bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulations between Three Types of Networks of Splicing Processors
Authors: Sánchez Couso José , Sanchez Martín José , Mitrana Victor , Păun Mihaela
Published: June 2021

Networks of splicing processors (NSP for short) embody a subcategory among the new computational models inspired by natural phenomena with theoretical potential to handle unsolvable problems efficiently. Current literature considers three variants in the context of networks managed by random-context filters. Despite the divergences on system complexity and control degree over the filters, the three variants were proved to hold the same computational power through the simulations of two computationally complete systems: Turing machines and 2-tag systems. However, the conversion between the three models by means of a Turing machine is unattainable because of the huge computational costs incurred. This research paper addresses this issue with the proposal of direct and efficient simulations between the aforementioned paradigms. The information about the nodes and edges (i.e., splicing rules, random-context filters, and connections between nodes) composing any network of splicing processors belonging to one of the three categories is used to design equivalent networks working under the other two models. We demonstrate that these new networks are able to replicate any computational step performed by the original network in a constant number of computational steps and, consequently, we prove that any outcome achieved by the original architecture can be accomplished by the constructed architectures without worsening the time complexity.
Differential Effects of Resistance- and Endurance-Based Exercise Programs on Muscular Fitness, Body Composition, and Cardiovascular Variables in Young Adult Women: Contextualizing the Efficacy of Self-Selected Exercise Modalities
Authors: Versic Sime , Idrizovic Kemal , Ahmeti Gentiana Beqa , Sekulic Damir , Majeric Matej
Published: June 2021

There is an evident lack of research simultaneously investigating endurance training (ET) and resistance training (RT) with regard to their potential influence on fitness and health status in young women. This study aimed to determine the effects of RT and ET three times a week over an eight-week period on anthropometric/body composition indices, blood pressure (BP), and muscular fitness in apparently healthy young women who participated in a self-preferred program. The sample of participants comprised 57 young healthy women (23.9 ± 3.08 years, 165.5 ± 5.8 cm, 66.8 ± 7.2 kg) divided into ET (n = 18), RT (n = 19), and non-exercising (C) (n = 20) groups. The variables consisted of anthropometric/body composition indices (body mass, BMI, body fat, and lean body mass), muscular fitness variables (lower body strength, upper body strength, abdominal strength, dynamometric force, and flexibility), and cardiovascular parameters (resting heart rate and systolic and diastolic BP). A pre- and post-testing design, with factorial analysis of variance for repeated measurements (ANOVA: Group × Measurement), including a consecutive post hoc test, was applied. The ANOVA indicated a similar improvement in body composition (increase in lean body mass and decrease in body fat percentage), resting heart rate, and flexibility in both of the exercise groups, with no significant changes in the C group. RT improved the participants’ strength and force capacities to a greater extent than ET. BP showed a trend of improvement in both of the training groups, but without statistically significant pre- to post-changes. Correlation analysis calculated with variables of pre- to post-differences (VDs) indicated poor associations between VDs, indicating relative independence of the obtained effects for the different variables in each training group. Although this investigation comprised apparently healthy young women, numerous positive changes indicated the efficacy of both programs in a relatively short period of time. While the participants in this study self-selected training programs, the evidenced positive effects can be at least partially related to this fact.
Current Evidence about Developmental Dysplasia of the Hip in Pregnancy
Authors: Simionescu Anca Angela , Cirstoiu Monica Mihaela , Cirstoiu Catalin , Stanescu Ana Maria Alexandra , Crețu Bogdan
Published: June 2021

In adults, developmental dysplasia of the hip (DDH) represents a spectrum of disorders. It is commonly found in women in routine orthopedic practice. Hip dysplasia is a leading precursor of joint laxity; when untreated, it can contribute to chronic modifications, such as thickening of the pulvinar and ligamentum teres (which can also elongate), hypertrophy of the transverse acetabular ligament, and osteoarthritis. DDH is presumed to be associated with alterations in pelvic morphology that may affect vaginal birth by the reduction in the transverse diameter of the pelvic inlet or outlet. Here, we provide an overview of the current knowledge of pregnancy-associated DDH. We primarily focused on how a surgical DDH treatment might influence the pelvic shape and size and the effects on the mechanism of birth. We presented the female pelvis from the standpoint of bone and ligament morphology relative to a pelvic osteotomy. Then, we described whether the pregnancy was impacted by previous surgical DDH treatments, performed from infancy to adulthood. In conclusion, hip dysplasia is not associated with high-risk complications during pregnancy or with increased difficulty in vaginal delivery.
Long-Term Effects of Renal Artery Denervation
Authors: Juknevičius Vytautas , Berūkštis Andrius , Juknevičienė Renata , Jasiūnas Eugenijus , Šerpytis Pranas , Laucevičius Aleksandras
Published: June 2021

