bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective role of endothelial calpain knockout in lipopolysaccharide-induced acute kidney injury via attenuation of the p38-iNOS pathway and NO/ROS production
Authors: Liu Zhifeng , Ji Jingjing , Zheng Dong , Su Lei , Peng Tianqing , Tang Jing 
Published: April 2020

AbstractTo explore the role of calpain and its signaling pathway in lipopolysaccharide (LPS)-induced acute kidney injury (AKI), animal models of endotoxemia were established by administration of LPS to mice with endothelial-specific Capn4 knockout (TEK/Capn4−/−), mice with calpastatin (an endogenous calpain inhibitor) overexpression (Tg-CAST) and mice with myeloid-specific Capn4 knockout (LYZ/Capn4−/−). Mouse pulmonary microvascular endothelial cells (PMECs) were used as a model of the microvascular endothelium and were stimulated with LPS. Renal function, renal inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) expression, cellular apoptosis, plasma and renal levels of NO and reactive oxygen species (ROS), and phosphorylation of mitogen-activated protein kinase (MAPK) family members (p38, ERK1/2, and JNK1/2) were examined. Moreover, a calpain inhibitor, calpastatin overexpression adenoviruses and MAPK inhibitors were used. Significant renal dysfunction was induced by LPS stimulation, and recovery was observed in TEK/Capn4−/− and Tg-CAST mice but not in LYZ/Capn4−/− mice. Endothelial Capn4 knockout also abrogated the LPS-induced increases in renal iNOS expression, caspase-3 activity and apoptosis and plasma and renal NO and ROS levels but did not obviously affect renal eNOS expression. Moreover, LPS increased both calpain and caspase-3 activity, and only the expression of iNOS in PMECs was accompanied by increased phosphorylation of p38 and JNK. Inhibiting calpain activity or p38 phosphorylation alleviated the increased iNOS expression, NO/ROS production, and cellular apoptosis induced by LPS. These results suggest that endothelial calpain plays a protective role in LPS-induced AKI by inhibiting p38 phosphorylation, thus attenuating iNOS expression and further decreasing NO and ROS overproduction-induced endothelial apoptosis.
Epigenetic mechanism of SETDB1 in brain: implications for neuropsychiatric disorders
Authors: Zhu Yueyan , Sun Daijing , Jakovcevski Mira , Jiang Yan 
Published: April 2020

AbstractNeuropsychiatric disorders are a collective of cerebral conditions with a multifactorial and polygenetic etiology. Dysregulation of epigenetic profiles in the brain is considered to play a critical role in the development of neuropsychiatric disorders. SET domain, bifurcate 1 (SETDB1), functioning as a histone H3K9 specific methyltransferase, is not only critically involved in transcriptional silencing and local heterochromatin formation, but also affects genome-wide neuronal epigenetic profiles and is essential for 3D genome integrity. Here, we provide a review of recent advances towards understanding the role of SETDB1 in the central nervous system during early neurodevelopment as well as in the adult brain, with a particular focus on studies that link its functions to neuropsychiatric disorders and related behavioral changes, and the exploration of novel therapeutic strategies targeting SETDB1.
The role of neutrophil death in chronic inflammation and cancer
Authors: Brostjan Christine , Oehler Rudolf 
Published: April 2020

AbstractThe lifespan of a neutrophil is short and limited by programmed cell death, followed by efferocytosis. When activated or exposed to insult, neutrophil death may be delayed to support neutrophil effector functions such as phagocytosis, cytokine release, and pathogen destruction by degranulation. However, neutrophils may also alter the type of cell death and thereby affect inflammatory responses and tissue remodeling. This review briefly introduces the various forms of neutrophil death including apoptosis, necrosis/necroptosis, and the formation of so-called “neutrophil extracellular traps” (NETs), and it summarizes the clearance of dead cells by efferocytosis. Importantly, distinct types of neutrophil death have been found to drive chronic inflammatory disorders and cancer. Thus, the tumor and its microenvironment can delay neutrophil apoptosis to exploit their pro-angiogenic and pro-metastatic properties. Conversely, neutrophils may enter rapid and suicidal cell death by forming extracellular traps, which are expelled DNA strands with neutrophil proteins. Components of these DNA–protein complexes such as histones, high-mobility group protein B1, or neutrophil elastase have been found to promote cancer cell proliferation, adhesion, migration, invasion, and thereby tumor metastasis. In other settings of chronic inflammatory disease such as gout, NETs have been found protective rather than detrimental, as they promoted the local degradation of pro-inflammatory cytokines by neutrophil proteases. Thus, the interaction of neutrophils with the tissue environment extends beyond the stage of the living cell and the type of neutrophil death shapes immune responses and tissue remodeling in health and disease.
Consistent RNA sequencing contamination in GTEx and other data sets
Authors: Nieuwenhuis Tim O. , Yang Stephanie Y. , Verma Rohan X. , Pillalamarri Vamsee , Arking Dan E. , Rosenberg Avi Z. , McCall Matthew N. , Halushka Marc K. 
Published: April 2020

