bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Representation of Biological Components in Methane‐Cycling Processes in Wetlands Improves Modeling Predictions
Authors: Villa Jorge A. 
Published: July 2020

AbstractWetlands are important natural sources of methane. However, methane predictions are unconstrained due in part to simplified representations in biogeochemical models of complex interactions between biological components and biophysical drivers. Chang et al. (2019, https://doi.org/10.1029/2019JG005355) demonstrate how mechanistic descriptions of processes mediated by biological components and their drivers help improve methane prediction in the thawing permafrost peatlands, where biological components are shifting as a response to current climate change. These findings underscore the need for accounting for the different methanogenic pathways in biogeochemical models to predict methane cycling under a changing climate scenario. This comment presents some implications of considering the methanogenic pathways when simulating different wetland ecosystems and discusses the relevance of including other processes mediated by biological components in the methane cycle in models.
Aging and menopause reprogram osteoclast precursors for aggressive bone resorption
Authors: Møller Anaïs Marie Julie , Delaissé Jean-Marie , Olesen Jacob Bastholm , Madsen Jonna Skov , Canto Luisa Matos , Bechmann Troels , Rogatto Silvia Regina , Søe Kent 
Published: July 2020

AbstractWomen gradually lose bone from the age of ~35 years, but around menopause, the rate of bone loss escalates due to increasing bone resorption and decreasing bone formation levels, rendering these individuals more prone to developing osteoporosis. The increased osteoclast activity has been linked to a reduced estrogen level and other hormonal changes. However, it is unclear whether intrinsic changes in osteoclast precursors around menopause can also explain the increased osteoclast activity. Therefore, we set up a protocol in which CD14+blood monocytes were isolated from 49 female donors (40–66 years old). Cells were differentiated into osteoclasts, and data on differentiation and resorption activity were collected. Using multiple linear regression analyses combining in vitro and in vivo data, we found the following: (1) age and menopausal status correlate with aggressive osteoclastic bone resorption in vitro; (2) the type I procollagen N-terminal propeptide level in vivo inversely correlates with osteoclast resorption activity in vitro; (3) the protein level of mature cathepsin K in osteoclasts in vitro increases with age and menopause; and (4) the promoter of the gene encoding the dendritic cell-specific transmembrane protein is less methylated with age. We conclude that monocytes are “reprogrammed” in vivo, allowing them to “remember” age, the menopausal status, and the bone formation status in vitro, resulting in more aggressive osteoclasts. Our discovery suggests that this may be mediated through DNA methylation. We suggest that this may have clinical implications and could contribute to understanding individual differences in age- and menopause-induced bone loss.
Chondroitin polymerizing factor (CHPF) promotes development of malignant melanoma through regulation of CDK1
Authors: Sun Wei , Zhao Fang , Xu Yu , Huang Kai , Guo Xianling , Zheng Biqiang , Liu Xin , Luo Zhiguo , Kong Yunyi , Xu Midie , Schadendorf Dirk , Chen Yong 
Published: July 2020

AbstractChondroitin polymerizing factor (CHPF) is an important member of glycosyltransferases involved in the biosynthesis of chondroitin sulfate (CS). However, the relationship between CHPF and malignant melanoma (MM) is still unknown. In this study, it was demonstrated that CHPF was up-regulated in MM tissues compared with the adjacent normal skin tissues and its high expression was correlated with more advanced T stage. Further investigations indicated that the over-expression/knockdown of CHPF could promote/inhibit proliferation, colony formation and migration of MM cells, while inhibiting/promoting cell apoptosis. Moreover, knockdown of CHPF could also suppress tumorigenicity of MM cells in vivo. RNA-sequencing followed by Ingenuity pathway analysis (IPA) was performed for exploring downstream of CHPF and identified CDK1 as the potential target. Furthermore, our study revealed that knockdown of CDK1 could inhibit development of MM in vitro, and alleviate the CHPF over-expression induced promotion of MM. In conclusion, our study showed, as the first time, CHPF as a tumor promotor for MM, whose function was carried out probably through the regulation of CDK1.
Reduced replication origin licensing selectively kills KRAS-mutant colorectal cancer cells via mitotic catastrophe
Authors: Gastl Bastian , Klotz-Noack Kathleen , Klinger Bertram , Ispasanie Sylvia , Salib Krenoula Hani Fouad , Zuber Johannes , Mamlouk Soulafa , Bublitz Natalie , Blüthgen Nils , Horst David , Morkel Markus , Schäfer Reinhold , Sers Christine 
Published: July 2020

