bluuebunny/crossref_metadata_2025 huggingface dataset:
Degraded Trees from Spruce Budworm Epidemics as Bioenergy Feedstock: A Profitability Analysis of Forest Operations
Authors: Béland Mathieu , Thiffault Evelyne , Barrette Julie , Mabee Warren
Published: September 2020

Natural disturbances are common in Canadian boreal managed forests. For example, during and after insect epidemics, foresters must deal with significant amounts of degraded or dead wood that cannot be processed into sawn timber or pulp. Bioenergy could be an alternative pathway for this wood. A case study in Quebec (Canada) was used to evaluate the profitability of pellet production for bioenergy using degraded trees from insect epidemics. A bioenergy scenario was simulated in which degraded trees were harvested for bioenergy alongside sound wood for timber and pulp. This scenario was compared to a reference scenario in which degraded trees were left on cutovers. Using wood pellets as a case study, the results showed that at current market prices, harvesting degraded trees for pellet production is not as profitable as leaving them in the forest. Nevertheless, the overall forest operations for procuring wood for timber and pulp were still profitable, even with very high degradation levels. Procuring degraded trees reduced the overall fixed costs per harvested m3 and allowed average savings of C$2.83/harvested m3. The silvicultural savings associated with lower site preparation needs following procurement of degraded trees ranged from C$0/ha to C$500/ha, resulting in average savings of C$2.31/harvested m3. Depending on the stand conditions, the distribution of fixed costs and silvicultural savings of biomass procurement could be either low or significant.
Analysis of the Thermal Retrofitting Potential of the External Walls of Podhale’s Historical Timber Buildings in the Aspect of the Non-Deterioration of Their Technical Condition
Authors: Fedorczak-Cisak Małgorzata , Radziszewska-Zielina Elżbieta , Orlik-Kożdoń Bożena , Steidl Tomasz , Tatara Tadeusz
Published: September 2020

The paper discusses thermal quality improvement in historic buildings. It is based on a case study of a wooden historical building in an architectural style typical of Zakopane, located in the Podhale region of Poland. The building’s historical value and timber structure prevent the application of typical thermal retrofitting solutions. This paper presents an analysis of the possibilities of the improvement of energy performance of a historic building (villa) which included: a review of the available energy performance improvement solutions applicable to this type of building, with a particular focus on applying internal insulation; a technical condition assessment using non-invasive methods, the identification of problematic areas in terms of the thermal retrofitting of buildings with timber walls and decks; in situ tests: thermovision tests which showed the places with temperature distribution field disturbances in the building’s envelope, focusing on thermal bridges; measurements of actual thermal transmittance coefficients for extant partitions; measurements of the building’s airtightness and the microclimate in selected rooms; numerical analysis: an assessment of the influence of the thermal bridges on the building’s existing condition, an analysis of water content changes in wall systems post-insulation. The presented approach enables the improvement of the energy performance of timber historical buildings while preserving the historical value of its architecture. It is innovative because it tries to fill in a research gap concerning a lack of relevant guidelines in Poland. The research questions that the authors asked were as follows. Is it possible to improve the thermal insulation of a building’s wooden walls without adversely affecting the building’s technical condition? With regard to the necessity to meet nZEB (nearly zero energy building) standards, is it feasible to improve the timber walls of historical buildings? The study found that under the correct assumptions and while maintaining a responsible approach to design, it is possible to improve the energy performance of historical buildings without interfering with historical heritage.
The Enhanced Average Model of the Smart Transformer with the Wye-Delta Connection of Dual Active Bridges
Authors: Milczarek Adam , Michna Mariusz
Published: September 2020

Nowadays, many power electronics converters (PECs) are connected to the distribution grid, increasing the energy quality requirements in point of common coupling (PCC). One of the promising solutions to improve the energy quality is a smart transformer (ST) characterised by additional benefits in relation to the classical transformer throughout the possibility to implement advanced functionalities in PCC. However, the ST contains a lot of power semiconductor switches, making a problem for simulation software and the computer hardware when the control algorithm and all the ST functionalities are investigated. Usually, the solver algorithms in simulation software are used to create many linear time-varying states spaces, which increases exponentially with the number of switches. Therefore, very important is a model averaging process of the selected advanced ST topology, which is the aim of the paper. The proposed ST average model is compared with full switching models of each ST power conversion stage. It allows for decreasing the simulation time a dozen times, enabling the control algorithm analysis with a full ST model. The proposed solution and results prove steady-state and dynamic behaviour of the average model and provide a comprehensive averaging process for a novel multiple active bridge direct current/direct current (DC/DC) converter inside the ST.
Study on Effects of Inlet Resistance on the Efficiency of Scroll Expander in Micro-Compressed Air Energy Storage System
Authors: Sun Aiqin , Wang Jidai , Chen Guangqing , Wang Jihong , Miao Shihong , Wang Dan , Wang Zhiwei , Ma Lan
Published: September 2020

As an important part of a micro-compressed air energy storage system, the scroll expander directly affects the efficiency of the whole energy storage system. The effects of resistance on the efficiency of scroll expander caused by inlet structure and size are discussed with theory analysis and experimental methods in this paper. Micro-compressed air energy storage system has aroused widespread attention because of its pollution-free, high flexibility, in the community, remote areas power supply. Comprehensive experimental work with the selections of different size and structure of the air inlet of the scroll expander was performed with the cutting angle of air inlet chamber of the scroll expander. The results of the experiments are discussed on how exergy efficiency and inlet flow of the scroll expander were affected resulting from the cutting angles dissected. The results show that a maximum value exists for exergy efficiency of the scroll expander. Therefore, the exergy efficiency of the scroll expander can be effectively improved by enlarging the air inlet port dimension and modifying the size of air chamber.
Performance Evaluation of External Light Shelves by Applying a Prism Sheet
Authors: Lee Heangwoo , Seo Janghoo
Published: September 2020

