bluuebunny/crossref_metadata_2025 huggingface dataset:
Socioeconomic Status, Institutional Power, and Body Mass Index among Chinese Adults
Authors: Li Weidong , Li Shuzhuo , Feldman Marcus W.
Published: October 2021

Despite the vast literature on the socioeconomic status (SES) gradient of obesity among adult people, no study has investigated the relationship between institutional power and body mass index. Using national survey data from the “China Labor-force Dynamics Survey 2016” (CLDS 2016), multistage cluster-stratified probability proportional to size (PPS) sampling was employed to select cases from 29 provinces, cities, and autonomous regions in China. This study adopts an institutional approach to explore the influences of SES and institutional power on the state of being overweight or severely overweight (obese) among Chinese adults. It is shown that SES has a non-linear influence on being overweight or obese, higher education has a negative effect on being overweight or obese, income has an inverted U-shaped effect on being overweight or obese, and having a managerial or administrative job has a positive effect on being overweight but less so on obesity. These findings reveal that disparities in health outcome and risks are due to inequality in SES. The work unit is a stronger predictor of adults being overweight or obese than occupation. Working in the public sector has a positive effect on being overweight relative to working in the private sector, and only state institutions and government departments have a positive association with obesity. Our results indicate that institutional structure still has effects on individuals’ life chances in the era of China’s market transition.
Differences in the Prevalence of SARS-CoV-2 Infection and Access to Care between Italians and Non-Italians in a Social-Housing Neighbourhood of Milan, Italy
Authors: Pagani Gabriele , Conti Federico , Giacomelli Andrea , Oreni Letizia , Beltrami Martina , Pezzati Laura , Casalini Giacomo , Rondanin Rossana , Prina Andrea , Zagari Antonino , Rusconi Stefano , Galli Massimo
Published: October 2021

The northern Italian region of Lombardy has been severely affected by the COVID-19 pandemic since its arrival in Europe. However, there are only a few published studies of the possible influence of social and cultural factors on its prevalence in the general population. This cross-sectional study of the San Siro social-housing neighbourhood of Milan, which was carried about between 23 December 2020 and 19 February 2021, found that the prevalence of anti-SARS-CoV-2 nucleocapsid antibodies in the population as a whole was 12.4% (253/2044 inhabitants), but there was a more than two-fold difference between non-Italians and Italians (23.3% vs. 9.1%). Multivariable analyses showed that being more than 50 years old, living in crowded accommodation, being a non-Italian, and having a low educational level were associated with higher odds of a positive SARS-CoV-2 test, whereas a higher level of education, retirement, and being a former or current cigarette smoker were inversely associated with SARS-CoV-2 infection. Our findings are in line with previous observations indicating that a lower socio-economic status may be a risk factor for COVID-19 and show that non-Italians are disproportionately affected by SARS-CoV-2 infection. This suggests that public health policies should focus more on disadvantaged populations.
Anticoagulants and the Hemostatic System: A Primer for Occupational Stress Researchers
Authors: Arble Eamonn , Arnetz Bengt B.
Published: October 2021

Anticoagulation, the body’s mechanism to prevent blood clotting, is an internal biomarker of an individual’s response to stress. Research has indicated that understanding the causes, processes, and consequences of anticoagulation can provide important insight into the experience of individuals facing emotional and occupational strain. Unfortunately, despite their importance, the mechanisms and implications of anticoagulation are unfamiliar to many researchers and practitioners working with trauma-exposed professionals. This paper provides an accessible primer on the topic of anticoagulation, including an overview of the biological process, the research connecting these processes with emotional and occupational functioning, as well as some potential methods for assessment.
Can Night Shift Work Affect Biological Age? Hints from a Cross-Sectional Study on Hospital Female Nurses
Authors: Carugno Michele , Maggioni Cristina , Ruggiero Vincenzo , Crespi Eleonora , Monti Paola , Ferrari Luca , Pesatori Angela Cecilia
Published: October 2021

Disruption of age-related processes seems to play a relevant role in health effects related to night shift (NS) work. We aim to verify whether NS work can influence biological age (BA), estimated through Zbieć-Piekarska’s epigenetic signature, based on methylation of five CpG sites in ELOVL2, C1orf132/MIR29B2C, TRIM59, KLF14, and FHL2. Forty-six female nurses working in NS were matched by age and length of employment with 51 female colleagues not working in NS. Each subject filled in a questionnaire (including the Effort Reward Imbalance (ERI) index to assess job stress) and gave a blood sample. Age acceleration (AA) was estimated by regressing BA on chronological age and taking the residuals. Multivariate linear regression models were applied. BA was not associated with NS. However, we did observe an increase in AA per each year in NS in subjects with overweight/obesity (β = 0.46, 95% CI: 0.05; 0.87, p = 0.03), experiencing work-related stress (β = 0.58, 95% CI: 0.10; 1.06, p = 0.018), or both (β = 0.66, 95% CI: 0.03; 1.29, p = 0.041). Although based on a small sample size, our findings suggest an increased BA only among hypersusceptible subjects and is worth further investigation, also in light of recent results suggesting a higher breast cancer risk in women with increased AA.
Exploring the Latent Manifold of City Patterns
Authors: Agoub Amgad , Kada Martin
Published: October 2021