Background and Objectives: Renal artery denervation (RDN) procedure is a broadly discussed method in the treatment of resistant hypertension. Many studies report short-term (3–12 months) results for blood pressure and arterial stiffness. The primary endpoints were changes in 24 h mean systolic blood pressure (BP) and office systolic BP 48 months after RDN. The secondary endpoints were changes in aortic pulse wave velocity and impact of polypharmacy on these variables. Materials and Methods: Renal artery denervation was performed in 73 patients treated for resistant hypertension; 49 patients remained in final analysis. Patient examination was carried out before the procedure, and subsequently at 3, 6, 12, 24, and 48 months later. Patients’ antihypertensive and overall medication regimens were carefully analysed. Results: Mean 24 h arterial blood pressure lowered and was sustained at lower levels for up to 48 months; median (interequartile range—IQR) from 158(23.5)/100(14.2) to 140(26.5)/86(16.2) mmHg. Mean reduction in 24 h ambulatory systolic BP was −11 ± 25 mmHg (95% CI, −20 to −2; p < 0.001), while office systolic BP reduced by −7 ± 23 mmHg (95%CI, −24 to −1; p < 0.02). A significant reduction in median aortic pulse wave velocity 12 months after the procedure (drop from baseline 11.2 [3.15] m/s (95%CI 6.1 to 16.2) to 9.8 [2.1] m/s (95%CI 6.1 to 13.7; p = 0.002)). After 48 months, there was no worsening compared to the baseline level of 10.3 [4.0] m/s (95% CI 6.9 to 17.8) (p > 0.05). The total mean number of antihypertensive drugs remained unchanged: 5.97(±1.1) vs. 5.24 (±1.45). A higher number of pills after 48 months was associated with higher aortic pulse wave velocity (1–5 pill group: 8.1 ± 1.6 m/s; 6–10 pill group: 10.9 ± 1.8 m/s; >11 pill group: 15.1 ± 2.6 m/s) (p = 0.003). Conclusions: Antihypertensive effect after renal denervation lasts up to 48 months with no worsening of arterial stiffness compared to baseline. In our study, polypharmacy was associated with increased arterial stiffness 48 months after the procedure.
Biological Activity Characterization of the Diagnostically Relevant Human Papillomavirus 16 E1C RNA
Authors: Varghese Christy Susan , Will Rainer , Tessmer Claudia , Hofmann Ilse , Hessling Bernd , Pawlita Michael , Höfler Daniela
Published: June 2021

The spliced human papillomavirus 16 (HPV16) E1C RNA is associated with high-grade precursor lesions and cervical cancer. This qualifies E1C as a biomarker for high-grade lesions in HPV-based cervical cancer precursor screening. Here, we aimed to characterize the biological activity of HPV16 E1C RNA. In HEK-293T cells overexpressing HPV16 E1C RNA, we detected 9 kDa E1C protein in the cytoplasm using immunological assays with a newly generated E1C-specific monoclonal antibody or in mass spectrometry only after proteasome inhibition with MG132, indicating instability of the E1C protein. In HPV16-transformed cervical cancer cell lines in which the level of endogenous E1C RNA is much lower, E1C protein was not detected even after proteasome inhibition. Transient E1C overexpression in HEK-293T cells, co-transfected with a firefly luciferase reporter gene under the control of the HPV16 upstream regulatory region (URR), activated the HPV16 URR by 38%. This activation was also present when E1C translation was abolished by mutation. However, a construct expressing a random RNA sequence with similar GC content and 45% homology to the E1C RNA sequence also stimulated URR activity, indicating that special E1C RNA motifs might be responsible for the activation. In HPV16-transformed cell lines W12-episomal (W12-epi), W12-integrated HPV (W12-int), CaSki and SiHa stably overexpressing E1C RNA from lentiviral transduction, levels of endogenous HPV16 RNAs E6*I and E7 remained unchanged, while E1^E4 levels were significantly reduced by 20–30% in W12-epi, W12-int and CaSki cells. Overall, our study shows that E1C RNA is active and might contribute to transformation independent of the E6*I or E7 pathways. However, E1C overexpression resulted in only subtle changes in HPV16 RNA expression and very low copies of endogenous E1C RNA were detected in cervical cancer cell lines. This could weigh towards a less prominent role of E1C RNA in natural HPV transformation.
The Rhizobacterium Pseudomonas alcaligenes AVO110 Induces the Expression of Biofilm-Related Genes in Response to Rosellinia necatrix Exudates
Authors: Pintado Adrián , Pérez-Martínez Isabel , Aragón Isabel M. , Gutiérrez-Barranquero José Antonio , de Vicente Antonio , Cazorla Francisco M. , Ramos Cayo
Published: June 2021

The rhizobacterium Pseudomonas alcaligenes AVO110 exhibits antagonism toward the phytopathogenic fungus Rosellinia necatrix. This strain efficiently colonizes R. necatrix hyphae and is able to feed on their exudates. Here, we report the complete genome sequence of P. alcaligenes AVO110. The phylogeny of all available P. alcaligenes genomes separates environmental isolates, including AVO110, from those obtained from infected human blood and oyster tissues, which cluster together with Pseudomonas otitidis. Core and pan-genome analyses showed that P. alcaligenes strains encode highly heterogenic gene pools, with the AVO110 genome encoding the largest and most exclusive variable region (~1.6 Mb, 1795 genes). The AVO110 singletons include a wide repertoire of genes related to biofilm formation, several of which are transcriptionally modulated by R. necatrix exudates. One of these genes (cmpA) encodes a GGDEF/EAL domain protein specific to Pseudomonas spp. strains isolated primarily from the rhizosphere of diverse plants, but also from soil and water samples. We also show that CmpA has a role in biofilm formation and that the integrity of its EAL domain is involved in this function. This study contributes to a better understanding of the niche-specific adaptations and lifestyles of P. alcaligenes, including the mycophagous behavior of strain AVO110.
Lactobacillus reuteri BM53-1 Produces a Compound That Inhibits Sticky Glucan Synthesis by Streptococcus mutans
Authors: Noda Masafumi , Sugihara Naho , Sugimoto Yoshimi , Hayashi Ikue , Sugimoto Sachiko , Danshiitsoodol Narandalai , Sugiyama Masanori
Published: June 2021

