bluuebunny/crossref_metadata_2025 huggingface dataset:
Shifts in the Bacterial Community of Supragingival Plaque Associated With Metabolic-Associated Fatty Liver Disease
Authors: Zhao Fen , Dong Ting , Yuan Ke-Yong , Wang Ning-Jian , Xia Fang-Zhen , Liu Di , Wang Zhi-Min , Ma Rui , Lu Ying-Li , Huang Zheng-Wei
Published: January 2021

Metabolic-associated fatty liver disease (MAFLD), also known as the hepatic manifestation of metabolic disorders, has become one of the most common chronic liver diseases worldwide. The associations between some oral resident microbes and MAFLD have been described. However, changes to the oral microbial community in patients with MAFLD remain unknown. In this study, variations to the supragingival microbiota of MAFLD patients were identified. The microbial genetic profile of supragingival plaque samples from 24 MAFLD patients and 22 healthy participants were analyzed by 16S rDNA sequencing and bioinformatics analysis. Clinical variables, including indicators of insulin resistance, obesity, blood lipids, and hepatocellular damage, were evaluated with laboratory tests and physical examinations. The results showed that the diversity of the supragingival microbiota in MAFLD patients was signiﬁcantly higher than that in healthy individuals. Weighted UniFrac principal coordinates analysis and partial least squares discriminant analysis showed that the samples from the MAFLD and control groups formed separate clusters (Adonis, P = 0.0120). There were 27 taxa with differential distributions (linear discriminant analysis, LDA>2.0) between two groups, among which Actinomyces spp. and Prevotella 2 spp. were over-represented in the MAFLD group with highest LDA score, while Neisseria spp. and Bergeyella spp. were more abundant in the control group. Co-occurrence networks of the top 50 abundant genera in the two groups suggested that the inter-genera relationships were also altered in the supragingival plaque of MAFLD patients. In addition, in genus level, as risk factors for the development of MAFLD, insulin resistance was positively correlated with the abundances of Granulicatella, Veillonella, Streptococcus, and Scardovia, while obesity was positively correlated to the abundances of Streptococcus, Oslenella, Scardovia, and Selenomonas. Metagenomic predictions based on Phylogenetic Investigation of Communities by Reconstruction of Unobserved States revealed that pathways related to sugar (mainly free sugar) metabolism were enriched in the supragingival plaque of the MAFLD group. In conclusion, as compared to healthy individuals, component and interactional dysbioses were observed in the supragingival microbiota of the MAFLD group.
Vitamin in the Crosshairs: Targeting Pantothenate and Coenzyme A Biosynthesis for New Antituberculosis Agents
Authors: Butman Hailey S. , Kotzé Timothy J. , Dowd Cynthia S. , Strauss Erick
Published: January 2021

Despite decades of dedicated research, there remains a dire need for new drugs against tuberculosis (TB). Current therapies are generations old and problematic. Resistance to these existing therapies results in an ever-increasing burden of patients with disease that is difficult or impossible to treat. Novel chemical entities with new mechanisms of action are therefore earnestly required. The biosynthesis of coenzyme A (CoA) has long been known to be essential inMycobacterium tuberculosis(Mtb), the causative agent of TB. The pathway has been genetically validated by seminal studiesin vitroandin vivo. In Mtb, the CoA biosynthetic pathway is comprised of nine enzymes: four to synthesize pantothenate (Pan) froml-aspartate and α-ketoisovalerate; five to synthesize CoA from Pan and pantetheine (PantSH). This review gathers literature reports on the structure/mechanism, inhibitors, and vulnerability of each enzyme in the CoA pathway. In addition to traditional inhibition of a single enzyme, the CoA pathway offers an antimetabolite strategy as a promising alternative. In this review, we provide our assessment of what appear to be the best targets, and, thus, which CoA pathway enzymes present the best opportunities for antitubercular drug discovery moving forward.
Water Resources Change in Central-Western Argentina Under the Paris Agreement Warming Targets
Authors: Rivera Juan A. , Naranjo Tamayo Elizabeth , Viale Maximiliano
Published: January 2021

This study documents the projected changes in several components (precipitation, runoff, snow cover and depth, soil moisture) of the hydrological cycle in Central-Western Argentina (CWA) based on the simulations from the IPSL-CM6A-LR model for the warming levels proposed in the Paris Agreement. These warming levels represent the future increase in mean annual temperature of 1.5 and 2°C compared to pre-industrial conditions. A novel regional approach, that uses a set of low-emissions shared socioeconomic pathways (SSP) compatible with the Paris Agreement goals, has been applied here for the evaluation of the potential impacts of temperature increase in both the mountainous areas of the Andes and the lowlands on the eastern portion of CWA. Our results show that the timing of reaching the 1.5°C warming level would be between 2032 and 2036 in the CWA lowlands east of the Andes, while this warming level in the Andes mountains of CWA would be 10–15 years earlier as result of the stronger warming with elevation. The higher 2°C warming level would be reached before 2050 in the Andes mountains. Even using the more aggressive mitigation pathways available in the scientific literature (SSP1-1.9 and SSP1-2.6), the IPSL-CM6A-LR model ensemble shows a robust drying signal in the wintertime precipitation over the Andes mountains, which is a concerning result because it implies a reduction of the already scarce water resources draining to the adjacent semi-arid foothills. Our results also show that this drying should be linked to the poleward expansion of the Hadley Circulation. In the lowlands farther east from the Andes, the summertime monsoonal precipitation provides the water resources that are projected to increase under the selected emissions pathways. The expected changes in the analyzed components of the hydrological cycle would be strengthened under the 2°C warming level, particularly the decline of snow amount and surface runoff in the Andes. The results of this study provide insights into the expected impacts of the 1.5 and 2°C warming levels in the CWA regional water resources, which may set the stage for the new discussions of possible options to mitigate them at country and regional levels.
Predicting Common Audiological Functional Parameters (CAFPAs) as Interpretable Intermediate Representation in a Clinical Decision-Support System for Audiology
Authors: Saak Samira K. , Hildebrandt Andrea , Kollmeier Birger , Buhl Mareike
Published: January 2021

