bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methanogenic archaea use a bacteria-like methyltransferase system to demethoxylate aromatic compounds
Authors: Kurth Julia M , Nobu Masaru K , Tamaki Hideyuki , de Jonge Nadieh , Berger Stefanie , Jetten Mike S M , Yamamoto Kyosuke , Mayumi Daisuke , Sakata Susumu , Bai Liping , Cheng Lei , Nielsen Jeppe Lund , Kamagata Yoichi , Wagner Tristan , Welte Cornelia U 
Published: June 2021

Abstract
Methane-generating archaea drive the final step in anaerobic organic compound mineralization and dictate the carbon flow of Earth’s diverse anoxic ecosystems in the absence of inorganic electron acceptors. Although such Archaea were presumed to be restricted to life on simple compounds like hydrogen (H2), acetate or methanol, an archaeon, Methermicoccus shengliensis, was recently found to convert methoxylated aromatic compounds to methane. Methoxylated aromatic compounds are important components of lignin and coal, and are present in most subsurface sediments. Despite the novelty of such a methoxydotrophic archaeon its metabolism has not yet been explored. In this study, transcriptomics and proteomics reveal that under methoxydotrophic growth M. shengliensis expresses an O-demethylation/methyltransferase system related to the one used by acetogenic bacteria. Enzymatic assays provide evidence for a two step-mechanisms in which the methyl-group from the methoxy compound is (1) transferred on cobalamin and (2) further transferred on the C1-carrier tetrahydromethanopterin, a mechanism distinct from conventional methanogenic methyl-transfer systems which use coenzyme M as final acceptor. We further hypothesize that this likely leads to an atypical use of the methanogenesis pathway that derives cellular energy from methyl transfer (Mtr) rather than electron transfer (F420H2 re-oxidation) as found for methylotrophic methanogenesis.
Mapping pleiotropic loci using a fast-sequential testing algorithm
Authors: Aguate Fernando M. , Vazquez Ana I. , Merriman Tony R. , de los Campos Gustavo 
Published: June 2021

AbstractPleiotropy (i.e., genes with effects on multiple traits) leads to genetic correlations between traits and contributes to the development of many syndromes. Identifying variants with pleiotropic effects on multiple health-related traits can improve the biological understanding of gene action and disease etiology, and can help to advance disease-risk prediction. Sequential testing is a powerful approach for mapping genes with pleiotropic effects. However, the existing methods and the available software do not scale to analyses involving millions of SNPs and large datasets. This has limited the adoption of sequential testing for pleiotropy mapping at large scale. In this study, we present a sequential test and software that can be used to test pleiotropy in large systems of traits with biobank-sized data. Using simulations, we show that the methods implemented in the software are powerful and have adequate type-I error rate control. To demonstrate the use of the methods and software, we present a whole-genome scan in search of loci with pleiotropic effects on seven traits related to metabolic syndrome (MetS) using UK-Biobank data (n~300 K distantly related white European participants). We found abundant pleiotropy and report 170, 44, and 18 genomic regions harboring SNPs with pleiotropic effects in at least two, three, and four of the seven traits, respectively. We validate our results using previous studies documented in the GWAS-catalog and using data from GTEx. Our results confirm previously reported loci and lead to several novel discoveries that link MetS-related traits through plausible biological pathways.
Next generation proteomics with drug sensitivity screening identifies sub-clones informing therapeutic and drug development strategies for multiple myeloma patients
Authors: Tierney Ciara , Bazou Despina , Majumder Muntasir M. , Anttila Pekka , Silvennoinen Raija , Heckman Caroline A. , Dowling Paul , O’Gorman Peter 
Published: June 2021