Understanding how cities evolve through time and how humans interact with their surroundings is a complex but essential task that is necessary for designing better urban environments. Recent developments in artificial intelligence can give researchers and city developers powerful tools, and through their usage, new insights can be gained on this issue. Discovering a high-level structure in a set of observations within a low-dimensional manifold is a common strategy used when applying machine learning techniques to tackle several problems while finding a projection from and onto the underlying data distribution. This so-called latent manifold can be used in many applications such as clustering, data visualization, sampling, density estimation, and unsupervised learning. Moreover, data of city patterns has some particularities, such as having superimposed or natural patterns that correspond to those of the depicted locations. In this research, multiple manifolds are explored and derived from city pattern images. A set of quantitative and qualitative tests are proposed to examine the quality of these manifolds. In addition, to demonstrate these tests, a novel specialized dataset of city patterns of multiple locations is created, with the dataset capturing a set of recognizable superimposed patterns.
In Silico Analysis of Fatty Acid Desaturases Structures in Camelina sativa, and Functional Evaluation of Csafad7 and Csafad8 on Seed Oil Formation and Seed Morphology
Authors: Raboanatahiry Nadia , Yin Yongtai , Chen Kang , He Jianjie , Yu Longjiang , Li Maoteng
Published: October 2021

Fatty acid desaturases add a second bond into a single bond of carbon atoms in fatty acid chains, resulting in an unsaturated bond between the two carbons. They are classified into soluble and membrane-bound desaturases, according to their structure, subcellular location, and function. The orthologous genes in Camelina sativa were identified and analyzed, and a total of 62 desaturase genes were identified. It was revealed that they had the common fatty acid desaturase domain, which has evolved separately, and the proteins of the same family also originated from the same ancestry. A mix of conserved, gained, or lost intron structure was obvious. Besides, conserved histidine motifs were found in each family, and transmembrane domains were exclusively revealed in the membrane-bound desaturases. The expression profile analysis of C. sativa desaturases revealed an increase in young leaves, seeds, and flowers. C. sativa ω3-fatty acid desaturases CsaFAD7 and CsaDAF8 were cloned and the subcellular localization analysis showed their location in the chloroplast. They were transferred into Arabidopsis thaliana to obtain transgenic lines. It was revealed that the ω3-fatty acid desaturase could increase the C18:3 level at the expense of C18:2, but decreases in oil content and seed weight, and wrinkled phenotypes were observed in transgenic CsaFAD7 lines, while no significant change was observed in transgenic CsaFAD8 lines in comparison to the wild-type. These findings gave insights into the characteristics of desaturase genes, which could provide an excellent basis for further investigation for C. sativa improvement, and overexpression of ω3-fatty acid desaturases in seeds could be useful in genetic engineering strategies, which are aimed at modifying the fatty acid composition of seed oil.
Oxytocin and Food Intake Control: Neural, Behavioral, and Signaling Mechanisms
Authors: Liu Clarissa M. , Spaulding Mai O. , Rea Jessica J. , Noble Emily E. , Kanoski Scott E.
Published: October 2021

The neuropeptide oxytocin is produced in the paraventricular hypothalamic nucleus and the supraoptic nucleus of the hypothalamus. In addition to its extensively studied influence on social behavior and reproductive function, central oxytocin signaling potently reduces food intake in both humans and animal models and has potential therapeutic use for obesity treatment. In this review, we highlight rodent model research that illuminates various neural, behavioral, and signaling mechanisms through which oxytocin’s anorexigenic effects occur. The research supports a framework through which oxytocin reduces food intake via amplification of within-meal physiological satiation signals rather than by altering between-meal interoceptive hunger and satiety states. We also emphasize the distributed neural sites of action for oxytocin’s effects on food intake and review evidence supporting the notion that central oxytocin is communicated throughout the brain, at least in part, through humoral-like volume transmission. Finally, we highlight mechanisms through which oxytocin interacts with various energy balance-associated neuropeptide and endocrine systems (e.g., agouti-related peptide, melanin-concentrating hormone, leptin), as well as the behavioral mechanisms through which oxytocin inhibits food intake, including effects on nutrient-specific ingestion, meal size control, food reward-motivated responses, and competing motivations.
Potential of Salivary Biomarkers in Autism Research: A Systematic Review
Authors: Janšáková Katarína , Kyselicová Klaudia , Ostatníková Daniela , Repiská Gabriela
Published: October 2021

The diagnostic process for autism spectrum disorders (ASD) is based on a behavioral analysis of the suspected individual. Despite intensive research, no specific and valid biomarker has been identified for ASD, but saliva, with its advantages such as non-invasive collection, could serve as a suitable alternative to other body fluids. As a source of nucleic acid of both human and microbial origin, protein and non-protein molecules, saliva offers a complex view on the current state of the organism. Additionally, the use of salivary markers seems to be less complicated not only for ASD screening but also for revealing the etiopathogenesis of ASD, since enrolling neurotypical counterparts willing to participate in studies may be more feasible. The aim of the presented review is to provide an overview of the current research performed on saliva in relation to ASD, mutual complementing, and discrepancies that result in difficulties applying the observed markers in clinical practice. We emphasize the methodological limitations of saliva collection and processing as well as the lack of information regarding ASD diagnosis, which is critically discussed.
Molecular Imaging of Human Skeletal Myoblasts (huSKM) in Mouse Post-Infarction Myocardium
Authors: Fiedorowicz Katarzyna , Wargocka-Matuszewska Weronika , Ambrożkiewicz Karolina A. , Rugowska Anna , Cheda Łukasz , Fiedorowicz Michał , Zimna Agnieszka , Drabik Monika , Borkowski Szymon , Świątkiewicz Maciej , Bogorodzki Piotr , Grieb Paweł , Hamankiewicz Paulina , Kolanowski Tomasz J. , Rozwadowska Natalia , Kozłowska Urszula , Klimczak Aleksandra , Kolasiński Jerzy , Rogulski Zbigniew , Kurpisz Maciej
Published: October 2021