AbstractTo unravel vulnerabilities of KRAS-mutant CRC cells, a shRNA-based screen specifically inhibiting MAPK pathway components and targets was performed in CaCo2 cells harboring conditional oncogenic KRASG12V. The custom-designed shRNA library comprised 121 selected genes, which were previously identified to be strongly regulated in response to MEK inhibition. The screen showed that CaCo2 cells expressing KRASG12V were sensitive to the suppression of the DNA replication licensing factor minichromosome maintenance complex component 7 (MCM7), whereas KRASwt CaCo2 cells were largely resistant to MCM7 suppression. Similar results were obtained in an isogenic DLD-1 cell culture model. Knockdown of MCM7 in a KRAS-mutant background led to replication stress as indicated by increased nuclear RPA focalization. Further investigation showed a significant increase in mitotic cells after simultaneous MCM7 knockdown and KRASG12V expression. The increased percentage of mitotic cells coincided with strongly increased DNA damage in mitosis. Taken together, the accumulation of DNA damage in mitotic cells is due to replication stress that remained unresolved, which results in mitotic catastrophe and cell death. In summary, the data show a vulnerability of KRAS-mutant cells towards suppression of MCM7 and suggest that inhibiting DNA replication licensing might be a viable strategy to target KRAS-mutant cancers.
The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications
Authors: Zhang Yuanyuan , Zhang Zemin 
Published: July 2020

AbstractImmunotherapy has revolutionized cancer treatment and rejuvenated the field of tumor immunology. Several types of immunotherapy, including adoptive cell transfer (ACT) and immune checkpoint inhibitors (ICIs), have obtained durable clinical responses, but their efficacies vary, and only subsets of cancer patients can benefit from them. Immune infiltrates in the tumor microenvironment (TME) have been shown to play a key role in tumor development and will affect the clinical outcomes of cancer patients. Comprehensive profiling of tumor-infiltrating immune cells would shed light on the mechanisms of cancer–immune evasion, thus providing opportunities for the development of novel therapeutic strategies. However, the highly heterogeneous and dynamic nature of the TME impedes the precise dissection of intratumoral immune cells. With recent advances in single-cell technologies such as single-cell RNA sequencing (scRNA-seq) and mass cytometry, systematic interrogation of the TME is feasible and will provide insights into the functional diversities of tumor-infiltrating immune cells. In this review, we outline the recent progress in cancer immunotherapy, particularly by focusing on landmark studies and the recent single-cell characterization of tumor-associated immune cells, and we summarize the phenotypic diversities of intratumoral immune cells and their connections with cancer immunotherapy. We believe such a review could strengthen our understanding of the progress in cancer immunotherapy, facilitate the elucidation of immune cell modulation in tumor progression, and thus guide the development of novel immunotherapies for cancer treatment.
Root exudate composition of grass and forb species in natural grasslands
Authors: Dietz Sophie , Herz Katharina , Gorzolka Karin , Jandt Ute , Bruelheide Helge , Scheel Dierk 
Published: July 2020

AbstractPlants exude a diverse cocktail of metabolites into the soil as response to exogenous and endogenous factors. So far, root exudates have mainly been studied under artificial conditions due to methodological difficulties. In this study, each five perennial grass and forb species were investigated for polar and semi-polar metabolites in exudates under field conditions. Metabolite collection and untargeted profiling approaches combined with a novel classification method allowed the designation of 182 metabolites. The composition of exuded polar metabolites depended mainly on the local environment, especially soil conditions, whereas the pattern of semi-polar metabolites was primarily affected by the species identity. The profiles of both polar and semi-polar metabolites differed between growth forms, with grass species being generally more similar to each other and more responsive to the abiotic environment than forb species. This study demonstrated the feasibility of investigating exudates under field conditions and to identify the driving factors of exudate composition.
Optimal Gestational Weight Gain for Tibetans Based on Prepregnancy Body Mass Index
Authors: Chen Dajie , Zhou Xianxian , Yan Shijiao , Li Wenzhen , Yang Xueyi , Lv Chuanzhu , Lu Zuxun 
Published: July 2020