To address the increased use of lighting energy in the building sector, research on the use of light shelves has been increasing. Previous studies have focused on applying operating techniques to improve daylighting performance, which reduces the economic efficiency of light shelves and the building energy savings. This study proposes the use of prism sheets to improve the performance of light shelves, a concept which was validated by evaluating the performance related to saving building energy and improving indoor light uniformity through a full-scale testbed. This study used an external light shelf with no prism sheet, a window with a prism sheet applied, and a window with both an external light shelf and prism sheet applied as Case 1, Case 2, and Case 3, respectively, and analyzed the illuminance distribution and lighting energy consumption required to maintain the optimal indoor illumination for each case. This study also derived the optimal specifications for each case to save building energy and considered the flow of natural light to analyze the performance evaluation results. The main findings are as follows: (1) the optimal specifications to improve daylighting performance were derived for Case 1, requiring the application of operating techniques; (2) Case 2 was not suitable for saving energy and improving light uniformity when compared to Case 1; and (3) Case 3 was effective in saving building energy. In Case 3, even when the light shelf was fixed at 20° without moving, it saved building energy and improved light uniformity compared to Case 1. However, the prism sheet in Case 3 should be detached during winter to maximize building energy savings.
Information Disclosure through Technology Licensing
Authors: Mukherjee Arijit , Bagchi Aniruddha
Published: September 2020

We show that even if information transmission through an honest outside agency is not possible due to the possibility of collusion between the firms and the outside agency, information transmission is still possible through technology licensing. However, unlike the case of a cost-free honest outside agency, where information transmission always occurs under a quantity setting oligopoly, information transmission through licensing does not always occur.
Fast Sampling Field Deployable Mud Gas Carbon Isotope Analyzer
Authors: Wu Sheng , Deev Andrei , Zhuang Yan , Lu Le , Wang Zhengyou , Tang Yongchun , Sneddon Andrew
Published: September 2020

We report the details of a field deployable mud gas carbon isotope analyzer for mud gas analysis based on coupling a gas chromatograph with a mid-infrared spectrometer using a quantum cascade laser and hollow waveguide. The GC–IR2 (gas chromatograph–infrared isotope ratio) system features a fast sampling cycle as short as 123 s for analyzing all three components, i.e., methane, ethane and propane. The samples are automatically diluted so the system could carry out effective measurements while sample concentrations vary from 400 ppm to 100% purity. The accuracy is guaranteed through periodic reference calibration, and variations due to field temperature changes are minimized.
“Incisive, Dissonant” Rationality vs. Aesthetic Modernism: Hedenius and Trotzig
Authors: Olsson Ulf
Published: September 2020

The Swedish “Welfare State” of the 1950s was described as a rational, well-organized society by leading Swedish philosopher, Professor Ingemar Hedenius. His biopolitical vision emphasized the scientific basis for social reforms, and he was an active opponent to any kind of religious thinking. Hedenius also worked as a literary critic, and he would use that role to confront literary representations of contemporary society that did not fit in with his promulgation of rationality. Hedenius furiously attacked Swedish writer Birgitta Trotzig’s A Landscape (1959). In her book, she challenges any harmonizing vision of society. She does it through representations of the body, and the gaze that does not shy away from the anguished and pained body, the body opening up and giving birth. The body in Trotzig’s work is also the tortured body of Christ. With the Swedish welfare state as a point of reference, this article explores the collision between what can be called a “rational modernism” and aesthetic modernism: Hedenius called Trotzig’s book “evil,” and Trotzig, when she commented upon this almost three decades later, saw Hedenius’s review as an authoritarian assault.
Prolongation of Electrocardiographic T Wave Parameters Recorded during the Head-Up Tilt Table Test as Independent Markers of Syncope Severity in Children
Authors: Markiewicz-Łoskot Grażyna , Kolarczyk Ewelina , Mazurek Bogusław , Łoskot Marianna , Szydłowski Lesław
Published: September 2020

The head-up tilt table test (HUTT) with the upright phase is used to help determine an imbalance of the sympathetic nervous system that is related to abnormal electrocardiographic repolarization in children with vasovagal syncope (VVS) and also in patients with the long QT syndrome (LQTS). The study attempted to evaluate T wave morphology and QT and TpTe (Tpeak–Tend) intervals recorded in ECG during the HUTT for a more accurate diagnosis of children with VVS. The group investigated 70 children with a negative HUTT result: 40 patients with VVS and 30 healthy volunteers without syncope. The RR interval as well as TpTe, and QTc intervals were measured in lead V5 of electrocardiogram (ECG) on admission to the hospital and during three phases of the HUTT. In syncopal children, which included 23 children with bifid or flat T waves and 17 patients with normal T waves in the upright phase, the QTc and TpTe were longer (p < 0.001) compared to the other test phases and longer (p < 0.001) than in the control group, respectively, with the risk of arrhythmias. Only in the control group, the TpTe was shorter (p < 0.001) in the upright phase than in the other tilt phases. The TpTe in the upright phase (>70 ms) was a good discriminator, and was better than the QTc (>427 ms). Prolongation of electrocardiographic TpTe and QT intervals, in addition to the (abnormal T wave morphology recorded during the HUTT, are helpful for identifying VVS children more predisposed to ventricular arrhythmias with a latent risk of LQTS. Further studies are required to assess the value of these repolarization parameters in clinical practice.
New Ways of Working? A Rapid Exploration of Emerging Evidence Regarding the Care of Older People during COVID19
Authors: Ní Shé Éidín , O’Donnell Deirdre , O’Shea Marie , Stokes Diarmuid
Published: September 2020