AbstractA challenge of next generation sequencing is read contamination. We use Genotype-Tissue Expression (GTEx) datasets and technical metadata along with RNA-seq datasets from other studies to understand factors that contribute to contamination. Here we report, of 48 analyzed tissues in GTEx, 26 have variant co-expression clusters of four highly expressed and pancreas-enriched genes (PRSS1, PNLIP, CLPS, and/or CELA3A). Fourteen additional highly expressed genes from other tissues also indicate contamination. Sample contamination is strongly associated with a sample being sequenced on the same day as a tissue that natively expresses those genes. Discrepant SNPs across four contaminating genes validate the contamination. Low-level contamination affects ~40% of samples and leads to numerous eQTL assignments in inappropriate tissues among these 18 genes. This type of contamination occurs widely, impacting bulk and single cell (scRNA-seq) data set analysis. In conclusion, highly expressed, tissue-enriched genes basally contaminate GTEx and other datasets impacting analyses.
Perovskite Solar Cells: A Porous Graphitic Carbon based Hole Transporter/Counter Electrode Material Extracted from an Invasive Plant Species Eichhornia Crassipes
Authors: Pitchaiya Selvakumar , Eswaramoorthy Nandhakumar , Natarajan Muthukumarasamy , Santhanam Agilan , Asokan Vijayshankar , Madurai Ramakrishnan Venkatraman , Rangasamy Balasundaraprabhu , Sundaram Senthilarasu , Ravirajan Punniamoorthy , Velauthapillai Dhayalan 
Published: April 2020

AbstractPerovskite solar cells (PSCs) composed of organic polymer-based hole-transporting materials (HTMs) are considered to be an important strategy in improving the device performance, to compete with conventional solar cells. Yet the use of such expensive and unstable HTMs, together with hygroscopic perovskite structure remains a concern – an arguable aspect for the prospect of onsite photovoltaic (PV) application. Herein, we have demonstrated the sustainable fabrication of efficient and air-stable PSCs composed of an invasive plant (Eichhornia crassipes) extracted porous graphitic carbon (EC-GC) which plays a dual role as HTM/counter electrode. The changes in annealing temperature (~450 °C, ~850 °C and ~1000 °C) while extracting the EC-GC, made a significant impact on the degree of graphitization - a remarkable criterion in determining the device performance. Hence, the fabricated champion device-1c: Glass/FTO/c-TiO2/mp-TiO2/CH3NH3PbI3−xClx/EC-GC10@CH3NH3PbI3−x Clx/EC-GC10) exhibited a PCE of 8.52%. Surprisingly, the introduced EC-GC10 encapsulated perovskite interfacial layer at the perovskite/HTM interface helps in overcoming the moisture degradation of the hygroscopic perovskite layer in which the same champion device-1c evinced better air stability retaining its efficiency ~94.40% for 1000 hours. We believe that this present work on invasive plant extracted carbon playing a dual role, together as an interfacial layer may pave the way towards a reliable perovskite photovoltaic device at low-cost.
Modelling human CNS injury with human neural stem cells in 2- and 3-Dimensional cultures
Authors: Vagaska Barbora , Gillham Olivia , Ferretti Patrizia 
Published: April 2020

AbstractThe adult human central nervous system (CNS) has very limited regenerative capability, and injury at the cellular and molecular level cannot be studied in vivo. Modelling neural damage in human systems is crucial to identifying species-specific responses to injury and potentially neurotoxic compounds leading to development of more effective neuroprotective agents. Hence we developed human neural stem cell (hNSC) 3-dimensional (3D) cultures and tested their potential for modelling neural insults, including hypoxic-ischaemic and Ca2+-dependent injury. Standard 3D conditions for rodent cells support neuroblastoma lines used as human CNS models, but not hNSCs, but in all cases changes in culture architecture alter gene expression. Importantly, response to damage differs in 2D and 3D cultures and this is not due to reduced drug accessibility. Together, this study highlights the impact of culture cytoarchitecture on hNSC phenotype and damage response, indicating that 3D models may be better predictors of in vivo response to damage and compound toxicity.
The relationship between chronotype and intelligence: the importance of work timing
Authors: Ujma Péter P. , Baudson Tanja G. , Bódizs Róbert , Dresler Martin 
Published: April 2020