Current treatment protocols for myocardial infarction improve the outcome of disease to some extent but do not provide the clue for full regeneration of the heart tissues. An increasing body of evidence has shown that transplantation of cells may lead to some organ recovery. However, the optimal stem cell population has not been yet identified. We would like to propose a novel pro-regenerative treatment for post-infarction heart based on the combination of human skeletal myoblasts (huSkM) and mesenchymal stem cells (MSCs). huSkM native or overexpressing gene coding for Cx43 (huSKMCx43) alone or combined with MSCs were delivered in four cellular therapeutic variants into the healthy and post-infarction heart of mice while using molecular reporter probes. Single-Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) performed right after cell delivery and 24 h later revealed a trend towards an increase in the isotopic uptake in the post-infarction group of animals treated by a combination of huSkMCx43 with MSC. Bioluminescent imaging (BLI) showed the highest increase in firefly luciferase (fluc) signal intensity in post-infarction heart treated with combination of huSkM and MSCs vs. huSkM alone (p < 0.0001). In healthy myocardium, however, nanoluciferase signal (nanoluc) intensity varied markedly between animals treated with stem cell populations either alone or in combinations with the tendency to be simply decreased. Therefore, our observations seem to show that MSCs supported viability, engraftment, and even proliferation of huSkM in the post-infarction heart.
Angiogenic Effects and Crosstalk of Adipose-Derived Mesenchymal Stem/Stromal Cells and Their Extracellular Vesicles with Endothelial Cells
Authors: Rautiainen Swarna , Laaksonen Timo , Koivuniemi Raili
Published: October 2021

Adipose-derived mesenchymal stem/stromal cells (ASCs) are an adult stem cell population able to self-renew and differentiate into numerous cell lineages. ASCs provide a promising future for therapeutic angiogenesis due to their ability to promote blood vessel formation. Specifically, their ability to differentiate into endothelial cells (ECs) and pericyte-like cells and to secrete angiogenesis-promoting growth factors and extracellular vesicles (EVs) makes them an ideal option in cell therapy and in regenerative medicine in conditions including tissue ischemia. In recent angiogenesis research, ASCs have often been co-cultured with an endothelial cell (EC) type in order to form mature vessel-like networks in specific culture conditions. In this review, we introduce co-culture systems and co-transplantation studies between ASCs and ECs. In co-cultures, the cells communicate via direct cell–cell contact or via paracrine signaling. Most often, ASCs are found in the perivascular niche lining the vessels, where they stabilize the vascular structures and express common pericyte surface proteins. In co-cultures, ASCs modulate endothelial cells and induce angiogenesis by promoting tube formation, partly via secretion of EVs. In vivo co-transplantation of ASCs and ECs showed improved formation of functional vessels over a single cell type transplantation. Adipose tissue as a cell source for both mesenchymal stem cells and ECs for co-transplantation serves as a prominent option for therapeutic angiogenesis and blood perfusion in vivo.
Salt Stress Promotes Abscisic Acid Accumulation to Affect Cell Proliferation and Expansion of Primary Roots in Rice
Authors: Huang Yingying , Zhou Jiahao , Li Yuxiang , Quan Ruidang , Wang Juan , Huang Rongfeng , Qin Hua
Published: October 2021

The primary root is the basic component of the root system and plays a key role in early seedling growth in rice. Its growth is easily affected by environmental cues, such as salt stress. Abscisic acid (ABA) plays an essential role in root development, but the molecular mechanism underlying ABA-regulated root growth in response to salt stress remains poorly understood. In this study, we report that salt stress inhibits primary root elongation and promotes primary root swelling. Moreover, salt stress induces the expression of ABA-responsive genes and ABA accumulation in the primary root, revealing that ABA plays an essential role in salt-modulated root growth. Transgenic lines of OsSAPK10-OE and OsABIL2-OE, which constitutively express OsSAPK10 or OsABIL2, with enhanced or attenuated ABA signaling, show increased and decreased sensitivity to salt, correspondingly. Microscopic analysis indicates that salt and ABA inhibits cell proliferation and promotes cell expansion in the root apical meristem. Transcriptome analysis showed that ABA induces the expression of EXPANSIN genes. Further investigations indicate that ABA exerts these effects largely through ABA signaling. Thus, our findings deepen our understanding of the role of ABA in controlling primary root growth in response to salt stress, and this knowledge can be used by breeders to cultivate rice varieties suitable for saline–alkali land.
Aging Resistance of Biocomposites Crosslinked with Silica and Quercetin
Authors: Masek Anna , Olejnik Olga
Published: October 2021

