bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Shale Source Rocks and Clay Mineral Diagenesis in the Permian Basin, USA: Inferences on Basin Thermal Maturity and Source Rock Potential
Authors: Green Hunter , Šegvić Branimir , Zanoni Giovanni , Omodeo-Salé Silvia , Adatte Thierry
Published: September 2020

The use of mineral diagenetic indices and organic matter maturity is useful for reconstructing the evolution of sedimentary basins and critical assessments for potential source rocks for petroleum exploration. In this study, the relationship of clay mineral diagenesis and organic matter thermal indices (Rock-Eval Tmax) and calculated vitrinite reflectance (%Ro) were used to constrain the maximum burial depths and temperatures of three distinct intervals within the northern Permian Basin, USA. X-ray diffraction of clay fractions (<2 µm) consists of illite, chlorite, and illite-smectite intermediates. Primary clay mineral diagenetic changes progressively increase in ordering from R0 to R1 I-S between 2359.5 and 2485.9 m and the appearance of chlorite at 2338.7 m. Rock-Eval pyrolysis data show 0 to 14 wt% TOC, HI values of 40 to 520 mgHC/g TOC, and S2 values of 0 to 62 mg HC/g, with primarily type II kerogen with calculated %Ro within the early to peak oil maturation window. Evaluation of the potential for oil generation is relatively good throughout the Tonya 401 and JP Chilton wells. Organic maturation indices (Tmax, %Ro) and peak burial temperatures correlate well with clay mineral diagenesis (R0–R1 I-S), indicating that maximum burial depths and temperatures were between 2.5 and 4 km and <100 °C and 140 °C, respectively. Additionally, the use of clay mineral-derived temperatures provides insight into discrepancies between several calculated %Ro equations and thus should be further investigated for use in the Permian Basin. Accordingly, these findings show that clay mineral diagenesis, combined with other paleothermal proxies, can considerably improve the understanding of the complex burial history of the Permian Basin in the context of the evolution of the southern margin of Laurentia.
Geology and Aquifer Sensitivity of Quaternary Glacial Deposits Overlying a Portion of the Mahomet Buried Bedrock Valley Aquifer System
Authors: Watson Andrew , Peterson Eric W. , Malone Dave , Tranel Lisa
Published: September 2020

To characterize the distribution of Holocene and Late Quaternary deposits and to assess the contamination potential of the Mahomet Aquifer, surficial geologic and aquifer sensitivity maps of the Gibson City East 7.5-Minute Quadrangle were created. Geologic data, extent, and thickness of the geologic materials were coupled with LiDAR topographic data and analyzed using ESRI’s ArcGIS 10.6.1. Aquifer sensitivity to contamination was calculated based on the depth to the first aquifer unit, aquifer thickness, and the lithology of the aquifer materials. The surficial geologic mapping identified five lithostratigraphic units: the Cahokia Formation, the Equality Formation, the Henry Formation, and the Yorkville and Batestown Members of the Lemont Formation. The southeast to northwest trending Illiana Morainic System is the most prominent feature in the study area and delineates the maximum extent of the glaciers during the Livingston Phase of glaciation. Postglacial deposits of the Cahokia Formation, alluvium, interfinger, and overlie with glacial outwash of the Henry Formation along channels and drainage ways downslope of the moraine. The areas of least sensitivity are located over the Illiana Morainic System, whereas the greatest potential to contamination occurs where the thickest deposits of the Henry Formation and Cahokia Formation lie at or just below the land surface.
Integrated Surface Water and Groundwater Analysis under the Effects of Climate Change, Hydraulic Fracturing and its Associated Activities: A Case Study from Northwestern Alberta, Canada
Authors: Saha Gopal Chandra , Quinn Michael
Published: September 2020

This study assessed how hydraulic fracturing (HF) (water withdrawals from nearby river water source) and its associated activities (construction of well pads) would affect surface water and groundwater in 2021–2036 under changing climate (RCP4.5 and RCP8.5 scenarios of the CanESM2) in a shale gas and oil play area (23,984.9 km2) of northwestern Alberta, Canada. An integrated hydrologic model (MIKE-SHE and MIKE-11 models), and a cumulative effects landscape simulator (ALCES) were used for this assessment. The simulation results show an increase in stream flow and groundwater discharge in 2021–2036 under both RCP4.5 and RCP8.5 scenarios with respect to those under the base modeling period (2000–2012). This occurs because of the increased precipitation and temperature predicted in the study area under both RCP4.5 and RCP8.5 scenarios. The results found that HF has very small (less than 1%) subtractive impacts on stream flow in 2021–2036 because of the large size of the study area, although groundwater discharge would increase minimally (less than 1%) due to the increase in the gradient between groundwater and surface water systems. The simulation results also found that the construction of well pads related to HF have very small (less than 1%) additive impacts on stream flow and groundwater discharge due to the non-significant changes in land use. The obtained results from this study provide valuable information for effective long-term water resources decision making in terms of seasonal and annual water extractions from the river, and allocation of water to the oil and gas industries for HF in the study area to meet future energy demand considering future climate change.
Effectiveness of SaBang-DolGi Walking Exercise Program on Physical and Mental Health of Menopausal Women
Authors: Noh EunHee , Kim JiYoun , Kim MunHee , Yi EunSurk
Published: September 2020