AbstractWith the introduction of novel therapeutic agents, survival in Multiple Myeloma (MM) has increased in recent years. However, drug-resistant clones inevitably arise and lead to disease progression and death. The current International Myeloma Working Group response criteria are broad and make it difficult to clearly designate resistant and responsive patients thereby hampering proteo-genomic analysis for informative biomarkers for sensitivity. In this proof-of-concept study we addressed these challenges by combining an ex-vivo drug sensitivity testing platform with state-of-the-art proteomics analysis. 35 CD138-purified MM samples were taken from patients with newly diagnosed or relapsed MM and exposed to therapeutic agents from five therapeutic drug classes including Bortezomib, Quizinostat, Lenalidomide, Navitoclax and PF-04691502. Comparative proteomic analysis using liquid chromatography-mass spectrometry objectively determined the most and least sensitive patient groups. Using this approach several proteins of biological significance were identified in each drug class. In three of the five classes focal adhesion-related proteins predicted low sensitivity, suggesting that targeting this pathway could modulate cell adhesion mediated drug resistance. Using Receiver Operating Characteristic curve analysis, strong predictive power for the specificity and sensitivity of these potential biomarkers was identified. This approach has the potential to yield predictive theranostic protein panels that can inform therapeutic decision making.
Modeling the metabolic profile of Mytilus edulis reveals molecular signatures linked to gonadal development, sex and environmental site
Authors: Kronberg Jaanika , Byrne Jonathan J. , Jansen Jeroen , Antczak Philipp , Hines Adam , Bignell John , Katsiadaki Ioanna , Viant Mark R. , Falciani Francesco 
Published: June 2021

AbstractThe monitoring of anthropogenic chemicals in the aquatic environment including their potential effects on aquatic organisms, is important for protecting life under water, a key sustainable development goal. In parallel with monitoring the concentrations of chemicals of concern, sentinel species are often used to investigate the biological effects of contaminants. Among these, bivalve molluscs such as mussels are filter-feeding and sessile, hence an excellent model system for measuring localized pollution. This study investigates the relationship between the metabolic state of the blue mussel (Mytilus edulis) and its physiology in different environments. We developed a computational model based on a reference site (relatively unpolluted) and integrated seasonal dynamics of metabolite relative concentrations with key physiological indicators and environmental parameters. The analysis of the model revealed that changes in metabolite levels during an annual cycle are influenced by water temperature and are linked to gonadal development. This work supports the importance of data-driven biology and its potential in environmental monitoring.
hsp-90 and unc-45 depletion induce characteristic transcriptional signatures in coexpression cliques of C. elegans
Authors: Schmauder Lukas , Richter Klaus 
Published: June 2021

AbstractNematode development is characterized by progression through several larval stages. Thousands of genes were found in large scale RNAi-experiments to block this development at certain steps, two of which target the molecular chaperone HSP-90 and its cofactor UNC-45. Aiming to define the cause of arrest, we here investigate the status of nematodes after treatment with RNAi against hsp-90 and unc-45 by employing an in-depth transcriptional analysis of the arrested larvae. To identify misregulated transcriptional units, we calculate and validate genome-wide coexpression cliques covering the entire nematode genome. We define 307 coexpression cliques and more than half of these can be related to organismal functions by GO-term enrichment, phenotype enrichment or tissue enrichment analysis. Importantly, hsp-90 and unc-45 RNAi induce or repress many of these cliques in a coordinated manner, and then several specifically regulated cliques are observed. To map the developmental state of the arrested nematodes we define the expression behaviour of each of the cliques during development from embryo to adult nematode. hsp-90 RNAi can be seen to arrest development close to the L4 larval stage with further deviations in daf-16 regulated genes. unc-45 RNAi instead leads to arrested development at young adult stage prior to the programmatic downregulation of sperm-cell specific genes. In both cases processes can be defined to be misregulated upon depletion of the respective chaperone. With most of the defined gene cliques showing concerted behaviour at some stage of development from embryo to late adult, the “clique map” together with the clique-specific GO-terms, tissue and phenotype assignments will be a valuable tool in understanding concerted responses on the genome-wide level in Caenorhabditis elegans.
Untangling the influence of biotic and abiotic factors on habitat selection by a tropical rodent
Authors: Ward-Fear Georgia , Brown Gregory P. , Pearson David , Shine Richard 
Published: June 2021