The application of machine learning for the development of clinical decision-support systems in audiology provides the potential to improve the objectivity and precision of clinical experts' diagnostic decisions. However, for successful clinical application, such a tool needs to be accurate, as well as accepted and trusted by physicians. In the field of audiology, large amounts of patients' data are being measured, but these are distributed over local clinical databases and are heterogeneous with respect to the applied assessment tools. For the purpose of integrating across different databases, the Common Audiological Functional Parameters (CAFPAs) were recently established as abstract representations of the contained audiological information describing relevant functional aspects of the human auditory system. As an intermediate layer in a clinical decision-support system for audiology, the CAFPAs aim at maintaining interpretability to the potential users. Thus far, the CAFPAs were derived by experts from audiological measures. For designing a clinical decision-support system, in a next step the CAFPAs need to be automatically derived from available data of individual patients. Therefore, the present study aims at predicting the expert generated CAFPA labels using three different machine learning models, namely the lasso regression, elastic nets, and random forests. Furthermore, the importance of different audiological measures for the prediction of specific CAFPAs is examined and interpreted. The trained models are then used to predict CAFPAs for unlabeled data not seen by experts. Prediction of unlabeled cases is evaluated by means of model-based clustering methods. Results indicate an adequate prediction of the ten distinct CAFPAs. All models perform comparably and turn out to be suitable choices for the prediction of CAFPAs. They also generalize well to unlabeled data. Additionally, the extracted relevant features are plausible for the respective CAFPAs, facilitating interpretability of the predictions. Based on the trained models, a prototype of a clinical decision-support system in audiology can be implemented and extended towards clinical databases in the future.
Volcanic Hazard Assessment for an Eruption Hiatus, or Post-eruption Unrest Context: Modeling Continued Dome Collapse Hazards for Soufrière Hills Volcano
Authors: Spiller Elaine T. , Wolpert Robert L. , Ogburn Sarah E. , Calder Eliza S. , Berger James O. , Patra Abani K. , Pitman E. Bruce
Published: January 2021

Effective volcanic hazard management in regions where populations live in close proximity to persistent volcanic activity involves understanding the dynamic nature of hazards, and associated risk. Emphasis until now has been placed on identification and forecasting of the escalation phase of activity, in order to provide adequate warning of what might be to come. However, understanding eruption hiatus and post-eruption unrest hazards, or how to quantify residual hazard after the end of an eruption, is also important and often key to timely post-eruption recovery. Unfortunately, in many cases when the level of activity lessens, the hazards, although reduced, do not necessarily cease altogether. This is due to both the imprecise nature of determination of the “end” of an eruptive phase as well as to the possibility that post-eruption hazardous processes may continue to occur. An example of the latter is continued dome collapse hazard from lava domes which have ceased to grow, or sector collapse of parts of volcanic edifices, including lava dome complexes. We present a new probabilistic model for forecasting pyroclastic density currents (PDCs) from lava dome collapse that takes into account the heavy-tailed distribution of the lengths of eruptive phases, the periods of quiescence, and the forecast window of interest. In the hazard analysis, we also consider probabilistic scenario models describing the flow’s volume and initial direction. Further, with the use of statistical emulators, we combine these models with physics-based simulations of PDCs at Soufrière Hills Volcano to produce a series of probabilistic hazard maps for flow inundation over 5, 10, and 20 year periods. The development and application of this assessment approach is the first of its kind for the quantification of periods of diminished volcanic activity. As such, it offers evidence-based guidance for dome collapse hazards that can be used to inform decision-making around provisions of access and reoccupation in areas around volcanoes that are becoming less active over time.
Post-Caldera Eruptions at Chalupas Caldera, Ecuador: Determining the Timing of Lava Dome Collapse, Hummock Emplacement and Dome Rejuvenation
Authors: Córdova Marco D. , Mothes Patricia Ann , Gaunt H. Elizabeth , Salgado Josué
Published: January 2021