Cariogenic bacteria, such as Streptococcus (S.) mutans and S. sobrinus, produce insoluble and sticky glucans as a biofilm material. The present study demonstrates that a lactic acid bacterium (LAB) named BM53-1 produces a substance that inhibits the sticky glucan synthesis. The BM53-1 strain was isolated from a flower of Actinidia polygama and identified as Lactobacillus reuteri. The substance that inhibits sticky glucan synthesis does not exhibit antibacterial activity against S. mutans. The cariogenic S. mutans produces glucans under the control of three glucosyltransferase (GTF) enzymes, named GtfB, GtfC, and GtfD. Although GtfB and GtfC produce insoluble glucans, GtfD forms soluble glucans. Through quantitative reverse-transcriptional (qRT)-PCR analysis, it was revealed that the BM53-1-derived glucan-production inhibitor (GI) enhances the transcriptions of gtfB and gtfC genes 2- to 7-fold at the early stage of cultivation. However, that of gtfD was not enhanced in the presence of the GI, indicating that the glucan stickiness produced by S. mutans was significantly weaker in the presence of the GI. Our result demonstrates that Lb. reuteri BM53-1 is useful to prevent dental caries.
How Do Quorum-Sensing Signals Mediate Algae–Bacteria Interactions?
Authors: Dow Lachlan
Published: June 2021

Quorum sensing (QS) describes a process by which bacteria can sense the local cell density of their own species, thus enabling them to coordinate gene expression and physiological processes on a community-wide scale. Small molecules called autoinducers or QS signals, which act as intraspecies signals, mediate quorum sensing. As our knowledge of QS has progressed, so too has our understanding of the structural diversity of QS signals, along with the diversity of bacteria conducting QS and the range of ecosystems in which QS takes place. It is now also clear that QS signals are more than just intraspecies signals. QS signals mediate interactions between species of prokaryotes, and between prokaryotes and eukaryotes. In recent years, our understanding of QS signals as mediators of algae–bacteria interactions has advanced such that we are beginning to develop a mechanistic understanding of their effects. This review will summarize the recent efforts to understand how different classes of QS signals contribute to the interactions between planktonic microalgae and bacteria in our oceans, primarily N-acyl-homoserine lactones, their degradation products of tetramic acids, and 2-alkyl-4-quinolones. In particular, this review will discuss the ways in which QS signals alter microalgae growth and metabolism, namely as direct effectors of photosynthesis, regulators of the cell cycle, and as modulators of other algicidal mechanisms. Furthermore, the contribution of QS signals to nutrient acquisition is discussed, and finally, how microalgae can modulate these small molecules to dampen their effects.
Multisystem Inflammatory Syndrome in an Adult (MIS-A) Successfully Treated with Anakinra and Glucocorticoids
Authors: Cattaneo Paolo , Volpe Alessandro , Cardellino Chiara Simona , Riccardi Niccolò , Bertoli Giulia , Ursini Tamara , Ustalli Arjola , Lodi Giovanni , Daroui Ivan , Angheben Andrea
Published: June 2021

During the current SARS-CoV-2 pandemic, a novel syndrome termed “multisystem inflammatory syndrome in children” (MIS-C) has emerged. MIS-C was linked to COVID-19 and shared some features with Kawasaki disease and Toxic Shock Syndrome, with a common pathogenetic substrate of hyperinflammation and cytokine storm. Lately, MIS was also described in adults (≥21 years of age) and named “MIS-A”. There is no consensus about the treatment of MIS-A; successful use of glucocorticoids and immunoglobulins has been reported in case series, but more solid evidence is lacking. Furthermore, the role of biologic agents with proven benefits against COVID-19, MIS-C, or Kawasaki disease is still unexplored. In this report, we detail the clinical picture and the diagnostic process that led to the diagnosis of MIS-A in a 27-year-old man, focusing on its treatment with anakinra and glucocorticoids, which resulted in full recovery. To our knowledge, this is the first report of the successful use of anakinra for MIS-A, a drug that has already proven useful in the treatment of refractive cases of MIS-C. Anakinra may also play a pivotal role for the treatment of MIS-A.
A Salmonella Typhi Controlled Human Infection Study for Assessing Correlation between Bactericidal Antibodies and Protection against Infection Induced by Typhoid Vaccination
Authors: Jones Elizabeth , Jin Celina , Stockdale Lisa , Dold Christina , Pollard Andrew J. , Hill Jennifer
Published: June 2021

Vi-polysaccharide conjugate vaccines are efficacious against typhoid fever in children living in endemic settings, their recent deployment is a promising step in the control of typhoid fever. However, there is currently no accepted correlate of protection. IgG and IgA antibodies generated in response to Vi conjugate or Vi plain polysaccharide vaccination are important but there are no definitive protective titre thresholds. We adapted a luminescence-based serum bactericidal activity (SBA) for use with S. Typhi and assessed whether bactericidal antibodies induced by either Vi tetanus toxoid conjugate (Vi-TT) or Vi plain polysaccharide (Vi-PS) were associated with protection in a controlled human infection model of typhoid fever. Both Vi-PS and Vi-TT induced significant increase in SBA titre after 28 days (Vi-PS; p < 0.0001, Vi-TT; p = 0.003), however higher SBA titre at the point of challenge did not correlate with protection from infection or reduced symptom severity. We cannot eliminate the role of SBA as part of a multifactorial immune response which protects against infection, however, our results do not support a strong role for SBA as a mechanism of Vi vaccine mediated protection in the CHIM setting.
Conversion of the Sensor Kinase DcuS to the Fumarate Sensitive State by Interaction of the Bifunctional Transporter DctA at the TM2/PASC-Linker Region
Authors: Stopp Marius , Schubert Christopher , Unden Gottfried
Published: June 2021