Health and social care staff have had to quickly adapt, respond and improve teamwork, as a response to the COVID-19 pandemic. Our objective was to rapidly summarize the emerging evidence of new ways of working in the care of older people during this period. We conducted an exploration of the emerging evidence within the timeframe of 1 March 2020 to 11 May 2020. To capture a broad perspective, we undertook thematic analysis of Twitter data which was extracted through a broad search for new ways of working in health and social care. For a more in-depth focus on the health and social care of older people, we undertook a systematic scoping of newspapers using the Nexis UK database. We undertook a validation workshop with members of the interprofessional working group of the Irish National Integrated Care Programme for Older People, and with researchers. A total of 317 tweets were extracted related to six new ways of working. There was evidence of using telehealth to provide ongoing care to patients; interprofessional work; team meetings using online platforms; trust and collaboration within teams; as well as teams feeling empowered to change at a local level. 34 newspaper articles were extracted related to new ways of working in the care of older people, originating in England (n = 17), Wales (n = 6), Scotland (n = 6), Ireland (n = 4) and Germany (n = 1). Four main themes were captured that focused on role expansion, innovations in communication, environmental restructuring and enablement. The results of this exploration of emerging evidence show that health and social care teams can transform very rapidly. Much of the change was based on goodwill as a response to the pandemic. Further analysis of empirical evidence of changing practices should include the perspectives of older people and should capture the resources needed to sustain innovations, as well as evaluate gaps in service provision.
Resistance Training Acutely Impairs Agility and Spike-Specific Performance Measures in Collegiate Female Volleyball Players Returning from the Off-Season
Authors: Doma Kenji , Connor Jonathan , Gahreman Daniel , Boullosa Daniel , Ahtiainen Juha P. , Nagata Akinori
Published: September 2020

This study examined the acute effects of resistance training (RT) on volleyball-specific performance. Sixteen female volleyball players undertook their initial, pre-season RT bout. Countermovement jump (CMJ), delayed onset of muscle soreness (DOMS), and sport-specific performances (i.e., run-up jump, agility, and spiking speed and accuracy) were measured before, 24 (T24), and 48 (T48) hours after RT. A significant increase in DOMS was observed at T24 and T48 (~207.6% ± 119.3%; p < 0.05; ES = 1.8 (95% CI: 0.94–2.57)), whilst agility was significantly impaired at T48 (1.7% ± 2.5%; p < 0.05; ES = 0.30 (95% CI: −0.99–0.40)). However, there were no differences in CMJ (~−2.21% ± 7.6%; p > 0.05; ES = −0.11 (95% CI: −0.80–0.58)) and run-up jump (~−1.4% ± 4.7%; p > 0.05; ES = −0.07 (95% CI: −0.76–0.63)). Spiking speed was significantly reduced (−3.5% ± 4.4%; p < 0.05; ES = −0.28 (95% CI: −0.43–0.97)), although accuracy was improved (38.3% ± 81.4%: p < 0.05) at T48. Thus, the initial, preseason RT bout compromised agility and spiking speed for several days post-exercise. Conversely, spiking accuracy improved, suggesting a speed–accuracy trade-off. Nonetheless, at least a 48-h recovery may be necessary after the initial RT bout for athletes returning from the off-season or injury.
Healthy Ageing in Place: Enablers and Barriers from the Perspective of the Elderly. A Qualitative Study
Authors: Bosch-Farré Cristina , Malagón-Aguilera Maria Carmen , Ballester-Ferrando David , Bertran-Noguer Carme , Bonmatí-Tomàs Anna , Gelabert-Vilella Sandra , Juvinyà-Canal Dolors
Published: September 2020

Background: Most elderly people wish to grow old at their own homes. The sociodemographic characteristics; home and neighbourhood conditions; and the social services support and networks are determinants in the possibility of “ageing in place”. The present study aimed to explore the ageing in place phenomenon, as well as the enablers and barriers that interact in a healthy ageing from the perspective of the elderly connected to local entities. Methods: A generic qualitative design was proposed in the Health Region of Girona in Catalonia (Spain). Seventy-one elderly people were purposefully selected. Six focus groups were conducted, and data were thematically analysed. Results: Three key themes were generated: (1) Participants experienced ageing differently. The physical and mental health, the family environment and financial stability were key elements for life quality. (2) The perception of the elderly’s role in the community depended on their age, health status and attitude towards life. (3) The participants identified several enablers and barriers to healthy ageing in place. Conclusions: The promotion of older people’s autonomy and wellbeing, together with the creation of an active network of health and social services, may improve the possibility for elderly to age at home and avoid or delay institutionalisation.
Simple, Low-Cost and Long-Lasting Film for Virus Inactivation Using Avian Coronavirus Model as Challenge
Authors: Colnago Luiz Alberto , Trevisol Iara Maria , Voss Rech Daiane , Forato Lucimara Aparecida , Igreja do Nascimento Mitre Cirlei , Gagliardi Leite José Paulo , Giglioti Rodrigo , Okino Cintia Hiromi
Published: September 2020

