bluuebunny/crossref_metadata_2025 huggingface dataset:
The Institutional Sources of Economic Transformation: Energy Policy from the Oil Crises to Climate Change
Authors: Finnegan Jared , Lipscy Phillip , Meckling Jonas , Metz Florence
Published: March 2021

Why are some governments more effective in promoting economic change than others? We develop a theory of the institutional sources of economic transformation. Domestic institutions condition the ability of policymakers to impose costs on consumers and producers. We argue that institutions can enable transformation through two central mechanisms: insulation and compensation. The institutional sources of transformation vary across policy types—whether policies impose costs primarily on consumers (demand-side policies) or on producers (supply-side policies). Proportional electoral rules and strong welfare states facilitate demand-side policies, whereas autonomous bureaucracies and corporatist interest intermediation facilitate supply-side policies. We test our theory by leveraging the 1973 oil crisis, an exogenous shock that compelled policymakers to simultaneously pursue transformational change across OECD countries. Panel analysis, case studies, and discourse network analysis support our hypotheses. The findings offer important lessons for contemporary climate change policy and low-carbon transitions.
Intentionality and Players of Effective Online Courses in Mathematics
Authors: Raza Salman Hussain , Reddy Emmenual
Published: March 2021

Mathematics is the engine, vehicle, driver, and language of today’s initiatives, innovations, and human endeavors. In this mathematical-driven world, the ability to perform mathematical tasks and logical reasoning is also essential in solving quotidian tasks and problems. Therefore, mathematical competency and problem-solving skills are kept as an integral component in almost every educational curriculum around the globe. However, there are numerous stumbling blocks along the way to successful teaching, conducive learning environment, and good student performances in almost all disciplines, but more prevalent and visible in mathematics. The major concerns of educators responsible for teaching mathematics and mathematics-related courses are to find effective and innovative ways to deliver mathematical content, to extend the concepts and theories beyond the classrooms, to integrate mathematics with important concepts such as gamification, data mining, learning analytics, deep learning, and effective tools such as mobile devices, learning management systems, and digital technology, and to maintain a good record of students’ performance. In online deliveries, these concerns are further escalated due to no or limited one-to-one interactions and lack of face time, to mention a few. This article investigates the efficacy and effectiveness of traditional and innovative pedagogical practices used in online mathematic courses at the University of the South Pacific (USP). It examines the interdependence of embedded activities and students’ achievement. The results indicate that these online mathematics courses were highly dominated by conventional approaches and were less interactive and engaging, resulting in lower success rates when compared to the courses from other disciplines. To recommend possible ways to enhance the quality of learning and teaching in online mathematics courses, selected online courses from the information system discipline were explored. The reasons for the high online presence in the course were investigated and activities that could lead to collaborative and active learning beyond the passive materials were data mined. The evidence drawn from the statistical analysis highlights the importance of including selected interactive and engaging activities in online learning space of mathematics courses to promote student engagement and help create a sense of community among geographically dispersed students. Overall, based on the observations and theoretical foundation from literature, it can be said that including regular and frequent active assessment strategies, such as weekly quizzes and discussion forums, could extend and promote interactive and engaging learning in online learning space.
Production of Biopolyamide Precursors 5-Amino Valeric Acid and Putrescine From Rice Straw Hydrolysate by Engineered Corynebacterium glutamicum
Authors: Sasikumar Keerthi , Hannibal Silvin , Wendisch Volker F. , Nampoothiri K. Madhavan
Published: March 2021

The non-proteinogenic amino acid 5-amino valeric acid (5-AVA) and the diamine putrescine are potential building blocks in the bio-polyamide industry. The production of 5-AVA and putrescine using engineered Corynebacterium glutamicum by the co-consumption of biomass-derived sugars is an attractive strategy and an alternative to their petrochemical synthesis. In our previous work, 5-AVA production from pure xylose by C. glutamicum was shown by heterologously expressing xylA from Xanthomonas campestris and xylB from C. glutamicum. Apart from this AVA Xyl culture, the heterologous expression of xylAXc and xylBCg was also carried out in a putrescine producing C. glutamicum to engineer a PUT Xyl strain. Even though, the pure glucose (40 g L–1) gave the maximum product yield by both the strains, the utilization of varying combinations of pure xylose and glucose by AVA Xyl and PUT Xyl in CGXII synthetic medium was initially validated. A blend of 25 g L–1 of glucose and 15 g L–1 of xylose in CGXII medium yielded 109 ± 2 mg L–1 putrescine and 874 ± 1 mg L–1 5-AVA after 72 h of fermentation. Subsequently, to demonstrate the utilization of biomass-derived sugars, the alkali (NaOH) pretreated-enzyme hydrolyzed rice straw containing a mixture of glucose (23.7 g L–1) and xylose (13.6 g L–1) was fermented by PUT Xyl and AVA Xyl to yield 91 ± 3 mg L–1 putrescine and 260 ± 2 mg L–1 5-AVA, respectively, after 72 h of fermentation. To the best of our knowledge, this is the first proof of concept report on the production of 5-AVA and putrescine using rice straw hydrolysate (RSH) as the raw material.
Comparison Between a Standard and SalivaDirect RNA Extraction Protocol for Molecular Diagnosis of SARS-CoV-2 Using Nasopharyngeal Swab and Saliva Clinical Samples
Authors: Rodríguez Flores Sofía N. , Rodríguez-Martínez Luis Mario , Reyes-Berrones Bernardita L. , Fernández-Santos Nadia A. , Sierra-Moncada Elthon J. , Rodríguez-Pérez Mario A.
Published: March 2021