AbstractSleep-wake patterns show substantial biological determination, but they are also subject to individual choice and societal pressure. Some evidence suggests that high IQ is associated with later sleep patterns. However, it is unclear whether the relationship between IQ and later sleep is due to biological or social effects, such as the timing of working hours. We investigated the association between habitual sleep timing during work days and work-free days, working time and membership in Mensa, an organization of highly intelligent individuals (IQ  ≥130) using a sample of 1,172 adults split between Mensa members and age- and sex-matched volunteers from a large web-based database. We found no difference in chronotype, and the later sleep timing of Mensa members on work days was fully accounted for by later work start times. Our results indicate that later sleep timing in those with higher IQs is not due to physiological differences, but rather due to later work schedules. Later working times and the resulting lower social jetlag may be one of the reasons why higher IQ is associated with lower prospective morbidity and mortality.
Expectation-propagation for weak radionuclide identification at radiation portal monitors
Authors: Altmann Yoann , Di Fulvio Angela , Paff Marc G. , Clarke Shaun D. , Davies Mike E. , McLaughlin Stephen , Hero Alfred O. , Pozzi Sara A. 
Published: April 2020

AbstractWe propose a sparsity-promoting Bayesian algorithm capable of identifying radionuclide signatures from weak sources in the presence of a high radiation background. The proposed method is relevant to radiation identification for security applications. In such scenarios, the background typically consists of terrestrial, cosmic, and cosmogenic radiation that may cause false positive responses. We evaluate the new Bayesian approach using gamma-ray data and are able to identify weapons-grade plutonium, masked by naturally-occurring radioactive material (NORM), in a measurement time of a few seconds. We demonstrate this identification capability using organic scintillators (stilbene crystals and EJ-309 liquid scintillators), which do not provide direct, high-resolution, source spectroscopic information. Compared to the EJ-309 detector, the stilbene-based detector exhibits a lower identification error, on average, owing to its better energy resolution. Organic scintillators are used within radiation portal monitors to detect gamma rays emitted from conveyances crossing ports of entry. The described method is therefore applicable to radiation portal monitors deployed in the field and could improve their threat discrimination capability by minimizing “nuisance” alarms produced either by NORM-bearing materials found in shipped cargoes, such as ceramics and fertilizers, or radionuclides in recently treated nuclear medicine patients.
A synchronized VUV light source based on high-order harmonic generation at FLASH
Authors: Appi Elisa , Papadopoulou Christina C. , Mapa Jose Louise , Wesavkar Nishad , Jusko Christoph , Mosel Philip , Ališauskas Skirmantas , Lang Tino , Heyl Christoph M. , Manschwetus Bastian , Brachmanski Maciej , Braune Markus , Lindenblatt Hannes , Trost Florian , Meister Severin , Schoch Patrizia , Treusch Rolf , Moshammer Robert , Hartl Ingmar , Morgner Uwe , Kovacev Milutin 
Published: April 2020

AbstractUltrafast measurements in the extreme ultraviolet (XUV) spectral region targeting femtosecond timescales rely until today on two complementary XUV laser sources: free electron lasers (FELs) and high-harmonic generation (HHG) based sources. The combination of these two source types was until recently not realized. The complementary properties of both sources including broad bandwidth, high pulse energy, narrowband tunability and femtosecond timing, open new opportunities for two-color pump-probe studies. Here we show first results from the commissioning of a high-harmonic beamline that is fully synchronized with the free-electron laser FLASH, installed at beamline FL26 with permanent end-station including a reaction microscope (REMI). An optical parametric amplifier synchronized with the FEL burst mode drives the HHG process. First commissioning tests including electron momentum measurements using REMI, demonstrate long-term stability of the HHG source over more than 14 hours. This realization of the combination of these light sources will open new opportunities for time-resolved studies targeting different science cases including core-level ionization dynamics or the electron dynamics during the transformation of a molecule within a chemical reaction probed on femtosecond timescales in the ultraviolet to soft X-ray spectral region.
Animal bioturbation preserved in Pleistocene magadiite at Lake Magadi, Kenya Rift Valley, and its implications for the depositional environment of bedded magadiite
Authors: Buatois Luis A. , Renaut Robin W. , Owen Richard Bernhart , Behrensmeyer Anna K. , Scott Jennifer J. 
Published: April 2020

