study the size and internal morphology of single microgels equilibrated in small liquid volumes of AMT solution. To probe the distribution of AMT micelles we used the fluorescent probe rhodamine B. The amount of AMT in the microgel was determined by a spectrophotometric technique. In separate experiments we studied the binding of AMT and the distribution between different microgels in a suspension. We found that collapsed, AMT-rich, and swollen AMT-lean phases coexisted in equilibrium or as long-lived metastable states at intermediate drug loading levels. In single microgels at I = 10 mM, the collapsed phase formed after loading deviated from the core-shell configuration by forming either discrete domains near the gel boundary or a calotte shaped domain. At I = 155 mM, single microgels, initially fully collapsed, displayed a swollen shell and a collapsed core after partial release of the AMT load. Suspensions displayed a bimodal distribution of swollen and collapsed microgels. The results support the hypothesis that the boundary between collapsed and swollen phases in the same microgel is stabilized by thermodynamic factors.
Evolutionary Genetics of Crop-Wild Complexes
Authors: Cortés Andrés J. , Cornille Amandine , Yockteng Roxana
Published: December 2021

Since Darwin’s time, the role of crop wild relatives (CWR), landraces, and cultivated genepools in shaping plant diversity and boosting food resources has been a major question [...]
Circulatory MicroRNAs in Plasma and Atrial Fibrillation in the General Population: The Rotterdam Study
Authors: Geurts Sven , Mens Michelle M. J. , Bos Maxime M. , Ikram M. Arfan , Ghanbari Mohsen , Kavousi Maryam
Published: December 2021

Background: MicroRNAs (miRNAs), small non-coding RNAs regulating gene expression, have been shown to play an important role in cardiovascular disease. However, limited population-based data regarding the relationship between circulatory miRNAs in plasma and atrial fibrillation (AF) exist. Moreover, it remains unclear if the relationship differs by sex. We therefore aimed to determine the (sex-specific) association between plasma circulatory miRNAs and AF at the population level. Methods: Plasma levels of miRNAs were measured using a targeted next-generation sequencing method in 1999 participants from the population-based Rotterdam Study. Logistic regression and Cox proportional hazards models were used to assess the associations of 591 well-expressed miRNAs with the prevalence and incidence of AF. Models were adjusted for cardiovascular risk factors. We further examined the link between predicted target genes of the identified miRNAs. Results: The mean age was 71.7 years (57.1% women), 98 participants (58 men and 40 women) had prevalent AF at baseline. Moreover, 196 participants (96 men and 100 women) developed AF during a median follow-up of 9.0 years. After adjusting for multiple testing, miR-4798-3p was significantly associated with the odds of prevalent AF among men (odds ratio, 95% confidence interval, 0.39, 0.24–0.66, p-value = 0.000248). No miRNAs were significantly associated with incident AF. MiR-4798-3p could potentially regulate the expression of a number of AF-related genes, including genes involved in calcium and potassium handling in myocytes, protection of cells against oxidative stress, and cardiac fibrosis. Conclusions: Plasma levels of miR-4798-3p were significantly associated with the odds of prevalent AF among men. Several target genes in relation to AF pathophysiology could potentially be regulated by miR-4798-3p that warrant further investigations in future experimental studies.
Dramatising Solidarity and Unification in Divided Palestine: The Chorus and the Ghost in Kamel EL-Basha’s Following the Footsteps of Hamlet (2013)
Authors: Abushalha Ziad
Published: December 2021

This essay explores how Kamel EL-Basha’s theatre production Following the Footsteps of Hamlet (2013) preaches unity and resistance in a post-2006 divided Palestine. After giving a brief historical account of the causes of the internal Palestinian political divisions that distract Palestinians from achieving liberation, the article traces how El-Basha uses theatrical devices such as the chorus and the ghost to materialise a sense of unification in the theatrical space. The analysis draws on other international theatrical practices like Einar Schleef’s (1980) ‘Choric Theatre’ and cites critical works such as Nietzsche’s The Birth of Tragedy (1872) to locate El-Basha’s theatrical practice in a broader context regarding the significance of the chorus in dramatising unity. The essay also traces how the performance of traditional Palestinian songs, ululation, dances like dabke and other rituals in the play, help foster Palestinian identity and shape their sumud (steadfastness) in facing the occupation. Finally, the essay focuses on the role of the ghost in evoking nostalgia in the audience for the days of unity and collective resistance promoted by the Palestinian leader Yasser Arafat before his death.
The Design of an Intelligent Robotic Wheelchair Supporting People with Special Needs, Including for Their Visual System
Authors: Cojocaru Dorian , Manta Liviu Florin , Pană Cristina Floriana , Dragomir Andrei , Mariniuc Alexandru Marin , Vladu Ionel Cristian
Published: December 2021

