bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-Wide Analysis of Purple Acid Phosphatase Genes in Brassica rapa and Their Association with Pollen Development and Phosphorus Deprivation Stress
Authors: Cai Yongfang , Qi Jiao , Li Chun , Miao Kehui , Jiang Baixue , Yang Xiaoshuang , Han Wenyu , Wang Yang , Gao Jing , Dong Xiangshu
Published: October 2021

PAPs (purple acid phosphatases) belong to the metallo-phosphoesterase superfamily and play important roles in developmental processes, phosphorus foraging, and recycling. However, the specific functions of BrPAPs in Brassica rapa are poorly understood. In this study, 39 BrPAPs were identified and divided into three major clades and nine subgroups. In 8 of the 39 BrPAPs, some invariant amino acid residues were lost or shifted. Based on an expression profiling analysis, BrPAP11, 14, 20, 24, 29, and 34 were specifically expressed in fertile floral buds, indicating their critical roles during pollen development. A total of 21 BrPAPs responded to Pi deprivation in either shoots or roots. Of these, BrPAP4, 5, 19, and 21 were upregulated in roots under Pi depravation conditions, while BrPAP12 was upregulated in the roots in normal conditions. BrPAP28 was upregulated in shoots under Pi depravation conditions, indicating its function shifted compared with its Arabidopsis homolog, AtPAP26. The present work contributes to further investigation of BrPAPs as candidate genes for genetic improvement studies of low phosphorus tolerance as well as for creating male sterile lines based on gene editing methods in Brassica rapa.
Phytochemical Traits and Biological Activity of Eryngium amethystinum and E. alpinum (Apiaceae)
Authors: Kremer Dario , Zovko Končić Marijana , Kosalec Ivan , Košir Iztok Jože , Potočnik Tanja , Čerenak Andreja , Srečec Siniša , Dunkić Valerija , Vuko Elma
Published: October 2021

Eryngium amethystinum L. is a wild vegetable used in Croatia. Both E. amethystinum and E. alpinum L. are decorative plants that can also be used in horticulture. To find out the hidden qualities of these two species, the following biological activities were studied: essential oil (EO) composition, analyzed by gas chromatography and gas chromatography with mass spectrometry (GC, GC–MS); phenolic compound content (PC), analyzed by high performance liquid chromatography (HPLC); total phenols as well as total flavonoids, analyzed by ultraviolet–visible spectrophotometry (UV/Vis); antioxidants, analyzed by 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity (DPPH), β-carotene-linoleic acid assay, chelating activity and reducing power of the extracts; and antimicrobial evaluation by micro-dilution assay and inhibition of Candida albicans blastospore germination. The major constituents of EO were β-caryophyllene (15.2%), α-pinene (10.2%) and 2,3,6-trimethylbenzaldehyde (9.3%) for E. amethystinum and caryophyllene oxide (27.9%), bicyclogermacrene (13.2%) and germacrene D (8.2%) for E. alpinum. The methanol extracts of both species showed a broad spectrum of antibacterial and antifungal activity with minimum inhibitory concentrations (MIC) less than or equal to 1.944 and 1.11 mg/mL, respectively.
Exploring Natural Alternatives for Annual Bluegrass Control
Authors: Taylor Jacob , McCarty Lambert , Kerr Robert
Published: October 2021

A field experiment was conducted to identify and examine the effectiveness of potential non-traditional chemical products and alternatives for controlling annual bluegrass (Poa annua L.), a plant with increasing herbicide resistant problems. In managed turf systems annual bluegrass can be a difficult winter annual weed to control having negative impacts on turfgrass quality. This study included 12 different treatments [untreated check, baking soda, white vinegar + lemon juice, Suppress herbicide, superphosphate (0-20-0), clove oil, Weed Zap, Avenger Weed Killer, Fiesta Turf Weed Killer, Ecologic Weed & Grass Killer, Alcohol (43% ethanol), and Pool Time Algicide] applied to a TifEagle bermudagrass (Cynodon dactylon × C. traansvalensis) putting green where a natural infestation of annual bluegrass was present. Treatments were assessed visually for annual bluegrass control and turf phytotoxicity 1, 2, and 4 weeks after application. Overall, no treatment provided long-term control which was non-selective. Control was short-lived with annual bluegrass recovery beginning approximately two weeks after applying treatments. Greatest Poa burndown (~85%) was temporarily (1 to 2 weeks after application) with a combination of caprylic and capric acids (Suppress Herbicide) and a combination of clove oil and dishwashing detergent but plants fully recovered by three weeks after application. These products also produced similar temporary turf phytotoxicity. Bermudagrass turf phytotoxicity from selective treatments was most evident one week after applying treatments and turf had mostly fully recovered by four weeks after treatment. Suitable alternatives were not identified from products tested.
Improving Phenolic Bioactive-Linked Functional Qualities of Sweet Potatoes Using Beneficial Lactic Acid Bacteria-Based Biotransformation Strategy
Authors: Chintha Pradeepika , Sarkar Dipayan , Pecota Kenneth , Dogramaci Munevver , Shetty Kalidas
Published: October 2021