AbstractWe aimed to estimate the optimal gestational weight gain (GWG) in Tibetan women and to evaluate the appropriateness of the Institute of Medicine (IOM) GWG recommendations for Tibetan women. We analyzed data from 1474 Tibetan women from a cross-sectional study conducted in 2019. According to the three different body mass index (BMI) classification criteria (WHO BMI categories, WHO Asian BMI categories, Chinese BMI categories), we estimated the association of GWG with pregnancy outcomes (neonate birthweight and mode of delivery) using a polynomial regression model, and the optimal GWG in each BMI group was calculated. The risk of adverse outcomes showed a U-shaped curve with increasing GWG. The optimal GWG of Tibetan women based on the WHO BMI categories was 17.2 kg (range, 13.3 to 20.9 kg) for underweight, 9.3 kg (5.8 to 12.9 kg) for normal weight, and 5.2 kg (1.3 to 9.1 kg) for overweight. Underweight Tibetan mothers may gain more gestational weight than recommend by the IOM guidelines. However, normal weight Tibetan mothers are likely to benefit from gaining less weight than that recommended by the IOM. The GWG recommendations based on the IOM guidelines might not be appropriate for Tibetan women, and ethnicity-specific recommendations for GWG should be properly addressed.
FMRP Regulates the Nuclear Export of Adam9 and Psen1 mRNAs: Secondary Analysis of an N6-Methyladenosine Dataset
Authors: Westmark Cara J. , Maloney Bryan , Alisch Reid S. , Sokol Deborah K. , Lahiri Debomoy K. 
Published: July 2020

AbstractFragile X mental retardation protein (FMRP) binds to and regulates the translation of amyloid-β protein precursor (App) mRNA, but the detailed mechanism remains to be determined. Differential methylation of App mRNA could underlie FMRP binding, message localization and translation efficiency. We sought to determine the role of FMRP and N6-methyladeonsine (m6A) on nuclear export of App mRNA. We utilized the m6A dataset by Hsu and colleagues to identify m6A sites in App mRNA and to determine if the abundance of message in the cytoplasm relative to the nucleus is altered in Fmr1 knockout mouse brain cortex. Given that processing of APP to Aβ and soluble APP alpha (sAPPα) contributes to disease phenotypes, we also investigated whether Fmr1KO associates with nuclear export of the mRNAs for APP protein processing enzymes, including β-site amyloid cleaving enzyme (Bace1), A disintegrin and metalloproteinases (Adams), and presenilins (Psen). Fmr1KO did not alter the nuclear/cytoplasmic abundance of App mRNA. Of 36 validated FMRP targets, 35 messages contained m6A peaks but only Agap2 mRNA was selectively enriched in Fmr1KO nucleus. The abundance of the APP processing enzymes Adam9 and Psen1 mRNA, which code for a minor alpha-secretase and gamma-secretase, respectively, were selectively enriched in wild type cytoplasm.
Comparison of uric acid reduction and renal outcomes of febuxostat vs allopurinol in patients with chronic kidney disease
Authors: Peng Yueh-Lung , Tain You-Lin , Lee Chien-Te , Yang Yi-Hsn , Huang Yaw-Bin , Wen Yen-Hsia , Hsu Chien-Ning 
Published: July 2020

AbstractWhether the clinical trial treatment effect of urate-lowering therapy (ULT) in patient with chronic kidney disease (CKD) is generalizable to real-word settings is unclear. This study aimed to compare febuxostat with allopurinol for uric acid reduction and renal protection in patients with CKD. Adult CKD patients newly treated with ULT were identified using electronic health records from 2010 to 2015 from a large healthcare delivery system in Taiwan. Patients with renal replacement therapy or undergoing ULT for <3 months were excluded. Propensity score–matched cohort study design was conducted to compare outcomes between patients initiated with febuxostat or allopurinol therapy. Cox regression analyses were employed to compare the adjusted hazards ratio (aHR) of incident event of estimated glomerular filtration rate (eGFR) ≥ 30% decrease, and the difference in longitudinal changes in serum uric acid (SUA) and eGFR between groups was analyzed using linear mixed model. Overall, 1050 CKD patients who initiated febuxostat (n = 525) or allopurinol (n = 525) treatment were observed for 2.5 years. Compared with allopurinol, febuxostat use was associated with higher rate of patients maintaining SUA target <6 mg/dL in >80% of follow-up time with a reduction in mean SUA change. There were no significant differences in the mean eGFR changes over time between the febuxostat and allopurinol groups or in the risk of eGFR decline ≥30% of baseline. Febuxostat was associated with greater reduction in SUA level than allopurinol in patients with CKD. However, febuxostat and allopurinol showed no difference in renal function changes during study follow-up. These findings require further investigation with long-term follow up in CKD patients with hyperuricemia.
The p.P888L SAP97 polymorphism increases the transient outward current (Ito,f) and abbreviates the action potential duration and the QT interval
Authors: Tinaquero David , Crespo-García Teresa , Utrilla Raquel G. , Nieto-Marín Paloma , González-Guerra Andrés , Rubio-Alarcón Marcos , Cámara-Checa Anabel , Dago María , Matamoros Marcos , Pérez-Hernández Marta , Tamargo María , Cebrián Jorge , Jalife José , Tamargo Juan , Bernal Juan Antonio , Caballero Ricardo , Delpón Eva ,   ITACA Investigators, Alonso-Martín Joaquín J. , Arribas Fernando , Atienza Felipe , Hernández-Madrid Antonio , López-Sendón José Luis , Pérez-Villacastín Julián , Toquero Jorge 
Published: July 2020

