bluuebunny/crossref_metadata_2025 huggingface dataset:
Passive Vaping from Sub-Ohm Electronic Cigarette Devices
Authors: Manigrasso Maurizio , Protano Carmela , Vitali Matteo , Avino Pasquale
Published: November 2021

To investigate passive vaping due to sub-ohm electronic cigarettes (e-cigs), aerosol number size distribution measurements (6 nm–10 µm) were performed during volunteer-vaping sessions. E-liquids, with vegetable glycerin (VG) and propylene glycol (PG), with a VG/PG ratio of 50/50 (with nicotine) and 80/20 (without nicotine), were vaped with a double-coil, single aerosol exit hole at 25–80 W electric power, corresponding to 130–365 kW m−2 heat fluxes and with an octa-coil, four aerosol exit holes atomizers, at 50–150 W electric power, corresponding to 133–398 kW m−2 heat fluxes. At the lowest heat flux, lower particle number concentrations (NTot) were observed for the nicotine-liquid than for the nicotine-free liquid, also due to its higher content of PG, more volatile than VG. For the octa-coil atomizer, at 265 and 398 kW m−2, NTot decreased below the first-generation e-cig, whereas volume concentrations greatly increased, due to the formation of super micron droplets. Higher volume concentrations were observed for the 80/20 VG/PG liquid, because of VG vaporization and of its decomposition products, greater than for PG. For the double coil atomizer, increasing the electric power from 40 W (208 kW m−2) to 80 W (365 kW m−2) possibly led to a critical heat flow condition, causing a reduction of the number concentrations for the VG/PG 50/50 liquid, an increase for the 80/20 VG/PG liquid and a decrease of the volume concentrations for both of them. Coherently, the main mode was at about 0.1 µm on both metrics for both liquids. For the other tests, two main modes (1 and 2 µm) were observed in the volume size distributions, the latter becoming wider at 100 and 150 W (265 and 398 kW m−2), suggesting the increased emission of light condensable decomposition products. The lower aerosol emissions observed at 150 W than at 100 W suggest the formation of gas-phase decomposition products. The observation of low-count high-volume aerosols addresses the relevance of the volume metric upon measuring the second-hand concentration of the aerosols released by sub-ohm e-cigarettes.
Source Apportionment of Fine Organic Particulate Matter (PM2.5) in Central Addis Ababa, Ethiopia
Authors: Tefera Worku , Kumie Abera , Berhane Kiros , Gilliland Frank , Lai Alexandra , Sricharoenvech Piyaporn , Patz Jonathan , Samet Jonathan , Schauer James J.
Published: November 2021

The development of infrastructure, a rapidly increasing population, and urbanization has resulted in increasing air pollution levels in the African city of Addis Ababa. Prior investigations into air pollution have not yet sufficiently addressed the sources of atmospheric particulate matter. This study aims to identify the major sources of fine particulate matter (PM2.5) and its seasonal contribution in Addis Ababa, Ethiopia. Twenty-four-hour average PM2.5 mass samples were collected every 6th day, from November 2015 through November 2016. Chemical species were measured in samples and source apportionment was conducted using a chemical mass balance (CMB) receptor model that uses particle-phase organic tracer concentrations to estimate source contributions to PM2.5 organic carbon (OC) and the overall PM2.5 mass. Vehicular sources (28%), biomass burning (18.3%), plus soil dust (17.4%) comprise about two-thirds of the PM2.5 mass, followed by sulfate (6.5%). The sources of air pollution vary seasonally, particularly during the main wet season (June–September) and short rain season (February–April): From motor vehicles, (31.0 ± 2.6%) vs. (24.7 ± 1.2%); biomass burning, (21.5 ± 5%) vs. (14 ± 2%); and soil dust, (11 ± 6.4%) vs. (22.7 ± 8.4%), respectively, are amongst the three principal sources of ambient PM2.5 mass in the city. We suggest policy measures focusing on transportation, cleaner fuel or energy, waste management, and increasing awareness on the impact of air pollution on the public’s health.
Comparison of Polydrug Use Prevalences and Typologies between Men Who Have Sex with Men and General Population Men, in Madrid and Barcelona
Authors: Guerras Juan-Miguel , Hoyos Juan , García de Olalla Patricia , de la Fuente Luis , Herrero Lidia , Palma David , del Romero Jorge , García-Pérez Jorge-Néstor , Belza María-José ,   The Methysos Project Group
Published: November 2021