The membrane-bound C4-dicarboxylate (C4DC) sensor kinase DcuS of Escherichia coli typically forms a protein complex with the C4DC transporter DctA. The DctA × DcuS complex is able to respond to C4DCs, whereas DcuS without DctA is in the permanent ON state. In DctA, the C-terminal helix 8b (H8b) serves as the site for interaction with DcuS. Here the interaction site in DcuS and the related structural and functional adaptation in DcuS were determined. The Linker connecting transmembrane helix 2 (TM2) and the cytosolic PASC (Per-ARNT-SIM) domain of DcuS, was identified as the major site for interaction with DctA-H8b by in vivo interaction studies. The Linker is known to convert the piston-type transmembrane signaling of TM2 to a tilting motion which relies on a resolution of the Linker-Linker’ homodimer in the presence of C4DCs. Absence of DctA caused decreased cross-linking in the Linker, as identified by oxidative Cys-cross-linking. This response resembled structurally and functionally that of fumarate activation in the DctA × DcuS complex. Overall, formation of the DctA × DcuS complex is based on the interaction of the DcuS Linker with DctA H8b; the interaction is required to set DcuS in the C4DC-responsive state by stabilizing the linker-linker’ homodimer in DcuS. This work identifies DctA as a structural co-regulator of DcuS sensor kinase.
Presence of Francisella tularensis subsp. holarctica DNA in the Aquatic Environment in France
Authors: Brunet Camille D. , Hennebique Aurélie , Peyroux Julien , Pelloux Isabelle , Caspar Yvan , Maurin Max
Published: June 2021

In 2018, the incidence of tularemia increased twofold in the west of France, with many pneumonic forms, suggesting environmental sources of infection. We investigated the presence of Francisellatularensis subsp. holarctica and other Francisella species DNA in the natural aquatic environment of this geographic area. Two sampling campaigns, in July 2019 and January 2020, allowed the collection of 87 water samples. Using a combination of real-time PCR assays, we tested the presence of either Francisella sp., F. tularensis/F. novicida, and F. tularensis subsp. holarctica, the latter being the only tularemia agent in Europe. Among 57 water samples of the first campaign, 15 (26.3%) were positive for Francisella sp., nine (15.8%) for F. tularensis and/or F. novicida, and four (7.0%) for F. tularensis subsp. holarctica. Ratios were 25/30 (83.3%), 24/30 (80.0%), and 4/30 (13.3%) for the second campaign. Among the thirty sites sampled during the two campaigns, nine were positive both times for Francisella sp., seven for F. tularensis and/or F. novicida, and one for F. tularensis subsp. holarctica. Altogether, our study reveals a high prevalence of Francisella sp. DNA (including the tularemia agent) in the studied aquatic environment. This aquatic environment could therefore participate in the endemicity of tularemia in the west of France.
Development and Characterization of Functional Starch-Based Films Incorporating Free or Microencapsulated Spent Black Tea Extract
Authors: Rajapaksha Surakshi Wimangika , Shimizu Naoto
Published: June 2021

Antioxidant polyphenols in black tea residue are an underused source of bioactive compounds. Microencapsulation can turn them into a valuable functional ingredient for different food applications. This study investigated the potential of using spent black tea extract (SBT) as an active ingredient in food packaging. Free or microencapsulated forms of SBT, using a pectin–sodium caseinate mixture as a wall material, were incorporated in a cassava starch matrix and films developed by casting. The effect of incorporating SBT at different polyphenol contents (0.17% and 0.34%) on the structural, physical, and antioxidant properties of the films, the migration of active compounds into different food simulants and their performance at preventing lipid oxidation were evaluated. The results showed that adding free SBT modified the film structure by forming hydrogen bonds with starch, creating a less elastic film with antioxidant activity (173 and 587 µg(GAE)/g film). Incorporating microencapsulated SBT improved the mechanical properties of active films and preserved their antioxidant activity (276 and 627 µg(GAE)/g film). Encapsulates significantly enhanced the release of antioxidant polyphenols into both aqueous and fatty food simulants. Both types of active film exhibited better barrier properties against UV light and water vapour than the control starch film and delayed lipid oxidation up to 35 d. This study revealed that starch film incorporating microencapsulated SBT can be used as a functional food packaging to protect fatty foods from oxidation.
Ginger Essential Oils-Loaded Nanoemulsions: Potential Strategy to Manage Bacterial Leaf Blight Disease and Enhanced Rice Yield
Authors: Adamu Abdullahi , Ahmad Khairulmazmi , Siddiqui Yasmeen , Ismail Intan Safinar , Asib Norhayu , Bashir Kutawa Abdulaziz , Adzmi Fariz , Ismail Mohd Razi , Berahim Zulkarami
Published: June 2021