Beneficial lactic acid bacteria (LAB) based fermentation is an effective biotransformation strategy to preserve and improve the human health-supporting functional qualities of plant-based food substrates. In this study, a food grade strain of Lactiplantibacillus plantarum was recruited to improve the retention, stability, and bioavailability of phenolic bioactives to enhance the antioxidant, anti-hyperglycemic, and anti-hypertensive functional qualities of three flesh-colored sweet potato varieties, Murasaki (off-white-fleshed), Evangeline (orange-fleshed), and NIC-413 (purple-fleshed). Liquid (cold water) extracts of the sweet potatoes, which are relevant for food grade applications, were fermented for 72 h at 37 °C. Total soluble phenolic content, phenolic profile, antioxidant, anti-hyperglycemic, and anti-hypertensive benefits relevant functional properties of fermented and unfermented sweet potato extracts were evaluated at 0, 24, 48, and 72 h time points using in vitro assay models. Overall, high total soluble phenolic content and total antioxidant activity were observed at 24 h, retaining this high level even after 72 h of fermentation. Additionally, moderate to high α-amylase, α-glucosidase, and angiotensin-I-converting enzyme inhibitory activities were observed in the fermented sweet potato extracts. The results suggested that LAB-based fermentation is an effective post-harvest processing strategy for a higher retention of phenolic bioactives and concurrently improves the human health protective bioactive functional qualities of sweet potatoes.
“Oh, You Shouldn’t Have!” Understanding Key Factors Impacting Cut Flowers Gifting Preferences in Germany
Authors: Rombach Meike , Dean David L. , Olynk Widmar Nicole J. , Bitsch Vera
Published: October 2021

Cut flower gifting preferences are relatively unexplored in Germany. This study proposes a model that investigates the impact of attitudinal, experiential, and socio-demographic factors on the cut flower gifting preferences of German consumers. For this purpose, an online survey with a representative sample of 978 German residents was conducted. Partial least squares structural equation modelling shows that active and passive engagement with plants and nature positively impact cut flower giving preferences through cut flower knowledge, cut flower fondness, and perceived versatility of cut flowers. For German women and men, the largest driver of cut flower giving preferences is the versatility of cut flowers. For women, cut flower fondness is the second largest driver of cut flower gifting preferences, whereas for men subjective knowledge was the second largest driver. Other socio-demographic factors (age, income, education) were not found to impact cut flower giving preferences.
Light Quality Environment and Photomorphological Responses of Young Olive Trees
Authors: Ladux Federico J. , Trentacoste Eduardo R. , Searles Peter S. , Rousseaux M. Cecilia
Published: October 2021

Tree densities have increased greatly in olive orchards over the last few decades. In many annual crop species, increased density reduces the horizontal red/far-red (R/FR) and blue/green (B/G) ratios during canopy development even before direct shading occurs, and such changes are known to alter plant morphology. This study with olive trees evaluated: (1) whether the leaf area index (LAI) of neighboring trees modifies the light quality environment prior to a tree being directly shaded and (2) the potential morphological responses of three olive cultivars to changes in light quality. Increasing LAI using different spatial arrangements of potted, three-year-old trees reduced the horizontal R/FR ratio more than that of the B/G ratio. Cultivar-specific responses to low R/FR ratio were observed for individual leaf area and aboveground/belowground biomass ratio using laterally positioned FR mirrors or green fences. No statistically significant responses were detected in response to green vegetation fences that reduced both horizontal R/FR and B/G ratios, but a cluster analysis grouped together the overall morphological responses to both FR mirrors and green fences. These results in olive trees suggest that cultivar differences in response to light quality may be relevant for understanding adaptation to dense orchards and identifying cultivars best suited to them.
Effects of Repeated Application of Organic Soil Amendments on Horticultural Soil Physicochemical Properties, Nitrogen Budget and Yield
Authors: Duddigan Sarah , Alexander Paul D. , Shaw Liz J. , Collins Chris D.
Published: October 2021

Application of organic amendments to soil is commonplace in domestic gardening. However, a vast array of materials could be labelled as ‘compost’ by retailers and suppliers. We investigated six different amendments currently used, or available for use, in horticulture: composted bark, composted bracken, spent mushroom compost, composted horse manure, garden waste compost (at two different application rates), and peat. Using a controlled field experiment, we examined the physicochemical differences between the amendments, the subsequent effects on soil characteristics, and resultant yield and biometrics of Lavatera trimiestris. Amended soils resulted in a significantly different multivariate soil environment and N budget when compared to the unamended control. However, the effect on yield and plant biometrics (number of flowers, plant height, etc.) depended on the amendment used. Application of garden compost resulted in up to a five-fold increase in yield. However, there was no significant difference in yields in soils amended with composted bark or peat, when compared to the unamended control. This has implications, as there is increasing pressure to remove peat from products available to domestic gardeners. The variability in the different amendments investigated in our research, in addition to the variable effects on plant growth parameters, suggests that repeated use of a single amendment may not be best practise for gardeners.
Agronomic Performance, Capsaicinoids, Polyphenols and Antioxidant Capacity in Genotypes of Habanero Pepper Grown in the Southeast of Coahuila, Mexico
Authors: Camposeco-Montejo Neymar , Flores-Naveda Antonio , Ruiz-Torres Norma , Álvarez-Vázquez Perpetuo , Niño-Medina Guillermo , Ruelas-Chacón Xochitl , Torres-Tapia María Alejandra , Rodríguez-Salinas Pablo , Villanueva-Coronado Victor , García-López Josué I.
Published: October 2021