Determining the lithology, extent, origin, and age of hummocks can be challenging, especially if these are covered by successive deposits and lush vegetation. At Chalupas caldera, a late-Pleistocene silicic center that lies astride the Eastern Cordillera of northern Ecuador, we have tried to overcome these difficulties by combining geological observations and sampling, laboratory analysis (geochemistry, scanning electron microscope analysis and radiometric dating) and remote sensing techniques. Chalupas is the second largest caldera in the Northern Volcanic Zone of South America and its VEI 7 eruption, which occurred ∼0.21 Ma, has garnered the attention of the volcanological community. Our research highlights new observations of the post-caldera activity at Chalupas, beginning with the growth of Quilindaña stratovolcano (∼0.170 Ma), followed by the formation of Buenavista dome that is located 5 km eastward of Quilindaña’s summit. At the eastern foot of Buenavista dome we identify hummocky terrain covering an area of ∼20 km2. Collectively, the suite of techniques that we used helped to highlight geological features that shed light on the provenance of the hummocks and demonstrate that this topography may have originated from gravitational breccia flows from Buenavista lava dome. Numerical simulations were also performed to represent breccia flow transit and emplacement over the present caldera landscape and to view the potential hazard footprints of a future Buenavista dome collapse. For modeling we employed volumes of 20–120 Mm3 to visualize the consecutive traces of mass flow deposition and how the traces correspond to the hummocky landscape. Following the partial collapse of Buenavista lava dome, its rejuvenation is represented by tephra layers of several small eruptions that are dated at about 40 ky BP. These tephras represent some of the youngest eruptive activity recognized at Chalupas caldera. Our results contribute to the overall knowledge about Chalupas and demonstrate that eruptions at this important caldera are more recent than was previously reported.
Pathways for Methane Emissions and Oxidation that Influence the Net Carbon Balance of a Subtropical Cypress Swamp
Authors: Ward Nicholas D. , Bianchi Thomas S. , Martin Jonathan B. , Quintero Carlos J. , Sawakuchi Henrique O. , Cohen Matthew J.
Published: January 2021

We evaluated the major pathways for methane emissions from wetlands to the atmosphere at four wetland sites in the Big Cypress National Preserve in southwest Florida. Methane oxidation was estimated based on the δ13C-CH4of surface water, porewater, and bubbles to evaluate mechanisms that limit surface water emissions. Spatially-scaled methane fluxes were then compared to organic carbon burial rates. The pathway with the lowest methane flux rate was diffusion from surface waters (3.50 ± 0.22 mmol m−2 d−1). Microbial activity in the surface water environment and/or shallow oxic sediment layer oxidized 26 ± 3% of the methane delivered from anerobic sediments to the surface waters. The highest rates of diffusion were observed at the site with the lowest extent of oxidation. Ebullition flux rates were 2.2 times greater than diffusion and more variable (7.79 ± 1.37 mmol m−2 d−1). Methane fluxes from non-inundated soils were 1.6 times greater (18.4 ± 5.14 mmol m−2 d−1) than combined surface water fluxes. Methane flux rates from cypress knees (emergent cypress tree root structures) were 3.7 and 2.3 times higher (42.0 ± 6.33 mmol m−2 d−1) than from surface water and soils, respectively. Cypress knee flux rates were highest at the wetland site with the highest porewater methane partial pressure, suggesting that the emergent root structures allow methane produced in anaerobic sediment layers to bypass oxidation in aerobic surface waters or shallow sediments. Scaled across the four wetlands, emissions from surface water diffusion, ebullition, non-inundated soils, and knees contributed to 14 ± 2%, 25 ± 6%, 34 ± 10%, and 26 ± 5% of total methane emissions, respectively. When considering only the three wetlands with cypress knees present, knee emissions contributed to 39 ± 5% of the total scaled methane emissions. Finally, the molar ratio of CH4emissions to OC burial ranged from 0.03 to 0.14 in the wetland centers indicating that all four wetland sites are net sources of atmospheric warming potential on 20–100 yr timescales, but net sinks over longer time scales (500 yr) with the exception of one wetland site that was a net source even over 500 yr time scales.
Preferred Pore Orientation as a Complement to Anisotropy of Magnetic Susceptibility: A Case Study of Lava Flows From Batur Volcano, Bali, Indonesia
Authors: Desi Wulan Ndari Nuresi Rantri , Suryanata Putu Billy , Bijaksana Satria , Dahrin Darharta , Atarita Fadhli Ramadhana , Pratama Aditya , Hafidz Abd , Fajar Silvia Jannatul
Published: January 2021

Anisotropy of magnetic susceptibility (AMS) analyses have been used widely in many applications that include studying lava flows. In this paper, we introduce an auxiliary parameter, i.e., preferred pore orientation, on the use of AMS for lava flow studies on the basaltic lava samples from Batur Volcano in Bali Indonesia. We also examine the effect of sample position in lava flow outcrop to the relationship between preferred pore orientation and AMS. The samples are subjected to petrographic analyses as well as to magnetic measurements and micro-computed tomography (μCT) imaging. Preferred pore orientations were obtained by quantified the long-axis of the vesicles from the images. The correlation was evaluated by measuring the angle between the maximum susceptibility axes and the preferred pore orientations. All samples show that the maximum susceptibility axes are parallel with the flow direction. Three out of six samples of two lava flows from the same eruption show a positive correlation between AMS and preferred pore orientation, where both parameters point to the northeast direction. A difference of sample position in the outcrop of lava flow was observed as a possible factor that influenced the results for the preferred pore orientations. Samples which were taken from the summit of the lava flow have pore orientation parallel to the lava flow direction. While samples which were taken from the foot slope of the lava flow have pore orientation perpendicular to the lava flow direction. This study provides further evidence that pore orientation might be positively correlated with the AMS.
Impact of Intraseasonal Oscillations on the Activity of Tropical Cyclones in Summer Over the South China Sea: Nonlocal Tropical Cyclones
Authors: Ling Zheng , Wang Yuqing , Wang Guihua , He Hailun
Published: January 2021