During the COVID-19 pandemic, a certified laboratory of Tamaulipas, Mexico has processed over 100,000 samples of COVID-19 suspected patients, working a minimum of 100 tests daily. Thus, it would be beneficial for such certified laboratories nationwide to reduce the time and cost involved in performing the diagnosis of COVID-19, from sample collection, transportation to local lab, processing of samples, and data acquisition. Here, 30 nasopharyngeal swab and saliva samples from the same COVID-19 individuals were assessed by a standard nucleic acid extraction protocol, including protein lysis with proteinase K followed by binding to column, washing, and elution, and by the SalivaDirect protocol based on protein lysis, skipping the other steps to reduce processing time and costs. The genomic RNA was amplified using a SARS-CoV-2 Real-Time PCR kit. A variation (P > 0.05) in the 95% CIs = 72.6%–96.7% was noted by using the SalivaDirect protocol and saliva samples (sensitivity of 88.2%) in comparison to those of standard protocol with oropharyngeal swab samples (95% CIs = 97.5%–100%; sensitivity of 100%) as reported elsewhere. However, when using nasopharyngeal swab samples in the SalivaDirect protocol (sensitivity of 93.6%; 95% CIs = 79.2%–99.2%), it was in concordance (P < 0.05) with those of the standard one. The logical explanation to this was that two samples with Ct values of 38, and 40 cycles for gene E produced two false negatives in the SalivaDirect protocol in relation to the standard one; thus, there was a reduction of the sensitivity of 6.4% in the overall assay performance.
Deficiency of Ku Induces Host Cell Exploitation in Human Cancer Cells
Authors: Saydam Okay , Saydam Nurten
Published: March 2021

Cancer metastasis is the major cause of death from cancer (Massague and Obenauf, 2016; Steeg, 2016). The extensive genetic heterogeneity and cellular plasticity of metastatic tumors set a prime barrier for the current cancer treatment protocols (Boumahdi and de Sauvage, 2020). In addition, acquired therapy resistance has become an insurmountable obstacle that abolishes the beneficial effects of numerous anti-cancer regimens (De Angelis et al., 2019; Boumahdi and de Sauvage, 2020). Here we report that deficiency of Ku leads to the exploitation of host cells in human cancer cell line models. We found that, upon conditional deletion of XRCC6 that codes for Ku70, HCT116 human colorectal cancer cells gain a parasitic lifestyle that is characterized by the continuous cycle of host cell exploitation. We also found that DAOY cells, a human medulloblastoma cell line, innately lack nuclear Ku70/Ku86 proteins and utilize the host-cell invasion/exit mechanism for maintenance of their survival, similarly to the Ku70 conditionally-null HCT116 cells. Our study demonstrates that a functional loss of Ku protein promotes an adaptive, opportunistic switch to a parasitic lifestyle in human cancer cells, providing evidence for a previously unknown mechanism of cell survival in response to severe genomic stress. We anticipate that our study will bring a new perspective for understanding the mechanisms of cancer cell evolution, leading to a shift in the current concepts of cancer therapy protocols directed to the prevention of cancer metastasis and therapy resistance.
Antiviral Essential Oil Components Against SARS-CoV-2 in Pre-procedural Mouth Rinses for Dental Settings During COVID-19: A Computational Study
Authors: Yadalam Pradeep Kumar , Varatharajan Kalaivani , Rajapandian K. , Chopra Priyanka , Arumuganainar Deepavalli , Nagarathnam Thilgavathi , Sohn Honglae , Madhavan Thirumurthy
Published: March 2021

COVID-19 mainly spreads through cough or sneeze droplets produced by an infected person. The viral particles are mostly present in the oral cavity. The risk of contracting COVID-19 is high in the dental profession due to the nature of procedures involved that produce aerosols. Along with other measures to limit the risk of infection, pre-procedural mouth rinses are beneficial in reducing the viral particles in the oral cavity. In this study, the antiviral efficacy of essential oil components has been determined specifically against SARS-CoV-2 by molecular docking and conceptual DFT approach. Based on the binding affinities of the components against the receptor binding domain of the S1 glycoprotein, cuminal, carvacrol, myrtanol, and pinocarveol were found to be highly active. The molecular descriptor values obtained through conceptual DFT also indicated the above-mentioned components to be active based on the correlation between the structure and the activity of the compounds. Therefore, pre-procedural mouth rinses with these components included may be specifically suitable for dental procedures during the COVID-19 period.
The Active Subunit of the Cytolethal Distending Toxin, CdtB, Derived From Both Haemophilus ducreyi and Campylobacter jejuni Exhibits Potent Phosphatidylinositol-3,4,5-Triphosphate Phosphatase Activity
Authors: Huang Grace , Boesze-Battaglia Kathleen , Walker Lisa P. , Zekavat Ali , Schaefer Zachary P. , Blanke Steven R. , Shenker Bruce J.
Published: March 2021