The bacterial leaf blight (BLB) caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most serious rice diseases, causing huge yield losses worldwide. Several technologies and approaches have been opted to reduce the damage; however, these have had limited success. Recently, scientists have been focusing their efforts on developing efficient and environmentally friendly nanobactericides for controlling bacterial diseases in rice fields. In the present study, a scanning electron microscope (SEM), transmission electron microscope (TEM), and a confocal laser scanning microscope (CLSM) were utilized to investigate the mode of actions of ginger EOs on the cell structure of Xoo. The ginger EOs caused the cells to grow abnormally, resulting in an irregular form with hollow layers, whereas the dimethylsulfoxide (DMSO) treatment showed a typical rod shape for the Xoo cell. Ginger EOs restricted the growth and production of biofilms by reducing the number of biofilms generated as indicated by CLSM. Due to the instability, poor solubility, and durability of ginger EOs, a nanoemulsions approach was used, and a glasshouse trial was performed to assess their efficacy on BLB disease control. The in vitro antibacterial activity of the developed nanobactericides was promising at different concentration (50–125 µL/mL) tested. The efficacy was concentration-dependent. There was significant antibacterial activity recorded at higher concentrations. A glasshouse trial revealed that developed nanobactericides managed to suppress BLB disease severity effectively. Treatment at a concentration of 125 μL/mL was the best based on the suppression of disease severity index, AUDPC value, disease reduction (DR), and protection index (PI). Furthermore, findings on plant growth, physiological features, and yield parameters were significantly enhanced compared to the positive control treatment. In conclusion, the results indicated that ginger essential oils loaded-nanoemulsions are a promising alternative to synthetic antibiotics in suppressing Xoo growth, regulating the BLB disease, and enhancing rice yield under a glasshouse trial.
Review of Functional and Pharmacological Activities of Berries
Authors: Golovinskaia Oksana , Wang Chin-Kun
Published: June 2021

Functional plant-based foods (such as fruits, vegetables, and berries) can improve health, have a preventive effect, and diminish the risk of different chronic diseases during in vivo and in vitro studies. Berries contain many phytochemicals, fibers, vitamins, and minerals. The primary phytochemicals in berry fruits are phenolic compounds including flavonoids (anthocyanins, flavonols, flavones, flavanols, flavanones, and isoflavonoids), tannins, and phenolic acids. Since berries have a high concentration of polyphenols, it is possible to use them for treating various diseases pharmacologically by acting on oxidative stress and inflammation, which are often the leading causes of diabetes, neurological, cardiovascular diseases, and cancer. This review examines commonly consumed berries: blackberries, blackcurrants, blueberries, cranberries, raspberries, black raspberries, and strawberries and their polyphenols as potential medicinal foods (due to the presence of pharmacologically active compounds) in the treatment of diabetes, cardiovascular problems, and other diseases. Moreover, much attention is paid to the bioavailability of active berry components. Hence, this comprehensive review shows that berries and their bioactive compounds possess medicinal properties and have therapeutic potential. Nevertheless, future clinical trials are required to study and improve the bioavailability of berries’ phenolic compounds and extend the evidence that the active compounds of berries can be used as medicinal foods against various diseases.
Understanding the Impact of Key Wine Components on the Use of a Non-Swelling Ion-Exchange Resin for Wine Protein Fining Treatment
Authors: Sun Lin , Srinivas Ananya , Runnebaum Ron C.
Published: June 2021

The impact of key classes of compounds found in wine on protein removal by the ion-exchange resin, Macro-Prep® High S, was examined by adsorption isotherm experiments. A model wine system, which contained a prototypical protein Bovine Serum Albumin (BSA), was used. We systematically changed concentrations of individual chemical components to generate and compare adsorption isotherm plots and to quantify adsorption affinity or capacity parameters of Macro-Prep® High S ion-exchange resin. The pH (hydronium ion concentration), ethanol concentration, and prototypical phenolics and polysaccharide compounds are known to impact interactions with proteins and thus could alter the adsorption affinity and capacity of Macro-Prep® High S ion-exchange resin. At low equilibrium protein concentrations (< ~0.3 (g BSA)/L) and at high equilibrium protein concentrations in model wines at various pH, the adsorption behavior followed the Langmuir isotherm, most likely due to the resin acting as a monolayer adsorbent. The resulting range of BSA capacity was between 0.15–0.18 (g BSA)/(g Macro-Prep® High S resin). With the addition of ethanol, catechin, caffeic acid, and polysaccharides, the protein adsorption behavior was observed to differ at higher equilibrium protein concentrations (> ~0.3 (g BSA)/L), likely as a result of Macro-Prep® acting as an unrestricted multilayer adsorbent at these conditions. These data can be used to inform the design and scale-up of ion-exchange columns for removing proteins from wines.
Comparison of the Phytochemical Composition and Antibacterial Activities of the Various Extracts from Leaves and Twigs of Illicium verum
Authors: Yang Emirlyn-Cheng , Hsieh Ya-Yun , Chuang Li-Yeh
Published: June 2021

Previous studies have revealed the numerous biological activities of the fruits of Illicium verum; however, the activities of its leaves and twigs have remained undiscovered. The study aimed to investigate the phytochemical components and antibacterial activity of the various extracts from the leaves and twigs of Illicium verum. The herbal extracts were prepared by supercritical CO2 extraction (SFE) and 95% ethanol extraction, followed by partition extraction based on solvent polarity. Analysis of antimicrobial activity was conducted through the usage of nine clinical antibiotic- resistant isolates, including Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii. Among the tested samples, the SFE extracts exhibited broader and stronger antibacterial activities against the test strains, with a range of MIC between 0.1–4.0 mg/mL and MBC between 0.2–4.5 mg/mL. Observations made through scanning electron microscopy revealed potential mechanism of the antimicrobial activities involved disruption of membrane integrity of the test pathogens. Evaluation of the chemical composition by gas chromatography-mass spectrometry indicated the presence of anethole, anisyl aldehyde, anisyl acetone and anisyl alcohol within the SFE extracts, demonstrating significant correlations with the antibacterial activities observed. Therefore, the leaves and twigs of Illicium verum hold great potential in being developed as new natural antibacterial agents.
Molecular Modifications and Control of Processes to Facilitate the Synergistic Degradation of Polybrominated Diphenyl Ethers in Soil by Plants and Microorganisms Based on Queuing Scoring Method
Authors: Wu Tong , Li Yu , Xiao Hailin , Fu Mingli
Published: June 2021

