bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Diversity and Structure of Apomictic and Sexually Reproducing Lindera Species (Lauraceae) in Japan
Authors: Nakamura Mizuho , Nanami Satoshi , Okuno Seiya , Hirota Shun K. , Matsuo Ayumi , Suyama Yoshihisa , Tokumoto Hayato , Yoshihara Shizue , Itoh Akira
Published: February 2021

Research Highlights: genetic diversity in populations were compared among related shrub species with different reproductive systems. Background and Objectives: Lindera species are dioecious trees or shrubs that produce seeds by mating of males and females. To evaluate the importance of genetic diversity for the persistence of natural populations, we compared genetic information among four Lindera species in Japan. Three are dioecious shrubs (Lindera praecox, Lindera umbellata, and Lindera obtusiloba) that produce seeds by sexual reproduction. The remaining species, Lindera glauca, reproduces by apomixis; only female plants are found in Japan. Materials and Methods: all four species were sampled across a wide geographic area, from Tohoku to Kyushu, Japan. Single nucleotide polymorphisms (SNPs) were detected by multiplexed ISSR genotyping by sequencing (MIG-seq) and the resulting genetic diversity parameters were compared among populations. Results: in all sexually reproducing species, the values of observed heterozygosity were close to the expected ones and the inbreeding coefficients were nearly 0. These results were supposed to be caused by their obligate outcrossing. The genetic difference increased, in ascending order, between a mother plant and its seeds, within populations, and across geographic space. We observed a substantial geographic component in the genetic structure of these species. For L. glauca, the genetic difference between a mother and its seeds, within populations, and across space were not significantly different from what would be expected from PCR errors. Genetic diversity within and among populations of L. glauca was extremely low. Conclusions: apomixis has the advantage of being able to found populations from a single individual, without mating, which may outweigh the disadvantages associated with the extremely low genetic diversity of L. glauca. This may explain why this species is so widely distributed in Japan. Provided that the current genotypes remain suited to environmental conditions, L. glauca may not be constrained by its limited genetic diversity.
Velocity Profile and Turbulence Structure Measurement Corrections for Sediment Transport-Induced Water-Worked Bed
Authors: Pu Jaan H.
Published: February 2021

When using point measurement for environmental or sediment laden flows, there is well-recognised risk for not having aligned measurements that causes misinterpretation of the measured velocity data. In reality, these kinds of mismeasurement mainly happen due to the misinterpretation of bed orientation caused by the complexity of its determination in natural flows, especially in bedload laden or rough bed flows. This study proposes a novel bed realignment method to improve the measured data benchmarking by three-dimensional (3D) bed profile orientation and implemented it into different sets of experimental data. More specifically, the effects of realignment on velocity profile and streamwise turbulence structure measurements were investigated. The proposed technique was tested against experimental data collected over a water-worked and an experimentally arranged well-packed beds. Different from the well-packed rough bed, the water-worked bed has been generated after long sediment transport and settling and hence can be used to verify the proposed bed-alignment technique thoroughly. During the flow analysis, the corrected velocity, turbulence intensity and Reynolds stress profiles were compared to the theoretical logarithmic law, exponential law and linear gravity (universal Reynolds stress distribution) profiles, respectively. It has been observed that the proposed method has improved the agreement of the measured velocity and turbulence structure data with their actual theoretical profiles, particularly in the near-bed region (where the ratio of the flow measurement vertical distance to the total water depth, z/h, is limited to ≤0.4).
Small Functional Foods: Comparative Phytochemical and Nutritional Analyses of Five Microgreens of the Brassicaceae Family
Authors: Marchioni Ilaria , Martinelli Marco , Ascrizzi Roberta , Gabbrielli Costanza , Flamini Guido , Pistelli Luisa , Pistelli Laura
Published: February 2021

Microgreens are the seedlings of herbs and vegetables which are harvested at the development stage of their two cotyledonary leaves, or sometimes at the emergence of their rudimentary first pair of true leaves. They are functional foods, the consumption of which is steadily increasing due to their high nutritional value. The species of the Brassicaceae family are good sources of bioactive compounds, with a favorable nutritional profile. The present study analyzed some phytochemical compounds with nutritional values, such as chlorophylls, polyphenols, carotenoids, anthocyanins, ascorbic acid, total and reducing sugars, and the antioxidant activity of five Brassicaceae species: broccoli (Brassica oleracea L.), daikon (Raphanus raphanistrum subsp. sativus (L.) Domin), mustard (Brassica juncea (L.) Czern.), rocket salad (Eruca vesicaria (L.) Cav.), and watercress (Nasturtium officinale R.Br.). Broccoli had the highest polyphenol, carotenoid and chlorophyll contents, as well as a good antioxidant ability. Mustard was characterized by high ascorbic acid and total sugar contents. By contrast, rocket salad exhibited the lowest antioxidant content and activity. The essential oil (EO) composition of all of these species was determined in order to identify their profile and isothiocyanates content, which are compounds with many reported health benefits. Isothiocyanates were the most abundant group in broccoli (4-pentenyl isothiocyanate), mustard (allyl isothiocyanate), and watercress (benzyl isothiocyanate) EOs, while rocket salad and daikon exhibited higher contents of monoterpene hydrocarbons (myrcene) and oxygenated diterpenes (phytol), respectively. Broccoli microgreens exhibited the overall best nutritional profile, appearing as the most promising species to be consumed as a functional food among those analyzed.
Physical Therapists’ Opinion of E-Health Treatment of Chronic Low Back Pain
Authors: Martínez de la Cal Jesús , Fernández-Sánchez Manuel , Matarán-Peñarrocha Guillermo Adolfo , Hurley Deirdre A. , Castro-Sánchez Adelaida María , Lara-Palomo Inmaculada Carmen
Published: February 2021