Human lymphocytes exposed toAggregatibacter actinomycetemcomitans(Aa) cytolethal distending toxin (Cdt) undergo cell cycle arrest and apoptosis. In previous studies, we demonstrated that the active Cdt subunit, CdtB, is a potent phosphatidylinositol (PI) 3,4,5-triphosphate phosphatase. Moreover, AaCdt-treated cells exhibit evidence of PI-3-kinase (PI-3K) signaling blockade characterized by reduced levels of PIP3, pAkt, and pGSK3β. We have also demonstrated that PI-3K blockade is a requisite of AaCdt-induced toxicity in lymphocytes. In this study, we extended our observations to include assessment of Cdts fromHaemophilus ducreyi(HdCdt) andCampylobacter jejuni(CjCdt). We now report that the CdtB subunit from HdCdt and CjCdt, similar to that of AaCdt, exhibit potent PIP3 phosphatase activity and that Jurkat cells treated with these Cdts exhibit PI-3K signaling blockade: reduced levels of pAkt and pGSK3β. Since non-phosphorylated GSK3β is the active form of this kinase, we compared Cdts for dependence on GSK3β activity. Two GSK3β inhibitors were employed, LY2090314 and CHIR99021; both inhibitors blocked the ability of Cdts to induce cell cycle arrest. We have previously demonstrated that AaCdt induces increases in the CDK inhibitor, p21CIP1/WAF1, and, further, that this was a requisite for toxin-induced cell deathviaapoptosis. We now demonstrate that HdCdt and CjCdt also share this requirement. It is also noteworthy that p21CIP1/WAF1was not involved in the ability of the three Cdts to induce cell cycle arrest. Finally, we demonstrate that, like AaCdt, HdCdt is dependent upon the host cell protein, cellugyrin, for its toxicity (and presumably internalization of CdtB); CjCdt was not dependent upon this protein. The implications of these findings as they relate to Cdt’s molecular mode of action are discussed.
Correlation and Causation Analysis Between COVID-19 and Environmental Factors in China
Authors: Zheng Zuofang , Dou Junxia , Cheng Conglan , Gao Hua
Published: March 2021

Coronavirus disease 2019 (COVID-19) is seriously threatening and altering human society. Although prevention and control measures play an important role in preventing the transmission of severe acute respiratory syndrome coronavirus, signals of climate impact can still be detected globally. In this paper, the data of 265 cities in China were analyzed. The results show that the correlations between COVID-19 and air quality index (AQI) and PM2.5 concentration were very weak and that the correlations between COVID-19 and meteorological factors were significantly different in different climate backgrounds. So, a fixed model is not enough to describe the correlations. Overall, high humidity, low wind speed, and relatively lower air temperature are conducive to the spread of COVID-19. The climate background suitable for the spread of COVID-19 in China is air temperature 0~15°C, specific humidity <3 g kg−1, and wind speed <3 m s−1. The Granger causality test shows that there is a causal relationship between daily average air temperature and the number of COVID-19 confirmed cases in some cities of China, and air temperature is indicative of the number of confirmed cases the next day. However, this phenomenon is not universal due to regional climate differences.
Influencing Followership: Understanding the Perspective of Those Leading Active Discussions on Quora
Authors: Nwadiugwu Martin C. , Nwadiugwu Cynthia C.
Published: March 2021

As social media influence become increasingly popular, understanding why some posts are highly followed than others, especially from the perspective of those leading the discussion allows us to gain insight on how followership is being influenced. A qualitative study of eight participants leading active discussions on Quora was conducted using semi-structured in-depth interviews, followed by thematic analysis. The open coding method was used to iteratively code related answers to develop themes. Results suggest that copyright tactics, controversial answers and sharing new information are some of the mechanisms for influencing followership. These mechanisms are built overtime through conscious strong engagement and by writing a consistently well-thought-out answer. The motivation for leading and writing answers on Quora were more intrinsic than extrinsic, and most participants believed influencing followership should not be a concern if one has the right message.
Stroke in SARS-CoV-2 Infection: A Pictorial Overview of the Pathoetiology
Authors: Aghayari Sheikh Neshin Saeideh , Shahjouei Shima , Koza Eric , Friedenberg Isabel , Khodadadi Faezeh , Sabra Mirna , Kobeissy Firas , Ansari Saeed , Tsivgoulis Georgios , Li Jiang , Abedi Vida , Wolk Donna M. , Zand Ramin
Published: March 2021

Since the early days of the pandemic, there have been several reports of cerebrovascular complications during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Numerous studies proposed a role for SARS-CoV-2 in igniting stroke. In this review, we focused on the pathoetiology of stroke among the infected patients. We pictured the results of the SARS-CoV-2 invasion to the central nervous system (CNS) via neuronal and hematogenous routes, in addition to viral infection in peripheral tissues with extensive crosstalk with the CNS. SARS-CoV-2 infection results in pro-inflammatory cytokine and chemokine release and activation of the immune system, COVID-19-associated coagulopathy, endotheliitis and vasculitis, hypoxia, imbalance in the renin-angiotensin system, and cardiovascular complications that all may lead to the incidence of stroke. Critically ill patients, those with pre-existing comorbidities and patients taking certain medications, such as drugs with elevated risk for arrhythmia or thrombophilia, are more susceptible to a stroke after SARS-CoV-2 infection. By providing a pictorial narrative review, we illustrated these associations in detail to broaden the scope of our understanding of stroke in SARS-CoV-2-infected patients. We also discussed the role of antiplatelets and anticoagulants for stroke prevention and the need for a personalized approach among patients with SARS-CoV-2 infection.
Structural Significance of the Mid-level Décollement Within the Western Sichuan Fold-And-Thrust Belt (WSFTB), Insights From Sandbox Modeling
Authors: Sun Chuang , Li Zhigang , Wu Shimin , He Zhiyuan , Zhao Shaotian , Wang Panfei
Published: March 2021