In addition to tropical cyclones (TCs) locally formed in the South China Sea (SCS), there are also TCs that initially form over the Northwest Pacific (NWP) and move westward to enter the SCS (often called nonlocal TCs). It is unclear how those nonlocal TCs are modulated by the intraseasonal climate variability. In this study, the impacts of two types of intraseasonal oscillations, namely the Madden–Julian Oscillation (MJO) and the quasi-biweekly oscillation (QBWO), on nonlocally formed TCs over the SCS in summer (May–September) are analyzed based on best-track TC data and global reanalysis during 1979–2018. Results show that in the convective phases of both MJO and QBWO, the western Pacific subtropical high shifted more eastward, and more TCs entered the SCS. This is mainly because more TCs formed in the NWP in the convective phases of intraseasonal oscillations and the genesis locations of the NWP TCs shifted westward and closer to the SCS. In addition to TC count, intraseasonal oscillations also affected the intensity of nonlocal TCs entered the SCS, with the influence of QBWO being more significant than MJO. In the convectively active phases of QBWO (phases 2–5), 34 nonlocal TCs reached typhoon intensity, while only two nonlocal TCs reached typhoon intensity in the convectively inactive phases (phases 1, 6, 7, 8). Further analysis indicates that nonlocal TCs often moved with the northwestward propagating convective signals of QBWO, resulting in more and stronger TCs that entered the SCS in the convective phases of QBWO. The mean location that the nonlocal TC entered the SCS also shifted northward with the northward propagation of intraseasonal oscillations.
CFD-Based Wind Assessment for Suburban Buildings. The Case Study of Aarhus University, Herning Campus
Authors: Strasszer David , Xydis George
Published: January 2021

The development in the field of wind turbines is continuously growing. However, most of the times, the energy of wind is exploited by using huge wind-power plants, while wind energy installations in urban and suburban areas, as space and available land, are a lot more limited, is something relatively new, with great potential though. The major challenge regarding small urban wind turbines can be summarized as a lack of understanding of the wind resource in the built environment, with a combination of missing measurements in this field that needed to be addressed. Aarhus University Campus Herning, located in the suburban area of Herning, is looking for a suitable place to install one small wind turbine (SWT). This study attempts to provide a comprehensive framework for SWTs and the characteristics of urban wind flow. The analysis helped in identifying the two most appropriate sites for SWTs installation sites in the AU Herning building.
Trends in Stable Isotopes and Climate Proxies From Late Changhsingian Ghost Landscapes of the Karoo Basin, South Africa
Authors: Gastaldo Robert A. , Tabor Neil J. , Neveling Johann
Published: January 2021

The stable carbon- and oxygen-isotope values derived from in situ pedogenic carbonate-cemented nodules and vertebrate apatite in the Daptocephalus and overlying Lystrosaurus Assemblage Zones of the Balfour Formation, Karoo Basin, South Africa, have formed the basis for previous interpretations of a unidirectional climate trend toward hyper-aridity across the biozone boundary. This assemblage-zone boundary has been considered by many authors to be equivalent to the Permian–Triassic boundary in the basin. To better understand the climate under which these vertebrate assemblages existed, we have analyzed the carbon- and oxygen-stable isotopes of pedogenic carbonate nodules sampled from fourteen horizons of intraformational pedogenic nodular conglomerate (PNC) at Old Lootsberg Pass, a classic locality at which the Permian–Triassic boundary is reported. Analysis of these refractory soil constituents provides insight into the climate under which these “ghost” soils formed, where no other physical record of their existence is found in the stratigraphy. A positive correlation between δ13CVPDB and δ18OVSMOW values of micrite cements is defined by analyses of carbonate nodules taken from a measured stratigraphic thickness of ∼200 m, which spans the biozone boundary as currently defined. For samples taken from the same lag deposit, similar and relatively narrow ranges of isotope values are encountered. Samples cluster into two isotopic groups. The values in the first group cluster more tightly in all sampled nodules (δ13CVPDB −2.3 to −6.5‰; δ18OVSMOW 13.8–15.1‰), and are interpreted to indicate that these originated from paleosols that formed under similar climate controls. Values from the second sample group display a wider variance between analyses (δ13CVPDB −5.2 to 14.0‰; δ18OVSMOW 8.8–15.5‰). These nodules are interpreted to indicate that they originated under polygenetic soil-forming conditions representing the reworking of either: (1) more than one paleosol, the calcite-cemented nodules of which represent precipitation under both closed and open-system controls; or (2) one or more compound-composite paleosols. Stable-isotope trends based on PNCs analyzed, thus far, demonstrate an overall shift over time in the ghost landscapes. More seasonally dry soils formed under a climate that can be characterized as warm/dry accompanied by lower precipitation in the lower part of the section. In contrast, soils in the upper part of the section formed under cool and moist conditions, with increased precipitation near the biozone boundary. Hence, latest Permian climate associated with the more seasonally dry landscapes demonstrate a trend toward cooler and wetter conditions, which is opposite to the trend widely held in the literature.
Establishing Propagation Nodes as a Basis for Preventing Large Wildfires: The Proposed Methodology
Authors: Quílez Raúl , Valbuena Luz , Vendrell Jordi , Uytewaal Kathleen , Ramirez Joaquín
Published: January 2021