The paper aims to study the applicability and limitations of the solution resulting from a design process for an intelligent system supporting people with special needs who are not physically able to control a wheelchair using classical systems. The intelligent system uses information from smart sensors and offers a control system that replaces the use of a joystick. The necessary movements of the chair in the environment can be determined by an intelligent vision system analyzing the direction of the patient’s gaze and point of view, as well as the actions of the head. In this approach, an important task is to detect the destination target in the 3D workspace. This solution has been evaluated, outdoor and indoor, under different lighting conditions. In order to design the intelligent wheelchair, and because sometimes people with special needs also have specific problems with their optical system (e.g., strabismus, Nystagmus) the system was tested on different subjects, some of them wearing eyeglasses. During the design process of the intelligent system, all the tests involving human subjects were performed in accordance with specific rules of medical security and ethics. In this sense, the process was supervised by a company specialized in health activities that involve people with special needs. The main results and findings are as follows: validation of the proposed solution for all indoor lightning conditions; methodology to create personal profiles, used to improve the HMI efficiency and to adapt it to each subject needs; a primary evaluation and validation for the use of personal profiles in real life, indoor conditions. The conclusion is that the proposed solution can be used for persons who are not physically able to control a wheelchair using classical systems, having with minor vision deficiencies or major vision impairment affecting one of the eyes.
Effects of Natural Antimicrobials on Xanthomonas Strains Growth
Authors: Mačionienė Irena , Čepukoit Dovilė , Šalomskienė Joana , Černauskas Darius , Burokienė Daiva , Šalaševičienė Alvija
Published: December 2021

The aim of this work was to investigate the most promising natural antimicrobials effective for the growth suppression of Xanthomonas spp. bacteria. The research objects were Xanthomonas spp. strains isolated from tubers and stem of plants growing in Lithuania: Xanthomonas translucens NRCIB X6, X. arboricola NRCIB X7, NRCIB X8, NRCIB X9, and NRCIB X10; the supernatants of lactic acid bacteria Lactococcus lactis strains 140/2, 57, and 768/5, Lactobacillus helveticus strains 14, 148/3, R, and 3, Lb. reuteri 3 and 7, Streptococcus thermophilus 43, Enterococcus faecium 59-30 and 41-2; endophytic bacterial strains Bacillus, Pseudomonas, and Paenibacillus spp.; and essential oils of lavender (Lavandula angustifolia), grapefruit (Citrus paradisi), pine (Pinus sylvestris), thyme (Thymus vulgaris), rosemary (Rosmarinus officinalis), peppermint (Mentha piperita), lemon (Citrus limetta), aqueous extracts of blueberries (Vaccinium myrtillus), and cranberries (Vaccinium vitis-idaea). The antimicrobial activity of tested substances was determined by agar diffusion method. Supernatants of Lb. reuteri strain 7 and Lb. helveticus strains 14, R, 3, and 148/3 were found to have a high antimicrobial activity against Xanthomonas spp. bacteria strains when compared to the positive control—1.0% copper sulfate (diameter of inhibition zones was 28.8 ± 0.7 mm). The diameter of inhibition zones of supernatants ranged from 23.3 ± 0.6 mm to 32.0 ± 0.1 mm. Thyme (2.0%) and lavender (2.0%) essential oils inhibited the growth of Xanthomonas spp. strains. The diameter of the inhibition zones was from 14.7 ± 0.8 mm to 22.8 ± 0.9 mm. The aqueous extracts of blueberries had a weak antimicrobial activity. The diameter of inhibition zones ranged from 11.0 ± 0.2 mm to 13.0 ± 0.2 mm.
Does Exposure to High Job Demands, Low Decision Authority, or Workplace Violence Mediate the Association between Employment in the Health and Social Care Industry and Register-Based Sickness Absence? A Longitudinal Study of a Swedish Cohort
Authors: Nyberg Anna , Peristera Paraskevi , Toivanen Susanna , Johansson Gun
Published: December 2021

Background: The aim of this paper was to investigate if job demands, decision authority, and workplace violence mediate the association between employment in the health and social care industry and register-based sickness absence. Methods: Participants from the Swedish Longitudinal Occupational Survey of Health who responded to questionnaires in 2006–2016 (n = 3951) were included. Multilevel autoregressive cross-lagged mediation models were fitted to the data. Employment in the health and social care industry at one time point was used as the predictor variable and register-based sickness absence >14 days as the outcome variable. Self-reported levels of job demands, decision authority, and exposure to workplace violence from the first time point were used as mediating variables. Results: The direct path between employment in the health and social care industry and sickness absence >14 days was, while adjusting for the reverse path, 0.032, p = 0.002. The indirect effect mediated by low decision authority was 0.002, p = 0.006 and the one mediated by exposure to workplace violence was 0.008, p = 0.002. High job demands were not found to mediate the association. Conclusion: Workplace violence and low decision authority may, to a small extent, mediate the association between employment in the health and social care industry and sickness absence.
Exploring Factors Associated with Patients Who Prefer Clinician-Sampling to HPV Self-Sampling: A Study Conducted in a Low-Resource Setting
Authors: Sormani Jessica , Kenfack Bruno , Wisniak Ania , Moukam Datchoua Alida , Lemoupa Makajio Sophie , Schmidt Nicole C. , Vassilakos Pierre , Petignat Patrick
Published: December 2021