In this paper, a combination of modification of the source and regulation of the process was used to control the degradation of PBDEs by plants and microorganisms. First, the key proteins that can degrade PBDEs in plants and microorganisms were searched in the PDB (Protein Data Bank), and a molecular docking method was used to characterize the binding ability of PBDEs to two key proteins. Next, the synergistic binding ability of PBDEs to the two key proteins was evaluated based on the queuing integral method. Based on this, three groups of three-dimensional quantitative structure-activity relationship (3D-QSAR) models of plant-microbial synergistic degradation were constructed. A total of 30 PBDE derivatives were designed using BDE-3 as the template molecule. Among them, the effect on the synergistic degradation of six PBDE derivatives, including BDE-3-4, was significantly improved (increased by more than 20%) and the environment-friendly and functional evaluation parameters were improved. Subsequently, studies on the synergistic degradation of PBDEs and their derivatives by plants and microorganisms, based on the molecular docking method, found that the addition of lipophilic groups by modification is beneficial to enhance the efficiency of synergistic degradation of PBDEs by plants and microorganisms. Further, while docking PBDEs, the number of amino acids was increased and the binding bond length was decreased compared to the template molecules, i.e., PBDE derivatives could be naturally degraded more efficiently. Finally, molecular dynamics simulation by the Taguchi orthogonal experiment and a full factorial experimental design were used to simulate the effects of various regulatory schemes on the synergistic degradation of PBDEs by plants and microorganisms. It was found that optimal regulation occurred when the appropriate amount of carbon dioxide was supplied to the plant and microbial systems. This paper aims to provide theoretical support for enhancing the synergistic degradation of PBDEs by plants and microorganisms in e-waste dismantling sites and their surrounding polluted areas, as well as, realize the research and development of green alternatives to PBDE flame retardants.
Activity of Compounds from Temperate Propolis against Trypanosoma brucei and Leishmania mexicana
Authors: Alotaibi Adullah , Ebiloma Godwin U. , Williams Roderick , Alfayez Ibrahim A. , Natto Manal J. , Alenezi Sameah , Siheri Weam , AlQarni Malik , Igoli John O. , Fearnley James , De Koning Harry P. , Watson David G.
Published: June 2021

Ethanolic extracts of samples of temperate zone propolis, four from the UK and one from Poland, were tested against three Trypanosoma brucei strains and displayed EC50 values < 20 µg/mL. The extracts were fractionated, from which 12 compounds and one two-component mixture were isolated, and characterized by NMR and high-resolution mass spectrometry, as 3-acetoxypinobanksin, tectochrysin, kaempferol, pinocembrin, 4′-methoxykaempferol, galangin, chrysin, apigenin, pinostrobin, cinnamic acid, coumaric acid, cinnamyl ester/coumaric acid benzyl ester (mixture), 4′,7-dimethoxykaempferol, and naringenin 4′,7-dimethyl ether. The isolated compounds were tested against drug-sensitive and drug-resistant strains of T. brucei and Leishmania mexicana, with the highest activities ≤ 15 µM. The most active compounds against T. brucei were naringenin 4′,7 dimethyl ether and 4′methoxy kaempferol with activity of 15–20 µM against the three T. brucei strains. The most active compounds against L. mexicana were 4′,7-dimethoxykaempferol and the coumaric acid ester mixture, with EC50 values of 12.9 ± 3.7 µM and 13.1 ± 1.0 µM. No loss of activity was found with the diamidine- and arsenical-resistant or phenanthridine-resistant T. brucei strains, or the miltefosine-resistant L. mexicana strain; no clear structure activity relationship was observed for the isolated compounds. Temperate propolis yields multiple compounds with anti-kinetoplastid activity.
Synthesis of 2-Substitued Indoles via Pd-Catalysed Cyclization in an Aqueous Micellar Medium
Authors: Siciliano Sofia , Cini Elena , Taddei Maurizio , Vinciarelli Giorgia
Published: June 2021

The synthesis of 2-substituted indoles starting from the corresponding unprotected 2-alkynylanilines was made possible in 3% TPGS-750-M water using Pd(OAc)2 alone as the catalyst. The reaction was sensitive to the heating mode respect to the nature of the starting material as, in many cases, convectional heating was better than microwave dielectric heating. The MW (microwave) delivery mode had also an influence in the formation of by-products and, consequently, product yields. A tandem Sonogashira-cyclisation reaction was also accomplished using Pd(OAc)2/Xphos in the nanomicellar water environment.
Synthesis, Enantiomeric Resolution and Biological Evaluation of HIV Capsid Inhibition Activity for Racemic, (S)- and (R)-PF74
Authors: Ruddell Stuart , Sugrue Elena , Memarzadeh Sarah , Hellam Lorna Mae , Wilson Sam J. , France David J.
Published: June 2021

PF74 is a capsid-targeting inhibitor of HIV replication that effectively perturbs the highly sensitive viral uncoating process. A lack of information regarding the optical purity (enantiomeric excess) of the single stereogenic centre of PF74 has resulted in ambiguity as to the potency of different samples of this compound. Herein is described the synthesis of enantiomerically enriched (S)- and (R)-PF74 and further enrichment of the samples (≥98%) using chiral HPLC resolution. The biological activities of each enantiomer were then evaluated, which determined (S)-PF74 (IC50 1.5 µM) to be significantly more active than (R)-PF74 (IC50 19 µM). Computational docking studies were then conducted to rationalise this large discrepancy in activity, which indicated different binding conformations for each enantiomer. The binding energy of the conformation adopted by the more active (S)-PF74 (ΔG = −73.8 kcal/mol) was calculated to be more favourable than the conformation adopted by the less active (R)-enantiomer (ΔG = −55.8 kcal/mol) in agreement with experimental observations.
Insertion of Phosphenium Ions into a Bicyclo[1.1.0]Tetraphosphabutane Iron Complex
Authors: Weber Martin , Balázs Gábor , Virovets Alexander V. , Peresypkina Eugenia , Scheer Manfred
Published: June 2021