AbstractSynapse-Associated Protein 97 (SAP97) is an anchoring protein that in cardiomyocytes targets to the membrane and regulates Na+ and K+ channels. Here we compared the electrophysiological effects of native (WT) and p.P888L SAP97, a common polymorphism. Currents were recorded in cardiomyocytes from mice trans-expressing human WT or p.P888L SAP97 and in Chinese hamster ovary (CHO)-transfected cells. The duration of the action potentials and the QT interval were significantly shorter in p.P888L-SAP97 than in WT-SAP97 mice. Compared to WT, p.P888L SAP97 significantly increased the charge of the Ca-independent transient outward (Ito,f) current in cardiomyocytes and the charge crossing Kv4.3 channels in CHO cells by slowing Kv4.3 inactivation kinetics. Silencing or inhibiting Ca/calmodulin kinase II (CaMKII) abolished the p.P888L-induced Kv4.3 charge increase, which was also precluded in channels (p.S550A Kv4.3) in which the CaMKII-phosphorylation is prevented. Computational protein-protein docking predicted that p.P888L SAP97 is more likely to form a complex with CaMKII than WT. The Na+ current and the current generated by Kv1.5 channels increased similarly in WT-SAP97 and p.P888L-SAP97 cardiomyocytes, while the inward rectifier current increased in WT-SAP97 but not in p.P888L-SAP97 cardiomyocytes. The p.P888L SAP97 polymorphism increases the Ito,f, a CaMKII-dependent effect that may increase the risk of arrhythmias.
Reliability and Influence on Decision Making of fully-automated vs. semi-automated Software Packages for Procedural Planning in TAVI
Authors: Meyer Alexander , Kofler Markus , Montagner Matteo , Unbehaun Axel , Sündermann Simon , Buz Semih , Klein Christoph , Stamm Christof , Solowjowa Natalia , Emmert Maximilian Y. , Falk Volkmar , Kempfert Jörg 
Published: July 2020

AbstractPrecise procedural planning is crucial to achieve excellent results in patients undergoing Transcatheter aortic valve implantation (TAVI). The aim of this study was to compare the semi-automated 3mensio (3 m) software to the fully-automated HeartNavigator3 (HN) software. We randomly selected 100 patients from our in-house TAVI-registry and compared aortic annulus and perimeter as well as coronary distances between 3m-measurements and post-hoc HN-measurements. Finally, we retrospectively simulated prosthesis choice based on HN-measurements and analyzed the differences compared to routinely used 3 m based strategy. We observed significant differences between the two software packages regarding area (3 m 464 ± 88 mm², HN 482 ± 96 mm², p < 0.001), perimeter (3 m 77 ± 7 mm, HN 79 ± 8 mm, p < 0.001) and coronary distances (LCA: 3 m 13 ± 3 mm, HN 12 ± 3 mm, p < 0.001; RCA: 3 m 16 ± 3 mm, HN 15 ± 3 mm, p < 0.001). Prosthesis choice simulation based on newly obtained HN-measurements would have led to a decision change in 18% of patients, with a further reduction to 4% following manual adjustment of HN-measurements. The fully-automatic HN-software provides higher values for annular metrics and lower annulus-to-coronary-ostia distances compared to 3m-software. Measurement differences did not influence clinical outcome. Both, the HN-software and the 3m-software are sophisticated, reliable and easy to use for the clinician. Manual adjustment of HN-measurements may increase precision in complex aortic annulus anatomy.
Electricity generation from food wastes and spent animal beddings with nutrients recirculation in catalytic fuel cell
Authors: Dahunsi S. O. 
Published: July 2020