(1) Background: Using new technologies to manage home exercise programmes is an approach that allows more patients to benefit from therapy. The objective of this study is to explore physical therapists’ opinions of the efficacy and disadvantages of implementing a web-based telerehabilitation programme for treating chronic low back pain (CLBP). (2) Methods: Nineteen physical therapists from academic and healthcare fields in both the public and private sector participated in the qualitative study. Texts extracted from a transcript of semi-structured, individual, in-depth interviews with each consenting participant were analysed to obtain the participants’ prevailing opinions. The interviews lasted approximately 40 min each. The participants’ responses were recorded. (3) Results: The results suggest that telerehabilitation can only be successful if patients become actively involved in their own treatment. However, exercise programmes for LBP are not always adapted to patient preferences. New technologies allow physical therapists to provide their patients with the follow-up and remote contact they demand, but long-term adherence to treatment stems from knowledge of the exercises and the correct techniques employed by the patients themselves. (4) Conclusions: Physical therapists treating patients with chronic non-specific low back pain believe that new technologies can provide highly effective means of reaching a greater number of patients and achieving significant savings in healthcare costs, despite the limitations of a telerehabilitation approach in developing an appropriate and effective patient-based physiotherapy programme.
I Quit! Effects of Work-Family Policies on the Turnover Intention
Authors: Medina-Garrido José Aurelio , Biedma-Ferrer José María , Rodríguez-Cornejo María Vanessa
Published: February 2021

The retention of key human resources is a challenge and a necessity for any organisation. This paper analyses the impact of the existence and accessibility of work-family policies on the well-being of workers and their intention to leave the organisation. To test the proposed hypotheses, we applied a structural equation model based on the partial least squares path modelling (PLS-SEM) approach to a sample of 558 service sector workers. The results show that the existence and accessibility of work-family policies directly reduce the intention to leave the organisation. Moreover, this relationship also occurs indirectly, by mediating the well-being that is generated by these work-family policies. We also analysed the moderating role that gender and hierarchy could have in the above relationships. In addition to the above theoretical implications, this study has practical implications. The findings show that employees with family and work balance problems experience lower emotional well-being, more health problems and eventually higher turnover rates. To avoid these problems, management must focus not only on the implementation of work-family policies but also on their accessibility, without subsequent retaliation or prejudice to employees. Additionally, management should pay special attention to female managers, given their greater difficulty in balancing work and family life.
Cord Blood Adipocytokines and Body Composition in Early Childhood: A Systematic Review and Meta-Analysis
Authors: Bagias Christos , Sukumar Nithya , Weldeselassie Yonas , Oyebode Oyinlola , Saravanan Ponnusamy
Published: February 2021

Childhood obesity is a growing epidemic. Early identification of high-risk groups will allow for the development of prevention strategies. Cord blood adipocytokines have been previously examined as biomarkers predicting future obesity. We conducted a systematic review looking at the association between cord blood leptin and adiponectin with adiposity up to 5 years of age. A literature review was performed between January 1994 and August 2020 using two bibliographic databases (Medline/Pubmed and EMBASE) and was registered on PROSPERO (CRD42017069024). Studies using skinfold thickness and direct methods of assessing body composition in full term neonates were considered. Partial correlation and multiple regression models were used to present the results. Meta-analysis was performed, were possible, using a random effects model. Cochran’s Q test was used to assess heterogeneity and I2 statistics to calculate the percentage of variation across studies. The potential for publication bias was assessed using funnel plots. Data from 22 studies were retrieved and reviewed by two independent reviewers. Cord blood leptin was positively associated with adiposity at birth (r = 0.487; 95% CI: 0.444, 0.531) but was inversely related to adiposity up to 3 years of age. The association was not sustained at 5 years. There was a weak positive association between adiponectin in cord blood and adiposity at birth (r = 0.201; 95% CI: 0.125, 0.277). No correlation was found between cord blood adiponectin in young children, but data were limited. This review supports that cord blood leptin and adiponectin are associated with adiposity at birth. The results of this study provide insight into the role of adipocytokines at birth on future metabolic health and their potential use as risk stratification tools.
The Experiences of Grief and Personal Growth in University Students: A Qualitative Study
Authors: Tan Jovita , Andriessen Karl
Published: February 2021