By reacting [{Cp‴Fe(CO)2}2(µ,η1:1-P4)] (1) with in situ generated phosphenium ions [Ph2P][A] ([A]− = [OTf]− = [O3SCF3]−, [PF6]−), a mixture of two main products of the composition [{Cp‴Fe(CO)2}2(µ,η1:1-P5(C6H5)2)][PF6] (2a and 3a) could be identified by extensive 31P NMR spectroscopic studies at 193 K. Compound 3a was also characterized by X-ray diffraction analysis, showing the rarely observed bicyclo[2.1.0]pentaphosphapentane unit. At room temperature, the novel compound [{Cp‴Fe}(µ,η4:1-P5Ph2){Cp‴(CO)2Fe}][PF6] (4) is formed by decarbonylation. Reacting 1 with in situ generated diphenyl arsenium ions gives short-lived intermediates at 193 K which disproportionate at room temperature into tetraphenyldiarsine and [{Cp‴Fe(CO)2}4(µ4,η1:1:1:1-P8)][OTf]2 (5) containing a tetracyclo[3.3.0.02,7.03,6]octaphosphaoctane ligand.
A Transcriptomic Approach to the Metabolism of Tetrapyrrolic Photosensitizers in a Marine Annelid
Authors: Santos Maria Leonor , D’Ambrosio Mariaelena , Rodrigo Ana P. , Parola A. Jorge , Costa Pedro M.
Published: June 2021

The past decade has seen growing interest in marine natural pigments for biotechnological applications. One of the most abundant classes of biological pigments is the tetrapyrroles, which are prized targets due their photodynamic properties; porphyrins are the best known examples of this group. Many animal porphyrinoids and other tetrapyrroles are produced through heme metabolic pathways, the best known of which are the bile pigments biliverdin and bilirubin. Eulalia is a marine Polychaeta characterized by its bright green coloration resulting from a remarkably wide range of greenish and yellowish tetrapyrroles, some of which have promising photodynamic properties. The present study combined metabolomics based on HPLC-DAD with RNA-seq transcriptomics to investigate the molecular pathways of porphyrinoid metabolism by comparing the worm’s proboscis and epidermis, which display distinct pigmentation patterns. The results showed that pigments are endogenous and seemingly heme-derived. The worm possesses homologs in both organs for genes encoding enzymes involved in heme metabolism such as ALAD, FECH, UROS, and PPOX. However, the findings also indicate that variants of the canonical enzymes of the heme biosynthesis pathway can be species- and organ-specific. These differences between molecular networks contribute to explain not only the differential pigmentation patterns between organs, but also the worm’s variety of novel endogenous tetrapyrrolic compounds.
Capsaicin-Sensitive Vagal Afferent Nerve-Mediated Interoceptive Signals in the Esophagus
Authors: Yu Mingwei , Chang Crystal , Undem Bradley J. , Yu Shaoyong
Published: June 2021

Heartburn and non-cardiac chest pain are the predominant symptoms in many esophageal disorders, such as gastroesophageal reflux disease (GERD), non-erosive reflux disease (NERD), functional heartburn and chest pain, and eosinophilic esophagitis (EoE). At present, neuronal mechanisms underlying the process of interoceptive signals in the esophagus are still less clear. Noxious stimuli can activate a subpopulation of primary afferent neurons at their nerve terminals in the esophagus. The evoked action potentials are transmitted through both the spinal and vagal pathways to their central terminals, which synapse with the neurons in the central nervous system to induce esophageal nociception. Over the last few decades, progress has been made in our understanding on the peripheral and central neuronal mechanisms of esophageal nociception. In this review, we focus on the roles of capsaicin-sensitive vagal primary afferent nodose and jugular C-fiber neurons in processing nociceptive signals in the esophagus. We briefly compare their distinctive phenotypic features and functional responses to mechanical and chemical stimulations in the esophagus. Then, we summarize activation and/or sensitization effects of acid, inflammatory cells (eosinophils and mast cells), and mediators (ATP, 5-HT, bradykinin, adenosine, S1P) on these two nociceptive C-fiber subtypes. Lastly, we discuss the potential roles of capsaicin-sensitive esophageal afferent nerves in processing esophageal sensation and nociception. A better knowledge of the mechanism of nociceptive signal processes in primary afferent nerves in the esophagus will help to develop novel treatment approaches to relieve esophageal nociceptive symptoms, especially those that are refractory to proton pump inhibitors.
Small Angle X-ray Scattering, Molecular Modeling, and Chemometric Studies from a Thrombin-Like (Lmr-47) Enzyme of Lachesis m. rhombeata Venom
Authors: De-Simone Salvatore Giovanni , Lechuga Guilherme Curty , Napoleão-Pêgo Paloma , Gomes Larissa Rodrigues , Provance David William , Nirello Vinícius Dias , Sodero Ana Carolina Rennó , Guedes Herbert Leonel de Mattos
Published: June 2021