The WSFTB is located outboard of the eastern Tibetan Plateau, western China. It has received great attention due to high earthquake risks and rich resources of oil and gas. For both issues, the detailed structural configuration and deformation mechanism behind it are of great importance, but remain unclear due to the complexity created by the presence of multiple décollements. The effect of regionally distributed shallow Triassic salt décollement (SD) and the basal one (BD) has been well understood. In this paper, we focus on the third décollement situated between them. We conducted three sandbox experiments by varying this mid-level décollement (MD) from absence to presence, and from frictional to viscous, to test the effect on diversity of regional structural configuration. Our experimental results illustrated that 1) Absence of MD facilitated decoupling on SD, forming the greatest contrast between subsurface deformation front and the blind one beneath SD; 2) Frictional MD itself showed little decoupling, while its weakness reduced the bulk strength of deep structural level, lowering decoupling effect on SD and leading to approximating deformation fronts in the shallow and deep; 3) The viscous MD, along with SD relieved the resistance on their interbed layer. Consequently, the fastest deformation propagation rate and farthest deformation front (in all the experiments) occurred in the middle structural level. The modeled fold and thrust structures are comparable with the southern, central and northern WSFTB respectively, suggesting that varied MD may control the along-strike structural variations presented. The results also indicate that MD can alter the deformation partition in depth of any other multiple décollement system.
Seismic Attenuation Tomography From 2018 Lombok Earthquakes, Indonesia
Authors: Priyono Awali , Nugraha Andri Dian , Muzli Muzli , Ardianto Ardianto , Aulia Atin Nur , Prabowo Billy Sugiartono , Zulfakriza Zulfakriza , Rosalia Shindy , Sasmi Annisa T. , Afif Haunan , Sahara David P. , Widiyantoro Sri , Wei Shengji , Husni Yayan M. , Sarjan Achmad Fajar Narotama
Published: March 2021

Local earthquake data was used to determine a three-dimensional (3D) seismic attenuation structure around the aftershock source region of the 2018 Lombok earthquake in Indonesia. The aftershocks were recorded by 13 seismic stations from August 4 to September 9, 2018. The selected data consist of 6,281 P-wave t∗ values from 914 events, which had good t∗ quality in at least four stations. Our results show that the two aftershock clusters northwest and northeast of Lombok Island have different attenuation characteristics. A low P-wave quality factor (low-Qp), low P-wave velocity (Vp), and high ratio of P-wave velocity and S-wave velocity (Vp/Vs), which coincide with a shallower earthquake (<20 km) northwest of Lombok Island, might be associated with a brittle area of basal and imbricated faults influenced by high fluid content. At the same time, the high-Qp, low Vp, and low Vp/Vs, which coincide with a deeper earthquake (>20 km) northeast of Lombok Island, might be associated with an area that lacks fluid content. The difference in fluid content between the northwest and northeast regions might be the cause of the early generation of aftershocks in the northwest area. The significant earthquake that happened on August 5, 2018, took place in a region with moderate Qp, close to the contrast of high and low-Qp and high Vp, which suggests that the earthquake started in a strong material before triggering the shallower aftershocks occurring in an area affected by fluid content. We also identified an old intrusive body on the northeast flank of the Rinjani volcano, which was characterized by a high-Qp, high-velocity, and a high Bouguer anomaly.
Downstream Evolution of Particulate Organic Matter Composition From Permafrost Thaw Slumps
Authors: Keskitalo Kirsi H. , Bröder Lisa , Shakil Sarah , Zolkos Scott , Tank Suzanne E. , van Dongen Bart E. , Tesi Tommaso , Haghipour Negar , Eglinton Timothy I. , Kokelj Steven V. , Vonk Jorien E.
Published: March 2021

Permafrost soils, which store almost half of the global belowground organic carbon (OC), are susceptible to thaw upon climate warming. On the Peel Plateau of northwestern Canada, the number and size of retrogressive thaw slumps (RTS) has increased in recent decades due to rising temperatures and higher precipitation. These RTS features caused by the rapid thaw of ice-rich permafrost release organic matter dominantly as particulate organic carbon (POC) to the stream network. In this study, we sampled POC and streambank sediments along a fluvial transect (∼12 km) downstream from two RTS features and assessed the composition and degradation status of the mobilized permafrost OC. We found that RTS features add old, Pleistocene-aged permafrost POC to the stream system that is traceable kilometers downstream. The POC released consists mainly of recalcitrant compounds that persists within stream networks, whereas labile compounds originate from the active layer and appear to largely degrade within the scar zone of the RTS feature. Thermokarst on the Peel Plateau is likely to intensify in the future, but our data suggest that most of the permafrost OC released is not readily degradable within the stream system and thus may have little potential for atmospheric evasion. Possibilities for the recalcitrant OC to degrade over decadal to millennial time scales while being transported via larger river networks, and within the marine environment, do however, still exist. These findings add to our understanding of the vulnerable Arctic landscapes and how they may interact with the global climate.
The Paleoclimate Significance of the δ13C Composition of Individual Hydrocarbon Compounds in the Maoming Oil Shales, China
Authors: Cao Xinxing , Song Zhiguang , Wang Sibo , Lyu Puliang
Published: March 2021