This study compares the prevalence of drug use and the typologies of polydrug use (PDU) in men who have sex with men (MSM) and general population men (GPM). Participants were men aged 16–64, living in the provinces of Madrid and Barcelona: 1720 were recruited in a GPM survey, and 2658 were HIV-negative MSM from HIV/STIs diagnosis services. Lifetime and last-year prevalence of drug use and prevalence ratios (PRs) of MSM to GPM for the different drugs were calculated using Poisson regression. Latent class analysis (LCA) was performed to identify typologies of PDU. Lifetime use of the drugs considered was higher in MSM, and even higher for drug use in the last-year: PRs for cannabis, hallucinogens and cocaine ranged from 2–5; for amphetamine, ecstasy and methamphetamine 12–16; and above 60 for ketamine, GHB/GBL, inhalants and mephedrone. In the LCA for lifetime PDU four classes arose from the GPM (No-PDU (79.6%); Conventional PDU (13.8%); Intensive conventional PDU (4.9%); Heavy PDU (1.8%)) and four among MSM (No-PDU (57.7%); Conventional PDU plus poppers (18.8%); PDU preferring chemsex drugs (6.4%); Heavy PDU (17.2%)). For PDU during the last-year, three classes arose in the GPM: No-PDU (94.7%); Conventional PDU (4.3%); Heavy PDU (0.9%). For MSM, we identified four classes: No-PDU (64.7%); Conventional PDU plus poppers (15.6%); PDU preferring chemsex drugs (6.2%); Heavy PDU (13.5%). MSM should be considered a priority group for the prevention of the use of all drugs but the heterogeneity of PDU typologies regarding users’ preference towards conventional and/or sexualised drugs needs to be taken into account.
Harmonization and Visualization of Data from a Transnational Multi-Sensor Personal Exposure Campaign
Authors: Novak Rok , Petridis Ioannis , Kocman David , Robinson Johanna Amalia , Kanduč Tjaša , Chapizanis Dimitris , Karakitsios Spyros , Flückiger Benjamin , Vienneau Danielle , Mikeš Ondřej , Degrendele Céline , Sáňka Ondřej , García Dos Santos-Alves Saul , Maggos Thomas , Pardali Demetra , Stamatelopoulou Asimina , Saraga Dikaia , Persico Marco Giovanni , Visave Jaideep , Gotti Alberto , Sarigiannis Dimosthenis
Published: November 2021

Use of a multi-sensor approach can provide citizens with holistic insights into the air quality of their immediate surroundings and their personal exposure to urban stressors. Our work, as part of the ICARUS H2020 project, which included over 600 participants from seven European cities, discusses the data fusion and harmonization of a diverse set of multi-sensor data streams to provide a comprehensive and understandable report for participants. Harmonizing the data streams identified issues with the sensor devices and protocols, such as non-uniform timestamps, data gaps, difficult data retrieval from commercial devices, and coarse activity data logging. Our process of data fusion and harmonization allowed us to automate visualizations and reports, and consequently provide each participant with a detailed individualized report. Results showed that a key solution was to streamline the code and speed up the process, which necessitated certain compromises in visualizing the data. A thought-out process of data fusion and harmonization of a diverse set of multi-sensor data streams considerably improved the quality and quantity of distilled data that a research participant received. Though automation considerably accelerated the production of the reports, manual and structured double checks are strongly recommended.
Short-Term Impacts of Meteorology, Air Pollution, and Internet Search Data on Viral Diarrhea Infection among Children in Jilin Province, China
Authors: Lu Wengao , Li Jingxin , Li Jinsong , Ai Danni , Song Hong , Duan Zhaojun , Yang Jian
Published: November 2021

The influence of natural environmental factors and social factors on children’s viral diarrhea remains inconclusive. This study aimed to evaluate the short-term effects of temperature, precipitation, air quality, and social attention on children’s viral diarrhea in temperate regions of China by using the distribution lag nonlinear model (DLNM). We found that low temperature affected the increase in children’s viral diarrhea infection for about 1 week, while high temperature and heavy precipitation affected the increase in children’s viral diarrhea infection risk for at least 3 weeks. As the increase of the air pollution index may change the daily life of the public, the infection of children’s viral diarrhea can be restrained within 10 days, but the risk of infection will increase after 2 weeks. The extreme network search may reflect the local outbreak of viral diarrhea, which will significantly improve the infection risk. The above factors can help the departments of epidemic prevention and control create early warnings of high-risk outbreaks in time and assist the public to deal with the outbreak of children’s viral diarrhea.
An Integrated Management System for Noncommunicable Diseases Program Implementation in a Sub-Saharan Setting
Authors: Miselli Maria Agata , Cavallin Francesco , Marwa Samwel , Ndunguru Bruno , Itambu Rehema John , Mutalemwa Katunzi , Rizzi Monica , Ciccarelli Giulia , Conte Simone , Taddei Stefano , Azzimonti Gaetano , Putoto Giovanni , Torelli Giovanni Fernando
Published: November 2021

Morbidity and mortality due to noncommunicable diseases (NCDs) are growing exponentially across Tanzania. The limited availability of dedicated services and the disparity between rural and urban areas represent key factors for the increased burden of NCDs in the country. From March 2019, an integrated management system was started in the Iringa District Council. The system implements an integrated management of hypertension and diabetes between the hospital and the peripheral health centers and introduces the use of paper-based treatment cards. The aim of the study was to present the results of the first 6 months’ roll-out of the system, which included 542 patients. Data showed that 46.1% of patients returned for the reassessment visit (±1 month), more than 98.4% of patients had blood pressure measured and were checked for complication, more than 88.6% of patients had blood sugar tested during follow-up visit, and blood pressure was at target in 42.8% of patients with hypertension and blood sugar in 37.3% of diabetic patients. Most patients who were lost to follow-up or did not reach the targets were those without medical insurance or living in remote peripheries. Our findings suggest that integrated management systems connecting primary health facilities and referral hospitals may be useful in care and follow-up of patients with hypertension and diabetes.
Evaluation of the Body Composition and Selected Physiological Variables of the Skin Surface Depending on Technical and Tactical Skills of Kickboxing Athletes in K1 Style
Authors: Rydzik Łukasz , Ambroży Tadeusz , Obmiński Zbigniew , Błach Wiesław , Ouergui Ibrahim
Published: November 2021