Human papillomavirus (HPV) self-sampling (Self-HPV) is a promising strategy to improve cervical cancer screening coverage in low-income countries. However, issues associated with women who prefer conventional HPV clinical-sampling over HPV self-sampling may affect screening participation. To address this issue, our study assessed factors associated with women’s preferences related to Self-HPV. This study was embedded in a large clinical trial recruiting women aged 30–49 years in a primary HPV-based study termed “3T-Approach” (for Test-Triage-Treatment), launched in 2018 at Dschang District Hospital, West Cameroon. Participants were invited to perform a Self-HPV. After the sampling and before receiving the results, participants completed a questionnaire about cervical cancer screening and their preferences and perceptions around Self-HPV. The median age of the 2201 participants was 40.6 (IQR 35–45) years. Most (1693 (76.9%)) preferred HPV self-sampling or had no preference for either method, and 508 (23.1%) preferred clinician-sampling. Factors associated with an increased likelihood of reporting a clinician-sampling preference were tertiary educational level (29.4% CI: 25.6–33.6 vs. 14.4% CI: 12.8–16.1) and being an employee with higher grade professional or managerial occupations (5.5% CI: 3.8–7.9 vs. 2.7% CI: 2.0–3.5). The main reported reason for women preferring clinician-sampling was a lack of “self-expertise”. Most women (>99%) would agree to repeat HPV self-sampling and would recommend it to their relatives. HPV self-sampling in the cultural context of central Africa was well accepted by participants, but some participants would prefer to undergo clinician sampling. Health systems should support well-educated women to increase self-confidence in using HPV self-sampling.
Novaluron Has Detrimental Effects on Sperm Functions
Authors: Hwang Ju-Mi , Bae Jeong-Won , Jung Eun-Ju , Lee Woo-Jin , Kwon Woo-Sung
Published: December 2021

Although novaluron is an insect growth regulator with a low mammalian acute toxicity and a low risk to the environment and nontarget organisms, toxic effects of novaluron have been reported. However, no studies have yet evaluated the effect of novaluron on reproduction. Therefore, we examined the effects of novaluron on sperm functions. The spermatozoa of ICR mice were incubated with various concentrations of novaluron to induce capacitation. Then, sperm motion parameters and capacitation status were evaluated using CASA program and H33258/chlortetracycline staining. In addition, PKA activity and tyrosine phosphorylation were evaluated by Western blotting. After exposure, various sperm motion parameters were significantly decreased in a dose-dependent manner. The acrosome reaction was also significantly decreased in the high concentration groups. Sperm viability was significantly reduced at the highest concentration. In addition, PKA activity and tyrosine phosphorylation were also significantly altered. Thus, novaluron affects sperm viability, sperm motility, and motion kinematics during capacitation. Furthermore, it may promote the reduction in acrosome reactions. The physiological suppression of sperm function may depend on abnormal tyrosine phosphorylation via the alteration of PKA activity. Therefore, we suggest that it is necessary to consider reproductive toxicity when using novaluron as a pesticide.
Links of Perceived Pornography Realism with Sexual Aggression via Sexual Scripts, Sexual Behavior, and Acceptance of Sexual Coercion: A Study with German University Students
Authors: Krahé Barbara , Tomaszewska Paulina , Schuster Isabell
Published: December 2021

Exposure to pornographic material has been linked to sexual aggression perpetration and victimization in a large body of research. Based on social learning theory and 3A theory of script learning, this study contributes to this research by testing the hypothesis that the more realistic pornography is perceived to be by young adults, the more likely they are to experience and engage in sexual aggression. Two underlying pathways were proposed: one path via scripts and patterns of sexual behavior regarding consensual sexual interactions that contain established risk factors for sexual aggression victimization and perpetration, and a second path via the acceptance of sexual coercion. In a cross-sectional study, 1181 university students in Germany (762 female; 419 male) completed measures of pornography use and perception, risky sexual scripts and sexual behavior, and acceptance of sexual coercion. As predicted, pornography realism was a positive predictor of risky sexual scripts, risky sexual behavior, and acceptance of sexual coercion. Indirect links with sexual aggression victimization and perpetration were found via both pathways. No gender differences in the associations were found. The implications for media literacy interventions addressing the realism of pornography are discussed.
Transgenerational Transmission of Trauma across Three Generations of Alevi Kurds
Authors: Kizilhan Jan , Noll-Hussong Michael , Wenzel Thomas
Published: December 2021