AbstractUnderstanding how animal populations respond to environmental factors is critical because large-scale environmental processes (e.g., habitat fragmentation, climate change) are impacting ecosystems at unprecedented rates. On an overgrazed floodplain in north-western Australia, a native rodent (Pale Field Rat, Rattus tunneyi) constructs its burrows primarily beneath an invasive tree (Chinee Apple, Ziziphus mauritiana) rather than native trees. The dense thorny foliage of the Chinee Apple may allow high rat densities either because of abiotic effects (shade, in a very hot environment) or biotic processes (protection from trampling and soil compaction by feral horses, and/or predation). To distinguish between these hypotheses, we manipulated Chinee Apple foliage to modify biotic factors (access to horses and predators) but not shade levels. We surveyed the rat population with Elliott traps under treatment and control trees and in the open woodland, in two seasons (the breeding season—January, and the nesting season—May). In the breeding season, we ran giving-up density experiments (GUD) with food trays, to assess the perceived risk of predation by rats across our three treatments. Selective trimming of foliage did not affect thermal regimes underneath the trees but did allow ingress of horses and we observed two collapsed burrows as a consequence (although long term impacts of horses were not measured). The perceived predation risk also increased (GUD values at food trays increased) and was highest in the open woodland. Our manipulation resulted in a shift in rat sex ratios (indicating female preference for breeding under control but not foliage-trimmed trees) and influenced rat behaviour (giving-up densities increased; large dominant males inhabited the control but not treatment trees). Our data suggest that the primary benefit of the Chinee Apple tree to native rodents lies in physical protection from predators and (potentially) feral horses, rather than in providing cooler microhabitat.
Measuring the structure and equation of state of polyethylene terephthalate at megabar pressures
Authors: Lütgert J. , Vorberger J. , Hartley N. J. , Voigt K. , Rödel M. , Schuster A. K. , Benuzzi-Mounaix A. , Brown S. , Cowan T. E. , Cunningham E. , Döppner T. , Falcone R. W. , Fletcher L. B. , Galtier E. , Glenzer S. H. , Laso Garcia A. , Gericke D. O. , Heimann P. A. , Lee H. J. , McBride E. E. , Pelka A. , Prencipe I. , Saunders A. M. , Schölmerich M. , Schörner M. , Sun P. , Vinci T. , Ravasio A. , Kraus D. 
Published: June 2021

AbstractWe present structure and equation of state (EOS) measurements of biaxially orientated polyethylene terephthalate (PET, $$({\hbox {C}}_{10} {\hbox {H}}_8 {\hbox {O}}_4)_n$$

(

C
10

H
8

O
4

)

n

, also called mylar) shock-compressed to ($$155 \pm 20$$

155
±
20

) GPa and ($$6000 \pm 1000$$

6000
±
1000

) K using in situ X-ray diffraction, Doppler velocimetry, and optical pyrometry. Comparing to density functional theory molecular dynamics (DFT-MD) simulations, we find a highly correlated liquid at conditions differing from predictions by some equations of state tables, which underlines the influence of complex chemical interactions in this regime. EOS calculations from ab initio DFT-MD simulations and shock Hugoniot measurements of density, pressure and temperature confirm the discrepancy to these tables and present an experimentally benchmarked correction to the description of PET as an exemplary material to represent the mixture of light elements at planetary interior conditions.
Exploring physicochemical and cytogenomic diversity of African cowpea and common bean
Authors: Catarino Sílvia , Brilhante Miguel , Essoh Anyse Pereira , Charrua Alberto B. , Rangel Josefa , Roxo Guilherme , Varela Eromise , Moldão Margarida , Ribeiro-Barros Ana , Bandeira Salomão , Moura Mónica , Talhinhas Pedro , Romeiras Maria M. 
Published: June 2021

AbstractIn sub-Saharan Africa, grain legumes (pulses) are essential food sources and play an important role in sustainable agriculture. Among the major pulse crops, the native cowpea (Vigna unguiculata) and introduced common bean (Phaseolus vulgaris) stand out. This paper has two main goals. First, we provide a comprehensive view of the available genetic resources of these genera in Africa, including data on germplasm collections and mapping biodiversity-rich areas. Second, we investigate patterns of physicochemical and cytogenomic variation across Africa to explore the geographical structuring of variation between native and introduced beans. Our results revealed that 73 Vigna and 5 Phaseolus species occur in tropical regions of Africa, with 8 countries accounting for more than 20 native species. Conversely, germplasm collections are poorly represented when compared to the worldwide collections. Regarding the nuclear DNA content, on average, V. unguiculata presents significantly higher values than P. vulgaris. Also, V. unguiculata is enriched in B, Mg, S, and Zn, while P. vulgaris has more Fe, Ca, and Cu. Overall, our study suggests that the physicochemical and cytogenomic diversity of native Vigna species is higher than previously thought, representing valuable food resources to reduce food insecurity and hunger, particularly of people living in African developing countries.
Healthy decisions in the cued-attribute food choice paradigm have high test-retest reliability
Authors: Barakchian Zahra , Beharelle Anjali Raja , Hare Todd A. 
Published: June 2021