Background: Experiencing the death of a close person, especially in emerging adults and students, can have profound effects on the bereaved individual’s life. As most research in this field has focused on negative effects of a loss, little is known about potential positive effects experienced by bereaved university students. This study investigated the experience of grief and personal growth in a sample of students from The University of Melbourne, Australia. Methods: Semi-structured interviews via Zoom/telephone with bereaved students (n = 14), who were invited to reflect on their loss and any personal growth potentially experienced. Thematic analysis of the data was based on a deductive and inductive approach. Results: The analysis identified four themes: (i) sharing of grief as a coping mechanism, (ii) balance between grief reactions and moving forward in life, (iii) lessons learned and personal growth, and (iv) adopting values from the deceased person and continuing bonds. Conclusions: Participants emphasized personal growth regarding self-perception and philosophical views on life. Following the loss, they preferred peer support, and used formal services only when they had a specific need. The findings indicate the importance of social support for bereaved students, and the complimentary role of peer and professional support. Hence, academic institutions should offer supportive services tailored to both students and professionals to help bereaved students.
The Effect of Chair-Based Exercise on Physical Function in Older Adults: A Systematic Review and Meta-Analysis
Authors: Klempel Natalie , Blackburn Nicole E. , McMullan Ilona L. , Wilson Jason J. , Smith Lee , Cunningham Conor , O’Sullivan Roger , Caserotti Paolo , Tully Mark A.
Published: February 2021

Physical activity is an important determinant of health in later life. The public health restrictions in response to COVID-19 have interrupted habitual physical activity behaviours in older adults. In response, numerous exercise programmes have been developed for older adults, many involving chair-based exercise. The aim of this systematic review was to synthesise the effects of chair-based exercise on the health of older adults. Ovid Medline, EMBASE, CINAHL, AMED, PyscInfo and SPORTDiscus databases were searched from inception to 1 April 2020. Chair-based exercise programmes in adults ≥50 years, lasting for at least 2 weeks and measuring the impact on physical function were included. Risk of bias of included studies were assessed using Cochrane risk of bias tool v2. Intervention content was described using TiDieR Criteria. Where sufficient studies (≥3 studies) reported data on an outcome, a random effects meta-analysis was performed. In total, 25 studies were included, with 19 studies in the meta-analyses. Seventeen studies had a low risk of bias and five had a high risk of bias. In this systematic review including 1388 participants, results demonstrated that chair-based exercise programmes improve upper extremity (handgrip strength: MD = 2.10; 95% CI = 0.76, 3.43 and 30 s arm curl test: MD = 2.82; 95% CI = 1.34, 4.31) and lower extremity function (30 s chair stand: MD 2.25; 95% CI = 0.64, 3.86). The findings suggest that chair-based exercises are effective and should be promoted as simple and easily implemented activities to maintain and develop strength for older adults.
Tactile Low Frequency Vibration in Dementia Management: A Scoping Review Protocol
Authors: Campbell Elsa A. , Kantor Jiří , Kantorová Lucia , Svobodová Zuzana , Wosch Thomas
Published: February 2021

Dementia is a growing issue in modern society. Non-pharmacological interventions such as music are suggested as the primary methods for symptom management. Therapeutic potential may also be found in sound/mechanical low frequency vibrations (LFV) that share the core characteristics of music, but these are lesser understood. The aim of the proposed scoping review is to explore the responses of persons with dementia to LFV, e.g., vibroacoustic therapy or whole-body vibration. The scoping review will follow the Joanna Briggs Institute methodology guidelines. An extensive search in BMC, CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, ERIC, MEDLINE (OvidSP), Pedro, ProQuest Central, PsycINFO, Scopus, Web of Science, and grey literature sources in Clinical Trials, Current Controlled Trials, Google Scholar, and manual search of relevant journals is planned to find all relevant research papers. The paper selection, full-text assessment, and data extraction will be performed by two independent reviewers. Participants’ responses to the interventions and the experiment designs, including methodological challenges, will be analysed and compared. Results may highlight potential gaps in reporting and comparing sound and mechanical vibration approaches and promote better understanding of their potential for managing the symptoms of dementia. Furthermore, the possible relationships between LFV and music-based interventions may become clearer.
A Ban on Smartphone Usage during Recess Increased Children’s Physical Activity
Authors: Pawlowski Charlotte Skau , Nielsen Jonas Vestergaard , Schmidt Tanja
Published: February 2021

School recess provides a unique opportunity for children to be active. However, many children perceive smartphones as a key barrier for engaging in physical activity during recess. The aim was to investigate if a ban on smartphone usage during recess changed children’s physical activity. During August–October 2020, children from grades 4–7 (10–14 years) at six Danish schools were banned from using their smartphones during recess for a four-week period. Questionnaire and systematic observation (SOPLAY) data were collected from 814 children before intervention (baseline) and 828 during the last week of intervention (follow-up). The mean frequency of physical activity significantly increased from baseline to follow-up (odds ratio = 1.370), as did physical activity on a moderate level (odds ratio = 1.387). Vigorous physical activity significantly decreased (odds ratio = 0.851). The increase in physical activity was found among both schools having outdoor and indoor recess, among both boys and girls, and nearly equally among grades 4–7. This suggests that implementing a ban on smartphone usage during recess would improve the everyday conditions for health among a broad range of schoolchildren. Future studies are needed to further investigate the association between recess physical activity and smartphone usage.
Greenhouse Gas Emissions and Energy Consumption of Coastal Ecosystem Enhancement Programme through Sustainable Artificial Reefs in Galicia
Authors: Carral Luis , Cartelle Barros Juan José , Carro Fidalgo Humberto , Camba Fabal Carolina , Munín Doce Alicia
Published: February 2021