Maoming oil shales are typical low-altitude lacustrine sediments that were deposited during the late Paleogene. The hydrocarbon composition and compound-specific stable carbon isotopic composition (δ13C) of organic matter in the profile samples of the oil shales have been analyzed. The results show that algae and aquatic plants are major parent sources of the organic matter in the oil shales associated with a small portion of terrestrial higher plant input. The δ13C composition of the bulk organic matter and the n-alkanes varies greatly on the profile from −26.9 to −15.8‰ and −31.7 to −16.2‰, respectively. While a good positive correlation among the δ13C composition of individual n-alkanes implies that these n-alkanes were originated from the similar source input. The δ13C composition of n-alkanes on the profile displays a positive excursion trend from the bottom to the top, and this excursion was likely related to the general decreasing trend of the partial pressure of atmospheric CO2 (pCO2) during the late Paleogene. The δ13C composition of the C30-4-methyl steranes ranges from −11.9 to −6.3‰, which is suggestive of Dinoflagellates-related source input. Coincidently, the high abundance C33-botryococcanes were detected in the samples on the top section of the profile and display an extremely positive carbon isotopic composition of −4.5 to −8.4‰, suggesting that the lower partial pressure of atmospheric CO2 had triggered a bicarbonate consumption mechanism for Botryococcus braunii B. Therefore, the δ13C composition of n-alkanes and C33-botryococcanes and their profile variation suggest that a general declining process associated with fluctuation in the partial pressure of atmospheric CO2 is likely the major reason for the rapid climatic changes toward the end of the late Paleogene.
Preparing Teacher Training Students for Evidence-Based Practice Promoting Students’ Research Competencies in Research-Learning Projects
Authors: Böttcher-Oschmann Franziska , Groß Ophoff Jana , Thiel Felicitas
Published: March 2021

Research-learning projects (RLP) enable teacher training students to acquire competencies for evidence-based practice (EBP) in the context of their university studies. The aim of this longitudinal study is to develop, implement, and evaluate a RLP format to promote competencies for EBP in teacher training students. These competencies can be broken down into the categories of using research, which involves reflection on and use of evidence to solve problems in teaching practice, and establishing research, which involves investigating a research question independently by applying research methods. In a longitudinal study we evaluate the increase in competencies based on a self-assessment of competencies (indirect measurement) focusing on establishing research, and a competence test (direct measurement) focusing on using research. We also add a retrospective pre-assessment version (quasi-indirect measurement) to consider response shift and over- or underestimation in self-assessments. Our findings show that teacher training students can be prepared for EBP through RLP. Further development potential for the RLP format is being discussed.
Premenopausal Women With a Diagnosis of Endometriosis Have a Significantly Higher Prevalence of a Diagnosis or Symptoms Suggestive of Restless Leg Syndrome: A Prospective Cross-Sectional Questionnaire Study
Authors: Tempest Nicola , Boyers Madeleine , Carter Alice , Lane Steven , Hapangama Dharani K.
Published: March 2021

Background

Endometriosis and restless leg syndrome (RLS) are both chronic conditions that can negatively affect a woman’s quality of life. A higher prevalence of RLS is seen in women and particularly in those who are pregnant, suggesting a possible ovarian hormonal influence. Endometriosis is a common (affecting 1 in 10 women) estrogen driven gynecological condition, and the prevalence of RLS in women with symptoms or a diagnosis of endometriosis is unknown.

Methods

A prospective, cross-sectional, observational self-completed questionnaire study was distributed to 650 pre-menopausal women attending the gynecological department at Liverpool Women`s Hospital over a period of 4 months. 584 questionnaires were returned and 465 completed questionnaires were included in the final dataset. Data on RLS-associated (The International Restless Leg Syndrome Study Group rating scale) and endometriosis-associated (modified-British Society of Gynaecological Endoscopists pelvic pain questionnaire) symptoms were collected.

Results

Women who reported a prior surgical diagnosis of endometriosis had a greater risk of having a prior formal diagnosis of RLS (OR 4.82, 95% CI 1.66,14.02) and suffering RLS symptoms (OR 2.13, 95% CI 1.34-3.39) compared with those without a diagnosis. When women with either a formal surgical diagnosis or symptoms associated with endometriosis were grouped together, they also have a significantly increased risk of having either a formal diagnosis or symptoms suggestive of RLS (OR 2.49, 95% CI 1.30, 3.64). In women suffering with endometriosis-associated symptoms, the cumulative endometriosis-associated symptom scores demonstrated a modest positive correlation with RLS severity scores (r=0.42 95% CI 0.25 to 0.57).