This research focuses on revealing the double role of quercetin accompanied by silica in epoxidized natural rubber. A crosslinking ability with antioxidative properties exists and reveals the dependence of these functions on quercetin content. Here, the aging resistance of self-healable biocomposites was analyzed. The self-healing properties were presented in our previous work. The stabilizing effect of quercetin applied as a crosslinking agent has been studied in epoxidized natural rubber with a 50 mol% of epoxidation (ENR-50). Some of five -OH moiety groups existing in the quercetin structure are able to react with epoxy rings of ENR-50 and cure this elastomer, whereas other free hydroxyl groups can donate the hydrogen molecule to a radical molecule, stabilizing it. The aging resistance of prepared composites was estimated by mechanical tests conducted before and after different types of aging, as well as by differences in color and surface energy between aged and un-aged samples. Changes within the oxygen function, which occurred as a result of the aging process, were observed using FT-IR absorbance spectroscopy. Furthermore, the impact of quercetin content on composites’ thermal stability was investigated by thermogravimetry (TGA). According to the results, a proper dose of quercetin can act as a crosslinker and antioxidant in ENR-50 at the same time.
Vaccines for Non-Viral Cancer Prevention
Authors: Bayó Cristina , Jung Gerhard , Español-Rego Marta , Balaguer Francesc , Benitez-Ribas Daniel
Published: October 2021

Cancer vaccines are a type of immune therapy that seeks to modulate the host’s immune system to induce durable and protective immune responses against cancer-related antigens. The little clinical success of therapeutic cancer vaccines is generally attributed to the immunosuppressive tumor microenvironment at late-stage diseases. The administration of cancer-preventive vaccination at early stages, such as pre-malignant lesions or even in healthy individuals at high cancer risk could increase clinical efficacy by potentiating immune surveillance and pre-existing specific immune responses, thus eliminating de novo appearing lesions or maintaining equilibrium. Indeed, research focus has begun to shift to these approaches and some of them are yielding encouraging outcomes.
Therapeutic Effect of an Antibody-Derived Peptide in a Galleria mellonella Model of Systemic Candidiasis
Authors: Ottaviano Emerenziana , Borghi Elisa , Giovati Laura , Falleni Monica , Tosi Delfina , Magliani Walter , Morace Giulia , Conti Stefania , Ciociola Tecla
Published: October 2021

The synthetic peptide T11F (TCRVDHRGLTF), with sequence identical to a fragment of the constant region of human IgM, and most of its alanine-substituted derivatives proved to possess a significant candidacidal activity in vitro. In this study, the therapeutic efficacy of T11F, D5A, the derivative most active in vitro, and F11A, characterized by a different conformation, was investigated in Galleria mellonella larvae infected with Candida albicans. A single injection of F11A and D5A derivatives, in contrast with T11F, led to a significant increase in survival of larvae injected with a lethal inoculum of C. albicans cells, in comparison with infected animals treated with saline. Peptide modulation of host immunity upon C. albicans infection was determined by hemocyte analysis and larval histology, highlighting a different immune stimulation by the studied peptides. F11A, particularly, was the most active in eliciting nodule formation, melanization and fat body activation, leading to a better control of yeast infection. Overall, the obtained data suggest a double role for F11A, able to simultaneously target the fungus and the host immune system, resulting in a more efficient pathogen clearance.
Regulatory B Cells Involvement in Autoimmune Phenomena Occurring in Pediatric Graves’ Disease Patients
Authors: Grubczak Kamil , Starosz Aleksandra , Stożek Karolina , Bossowski Filip , Moniuszko Marcin , Bossowski Artur
Published: October 2021

Graves’s disease is the most common type of autoimmune hyperthyroidism. Numerous studies indicate different factors contributing to the onset of the disease. Despite years of research, the exact pathomechanism of Graves’ disease still remains unresolved, especially in the context of immune response. B cells can play a dual role in autoimmune reactions, on the one hand, as a source of autoantibody mainly targeted in the thyroid hormone receptor (TSHR) and, on the other, by suppressing the activity of proinflammatory cells (as regulatory B cells). To date, data on the contribution of Bregs in Graves’ pathomechanism, especially in children, are scarce. Here, we investigated the frequencies of Bregs before and during a methimazole therapy approach. We reported higher Foxp3+ and IL-10+ Breg levels with CD38- phenotype and reduced numbers of CD38 + Foxp3 + IL-10+ in pediatric Graves’ patients. In addition, selected Breg subsets were found to correlate with TSH and TRAb levels significantly. Noteworthy, certain subpopulations of Bregs were demonstrated as prognostic factors for methimazole therapy outcome. Our data demonstrate the crucial role of Bregs and their potential use as a biomarker in Graves’ disease management.
Protection of Teleost Fish against Infectious Diseases through Oral Administration of Vaccines: Update 2021
Authors: Bøgwald Jarl , Dalmo Roy A.
Published: October 2021