The principle of sustainability should condition a project in which artificial reefs are being installed to protect biodiversity as well as enhance costal ecosystems. In particular, this principle should be taken into account in the logistical processes related to manufacture and transport. This study assesses the global warming potential (GWP) and cumulative energy demand (CED) of developing a coastal ecosystem enhancement programme in the estuary region of Galicia, north-western Spain. The focus is on the processes involved in creating green artificial reefs (GARs): manufacture, transport and installation. The starting point is the supply chain for the green artificial reef (GAR) units; greenhouse gas emissions (GHG) and energy needs for each phase are analysed. Various scenarios are considered to determine which options are indeed available when it comes to establishing the supply chain. Different types of energy supplies, different options for the location of production centres, as well as different means of transport were studied. Results reveal the critical phases for selecting how the GAR units must be produced, transported by road and sea and then installed in their permanent location.
Evaluation of Marine Agarose Biomaterials for Tissue Engineering Applications
Authors: Irastorza-Lorenzo Ainhoa , Sánchez-Porras David , Ortiz-Arrabal Olimpia , de Frutos María José , Esteban Emilio , Fernández Javier , Janer Agustín , Campos Antonio , Campos Fernando , Alaminos Miguel
Published: February 2021

Five agarose types (D1LE, D2LE, LM, MS8 and D5) were evaluated in tissue engineering and compared for the first time using an array of analysis methods. Acellular and cellular constructs were generated from 0.3–3%, and their biomechanical properties, in vivo biocompatibility (as determined by LIVE/DEAD, WST-1 and DNA release, with n = 6 per sample) and in vivo biocompatibility (by hematological and biochemical analyses and histology, with n = 4 animals per agarose type) were analyzed. Results revealed that the biomechanical properties of each hydrogel were related to the agarose concentration (p < 0.001). Regarding the agarose type, the highest (p < 0.001) Young modulus, stress at fracture and break load were D1LE, D2LE and D5, whereas the strain at fracture was higher in D5 and MS8 at 3% (p < 0.05). All agaroses showed high biocompatibility on human skin cells, especially in indirect contact, with a correlation with agarose concentration (p = 0.0074 for LIVE/DEAD and p = 0.0014 for WST-1) and type, although cell function tended to decrease in direct contact with highly concentrated agaroses. All agaroses were safe in vivo, with no systemic effects as determined by hematological and biochemical analysis and histology of major organs. Locally, implants were partially encapsulated and a pro-regenerative response with abundant M2-type macrophages was found. In summary, we may state that all these agarose types can be safely used in tissue engineering and that the biomechanical properties and biocompatibility were strongly associated to the agarose concentration in the hydrogel and partially associated to the agarose type. These results open the door to the generation of specific agarose-based hydrogels for definite clinical applications such as the human skin, cornea or oral mucosa.
Interaction of Conazole Pesticides Epoxiconazole and Prothioconazole with Human and Bovine Serum Albumin Studied Using Spectroscopic Methods and Molecular Modeling
Authors: Golianová Katarína , Havadej Samuel , Verebová Valéria , Uličný Jozef , Holečková Beáta , Staničová Jana
Published: February 2021

The interactions of epoxiconazole and prothioconazole with human serum albumin and bovine serum albumin were investigated using spectroscopic methods complemented with molecular modeling. Spectroscopic techniques showed the formation of pesticide/serum albumin complexes with the static type as the dominant mechanism. The association constants ranged from 3.80 × 104–6.45 × 105 L/mol depending on the pesticide molecule (epoxiconazole, prothioconazole) and albumin type (human or bovine serum albumin). The calculated thermodynamic parameters revealed that the binding of pesticides into serum albumin macromolecules mainly depended on hydrogen bonds and van der Waals interactions. Synchronous fluorescence spectroscopy and the competitive experiments method showed that pesticides bind to subdomain IIA, near tryptophan; in the case of bovine serum albumin also on the macromolecule surface. Concerning prothioconazole, we observed the existence of an additional binding site at the junction of domains I and III of serum albumin macromolecules. These observations were corroborated well by molecular modeling predictions. The conformation changes in secondary structure were characterized by circular dichroism, three-dimensional fluorescence, and UV/VIS absorption methods.
The Role of Central Serotonin Neurons and 5-HT Heteroreceptor Complexes in the Pathophysiology of Depression: A Historical Perspective and Future Prospects
Authors: Borroto-Escuela Dasiel O. , Ambrogini Patrizia , Chruścicka Barbara , Lindskog Maria , Crespo-Ramirez Minerva , Hernández-Mondragón Juan C. , Perez de la Mora Miguel , Schellekens Harriët , Fuxe Kjell
Published: February 2021