Background: Thus far, most researchers on genocide and transgenerational transmissions have focused on the National Socialist Holocaust as the most abhorrent example of this severe human rights violation. Few data have been published on other ethnic or religious groups affected by genocidal actions in this context. Methodology: Using a mixed-method approach integrating qualitative interviews with standardized instruments (SCID and PDS), this study examines how individual and collective trauma have been handed down across three generations in an Alevi Kurd community whose members (have) suffered genocidal perpetrations over a longer time period (a “genocidal environment”). Qualitative, open-ended interviews with members of three generations answering questions yielded information on (a) how their lives are shaped by the genocidal experiences from the previous generation and related victim experiences, (b) how the genocidal events were communicated in family narratives, and (c) coping strategies used. The first generation is the generation which directly suffered the genocidal actions. The second generation consists of children of those parents who survived the genocidal actions. Together with their family (children, partner, relatives), this generation suffered forced displacement. Members of the third generation were born in the diaspora where they also grew up. Results: Participants reported traumatic memories, presented in examples in this publication. The most severe traumatic memories included the Dersim massacre in 1937–1938 in Turkey, with 70,000–80,000 victims killed, and the enforced resettlement in western Turkey. A content analysis revealed that the transgenerational transmission of trauma continued across three generations. SCID and PDS data indicated high rates of distress in all generations. Conclusions: Genocidal environments such as that of the Kurdish Alevis lead to transgenerational transmission mediated by complex factors.
Janus Kinase Inhibitors Ameliorated Gastrointestinal Amyloidosis and Hypoalbuminemia in Persistent Dermatitis Mouse Model
Authors: Nakanishi Takehisa , Mizutani Kento , Iida Shohei , Matsushima Yoshiaki , Umaoka Ai , Kondo Makoto , Habe Koji , Yamanaka Keiichi
Published: December 2021

Malnutrition is not only regarded as a complication of rheumatoid arthritis and inflammatory bowel disease but also that of inflammatory skin disease; however, the mechanisms and efficacy of its treatment have not been elucidated. Using a mouse model of dermatitis, we investigated the pathophysiology of malnutrition in inflammatory skin conditions and efficacy of its treatment. We employed spontaneous skin inflammation mice models overexpressing human caspase-1 in the epidermal keratinocytes. Body weight, nutrition level, and α1-antitrypsin fecal concentration were measured. The gastrointestinal tract was histologically and functionally investigated. Fluorescein isothiocyanate (FITC)-dextran was forcibly fed on an empty stomach, and plasma FITC-dextran was measured. The treatment efficacy of antibodies against tumor necrosis factor-α (TNF-α) and interleukin (IL)-α/β as well as Janus kinase (JAK) inhibitors was investigated. Compared with wild-type littermates, the inflammatory skin mice models showed a lowered body weight, reduction of serum albumin level, amyloid deposition in the stomach, small intestine, and large intestine, and increased α1-antitrypsin fecal concentration. However, the plasma FITC-dextran was unchanged between the dermatitis models and wild-type littermates. The over-produced serum amyloid A1 in the liver was detected in the plasma in the dermatitis model. Antibodies against TNF-α and IL-α/β showed partial effects on amyloid deposition; however, JAK inhibitors improved gastrointestinal amyloidosis with the improvement of skin symptoms. Chronic dermatitis is closely related to secondary amyloidosis in the gastrointestinal tract, resulting in hypoalbuminemia. Therefore, active control of skin inflammation is essential for preventing gastrointestinal complications.
Polyurethane Foam Rafts Supported In Vitro Cultures of Rindera graeca Roots for Enhanced Production of Rinderol, Potent Proapoptotic Naphthoquinone Compound
Authors: Kawka Mateusz , Bubko Irena , Koronkiewicz Mirosława , Gruber-Bzura Beata , Graikou Konstantia , Chinou Ioanna , Jeziorek Małgorzata , Pietrosiuk Agnieszka , Sykłowska-Baranek Katarzyna
Published: December 2021

Unique phytochemical profile of plants belonging to Boraginaceae family provides a prolific resource of lipophilic pigments from the group of naphthoquinone derivatives. To overcome low compound content, the major obstacle of plant-based production, immobilization of Rindera graeca roots in in vitro cultures was implemented for efficient production of rinderol, novel furanonaphthoquinone derivative with anticancer properties. Chromatographic procedures revealed rinderol presence in extracts of all investigated root lines, derived both from root biomass and post-culture medium. Unexpectedly, in the second stage of the experiment, rinderol production was ceased in control, unmodified culture systems. On the contrary, roots immobilized on PUF rafts uniformly and stably produced rinderol, and its highest amount was noted for transformed root lines after 42 days of cultivation (222.98 ± 10.47 µg/flask). PUF occurred to be the main place of compound accumulation. Moreover, investigation of rinderol biological activity revealed its fast-acting cell death induction in HeLa cervical cancer cells at relatively low concentrations. Presented results revealed successful application of R. graeca roots immobilization on PUF rafts for production and in situ product removal of rinderol, novel lipophilic furanonaphthoquinone with suggested proapoptotic activity.
Engineering the Catalytic Properties of Two-Domain Laccase from Streptomyces griseoflavus Ac-993
Authors: Kolyadenko Ilya , Scherbakova Anastasia , Kovalev Kirill , Gabdulkhakov Azat , Tishchenko Svetlana
Published: December 2021