AbstractA biochemical system was used for electricity generation from food waste (FW) and spent animal beddings (SAB). The wastes were blended and fermented anaerobically to produce fermentation liquids used as fuels for running a catalytic fuel cell. The fermentation liquids were analyzed for their components. The results show the organic contents i.e. volatile solids of both FW and SAB to be 23.4 and 20.9 g/L while the carbon contents were 6.5 and 6.1 g/L respectively. The media were however very rich in volatile fatty acids (VFAs). When used, the fermentation liquids from FW and SAB generated mean open-circuit voltages of 0.64 and 0.53 V and mean maximum power densities (Pmean) of 1.6 and 1.3 mW/cm2 respectively. The fuel cell showed very high efficiency in the conversion of all VFAs especially butyric acid with the highest been 97% for FW and 96% for SAB.
Increasing level of liquid pig manure reduces Eisenia andrei and Enchytraeus crypticus reproduction in subtropical soils
Authors: Segat Julia Corá , Sousa José Paulo , Baretta Dilmar , Klauberg-Filho Osmar 
Published: July 2020

AbstractWastes generated in pig production are widely used as agricultural fertilizers. Nevertheless, such form of disposal supplies large amounts of waste in soils annually and can cause environmental pollution. The ecological risk of this practice to soil organisms has received little attention. Ecotoxicological tests are used to evaluate the toxicity of contaminants added to the soil biota. The aimed to evaluate the effect of liquid pig manure (LPM) on the reproduction of Eisenia andrei and Enchytraeus crypticus when applied in natural soils. LPM doses caused effects on earthworm reproduction in both soils, with EC50 of 112 and 150 m3 ha−1 in the Entisol and Nitosol, respectively. On enchytraeids, LPM had bigger effects, leading to EC50 of 17.7 and 45.0 m3 ha−1 in the Entisol and Nitosol, respectively. The results emphasize the importance to consider the ecological risks of LPM of conducting studies with natural soils and edaphic fauna as indicators.
Modeling, state estimation, and optimal control for the US COVID-19 outbreak
Authors: Tsay Calvin , Lejarza Fernando , Stadtherr Mark A. , Baldea Michael 
Published: July 2020

AbstractThe novel coronavirus SARS-CoV-2 and resulting COVID-19 disease have had an unprecedented spread and continue to cause an increasing number of fatalities worldwide. While vaccines are still under development, social distancing, extensive testing, and quarantining of confirmed infected subjects remain the most effective measures to contain the pandemic. These measures carry a significant socioeconomic cost. In this work, we introduce a novel optimization-based decision-making framework for managing the COVID-19 outbreak in the US. This includes modeling the dynamics of affected populations, estimating the model parameters and hidden states from data, and an optimal control strategy for sequencing social distancing and testing events such that the number of infections is minimized. The analysis of our extensive computational efforts reveals that social distancing and quarantining are most effective when implemented early, with quarantining of confirmed infected subjects having a much higher impact. Further, we find that “on-off” policies alternating between strict social distancing and relaxing such restrictions can be effective at “flattening” the curve while likely minimizing social and economic cost.
Modulation of acoustic navigation behaviour by spatial learning in the echolocating bat Rhinolophus ferrumequinum nippon
Authors: Yamada Yasufumi , Mibe Yurina , Yamamoto Yuya , Ito Kentaro , Heim Olga , Hiryu Shizuko 
Published: July 2020

AbstractUsing echolocation, bats receive acoustic information on their surroundings, which is assumed to help them sophisticatedly navigate complex environments. In this study, to understand spatial learning and acoustic sensing in bats, we investigated how flight and echolocation control changed in Rhinolophus ferrumequinum nippon as they learnt about their surroundings in an obstacle course that they flew through repeatedly. In these experiments, two testing environments (acoustically permeable and acoustically reflective) were prepared using chains and acrylic boards as obstacles to evaluate the interactive effects of spatial learning and flight environments. We found that bats reduced the meandering width of their flights and pulse emissions, and also seemed to reduce their shifts in pulse direction as they learnt more about their environments in both conditions. Throughout all our experiments, the bats with slower flight speeds tended to emit more pulses, which suggests that the number of pulse emissions reflects the echolocation tactics of each bat. The maximum flight speed was especially increased in the acoustically permeable condition, with frequent emissions of multiple pulses (≧triplets) in the early stages of flight, suggesting that bats adjust their flight plan based on how much of their surroundings they are able to sense in advance.