Background: Kickboxing is a combat sport with high demands on fitness and coordination skills. Scientific research shows that kickboxing fights induce substantial physiological stress. Therefore, it is important to determine the body composition of athletes before competitions and to analyze the skin temperature and skin pH during the fight. Methods: This study aimed to determine the body composition, skin temperature, and skin pH in kickboxers during a fight according to K1 rules. A total of 24 kickboxers (age range: 19 to 28 years) competing in a local K1 kickboxing league participated in the present study. Results: Changes in skin temperature and pH were observed and significant correlations were found between body composition and weight category. Conclusions: Changes in skin temperature and pH were demonstrated after each round of the bout. Level of body fat and muscle tissue significantly correlates with technical-tactical skills of the K1 athletes studied.
Validation and Measurement Invariance of the Body Appreciation Scale-2 between Genders in a Malaysian Sample
Authors: Tan Chee-Seng , Cheng Siew-May , Cong Chin Wen , Abu Bakar Afi Roshezry Bin , Michael Edwin , Mohd Wazir Mohamad Iqbaal Bin , Mat Alim Muliyati Binti , Ahmad Tajudin Bazlin Darina Binti , Mohamed Rosli Nor Ez-Zatul Hanani Binti , Asmi Alfian Bin
Published: November 2021

The 10-item Body Appreciation Scale-2 (BAS-2) is a measurement for individuals to self-report the extent to which they accept and respect their bodies. Although the BAS-2 has been translated into the Malay language and found to have promising qualities, the psychometric characteristics of the English version of BAS-2 remain unknown in the Malaysian context. The present study thus administered the English version BAS-2 and selfie-editing frequency scale to 797 individuals aged 18 to 56 years old in Malaysia. The dataset that was randomly divided into two halves were submitted to exploratory factor analysis and confirmatory factor analysis respectively. Both of the factor analyses consistently support a one-factor model. The Cronbach’s alpha and McDonald omega coefficients were greater than 0.90, indicating that the BAS-2 has good internal consistency. The incremental validity is also evident. A hierarchical multiple regression showed that the BAS-2 score had a positive relationship with selfie-editing frequency after controlling for age and gender. Moreover, the measurement invariance test supported scalar invariance between genders, and an analysis of covariance did not find significant gender differences. Overall, the findings replicate past findings and regularly support the usability of the BAS-2 in the Malaysian context. The implications of the BAS-2 and future directions are also discussed.
Increasing Disaster Medical Assistance Teams’ Intent to Engage with Specific Hazards
Authors: Iyama Keita , Kakamu Takeyasu , Yamashita Kazunori , Sato Yoshinobu , Shimada Jiro , Tasaki Osamu , Hasegawa Arifumi
Published: November 2021

To ensure human resource availability for a smooth response during various types of disasters, there is a need to improve the intent of those involved in responding to each hazard type. However, Disaster Medical Assistance Team personnel’s intent to engage with specific hazards has yet to be clarified. This study therefore aimed to clarify the factors affecting Disaster Medical Assistance Team members’ (n = 178) intent to engage with each type of hazard through an anonymous web questionnaire survey containing 20 questions. Our results show that the intent to engage in disaster response activities was significantly lower for chemical (50), biological (47), radiological/nuclear (58), and explosive (52) incidents compared with natural (82) and man-made hazards (82) (p < 0.01). Multiple regression analysis showed that incentives were the most common factor affecting responders’ intent to engage with all hazard types, followed by self-confidence. Thus, creating a system that provides generous incentives could effectively improve disaster responders’ intent to engage with specific hazards. Another approach could be education and training to increase disaster responders’ confidence. We believe that the successful implementation of these measures would improve the intent of responders to engage with hazards and promote the recruitment of sufficient human resources.
Complexities of Socio-Labor Integration in Chile: Migrating Colombian Women’s Experiences
Authors: Segovia Jimena Silva , Castillo Ravanal Estefany
Published: November 2021

The objective of the article is to understand Afro-Colombian women’s emotional experiences of the migratory process, and their labor insertion in Chilean territory. The Antofagasta region is one of the doors that connects Chile with its neighbors; at the same time, it is a national territory that is linked to important economic and human movements due to its mining activity. In the analysis of the data collected through of group and individual interviews conducted in the city of Antofagasta, we found experiences of xenophobia, labor abuse, discrimination, prejudices, and stereotypes articulated, along with the tendency of Chilean culture to value European traits over native Latin American traits.
Co-Immobilization of Rhizopus oryzae and Candida rugosa Lipases onto mMWCNTs@4-arm-PEG-NH2—A Novel Magnetic Nanotube–Polyethylene Glycol Amine Composite—And Its Applications for Biodiesel Production
Authors: Abdulmalek Saadiah A. , Li Kai , Wang Jianhua , Ghide Michael Kidane , Yan Yunjun
Published: November 2021