Laccases catalyze the oxidation of substrates with the concomitant reduction of oxygen to water. Recently, we found that polar residues located in tunnels leading to Cu2 and Cu3 ions control oxygen entrance (His 165) and proton transport (Arg 240) of two-domain laccase (2D) from Streptomyces griseoflavus (SgfSL). In this work, we have focused on optimizing the substrate-binding pocket (SBP) of SgfSL while simultaneously adjusting the oxygen reduction process. SgfSL variants with three single (Met199Ala, Met199Gly, and Tyr230Ala) and three double amino acid residues substitutions (Met199Gly/His165Ala, His165Ala/Arg240His, Met199Gly/Arg240His) were constructed, purified, and investigated. Combination of substitutions in the SBP and in the tunnel leading to Cu2 ion (Met199Gly/Arg240His) increased SgfSL catalytic activity towards ABTS by 5-fold, and towards 2.6-DMP by 16-fold. The high activity of the Met199Gly/Arg240His variant can be explained by the combined effect of the SBP geometry optimization (Met199Gly) and increased proton flux via the tunnel leading to Cu2 ion (Arg240His). Moreover, the variant with Met199Gly and His165Ala mutations did not significantly increase SgfSL’s activity, but led to a drastic shift in the optimal pH of 2.6-DMP oxidation. These results indicate that His 165 not only regulates oxygen access, but it also participates in proton transport in 2D laccases.
Fibrosis Protein-Protein Interactions from Google Matrix Analysis of MetaCore Network
Authors: Kotelnikova Ekaterina , Frahm Klaus M. , Shepelyansky Dima L. , Kunduzova Oksana
Published: December 2021

Protein–protein interactions is a longstanding challenge in cardiac remodeling processes and heart failure. Here, we use the MetaCore network and the Google matrix algorithms for prediction of protein–protein interactions dictating cardiac fibrosis, a primary cause of end-stage heart failure. The developed algorithms allow identification of interactions between key proteins and predict new actors orchestrating fibroblast activation linked to fibrosis in mouse and human tissues. These data hold great promise for uncovering new therapeutic targets to limit myocardial fibrosis.
Reciprocal Homer1a and Homer2 Isoform Expression Is a Key Mechanism for Muscle Soleus Atrophy in Spaceflown Mice
Authors: Blottner Dieter , Trautmann Gabor , Furlan Sandra , Gambara Guido , Block Katharina , Gutsmann Martina , Sun Lian-Wen , Worley Paul F. , Gorza Luisa , Scano Martina , Lorenzon Paola , Vida Imre , Volpe Pompeo , Salanova Michele
Published: December 2021

The molecular mechanisms of skeletal muscle atrophy under extended periods of either disuse or microgravity are not yet fully understood. The transition of Homer isoforms may play a key role during neuromuscular junction (NMJ) imbalance/plasticity in space. Here, we investigated the expression pattern of Homer short and long isoforms by gene array, qPCR, biochemistry, and laser confocal microscopy in skeletal muscles from male C57Bl/N6 mice (n = 5) housed for 30 days in space (Bion-flight = BF) compared to muscles from Bion biosatellite on the ground-housed animals (Bion ground = BG) and from standard cage housed animals (Flight control = FC). A comparison study was carried out with muscles of rats subjected to hindlimb unloading (HU). Gene array and qPCR results showed an increase in Homer1a transcripts, the short dominant negative isoform, in soleus (SOL) muscle after 30 days in microgravity, whereas it was only transiently increased after four days of HU. Conversely, Homer2 long-form was downregulated in SOL muscle in both models. Homer immunofluorescence intensity analysis at the NMJ of BF and HU animals showed comparable outcomes in SOL but not in the extensor digitorum longus (EDL) muscle. Reduced Homer crosslinking at the NMJ consequent to increased Homer1a and/or reduced Homer2 may contribute to muscle-type specific atrophy resulting from microgravity and HU disuse suggesting mutual mechanisms.
Recent Advances in Anticoagulant Treatment of Immune Thrombosis: A Focus on Direct Oral Anticoagulants in Heparin-Induced Thrombocytopenia and Anti-Phospholipid Syndrome
Authors: Carré Julie , Jourdi Georges , Gendron Nicolas , Helley Dominique , Gaussem Pascale , Darnige Luc
Published: December 2021