Objective: We investigated the effectiveness of a 12-week SaBang-DolGi walking exercise program on the physical and mental health of menopausal women and aimed to provide the basic data needed to develop health promotion programs for the active and healthy aging of menopausal women. Materials and methods: The participants comprised 40 women aged 50–65 years who were divided into two randomly selected groups in training sessions (exercising group, n = 21 and control group, n = 19). A physical (grip, muscle and endurance) test and mental health test (simple mental health test II) were conducted using questionnaires with the aim of examining subjects’ physical and mental health before and after exercise. Results: After the intervention, the participants experienced positive changes in the physical dimension, with significant enhancements particularly in mental well-being and menopause-related health and subdomains. Controlled and regular exercise for 12 weeks was significantly correlated with a positive change in vitality and mental health. Conclusions: We found that the SaBang-DolGi walking exercise program helps to promote the physical and mental health of menopausal women who are exposed to the various stresses and depressions that accompany physical deterioration; the program was found to encourage active and healthy aging.
Evaluation of Green Coffee-Roasting Biogas with Modeling Valorization of Possible Solutions
Authors: Campo Giuseppe , Cerutti Alberto , Ravina Marco , Panepinto Deborah , Riggio Vincenzo A. , Zanetti Mariachiara
Published: September 2020

According to the European Union Directive 2009/28/EC, the goals of obtaining 20% of all energy requirements from renewable sources and a 20% reduction in primary energy use must be fulfilled by 2020. In this work, an evaluation was performed, from the environmental and energy point of view, of anaerobic digestion as a valid solution for the treatment of the byproducts obtained from the coffee-roasting process. In particular, thermophilic anaerobic digestion tests were carried out. Output values from the laboratory were used as input for the MCBioCH4 model to evaluate the produced flow of biogas and biomethane and two different biogas valorization alternatives, namely, the traditional exploitation of biogas for heat/energy production and biomethane conversion. The results of the preliminary simulation showed that a full-scale implementation of the coffee waste biogas production process is technically feasible and environmentally sustainable. Furthermore, the performed analysis validates a general methodology for energy production compatibility planning.
How Can Adolescents Benefit from the Use of Social Networks? The iGeneration on Instagram
Authors: Cipolletta Sabrina , Malighetti Clelia , Cenedese Chiara , Spoto Andrea
Published: September 2020

In the last few years, Instagram has been a topic of much contention, as it has been shown to be associated with both risks and benefits for young users. This study explores the influence of the use of Instagram on adolescents’ constructions of self and interpersonal experience. Forty Italian adolescents aged between 11 and 16 years were interviewed and completed repertory grids. The results showed that the adolescents’ self-construction and distance from others were mostly influenced by receiving, or not receiving, positive feedback, rather than by using Instagram itself. Specifically, there was an increase in self-acceptance and social desirability after receiving a “like” and an increase in social isolation after receiving no “likes”. The regression model also showed a decrease in self-acceptance on Instagram in the case of female adolescents, and in participants who edited photos. These findings are useful for understanding the constant need for approval adolescents require today and could be used as a guiding tool for future studies and intervention policies. The present study offers an innovative methodology that refers to the relevant dimensions of adolescents’ self-construction rather than investigating the more general relationship between personality traits and social networks’ use.
Work-Family Conflict and Depressive Symptoms Among Chinese Employees: Cross-Level Interaction of Organizational Justice Climate and Family Flexibility
Authors: Zhou Mingjie , Zhang Jinfeng , Li Fugui , Chen Chen
Published: September 2020

This study aims to examine how organizational and family factors protect employees from depressive symptoms induced by work-family conflict. With a cross-sectional design, a total of 2184 Chinese employees from 76 departments completed measures of work-family conflict, organizational justice, family flexibility, and depressive symptoms. The results showed that work-family conflict including work-to-family conflict and family-to-work conflict was positively associated with depressive symptoms. In cross-level analysis, organizational justice climate weakened the adverse effect of work-family conflict on depressive symptoms and the buffering effects of procedural and distributive justice climate in the association between work-family conflict and depressive symptoms depended on family flexibility. Specifically, compared with employees with high family flexibility, procedural and distributive justice climate had a stronger buffering effect for employees with low family flexibility. These results indicate that organization and family could compensate each other to mitigate the effect of work-family conflict on employees’ depressive symptoms. Cultivating justice climate in organization and enhancing family flexibility might be an effective way to reduce employees’ depressive symptoms.
Prevalence and Risk Factors of Elevated Blood Pressure and Elevated Blood Glucose among Residents of Kajiado County, Kenya: A Population-Based Cross-Sectional Survey
Authors: Ongosi Anita Nyaboke , Wilunda Calistus , Musumari Patou Masika , Techasrivichien Teeranee , Wang Chia-Wen , Ono-Kihara Masako , Serrem Charlotte , Kihara Masahiro , Nakayama Takeo
Published: September 2020

Kenya is experiencing a rising burden of non-communicable diseases (NCDs), yet data to inform effective interventions are limited. We investigated the prevalence of elevated blood pressure, elevated blood glucose and their determinants in a rapidly urbanizing area in Kenya. Data on socio-demographics, dietary and behavioural risk factors, anthropometric measurements, blood pressure, blood glucose, plasma lipids and urinary biomarkers were collected from 221 men and 372 women (25–64 years). Multivariable logistic regression models assessed correlates of elevated blood pressure (EBP) and elevated blood glucose (EBG). Participants’ mean age was 38.0. ± 11.1 years. The prevalence rates of pre-hypertension and hypertension were 49.0% and 31.6% in men and 43.7% and 20.1% in women, respectively, while those of pre-diabetes and diabetes were 8.4% and 8.0% in men and 11.6% and 7.4% in women, respectively. The prevalence of Body Mass Index (BMI) ≥ 25 kg/m2 was higher in women (60.2%) than in men (39.7%). However, both the risk of EBP and EBG were stronger among men than among women. The high prevalence rates of EBP, EBG and overweight/obesity coupled with low physical activity and low fruit and vegetable intake predispose this population to a higher NCD risk. Interventions to mitigate this risk considering the sex differences are urgently required.
Minimum Sizes of Respiratory Particles Carrying SARS-CoV-2 and the Possibility of Aerosol Generation
Authors: Lee Byung
Published: September 2020