AbstractFood choice paradigms are commonly used to study decision mechanisms, individual differences, and intervention efficacy. Here, we measured behavior from twenty-three healthy young adults who completed five repetitions of a cued-attribute food choice paradigm over two weeks. This task includes cues prompting participants to explicitly consider the healthiness of the food items before making a selection, or to choose naturally based on whatever freely comes to mind. We found that the average patterns of food choices following both cue types and ratings about the palatability (i.e. taste) and healthiness of the food items were similar across all five repetitions. At the individual level, the test-retest reliability for choices in both conditions and healthiness ratings was excellent. However, test-retest reliability for taste ratings was only fair, suggesting that estimates about palatability may vary more from day to day for the same individual.
Comparison of microsatellite instability detection by immunohistochemistry and molecular techniques in colorectal and endometrial cancer
Authors: Dedeurwaerdere Franceska , Claes Kathleen BM , Van Dorpe Jo , Rottiers Isabelle , Van der Meulen Joni , Breyne Joke , Swaerts Koen , Martens Geert 
Published: June 2021

AbstractDNA mismatch repair deficiency (dMMR) testing is crucial for diagnosing Lynch syndrome and detection of microsatellite unstable (MSI) tumors eligible for immunotherapy. The aim of this study was to compare the relative diagnostic performance of three molecular MSI assays: polymerase chain reaction (PCR), MSI testing by Idylla and next-generation-sequencing (NGS) on 49 tumor samples (28 colorectal and 21 endometrial adenocarcinomas) versus immunohistochemistry (IHC). Discrepancies were investigated by MLH1 methylation analysis and integrated with germline results if available. Overall, the molecular assays achieved equivalent diagnostic performance for MSI detection with area under the ROC curves (AUC) of respectively 0.91 for Idylla and PCR, and 0.93 for NGS. In colorectal cancers with tumor cell percentages ≥ 30% all three molecular assays achieved 100% sensitivity and specificity (AUC = 1) versus IHC. Also, in endometrial cancers, all three molecular assays showed equivalent diagnostic performance, albeit at a clearly lower sensitivity ranging from 58% for Idylla to 75% for NGS, corresponding to negative predictive values from 78 to 86%. PCR, Idylla and NGS show similar diagnostic performance for dMMR detection in colorectal and endometrial cancers. Molecular MSI analysis has lower sensitivity for dMMR detection in endometrial cancer indicating that combined use of both IHC and molecular methods is recommended.Clinical Trial Number/IRB: B1172020000040, Ethical Committee, AZ Delta General Hospital.
A unifying model to estimate thermal tolerance limits in ectotherms across static, dynamic and fluctuating exposures to thermal stress
Authors: Jørgensen Lisa Bjerregaard , Malte Hans , Ørsted Michael , Klahn Nikolaj Andreasen , Overgaard Johannes 
Published: June 2021

AbstractTemperature tolerance is critical for defining the fundamental niche of ectotherms and researchers classically use either static (exposure to a constant temperature) or dynamic (ramping temperature) assays to assess tolerance. The use of different methods complicates comparison between studies and here we present a mathematical model (and R-scripts) to reconcile thermal tolerance measures obtained from static and dynamic assays. Our model uses input data from several static or dynamic experiments and is based on the well-supported assumption that thermal injury accumulation rate increases exponentially with temperature (known as a thermal death time curve). The model also assumes thermal stress at different temperatures to be additive and using experiments with Drosophila melanogaster, we validate these central assumptions by demonstrating that heat injury attained at different heat stress intensities and durations is additive. In a separate experiment we demonstrate that our model can accurately describe injury accumulation during fluctuating temperature stress and further we validate the model by successfully converting literature data of ectotherm heat tolerance (both static and dynamic assays) to a single, comparable metric (the temperature tolerated for 1 h). The model presented here has many promising applications for the analysis of ectotherm thermal tolerance and we also discuss potential pitfalls that should be considered and avoided using this model.
A homozygous nonsense mutation in DCBLD2 is a candidate cause of developmental delay, dysmorphic features and restrictive cardiomyopathy
Authors: Alhamoudi Kheloud M. , Barhoumi Tlili , Al-Eidi Hamad , Asiri Abdulaziz , Nashabat Marwan , Alaamery Manal , Alharbi Masheal , Alhaidan Yazeid , Tabarki Brahim , Umair Muhammad , Alfadhel Majid 
Published: June 2021