Serotonin communication operates mainly in the extracellular space and cerebrospinal fluid (CSF), using volume transmission with serotonin moving from source to target cells (neurons and astroglia) via energy gradients, leading to the diffusion and convection (flow) of serotonin. One emerging concept in depression is that disturbances in the integrative allosteric receptor–receptor interactions in highly vulnerable 5-HT1A heteroreceptor complexes can contribute to causing major depression and become novel targets for the treatment of major depression (MD) and anxiety. For instance, a disruption and/or dysfunction in the 5-HT1A-FGFR1 heteroreceptor complexes in the raphe-hippocampal serotonin neuron systems can contribute to the development of MD. It leads inter alia to reduced neuroplasticity and potential atrophy in the raphe-cortical and raphe-striatal 5-HT pathways and in all its forebrain networks. Reduced 5-HT1A auto-receptor function, increased plasticity and trophic activity in the midbrain raphe 5-HT neurons can develop via agonist activation of allosteric receptor–receptor interactions in the 5-HT1A-FGFR1 heterocomplex. Additionally, the inhibitory allosteric receptor–receptor interactions in the 5-HT1AR-5-HT2AR isoreceptor complex therefore likely have a significant role in modulating mood, involving a reduction of postjunctional 5-HT1AR protomer signaling in the forebrain upon activation of the 5-HT2AR protomer. In addition, oxytocin receptors (OXTRs) play a significant and impressive role in modulating social and cognitive related behaviors like bonding and attachment, reward and motivation. Pathological blunting of the OXTR protomers in 5-HT2AR and especially in 5-HT2CR heteroreceptor complexes can contribute to the development of depression and other types of psychiatric diseases involving disturbances in social behaviors. The 5-HTR heterocomplexes are novel targets for the treatment of MD.
Phosphodiesterase Inhibitors in Acute Lung Injury: What Are the Perspectives?
Authors: Mokra Daniela , Mokry Juraj
Published: February 2021

Despite progress in understanding the pathophysiology of acute lung damage, currently approved treatment possibilities are limited to lung-protective ventilation, prone positioning, and supportive interventions. Various pharmacological approaches have also been tested, with neuromuscular blockers and corticosteroids considered as the most promising. However, inhibitors of phosphodiesterases (PDEs) also exert a broad spectrum of favorable effects potentially beneficial in acute lung damage. This article reviews pharmacological action and therapeutical potential of nonselective and selective PDE inhibitors and summarizes the results from available studies focused on the use of PDE inhibitors in animal models and clinical studies, including their adverse effects. The data suggest that xanthines as representatives of nonselective PDE inhibitors may reduce acute lung damage, and decrease mortality and length of hospital stay. Various (selective) PDE3, PDE4, and PDE5 inhibitors have also demonstrated stabilization of the pulmonary epithelial–endothelial barrier and reduction the sepsis- and inflammation-increased microvascular permeability, and suppression of the production of inflammatory mediators, which finally resulted in improved oxygenation and ventilatory parameters. However, the current lack of sufficient clinical evidence limits their recommendation for a broader use. A separate chapter focuses on involvement of cyclic adenosine monophosphate (cAMP) and PDE-related changes in its metabolism in association with coronavirus disease 2019 (COVID-19). The chapter illuminates perspectives of the use of PDE inhibitors as an add-on treatment based on actual experimental and clinical trials with preliminary data suggesting their potential benefit.
Functionalization of Crosslinked Sodium Alginate/Gelatin Wet-Spun Porous Fibers with Nisin Z for the Inhibition of Staphylococcus aureus-Induced Infections
Authors: Homem Natália C. , Tavares Tânia D. , Miranda Catarina S. , Antunes Joana C. , Amorim M. Teresa P. , Felgueiras Helena P.
Published: February 2021

Nisin Z, an amphipathic peptide, with a significant antibacterial activity against Gram-positive bacteria and low toxicity in humans, has been studied for food preservation applications. Thus far, very little research has been done to explore its potential in biomedicine. Here, we report the modification of sodium alginate (SA) and gelatin (GN) blended microfibers, produced via the wet-spinning technique, with Nisin Z, with the purpose of eradicating Staphylococcus aureus-induced infections. Wet-spun SAGN microfibers were successfully produced at a 70/30% v/v of SA (2 wt%)/GN (1 wt%) polymer ratio by extrusion within a calcium chloride (CaCl2) coagulation bath. Modifications to the biodegradable fibers’ chemical stability and structure were then introduced via crosslinking with CaCl2 and glutaraldehyde (SAGNCL). Regardless of the chemical modification employed, all microfibers were labelled as homogeneous both in size (≈246.79 µm) and shape (cylindrical and defect-free). SA-free microfibers, with an increased surface area for peptide immobilization, originated from the action of phosphate buffer saline solution on SAGN fibers, were also produced (GNCL). Their durability in physiological conditions (simulated body fluid) was, however, compromised very early in the experiment (day 1 and 3, with and without Nisin Z, respectively). Only the crosslinked SAGNCL fibers remained intact for the 28 day-testing period. Their thermal resilience in comparison with the unmodified and SA-free fibers was also demonstrated. Nisin Z was functionalized onto the unmodified and chemically altered fibers at an average concentration of 178 µg/mL. Nisin Z did not impact on the fiber’s morphology nor on their chemical/thermal stability. However, the peptide improved the SA fibers (control) structural integrity, guaranteeing its stability for longer, in physiological conditions. Its main effect was detected on the time-kill kinetics of the bacteria S. aureus. SAGNCL and GNCL loaded with Nisin Z were capable of progressively eliminating the bacteria, reaching an inhibition superior to 99% after 24 h of culture. The peptide-modified SA and SAGN were not as effective, losing their antimicrobial action after 6 h of incubation. Bacteria elimination was consistent with the release kinetics of Nisin Z from the fibers. In general, data revealed the increased potential and durable effect of Nisin Z (significantly superior to its free, unloaded form) against S. aureus-induced infections, while loaded onto prospective biomedical wet-spun scaffolds.
The Role of IGF/IGF-1R Signaling in Hepatocellular Carcinomas: Stemness-Related Properties and Drug Resistance
Authors: Ngo Mai-Huong Thi , Jeng Han-Yin , Kuo Yung-Che , Diony Nanda Josephine , Brahmadhi Ageng , Ling Thai-Yen , Chang Te-Sheng , Huang Yen-Hua
Published: February 2021