This study calculates and elucidates the minimum size of respiratory particles that are potential carriers of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); furthermore, it evaluates the aerosol generation potential of SARS-CoV-2. The calculations are based on experimental results and theoretical models. In the case of maximum viral-loading derived from experimental data of COVID-19 patients, 8.97 × 10−5% of a respiratory fluid particle from a COVID-19 patient is occupied by SARS-CoV-2. Hence, the minimum size of a respiratory particle that can contain SARS-CoV-2 is calculated to be approximately 9.3 μm. The minimum size of the particles can decrease due to the evaporation of water on the particle surfaces. There are limitations to this analysis: (a) assumption that the viruses are homogeneously distributed in respiratory fluid particles and (b) considering a gene copy as a single virion in unit conversions. However, the study shows that high viral loads can decrease the minimum size of respiratory particles containing SARS-CoV-2, thereby increasing the probability of aerosol generation of the viruses. The aerosol generation theory created in this study for COVID-19 has the potential to be applied to other contagious diseases that are caused by respiratory infectious microorganisms.
Exploring the Role of Gut Bacteria in Health and Disease in Preterm Neonates
Authors: Lee Jimmy Kok-Foo , Hern Tan Loh Teng , Ramadas Amutha , Ab Mutalib Nurul-Syakima , Lee Learn-Han
Published: September 2020

The mortality rate of very preterm infants with birth weight <1500 g is as high as 15%. The survivors till discharge have a high incidence of significant morbidity, which includes necrotising enterocolitis (NEC), early-onset neonatal sepsis (EONS) and late-onset neonatal sepsis (LONS). More than 25% of preterm births are associated with microbial invasion of amniotic cavity. The preterm gut microbiome subsequently undergoes an early disruption before achieving bacterial maturation. It is postulated that bacterial gut colonisation at birth and postnatal intestinal dysbacteriosis precede the development of NEC and LONS in very preterm infants. In fact, bacterial colonization patterns in preterm infants greatly differ from term infants due to maternal chorioamnionitis, gestational age, delivery method, feeding type, antibiotic exposure and the environment factor in neonatal intensive care unit (NICU). In this regard, this review provides an overview on the gut bacteria in preterm neonates’ meconium and stool. More than 50% of preterm meconium contains bacteria and the proportion increases with lower gestational age. Researchers revealed that the gut bacterial diversity is reduced in preterm infants at risk for LONS and NEC. Nevertheless, the association between gut dysbacteriosis and NEC is inconclusive with regards to relative bacteria abundance and between-sample beta diversity indices. With most studies show a disruption of the Proteobacteria and Firmicutes preceding the NEC. Hence, this review sheds light on whether gut bacteria at birth either alone or in combination with postnatal gut dysbacteriosis are associated with mortality and the morbidity of LONS and NEC in very preterm infants.
Important Factors Affecting User Experience Design and Satisfaction of a Mobile Health App—A Case Study of Daily Yoga App
Authors: Yu Na , Huang Yi-Ting
Published: September 2020

In recent years, mobile health (mHealth) has gained popularity. Yoga apps help users to exercise at home and improve their health. It is worth discussing how to give yogis a better experience and higher satisfaction to improve their willingness to keep using yoga apps. In this study, the Daily Yoga app was selected as the research object to explore important factors related to its user experience design and user satisfaction. Through a literature review and Delphi method composed of eight experts, this study put forward the important criteria framework of user experience design for the Daily Yoga app and then, used the DEMATEL (Decision Making and Trial Evaluation Laboratory)-based ANP (Analytic Network Process) method to determine the factors’ importance order and the causal relationships among them. Finally, combined with the results of an importance–performance analysis of 16 real users, we discuss the improvement measures. The research results show that the yoga class is the most critical factor in the user experience design of the Daily Yoga app, the target plan is a factor that is in great need of improvement, and having an attractive interface can improve user experience. The evaluation model of the study can act as a reference for improving user experience with the Daily Yoga app, and can also be widely used in the process of user experience design, questionnaire production, and evaluation optimization of mHealth app and related applications.
Semaphorin4A-Plexin D1 Axis Induces Th2 and Th17 While Represses Th1 Skewing in an Autocrine Manner
Authors: Carvalheiro Tiago , Rafael-Vidal Carlos , Malvar-Fernandez Beatriz , Lopes Ana P. , Pego-Reigosa Jose M. , Radstake Timothy R. D. J. , Garcia Samuel
Published: September 2020