The genetic improvement program of the Seed Technology Training and Development Center works on the agronomic characterization and the content of bioactive compounds in eight genotypes of habanero pepper. The objective is to select genotypes with good agronomic performance that allow the generation of inbred lines to obtain hybrids. In this study, the agronomic performance and the content of bioactive compounds (capsaicinoids, polyphenols, and antioxidant capacity) were evaluated in eight genotypes of habanero pepper grown in the southeast of Coahuila, Mexico, identified as HNC-1, HNC-2, HNC-3, HNC-4, HNC-5, HNC-6, HNC-7, and HCC-8. The plants were grown in a greenhouse for 127 days, under a completely randomized design with four replications each. The results revealed that the yield (g·plant−1) and number of fruits per plant did not show significant differences between genotypes. However, for the fruit length, the genotypes HCC-8, HNC-7, HNC-6, and HNC-5 stood out with over 40 mm, while in equatorial diameter of the fruit, HCC-8, HNC-4, and HNC-2 stood out with 26.45, 26.46, and 25.12 mm, respectively. The results of the chemical analyses allowed us to identify that HNC-5 and HNC-6 had the highest capsaicin concentration (931.38 and 959.77 mg·kg−1), dihydrocapsaicin (434.95 and 445.89 mg·kg−1), Scoville Heat Units greater than 210,000, total phenols (67.54 and 71.15 mg/100 g) and total flavonoids (34.21 and 38.29 mg/100 g), respectively. The HNC-1 and HNC-6 genotypes had the highest carotenoids concentration with 103.96 and 105.07 mg/100 g, and HCC-8 registered the highest anthocyanin content with 22.08 mg C3GE/100 g. The antioxidant capacities showed significant differences (p ≤ 0.05) between genotypes, with a range of 43.22 to 110.39 µmol TE/100 g, 72.37 to 186.56 µmol TE/100 g, and 191.41 to 244.98 µmol TE/100 g for the tests of DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2′azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)), and FRAP (ferric reducing antioxidant power). The results of this research will be used to select habanero pepper genotypes that can be used in genetic improvement programs to increase the productive potential and the content of bioactive compounds in the fruits to expand their applications in the food industry.
Enzymatic Browning in Banana Blossoms and Techniques for Its Reduction
Authors: Kaewjumpol Geerada , Srisamlee Surasak , Beckles Diane M. , Luengwilai Kietsuda
Published: October 2021

Banana blossoms are rich in fiber and nutrients and are a popular plant-based, vegan alternative to fish. However undesirable browning, usually visible at the peduncle cut-end, negatively impacts consumer acceptability of banana blossoms. The aim of this work was to develop safe alternatives to prevent browning in banana blossoms. First, the activities of primary enzymes associated with tissue browning, i.e., polyphenol oxidase (PPO), peroxidase (POD) and phenylalanine ammonia lyase (PAL), were assayed. Our data showed that PPO and POD were the key enzymes responsible for blossom browning as they increased in activity, reaching a maximum at pH 7, as browning developed. In contrast, PAL activity decreased, and total phenolic content did not change as browning progressed, indicating PAL was not induced by cutting and may not be involved in blossom browning. Second, to find antibrowning agents for banana blossoms that can substitute for the use of sodium metabisulfite (SMS), different organic acids of varying concentrations were tested. Among organic acids studied, treatment with 3% (w/v) oxalic acid was the most effective method and thus could be a safe substitution for SMS to prevent browning in banana blossoms.
Airline Cabin Crew Team System’s Positive Evaluation Factors and Their Impact on Personal Health and Team Potency
Authors: Ko Youkyung , Lee Hwaneui , Hyun Sunghyup Sean
Published: October 2021

Recently, many airline companies have trialed introducing team systems to manage crew members and enhance competitiveness systematically through the efficiency of manpower operation. Cabin crew members share in a sense of unity when spending time with team members outside of work hours. Cabin crews must be able to resolve unexpected issues—fires, aircraft defects, medical emergencies, and sudden airflow changes—quickly and accurately. As unexpected issues may result in major accidents, it is crucial that cabin crew members can take responsibility for passenger safety and offer satisfactory services to customers. Furthermore, most cabin duties require cooperation and are highly interdependent; thus, respect and teamwork are essential. This empirical study aims to identify and examine the positive factors of the team system used to evaluate causalities in job satisfaction, team potency, and mental health. The research model is developed based on a theoretical review, focusing on five positive factors—sense of belonging, mutual support, communication, motivation, and work flexibility—and dependent variables: job satisfaction, team potency, and mental health. Sense of belonging, communication, and work flexibility significantly affected team potency along with job satisfaction. This study has practical implications, providing guidance for the sustainable development of team systems for airline crew management.
Spatio-Temporal Variation Analysis of the Biological Boundary Temperature Index Based on Accumulated Temperature: A Case Study of the Yangtze River Basin
Authors: Shi Guangxun , Ye Peng , Yang Xianwu
Published: October 2021