The COVID-19 infection, caused by SARS-CoV-2, is inequitably distributed and more lethal among populations with lower socioeconomic status. Direct contact with contaminated surfaces has been among the virus sources, as it remains infective up to days. Several disinfectants have been shown to inactivate SARS-CoV-2, but they rapidly evaporate, are flammable or toxic and may be scarce or inexistent for vulnerable populations. Therefore, we are proposing simple, easy to prepare, low-cost and efficient antiviral films, made with a widely available dishwashing detergent, which can be spread on hands and inanimate surfaces and is expected to maintain virucidal activity for longer periods than the current sanitizers. Avian coronavirus (ACoV) was used as model of the challenge to test the antivirus efficacy of the proposed films. Polystyrene petri dishes were covered with a thin layer of detergent formula. After drying, the films were exposed to different virus doses for 10 min and virus infectivity was determined using embryonated chicken eggs, and RNA virus quantification in allantoic fluids by RT-qPCR. The films inactivated the ACoV (ranging from 103.7 to 106.7 EID50), which is chemically and morphologically similar to SARS-CoV-2, and may constitute an excellent alternative to minimize the spread of COVID-19.
Oxidative Stress and Analysis of Selected SNPs of ACHE (rs 2571598), BCHE (rs 3495), CAT (rs 7943316), SIRT1 (rs 10823108), GSTP1 (rs 1695), and Gene GSTM1, GSTT1 in Chronic Organophosphates Exposed Groups from Cameroon and Pakistan
Authors: Mbah Ntepe Leonel Javeres , Habib Rabia , Judith Laure Ngondi , Raza Saqlain , Nepovimova Eugenie , Kuca Kamil , Batool Sajida , Muhammad Nurulain Syed
Published: September 2020

The detrimental effects of organophosphates (OPs) on human health are thought to be of systemic, i.e., irreversible inhibition of acetylcholinesterase (AChE) at nerve synapses. However, several studies have shown that AChE inhibition alone cannot explain all the toxicological manifestations in prolonged exposure to OPs. The present study aimed to assess the status of antioxidants malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) (reduced), catalase, and ferric reducing antioxidant power (FRAP) in chronic OP-exposed groups from Cameroon and Pakistan. Molecular analysis of genetic polymorphisms (SNPs) of glutathione transferases (GSTM1, GSTP1, GSTT1), catalase gene (CAT, rs7943316), sirtuin 1 gene (SIRT1, rs10823108), acetylcholinesterase gene (ACHE, rs2571598), and butyrylcholinesterase gene (BCHE, rs3495) were screened in the OP-exposed individuals to find the possible causative association with oxidative stress and toxicity. Cholinesterase and antioxidant activities were measured by colorimetric methods using a spectrophotometer. Salting-out method was employed for DNA extraction from blood followed by restriction fragment length polymorphism (RFLP) for molecular analysis. Cholinergic enzymes were significantly decreased in OP-exposed groups. Catalase and SOD were decreased and MDA and FRAP were increased in OP-exposed groups compared to unexposed groups in both groups. GSH was decreased only in Pakistani OPs-exposed group. Molecular analysis of ACHE, BCHE, Catalase, GSTP1, and GSTM1 SNPs revealed a tentative association with their phenotypic expression that is level of antioxidant and cholinergic enzymes. The study concludes that chronic OPs exposure induces oxidative stress which is associated with the related SNP polymorphism. The toxicogenetics of understudied SNPs were examined for the first time to our understanding. The findings may lead to a newer area of investigation on OPs induced health issues and toxicogenetics.
Quercetin as an Agent for Protecting the Bone: A Review of the Current Evidence
Authors: Wong Sok Kuan , Chin Kok-Yong , Ima-Nirwana Soelaiman
Published: September 2020

Quercetin is a flavonoid abundantly found in fruits and vegetables. It possesses a wide spectrum of biological activities, thus suggesting a role in disease prevention and health promotion. The present review aimed to uncover the bone-sparing effects of quercetin and its mechanism of action. Animal studies have found that the action of quercetin on bone is largely protective, with a small number of studies reporting negative outcomes. Quercetin was shown to inhibit RANKL-mediated osteoclastogenesis, osteoblast apoptosis, oxidative stress and inflammatory response while promoting osteogenesis, angiogenesis, antioxidant expression, adipocyte apoptosis and osteoclast apoptosis. The possible underlying mechanisms involved are regulation of Wnt, NF-κB, Nrf2, SMAD-dependent, and intrinsic and extrinsic apoptotic pathways. On the other hand, quercetin was shown to exert complex and competing actions on the MAPK signalling pathway to orchestrate bone metabolism, resulting in both stimulatory and inhibitory effects on bone in parallel. The overall interaction is believed to result in a positive effect on bone. Considering the important contributions of quercetin in regulating bone homeostasis, it may be considered an economical and promising agent for improving bone health. The documented preclinical findings await further validation from human clinical trials.
Elucidating the Role of Ezh2 in Tolerogenic Function of NOD Bone Marrow-Derived Dendritic Cells Expressing Constitutively Active Stat5b
Authors: Zerif Echarki , Khan Farhan Ullah , Raki Ahmed Aziz , Lullier Véronique , Gris Denis , Dupuis Gilles , Amrani Abdelaziz
Published: September 2020