Semaphorin (Sema)4A is a transmembrane glycoprotein that is elevated in several autoimmune diseases such as systemic sclerosis, rheumatoid arthritis and multiple sclerosis. Sema4A has a key role in the regulation of Thelper Th1 and Th2 differentiation and we recently demonstrated that CD4+ T cell activation induces the expression of Sema4A. However, the autocrine role of Sema4A on Th cell differentiation remains unknown. Naïve Th cells from healthy controls were cell sorted and differentiated into Th1, Th2 and Th17 in the presence or absence of a neutralizing antibody against the Sema4A receptor PlexinD1. Gene expression was determined by quantitative PCR and protein expression by ELISA and flow cytometry. We found that the expression of Sema4A is induced during Th1, Th2 and Th17 differentiation. PlexinD1 neutralization induced the differentiation of Th1 cells, while reduced the Th2 and Th17 skewing. These effects were associated with an upregulation of the transcription factor T-bet by Th1 cells, and to downregulation of GATA3 and RORγt in Th2 cells and Th17 cells, respectively. Finally, PlexinD1 neutralization regulates the systemic sclerosis patients serum-induced cytokine production by CD4+ T cells. Therefore, the autocrine Sema4A-PlexinD1 signaling acts as a negative regulator of Th1 skewing but is a key mediator on Th2 and Th17 differentiation, suggesting that dysregulation of this axis might be implicated in the pathogenesis of CD4+ T cell-mediated diseases.
Non-Coding RNAs, a Novel Paradigm for the Management of Gastrointestinal Stromal Tumors
Authors: Amirnasr Azadeh , Sleijfer Stefan , Wiemer Erik A. C.
Published: September 2020

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal malignancies found in the gastrointestinal tract. At a molecular level, most GISTs are characterized by gain-of-function mutations in V-Kit Hardy–Zuckerman 4 Feline Sarcoma Viral Oncogene Homolog (KIT) and Platelet Derived Growth Factor Receptor Alpha (PDGFRA), leading to constitutive activated signaling through these receptor tyrosine kinases, which drive GIST pathogenesis. In addition to surgery, treatment with the tyrosine kinase inhibitor imatinib forms the mainstay of GIST treatment, particularly in the advanced setting. Nevertheless, the majority of GISTs develop imatinib resistance. Biomarkers that indicate metastasis, drug resistance and disease progression early on could be of great clinical value. Likewise, novel treatment strategies that overcome resistance mechanisms are equally needed. Non-coding RNAs, particularly microRNAs, can be employed as diagnostic, prognostic or predictive biomarkers and have therapeutic potential. Here we review which non-coding RNAs are deregulated in GISTs, whether they can be linked to specific clinicopathological features and discuss how they can be used to improve the clinical management of GISTs.
How Severe Anaemia Might Influence the Risk of Invasive Bacterial Infections in African Children
Authors: Abuga Kelvin M. , Muriuki John Muthii , Williams Thomas N. , Atkinson Sarah H.
Published: September 2020

Severe anaemia and invasive bacterial infections are common causes of childhood sickness and death in sub-Saharan Africa. Accumulating evidence suggests that severely anaemic African children may have a higher risk of invasive bacterial infections. However, the mechanisms underlying this association remain poorly described. Severe anaemia is characterized by increased haemolysis, erythropoietic drive, gut permeability, and disruption of immune regulatory systems. These pathways are associated with dysregulation of iron homeostasis, including the downregulation of the hepatic hormone hepcidin. Increased haemolysis and low hepcidin levels potentially increase plasma, tissue and intracellular iron levels. Pathogenic bacteria require iron and/or haem to proliferate and have evolved numerous strategies to acquire labile and protein-bound iron/haem. In this review, we discuss how severe anaemia may mediate the risk of invasive bacterial infections through dysregulation of hepcidin and/or iron homeostasis, and potential studies that could be conducted to test this hypothesis.
Growth Differentiation Factor 15 Ameliorates Anti-Glomerular Basement Membrane Glomerulonephritis in Mice
Authors: Moschovaki-Filippidou Foteini , Steiger Stefanie , Lorenz Georg , Schmaderer Christoph , Ribeiro Andrea , von Rauchhaupt Ekaterina , Cohen Clemens D. , Anders Hans-Joachim , Lindenmeyer Maja , Lech Maciej
Published: September 2020

Growth differentiation factor 15 (GDF15) is a member of the transforming growth factor-β (TGF-β) cytokine family and an inflammation-associated protein. Here, we investigated the role of GDF15 in murine anti-glomerular basement membrane (GBM) glomerulonephritis. Glomerulonephritis induction in mice induced systemic expression of GDF15. Moreover, we demonstrate the protective effects for GDF15, as GDF15-deficient mice exhibited increased proteinuria with an aggravated crescent formation and mesangial expansion in anti-GBM nephritis. Herein, GDF15 was required for the regulation of T-cell chemotactic chemokines in the kidney. In addition, we found the upregulation of the CXCR3 receptor in activated T-cells in GDF15-deficient mice. These data indicate that CXCL10/CXCR3-dependent-signaling promotes the infiltration of T cells into the organ during acute inflammation controlled by GDF15. Together, these results reveal a novel mechanism limiting the migration of lymphocytes to the site of inflammation during glomerulonephritis.
Pediatric Tuberculosis: The Impact of “Omics” on Diagnostics Development
Authors: Jakhar Shailja , Bitzer Alexis A. , Stromberg Loreen R. , Mukundan Harshini
Published: September 2020