Immersion and intraperitoneal injection are the two most common methods used for the vaccination of fish. Because both methods require that fish are handled and thereby stressed, oral administration of vaccines as feed supplements is desirable. In addition, in terms of revaccination (boosting) of adult fish held in net pens, oral administration of vaccines is probably the only feasible method to obtain proper protection against diseases over long periods of time. Oral vaccination is considered a suitable method for mass immunization of large and stress-sensitive fish populations. Moreover, oral vaccines may preferably induce mucosal immunity, which is especially important to fish. Experimental oral vaccine formulations include both non-encapsulated and encapsulated antigens, viruses and bacteria. To develop an effective oral vaccine, the desired antigens must be protected against the harsh environments in the stomach and gut so they can remain intact when they reach the lower gut/intestine where they normally are absorbed and transported to immune cells. The most commonly used encapsulation method is the use of alginate microspheres that can effectively deliver vaccines to the intestine without degradation. Other encapsulation methods include chitosan encapsulation, poly D,L-lactide-co-glycolic acid and liposome encapsulation. Only a few commercial oral vaccines are available on the market, including those against infectious pancreatic necrosis virus (IPNV), Spring viremia carp virus (SVCV), infectious salmon anaemia virus (ISAV) and Piscirickettsia salmonis. This review highlights recent developments of oral vaccination in teleost fish.
Stage Specificity, the Dynamic Regulators and the Unique Orchid Arundina graminifolia
Authors: Ahmad Sagheer , Lu Chuqiao , Wei Yonglu , Gao Jie , Jin Jianpeng , Zheng Chuanyuan , Zhu Genfa , Yang Fengxi
Published: October 2021

Orchids take years to reach flowering, but the unique bamboo orchid (Arundina graminifolia) achieves reproductive maturity in six months and then keeps on year round flowering. Therefore, studying different aspects of its growth, development and flowering is key to boost breeding programs for orchids. This study uses transcriptome tools to discuss genetic regulation in five stages of flower development and four tissue types. Stage specificity was focused to distinguish genes specifically expressed in different stages of flower development and tissue types. The top 10 highly expressed genes suggested unique regulatory patterns for each stage or tissue. The A. graminifolia sequences were blasted in Arabidopsis genome to validate stage specific genes and to predict important hormonal and cell regulators. Moreover, weighted gene co-expression network analysis (WGCNA) modules were ascertained to suggest highly influential hubs for early and late stages of flower development, leaf and root. Hormonal regulators were abundant in all data sets, such as auxin (LAX2, GH3.1 and SAUR41), cytokinin (LOG1), gibberellin (GASA3 and YAB4), abscisic acid (DPBF3) and sucrose (SWEET4 and SWEET13). Findings of this study, thus, give a fine sketch of genetic variability in Orchidaceae and broaden our understanding of orchid flower development and the involvement of multiple pathways.
Cardiac Telocytes 16 Years on—What Have We Learned So Far, and How Close Are We to Routine Application of the Knowledge in Cardiovascular Regenerative Medicine?
Authors: Klein Martin , Csöbönyeiová Mária , Žiaran Stanislav , Danišovič Ľuboš , Varga Ivan
Published: October 2021

The regeneration of a diseased heart is one of the principal challenges of modern cardiovascular medicine. There has been ongoing research on stem-cell-based therapeutic approaches. A cell population called telocytes (TCs) described only 16 years ago largely contributed to the research area of cardiovascular regeneration. TCs are cells with small bodies and extremely long cytoplasmic projections called telopodes, described in all layers of the heart wall. Their functions include cell-to-cell signaling, stem-cell nursing, mechanical support, and immunoregulation, to name but a few. The functional derangement or quantitative loss of TCs has been implicated in the pathogenesis of myocardial infarction, heart failure, arrhythmias, and many other conditions. The exact pathomechanisms are still unknown, but the loss of regulative, integrative, and nursing functions of TCs may provide important clues. Therefore, a viable avenue in the future modern management of these conditions is TC-based cell therapy. TCs have been previously transplanted into a mouse model of myocardial infarction with promising results. Tandem transplantation with stem cells may provide additional benefit; however, many underresearched areas need to be addressed in future research before routine application of TC-based cell therapy in human subjects. These include the standardization of protocols for isolation, cultivation, and transplantation, quantitative optimization of TC transplants, cost-effectivity analysis, and many others.
Androgen Receptor Activation in Glioblastoma Can Be Achieved by Ligand-Independent Signaling through EGFR—A Potential Therapeutic Target
Authors: Zalcman Nomi , Gutreiman Mijal , Shahar Tal , Weller Michael , Lavon Iris
Published: October 2021