Tolerogenic dendritic cells (toDCs) are crucial to controlling the development of autoreactive T cell responses and the prevention of autoimmunity. We have reported that NOD.CD11cStat5b-CA transgenic mice expressing a constitutively active (CA) form of Stat5b under the control of a CD11c promoter are protected from diabetes and that Stat5b-CA-expressing DCs are tolerogenic and halt ongoing diabetes in NOD mice. However, the molecular mechanisms by which Stat5b-CA modulates DC tolerogenic function are not fully understood. Here, we used bone marrow-derived DCs (BMDCs) from NOD.CD11cStat5b-CA transgenic mice (Stat5b-CA.BMDCs) and found that Stat5b-CA.BMDCs displayed high levels of MHC class II, CD80, CD86, PD-L1, and PD-L2 and produced elevated amounts of TGFβ but low amounts of TNFα and IL-23. Stat5b-CA.BMDCs upregulated Irf4 and downregulated Irf8 genes and protein expression and promoted CD11c+CD11b+ DC2 subset differentiation. Interestingly, we found that the histone methyltransferase Ezh2 and Stat5b-CA bound gamma-interferon activated site (GAS) sequences in the Irf8 enhancer IRF8 transcription, whereas Stat5b but not Ezh2 bound GAS sequences in the Irf4 promoter to enhance IRF4 transcription. Injection of Stat5b-CA.BMDCs into prediabetic NOD mice halted progression of islet inflammation and protected against diabetes. Importantly, inhibition of Ezh2 in tolerogenic Stat5b-CA.BMDCs reduced their ability to prevent diabetes development in NOD recipient mice. Taken together, our data suggest that the active form of Stat5b induces tolerogenic DC function by modulating IRF4 and IRF8 expression through recruitment of Ezh2 and highlight the fundamental role of Ezh2 in Stat5b-mediated induction of tolerogenic DC function.
Role of Arginine Methylation in Alternative Polyadenylation of VEGFR-1 (Flt-1) pre-mRNA
Authors: Ikeda Takayuki , Saito-Takatsuji Hidehito , Yoshitomi Yasuo , Yonekura Hideto
Published: September 2020

Mature mRNA is generated by the 3ʹ end cleavage and polyadenylation of its precursor pre-mRNA. Eukaryotic genes frequently have multiple polyadenylation sites, resulting in mRNA isoforms with different 3ʹ-UTR lengths that often encode different C-terminal amino acid sequences. It is well-known that this form of post-transcriptional modification, termed alternative polyadenylation, can affect mRNA stability, localization, translation, and nuclear export. We focus on the alternative polyadenylation of pre-mRNA for vascular endothelial growth factor receptor-1 (VEGFR-1), the receptor for VEGF. VEGFR-1 is a transmembrane protein with a tyrosine kinase in the intracellular region. Secreted forms of VEGFR-1 (sVEGFR-1) are also produced from the same gene by alternative polyadenylation, and sVEGFR-1 has a function opposite to that of VEGFR-1 because it acts as a decoy receptor for VEGF. However, the mechanism that regulates the production of sVEGFR-1 by alternative polyadenylation remains poorly understood. In this review, we introduce and discuss the mechanism of alternative polyadenylation of VEGFR-1 mediated by protein arginine methylation.
Hsp70 and NF-kB Mediated Control of Innate Inflammatory Responses in a Canine Macrophage Cell Line
Authors: Lyu Qingkang , Wawrzyniuk Magdalena , Rutten Victor P. M. G. , van Eden Willem , Sijts Alice J. A. M. , Broere Femke
Published: September 2020

The pathogenesis of many inflammatory diseases is associated with the uncontrolled activation of nuclear factor kappa B (NF-κB) in macrophages. Previous studies have shown that in various cell types, heat shock protein 70 (Hsp70) plays a crucial role in controlling NF-κB activity. So far, little is known about the role of Hsp70 in canine inflammatory processes. In this study we investigated the potential anti-inflammatory effects of Hsp70 in canine macrophages as well as the mechanisms underlying these effects. To this end, a canine macrophage cell line was stressed with arsenite, a chemical stressor, which upregulated Hsp70 expression as detected by flow cytometry and qPCR. A gene-edited version of this macrophage cell line lacking inducible Hsp70 was generated using CRISPR-Cas9 technology. To determine the effects of Hsp70 on macrophage inflammatory properties, arsenite-stressed wild-type and Hsp70 knockout macrophages were exposed to lipopolysaccharide (LPS), and the expression of the inflammatory cytokines IL-6, IL-1β and tumor necrosis factor-α (TNF-α) and levels of phosphorylated NF-κB were determined by qPCR and Western Blotting, respectively. Our results show that non-toxic concentrations of arsenite induced Hsp70 expression in canine macrophages; Hsp70 upregulation significantly inhibited the LPS-induced expression of the pro-inflammatory mediators TNF-α and IL-6, as well as NF-κB activation in canine macrophages. Furthermore, the gene editing of inducible Hsp70 by CRISPR-Cas9-mediated gene editing neutralized this inhibitory effect of cell stress on NF-κB activation and pro-inflammatory cytokine expression. Collectively, our study reveals that Hsp70 may regulate inflammatory responses through NF-κB activation and cytokine expression in canine macrophages.
A Mechanosensitive Channel, Mouse Transmembrane Channel-Like Protein 1 (mTMC1) Is Translated from a Splice Variant mTmc1ex1 but Not from the Other Variant mTmc1ex2
Authors: Yamaguchi Soichiro , Hamamura Maho , Otsuguro Ken-ichi
Published: September 2020