For more than 10 years, direct oral anticoagulants (DOACs) have been increasingly prescribed for the prevention and treatment of thrombotic events. However, their use in immunothrombotic disorders, namely heparin-induced thrombocytopenia (HIT) and antiphospholipid syndrome (APS), is still under investigation. The prothrombotic state resulting from the autoimmune mechanism, multicellular activation, and platelet count decrease, constitutes similarities between HIT and APS. Moreover, they both share the complexity of the biological diagnosis. Current treatment of HIT firstly relies on parenteral non-heparin therapies, but DOACs have been included in American and French guidelines for a few years, providing the advantage of limiting the need for treatment monitoring. In APS, vitamin K antagonists are conversely the main treatment (+/− anti-platelet agents), and the use of DOACs is either subject to precautionary recommendations or is not recommended in severe APS. While some randomized controlled trials have been conducted regarding the use of DOACs in APS, only retrospective studies have examined HIT. In addition, vaccine-induced immune thrombotic thrombocytopenia (VITT) is now a part of immunothrombotic disorders, and guidelines have been created concerning an anticoagulant strategy in this case. This literature review aims to summarize available data on HIT, APS, and VITT treatments and define the use of DOACs in therapeutic strategies.
Developing Consensus Standard Operating Procedures (SOPs) to Evaluate New Types of Insecticide-Treated Nets
Authors: Lissenden Natalie , Armistead Jennifer S. , Gleave Katherine , Irish Seth R. , Martin Jackline L. , Messenger Louisa A. , Moore Sarah J. , Ngufor Corine , Protopopoff Natacha , Oxborough Richard , Spiers Angus , Lees Rosemary S.
Published: December 2021

In response to growing concerns over the sustained effectiveness of pyrethroid-only based control tools, new products are being developed and evaluated. Some examples of these are dual-active ingredient (AI) insecticide-treated nets (ITNs) which contain secondary insecticides, or synergist ITNs which contain insecticide synergist, both in combination with a pyrethroid. These net types are often termed ‘next-generation’ insecticide-treated nets. Several of these new types of ITNs are being evaluated in large-scale randomized control trials (RCTs) and pilot deployment schemes at a country level. However, no methods for measuring the biological durability of the AIs or synergists on these products are currently recommended. In this publication, we describe a pipeline used to collate and interrogate several different methods to produce a singular ‘consensus standard operating procedure (SOP)’, for monitoring the biological durability of three new types of ITNs: pyrethroid + piperonyl butoxide (PBO), pyrethroid + pyriproxyfen (PPF), and pyrethroid + chlorfenapyr (CFP). This process, convened under the auspices of the Innovation to Impact programme, sought to align methodologies used for conducting durability monitoring activities of next-generation ITNs.
Lobesia botrana: A Biological Control Approach with a Biopesticide Based on Entomopathogenic Fungi in the Winter Season in Chile
Authors: Altimira Fabiola , De La Barra Nathalia , Godoy Paulo , Roa Juan , Godoy Sebastián , Vitta Nancy , Tapia Eduardo
Published: December 2021

Lobesia botrana (Denis and Shiffermüller) (Lepidoptera: Tortricidae) is one of the main pests that affect the production and export of table grapes in Chile. Because this pest has quarantine status, the fruit must be fumigated with methyl bromide, which reduces the fruit’s export competitiveness in the destination market. In the present study, to help resolve this issue, six native entomopathogenic fungi were identified through multilocus analysis, including three Beauveria pseudobassiana and three Metarhizium robertsii. These fungi were evaluated in the laboratory to control L. botrana in its pupal stage in a silk cocoon and compared against a biological control product. Formulations with additional carbon sources improved the performance of the fungi. The treatments with outstanding performance contained the fungal strains B. pseudobassiana RGM 2184 and M. robertsii RGM 678. These strains were evaluated in the field during the winter season in two different regions of the country; the strains reached maximum efficacies of 80% and 88%, respectively, at 21 days post first application. Therefore, entomopathogenic fungi can contribute to reducing pupal populations in winter, thereby decreasing the moth population in spring–summer.
Production of PP Composites Reinforced with Flax and Hemp Woven Mesh Fabrics via Compression Molding
Authors: Boccarusso Luca , De Fazio Dario , Durante Massimo
Published: December 2021