Introduction: Snakebite envenomation is considered a neglected tropical disease, and SVTLEs critical elements are involved in serious coagulopathies that occur on envenoming. Although some enzymes of this group have been structurally investigated, it is essential to characterize other proteins to better understand their unique properties such as the Lachesis muta rhombeata 47 kDa (Lmr-47) venom serine protease. Methods: The structure of Lmr-47 was studied in solution, using SAXS, DLS, CD, and in silico by homology modeling. Molecular docking experiments simulated 21 competitive inhibitors. Results: At pH 8.0, Lmr-47 has an Rg of 34.5 ± 0.6 Å, Dmax of 130 Å, and SR of 50 Å, according to DLS data. Kratky plot analysis indicates a rigid shape at pH 8.0. Conversely, the pH variation does not change the center of mass’s intrinsic fluorescence, possibly indicating the absence of fluorescent amino acids in the regions affected by pH variation. CD experiments show a substantially random coiled secondary structure not affected by pH. The low-resolution model of Lmr-47 presented a prolate elongated shape at pH 8.0. Using the 3D structure obtained by molecular modeling, docking experiments identified five good and three suitable competitive inhibitors. Conclusion: Together, our work provided insights into the structure of the Lmr-47 and identified inhibitors that may enhance our understanding of thrombin-like family proteins.
Development of a High-Fibre Multigrain Bar Technology with the Addition of Curly Kale
Authors: Kowalska Hanna , Kowalska Jolanta , Ignaczak Anna , Masiarz Ewelina , Domian Ewa , Galus Sabina , Ciurzyńska Agnieszka , Salamon Agnieszka , Zając Agnieszka , Marzec Agata
Published: June 2021

The aim of this study was to find the effect of kale and dietary fibre (DF) on the physicochemical properties, nutritional value and sensory quality of multigrain bars. A recipe of multigrain bars was prepared with the addition of fresh kale (20% and 30%) and DF preparations (apple, blackcurrant, chokeberry and hibiscus). The bars were baked at 180 °C for 20 min. These snack bars, based on pumpkin seeds, sunflower seeds, flaxseed and wholegrain oatmeal, are a high-calorie product (302–367 kcal/100 g). However, the composition of the bars encourages consumption. In addition to the ability to quickly satisfy hunger, such bars are rich in many natural ingredients that are considered pro-health (high fibre content (9.1–11.6 g/100 g), protein (11.2–14.3 g/100 g), fat (17.0–21.1 g/100 g, including unsaturated fatty acids), carbohydrates (20.5–24.0 g/100 g), as well as vitamins, minerals and a large number of substances from the antioxidant group. The addition of kale caused a significant increase of water content, but reduction in the value of all texture parameters (TPA profiles) as well as calorific values. The content of polyphenols was strongly and positively correlated with the antioxidant activity (r = 0.92). In the bars with 30% addition of kale (422 mg GA/100 g d.m.), the content of polyphenols was significantly higher than based ones (334 mg GA/100 g d.m.). Bars with the addition of the DF were characterized by a higher antioxidant activity, and the content of carotenoids, chlorophyll A and B and polyphenols. High sensory quality was demonstrated for all (from 4.8 to 7.1 on a 10-point scale). The addition of fibre preparations was also related to technological aspects and allows to create attractive bars without additional chemicals.
1,3,5-Triazine Nitrogen Mustards with Different Peptide Group as Innovative Candidates for AChE and BACE1 Inhibitors
Authors: Maliszewski Dawid , Wróbel Agnieszka , Kolesińska Beata , Frączyk Justyna , Drozdowska Danuta
Published: June 2021

A series of new analogs of nitrogen mustards (4a–4h) containing the 1,3,5-triazine ring substituted with dipeptide residue were synthesized and evaluated for the inhibition of both acetylcholinesterase (AChE) and β-secretase (BACE1) enzymes. The AChE inhibitory activity studies were carried out using Ellman’s colorimetric method, and the BACE1 inhibitory activity studies were carried out using fluorescence resonance energy transfer (FRET). All compounds displayed considerable AChE and BACE1 inhibition. The most active against both AChE and BACE1 enzymes were compounds A and 4a, with an inhibitory concentration of AChE IC50 = 0.051 µM; 0.055 µM and BACE1 IC50 = 9.00 µM; 11.09 µM, respectively.
CD47 in the Brain and Neurodegeneration: An Update on the Role in Neuroinflammatory Pathways
Authors: Gheibihayat Seyed Mohammad , Cabezas Ricardo , Nikiforov Nikita G. , Jamialahmadi Tannaz , Johnston Thomas P. , Sahebkar Amirhossein
Published: June 2021

CD47 is a receptor belonging to the immunoglobulin (Ig) superfamily and broadly expressed on cell membranes. Through interactions with ligands such as SIRPα, TSP-1, integrins, and SH2-domain bearing protein tyrosine phosphatase substrate-1 (SHPS-1), CD47 regulates numerous functions like cell adhesion, proliferation, apoptosis, migration, homeostasis, and the immune system. In this aspect, previous research has shown that CD47 modulates phagocytosis via macrophages, the transmigration of neutrophils, and the activation of T-cells, dendritic cells, and B-cells. Moreover, several studies have reported the increased expression of the CD47 receptor in a variety of diseases, including acute lymphoblastic leukemia (ALL), chronic myeloid leukemia, non-Hodgkin’s lymphoma (NHL), multiple myeloma (MM), bladder cancer, acute myeloid leukemia (AML), Gaucher disease, Multiple Sclerosis and stroke among others. The ubiquitous expression of the CD47 cell receptor on most resident cells of the CNS has previously been established through different methodologies. However, there is little information concerning its precise functions in the development of different neurodegenerative pathologies in the CNS. Consequently, further research pertaining to the specific functions and roles of CD47 and SIRP is required prior to its exploitation as a druggable approach for the targeting of various neurodegenerative diseases that affect the human population. The present review attempts to summarize the role of both CD47 and SIRP and their therapeutic potential in neurodegenerative disorders.