This article describes the successful synthesis of a novel nanocomposite of superparamagnetic multi-walled nanotubes with a four-arm polyethylene glycol amine polymer (mMWCNTs@4-arm-PEG-NH2). This composite was then employed as a support for the covalent co-immobilization of Rhizopus oryzae and Candida rugosa lipases under appropriate conditions. The co-immobilized lipases (CIL-mMWCNTs@4-arm-PEG-NH2) exhibited maximum specific activity of 99.626U/mg protein, which was 34.5-fold superior to that of free ROL, and its thermal stability was greatly improved. Most significantly, CIL-mMWCNTs@4-arm-PEG-NH2 was used to prepare biodiesel from waste cooking oil under ultrasound conditions, and within 120 min, the biodiesel conversion rate reached 97.64%. This was due to the synergy effect between ROL and CRL and the ultrasound-assisted enzymatic process, resulting in an increased biodiesel yield in a short reaction time. Moreover, after ten reuse cycles, the co-immobilized lipases still retained a biodiesel yield of over 78.55%, exhibiting excellent operational stability that is attractive for practical applications. Consequently, the combined use of a novel designed carrier, the co-immobilized lipases with synergy effect, and the ultrasound-assisted enzymatic reaction exhibited potential prospects for future applications in biodiesel production and various industrial applications.
From Molecular Recognition to the “Vehicles” of Evolutionary Complexity: An Informational Approach
Authors: Marijuán Pedro C. , Navarro Jorge
Published: November 2021

Countless informational proposals and models have explored the singular characteristics of biological systems: from the initial choice of information terms in the early days of molecular biology to the current bioinformatic avalanche in this “omic” era. However, this was conducted, most often, within partial, specialized scopes or just metaphorically. In this paper, we attempt a consistent informational discourse, initially based on the molecular recognition paradigm, which addresses the main stages of biological organization in a new way. It considers the interconnection between signaling systems and information flows, between informational architectures and biomolecular codes, between controlled cell cycles and multicellular complexity. It also addresses, in a new way, a central issue: how new evolutionary paths are opened by the cumulated action of multiple variation engines or mutational ‘vehicles’ evolved for the genomic exploration of DNA sequence space. Rather than discussing the possible replacement, extension, or maintenance of traditional neo-Darwinian tenets, a genuine informational approach to evolutionary phenomena is advocated, in which systemic variation in the informational architectures may induce differential survival (self-construction, self-maintenance, and reproduction) of biological agents within their open ended environment.
Senolytic Therapy for Cerebral Ischemia-Reperfusion Injury
Authors: Lim Songhyun , Kim Tae Jung , Kim Young-Ju , Kim Cheesue , Ko Sang-Bae , Kim Byung-Soo
Published: November 2021

Ischemic stroke is one of the leading causes of death, and even timely treatment can result in severe disabilities. Reperfusion of the ischemic stroke region and restoration of the blood supply often lead to a series of cellular and biochemical consequences, including generation of reactive oxygen species (ROS), expression of inflammatory cytokines, inflammation, and cerebral cell damage, which is collectively called cerebral ischemia-reperfusion (IR) injury. Since ROS and inflammatory cytokines are involved in cerebral IR injury, injury could involve cellular senescence. Thus, we investigated whether senolytic therapy that eliminates senescent cells could be an effective treatment for cerebral IR injury. To determine whether IR induces neural cell senescence in vitro, astrocytes were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). OGD/R induced astrocyte senescence and senescent cells in OGD/R-injured astrocytes were effectively eliminated in vitro by ABT263, a senolytic agent. IR in rats with intraluminal middle cerebral artery occlusion induced cellular senescence in the ischemic region. The senescent cells in IR-injured rats were effectively eliminated by intravenous injections of ABT263. Importantly, ABT263 treatment significantly reduced the infarct volume and improved neurological function in behavioral tests. This study demonstrated, for the first time, that senolytic therapy has therapeutic potential for cerebral IR injury.
Pharmacological Modulation of Ubiquitin-Proteasome Pathways in Oncogenic Signaling
Authors: Sharma Anmol , Khan Heena , Singh Thakur , Grewal Amarjot , Najda Agnieszka , Kawecka-Radomska Małgorzata , Kamel Mohamed , Altyar Ahmed , Abdel-Daim Mohamed
Published: November 2021

The ubiquitin-proteasome pathway (UPP) is involved in regulating several biological functions, including cell cycle control, apoptosis, DNA damage response, and apoptosis. It is widely known for its role in degrading abnormal protein substrates and maintaining physiological body functions via ubiquitinating enzymes (E1, E2, E3) and the proteasome. Therefore, aberrant expression in these enzymes results in an altered biological process, including transduction signaling for cell death and survival, resulting in cancer. In this review, an overview of profuse enzymes involved as a pro-oncogenic or progressive growth factor in tumors with their downstream signaling pathways has been discussed. A systematic literature review of PubMed, Medline, Bentham, Scopus, and EMBASE (Elsevier) databases was carried out to understand the nature of the extensive work done on modulation of ubiquitin-proteasome pathways in oncogenic signaling. Various in vitro, in vivo studies demonstrating the involvement of ubiquitin-proteasome systems in varied types of cancers and the downstream signaling pathways involved are also discussed in the current review. Several inhibitors of E1, E2, E3, deubiquitinase enzymes and proteasome have been applied for treating cancer. Some of these drugs have exhibited successful outcomes in in vivo studies on different cancer types, so clinical trials are going on for these inhibitors. This review mainly focuses on certain ubiquitin-proteasome enzymes involved in developing cancers and certain enzymes that can be targeted to treat cancer.
Comprehensive Analysis of Combinatorial Pharmacological Treatments to Correct Nonsense Mutations in the CFTR Gene
Authors: Venturini Arianna , Borrelli Anna , Musante Ilaria , Scudieri Paolo , Capurro Valeria , Renda Mario , Pedemonte Nicoletta , Galietta Luis J. V.
Published: November 2021