Active accumulated temperature is an important index of agricultural heat resources in a region. Based on the temperature data of the Yangtze River Basin from 1970 to 2014, this paper analyzed the characteristics of the temporal and spatial variations of the biological boundary temperature in the Yangtze River Basin. The main conclusions were drawn as follows: (1) since 1970, the accumulated temperature of ≥0 °C in the northern subtropical zone, mid-subtropical zone, and plateau climate zone showed overall increasing trends, and the trends were 122 (p < 0.001), 87.7 (p < 0.001), and 75.3 °C/10a (p < 0.001), respectively. The accumulated temperature of ≥5 °C showed an upward trend, and the change tendency rates were 122.6 (p < 0.001), 90.5 (p < 0.001), and 81.4 °C/10a (p < 0.001), respectively. The accumulated temperature of ≥10 °C showed overall increasing trends and the trends were 115.7 (p < 0.001), 92.5 (p < 0.001), and 78.9 °C/10a (p < 0.001). Accumulated temperatures of ≥0 °C, ≥5 °C, and ≥10 °C in the northern subtropical zone increased significantly higher than that in the mid-subtropical zone and plateau climate zone. (2) The accumulated temperatures of ≥0 °C, ≥5 °C, and ≥10 °C in the northern subtropical zone showed an abrupt change in 1997. In the mid-subtropical zone and plateau climate zone, there was an abrupt change in the accumulated temperatures of ≥0 °C and ≥5 °C in 1994, and in the northern subtropical zone, the abrupt change of the accumulated temperature ≥10 °C occurred in 1998. (3) There are obvious differences in the biological boundary temperature within the Yangtze River Basin, and the stations with large increases are mainly distributed in the middle and lower reaches, such as the Hanshui Basin, the Poyang Lake Basin, the Taihu Lake Basin, and the middle and lower reaches of the mainstream area. The initial day, final day, and continuous days showed a trend of advancement, postponement, and extension, respectively. Besides, the heat resources showed significant increasing trends, which is of guiding significance for the future production and development of agriculture in the region. With the increase of heat resources in the Yangtze River Basin, appropriate late-maturing varieties should be selected in variety breeding, to make full use of heat resources and improve the quality of agricultural products. Secondly, the planting system should be adjusted and the multiple cropping index improved to steadily increase agricultural output. This brings new opportunities to adjust the structure of the agricultural industry and increase farmers’ income, in the Yangtze River basin.
proNGF Involvement in the Adult Neurogenesis Dysfunction in Alzheimer’s Disease
Authors: Olabiyi Bolanle Fatimat , Fleitas Catherine , Zammou Bahira , Ferrer Isidro , Rampon Claire , Egea Joaquim , Espinet Carme
Published: October 2021

In recent decades, neurogenesis in the adult brain has been well demonstrated in a number of animal species, including humans. Interestingly, work with rodents has shown that adult neurogenesis in the dentate gyrus (DG) of the hippocampus is vital for some cognitive aspects, as increasing neurogenesis improves memory, while its disruption triggers the opposite effect. Adult neurogenesis declines with age and has been suggested to play a role in impaired progressive learning and memory loss seen in Alzheimer’s disease (AD). Therefore, therapeutic strategies designed to boost adult hippocampal neurogenesis may be beneficial for the treatment of AD. The precursor forms of neurotrophins, such as pro-NGF, display remarkable increase during AD in the hippocampus and entorhinal cortex. In contrast to mature NGF, pro-NGF exerts adverse functions in survival, proliferation, and differentiation. Hence, we hypothesized that pro-NGF and its p75 neurotrophin receptor (p75NTR) contribute to disrupting adult hippocampal neurogenesis during AD. To test this hypothesis, in this study, we took advantage of the availability of mouse models of AD (APP/PS1), which display memory impairment, and AD human samples to address the role of pro-NGF/p75NTR signaling in different aspects of adult neurogenesis. First, we observed that DG doublecortin (DCX) + progenitors express p75NTR both, in healthy humans and control animals, although the percentage of DCX+ cells are significantly reduced in AD. Interestingly, the expression of p75NTR in these progenitors is significantly decreased in AD conditions compared to controls. In order to assess the contribution of the pro-NGF/p75NTR pathway to the memory deficits of APP/PS1 mice, we injected pro-NGF neutralizing antibodies (anti-proNGF) into the DG of control and APP/PS1 mice and animals are subjected to a Morris water maze test. Intriguingly, we observed that anti-pro-NGF significantly restored memory performance of APP/PS1 animals and significantly increase the percentage of DCX+ progenitors in the DG region of these animals. In summary, our results suggest that pro-NGF is involved in disrupting spatial memory in AD, at least in part by blocking adult neurogenesis. Moreover, we propose that adult neurogenesis alteration should be taken into consideration for better understanding of AD pathology. Additionally, we provide a new molecular entry point (pro-NGF/p75NTR signaling) as a promising therapeutic target in AD.
Nanobody-Based Theranostic Agents for HER2-Positive Breast Cancer: Radiolabeling Strategies
Authors: Hrynchak Ivanna , Santos Liliana , Falcão Amílcar , Gomes Célia M. , Abrunhosa Antero J.
Published: October 2021

The overexpression of human epidermal growth factor 2 (HER2) in breast cancer (BC) has been associated with a more aggressive tumor subtype, poorer prognosis and shorter overall survival. In this context, the development of HER2-targeted radiotracers is crucial to provide a non-invasive assessment of HER2 expression to select patients for HER2-targeted therapies, monitor response and identify those who become resistant. Antibodies represent ideal candidates for this purpose, as they provide high contrast images for diagnosis and low toxicity in the therapeutic setting. Of those, nanobodies (Nb) are of particular interest considering their favorable kinetics, crossing of relevant biological membranes and intratumoral distribution. The purpose of this review is to highlight the unique characteristics and advantages of Nb-based radiotracers in BC imaging and therapy. Additionally, radiolabeling methods for Nb including direct labeling, indirect labeling via prosthetic group and indirect labeling via complexation will be discussed, reporting advantages and drawbacks. Furthermore, the preclinical to clinical translation of radiolabeled Nbs as promising theranostic agents will be reported.
Antibacterial Activity of Medicinal Plants and Their Constituents in the Context of Skin and Wound Infections, Considering European Legislation and Folk Medicine—A Review
Authors: Bittner Fialová Silvia , Rendeková Katarína , Mučaji Pavel , Nagy Milan , Slobodníková Lívia
Published: October 2021