Androgen receptor (AR) is a ligand-mediated transcription factor that belongs to the superfamily of steroid receptors. AR is overexpressed in most glioblastomas and is a potential therapeutic target. In prostate and breast cancers, AR activation can be achieved also by a ligand-independent signaling through receptor tyrosine kinases such as epidermal growth factor receptor (EGFR). Considering its major role in glioblastoma, we explored whether EGFR is involved in AR signaling in this tumor. Analysis of mRNA expression in 28 glioblastoma samples with quantitative real-time reverse-transcription polymerase chain reaction revealed a positive and significant correlation between AR and EGFR mRNA expression levels (R = 0.47, p = 0.0092), which was validated by The Cancer Genome Atlas dataset (n = 671) analysis (R = 0.3, p = 0.00006). Using Western blotting and immunofluorescence staining, we showed that the transduced overexpression of EGFR or its variant EGFRvIII in the U87MG cells induced AR protein overexpression and nuclear translocation and Protein kinase B (AKT) S473 and AR S210/213 phosphorylation. The EGFR kinase inhibitor afatinib and the AKT inhibitor MK2206 reduced AR nuclear translocation. Afatinib diminished AKT phosphorylation at 30 min and 6 h in the EGFR- and EGFRvIII-overexpressing cells, respectively, and decreased AR phosphorylation in EGFR-overexpressing cells at 4 h. Afatinib or MK2206 combination therapy with the AR antagonist enzalutamide in the EGFR and EGFRvIII-overexpressing cells had synergistic efficacy. Our findings suggest that EGFR signaling is involved in AR activation in glioblastoma and buttresses the concept of combining an EGFR signaling inhibitor with AR antagonists as a potential glioblastoma treatment.
Synthesis and Characterization of Novel Succinyl Chitosan-Dexamethasone Conjugates for Potential Intravitreal Dexamethasone Delivery
Authors: Dubashynskaya Natallia V. , Bokatyi Anton N. , Golovkin Alexey S. , Kudryavtsev Igor V. , Serebryakova Maria K. , Trulioff Andrey S. , Dubrovskii Yaroslav A. , Skorik Yury A.
Published: October 2021

The development of intravitreal glucocorticoid delivery systems is a current global challenge for the treatment of inflammatory diseases of the posterior segment of the eye. The main advantages of these systems are that they can overcome anatomical and physiological ophthalmic barriers and increase local bioavailability while prolonging and controlling drug release over several months to improve the safety and effectiveness of glucocorticoid therapy. One approach to the development of optimal delivery systems for intravitreal injections is the conjugation of low-molecular-weight drugs with natural polymers to prevent their rapid elimination and provide targeted and controlled release. This study focuses on the development of a procedure for a two-step synthesis of dexamethasone (DEX) conjugates based on the natural polysaccharide chitosan (CS). We first used carbodiimide chemistry to conjugate DEX to CS via a succinyl linker, and we then modified the obtained systems with succinic anhydride to impart a negative ζ-potential to the polymer particle surface. The resulting polysaccharide carriers had a degree of substitution with DEX moieties of 2–4%, a DEX content of 50–85 μg/mg, and a degree of succinylation of 64–68%. The size of the obtained particles was 400–1100 nm, and the ζ-potential was −30 to −33 mV. In vitro release studies at pH 7.4 showed slow hydrolysis of the amide and ester bonds in the synthesized systems, with a total release of 8–10% for both DEX and succinyl dexamethasone (SucDEX) after 1 month. The developed conjugates showed a significant anti-inflammatory effect in TNFα-induced and LPS-induced inflammation models, suppressing CD54 expression in THP-1 cells by 2- and 4-fold, respectively. Thus, these novel succinyl chitosan-dexamethasone (SucCS-DEX) conjugates are promising ophthalmic carriers for intravitreal delivery.
FosL1 Is a Novel Target of Levetiracetam for Suppressing the Microglial Inflammatory Reaction
Authors: Niidome Kouji , Taniguchi Ruri , Yamazaki Takeshi , Tsuji Mayumi , Itoh Kouichi , Ishihara Yasuhiro
Published: October 2021

We previously showed that the antiepileptic drug levetiracetam (LEV) inhibits microglial activation, but the mechanism remains unclear. The purpose of this study was to identify the target of LEV in microglial activity suppression. The mouse microglial BV-2 cell line, cultured in a ramified form, was pretreated with LEV and then treated with lipopolysaccharide (LPS). A comprehensive analysis of LEV targets was performed by cap analysis gene expression sequencing using BV-2 cells, indicating the transcription factors BATF, Nrf-2, FosL1 (Fra1), MAFF, and Spic as candidates. LPS increased AP-1 and Spic transcriptional activity, and LEV only suppressed AP-1 activity. FosL1, MAFF, and Spic mRNA levels were increased by LPS, and LEV only attenuated FosL1 mRNA expression, suggesting FosL1 as an LEV target. FosL1 protein levels were increased by LPS treatment and decreased by LEV pretreatment, similar to FosL1 mRNA levels. The FosL1 siRNA clearly suppressed the expression of TNFα and IL-1β. Pilocarpine-induced status epilepticus increased hippocampus FosL1 expression, along with inflammation. LEV treatment significantly suppressed FosL1 expression. Together, LEV reduces FosL1 expression and AP-1 activity in activated microglia, thereby suppressing neuroinflammation. LEV might be a candidate for the treatment of several neurological diseases involving microglial activation.
The Role of Phosphatidylinositol 3-Kinase Catalytic Subunit Type 3 in the Pathogenesis of Human Cancer
Authors: Chu Chien-An , Wang Yi-Wen , Chen Yi-Lin , Chen Hui-Wen , Chuang Jing-Jing , Chang Hong-Yi , Ho Chung-Liang , Chang Chen , Chow Nan-Haw , Lee Chung-Ta
Published: October 2021

Phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3), the mammalian ortholog of yeast vesicular protein sorting 34 (Vps34), belongs to the phosphoinositide 3-kinase (PI3K) family. PIK3C3 can phosphorylate phosphatidylinositol (PtdIns) to generate phosphatidylinositol 3-phosphate (PI3P), a phospholipid central to autophagy. Inhibition of PIK3C3 successfully inhibits autophagy. Autophagy maintains cell survival when modifications occur in the cellular environment and helps tumor cells resist metabolic stress and cancer treatment. In addition, PIK3C3 could induce oncogenic transformation and enhance tumor cell proliferation, growth, and invasion through mechanisms independent of autophagy. This review addresses the structural and functional features, tissue distribution, and expression pattern of PIK3C3 in a variety of human tumors and highlights the underlying mechanisms involved in carcinogenesis. The implications in cancer biology, patient prognosis prediction, and cancer therapy are discussed. Altogether, the discovery of pharmacological inhibitors of PIK3C3 could reveal novel strategies for improving treatment outcomes for PIK3C3-mediated human diseases.
Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications
Authors: Desaulniers Daniel , Vasseur Paule , Jacobs Abigail , Aguila M. Cecilia , Ertych Norman , Jacobs Miriam N.
Published: October 2021

Epigenetics involves a series of mechanisms that entail histone and DNA covalent modifications and non-coding RNAs, and that collectively contribute to programing cell functions and differentiation. Epigenetic anomalies and DNA mutations are co-drivers of cellular dysfunctions, including carcinogenesis. Alterations of the epigenetic system occur in cancers whether the initial carcinogenic events are from genotoxic (GTxC) or non-genotoxic (NGTxC) carcinogens. NGTxC are not inherently DNA reactive, they do not have a unifying mode of action and as yet there are no regulatory test guidelines addressing mechanisms of NGTxC. To fil this gap, the Test Guideline Programme of the Organisation for Economic Cooperation and Development is developing a framework for an integrated approach for the testing and assessment (IATA) of NGTxC and is considering assays that address key events of cancer hallmarks. Here, with the intent of better understanding the applicability of epigenetic assays in chemical carcinogenicity assessment, we focus on DNA methylation and histone modifications and review: (1) epigenetic mechanisms contributing to carcinogenesis, (2) epigenetic mechanisms altered following exposure to arsenic, nickel, or phenobarbital in order to identify common carcinogen-specific mechanisms, (3) characteristics of a series of epigenetic assay types, and (4) epigenetic assay validation needs in the context of chemical hazard assessment. As a key component of numerous NGTxC mechanisms of action, epigenetic assays included in IATA assay combinations can contribute to improved chemical carcinogen identification for the better protection of public health.
New Approach of Measuring Human Personality Traits Using Ontology-Based Model from Social Media Data
Authors: Alamsyah Andry , Dudija Nidya , Widiyanesti Sri
Published: October 2021

Human online activities leave digital traces that provide a perfect opportunity to understand their behavior better. Social media is an excellent place to spark conversations or state opinions. Thus, it generates large-scale textual data. In this paper, we harness those data to support the effort of personality measurement. Our first contribution is to develop the Big Five personality trait-based model to detect human personalities from their textual data in the Indonesian language. The model uses an ontology approach instead of the more famous machine learning model. The former better captures the meaning and intention of phrases and words in the domain of human personality. The legacy and more thorough ways to assess nature are by doing interviews or by giving questionnaires. Still, there are many real-life applications where we need to possess an alternative method, which is cheaper and faster than the legacy methodology to select individuals based on their personality. The second contribution is to support the model implementation by building a personality measurement platform. We use two distinct features for the model: an n-gram sorting algorithm to parse the textual data and a crowdsourcing mechanism that facilitates public involvement contributing to the ontology corpus addition and filtering.
A Fine-Scale Hotspot at the Edge: Epigean Arthropods from the Atacama Coast (Paposo-Taltal, Antofagasta Region, Chile)
Authors: Pizarro-Araya Jaime , Alfaro Fermín M. , Ojanguren-Affilastro Andrés A. , Moreira-Muñoz Andrés
Published: October 2021

The Atacama Desert at its margins harbors a unique biodiversity that is still very poorly known, especially in coastal fog oases spanning from Perú towards the Atacama coast. An outstanding species-rich fog oasis is the latitudinal fringe Paposo-Taltal, that is considered an iconic site of the Lomas formation. This contribution is the first to reveal the knowledge on arthropods of this emblematic coastal section. We used pitfall traps to study the taxonomic composition, richness, and abundance of terrestrial arthropods in 17 sample sites along a 100 km section of the coast between 24.5 and 25.5 southern latitude, in a variety of characteristic habitats. From a total of 9154 individuals, we were able to identify 173 arthropod species grouped into 118 genera and 57 families. The most diverse group were insects, with 146 species grouped in 97 genera and 43 families, while arachnids were represented by 27 species grouped into 21 genera and 14 families. Current conservation challenges on a global scale are driving the creation and evaluation of potential conservation sites in regions with few protected areas, such as the margins of the Atacama Desert. Better taxonomic, distributional, and population knowledge is urgently needed to perform concrete conservation actions in a biodiversity hotspot at a desert edge.
Implications of Sublethal Insecticide Exposure and the Development of Resistance on Mosquito Physiology, Behavior, and Pathogen Transmission
Authors: Andreazza Felipe , Oliveira Eugênio E. , Martins Gustavo Ferreira
Published: October 2021