AbstractMagadiite, a rare hydrous sodium-silicate mineral [NaSi7O13(OH)3·4(H2O)], was discovered about 50 years ago in sediments around Lake Magadi, a hypersaline alkaline lake fed by hot springs in the semi-arid southern Kenya Rift Valley. Today this harsh lacustrine environment excludes most organisms except microbial extremophiles, a few invertebrates (mostly insects), highly adapted fish (Alcolapia sp.), and birds including flamingos. Burrows discovered in outcrops of the High Magadi Beds (~25–9 ka) that predate the modern saline (trona) pan show that beetles and other invertebrates inhabit this extreme environment when conditions become more favourable. Burrows (cm-scale) preserved in magadiite in the High Magadi Beds are filled with mud, silt and sand from overlying sediments. Their stratigraphic context reveals upward-shallowing cycles from mud to interlaminated mud-magadiite to magadiite in dm-scale units. The burrows were formed when the lake floor became fresher and oxygenated, after a period when magadiite precipitated in shallow saline waters. The burrows, probably produced by beetles, show that trace fossils can provide evidence for short-term (possibly years to decades) changes in the contemporary environment that might not otherwise be recognised or preserved physically or chemically in the sediment record.
Assigning a role for chemosensory signal transduction in Campylobacter jejuni biofilms using a combined omics approach
Authors: Tram Greg , Klare William P. , Cain Joel A. , Mourad Basem , Cordwell Stuart J. , Day Christopher J. , Korolik Victoria 
Published: April 2020

AbstractBiofilms of the gastroenteric pathogen C. jejuni may serve an important role in the transmission of infection from reservoirs of infection to humans. Herein, we undertook a combinatorial approach examining differential gene expression and protein abundance during biofilm formation in C. jejuni. Biofilms induced a substantial rearrangement of the C. jejuni transcriptome and proteome, with ~600 genes differentially expressed when compared to planktonic cells. Genes and proteins induced in biofilms were involved in iron metabolism and acquisition, cell division, glycan production and attachment, while those repressed were associated with metabolism, amino acid usage, and large tracts of the chemotaxis pathway. We further examined the role of chemotaxis in C. jejuni biofilm formation by examining isogenic strains with deletions of the cheV and cheW signal transduction genes. Both ∆cheV and ∆cheW exhibited a significant decrease in directed motility when compared to wild-type C. jejuni as well as demonstrating an increase in autoagglutination ability and biofilm formation. A subtle difference was also observed between the phenotypes of ∆cheV and ∆cheW mutants, both in motility and biofilm formation. This suggests roles for CheV and CheW and may present signal transduction as a potential method for modulating C. jejuni biofilm formation.
A high-resolution wind damage model for Europe
Authors: Koks E. E. , Haer. T. 
Published: April 2020

AbstractExtreme wind events are among the costliest natural disasters in Europe, causing severe damages every year. Despite the significant impact, damages related to windstorms are an understudied topic in academia. For damage estimates, the community mostly relies on post-disaster insurance data, which is often not publicly available. Few studies offer more generic tools, but again these are often based on non-disclosed insurance data. To offer a generic, high-resolution, reproducible, and publicly accessible tool, this study presents a wind damage model that is built around publicly available hazard, exposure, and vulnerability data. We apply the model to assess building damages related to extratropical storms in Europe, but the methodology is applicable globally, given data availability, and to other hazards for which similar risk frameworks can be applied. The results show that for Europe, coastal regions are affected the most, with the United Kingdom, Ireland, Germany, France, the Netherlands, and Denmark as most affected countries. We find that the modelled damage estimates are in line with reported damages for a series of historical storms. The model is distributed as an open-source model to offer a transparent and useable windstorm damage model to a broad audience.
Development of new genetic resources for faba bean (Vicia faba L.) breeding through the discovery of gene-based SNP markers and the construction of a high-density consensus map
Authors: Carrillo-Perdomo E. , Vidal A. , Kreplak J. , Duborjal H. , Leveugle M. , Duarte J. , Desmetz C. , Deulvot C. , Raffiot B. , Marget P. , Tayeh N. , Pichon J. P. , Falque M. , Martin O. C. , Burstin J. , Aubert G. 
Published: April 2020