Bacterial infections of skin and wounds may seriously decrease the quality of life and even cause death in some patients. One of the largest concerns in their treatment is the growing antimicrobial resistance of bacterial infectious agents and the spread of resistant strains not only in the hospitals but also in the community. This trend encourages researchers to seek for new effective and safe therapeutical agents. The pharmaceutical industry, focusing mainly on libraries of synthetic compounds as a drug discovery source, is often failing in the battle with bacteria. In contrast, many of the natural compounds, and/or the whole and complex plants extracts, are effective in this field, inactivating the resistant bacterial strains or decreasing their virulence. Natural products act comprehensively; many of them have not only antibacterial, but also anti-inflammatory effects and may support tissue regeneration and wound healing. The European legislative is in the field of natural products medicinal use formed by European Medicines Agency (EMA), based on the scientific work of its Committee on Herbal Medicinal Products (HMPC). HMPC establishes EU monographs covering the therapeutic uses and safe conditions for herbal substances and preparations, mostly based on folk medicine, but including data from scientific research. In this review, the medicinal plants and their active constituents recommended by EMA for skin disorders are discussed in terms of their antibacterial effect. The source of information about these plant products in the review is represented by research articles listed in scientific databases (Science Direct, PubMed, Scopus, Web of Science, etc.) published in recent years.
Quercetin-3-Glucoside Extracted from Apple Pomace Induces Cell Cycle Arrest and Apoptosis by Increasing Intracellular ROS Levels
Authors: Nile Arti , Nile Shivraj Hariram , Shin Juhyun , Park Gyunseok , Oh Jae-Wook
Published: October 2021

Cervical cancer is a life-threatening disease and the fourth most common cancer among women worldwide. Apple pomace is a multifunctional phenolic compound possessing effective biological activity against cervical cancer cells. This study aimed to investigate the anticancer effects of quercetin-3-glucoside (Q3G) extracted from apple pomace in HeLa cell lines and analyze its molecular mechanisms. High-performance liquid chromatography revealed that Q3G, coumaric acid, phloridzin, quercetin, and phloretin are the major polyphenolic compounds constituting apple pomace. Among them, Q3G possessed the greatest antioxidant and anti-inflammatory effects in vitro and exhibited significant cytotoxic effects in HeLa cells in a dose-and time-dependent manner. Flow cytometric analysis indicated that Q3G induced cell cycle arrest at the S phase in a time-dependent manner by altering cyclin-dependent kinase 2. Moreover, it induced apoptosis via chromosomal DNA degradation and increased reactive oxygen species generation. Furthermore, Q3G treatment altered the apoptosis-associated protein expression in the cells by activating caspase-9/-3, downregulating anti-apoptosis protein B-cell lymphoma (Bcl)-2 expressions and up regulating the pro-apoptotic Bcl-2-associated X protein. BH3-interacting domain death agonist cleavage occurred prior to the degradation of an anti-apoptotic Mu-2-related death-inducing gene involved in cell death signaling. Consequently, apple pomace Q3G holds promise as an anti-inflammatory and anticancer agent for treating cervical cancer.
Atrophy of White Adipose Tissue Accompanied with Decreased Insulin-Stimulated Glucose Uptake in Mice Lacking the Small GTPase Rac1 Specifically in Adipocytes
Authors: Hasegawa Kiko , Takenaka Nobuyuki , Tanida Kenya , Chan Man Piu , Sakata Mizuki , Aiba Atsu , Satoh Takaya
Published: October 2021

Insulin stimulates glucose uptake in adipose tissue and skeletal muscle by inducing plasma membrane translocation of the glucose transporter GLUT4. Although the small GTPase Rac1 is a key regulator downstream of phosphoinositide 3-kinase (PI3K) and the protein kinase Akt2 in skeletal muscle, it remains unclear whether Rac1 also regulates glucose uptake in white adipocytes. Herein, we investigated the physiological role of Rac1 in white adipocytes by employing adipocyte-specific rac1 knockout (adipo-rac1-KO) mice. Subcutaneous and epididymal white adipose tissues (WATs) in adipo-rac1-KO mice showed significant reductions in size and weight. Actually, white adipocytes lacking Rac1 were smaller than controls. Insulin-stimulated glucose uptake and GLUT4 translocation were abrogated in rac1-KO white adipocytes. On the other hand, GLUT4 translocation was augmented by constitutively activated PI3K or Akt2 in control, but not in rac1-KO, white adipocytes. Similarly, to skeletal muscle, the involvement of another small GTPase RalA downstream of Rac1 was demonstrated. In addition, mRNA levels of various lipogenic enzymes were down-regulated in rac1-KO white adipocytes. Collectively, these results suggest that Rac1 is implicated in insulin-dependent glucose uptake and lipogenesis in white adipocytes, and reduced insulin responsiveness due to the deficiency of Rac1 may be a likely explanation for atrophy of WATs.
Utilizing an Amino Acid Scaffold to Construct Heteroditopic Receptors Capable of Interacting with Salts under Interfacial Conditions
Authors: Jagleniec Damian , Walczak Natalia , Dobrzycki Łukasz , Romański Jan
Published: October 2021

A 4-nitro-L-phenylalanine scaffold was used to construct effective ion pair receptors capable of binding anions in an enhanced manner with the assistance of alkali metal cations. A benzocrown ether was linked to a receptor platform via the amide function so as to support the squaramide function in anion binding and to allow all three NHs to act simultaneously. The binding properties of the receptors were determined using UV-vis, 1H NMR, 2D NMR, and DOSY spectroscopy in MeCN and in the solid state by X-ray measurements. Ion pair receptor 2 was found to interact with the most strongly with salts, and the removal of its key structural elements was shown to hinder the receptor action. The amide proton was recognized to switch from having involvement in an intramolecular hydrogen bond to interacting with anions upon complexation. Apart from carboxylates, which promote deprotonation, and other monovalent salts creating 1:1 complexes with the receptor, more complex equilibria were established upon the complexation of 2 with sulfates. Receptor 2 was shown to be capable of the extraction of ion pairs from the aqueous to organic phase and of the cation-enhanced transport chloride and sulfate anions across a bulk chloroform membrane. These features may open the door for its use in regulating ion concertation under interfacial conditions and acting as a potential drug to treat channelopathies.
Convergent Canonical Pathways in Autism Spectrum Disorder from Proteomic, Transcriptomic and DNA Methylation Data
Authors: Mahony Caitlyn , O’Ryan Colleen
Published: October 2021