Mechanical stimuli caused by sound waves are detected by hair cells in the cochlea through the opening of mechanoelectrical transduction (MET) channels. Transmembrane channel-like protein 1 (TMC1) has been revealed to be the pore-forming component of the MET channel. The two splice variants for mouse Tmc1 (mTmc1ex1 and mTmc1ex2) were reported to be expressed in the cochlea of infant mice, though only the sequence of mTmc1ex2 had been deposited in GenBank. However, due to the presence of an upstream open reading frame (uORF) and the absence of a typical Kozak sequence in mTmc1ex2, we questioned whether mTMC1 was translated from mTmc1ex2. Therefore, in this study, we evaluated which splice variant was protein-coding mRNA. Firstly, the results of RT-PCR and cDNA cloning of mTmc1 using mRNA isolated from the cochlea of five-week-old mice suggested that more Tmc1ex1 were expressed than mTmc1ex2. Secondly, mTMC1 was translated from mTmc1ex1 but not from mTmc1ex2 in a heterologous expression system. Finally, analyses using site-directed mutagenesis revealed that the uORF and the weak Kozak sequence in mTmc1ex2 prevented the translation of mTMC1 from mTmc1ex2. These results suggest that mTmc1ex1 plays a main role in the expression of mTMC1 in the mouse cochlea, and therefore, mTmc1ex1 should be the mRNA for mTMC1 hereafter.
Characteristics of CD133-Sustained Chemoresistant Cancer Stem-Like Cells in Human Ovarian Carcinoma
Authors: Liu Chao Lien , Chen Ying Jen , Fan Ming Huei , Liao Yi Jen , Mao Tsui Lien
Published: September 2020

Cancer stem cells (CSCs) are considered to be the origin of ovarian cancer (OC) development, recurrence, and chemoresistance. We investigated changes in expression levels of the CSC biomarker, cluster of differentiation 133 (CD133), from primary OC cell lines to induction of CSC-spheres in an attempt to explore the mechanisms related to modulation of stemness, drug resistance, and tumorigenesis in CSCs, thus facilitating the search for new therapeutics for OC. The effect of CD133 overexpression on the induction of CSC properties was evaluated by sphere-forming assays, RT-qPCR, flow cytometry, cell viability assays, and in vivo xenograft experiments. Moreover, the potential signaling molecules that participate in CD133 maintenance of stemness were screened by RNA-sequencing. CD133 expression was upregulated during OCSC induction and chemotherapeutic drug treatment over time, which increased the expressions of stemness-related markers (SOX2, OCT4, and Nanog). CD133 overexpression also promoted tumorigenesis in NOD/SCID mice. Several signalings were controlled by CD133 spheres, including extracellular matrix receptor interactions, chemokine signaling, and Wnt signaling, all of which promote cell survival and cell cycle progression. Our findings suggest that CD133 possesses the ability to maintain functional stemness and tumorigenesis of OCSCs by promoting cell survival signaling and may serve as a potential target for stem cell-targeted therapy of OC.
Cardiovascular Damage in COVID-19: Therapeutic Approaches Targeting the Renin-Angiotensin-Aldosterone System
Authors: Lumpuy-Castillo Jairo , Lorenzo-Almorós Ana , Pello-Lázaro Ana María , Sánchez-Ferrer Carlos , Egido Jesús , Tuñón José , Peiró Concepción , Lorenzo Óscar
Published: September 2020

Coronavirus disease 2019 (COVID-19) is usually more severe and associated with worst outcomes in individuals with pre-existing cardiovascular pathologies, including hypertension or atherothrombosis. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can differentially infect multiple tissues (i.e., lung, vessel, heart, liver) in different stages of disease, and in an age- and sex-dependent manner. In particular, cardiovascular (CV) cells (e.g., endothelial cells, cardiomyocytes) could be directly infected and indirectly disturbed by systemic alterations, leading to hyperinflammatory, apoptotic, thrombotic, and vasoconstrictive responses. Until now, hundreds of clinical trials are testing antivirals and immunomodulators to decrease SARS-CoV-2 infection or related systemic anomalies. However, new therapies targeting the CV system might reduce the severity and lethality of disease. In this line, activation of the non-canonical pathway of the renin-angiotensin-aldosterone system (RAAS) could improve CV homeostasis under COVID-19. In particular, treatments with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARB) may help to reduce hyperinflammation and viral propagation, while infusion of soluble ACE2 may trap plasma viral particles and increase cardioprotective Ang-(1–9) and Ang-(1–7) peptides. The association of specific ACE2 polymorphisms with increased susceptibility of infection and related CV pathologies suggests potential genetic therapies. Moreover, specific agonists of Ang-(1–7) receptor could counter-regulate the hypertensive, hyperinflammatory, and hypercoagulable responses. Interestingly, sex hormones could also regulate all these RAAS components. Therefore, while waiting for an efficient vaccine, we suggest further investigations on the non-canonical RAAS pathway to reduce cardiovascular damage and mortality in COVID-19 patients.
Agent-Based Modeling of T Cell Receptor Cooperativity
Authors: Siokis Anastasios , Robert Philippe A. , Meyer-Hermann Michael
Published: September 2020

Immunological synapse (IS) formation is a key event during antigen recognition by T cells. Recent experimental evidence suggests that the affinity between T cell receptors (TCRs) and antigen is actively modulated during the early steps of TCR signaling. In this work, we used an agent-based model to study possible mechanisms for affinity modulation during IS formation. We show that, without any specific active mechanism, the observed affinity between receptors and ligands evolves over time and depends on the density of ligands of the antigen peptide presented by major histocompatibility complexes (pMHC) and TCR molecules. A comparison between the presence or absence of TCR–pMHC centrally directed flow due to F-actin coupling suggests that centripetal transport is a potential mechanism for affinity modulation. The model further suggests that the time point of affinity measurement during immune synapse formation is critical. Finally, a mathematical model of F-actin foci formation incorporated in the agent-based model shows that TCR affinity can potentially be actively modulated by positive/negative feedback of the F-actin foci on the TCR-pMHC association rate kon.
P2 × 7 Receptor Inhibits Astroglial Autophagy via Regulating FAK- and PHLPP1/2-Mediated AKT-S473 Phosphorylation Following Kainic Acid-Induced Seizures
Authors: Lee Duk-Shin , Kim Ji-Eun
Published: September 2020