Conclusions

This is the first study highlighting an association between the symptoms relevant to the two chronic conditions RLS and endometriosis, showing that women with a reported prior surgical diagnosis or symptoms suggestive of endometriosis have a significantly higher prevalence of a prior formal diagnosis or symptoms suggestive of RLS. This data will help in facilitating the discovery of novel therapeutic targets relevant to both conditions. The simultaneous treatment of these conditions could potentially lead to improvement in the overall quality of life for these women.
Combined Approaches to Predict Microplastic Emissions Within an Urbanized Estuary (Warnow, Southwestern Baltic Sea)
Authors: Piehl Sarah , Hauk Rahel , Robbe Esther , Richter Boris , Kachholz Frauke , Schilling Jannik , Lenz Robin , Fischer Dieter , Fischer Franziska , Labrenz Matthias , Schernewski Gerald
Published: March 2021

Microplastic river emissions are known to be one of the major sources for marine microplastic pollution. Especially urbanized estuaries localized at the land-sea interface and subjected to microplastic emissions from various sources exhibit a high microplastic discharge potential to adjacent coasts. To adapt effective measures against microplastic emissions a more detailed knowledge on the importance of various microplastic sources is necessary. As field data is scarce we combined different approaches to assess microplastic emissions into the Warnow estuary, southwestern Baltic Sea. Resulting microplastic emission estimates are based on in-situ measurements for the catchment emissions, whereas for the remaining microplastic sources within the estuary literature data on microplastic abundances, and various parameters were used (e.g. demographical, hydrological, geographical). The evaluation of the different emission scenarios revealed that the majority of microplastic is likely discharged by the Warnow river catchment (49.4%) and the separated city stormwater system (43.1%) into the estuary, followed by combined sewer discharges (6.1%). Wastewater treatment plant emissions exhibit the lowest percentage (1.4%). Our approach to estimate anti-fouling paint particles emissions from leisure and commercial shipping activities was associated with highest uncertainties. However, our results indicate the importance of this source highlighting the necessity for future research on the topic. Based on our assumptions for microplastic retention within the estuary, we estimate a potential annual emission of 152–291 billion microplastics (majority within the size class 10–100 µm) to the Baltic Sea. Considering all uncertainties of the different applied approaches, we could assess the importance of various microplastic sources which can be used by authorities to prioritize and establish emission reduction measures. Additionally, the study provides parameters for microplastic emission estimates that can be transferred from our model system to other urbanized Baltic estuaries.
Declines in Common and Migratory Breeding Landbird Species in South Korea Over the Past Two Decades
Authors: Kim Hankyu , Mo Yongwon , Choi Chang-Yong , McComb Brenda C. , Betts Matthew G.
Published: March 2021

Population declines in terrestrial bird species have been reported across temperate regions in the world and are attributed to habitat loss, climate change, or other direct mortality sources. North American and European studies indicate that long-distance migrants, common species, and species associated with grasslands and agricultural lands are declining at the greatest rates. However, data from East Asia on avian population trends and associated drivers are extremely sparse. We modeled changes in occupancy of 52 common breeding landbird species in South Korea between 1997–2005 and 2013–2019. Thirty-eight percent of the species showed evidence of declines, and seven of these were declining severely (46–95%). Occupancy of Black-capped Kingfisher (Halcyon pileata) populations have dropped the most precipitously over the study period. Among declining species, long-distance migrants (9/20) and common species (14/20) showed more rapid declines than other groups. Declines of five species were associated with climate change, and two species appeared to be affected by land-cover change. However, causes of change in occupancy of other species (46/52) remains cryptic. Based on our results, we suggest an immediate re-evaluation of species’ conservation status and legal protection levels for seven severely declining species in South Korea, and a dedicated survey design and analysis effort for the continued monitoring landbird populations. Because many species exhibiting declines migrate from beyond national boundaries, international collaborations will be required to better quantify population trends across the full annual cycle, and to understand mechanisms for these declines.
The Low Opportunity Costs of the Amazon Soy Moratorium
Authors: Rausch Lisa L. , Gibbs Holly K.
Published: March 2021

Brazil’s Amazon Soy Moratorium (ASM) contributed to overall reductions in Amazon deforestation since its implementation in 2006. Under the ASM, the Amazon soy sector maintains access to the growing share of the market that operates under zero-deforestation commitments. The ASM has been criticized as unfair to law-abiding producers. Only 1% of the approximately 14,000 soy farms in the Amazon Biome have soy-suitable, forested areas that could be deforested lawfully (49,273 ha). More than half of Amazon soy farms have soy-suitable areas that were deforested before 2008 and used for soy in 2019 (1.7 Mha). Taken together, these findings suggest that the opportunity costs of the ASM on current soy farms are low relative to the market access benefits.
EZH2-Mediated microRNA-375 Upregulation Promotes Progression of Breast Cancer via the Inhibition of FOXO1 and the p53 Signaling Pathway
Authors: Guan Xin , Shi Aiping , Zou Yabin , Sun Meiyang , Zhan Yue , Dong Yi , Fan Zhimin
Published: March 2021