Insulin-like Growth Factor (IGF)/IGF-1 Receptor (IGF-1R) signaling is known to regulate stem cell pluripotency and differentiation to trigger cell proliferation, organ development, and tissue regeneration during embryonic development. Unbalanced IGF/IGF-1R signaling can promote cancer cell proliferation and activate cancer reprogramming in tumor tissues, especially in the liver. Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death, with a high incidence and mortality rate in Asia. Most patients with advanced HCC develop tyrosine kinase inhibitor (TKI)-refractoriness after receiving TKI treatment. Dysregulation of IGF/IGF-1R signaling in HCC may activate expression of cancer stemness that leads to TKI refractoriness and tumor recurrence. In this review, we summarize the evidence for dysregulated IGF/IGF-1R signaling especially in hepatitis B virus (HBV)-associated HCC. The regulation of cancer stemness expression and drug resistance will be highlighted. Current clinical treatments and potential therapies targeting IGF/IGF-1R signaling for the treatment of HCC will be discussed.
Dermal Drivers of Injury-Induced Inflammation: Contribution of Adipocytes and Fibroblasts
Authors: Cooper Paula O. , Haas MaryEllen R. , Noonepalle Satish kumar R. , Shook Brett A.
Published: February 2021

Irregular inflammatory responses are a major contributor to tissue dysfunction and inefficient repair. Skin has proven to be a powerful model to study mechanisms that regulate inflammation. In particular, skin wound healing is dependent on a rapid, robust immune response and subsequent dampening of inflammatory signaling. While injury-induced inflammation has historically been attributed to keratinocytes and immune cells, a vast body of evidence supports the ability of non-immune cells to coordinate inflammation in numerous tissues and diseases. In this review, we concentrate on the active participation of tissue-resident adipocytes and fibroblasts in pro-inflammatory signaling after injury, and how altered cellular communication from these cells can contribute to irregular inflammation associated with aberrant wound healing. Furthering our understanding of how tissue-resident mesenchymal cells contribute to inflammation will likely reveal new targets that can be manipulated to regulate inflammation and repair.
Identification of Two Dysfunctional Variants in the ABCG2 Urate Transporter Associated with Pediatric-Onset of Familial Hyperuricemia and Early-Onset Gout
Authors: Toyoda Yu , Pavelcová Kateřina , Bohatá Jana , Ješina Pavel , Kubota Yu , Suzuki Hiroshi , Takada Tappei , Stiburkova Blanka
Published: February 2021

The ABCG2 gene is a well-established hyperuricemia/gout risk locus encoding a urate transporter that plays a crucial role in renal and intestinal urate excretion. Hitherto, p.Q141K—a common variant of ABCG2 exhibiting approximately one half the cellular function compared to the wild-type—has been reportedly associated with early-onset gout in some populations. However, compared with adult-onset gout, little clinical information is available regarding the association of other uricemia-associated genetic variations with early-onset gout; the latent involvement of ABCG2 in the development of this disease requires further evidence. We describe a representative case of familial pediatric-onset hyperuricemia and early-onset gout associated with a dysfunctional ABCG2, i.e., a clinical history of three generations of one Czech family with biochemical and molecular genetic findings. Hyperuricemia was defined as serum uric acid (SUA) concentrations 420 μmol/L for men or 360 μmol/L for women and children under 15 years on two measurements, performed at least four weeks apart. The proband was a 12-year-old girl of Roma ethnicity, whose SUA concentrations were 397–405 µmol/L. Sequencing analyses focusing on the coding region of ABCG2 identified two rare mutations—c.393G>T (p.M131I) and c.706C>T (p.R236X). Segregation analysis revealed a plausible link between these mutations and hyperuricemia and the gout phenotype in family relatives. Functional studies revealed that p.M131I and p.R236X were functionally deficient and null, respectively. Our findings illustrate why genetic factors affecting ABCG2 function should be routinely considered in clinical practice as part of a hyperuricemia/gout diagnosis, especially in pediatric-onset patients with a strong family history.
OTUD6A Is an Aurora Kinase A-Specific Deubiquitinase
Authors: Kim Hyo Jin , Kim Jongchan
Published: February 2021

Aurora kinases are serine/threonine kinases required for cell proliferation and are overexpressed in many human cancers. Targeting Aurora kinases has been a therapeutic strategy in cancer treatment. Here, we attempted to identify a deubiquitinase (DUB) that regulates Aurora kinase A (Aurora-A) protein stability and/or kinase activity as a potential cancer therapeutic target. Through pull-down assays with the human DUB library, we identified OTUD6A as an Aurora-A-specific DUB. OTUD6A interacts with Aurora-A through OTU and kinase domains, respectively, and deubiquitinates Aurora-A. Notably, OTUD6A promotes the protein half-life of Aurora-A and activates Aurora-A by increasing phosphorylation at threonine 288 of Aurora-A. From qPCR screening, we identified and validated that the cancer gene CKS2 encoding Cyclin-dependent kinases regulatory subunit 2 is the most upregulated cell cycle regulator when OTUD6A is overexpressed. The results suggest that OTUD6A may serve as a therapeutic target in human cancers.
Nanoparticles in the Food Industry and Their Impact on Human Gut Microbiome and Diseases
Authors: Ghebretatios Merry , Schaly Sabrina , Prakash Satya
Published: February 2021