For many decades, insecticides have been used to control mosquito populations in their larval and adult stages. Although changes in the population genetics, physiology, and behavior of mosquitoes exposed to lethal and sublethal doses of insecticides are expected, the relationships between these changes and their abilities to transmit pathogens remain unclear. Thus, we conducted a comprehensive review on the sublethal effects of insecticides and their contributions to insecticide resistance in mosquitoes, with the main focus on pyrethroids. We discuss the direct and acute effects of sublethal concentrations on individuals and populations, the changes in population genetics caused by the selection for resistance after insecticide exposure, and the major mechanisms underlying such resistance. Sublethal exposures negatively impact the individual’s performance by affecting their physiology and behavior and leaving them at a disadvantage when compared to unexposed organisms. How these sublethal effects could change mosquito population sizes and diversity so that pathogen transmission risks can be affected is less clear. Furthermore, despite the beneficial and acute aspects of lethality, exposure to higher insecticide concentrations clearly impacts the population genetics by selecting resistant individuals, which may bring further and complex interactions for mosquitoes, vertebrate hosts, and pathogens. Finally, we raise several hypotheses concerning how the here revised impacts of insecticides on mosquitoes could interplay with vector-mediated pathogens’ transmission.
Frontiers Approaches to the Diagnosis of Thrips (Thysanoptera): How Effective Are the Molecular and Electronic Detection Platforms?
Authors: Ghosh Amalendu , Jangra Sumit , Dietzgen Ralf G. , Yeh Wen-Bin
Published: October 2021

Thrips are insect pests of economically important agricultural, horticultural, and forest crops. They cause damage by sucking plant sap and by transmitting several tospoviruses, ilarviruses, carmoviruses, sobemoviruses, and machlomoviruses. Accurate and timely identification is the key to successful management of thrips species. However, their small size, cryptic nature, presence of color and reproductive morphs, and intraspecies genetic variability make the identification of thrips species challenging. The use of molecular and electronic detection platforms has made thrips identification rapid, precise, sensitive, high throughput, and independent of developmental stages. Multi-locus phylogeny based on mitochondrial, nuclear, and other markers has resolved ambiguities in morphologically indistinguishable thrips species. Microsatellite, RFLP, RAPD, AFLP, and CAPS markers have helped to explain population structure, gene flow, and intraspecies heterogeneity. Recent techniques such as LAMP and RPA have been employed for sensitive and on-site identification of thrips. Artificial neural networks and high throughput diagnostics facilitate automated identification. This review also discusses the potential of pyrosequencing, microarrays, high throughput sequencing, and electronic sensors in delimiting thrips species.
“What’s This Bug?” Questions from the Public Provide Relevant Information on Species Distribution and Human–Insect Interactions
Authors: Drapeau Picard André-Philippe , Giroux Marjolaine , Saint-Germain Michel , Larrivée Maxim
Published: October 2021

In general, insects and arthropods polarizing: they either fascinate people, disgust people, or both, and they generate lots of questions. Museums are perceived as reliable sources of information and, as such, a go-to destination for the public to receive answers. Since its opening in 1990, the Montreal Insectarium has offered an entomological information service, allowing the public to send questions, photographs, and specimens for identification. All requests are answered by entomologists. Spatiotemporal variations in taxonomic, geographic, and thematic profiles of the 4163 requests received in 2010–2011 and 2017–2018 were analyzed. Requests came from 35 countries, and most of those requests came from Canada. The majority of requests were identification requests. Representing 25% of identification requests, the five most frequent species were the eastern dobsonfly Corydalus cornutus, the masked hunter Reduvius personatus, the giant water bug Lethocerus americanus, the western conifer-seed bug Leptoglossus occidentalis, and the Japanese beetle Popillia japonica. A comparison with the data from the citizen science platform iNaturalist shows that the EIS can be a valuable tool for invasive species detection. Frequent subjects included school projects, entomophagy (eating insects), and wasp and bee nests. Finally, we discuss the role of entomologists in providing scientific information but also in addressing common concerns regarding cohabitation with arthropods.
Bumble Bee Foraged Pollen Analyses in Spring Time in Southern Estonia Shows Abundant Food Sources
Authors: Bontšutšnaja Anna , Karise Reet , Mänd Marika , Smagghe Guy
Published: October 2021

Agricultural landscapes usually provide higher quantities of single-source food, which are noticeably lacking in diversity and might thus have low nutrient value for bumble bee colony development. Here, in this study, we analysed the pollen foraging preferences over a large territory of a heterogeneous agricultural landscape: southern Estonia. We aimed to assess the botanical diversity of bumble bee food plants in the spring time there. We looked for preferences for some food plants or signs of food shortage that could be associated with any particular landscape features. For this purpose, we took Bombus terrestris commercial hives to the landscape, performed microscopy analyses and improved the results with the innovative DNA metabarcoding technique to determine the botanical origin of bumble bee-collected pollen. We found high variability of forage plants with no strong relationship with any particular landscape features. Based on the low number of plant species in single flights, we deduce that the availability of main forage plants is sufficient indicating rich forage availabilities. Despite specific limitations, we saw strong correlations between microscopy and DNA metabarcoding data usable for quantification analyses. As a conclusion, we saw that the spring-time vegetation in southern Estonia can support bumble bee colony development regardless of the detailed landscape structure. The absence of clearly dominating food preference by the tested generalist bumble bee species B. terrestris makes us suggest that other bumble bee species, at least food generalists, should also find plenty of forage in their early development phase.