Cystic fibrosis (CF) is caused by loss of function of the CFTR chloride channel. A substantial number of CF patients carry nonsense mutations in the CFTR gene. These patients cannot directly benefit from pharmacological correctors and potentiators that have been developed for other types of CFTR mutations. We evaluated the efficacy of combinations of drugs targeting at various levels the effects of nonsense mutations: SMG1i to protect CFTR mRNA from nonsense-mediated decay (NMD), G418 and ELX-02 for readthrough, VX-809 and VX-445 to promote protein maturation and function, PTI-428 to enhance CFTR protein synthesis. We found that the extent of rescue and sensitivity to the various agents is largely dependent on the type of mutation, with W1282X and R553X being the mutations most and least sensitive to pharmacological treatments, respectively. In particular, W1282X-CFTR was highly responsive to NMD suppression by SMG1i but also required treatment with VX-445 corrector to show function. In contrast, G542X-CFTR required treatment with readthrough agents and VX-809. Importantly, we never found cooperativity between the NMD inhibitor and readthrough compounds. Our results indicate that treatment of CF patients with nonsense mutations requires a precision medicine approach with the design of specific drug combinations for each mutation.
Regulation of Limbal Epithelial Stem Cells: Importance of the Niche
Authors: Robertson Sarah Y. T. , Roberts JoAnn S. , Deng Sophie X.
Published: November 2021

Limbal epithelial stem/progenitor cells (LSCs) reside in a niche that contains finely tuned balances of various signaling pathways including Wnt, Notch, BMP, Shh, YAP, and TGFβ. The activation or inhibition of these pathways is frequently dependent on the interactions of LSCs with various niche cell types and extracellular substrates. In addition to receiving molecular signals from growth factors, cytokines, and other soluble molecules, LSCs also respond to their surrounding physical structure via mechanotransduction, interaction with the ECM, and interactions with other cell types. Damage to LSCs or their niche leads to limbal stem cell deficiency (LSCD). The field of LSCD treatment would greatly benefit from an understanding of the molecular regulation of LSCs in vitro and in vivo. This review synthesizes current literature around the niche factors and signaling pathways that influence LSC function. Future development of LSCD therapies should consider all these niche factors to achieve improved long-term restoration of the LSC population.
Single-Cell RNA Sequencing Reveals Heterogeneity and Functional Diversity of Lymphatic Endothelial Cells
Authors: den Braanker Hannah , van Stigt Astrid , Kok Marc , Lubberts Erik , Bisoendial Radjesh
Published: November 2021

Lymphatic endothelial cells (LECs) line the lymphatic vasculature and play a central role in the immune response. LECs have abilities to regulate immune transport, to promote immune cell survival, and to cross present antigens to dendritic cells. Single-cell RNA sequencing (scRNA) technology has accelerated new discoveries in the field of lymphatic vascular biology. This review will summarize these new findings in regard to embryonic development, LEC heterogeneity with associated functional diversity, and interactions with other cells. Depending on the organ, location in the lymphatic vascular tree, and micro-environmental conditions, LECs feature unique properties and tasks. Furthermore, adjacent stromal cells need the support of LECs for fulfilling their tasks in the immune response, such as immune cell transport and antigen presentation. Although aberrant lymphatic vasculature has been observed in a number of chronic inflammatory diseases, the knowledge on LEC heterogeneity and functional diversity in these diseases is limited. Combining scRNA sequencing data with imaging and more in-depth functional experiments will advance our knowledge of LECs in health and disease. Building the case, the LEC could be put forward as a new therapeutic target in chronic inflammatory diseases, counterweighting the current immune-cell focused therapies.
CD38 Correlates with an Immunosuppressive Treg Phenotype in Lupus-Prone Mice
Authors: Pérez-Lara Jocelyn C. , Espinosa Enrique , Santos-Argumedo Leopoldo , Romero-Ramírez Héctor , López-Herrera Gabriela , García-García Fabio , Sandoval-Montes Claudia , Ortiz-Navarrete Vianney , Flores-Muñoz Mónica , Rodríguez-Alba Juan C.
Published: November 2021