Recently, we have reported that blockade/deletion of P2X7 receptor (P2X7R), an ATP-gated ion channel, exacerbates heat shock protein 25 (HSP25)-mediated astroglial autophagy (clasmatodendrosis) following kainic acid (KA) injection. In P2X7R knockout (KO) mice, prolonged astroglial HSP25 induction exerts 5′ adenosine monophosphate-activated protein kinase/unc-51 like autophagy activating kinase 1-mediated autophagic pathway independent of mammalian target of rapamycin (mTOR) activity following KA injection. Sustained HSP25 expression also enhances AKT-serine (S) 473 phosphorylation leading to astroglial autophagy via glycogen synthase kinase-3β/bax interacting factor 1 signaling pathway. However, it is unanswered how P2X7R deletion induces AKT-S473 hyperphosphorylation during autophagic process in astrocytes. In the present study, we found that AKT-S473 phosphorylation was increased by enhancing activity of focal adhesion kinase (FAK), independent of mTOR complex (mTORC) 1 and 2 activities in isolated astrocytes of P2X7R knockout (KO) mice following KA injection. In addition, HSP25 overexpression in P2X7R KO mice acted as a chaperone of AKT, which retained AKT-S473 phosphorylation by inhibiting the pleckstrin homology domain and leucine-rich repeat protein phosphatase (PHLPP) 1- and 2-binding to AKT. Therefore, our findings suggest that P2X7R may be a fine-tuner of AKT-S473 activity during astroglial autophagy by regulating FAK phosphorylation and HSP25-mediated inhibition of PHLPP1/2-AKT binding following KA treatment.
Targeting Cell Cycle in Breast Cancer: CDK4/6 Inhibitors
Authors: Piezzo Michela , Cocco Stefania , Caputo Roberta , Cianniello Daniela , Gioia Germira Di , Lauro Vincenzo Di , Fusco Giuseppina , Martinelli Claudia , Nuzzo Francesco , Pensabene Matilde , Laurentiis Michelino De
Published: September 2020

Deregulation of cell cycle, via cyclin D/CDK/pRb pathway, is frequently observed in breast cancer lending support to the development of drugs targeting the cell cycle control machinery, like the inhibitors of the cycline-dependent kinases (CDK) 4 and 6. Up to now, three CDK4/6 inhibitors have been approved by FDA for the treatment of hormone receptor-positive (HR+), HER2-negative metastatic breast cancer. These agents have been effective in improving the clinical outcomes, but the development of intrinsic or acquired resistance can limit the efficacy of these treatments. Clinical and translational research is now focused on investigation of the mechanism of sensitivity/resistance to CDK4/6 inhibition and novel therapeutic strategies aimed to improve clinical outcomes. This review summarizes the available knowledge regarding CDK4/6 inhibitor, the discovery of new biomarkers of response, and the biological rationale for new combination strategies of treatment.
The Role of Transforming Growth Factor-Beta in Retinal Ganglion Cells with Hyperglycemia and Oxidative Stress
Authors: Chen Hsin-Yi , Ho Yi-Jung , Chou Hsiu-Chuan , Liao En-Chi , Tsai Yi-Ting , Wei Yu-Shan , Lin Li-Hsun , Lin Meng-Wei , Wang Yi-Shiuan , Ko Mei-Lan , Chan Hong-Lin
Published: September 2020

A characteristic of diabetes mellitus is hyperglycemia, which is considered with an emphasis on the diabetic retinopathy of progressive neurodegenerative disease. Retinal ganglion cells (RGCs) are believed to be important cells affected in the pathogenesis of diabetic retinopathy. Transforming growth factor-beta (TGF-β) is a neuroprotective protein that helps to withstand various neuronal injuries. To investigate the potential roles and regulatory mechanisms of TGF-β in hyperglycemia-triggered damage of RGCs in vitro, we established RGCs in 5.5, 25, 50, and 100 mM D-glucose supplemented media and focused on the TGF-β-related oxidative stress pathway in combination with hydrogen peroxide (H2O2). Functional experiments showed that TGF-β1/2 protein expression was upregulated in RGCs with hyperglycemia. The knockdown of TGF-β enhanced the accumulation of reactive oxygen species (ROS), inhibited the cell proliferation rate, and reduced glutathione content in hyperglycemia. Furthermore, the results showed that the TGF-β-mediated enhancement of antioxidant signaling was correlated with the activation of stress response proteins and the antioxidant pathway, such as aldehyde dehydrogenase 3A1 (ALDH3A1), heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor (Nrf2), and hypoxia-inducible factor (HIF-1α). Summarizing, our results demonstrated that TGF-β keeps RGCs from hyperglycemia-triggered harm by promoting the activation of the antioxidant pathway, suggesting a potential anti-diabetic therapy for the treatment of diabetic retinopathy.
Vitamin D and Cardiovascular Disease, with Emphasis on Hypertension, Atherosclerosis, and Heart Failure
Authors: Latic Nejla , Erben Reinhold G.
Published: September 2020