The use of inorganic nanoparticles (NPs) has expanded into various industries including food manufacturing, agriculture, cosmetics, and construction. This has allowed NPs access to the human gastrointestinal tract, yet little is known about how they may impact human health. As the gut microbiome continues to be increasingly implicated in various diseases of unknown etiology, researchers have begun studying the potentially toxic effects of these NPs on the gut microbiome. Unfortunately, conflicting results have limited researcher’s ability to evaluate the true impact of NPs on the gut microbiome in relation to health. This review focuses on the impact of five inorganic NPs (silver, iron oxide, zinc oxide, titanium dioxide, and silicon dioxide) on the gut microbiome and gastrointestinal tract with consideration for various methodological differences within the literature. This is important as NP-induced changes to the gut could lead to various gut-related diseases. These include irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), celiac disease, and colorectal cancer. Research in this area is necessary as the use of NPs in various industries continues to grow along with the number of people suffering from chronic gastrointestinal diseases.
Development of Genetic Modification Tools for Hanseniasporauvarum
Authors: Badura Jennifer , van Wyk Niël , Brezina Silvia , Pretorius Isak S. , Rauhut Doris , Wendland Jürgen , von Wallbrunn Christian
Published: February 2021

Apiculate yeasts belonging to the genus Hanseniaspora are commonly isolated from viticultural settings and often dominate the initial stages of grape must fermentations. Although considered spoilage yeasts, they are now increasingly becoming the focus of research, with several whole-genome sequencing studies published in recent years. However, tools for their molecular genetic manipulation are still lacking. Here, we report the development of a tool for the genetic modification of Hanseniaspora uvarum. This was employed for the disruption of the HuATF1 gene, which encodes a putative alcohol acetyltransferase involved in acetate ester formation. We generated a synthetic marker gene consisting of the HuTEF1 promoter controlling a hygromycin resistance open reading frame (ORF). This new marker gene was used in disruption cassettes containing long-flanking (1000 bp) homology regions to the target locus. By increasing the antibiotic concentration, transformants were obtained in which both alleles of the putative HuATF1 gene were deleted in a diploid H. uvarum strain. Phenotypic characterisation including fermentation in Müller-Thurgau must showed that the null mutant produced significantly less acetate ester, particularly ethyl acetate. This study marks the first steps in the development of gene modification tools and paves the road for functional gene analyses of this yeast.
Instability of the NS1 Glycoprotein from La Reunion 2018 Dengue 2 Virus (Cosmopolitan-1 Genotype) in Huh7 Cells Is Due to Lysine Residues on Positions 272 and 324
Authors: Ogire Eva , Diaz Olivier , Vidalain Pierre-Olivier , Lotteau Vincent , Desprès Philippe , Roche Marjolaine
Published: February 2021

La Reunion island in the South West Indian Ocean is now endemic for dengue following the introduction of dengue virus serotype 2 (DENV-2) cosmopolitan-I genotype in 2017. DENV-2 infection causes a wide spectrum of clinical manifestations ranging from flu-like disease to severe dengue. The nonstructural glycoprotein 1 (NS1) has been identified as playing a key role in dengue disease severity. The intracellular NS1 exists as a homodimer, whereas a fraction is driven towards the plasma membrane or released as a soluble hexameric protein. Here, we characterized the NS1 glycoproteins from clinical isolates DES-14 and RUN-18 that were collected during the DENV-2 epidemics in Tanzania in 2014 and La Reunion island in 2018, respectively. In relation to hepatotropism of the DENV, expression of recombinant DES-14 NS1 and RUN-18 NS1 glycoproteins was compared in human hepatoma Huh7 cells. We observed that RUN-18 NS1 was poorly stable in Huh7 cells compared to DES-14 NS1. The instability of RUN-18 NS1 leading to a low level of NS1 secretion mostly relates to lysine residues on positions 272 and 324. Our data raise the issue of the consequences of a defect in NS1 stability in human hepatocytes in relation to the major role of NS1 in the pathogenesis of the DENV-2 infection.
Allosteric Modulation of GPCRs of Class A by Cholesterol
Authors: Jakubík Jan , El-Fakahany Esam E.
Published: February 2021

G-protein coupled receptors (GPCRs) are membrane proteins that convey extracellular signals to the cellular milieu. They represent a target for more than 30% of currently marketed drugs. Here we review the effects of membrane cholesterol on the function of GPCRs of Class A. We review both the specific effects of cholesterol mediated via its direct high-affinity binding to the receptor and non-specific effects mediated by cholesterol-induced changes in the properties of the membrane. Cholesterol binds to many GPCRs at both canonical and non-canonical binding sites. It allosterically affects ligand binding to and activation of GPCRs. Additionally, it changes the oligomerization state of GPCRs. In this review, we consider a perspective of the potential for the development of new therapies that are targeted at manipulating the level of membrane cholesterol or modulating cholesterol binding sites on to GPCRs.
Probing Protein Folding with Sequence-Reversed α-Helical Bundles
Authors: Kefala Aikaterini , Amprazi Maria , Mylonas Efstratios , Kotsifaki Dina , Providaki Mary , Pozidis Charalambos , Fotiadou Melina , Kokkinidis Michael
Published: February 2021