In Spain, traditional forest fire management practices have been conducted for many decades, for both prevention- and extinction-oriented purposes. This management model has been forced to shift as a result of changes in fire behavior and has also been adapted to the use of new technologies. The challenge presented by wildfires is amplified due to socioeconomic changes in the last 40 years and inadequate land management in the context of climate change. The principal objective of this work is to establish the most adequate methodology to define the “propagation nodes” in a territory. To do that, the new simulation modes offered by the WildFire AnalystTM simulator (WFA) have been explored to obtain fire behavior data. Likewise, the behavior of large fires in the area has been extrapolated to future scenarios, according to forecasts of different climate change, analyzing extreme weather conditions that can occur in such scenarios (ONU, 2019). The WFA simulator (Tecnosylva, 2014) works efficiently in simulating fire, proving greatly useful in both real suppression operations and fire prevention analysis. It can very accurately generate large wildfires' main pathways without making any kind of adjustments; this is quite useful when planning operations at the head of a fire. It also allows evacuation time evaluation for a given Wildland Urban Interface zone. The area selected for this study is called Sot de Chera, in the Valencia region (Spain). The methodology employed here uses the simulation with WFA setting extreme meteorological and phenological windows associated with wind-driven fires or convection fires dominated with wind, from different starting points looking for the areas where they are grouped. In other words, it is a matter of identifying on the territory the areas where the heads of these higher-intensity fires will arrive, in order to offer realistic control possibilities to the firefighting teams. The results of the simulation identify the heads of the fires with the greatest rate of spread and intensity, exceeding suppression capabilities and efforts, allowing thus to plan for appropriate fuel management strategies to effectively manage emergency responses to fires in these areas.
Precision Genome Engineering for the Breeding of Tomatoes: Recent Progress and Future Perspectives
Authors: Vu Tien Van , Das Swati , Tran Mil Thi , Hong Jong Chan , Kim Jae-Yean
Published: January 2021

Currently, poor biodiversity has raised challenges in the breeding and cultivation of tomatoes, which originated from the Andean region of Central America, under global climate change. Meanwhile, the wild relatives of cultivated tomatoes possess a rich source of genetic diversity but have not been extensively used for the genetic improvement of cultivated tomatoes due to the possible linkage drag of unwanted traits from their genetic backgrounds. With the advent of new plant breeding techniques (NPBTs), especially CRISPR/Cas-based genome engineering tools, the high-precision molecular breeding of tomato has become possible. Further, accelerated introgression or de novo domestication of novel and elite traits from/to the wild tomato relatives to/from the cultivated tomatoes, respectively, has emerged and has been enhanced with high-precision tools. In this review, we summarize recent progress in tomato precision genome editing and its applications for breeding, with a special focus on CRISPR/Cas-based approaches. Future insights and precision tomato breeding scenarios in the CRISPR/Cas era are also discussed.
Promoter PPSP1–5-BnPSP-1 From Ramie (Boehmeria nivea L. Gaud.) Can Drive Phloem-Specific GUS Expression in Arabidopsis thaliana
Authors: Wang Yunhe , Bao Yaning , Zheng Yancheng , Guo Ping’an , Peng Dingxiang , Wang Bo
Published: January 2021

Isolation of phloem-specific promoters is one of the basic conditions for improving the fiber development and resistance of ramie phloem using genetic engineering. In this study, we isolated a ramie endogenous promoter (named PPSP1-BnPSP-1) and analyzed the function of its truncated fragments in Arabidopsis. The results show that PPSP1-BnPSP-1 can drive the GUS reporter gene to be specifically expressed in the veins of Arabidopsis. After hormone and simulated drought treatment of the independent Arabidopsis lines carrying PPSP1-BnPSP-1 and its truncated fragments, only PPSP1–5-BnPSP-1 (−600 to −1 bp region of PPSP1-BnPSP-1) is stably expressed and exhibits phloem specificity. Our findings suggest that PPSP1–5-BnPSP-1 can be used as a phloem specific promoter for further research.
Using The Cancer Genome Atlas as an Inquiry Tool in the Undergraduate Classroom
Authors: Hankey William , Zanghi Nicholas , Crow Mackenzie M. , Dow Whitney H. , Kratz Austin , Robinson Ashley M. , Robinson Meaghan R. , Segarra Verónica A.
Published: January 2021

Undergraduate students in the biomedical sciences are often interested in future health-focused careers. This presents opportunities for instructors in genetics, molecular biology, and cancer biology to capture their attention using lab experiences built around clinically relevant data. As biomedical science in general becomes increasingly dependent on high-throughput data, well-established scientific databases such as The Cancer Genome Atlas (TCGA) have become publicly available tools for medically relevant inquiry. The best feature of this database is that it bridges the molecular features of cancer to human clinical outcomes—allowing students to see a direct connection between the molecular sciences and their future professions. We have developed and tested a learning module that leverages the power of TCGA datasets to engage students to use the data to generate and test hypotheses and to apply statistical tests to evaluate significance.
Selection and Validation of the Optimal Panel of Reference Genes for RT-qPCR Analysis in the Developing Rat Cartilage
Authors: Liu Liang , Han Hui , Li Qingxian , Chen Ming , Zhou Siqi , Wang Hui , Chen Liaobin
Published: January 2021