Hemp and flax fibers are among the most interesting vegetable fibers that can be used to reinforce polymeric matrices. In line with the global environmental requests, the use of these fibers especially coupled with thermoforming polymers are increasing more and more in order to expand their applications and replace synthetic fibers and thermosetting plastics. However, one of the major limitations of vegetable fibers is their poor adhesion with polymeric matrices that is often overcome by fibers chemical treatments or by using coupling agents within the matrix. Aiming to produce polypropylene (PP) bio composite laminates reinforced by hemp and flax fibers without additional process steps, this paper deals on the study of their production via the compression molding technique by using woven fabrics characterized by a large mesh size able to ensure a mechanical anchoring between fibers and matrix. Two different forming strategies that differ in the time required for reaching the maximum values of compression pressure and in the dwelling time at this value were used in order to investigate how the yarn impregnation was affected by them. To expand the applications of composites under investigation, tensile, bending, Izod, heat deflection temperature (HDT) and bearing tests were carried out. The results highlighted how the use of a waiting time before the reaching of the maximum moulding pressure allowed a better matrix flow within the vegetable yarn leading to higher mechanical performances.
Comparative Genomics and Gene Pool Analysis Reveal the Decrease of Genome Diversity and Gene Number in Rice Blast Fungi by Stable Adaption with Rice
Authors: Wu Qi , Wang Yi , Liu Li-Na , Shi Kai , Li Cheng-Yun
Published: December 2021

Magnaporthe oryzae caused huge losses in rice and wheat production worldwide. Comparing to long-term co-evolution history with rice, wheat-infecting isolates were new-emerging. To reveal the genetic differences between rice and wheat blast on global genomic scale, 109 whole-genome sequences of M. oryzae from rice, wheat, and other hosts were reanalyzed in this study. We found that the rice lineage had gone through stronger selective sweep and fewer conserved genes than those of Triticum and Lolium lineages, which indicated that rice blast fungi adapted to rice by gene loss and rapid evolution of specific loci. Furthermore, 228 genes associated with host adaptation of M. oryzae were found by presence/absence variation (PAV) analyses. The functional annotation of these genes found that the fine turning of genes gain/loss involved with transport and transcription factor, thiol metabolism, and nucleotide metabolism respectively are major mechanisms for rice adaption. This result implies that genetic base of specific host plant may lead to gene gain/loss variation of pathogens, so as to enhance their adaptability to host. Further characterization of these specific loci and their roles in adaption and evaluation of the fungi may eventually lead to understanding of interaction mechanism and develop new strategies of the disease management.
Whole Genome Sequencing and Annotation of Naematelia aurantialba (Basidiomycota, Edible-Medicinal Fungi)
Authors: Sun Tao , Zhang Yixuan , Jiang Hao , Yang Kai , Wang Shiyu , Wang Rui , Li Sha , Lei Peng , Xu Hong , Qiu Yibin , Sun Dafeng
Published: December 2021

Naematelia aurantialba is a rare edible fungus with both nutritional and medicinal values and especially rich in bioactive polysaccharides. However, due to the lack of genomic information, researches on the mining of active compounds, artificial breeding and cultivation, genetics, and molecular biology are limited. To facilitate the medicinal and food applications of N. aurantialba, we sequenced and analyzed the whole genome of N. aurantialba for the first time. The 21-Mb genome contained 15 contigs, and a total of 5860 protein-coding genes were predicted. The genome sequence shows that 296 genes are related to polysaccharide synthesis, including 15 genes related to nucleoside-activated sugar synthesis and 11 genes related to glucan synthesis. The genome also contains genes and gene clusters for the synthesis of other active substances, including terpenoids, unsaturated fatty acids, and bioactive proteins. In addition, it was also found that N. aurantialba was more closely related to Naematelia encephala than to Tremella fuciformis. In short, this study provides a reference for molecular cognition of N. aurantialba and related researches.
Methylation of 2-Aryl-2-(3-indolyl)acetohydroxamic Acids and Evaluation of Cytotoxic Activity of the Products
Authors: Aksenov Dmitrii A. , Aksenov Alexander V. , Prityko Lidiya A. , Aksenov Nicolai A. , Frolova Liliya V. , Rubin Michael
Published: December 2021

2-Aryl-2-(3-indolyl)acetohydroxamic acids demonstrate promising antitumor activity, but quickly metabolize in vivo via glucuronidation of hydroxamic acid residue. In an attempt to improve their pharmacokinetics, methyl esters were synthesized via a newly developed protocol for chemoselective mono-methylation of hydroxamic acids. The cytotoxicity of these derivatives against the HeLa cell line was evaluated and found to be inferior compared to the parent lead compounds.
Microstructure and Mechanical Properties of Friction Stir-Welded Dissimilar Joints of ZK60 and Mg-4.6Al-1.2Sn-0.7Zn Alloys
Authors: Xie Liangwen , Zhu Xianyong , Fan Yuexiang , Sun Weijia , Wang Peng , Jiang Cheng , Xiao Xiong , Yang Song , Song Yulai
Published: December 2021