Tuberculosis (TB) is a major public health concern for all ages. However, the disease presents a larger challenge in pediatric populations, partially owing to the lack of reliable diagnostic standards for the early identification of infection. Currently, there are no biomarkers that have been clinically validated for use in pediatric TB diagnosis. Identification and validation of biomarkers could provide critical information on prognosis of disease, and response to treatment. In this review, we discuss how the “omics” approach has influenced biomarker discovery and the advancement of a next generation rapid point-of-care diagnostic for TB, with special emphasis on pediatric disease. Limitations of current published studies and the barriers to their implementation into the field will be thoroughly reviewed within this article in hopes of highlighting future avenues and needs for combating the problem of pediatric tuberculosis.
Lipid Composition Affects the Efficiency in the Functional Reconstitution of the Cytochrome c Oxidase
Authors: Hugentobler Katharina Gloria , Heinrich Dorothea , Berg Johan , Heberle Joachim , Brzezinski Peter , Schlesinger Ramona , Block Stephan
Published: September 2020

The transmembrane protein cytochrome c oxidase (CcO) is the terminal oxidase in the respiratory chain of many aerobic organisms and catalyzes the reduction of dioxygen to water. This process maintains an electrochemical proton gradient across the membrane hosting the oxidase. CcO is a well-established model enzyme in bioenergetics to study the proton-coupled electron transfer reactions and protonation dynamics involved in these processes. Its catalytic mechanism is subject to ongoing intense research. Previous research, however, was mainly focused on the turnover of oxygen and electrons in CcO, while studies reporting proton turnover rates of CcO, that is the rate of proton uptake by the enzyme, are scarce. Here, we reconstitute CcO from R. sphaeroides into liposomes containing a pH sensitive dye and probe changes of the pH value inside single proteoliposomes using fluorescence microscopy. CcO proton turnover rates are quantified at the single-enzyme level. In addition, we recorded the distribution of the number of functionally reconstituted CcOs across the proteoliposome population. Studies are performed using proteoliposomes made of native lipid sources, such as a crude extract of soybean lipids and the polar lipid extract of E. coli, as well as purified lipid fractions, such as phosphatidylcholine extracted from soybean lipids. It is shown that these lipid compositions have only minor effects on the CcO proton turnover rate, but can have a strong impact on the reconstitution efficiency of functionally active CcOs. In particular, our experiments indicate that efficient functional reconstitution of CcO is strongly promoted by the addition of anionic lipids like phosphatidylglycerol and cardiolipin.
Interleukin-1β Alters Hebbian Synaptic Plasticity in Multiple Sclerosis
Authors: Stampanoni Bassi Mario , Buttari Fabio , Nicoletti Carolina Gabri , Mori Francesco , Gilio Luana , Simonelli Ilaria , De Paolis Nicla , Marfia Girolama Alessandra , Furlan Roberto , Finardi Annamaria , Centonze Diego , Iezzi Ennio
Published: September 2020

In multiple sclerosis (MS), inflammation alters synaptic transmission and plasticity, negatively influencing the disease course. In the present study, we aimed to explore the influence of the proinflammatory cytokine IL-1β on peculiar features of associative Hebbian synaptic plasticity, such as input specificity, using the paired associative stimulation (PAS). In 33 relapsing remitting-MS patients and 15 healthy controls, PAS was performed on the abductor pollicis brevis (APB) muscle. The effects over the motor hot spot of the APB and abductor digiti minimi (ADM) muscles were tested immediately after PAS and 15 and 30 min later. Intracortical excitability was tested with paired-pulse transcranial magnetic stimulation (TMS). The cerebrospinal fluid (CSF) levels of IL-1β were calculated. In MS patients, PAS failed to induce long-term potentiation (LTP)-like effects in the APB muscle and elicited a paradoxical motor-evoked potential (MEP) increase in the ADM. IL-1β levels were negatively correlated with the LTP-like response in the APB muscle. Moreover, IL-1β levels were associated with synaptic hyperexcitability tested with paired-pulse TMS. Synaptic hyperexcitability caused by IL-1β may critically contribute to alter Hebbian plasticity in MS, inducing a loss of topographic specificity.
Discoidin Domain Receptors 1 Inhibition Alleviates Osteoarthritis via Enhancing Autophagy
Authors: Chou Hsin-Chaio , Chen Chung-Hwan , Chou Liang-Yin , Cheng Tsung-Lin , Kang Lin , Chuang Shu-Chun , Lin Yi-Shan , Ho Mei-Ling , Wang Yan-Hsiung , Lin Sung-Yen , Wang Chau-Zen
Published: September 2020

We recently reported that the chondrocyte-specific knockout of discoidin domain receptors 1 (Ddr1) delayed endochondral ossification (EO) in the growth plate by reducing the chondrocyte hypertrophic terminal differentiation, and apoptosis. The biologic and phenotypic changes in chondrocytes in the articular cartilage with osteoarthritis (OA) are similar to the phenomena observed in the process of EO. Additionally, autophagy can promote chondrocyte survival and prevent articular cartilage from degradation in OA. On this basis, we explored the effect of Ddr1 inhibition on OA prevention and further investigated the roles of autophagy in treating OA with a Ddr1 inhibitor (7 rh). The anterior cruciate ligament transection (ACLT)–OA model was used to investigate the role of 7 rh in vivo. Forty 8-week-old mice were randomly assigned to four groups, including the sham group, ACLT group, and two treated groups (ACLT with 7 rh 6.9 nM or 13.8 nM). According to the study design, normal saline or 7 rh were intra-articular (IA) injected into studied knees 3 times per week for 2 weeks and then once per week for 4 weeks. The results showed that 7 rh treatment significantly improved the functional performances (the weight-bearing ability and the running endurance), decreased cartilage degradation, and also reduced the terminal differentiation markers (collagen type X, Indian hedgehog, and matrix metalloproteinase 13). Moreover, 7 rh decreased chondrocyte apoptosis by regulating chondrocyte autophagy through reducing the expression of the mammalian target of rapamycin and enhancing the light chain 3 and beclin-1 expression. These results demonstrated that the IA injection of 7 rh could reduce the chondrocyte apoptosis and promote chondrocyte autophagy, leading to the attenuation of cartilage degradation. Our observations suggested that the IA injection of 7 rh could represent a potential disease-modifying therapy to prevention OA progression.
Natural Agents Targeting Mitochondria in Cancer
Authors: Mani Shalini , Swargiary Geeta , Singh Keshav K.
Published: September 2020