AbstractFaba bean (Vicia faba L.) is a pulse crop of high nutritional value and high importance for sustainable agriculture and soil protection. With the objective of identifying gene-based SNPs, transcriptome sequencing was performed in order to reduce faba bean genome complexity. A set of 1,819 gene-based SNP markers polymorphic in three recombinant line populations was selected to enable the construction of a high-density consensus genetic map encompassing 1,728 markers well distributed in six linkage groups and spanning 1,547.71 cM with an average inter-marker distance of 0.89 cM. Orthology-based comparison of the faba bean consensus map with legume genome assemblies highlighted synteny patterns that partly reflected the phylogenetic relationships among species. Solid blocks of macrosynteny were observed between faba bean and the most closely-related sequenced legume species such as pea, barrel medic or chickpea. Numerous blocks could also be identified in more divergent species such as common bean or cowpea. The genetic tools developed in this work can be used in association mapping, genetic diversity, linkage disequilibrium or comparative genomics and provide a backbone for map-based cloning. This will make the identification of candidate genes of interest more efficient and will accelerate marker-assisted selection (MAS) and genomic-assisted breeding (GAB) in faba bean.
CRISPR-mediated gene targeting of CK1δ/ε leads to enhanced understanding of their role in endocytosis via phosphoregulation of GAPVD1
Authors: Guillen Rodrigo X. , Beckley Janel R. , Chen Jun-Song , Gould Kathleen L. 
Published: April 2020

AbstractHuman casein kinase 1 delta (CK1δ) and epsilon (CK1ε) are members of a conserved family of abundant, ubiquitously expressed serine/threonine kinases that regulate multiple cellular processes including circadian rhythm and endocytosis. Here, we have investigated the localization and interactomes of endogenously tagged CK1δ and CK1ε during interphase and mitosis. CK1δ and CK1ε localize to centrosomes throughout the cell cycle, and in interphase cells to the nucleus, and in both a diffuse and punctate pattern in the cytoplasm. Also, for the first time, they were detected at the midbody during cell division. Mass spectrometry analysis identified a total of 181 proteins co-purifying with a Venus multifunctional (VM)-tagged CK1δ and/or CK1ε. GTPase-activating protein and VPS9 domain-containing protein 1 (GAPVD1), a protein required for efficient endocytosis, was consistently one of the most abundant interacting partners. We demonstrate that GAPVD1 is a substrate of CK1δ/ε with up to 38 phosphorylated residues in vitro and in vivo. Wildtype and a phosphomimetic mutant of GAPVD1, but not a phospho-ablating mutant, were able to rescue defects in transferrin and EGF internalization caused by loss of endogenous GAPVD1. Our results indicate that GAPVD1 is an important interacting partner and substrate of CK1δ/ε for endocytosis.
Plasma Donors in the Southwestern United States Positively Contribute to the Diverse Therapeutic Antibody Profile of Immune Globulin Products
Authors: Ciencewicki Jonathan M. , Schouest Katherine R. , Gierman Todd M. , Vandeberg Peter J. , Gooch Barry D. 
Published: April 2020

AbstractHuman-plasma-derived immune globulin (IG) is used in augmentation therapy to provide protective levels of antibodies to patients with primary immune deficiency diseases (PIDD) and for prophylaxis against infectious diseases. To maintain the breadth of antibodies necessary for clinical protection, it is important to understand regional patterns of antibody seroprevalence in source plasma from which IG products are manufactured. In this study, source plasma from donation centers in various locations of the Southwestern quarter of the United States was surveyed for antibody titers to hepatitis A virus (HAV), measles virus (MeV), and cytomegalovirus (CMV). A broad range of anti-HAV Ig plasma titers was observed among these centers, with some centers exhibiting 3–5 times the titers of the others. Minor to no differences were observed for levels of anti-MeV and anti-CMV, respectively. Importantly, elevated anti-HAV Ig titers were broadly observed across plasma units obtained from the centers exhibiting high titers, indicative of a potential regional phenomenon among donors as opposed to few donors with singularly high titers. Plasma from these high-titer centers conferred significantly greater neutralization against HAV in vitro. The outcomes of this study give a glimpse of the antibody diversity inherent in human plasma used to manufacture IG products..