In order to clarify the microstructural evolution and the mechanical property of dissimilar friction stir-welded joints of ZK60 and Mg-4.6Al-1.2Sn-0.7Zn magnesium alloys, two types of arrangement with ZK60 at advancing side (AS) or retreating side (RS) were adopted. The macrostructure and the microstructure of the dissimilar welded joints were discussed, and the microhardness and the transverse tensile properties of the joints were measured. There are three stirring sub-zones with different compositions and two clear interfaces within the joints. Due to the effect of both the original grain size of base materials and the growth of recrystallized grains, in the stir zone (SZ), the grain size of ZK60 increased slightly, while the grain size of Mg-4.6Al-1.2Sn-0.7Zn decreased significantly. The dissolution of precipitates was gradually significant from RS to AS within the SZ due to the gradual increase in strain and heat. The grain refinement led to an increase in hardness, while the dissolution of precipitates resulted in a decrease in hardness. The performance of the joints obtained with ZK60 placed on the RS is slightly better than that of that on the AS. The tensile fracture of both joints occurred at the interface between SZ and the thermos-mechanical affected zone at the AS, and showed a quasi-dissociative fracture.
Marine-Derived Indole Alkaloids and Their Biological and Pharmacological Activities
Authors: Wibowo Joko Tri , Ahmadi Peni , Rahmawati Siti Irma , Bayu Asep , Putra Masteria Yunovilsa , Kijjoa Anake
Published: December 2021

Novel secondary metabolites from marine macroorganisms and marine-derived microorganisms have been intensively investigated in the last few decades. Several classes of compounds, especially indole alkaloids, have been a target for evaluating biological and pharmacological activities. As one of the most promising classes of compounds, indole alkaloids possess not only intriguing structural features but also a wide range of biological/pharmacological activities including antimicrobial, anti-inflammatory, anticancer, antidiabetic, and antiparasitic activities. This review reports the indole alkaloids isolated during the period of 2016–2021 and their relevant biological/pharmacological activities. The marine-derived indole alkaloids reported from 2016 to 2021 were collected from various scientific databases. A total of 186 indole alkaloids from various marine organisms including fungi, bacteria, sponges, bryozoans, mangroves, and algae, are described. Despite the described bioactivities, further evaluation including their mechanisms of action and biological targets is needed to determine which of these indole alkaloids are worth studying to obtain lead compounds for the development of new drugs.
Effect of the Initial Texture, Recrystallization and Re-Dissolution Process on the Evolution of Texture during Solution Treatment of the 7A65 Hot Rolled Plate
Authors: Wang Hao , Jia Lina , Wang Wenbo , Ye Chengtong , Li Chen , Zhang Xinquan , Zhang Hu
Published: December 2021

The evolution of textures, the degree of recrystallization and the mechanical properties of 7A65 hot rolled plates during re-dissolution were studied with different thicknesses (25 mm, 65 mm, 120 mm) and different degrees of deformation. It was found that different plates exhibited different trends of re-dissolution because the degrees of deformation increased and the degrees of recrystallization were different during the solution treatment. With the increase of deformation and static recrystallization degrees, texture types changed from Cube, R-Cube to Brass, R, Cube and Copper during the re-dissolution process. The value of the Schmid factor (µ¯) was calculated and the value along the rolling direction was significantly larger than along the transverse direction, which led to a lower yield strength along the rolling direction. In terms of the average contribution of the yield strength, the strengthening of the grain boundary including LAGBs (low-angle grain boundaries) was found to play a more significant role than the effect of solid atoms and dislocation densities. Therefore, the 25 mm plate exhibits the best mechanical properties, with a yield strength of 565.7 MPa along the rolling direction.
What Flips the Switch? Signals and Stress Regulating Extraintestinal Pathogenic Escherichia coli Type 1 Fimbriae (Pili)
Authors: Bessaiah Hicham , Anamalé Carole , Sung Jacqueline , Dozois Charles M.
Published: December 2021

Pathogens are exposed to a multitude of harmful conditions imposed by the environment of the host. Bacterial responses against these stresses are pivotal for successful host colonization and pathogenesis. In the case of many E. coli strains, type 1 fimbriae (pili) are an important colonization factor that can contribute to diseases such as urinary tract infections and neonatal meningitis. Production of type 1 fimbriae in E. coli is dependent on an invertible promoter element, fimS, which serves as a phase variation switch determining whether or not a bacterial cell will produce type 1 fimbriae. In this review, we present aspects of signaling and stress involved in mediating regulation of type 1 fimbriae in extraintestinal E. coli; in particular, how certain regulatory mechanisms, some of which are linked to stress response, can influence production of fimbriae and influence bacterial colonization and infection. We suggest that regulation of type 1 fimbriae is potentially linked to environmental stress responses, providing a perspective for how environmental cues in the host and bacterial stress response during infection both play an important role in regulating extraintestinal pathogenic E. coli colonization and virulence.