Breast cancer (BC) is the most common gynecologic tumor worldwide where aberrant expression of microRNAs (miRNAs) is frequently involved. Here, we evaluated the function of miR-375 on BC development and the molecules implicated. Differentially expressed genes between tumor and paired normal tissues from BC patients were screened out by microarray analyses. miR-375 was abundantly expressed in BC tissues and cells, and it was correlated with the poor prognosis of patients. Downregulation of miR-375 was introduced into BC cell lines MCF-7 and HCC1954, after which the viability, colony formation, migration, and invasion were suppressed, while the apoptosis of cells was increased, and the xenograft tumors in nude mice were reduced as well. EZH2 increased methylation and phosphorylation of signal transducer and activator of transcription 3 (STAT3) and increased transcription activity of miR-375, while miR-375 directly targeted FOXO1. Either overexpression of EZH2 or downregulation of FOXO1 blocked the functions of anti-miR-375 in cells and animals. FOXO1 was found as an activator of the p53 signaling pathway. This study showed that miR-375 is an important oncogene in BC. EZH2 is an upstream regulator of miR-375 through mediating the methylation of STAT3, while FOXO1 is a downstream target mRNA of miR-375 that activates the p53 signaling pathway to suppress BC development.
Integrin Activation Enables Sensitive Detection of Functional CD4+ and CD8+ T Cells: Application to Characterize SARS-CoV-2 Immunity
Authors: Schöllhorn Anna , Schuhmacher Juliane , Besedovsky Luciana , Fendel Rolf , Jensen Anja T. R. , Stevanović Stefan , Lange Tanja , Rammensee Hans-Georg , Born Jan , Gouttefangeas Cécile , Dimitrov Stoyan
Published: March 2021

We have previously shown that conformational change in the β2-integrin is a very early activation marker that can be detected with fluorescent multimers of its ligand intercellular adhesion molecule (ICAM)-1 for rapid assessment of antigen-specific CD8+ T cells. In this study, we describe a modified protocol of this assay for sensitive detection of functional antigen-specific CD4+ T cells using a monoclonal antibody (clone m24 Ab) specific for the open, high-affinity conformation of the β2-integrin. The kinetics of β2-integrin activation was different on CD4+ and CD8+ T cells (several hours vs. few minutes, respectively); however, m24 Ab readily stained both cell types 4–6 h after antigen stimulation. With this protocol, we were able to monitor ex vivo effector and memory CD4+ and CD8+ T cells specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), cytomegalovirus (CMV), Epstein–Barr virus (EBV), and hepatitis B virus (HBV) in whole blood or cryopreserved peripheral blood mononuclear cells (PBMCs) of infected or vaccinated individuals. By costaining β2-integrin with m24 and CD154 Abs, we assessed extremely low frequencies of polyfunctional CD4+ T cell responses. The novel assay used in this study allows very sensitive and simultaneous screening of both CD4+ and CD8+ T cell reactivities, with versatile applicability in clinical and vaccination studies.
Lactic Acid Fermentation Is Required for NLRP3 Inflammasome Activation
Authors: Lin Hsin-Chung , Chen Yu-Jen , Wei Yau-Huei , Lin Hsin-An , Chen Chien-Chou , Liu Tze-Fan , Hsieh Yi-Lin , Huang Kuo-Yang , Lin Kuan-Hung , Wang Hsueh-Hsiao , Chen Lih-Chyang
Published: March 2021

Activation of the Nod-like receptor 3 (NLRP3) inflammasome is important for activation of innate immune responses, but improper and excessive activation can cause inflammatory disease. We previously showed that glycolysis, a metabolic pathway that converts glucose into pyruvate, is essential for NLRP3 inflammasome activation in macrophages. Here, we investigated the role of metabolic pathways downstream glycolysis – lactic acid fermentation and pyruvate oxidation—in activation of the NLRP3 inflammasome. Using pharmacological or genetic approaches, we show that decreasing lactic acid fermentation by inhibiting lactate dehydrogenase reduced caspase-1 activation and IL-1β maturation in response to various NLRP3 inflammasome agonists such as nigericin, ATP, monosodium urate (MSU) crystals, or alum, indicating that lactic acid fermentation is required for NLRP3 inflammasome activation. Inhibition of lactate dehydrogenase with GSK2837808A reduced lactate production and activity of the NLRP3 inflammasome regulator, phosphorylated protein kinase R (PKR), but did not reduce the common trigger of NLRP3 inflammasome, potassium efflux, or reactive oxygen species (ROS) production. By contrast, decreasing the activity of pyruvate oxidation by depletion of either mitochondrial pyruvate carrier 2 (MPC2) or pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) enhanced NLRP3 inflammasome activation, suggesting that inhibition of mitochondrial pyruvate transport enhanced lactic acid fermentation. Moreover, treatment with GSK2837808A reduced MSU-mediated peritonitis in mice, a disease model used for studying the consequences of NLRP3 inflammasome activation. Our results suggest that lactic acid fermentation is important for NLRP3 inflammasome activation, while pyruvate oxidation is not. Thus, reprograming pyruvate metabolism in mitochondria and in the cytoplasm should be considered as a novel strategy for the treatment of NLRP3 inflammasome-associated diseases.
VaximmutorDB: A Web-Based Vaccine Immune Factor Database and Its Application for Understanding Vaccine-Induced Immune Mechanisms
Authors: Berke Kimberly , Sun Peter , Ong Edison , Sanati Nasim , Huffman Anthony , Brunson Timothy , Loney Fred , Ostrow Joseph , Racz Rebecca , Zhao Bin , Xiang Zuoshuang , Masci Anna Maria , Zheng Jie , Wu Guanming , He Yongqun
Published: March 2021