AbstractDCBLD2 encodes discodin, CUB and LCCL domain-containing protein 2, a type-I transmembrane receptor that is involved in intracellular receptor signalling pathways and the regulation of cell growth. In this report, we describe a 5-year-old female who presented severe clinical features, including restrictive cardiomyopathy, developmental delay, spasticity and dysmorphic features. Trio-whole-exome sequencing and segregation analysis were performed to identify the genetic cause of the disease within the family. A novel homozygous nonsense variant in the DCBLD2 gene (c.80G > A, p.W27*) was identified as the most likely cause of the patient’s phenotype. This nonsense variant falls in the extracellular N-terminus of DCBLD2 and thus might affect proper protein function of the transmembrane receptor. A number of in vitro investigations were performed on the proband’s skin fibroblasts compared to normal fibroblasts, which allowed a comprehensive assessment resulting in the functional characterization of the identified DCBLD2 nonsense variant in different cellular processes. Our data propose a significant association between the identified variant and the observed reduction in cell proliferation, cell cycle progression, intracellular ROS, and Ca2 + levels, which would likely explain the phenotypic presentation of the patient as associated with lethal restrictive cardiomyopathy.
Associations between vitamin E, oxidative stress markers, total homocysteine levels, and physical activity or cognitive capacity in older adults
Authors: Alghadir Ahmad H. , Gabr Sami A. , Anwer Shahnawaz , Li Heng 
Published: June 2021

AbstractThis study examined the associations between vitamin E, oxidative stress markers, total homocysteine levels, and physical activity or cognitive capacity in older adults. One hundred and six older adults (62 men, 44 women) within the age range of 56–81 years participated. The Global Physical Activity Questionnaire and the Loewenstein Occupational Therapy Cognitive Assessment were used to assess physical activity and cognitive function, respectively. Vitamin E (e.g., α-tocopherol and γ-tocopherol), oxidative stress markers (e.g., total antioxidant capacity and nitric oxide), and total homocysteine were estimated. There were significant associations between physical activity (high versus moderate versus poor) and all biomarkers (allp = 0.000, andp = 0.010 for γ-tocopherol). While total homocysteine and total antioxidant capacity were significantly associated with cognitive capacity (p = 0.000), vitamin E levels (e.g., α-tocopherol and γ-tocopherol) and nitric oxide (p = 0.354, 0.103 and 0.060, respectively) were not related to cognitive capacity in older adults. This study concludes that physical activity was associated with Vitamin E, oxidative stress markers, total homocysteine, and cognitive capacity in older adults. Although cognitive capacity was associated with total homocysteine and total antioxidant capacity, it was unrelated to vitamin E levels and nitric oxide in older adults.
Lipid biomarkers in statin users with coronary artery disease annotated by coronary computed tomography angiography
Authors: Michelucci Elena , Giorgi Nicoletta Di , Finamore Francesco , Smit Jeff M. , Scholte Arthur J. H. A. , Signore Giovanni , Rocchiccioli Silvia 
Published: June 2021

AbstractMolecular markers are suggested to improve the diagnostic and prognostic accuracy in patients with coronary artery disease (CAD) beyond current clinical scores based on age, gender, symptoms and traditional risk factors. In this context, plasma lipids are emerging as predictors of both plaque composition and risk of future events. We aim to identify plasma lipid biomarkers associated to CAD indexes of stenosis severity, plaque lipid content and a comprensive score of CAD extent and its risk. We used a simple high performance liquid chromatography-tandem mass spectrometry method to identify 69 plasma lipids in 132 subjects referred to Coronary Computed Tomography Angiography (CCTA) for suspected CAD, all under statin treatment. Patients were stratified in groups using three different CCTA-based annotations: CTA-risk score, lipid plaque prevalence (LPP) ratio and the coronary artery disease-reporting and data system (CAD-RADS). We identified a common set of lipid biomarkers composed of 7 sphingomyelins and 3 phosphatidylethanolamines, which discriminates between high risk CAD patients and controls regardless of the CAD annotations used (CTA score, LPP ratio, or CAD-RADS). These results highlight the potential of circulating lipids as biomarkers of stenosis severity, non calcified plaque composition and overall plaque risk of events.