Mitochondria are the key energy provider to highly proliferating cancer cells, and are subsequently considered one of the critical targets in cancer therapeutics. Several compounds have been studied for their mitochondria-targeting ability in cancer cells. These studies’ outcomes have led to the invention of “mitocans”, a category of drug known to precisely target the cancer cells’ mitochondria. Based upon their mode of action, mitocans have been divided into eight classes. To date, different synthetic compounds have been suggested to be potential mitocans, but unfortunately, they are observed to exert adverse effects. Many studies have been published justifying the medicinal significance of large numbers of natural agents for their mitochondria-targeting ability and anticancer activities with minimal or no side effects. However, these natural agents have never been critically analyzed for their mitochondria-targeting activity. This review aims to evaluate the various natural agents affecting mitochondria and categorize them in different classes. Henceforth, our study may further support the potential mitocan behavior of various natural agents and highlight their significance in formulating novel potential anticancer therapeutics.
Role of Alternatively Spliced Messenger RNA (mRNA) Isoforms of the Insulin-Like Growth Factor 1 (IGF1) in Selected Human Tumors
Authors: Kasprzak Aldona , Szaflarski Witold
Published: September 2020

Insulin-like growth factor 1 (IGF1) is a key regulator of tissue growth and development that is also implicated in the initiation and progression of various cancers. The human IGF1 gene contains six exons and five long introns, the transcription of which is controlled by two promoters (P1 and P2). Alternate promoter usage, as well as alternative splicing (AS) of IGF1, results in the expression of six various variants (isoforms) of mRNA, i.e., IA, IB, IC, IIA, IIB, and IIC. A mature 70-kDa IGF1 protein is coded only by exons 3 and 4, while exons 5 and 6 are alternatively spliced code for the three C-terminal E peptides: Ea (exon 6), Eb (exon 5), and Ec (fragments of exons 5 and 6). The most abundant of those transcripts is IGF1Ea, followed by IGF1Eb and IGF1Ec (also known as mechano-growth factor, MGF). The presence of different IGF1 transcripts suggests tissue-specific auto- and/or paracrine action, as well as separate regulation of both of these gene promoters. In physiology, the role of different IGF1 mRNA isoforms and pro-peptides is best recognized in skeletal muscle tissue. Their functions include the development and regeneration of muscles, as well as maintenance of proper muscle mass. In turn, in nervous tissue, a neuroprotective function of short peptides, produced as a result of IGF1 expression and characterized by significant blood-brain barrier penetrance, has been described and could be a potential therapeutic target. When it comes to the regulation of carcinogenesis, the potential biological role of different var iants of IGF1 mRNAs and pro-peptides is also intensively studied. This review highlights the role of IGF1 isoform expression (mRNAs, proteins) in physiology and different types of human tumors (e.g., breast cancer, cervical cancer, colorectal cancer, osteosarcoma, prostate and thyroid cancers), as well as mechanisms of IGF1 spliced variants involvement in tumor biology.
Cellular and Molecular Mechanisms of Environmental Pollutants on Hematopoiesis
Authors: Scharf Pablo , Broering Milena Fronza , Oliveira da Rocha Gustavo Henrique , Farsky Sandra Helena Poliselli
Published: September 2020

Hematopoiesis is a complex and intricate process that aims to replenish blood components in a constant fashion. It is orchestrated mostly by hematopoietic progenitor cells (hematopoietic stem cells (HSCs)) that are capable of self-renewal and differentiation. These cells can originate other cell subtypes that are responsible for maintaining vital functions, mediate innate and adaptive immune responses, provide tissues with oxygen, and control coagulation. Hematopoiesis in adults takes place in the bone marrow, which is endowed with an extensive vasculature conferring an intense flow of cells. A myriad of cell subtypes can be found in the bone marrow at different levels of activation, being also under constant action of an extensive amount of diverse chemical mediators and enzymatic systems. Bone marrow platelets, mature erythrocytes and leukocytes are delivered into the bloodstream readily available to meet body demands. Leukocytes circulate and reach different tissues, returning or not returning to the bloodstream. Senescent leukocytes, specially granulocytes, return to the bone marrow to be phagocytized by macrophages, restarting granulopoiesis. The constant high production and delivery of cells into the bloodstream, alongside the fact that blood cells can also circulate between tissues, makes the hematopoietic system a prime target for toxic agents to act upon, making the understanding of the bone marrow microenvironment vital for both toxicological sciences and risk assessment. Environmental and occupational pollutants, therapeutic molecules, drugs of abuse, and even nutritional status can directly affect progenitor cells at their differentiation and maturation stages, altering behavior and function of blood compounds and resulting in impaired immune responses, anemias, leukemias, and blood coagulation disturbances. This review aims to describe the most recently investigated molecular and cellular toxicity mechanisms of current major environmental pollutants on hematopoiesis in the bone marrow.
Synapse and Receptor Alterations in Two Different S100B-Induced Glaucoma-Like Models
Authors: Benning Lara , Reinehr Sabrina , Grotegut Pia , Kuehn Sandra , Stute Gesa , Dick H. Burkhard , Joachim Stephanie C.
Published: September 2020