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with extensive genetic and aetiological heterogeneity. While the underlying molecular mechanisms involved remain unclear, significant progress has been facilitated by recent advances in high-throughput transcriptomic, epigenomic and proteomic technologies. Here, we review recently published ASD proteomic data and compare proteomic functional enrichment signatures with those of transcriptomic and epigenomic data. We identify canonical pathways that are consistently implicated in ASD molecular data and find an enrichment of pathways involved in mitochondrial metabolism and neurogenesis. We identify a subset of differentially expressed proteins that are supported by ASD transcriptomic and DNA methylation data. Furthermore, these differentially expressed proteins are enriched for disease phenotype pathways associated with ASD aetiology. These proteins converge on protein–protein interaction networks that regulate cell proliferation and differentiation, metabolism, and inflammation, which demonstrates a link between canonical pathways, biological processes and the ASD phenotype. This review highlights how proteomics can uncover potential molecular mechanisms to explain a link between mitochondrial dysfunction and neurodevelopmental pathology.
The Phenoxyalkyltriazine Antagonists for 5-HT6 Receptor with Promising Procognitive and Pharmacokinetic Properties In Vivo in Search for a Novel Therapeutic Approach to Dementia Diseases
Authors: Sudoł Sylwia , Cios Agnieszka , Jastrzębska-Więsek Magdalena , Honkisz-Orzechowska Ewelina , Mordyl Barbara , Wilczyńska-Zawal Natalia , Satała Grzegorz , Kucwaj-Brysz Katarzyna , Partyka Anna , Latacz Gniewomir , Olejarz-Maciej Agnieszka , Wesołowska Anna , Handzlik Jadwiga
Published: October 2021

Among the serotonin receptors, one of the most recently discovered 5-HT6 subtype is an important protein target and its ligands may play a key role in the innovative treatment of cognitive disorders. However, none of its selective ligands have reached the pharmaceutical market yet. Recently, a new chemical class of potent 5-HT6 receptor agents, the 1,3,5-triazine-piperazine derivatives, has been synthesized. Three members, the ortho and meta dichloro- (1,2) and the unsubstituted phenyl (3) derivatives, proved to be of special interest due to their high affinities (1,2) and selectivity (3) toward 5-HT6 receptor. Thus, a broader pharmacological profile for 1–3, including comprehensive screening of the receptor selectivity and drug-like parameters in vitro as well as both, pharmacokinetic and pharmacodynamic properties in vivo, have been investigated within this study. A comprehensive analysis of the obtained results indicated significant procognitive-like activity together with beneficial drug-likeness in vitro and pharmacokinetics in vivo profiles for both, (RS)-4-[1-(2,3-dichlorophenoxy)propyl]-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (2) and (RS)-4-(4-methylpiperazin-1-yl)-6-(1-phenoxypropyl)-1,3,5-triazin-2-amine (3), but insensibly predominant for compound 2. Nevertheless, both compounds (2 and 3) seem to be good Central Nervous System drug candidates in search for novel therapeutic approach to dementia diseases, based on the 5-HT6 receptor target.
GPR21 Inhibition Increases Glucose-Uptake in HepG2 Cells
Authors: Kinsella Gemma K. , Cannito Stefania , Bordano Valentina , Stephens John C. , Rosa Arianna C. , Miglio Gianluca , Guaschino Valeria , Iannaccone Valeria , Findlay John B.C. , Benetti Elisa
Published: October 2021

GPR21 is a constitutively active, orphan, G-protein-coupled receptor, with in vivo studies suggesting its involvement in the modulation of insulin sensitivity. However, its precise contribution is not fully understood. As the liver is both a major target of insulin signalling and critically involved in glucose metabolism, the aim of this study was to examine the role of GPR21 in the regulation of glucose uptake and production in human hepatocytes. In particular, HepG2 cells, which express GPR21, were adopted as cellular models. Compared with untreated cells, a significant increase in glucose uptake was measured in cells treated with siRNA to downregulate GPR21 expression or with the GPR21-inverse agonist, GRA2. Consistently, a significantly higher membrane translocation of GLUT-2 was measured under these conditions. These effects were accompanied by an increased ratio of phAKT(Ser473)/tot-AKT and phGSK-3β(Ser9)/tot-GSK-3β, thus indicating a marked activation of the insulin signalling pathway. Moreover, a significant reduction in ERK activation was observed with GPR21 inhibition. Collectively, these results indicate that GPR21 mediates the negative effects on glucose uptake by the liver cells. In addition, they suggest that the pharmacological inhibition of GPR21 could be a novel strategy to improve glucose homeostasis and counteract hepatic insulin resistance.
Multiomics and Health: A Holistic Approach to Better Understand the Role of the Microbiome
Authors: Toranzos Gary A. , Santiago-Rodriguez Tasha M.
Published: October 2021

The present Special Issue focuses on the latest approaches to health and public health microbiology using multiomics [...]
The Ryanodine Receptor as a Sensor for Intracellular Environments in Muscles
Authors: Kobayashi Takuya , Kurebayashi Nagomi , Murayama Takashi
Published: October 2021