CD38 is a transmembrane glycoprotein expressed by T-cells. It has been reported that patients with systemic lupus erythematosus (SLE) showed increased CD38+CD25+ T-cells correlating with immune activation and clinical signs. Contrariwise, CD38 deficiency in murine models has shown enhanced autoimmunity development. Recent studies have suggested that CD38+ regulatory T-cells are more suppressive than CD38− regulatory T-cells. Thus, we have suggested that CD38 overexpression in SLE patients could play a role in regulating immune activation cells instead of enhancing it. This study found a correlation between CD38 with FoxP3 expression and immunosuppressive molecules (CD69, IL-10, CTLA-4, and PD-1) in T-cells from lupus-prone mice (B6.MRL-Faslpr/J). Additionally, B6.MRL-Faslpr/J mice showed a decreased proportion of CD38+ Treg cells regarding wild-type mice (WT). Furthermore, Regulatory T-Cells (Treg cells) from CD38-/- mice showed impairment in expressing immunosuppressive molecules and proliferation after stimulation through the T-cell receptor (TCR). Finally, we demonstrated an increased ratio of IFN-γ/IL-10 secretion in CD38-/- splenocytes stimulated with anti-CD3 compared with the WT. Altogether, our data suggest that CD38 represents an element in maintaining activated and proliferative Treg cells. Consequently, CD38 could have a crucial role in immune tolerance, preventing SLE development through Treg cells.
Towards a Cardoon (Cynara cardunculus var. altilis)-Based Biorefinery: A Case Study of Improved Cell Cultures via Genetic Modulation of the Phenylpropanoid Pathway
Authors: Paolo Dario , Locatelli Franca , Cominelli Eleonora , Pirona Raul , Pozzo Sara , Graziani Giulia , Ritieni Alberto , De Palma Monica , Docimo Teresa , Tucci Marina , Sparvoli Francesca
Published: November 2021

Cultivated cardoon (Cynara cardunculus var. altilis L.) is a promising candidate species for the development of plant cell cultures suitable for large-scale biomass production and recovery of nutraceuticals. We set up a protocol for Agrobacterium tumefaciens-mediated transformation, which can be used for the improvement of cardoon cell cultures in a frame of biorefinery. As high lignin content determines lower saccharification yields for the biomass, we opted for a biotechnological approach, with the purpose of reducing lignin content; we generated transgenic lines overexpressing the Arabidopsis thaliana MYB4 transcription factor, a known repressor of lignin/flavonoid biosynthesis. Here, we report a comprehensive characterization, including metabolic and transcriptomic analyses of AtMYB4 overexpression cardoon lines, in comparison to wild type, underlining favorable traits for their use in biorefinery. Among these, the improved accessibility of the lignocellulosic biomass to degrading enzymes due to depletion of lignin content, the unexpected increased growth rates, and the valuable nutraceutical profiles, in particular for hydroxycinnamic/caffeoylquinic and fatty acids profiles.
Improvement of an Effective Protocol for Directed Differentiation of Human Adipose Tissue-Derived Adult Mesenchymal Stem Cells to Corneal Endothelial Cells
Authors: Marta Cadenas-Martin , Adrian Moratilla , Jorge Fernández-Delgado , Francisco Arnalich-Montiel , De Miguel Maria P.
Published: November 2021

Corneal disease affects 12.5 million individuals worldwide, with 2 million new cases each year. The standard treatment consists of a corneal transplantation from a human donor; however, the worldwide demand significantly exceeds the available supply. Lamellar endothelial keratoplasty, the replacement of only the endothelial layer of the cornea, can partially solve the problem. Progressive efforts have succeeded in expanding hCECs; however, the ability to expand hCECs is still limited, and new sources of CECs are being sought. Crucial advances have been achieved by the directed differentiation of embryonic or induced pluripotent stem cells, but these cells have disadvantages, such as the use of oncogenes, and are still difficult to establish. We aimed to transfer such knowledge to obtain hCECs from adipose tissue-derived adult mesenchymal stem cells (ADSC) by modifying four previously published procedures. We present several protocols capable of the directed differentiation of human ADSCs to hCECs. In our hands, the protocol by Ali et al. was the best adapted to such differentiation in terms of efficiency, time, and financial cost; however, the protocol by Wagoner et al. was the best for CEC marker expression. Our results broaden the type of cells of autologous extraocular origin that could be employed in the clinical setting for corneal endothelial deficiency.
Ultra-Fine Control of Silica Shell Thickness on Silver Nanoparticle-Assembled Structures
Authors: Hahm Eunil , Jo Ahla , Kang Eun Ji , Bock Sungje , Pham Xuan-Hung , Chang Hyejin , Jun Bong-Hyun
Published: November 2021

To study the distance-dependent electromagnetic field effects related to the enhancement and quenching mechanism of surface-enhanced Raman scattering (SERS) or fluorescence, it is essential to precisely control the distance from the surface of the metal nanoparticle (NP) to the target molecule by using a dielectric layer (e.g., SiO2, TiO2, and Al2O3). However, precisely controlling the thickness of this dielectric layer is challenging. Herein, we present a facile approach to control the thickness of the silica shell on silver nanoparticle-assembled silica nanocomposites, SiO2@Ag NPs, by controlling the number of reacting SiO2@Ag NPs and the silica precursor. Uniform silica shells with thicknesses in the range 5–40 nm were successfully fabricated. The proposed method for creating a homogeneous, precise, and fine silica coating on nanocomposites can potentially contribute to a comprehensive understanding of the distance-dependent electromagnetic field effects and optical properties of metal NPs.
Establishment of Human-Induced Pluripotent Stem Cell-Derived Neurons—A Promising In Vitro Model for a Molecular Study of Rabies Virus and Host Interaction
Authors: Chailangkarn Thanathom , Tanwattana Nathiphat , Jaemthaworn Thanakorn , Sriswasdi Sira , Wanasen Nanchaya , Tangphatsornruang Sithichoke , Leetanasaksakul Kantinan , Jantraphakorn Yuparat , Nawae Wanapinun , Chankeeree Penpicha , Lekcharoensuk Porntippa , Lumlertdacha Boonlert , Kaewborisuth Challika
Published: November 2021