Glaucoma is identified by an irreversible retinal ganglion cell (RGC) loss and optic nerve damage. Over the past few years, the immune system gained importance in its genesis. In a glaucoma-like animal model with intraocular S100B injection, RGC death occurs at 14 days. In an experimental autoimmune glaucoma model with systemic S100B immunization, a loss of RGCs is accompanied by a decreased synaptic signal at 28 days. Here, we aimed to study synaptic alterations in these two models. In one group, rats received a systemic S100B immunization (n = 7/group), while in the other group, S100B was injected intraocularly (n = 6–7/group). Both groups were compared to appropriate controls and investigated after 14 days. While inhibitory post-synapses remained unchanged in both models, excitatory post-synapses degenerated in animals with intraocular S100B injection (p = 0.03). Excitatory pre-synapses tendentially increased in animals with systemic S100B immunization (p = 0.08) and significantly decreased in intraocular ones (p = 0.04). Significantly more N-methyl-d-aspartate (NMDA) receptors (both p ≤ 0.04) as well as gamma-aminobutyric acid (GABA) receptors (both p < 0.03) were observed in S100B animals in both models. We assume that an upregulation of these receptors causes the interacting synapse types to degenerate. Heightened levels of excitatory pre-synapses could be explained by remodeling followed by degeneration.
Development of a Rat Model for Glioma-Related Epilepsy
Authors: Bouckaert Charlotte , Germonpré Charlotte , Verhoeven Jeroen , Chong Seon-Ah , Jacquin Lucas , Mairet-Coello Georges , André Véronique Marie , Leclercq Karine , Vanhove Christian , De Vos Filip , Van den Broecke Caroline , Goethals Ingeborg , Descamps Benedicte , Donche Sam , Carrette Evelien , Wadman Wytse , Boon Paul , Vonck Kristl , Raedt Robrecht
Published: September 2020

Seizures are common in patients with high-grade gliomas (30–60%) and approximately 15–30% of glioblastoma (GB) patients develop drug-resistant epilepsy. Reliable animal models are needed to develop adequate treatments for glioma-related epilepsy. Therefore, fifteen rats were inoculated with F98 GB cells (GB group) and four rats with vehicle only (control group) in the right entorhinal cortex. MRI was performed to visualize tumor presence. A subset of seven GB and two control rats were implanted with recording electrodes to determine the occurrence of epileptic seizures with video-EEG recording over multiple days. In a subset of rats, tumor size and expression of tumor markers were investigated with histology or mRNA in situ hybridization. Tumors were visible on MRI six days post-inoculation. Time-dependent changes in tumor morphology and size were visible on MRI. Epileptic seizures were detected in all GB rats monitored with video-EEG. Twenty-one days after inoculation, rats were euthanized based on signs of discomfort and pain. This study describes, for the first time, reproducible tumor growth and spontaneous seizures upon inoculation of F98 cells in the rat entorhinal cortex. The development of this new model of GB-related epilepsy may be valuable to design new therapies against tumor growth and associated epileptic seizures.
Sauchinone Protects Renal Mesangial Cell Dysfunction against Angiotensin II by Improving Renal Fibrosis and Inflammation
Authors: Yoon Jung Joo , Lee Hyeon Kyoung , Kim Hye Yoom , Han Byung Hyuk , Lee Ho Sub , Lee Yun Jung , Kang Dae Gill
Published: September 2020

Abnormal and excessive growth of mesangial cells is important in the pathophysiologic processes of diabetes-associated interstitial fibrosis and glomerulosclerosis, leading to diabetic nephropathy, which eventually turns into end-stage renal disease. Sauchinone, a biologically-active lignan isolated from aerial parts of Saururus chinensis, has anti-inflammatory and anti-viral activities effects on various cell types. However, there are no studies reporting the effects of sauchinone on diabetic nephropathy. The present study aims to investigate the role of sauchinone in mesangial cell proliferation and fibrosis induced by angiotensin II, as well as the underlying mechanisms of these processes. Human renal mesangial cells were induced by angiotensin II (AngII, 10 μM) in the presence or absence of sauchinone (0.1–1 μM) and incubated for 48 h. In this study, we found that AngII induced mesangial cell proliferation, while treatment with sauchinone inhibited the cell proliferation in a dose-dependent manner. Pre-treatment with sauchinone induced down-regulation of cyclins/CDKs and up-regulation of CDK inhibitor, p21, and p27kip1 expression. In addition, AngII-enhanced expression of fibrosis biomarkers such as fibronectin, collagen IV, and connective tissue growth factor (CTGF), which was markedly attenuated by sauchinone. Sauchinone also decreased AngII-induced TGF-β1 and Smad-2, Smad-3, and Smad-4 expression. This study further revealed that sauchinone ameliorated AngII-induced mesangial inflammation through disturbing activation of inflammatory factors, and NLRP3 inflammasome, which is composed of the NLRP3 protein, procaspase-1, and apoptosis-associated speck-like protein containing a CARD (ASC). Moreover, pretreatment of sauchinone inhibited NF-κB translocation and ROS production in AngII-exposed mesangial cells. These data suggest that sauchinone has a protective effect on renal proliferation, fibrosis and inflammation. Therefore, sauchinone might be a potential pharmacological agent in prevention of AngII-induced renal damage leading to diabetic nephropathy.
Immunomodulatory Role of Microbial Surfactants, with Special Emphasis on Fish
Authors: Giri Sib Sankar , Kim Hyoun Joong , Kim Sang Guen , Kim Sang Wha , Kwon Jun , Lee Sung Bin , Park Se Chang
Published: September 2020