Vaccines stimulate various immune factors critical to protective immune responses. However, a comprehensive picture of vaccine-induced immune factors and pathways have not been systematically collected and analyzed. To address this issue, we developed VaximmutorDB, a web-based database system of vaccine immune factors (abbreviated as “vaximmutors”) manually curated from peer-reviewed articles. VaximmutorDB currently stores 1,740 vaccine immune factors from 13 host species (e.g., human, mouse, and pig). These vaximmutors were induced by 154 vaccines for 46 pathogens. Top 10 vaximmutors include three antibodies (IgG, IgG2a and IgG1), Th1 immune factors (IFN-γ and IL-2), Th2 immune factors (IL-4 and IL-6), TNF-α, CASP-1, and TLR8. Many enriched host processes (e.g., stimulatory C-type lectin receptor signaling pathway, SRP-dependent cotranslational protein targeting to membrane) and cellular components (e.g., extracellular exosome, nucleoplasm) by all the vaximmutors were identified. Using influenza as a model, live attenuated and killed inactivated influenza vaccines stimulate many shared pathways such as signaling of many interleukins (including IL-1, IL-4, IL-6, IL-13, IL-20, and IL-27), interferon signaling, MARK1 activation, and neutrophil degranulation. However, they also present their unique response patterns. While live attenuated influenza vaccine FluMist induced significant signal transduction responses, killed inactivated influenza vaccine Fluarix induced significant metabolism of protein responses. Two different Yellow Fever vaccine (YF-Vax) studies resulted in overlapping gene lists; however, they shared more portions of pathways than gene lists. Interestingly, live attenuated YF-Vax simulates significant metabolism of protein responses, which was similar to the pattern induced by killed inactivated Fluarix. A user-friendly web interface was generated to access, browse and search the VaximmutorDB database information. As the first web-based database of vaccine immune factors, VaximmutorDB provides systematical collection, standardization, storage, and analysis of experimentally verified vaccine immune factors, supporting better understanding of protective vaccine immunity.
Making Insulin and Staying Out of Autoimmune Trouble: The Beta-Cell Conundrum
Authors: Carré Alexia , Mallone Roberto
Published: March 2021

Autoimmune type 1 diabetes (T1D) results from the intricate crosstalk of various immune cell types. CD8+ T cells dominate the pro-inflammatory milieu of islet infiltration (insulitis), and are considered as key effectors of beta-cell destruction, through the recognition of MHC Class I-peptide complexes. The pathways generating MHC Class I-restricted antigens in beta cells are poorly documented. Given their specialized insulin secretory function, the associated granule processing and degradation pathways, basal endoplasmic reticulum stress and susceptibility to additional stressors, alternative antigen processing and presentation (APP) pathways are likely to play a significant role in the generation of the beta-cell immunopeptidome. As direct evidence is missing, we here intersect the specificities of beta-cell function and the literature about APP in other cellular models to generate some hypotheses on APPs relevant to beta cells. We further elaborate on the potential role of these pathways in T1D pathogenesis, based on the current knowledge of antigens presented by beta cells. A better understanding of these pathways may pinpoint novel mechanisms amenable to therapeutic targeting to modulate the immunogenicity of beta cells.
Missing Insight Into T and B Cell Responses in Dermatitis Herpetiformis
Authors: Kemppainen Esko , Salmi Teea , Lindfors Katri
Published: March 2021

Dermatitis herpetiformis is a cutaneous form of celiac disease manifesting as an itching rash typically on the elbows, knees and buttocks. It is driven by the ingestion of gluten-containing cereals and characterized by granular deposits of immunoglobulin A in the papillary dermis. These antibodies target transglutaminase (TG) 3 and in the majority of patients they are also found in circulation. The circulating antibodies disappear and skin symptoms resolve as a result of gluten-free diet but the cutaneous anti-TG3 IgA deposits may persist for several years. In dermatitis herpetiformis, plasma cells secreting antibodies against TG3 are located in the intestinal mucosa similarly to those producing TG2 antibodies characteristic for celiac disease. In fact, both TG2- and TG3-specific plasma cells and gluten responsive T cells are found in dermatitis herpetiformis patients but the interplay between these cell populations is unknown. The small bowel mucosal damage in celiac disease is believed to be mediated by co-operation of cytotoxic intraepithelial T cells and the inflammatory milieu contributed by gluten-reactive CD4+ T cells, whereas the skin lesions in dermatitis herpetiformis appear to be devoid of gluten reactive T cells. Thus, how celiac disease-type intestinal T and B cell responses develop into an autoimmune condition affecting the skin is still incompletely understood. Finally, the skin and small bowel lesions may reappear upon reintroduction of gluten in patients treated with gluten-free diet but virtually nothing is known about the long-lived B cell and memory T cell populations activating in response to dietary gluten in dermatitis herpetiformis.