Real-time fluorescence quantitative PCR (RT-qPCR) is widely used to detect gene expression levels, and selection of reference genes is crucial to the accuracy of RT-qPCR results. Minimum Information for Publication of RT-qPCR Experiments (MIQE) proposes that using the panel of reference genes for RT-qPCR is conducive to obtaining accurate experimental results. However, the selection of the panel of reference genes for RT-qPCR in rat developing cartilage has not been well documented. In this study, we selected eight reference genes commonly used in rat cartilage from literature (GAPDH, ACTB, 18S, GUSB, HPRT1, RPL4, RPL5, and SDHA) as candidates. Then, we screened out the optimal panel of reference genes in female and male rat cartilage of fetus (GD20), juvenile (PW6), and puberty (PW12) in physiology with stability analysis software of genes expression. Finally, we verified the reliability of the selected panel of reference genes with the rat model of intrauterine growth retardation (IUGR) induced by prenatal dexamethasone exposure (PDE). The results showed that the optimal panel of reference genes in cartilage at GD20, PW6, and PW12 in physiology was RPL4 + RPL5, which was consistent with the IUGR model, and there was no significant gender difference. Further, the results of standardizing the target genes showed that RPL4 + RPL5 performed smaller intragroup differences than other panels of reference genes or single reference genes. In conclusion, we found that the optimal panel of reference genes in female and male rat developing cartilage was RPL4 + RPL5, and there was no noticeable difference before and after birth.
Refinement of Draft Genome Assemblies of Pigeonpea (Cajanus cajan)
Authors: Marla Soma S. , Mishra Pallavi , Maurya Ranjeet , Singh Mohar , Wankhede Dhammaprakash Pandhari , Kumar Anil , Yadav Mahesh C. , Subbarao N. , Singh Sanjeev K. , Kumar Rajesh
Published: January 2021

Genome assembly of short reads from large plant genomes remains a challenge in computational biology despite major developments in next generation sequencing. Of late several draft assemblies have been reported in sequenced plant genomes. The reported draft genome assemblies of Cajanus cajan have different levels of genome completeness, a large number of repeats, gaps, and segmental duplications. Draft assemblies with portions of genome missing are shorter than the referenced original genome. These assemblies come with low map accuracy affecting further functional annotation and the prediction of gene components as desired by crop researchers. Genome coverage, i.e., the number of sequenced raw reads mapped onto a certain location of the genome is an important quality indicator of completeness and assembly quality in draft assemblies. The present work aimed to improve the coverage in reported de novo sequenced draft genomes (GCA_000340665.1 and GCA_000230855.2) of pigeonpea, a legume widely cultivated in India. The two recently sequenced assemblies, A1 and A2 comprised 72% and 75% of the estimated coverage of the genome, respectively. We employed an assembly reconciliation approach to compare the draft assemblies and merge them, filling the gaps by employing an algorithm size sorting mate-pair library to generate a high quality and near complete assembly with enhanced contiguity. The majority of gaps present within scaffolds were filled with right-sized mate-pair reads. The improved assembly reduced the number of gaps than those reported in draft assemblies resulting in an improved genome coverage of 82.4%. Map accuracy of the improved assembly was evaluated using various quality metrics and for the presence of specific trait-related functional genes. Employed pair-end and mate-pair local libraries helped us to reduce gaps, repeats, and other sequence errors resulting in lengthier scaffolds compared to the two draft assemblies. We reported the prediction of putative host resistance genes against Fusarium wilt disease by their performance and evaluated them both in wet laboratory and field phenotypic conditions.
Exploring the Relationship Between Psychiatric Traits and the Risk of Mouth Ulcers Using Bi-Directional Mendelian Randomization
Authors: Wang Kai , Ding Lin , Yang Can , Hao Xingjie , Wang Chaolong
Published: January 2021

Background

Although the association between mouth ulcers and psychiatric traits has been reported by observational studies, their causal relationship remains unclear. Mendelian randomization (MR), powered by large-scale genome-wide association studies (GWAS), provides an opportunity to clarify the causality between mouth ulcers and psychiatric traits.

Methods

We collected summary statistics of mouth ulcers (sample size n = 461,106) and 10 psychiatric traits from the largest publicly available GWAS on Europeans, including anxiety disorder (n = 83,566), attention deficit/hyperactivity disorder (n = 53,293), autism spectrum disorder (n = 46,350), bipolar disorder (n = 51,710), insomnia (n = 1,331,010), major depressive disorder (n = 480,359), mood instability (n = 363,705), neuroticism (n = 168,105), schizophrenia (n = 105,318), and subjective wellbeing (n = 388,538). We applied three two-sample bi-directional MR analysis methods, namely the Inverse Variance Weighted (IVW) method, the MR pleiotropy residual sum and outlier (MR-PRESSO) method, and the weighted median method, to assess the causal relationship between each psychiatric trait and mouth ulcers.