Vitamin D deficiency is the most common nutritional deficiency, affecting almost one billion people worldwide. Vitamin D is mostly known for its role in intestinal calcium absorption and bone mineralization. However, the observation of seasonal changes in blood pressure and the subsequent identification of vitamin D receptor (VDR) and 1α-hydroxylase in cardiomyocytes, as well as endothelial and vascular smooth muscle cells, implicated a role of vitamin D in the cardiovascular system. Animal studies provided compelling evidence that vitamin D signaling is essential for cardiovascular integrity, especially for the regulation of vascular tone and as an antifibrotic and antihypertrophic signaling pathway in the heart. In addition, observational studies reported an association between vitamin D deficiency and risk of hypertension, atherosclerosis, and heart failure. However, recent clinical intervention studies failed to prove the causal relationship between vitamin D supplementation and beneficial effects on cardiovascular health. In this review, we aim to highlight our current understanding of the role of vitamin D in the cardiovascular system and to find potential explanations for the large discrepancies between the outcome of experimental studies and clinical intervention trials.
Genetic and Epigenetic Aspects of Atopic Dermatitis
Authors: Nedoszytko Bogusław , Reszka Edyta , Gutowska-Owsiak Danuta , Trzeciak Magdalena , Lange Magdalena , Jarczak Justyna , Niedoszytko Marek , Jablonska Ewa , Romantowski Jan , Strapagiel Dominik , Skokowski Jarosław , Siekierzycka Anna , Nowicki Roman , Dobrucki Iwona , Zaryczańska Anna , Kalinowski Leszek
Published: September 2020

Atopic dermatitis is a heterogeneous disease, in which the pathogenesis is associated with mutations in genes encoding epidermal structural proteins, barrier enzymes, and their inhibitors; the role of genes regulating innate and adaptive immune responses and environmental factors inducing the disease is also noted. Recent studies point to the key role of epigenetic changes in the development of the disease. Epigenetic modifications are mainly mediated by DNA methylation, histone acetylation, and the action of specific non-coding RNAs. It has been documented that the profile of epigenetic changes in patients with atopic dermatitis (AD) differs from that observed in healthy people. This applies to the genes affecting the regulation of immune response and inflammatory processes, e.g., both affecting Th1 bias and promoting Th2 responses and the genes of innate immunity, as well as those encoding the structural proteins of the epidermis. Understanding of the epigenetic alterations is therefore pivotal to both create new molecular classifications of atopic dermatitis and to enable the development of personalized treatment strategies.
Genome-Wide Analysis of Peptidoglycan Recognition Protein Genes in Fig Wasps (Hymenoptera, Chalcidoidea)
Authors: Hou Hong-Xia , Guo Meng-Yuan , Geng Jin , Wei Xian-Qin , Huang Da-Wei , Xiao Jin-Hua
Published: September 2020

The innate immunity is the most important defense against pathogen of insects, and the peptidoglycan recognition proteins (PGRPs) play an important role in the processes of immune recognition and initiation of Toll, IMD and other signal pathways. In fig wasps, pollinators and non-pollinators present different evolutionary histories and lifestyles, even though both are closely associated with fig syconia, which may indicate their different patterns in the evolution of PGRPs. By manual annotation, we got all the PGRP genes of 12 fig wasp species, containing seven pollinators and five non-pollinators, and investigated their putative different evolutionary patterns. We found that the number of PGRP genes in pollinators was significantly lower than in non-pollinators, and the number of catalytic PGRP presented a declining trend in pollinators. More importantly, PGRP-SA is associated with initiating the Toll pathway, as well as gram-negative bacteria-binding proteins (GNBPs), which were completely lost in pollinators, which led us to speculate that the initiation of Toll pathway was simpler in pollinators than in non-pollinators. We concluded that fig pollinators owned a more streamlined innate immune recognition system than non-pollinators. Our results provide molecular evidence for the adaptive evolution of innate immunity in insects of host specificity.
Are Microsatellite Patterns Specific for Tumor Types? A Pilot Investigation
Authors: Haiduk Tiffany , Brockmann Michael , Schmitt Christoph , Tillmann Ramona-Liza , Pieper Monika , Lüsebrink Jessica , Schildgen Oliver , Schildgen Verena
Published: September 2020

Microsatellite testing is an emerging field of molecular pathology, as microsatellite instability (MSI) appears to be a predictive biomarker for some cancers. Although multiple studies on microsatellites have been published, recent observations suggest that the microsatellites that define instability differ between tumor entities. This assumption is confirmed by the present study that compared different MSI assays validated for colorectal cancer. Whilst all assays deliver the same MSI/MSS status for colorectal cancers, they differ for tonsillar tumors, leading to the hypothesis that MSI patterns are tumor-type specific.
Near-Surface Transport Properties and Lagrangian Statistics during Two Contrasting Years in the Adriatic Sea
Authors: Hariri Saeed
Published: September 2020

This paper describes the near-surface transport properties and Lagrangian statistics in the Adriatic semi-enclosed basin using synthetic drifters. Lagrangian transport models were used to simulate synthetic trajectories from the mean flow fields obtained by the Massachusetts Institute of Technology general circulation model (MITgcm), implemented in the Adriatic from October 2006 until December 2008. In particular, the surface circulation properties in two contrasting years (2007 had a mild winter and cold fall, while 2008 had a normal winter and hot summer) are compared here. In addition, the Lagrangian statistics for the entire Adriatic Basin after removing the Eulerian mean circulation for numerical particles were calculated. The results indicate that the numerical particles were slower in this simulation when compared with the real drifters. This is because of the reduced energetic flow field generated by the MIT general circulation model during the selected years. The numerical results showed that the balanced effects of the wind-driven recirculation in the northernmost area(which would be a sea response to the Bora wind field) and the Po River discharge cause the residence times to be similar during the two selected years (182 and 185 days in 2007 and 2008, respectively). Furthermore, the mean angular momentum, diffusivity, and Lagrangian velocity covariance values are smaller than in the real drifter observations, while the maximum Lagrangian integral time scale is the same.