Rabies is a deadly viral disease caused by the rabies virus (RABV), transmitted through a bite of an infected host, resulting in irreversible neurological symptoms and a 100% fatality rate in humans. Despite many aspects describing rabies neuropathogenesis, numerous hypotheses remain unanswered and concealed. Observations obtained from infected primary neurons or mouse brain samples are more relevant to human clinical rabies than permissive cell lines; however, limitations regarding the ethical issue and sample accessibility become a hurdle for discovering new insights into virus–host interplays. To better understand RABV pathogenesis in humans, we generated human-induced pluripotent stem cell (hiPSC)-derived neurons to offer the opportunity for an inimitable study of RABV infection at a molecular level in a pathologically relevant cell type. This study describes the characteristics and detailed proteomic changes of hiPSC-derived neurons in response to RABV infection using LC-MS/MS quantitative analysis. Gene ontology (GO) enrichment of differentially expressed proteins (DEPs) reveals temporal changes of proteins related to metabolic process, immune response, neurotransmitter transport/synaptic vesicle cycle, cytoskeleton organization, and cell stress response, demonstrating fundamental underlying mechanisms of neuropathogenesis in a time-course dependence. Lastly, we highlighted plausible functions of heat shock cognate protein 70 (HSC70 or HSPA8) that might play a pivotal role in regulating RABV replication and pathogenesis. Our findings acquired from this hiPSC-derived neuron platform help to define novel cellular mechanisms during RABV infection, which could be applicable to further studies to widen views of RABV-host interaction.
Z-DNA as a Tool for Nuclease-Free DNA Methyltransferase Assay
Authors: Kim Sook Ho , Jung Hae Jun , Hong Seok-Cheol
Published: November 2021

Methylcytosines in mammalian genomes are the main epigenetic molecular codes that switch off the repertoire of genes in cell-type and cell-stage dependent manners. DNA methyltransferases (DMT) are dedicated to managing the status of cytosine methylation. DNA methylation is not only critical in normal development, but it is also implicated in cancers, degeneration, and senescence. Thus, the chemicals to control DMT have been suggested as anticancer drugs by reprogramming the gene expression profile in malignant cells. Here, we report a new optical technique to characterize the activity of DMT and the effect of inhibitors, utilizing the methylation-sensitive B-Z transition of DNA without bisulfite conversion, methylation-sensing proteins, and polymerase chain reaction amplification. With the high sensitivity of single-molecule FRET, this method detects the event of DNA methylation in a single DNA molecule and circumvents the need for amplification steps, permitting direct interpretation. This method also responds to hemi-methylated DNA. Dispensing with methylation-sensitive nucleases, this method preserves the molecular integrity and methylation state of target molecules. Sparing methylation-sensing nucleases and antibodies helps to avoid errors introduced by the antibody’s incomplete specificity or variable activity of nucleases. With this new method, we demonstrated the inhibitory effect of several natural bio-active compounds on DMT. All taken together, our method offers quantitative assays for DMT and DMT-related anticancer drugs.
The Emerging Role of Ionic Liquid-Based Approaches for Enhanced Skin Permeation of Bioactive Molecules: A Snapshot of the Past Couple of Years
Authors: Gomes Ana , Aguiar Luísa , Ferraz Ricardo , Teixeira Cátia , Gomes Paula
Published: November 2021

Topical and transdermal delivery systems are of undeniable significance and ubiquity in healthcare, to facilitate the delivery of active pharmaceutical ingredients, respectively, onto or across the skin to enter systemic circulation. From ancient ointments and potions to modern micro/nanotechnological devices, a variety of approaches has been explored over the ages to improve the skin permeation of diverse medicines and cosmetics. Amongst the latest investigational dermal permeation enhancers, ionic liquids have been gaining momentum, and recent years have been prolific in this regard. As such, this review offers an outline of current methods for enhancing percutaneous permeation, highlighting selected reports where ionic liquid-based approaches have been investigated for this purpose. Future perspectives on use of ionic liquids for topical delivery of bioactive peptides are also presented.
Latently KSHV-Infected Cells Promote Further Establishment of Latency upon Superinfection with KSHV
Authors: Gam ze Letova Chen , Kalt Inna , Shamay Meir , Sarid Ronit
Published: November 2021

Kaposi’s sarcoma-associated herpesvirus (KSHV) is a cancer-related virus which engages in two forms of infection: latent and lytic. Latent infection allows the virus to establish long-term persistent infection, whereas the lytic cycle is needed for the maintenance of the viral reservoir and for virus spread. By using recombinant KSHV viruses encoding mNeonGreen and mCherry fluorescent proteins, we show that various cell types that are latently-infected with KSHV can be superinfected, and that the new incoming viruses establish latent infection. Moreover, we show that latency establishment is enhanced in superinfected cells compared to primary infected ones. Further analysis revealed that cells that ectopically express the major latency protein of KSHV, LANA-1, prior to and during infection exhibit enhanced establishment of latency, but not cells expressing LANA-1 fragments. This observation supports the notion that the expression level of LANA-1 following infection determines the efficiency of latency establishment and avoids loss of viral genomes. These findings imply that a host can be infected with more than a single viral genome and that superinfection may support the maintenance of long-term latency.
Model Identifies Genetic Predisposition of Alzheimer’s Disease as Key Decider in Cell Susceptibility to Stress
Authors: Stefani Ioanna C. , de Thé François-Xavier Blaudin , Kontoravdi Cleo , Polizzi Karen M.
Published: November 2021