Recurrent protein folding motifs include various types of helical bundles formed by α-helices that supercoil around each other. While specific patterns of amino acid residues (heptad repeats) characterize the highly versatile folding motif of four-α-helical bundles, the significance of the polypeptide chain directionality is not sufficiently understood, although it determines sequence patterns, helical dipoles, and other parameters for the folding and oligomerization processes of bundles. To investigate directionality aspects in sequence-structure relationships, we reversed the amino acid sequences of two well-characterized, highly regular four-α-helical bundle proteins and studied the folding, oligomerization, and structural properties of the retro-proteins, using Circular Dichroism Spectroscopy (CD), Size Exclusion Chromatography combined with Multi-Angle Laser Light Scattering (SEC-MALS), and Small Angle X-ray Scattering (SAXS). The comparison of the parent proteins with their retro-counterparts reveals that while the α-helical character of the parents is affected to varying degrees by sequence reversal, the folding states, oligomerization propensities, structural stabilities, and shapes of the new molecules strongly depend on the characteristics of the heptad repeat patterns. The highest similarities between parent and retro-proteins are associated with the presence of uninterrupted heptad patterns in helical bundles sequences.
The Modeling and Forecasting of Carabid Beetle Distribution in Northwestern China
Authors: Liu Xueqin , Wang Hui , He Dahan , Wang Xinpu , Bai Ming
Published: February 2021

Beetles are key insect species in global biodiversity and play a significant role in steppe ecosystems. In the temperate steppe of China, the increasing degeneration of the grasslands threatens beetle species and their habitat. Using Generalized Additive Models (GAMs), we aimed to predict and map beetle richness patterns within the temperate steppe of Ningxia (China). We tested 19 environmental predictors including climate, topography, soil moisture and space as well as vegetation. Climatic variables (temperature, precipitation, soil temperature) consistently appeared among the most important predictors for beetle groups modeled. GAM generated predictive cartography for the study area. Our models explained a significant percentage of the variation in carabid beetle richness (79.8%), carabid beetle richness distribution seems to be mainly influenced by temperature and precipitation. The results have important implications for management and conservation strategies and also provides evidence for assessing and making predictions of beetle diversity across the steppe.
Expression of VEGF in Peripheral Serum Is a Possible Prognostic Factor in Bone-Regeneration via Masquelet-Technique—A Pilot Study
Authors: Tanner Michael C. , Boxriker Sonja , Haubruck Patrick , Child Christopher , Westhauser Fabian , Fischer Christian , Schmidmaier Gerhard , Moghaddam Arash
Published: February 2021

Two-step Masquelet-technique established a new procedure in the treatment of osseous defects, addressing prerequisites postulated by the “diamond concept”. Increase in blood perfusion and growth factors are enhanced by the “Masquelet-membrane”. To describe this, we measured serum levels of Vascular Endothelial Growth Factor (VEGF) of patients with atrophic non-unions of long bones undergoing Masquelet-technique. From over 500 non-union patients undergoing Masquelet-technique with prospective follow-up we randomly selected 30 patients. 23 were included, 7 lost to follow-up or excluded because of incomplete data. Serum was drawn at specified intervals before and after surgery. Patients were followed for at least 6 months after step 2. Classification into both groups was performed according to radiological results and clinical outcome 6 months after step 2. Concentration of VEGF in patients’ serum was performed via ELISA. 14 achieved osseous consolidation (responder group), 9 cases did not (non-responder). Responders showed a significant increase of serum-VEGF in the first and second week when compared to the preoperative values of step 1. Non-responders showed a significant increase of VEGF in the second week after Steps 1 and 2. Comparison of groups showed significantly higher increase of serum-VEGF week2 after step 1 and preoperative to step 2 for responders. Results show one possibility of illustrating therapeutic progress by monitoring growth factors and possibly allowing prognostic conclusions thereof. This might lead to a more targeted treatment protocol.
The Rheumatology Drugs for COVID-19 Management: Which and When?
Authors: Atzeni Fabiola , Masala Ignazio Francesco , Rodríguez-Carrio Javier , Ríos-Garcés Roberto , Gerratana Elisabetta , La Corte Laura , Giallanza Manuela , Nucera Valeria , Riva Agostino , Espinosa Gerard , Cervera Ricard
Published: February 2021

Introduction: While waiting for the development of specific antiviral therapies and vaccines to effectively neutralize the SARS-CoV2, a relevant therapeutic strategy is to counteract the hyperinflammatory status, characterized by an increase mainly of interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, and tumor necrosis factor (TNF)-α, which hallmarks the most severe clinical cases. ‘Repurposing’ immunomodulatory drugs and applying clinical management approved for rheumatic diseases represents a game-changer option. In this article, we will review the drugs that have indication in patients with COVID-19, including corticosteroids, antimalarials, anti-TNF, anti-IL-1, anti-IL-6, baricitinib, intravenous immunoglobulins, and colchicine. The PubMed, Medline, and Cochrane Library databases were searched for English-language papers concerning COVID-19 treatment published between January 2020 and October 2020. Results were summarized as a narrative review due to large heterogeneity among studies. In the absence of specific treatments, the use of immunomodulatory drugs could be advisable in severe COVID-19 patients, but clinical outcomes are still suboptimal. An early detection and treatment of the complications combined with a multidisciplinary approach could allow a better recovery of these patients.