The ryanodine receptor (RyR) is a Ca2+ release channel in the sarcoplasmic reticulum of skeletal and cardiac muscles and plays a key role in excitation–contraction coupling. The activity of the RyR is regulated by the changes in the level of many intracellular factors, such as divalent cations (Ca2+ and Mg2+), nucleotides, associated proteins, and reactive oxygen species. Since these intracellular factors change depending on the condition of the muscle, e.g., exercise, fatigue, or disease states, the RyR channel activity will be altered accordingly. In this review, we describe how the RyR channel is regulated under various conditions and discuss the possibility that the RyR acts as a sensor for changes in the intracellular environments in muscles.
Evaluating Molecular Docking Software for Small Molecule Binding to G-Quadruplex DNA
Authors: Dickerhoff Jonathan , Warnecke Kassandra R. , Wang Kaibo , Deng Nanjie , Yang Danzhou
Published: October 2021

G-quadruplexes are four-stranded nucleic acid secondary structures of biological significance and have emerged as an attractive drug target. The G4 formed in the MYC promoter (MycG4) is one of the most studied small-molecule targets, and a model system for parallel structures that are prevalent in promoter DNA G4s and RNA G4s. Molecular docking has become an essential tool in structure-based drug discovery for protein targets, and is also increasingly applied to G4 DNA. However, DNA, and in particular G4, binding sites differ significantly from protein targets. Here we perform the first systematic evaluation of four commonly used docking programs (AutoDock Vina, DOCK 6, Glide, and RxDock) for G4 DNA-ligand binding pose prediction using four small molecules whose complex structures with the MycG4 have been experimentally determined in solution. The results indicate that there are considerable differences in the performance of the docking programs and that DOCK 6 with GB/SA rescoring performs better than the other programs. We found that docking accuracy is mainly limited by the scoring functions. The study shows that current docking programs should be used with caution to predict G4 DNA-small molecule binding modes.
A Novel GUCA1A Variant Associated with Cone Dystrophy Alters cGMP Signaling in Photoreceptors by Strongly Interacting with and Hyperactivating Retinal Guanylate Cyclase
Authors: Biasi Amedeo , Marino Valerio , Dal Cortivo Giuditta , Maltese Paolo Enrico , Modarelli Antonio Mattia , Bertelli Matteo , Colombo Leonardo , Dell’Orco Daniele
Published: October 2021

Guanylate cyclase-activating protein 1 (GCAP1), encoded by the GUCA1A gene, is a neuronal calcium sensor protein involved in shaping the photoresponse kinetics in cones and rods. GCAP1 accelerates or slows the cGMP synthesis operated by retinal guanylate cyclase (GC) based on the light-dependent levels of intracellular Ca2+, thereby ensuring a timely regulation of the phototransduction cascade. We found a novel variant of GUCA1A in a patient affected by autosomal dominant cone dystrophy (adCOD), leading to the Asn104His (N104H) amino acid substitution at the protein level. While biochemical analysis of the recombinant protein showed impaired Ca2+ sensitivity of the variant, structural properties investigated by circular dichroism and limited proteolysis excluded major structural rearrangements induced by the mutation. Analytical gel filtration profiles and dynamic light scattering were compatible with a dimeric protein both in the presence of Mg2+ alone and Mg2+ and Ca2+. Enzymatic assays showed that N104H-GCAP1 strongly interacts with the GC, with an affinity that doubles that of the WT. The doubled IC50 value of the novel variant (520 nM for N104H vs. 260 nM for the WT) is compatible with a constitutive activity of GC at physiological levels of Ca2+. The structural region at the interface with the GC may acquire enhanced flexibility under high Ca2+ conditions, as suggested by 2 μs molecular dynamics simulations. The altered interaction with GC would cause hyper-activity of the enzyme at both low and high Ca2+ levels, which would ultimately lead to toxic accumulation of cGMP and Ca2+ in the photoreceptor outer segment, thus triggering cell death.
Differential Marker Expression between Keratinocyte Stem Cells and Their Progeny Generated from a Single Colony
Authors: Ali Dema , Alhattab Dana , Jafar Hanan , Alzubide Malak , Sharar Nour , Bdour Salwa , Awidi Abdalla
Published: October 2021

The stemness in keratinocyte stem cells (KSCs) is determined by their gene expression patterns. KSCs are crucial in maintaining epidermal homeostasis and wound repair and are widely used candidates for therapeutic applications. Although several studies have reported their positive identifiers, unique biomarkers for KSCs remain elusive. Here, we aim to identify potential candidate stem cell markers. Human epidermal keratinocytes (HEKs) from neonatal foreskin tissues were isolated and cultured. Single-cell clonal analysis identified and characterized three types of cells: KSCs (holoclones), transient amplifying cells (TACs; meroclones), and differentiated cells (DSCs; paraclones). The clonogenic potential of KSCs demonstrated the highest proliferation potential of KSCs, followed by TACs and DSCs, respectively. Whole-transcriptome analysis using microarray technology unraveled the molecular signatures of these cells. These results were validated by quantitative real-time polymerase chain reaction and flow cytometry analysis. A total of 301 signature upregulated and 149 downregulated differentially expressed genes (DEGs) were identified in the KSCs, compared to TACs and DSCs. Furthermore, DEG analyses revealed new sets of genes related to cell proliferation, cell adhesion, surface makers, and regulatory factors. In conclusion, this study provides a useful source of information for the identification of potential SC-specific candidate markers.
ZNF521 Enhances MLL-AF9-Dependent Hematopoietic Stem Cell Transformation in Acute Myeloid Leukemias by Altering the Gene Expression Landscape
Authors: Chiarella Emanuela , Aloisio Annamaria , Scicchitano Stefania , Todoerti Katia , Cosentino Emanuela G. , Lico Daniela , Neri Antonino , Amodio Nicola , Bond Heather Mandy , Mesuraca Maria
Published: October 2021