Results

We found significant effects of autism spectrum disorder, insomnia, major depressive disorder, and subjective wellbeing on mouth ulcers, with the corresponding odds ratio (OR) from the IVW method being 1.160 [95% confidence interval (CI): 1.066–1.261, P = 5.39 × 10–4], 1.092 (1.062–1.122, P = 3.37 × 10–10), 1.234 (1.134–1.342, P = 1.03 × 10–6), and 0.703 (0.571–0.865, P = 8.97 × 10–4), respectively. We also observed suggestive evidence for mood instability to cause mouth ulcers [IVW, OR = 1.662 (1.059–2.609), P = 0.027]. These results were robust to weak instrument bias and heterogeneity. We found no evidence on causal effects between other psychiatric traits and mouth ulcers, in either direction.

Conclusion

Our findings suggest a protective effect of subjective wellbeing and risk effects of autism spectrum disorder, insomnia, major depressive disorder, and mood instability on mouth ulcers. These results clarify the causal relationship between psychiatric traits and the development of mouth ulcers.
ATTfold: RNA Secondary Structure Prediction With Pseudoknots Based on Attention Mechanism
Authors: Wang Yili , Liu Yuanning , Wang Shuo , Liu Zhen , Gao Yubing , Zhang Hao , Dong Liyan
Published: January 2021

Accurate RNA secondary structure information is the cornerstone of gene function research and RNA tertiary structure prediction. However, most traditional RNA secondary structure prediction algorithms are based on the dynamic programming (DP) algorithm, according to the minimum free energy theory, with both hard and soft constraints. The accuracy is particularly dependent on the accuracy of soft constraints (from experimental data like chemical and enzyme detection). With the elongation of the RNA sequence, the time complexity of DP-based algorithms will increase geometrically, as a result, they are not good at coping with relatively long sequences. Furthermore, due to the complexity of the pseudoknots structure, the secondary structure prediction method, based on traditional algorithms, has great defects which cannot predict the secondary structure with pseudoknots well. Therefore, few algorithms have been available for pseudoknots prediction in the past. The ATTfold algorithm proposed in this article is a deep learning algorithm based on an attention mechanism. It analyzes the global information of the RNA sequence via the characteristics of the attention mechanism, focuses on the correlation between paired bases, and solves the problem of long sequence prediction. Moreover, this algorithm also extracts the effective multi-dimensional features from a great number of RNA sequences and structure information, by combining the exclusive hard constraints of RNA secondary structure. Hence, it accurately determines the pairing position of each base, and obtains the real and effective RNA secondary structure, including pseudoknots. Finally, after training the ATTfold algorithm model through tens of thousands of RNA sequences and their real secondary structures, this algorithm was compared with four classic RNA secondary structure prediction algorithms. The results show that our algorithm significantly outperforms others and more accurately showed the secondary structure of RNA. As the data in RNA sequence databases increase, our deep learning-based algorithm will have superior performance. In the future, this kind of algorithm will be more indispensable.
Entry Denied: COVID-19, Race, Migration, and Global Health
Authors: Sirleaf Matiangai
Published: January 2021

This essay uses the novel coronavirus pandemic as an entry point to explore the intersections between race, migration, and global health. The pandemic is simultaneously reviving stereotypical colonial imaginations about disease directionality, but also challenging racialized hierarchies of diseases. This essay illuminates how the racialization of diseases is reflected in historic and ongoing United States' migration law and policy as well as the global health law regime. By demonstrating the close relationship between often separately treated areas, the essay clarifies underlying currents in global health and migration law and policy that stem from fears of the racialized other. Rendering these intersections visible creates avenues for rethinking and reshaping both theory and praxis toward anti-subordination efforts.
Cleavage of HMGB1 by Proteolytic Enzymes Associated with Inflammatory Conditions
Authors: Sowinska Agnieszka , Rensing Merlin , Klevenvall Lena , Neog Manoj , Lundbäck Peter , Harris Helena Erlandsson
Published: January 2021

Extracellular HMGB1 acts as an alarmin in multiple autoimmune diseases. While its release and functions have been extensively studied, there is a substantial lack of knowledge regarding HMGB1 regulation at the site of inflammation. Herein we show that enzymes present in arthritis-affected joints process HMGB1 into smaller peptides in vitro. Gel electrophoresis, Western blotting and mass spectrometry analyses indicate cleavage sites for human neutrophil elastase, cathepsin G, and matrix metalloproteinase 3 within the HMGB1 structure. While human neutrophil elastase and matrix metalloproteinase 3 might alter the affinity of HMGB1 to its receptors by cleaving the acidic C-terminal tail, cathepsin G rapidly and completely degraded the alarmin. Contrary to a previous report we demonstrate that HMGB1 is not a substrate for dipeptidyl peptidase IV. We also provide novel information regarding the presence of these proteases in synovial fluid of juvenile idiopathic arthritis patients. Correlation analysis of protease levels and HMGB1 levels in synovial fluid samples did not, however, reveal any direct relationship between the recorded levels. This study provides knowledge of proteolytic processing of HMGB1 relevant for the regulation of HMGB1 during inflammatory disease.
What Makes Antibodies Against G Protein-Coupled Receptors so Special? A Novel Concept to Understand Chronic Diseases
Authors: Riemekasten Gabriela , Petersen Frank , Heidecke Harald
Published: January 2021