Accumulation of unfolded/misfolded proteins in neuronal cells perturbs endoplasmic reticulum homeostasis, triggering a stress cascade called unfolded protein response (UPR), markers of which are upregulated in Alzheimer’s disease (AD) brain specimens. We measured the UPR dynamic response in three human neuroblastoma cell lines overexpressing the wild-type and two familial AD (FAD)-associated mutant forms of amyloid precursor protein (APP), the Swedish and Swedish-Indiana mutations, using gene expression analysis. The results reveal a differential response to subsequent environmental stress depending on the genetic background, with cells overexpressing the Swedish variant of APP exhibiting the highest global response. We further developed a dynamic mathematical model of the UPR that describes the activation of the three branches of this stress response in response to unfolded protein accumulation. Model-based analysis of the experimental data suggests that the mutant cell lines experienced a higher protein load and subsequent magnitude of transcriptional activation compared to the cells overexpressing wild-type APP, pointing to higher susceptibility of mutation-carrying cells to stress. The model was then used to understand the effect of therapeutic agents salubrinal, lithium, and valproate on signalling through different UPR branches. This study proposes a novel integrated platform to support the development of therapeutics for AD.
Inhibitors of the Sec61 Complex and Novel High Throughput Screening Strategies to Target the Protein Translocation Pathway
Authors: Pauwels Eva , Schülein Ralf , Vermeire Kurt
Published: November 2021

Proteins targeted to the secretory pathway start their intracellular journey by being transported across biological membranes such as the endoplasmic reticulum (ER). A central component in this protein translocation process across the ER is the Sec61 translocon complex, which is only intracellularly expressed and does not have any enzymatic activity. In addition, Sec61 translocon complexes are difficult to purify and to reconstitute. Screening for small molecule inhibitors impairing its function has thus been notoriously difficult. However, such translocation inhibitors may not only be valuable tools for cell biology, but may also represent novel anticancer drugs, given that cancer cells heavily depend on efficient protein translocation into the ER to support their fast growth. In this review, different inhibitors of protein translocation will be discussed, and their specific mode of action will be compared. In addition, recently published screening strategies for small molecule inhibitors targeting the whole SRP-Sec61 targeting/translocation pathway will be summarized. Of note, slightly modified assays may be used in the future to screen for substances affecting SecYEG, the bacterial ortholog of the Sec61 complex, in order to identify novel antibiotic drugs.
Measuring Discrimination against Older People Applying the Fraboni Scale of Ageism
Authors: Hofmeister-Tóth Ágnes , Neulinger Ágnes , Debreceni János
Published: November 2021

The progressive aging of developed societies, caused by profound demographic changes, brings with it the necessity of confronting the subject of discrimination against older people. In the last 50 years, many scales of ageism have been developed to measure beliefs and attitudes towards older adults. The purpose of our study was to adapt the full Fraboni Scale of Ageism (FSA) to Hungarian language and assess its reliability, validity, and psychometric properties. The sample of the study was representative of the Hungarian population, and the data collection took place online. In our study, we compare the dimensions of the scale with other international studies and present the attitudes and biases of the Hungarian population against the older people. The results of the study indicate that attitudes toward older people are more positive among women, older people, and people living in villages. In this study, we concluded that the Hungarian version of the Fraboni Scale of Ageism is a suitable instrument for both measuring the extent of ageism in the Hungarian population and contributing to further testing the international reliability, validity, and psychometric properties of the Fraboni Scale of Ageism.
Ozone Induces Distress Behaviors in Fig Wasps with a Reduced Chance of Recovery
Authors: Vanderplanck Maryse , Lapeyre Benoit , Lucas Shéhérazade , Proffit Magali
Published: November 2021

Among anthropogenic environmental risks, air pollution has the potential to impact animal and plant physiology, as well as their interactions and the long-term survival of populations, which could threaten the functioning of ecosystems. What is especially alarming is that the concentration of tropospheric ozone (O3) has dramatically increased since pre-industrial times. However, the direct effects of O3 on the behavior of pollinators themselves have not been investigated so far even though insect behavior is key to their ecological interactions, which underpin the stability of ecological networks responsible for species biodiversity in ecosystems. In this study, we aim to determine the potential effects of O3 episodes at different field-realistic concentrations (0, 40, 80, 120, and 200 ppb for 60 min) on the behavior of the fig wasp Blastophaga psenes by monitoring exposed individuals hourly for 5 h after exposure. We found that ozone episodes induced major changes in insect behavior, which were already significant at 80 ppb with individuals displaying abnormal motility. The tracking over time clearly showed that exposed individuals might only have a reduced chance of recovery, with a decreasing proportion of active fig wasps despite the cessation of an O3 episode. These findings illustrate that O3 episodes can affect pollinator behavior, which may have detrimental implications for pollination systems. It is, therefore, of importance to assess the effects of O3 on insect behavior in order to predict how it could modify ecological interactions and species biodiversity in ecosystems.