Leukemias derived from the MLL-AF9 rearrangement rely on dysfunctional transcriptional networks. ZNF521, a transcription co-factor implicated in the control of hematopoiesis, has been proposed to sustain leukemic transformation in collaboration with other oncogenes. Here, we demonstrate that ZNF521 mRNA levels correlate with specific genetic aberrations: in particular, the highest expression is observed in AMLs bearing MLL rearrangements, while the lowest is detected in AMLs with FLT3-ITD, NPM1, or CEBPα double mutations. In cord blood-derived CD34+ cells, enforced expression of ZNF521 provides a significant proliferative advantage and enhances MLL-AF9 effects on the induction of proliferation and the expansion of leukemic progenitor cells. Transcriptome analysis of primary CD34+ cultures displayed subsets of genes up-regulated by MLL-AF9 or ZNF521 single transgene overexpression as well as in MLL-AF9/ZNF521 combinations, at either the early or late time points of an in vitro leukemogenesis model. The silencing of ZNF521 in the MLL-AF9 + THP-1 cell line coherently results in an impairment of growth and clonogenicity, recapitulating the effects observed in primary cells. Taken together, these results underscore a role for ZNF521 in sustaining the self-renewal of the immature AML compartment, most likely through the perturbation of the gene expression landscape, which ultimately favors the expansion of MLL-AF9-transformed leukemic clones.
The FGFR Family Inhibitor AZD4547 Exerts an Antitumor Effect in Ovarian Cancer Cells
Authors: Na Yu Ran , Kim Jin Young , Song Chang Ho , Kim Mikyung , Do Yen Thi , Vo Tam Thuy Lu , Choi Eunsom , Ha Eunyoung , Seo Ji Hae , Shin So-Jin
Published: October 2021

The dysregulation of fibroblast growth factor (FGF) signaling has been implicated in tumorigenesis, tumor progression, angiogenesis, and chemoresistance. The small-molecule AZD4547 is a potent inhibitor of FGF receptors. This study was performed to investigate the antitumor effects and determine the mechanistic details of AZD4547 in ovarian cancer cells. AZD4547 markedly inhibited the proliferation and increased the apoptosis of ovarian cancer cells. AZD4547 also suppressed the migration and invasion of ovarian cancer cells under nontoxic conditions. Furthermore, it attenuated the formation of spheroids and the self-renewal capacities of ovarian cancer stem cells and exerted an antiangiogenic effect. It also suppressed in vivo tumor growth in mice. Collectively, this study demonstrated the antitumor effect of AZD4547 in ovarian cancer cells and suggests that it is a promising agent for ovarian cancer therapy.
Neutrophil Pathways of Inflammation Characterize the Blood Transcriptomic Signature of Patients with Psoriasis and Cardiovascular Disease
Authors: Kvist-Hansen Amanda , Kaiser Hannah , Wang Xing , Krakauer Martin , Gørtz Peter Michael , McCauley Benjamin D. , Zachariae Claus , Becker Christine , Hansen Peter Riis , Skov Lone
Published: October 2021

Background: Patients with psoriasis have an increased risk of atherosclerotic cardiovascular disease (CVD). The molecular mechanisms behind this connection are not fully understood, but the involvement of neutrophils have drawn attention as a shared inflammatory factor. Methods: RNA sequencing using the Illumina platform was performed on blood from 38 patients with moderate to severe psoriasis; approximately half had prior CVD. The neutrophil to lymphocyte ratio (NLR) was obtained from blood samples. Subclinical atherosclerosis was assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography and ultrasound imaging. Transcriptomic analysis for differential expression and functional enrichment were performed, followed by correlation analyses of differentially expressed genes (DEGs), NLR and subclinical measurers of CVD. Results: 291 genes were differentially expressed between patients with psoriasis with and without CVD. These included 208 upregulated and 83 downregulated DEGs. Neutrophil degranulation was identified as the most significant process related to the upregulated DEGs. Genes for the neutrophil-associated markers MPO, MMP9, LCN2, CEACAM1, CEACAM6 and CEACAM8 were identified as being of special interest and their mRNA levels correlated with NLR, high-sensitive C-reactive protein and markers of subclinical CVD. Conclusions: Patients with psoriasis and CVD had an increased expression of genes related to neutrophil degranulation in their blood transcriptome compared with patients with psoriasis without CVD. NLR may be a potential biomarker of subclinical CVD in psoriasis.
Combating Fake News with Transformers: A Comparative Analysis of Stance Detection and Subjectivity Analysis
Authors: Kasnesis Panagiotis , Toumanidis Lazaros , Patrikakis Charalampos Z.
Published: October 2021

The widespread use of social networks has brought to the foreground a very important issue, the veracity of the information circulating within them. Many natural language processing methods have been proposed in the past to assess a post’s content with respect to its reliability; however, end-to-end approaches are not comparable in ability to human beings. To overcome this, in this paper, we propose the use of a more modular approach that produces indicators about a post’s subjectivity and the stance provided by the replies it has received to date, letting the user decide whether (s)he trusts or does not trust the provided information. To this end, we fine-tuned state-of-the-art transformer-based language models and compared their performance with previous related work on stance detection and subjectivity analysis. Finally, we discuss the obtained results.