Expressions of G protein-coupled receptors (GPCR) on immune and tissue resident cells are the consequence of the cellular environment, which is highly variable. As discussed here, antibodies directed to GPCR (GPCR abs), their levels and correlations to other abs, serve as biomarkers for various diseases. They also could reflect the individual interplay between the environment and the immune system. Thus, GPCR abs could display pathogenic chronic conditions and could help to identify disease-related pathways. Moreover, by acting as ligands to their corresponding receptors, GPCR abs modulate autoimmune as well as non-autoimmune diseases. This article introduces GPCR abs as drivers for diseases by their capability to induce a specific signaling and by determining immune cell homeostasis. The identification of the individual GPCR ab function is challenging but might be pivotal in the comprehension of the aetiology of diseases. This, hopefully, will lead to the identification of novel therapeutic strategies. This article provides an overview about concepts and recent developments in research. Accordingly, GPCR abs could represent ideal candidates for precision medicine. Here, we introduce the term antibodiom to cover the network of abs with GPCR abs as prominent players.
Anti-CD2 Antibody-Coated Nanoparticles Containing IL-2 Induce NK Cells That Protect Lupus Mice via a TGF-β-Dependent Mechanism
Authors: Horwitz David A. , Liu Aijing , Bickerton Sean , Castaldo Giuseppe , Matarese Giuseppe , Fahmy Tarek M. , La Cava Antonio
Published: January 2021

We recently reported that the treatment with nanoparticles (NPs) loaded with tolerogenic cytokines suppressed the manifestations of lupus-like disease induced by the transfer of donor CD4+T cells from DBA/2 mice into (C57BL/6 × DBA/2)F1 (BDF1) mice. Although the protective effects were ascribed to the induction of adaptive CD4+and CD8+T regulatory cells, the results suggested that another population of immune cells could be involved. Here we report that NK cells critically contribute to the protection from lupus-like disease conferred by NPs to BDF1 mice, and that this effect is TGF-β-dependent.
Alterations of the Fecal Microbiota in Chinese Patients With Multiple Sclerosis
Authors: Ling Zongxin , Cheng Yiwen , Yan Xiumei , Shao Li , Liu Xia , Zhou Dajin , Zhang Lijuan , Yu Kunqiang , Zhao Longyou
Published: January 2021

Mounting evidence indicates that alterations in the intestinal microbiota may be associated with neurological disorders such as multiple sclerosis (MS). MS is a putative autoimmune disease of the central nervous system. However, it has not been determined whether the intestinal microbiota and host immune status are altered in Chinese patients with stable MS. In our study, 22 Chinese patients with stable MS and 33 healthy controls were enrolled for fecal microbiota analysis and host immunity evaluation. The microbial diversity and composition, bacterial co-occurrence correlations, predictive functional profiles, and microbiota-cytokine correlations between the two groups were compared. We observed that while the overall structure of the fecal microbiota did not change significantly, the abundances of several key functional bacteria, primarily Faecalibacterium, decreased remarkably. Faecalibacterium and Granulicatella could be used to distinguish between patients with MS and healthy controls with an area under the curve of 0.832. PiCRUSt analysis revealed that genes associated with fructose, mannose, and fatty acid metabolism were significantly enriched in the MS microbiota. In addition, we also observed that the levels of several pro- and anti-inflammatory cytokines and chemokines, such as IL-1ra, IL-8, IL-17, and TNF-α changed observably, and the abundances of key functional bacteria like butyrate producers correlated with the changes in the cytokine levels. Our present study indicated that altered composition of the fecal microbiota might play vital roles in the etiopathogenesis of MS by regulating host immunity, which suggests that microbiota-targeting patient-tailored early intervention techniques might serve as novel therapeutic approaches for MS.
Reverse Signaling by MHC-I Molecules in Immune and Non-Immune Cell Types
Authors: Muntjewerff Elke M. , Meesters Luca D. , Bogaart Geert van den , Revelo Natalia H.
Published: January 2021

Major histocompatibility complex (MHC) molecules are well-known for their role in antigen (cross-) presentation, thereby functioning as key players in the communication between immune cells, for example dendritic cells (DCs) and T cells, or immune cells and their targets, such as T cells and virus-infected or tumor cells. However, much less appreciated is the fact that MHC molecules can also act as signaling receptors. In this process, here referred to as reverse MHC class I (MHC-I) signaling, ligation of MHC molecules can lead to signal-transduction and cell regulatory effects in the antigen presenting cell. In the case of MHC-I, reverse signaling can have several outcomes, including apoptosis, migration, induced or reduced proliferation and cytotoxicity towards target cells. Here, we provide an overview of studies showing the signaling pathways and cell outcomes upon MHC-I stimulation in various immune and non-immune cells. Signaling molecules like RAC-alpha serine/threonine-protein kinase (Akt1), extracellular signal-regulated kinases 1/2 (ERK1/2), and nuclear factor-κB (NF-κB) were common signaling molecules activated upon MHC-I ligation in multiple cell types. For endothelial and smooth muscle cells, thein vivorelevance of reverse MHC-I signaling has been established, namely in the context of adverse effects after tissue transplantation. For other cell types, the role of reverse MHC-I signaling is less clear, since aspects like thein vivorelevance, natural MHC-I ligands and the extended downstream pathways are not fully known.The existing evidence, however, suggests that reverse MHC-I signaling is involved in the regulation of the defense against bacterial and viral infections and against malignancies. Thereby, reverse MHC-I signaling is a potential target for therapies against viral and bacterial infections, cancer immunotherapies and management of organ transplantation outcomes.