Microbial surfactants (biosurfactants) are a broad category of surface-active biomolecules with multifunctional properties. They self-assemble in aqueous solutions and are adsorbed on various interfaces, causing a decrease in surface tension, as well as interfacial tension, solubilization of hydrophobic compounds, and low critical micellization concentrations. Microbial biosurfactants have been investigated and applied in several fields, including bioremediation, biodegradation, food industry, and cosmetics. Biosurfactants also exhibit anti-microbial, anti-biofilm, anti-cancer, anti-inflammatory, wound healing, and immunomodulatory activities. Recently, it has been reported that biosurfactants can increase the immune responses and disease resistance of fish. Among various microbial surfactants, lipopeptides, glycolipids, and phospholipids are predominantly investigated. This review presents the various immunological activities of biosurfactants, mainly glycolipids and lipopeptides. The applications of biosurfactants in aquaculture, as well as their immunomodulatory activities, that make them novel therapeutic candidates have been also discussed in this review.
Functional Characterization of a Dendrobium officinale Geraniol Synthase DoGES1 Involved in Floral Scent Formation
Authors: Zhao Conghui , Yu Zhenming , Silva Jaime A. Teixeira da , He Chunmei , Wang Haobin , Si Can , Zhang Mingze , Zeng Danqi , Duan Jun
Published: September 2020

Floral scent is a key ornamental trait that determines the quality and commercial value of orchids. Geraniol, an important volatile monoterpene in orchids that attracts pollinators, is also involved in responses to stresses but the geraniol synthase (GES) responsible for its synthesis in the medicinal orchid Dendrobium officinale has not yet been identified. In this study, three potential geraniol synthases were mined from the D. officinale genome. DoGES1, which was localized in chloroplasts, was characterized as a geraniol synthase. DoGES1 was highly expressed in flowers, especially in petals. DoGES1 transcript levels were high in the budding stage of D. officinale flowers at 11:00 a.m. DoGES1 catalyzed geraniol in vitro, and transient expression of DoGES1 in Nicotiana benthamiana leaves resulted in the accumulation of geraniol in vivo. These findings on DoGES1 advance our understanding of geraniol biosynthesis in orchids, and lay the basis for genetic modification of floral scent in D. officinale or in other ornamental orchids.
Expression of a Large Single-Chain 13F6 Antibody with Binding Activity against Ebola Virus-Like Particles in a Plant System
Authors: Lim Sohee , Kim Do-Sun , Ko Kisung
Published: September 2020

Pathogenic animal and human viruses present a growing and persistent threat to humans worldwide. Ebola virus (EBOV) causes zoonosis in humans. Here, two structurally different anti-Ebola 13F6 antibodies, recognizing the heavily glycosylated mucin-like domain (MLD) of the glycoprotein (GP), were expressed in transgenic Nicotiana tabacum plants and designed as inexpensive and effective diagnostic antibodies against Ebola virus disease (EVD). The first was anti-EBOV 13F6 full size antibody with heavy chain (HC) and light chain (LC) (monoclonal antibody, mAb 13F6-FULL), while the second was a large single-chain (LSC) antibody (mAb 13F6-LSC). mAb 13F6-LSC was constructed by linking the 13F6 LC variable region (VL) with the HC of mAb 13F6-FULL using a peptide linker and extended to the C-terminus using the endoplasmic reticulum (ER) retention motif KDEL. Agrobacterium-mediated plant transformation was employed to express the antibodies in N. tabacum. PCR, RT-PCR, and immunoblot analyses confirmed the gene insertion, transcription, and protein expression of these antibodies, respectively. The antibodies tagged with the KDEL motif displayed high-mannose type N-glycan structures and efficient binding to EBOV-like particles (VLPs). Thus, various forms of anti-EBOV plant-derived mAbs 13F6-FULL and LSC with efficient binding affinity to EBOV VLP can be produced in the plant system.
A Review of Starch Biosynthesis in Relation to the Building Block-Backbone Model
Authors: Tetlow Ian J. , Bertoft Eric
Published: September 2020

Starch is a water-insoluble polymer of glucose synthesized as discrete granules inside the stroma of plastids in plant cells. Starch reserves provide a source of carbohydrate for immediate growth and development, and act as long term carbon stores in endosperms and seed tissues for growth of the next generation, making starch of huge agricultural importance. The starch granule has a highly complex hierarchical structure arising from the combined actions of a large array of enzymes as well as physicochemical self-assembly mechanisms. Understanding the precise nature of granule architecture, and how both biological and abiotic factors determine this structure is of both fundamental and practical importance. This review outlines current knowledge of granule architecture and the starch biosynthesis pathway in relation to the building block-backbone model of starch structure. We highlight the gaps in our knowledge in relation to our understanding of the structure and synthesis of starch, and argue that the building block-backbone model takes accurate account of both structural and biochemical data.