bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrinsic S phase checkpoint enforced by an antiproliferative oncosuppressor cytokine
Authors: Mallucci Livio , Wells Valerie 
Published: November 2021

AbstractThe cell cycle is strictly programmed with control mechanisms that dictate order in cell cycle progression to ensure faithful DNA replication, whose deviance may lead to cancer. Checkpoint control at the G1/S, S/G2 and G2/M portals have been defined but no statutory time-programmed control for securing orderly transition through S phase has so far been identified. Here we report that in normal cells DNA synthesis is controlled by a checkpoint sited within the early part of S phase, enforced by the βGBP cytokine an antiproliferative molecule otherwise known for its oncosuppressor properties that normal cells constitutively produce for self-regulation. Suppression of active Ras and active MAPK, block of cyclin A gene expression and suppression of CDK2-cyclin A activity are events which while specific to the control of a cell cycle phase in normal cells are part of the apoptotic network in cancer cells.
Higher intake of whole grains and dietary fiber are associated with lower risk of liver cancer and chronic liver disease mortality
Authors: Liu Xing , Yang Wanshui , Petrick Jessica L. , Liao Linda M. , Wang Weibing , He Na , Campbell Peter T. , Zhang Zuo-Feng , Giovannucci Edward , McGlynn Katherine A. , Zhang Xuehong 
Published: November 2021

AbstractThe relationship between dietary factors and liver disease remains poorly understood. This study evaluated the associations of whole grain and dietary fiber intake with liver cancer risk and chronic liver disease mortality. The National Institutes of Health–American Association of Retired Persons Diet and Health Study cohort recruited 485, 717 retired U.S. participants in 1995–1996. Follow-up through 2011 identified 940 incident liver cancer cases and 993 deaths from chronic liver disease. Compared with the lowest, the highest quintile of whole grain intake was associated with lower liver cancer risk (Hazard ratio [HR]Q5 vs. Q1 = 0.78, 95% confidence interval [CI]: 0.63–0.96) and chronic liver disease mortality (HRQ5 vs. Q1 = 0.44, 95% CI: 0.35–0.55) in multivariable Cox models. Dietary fiber was also associated with lower liver cancer risk (HRQ5 vs. Q1 = 0.69, 95% CI: 0.53–0.90) and chronic liver disease mortality (HRQ5 vs. Q1 = 0.37, 95% CI: 0.29–0.48). Fiber from vegetables, beans and grains showed potential protective effect. Here, we show that higher intake of whole grain and dietary fiber are associated with lower risk of liver cancer and liver disease mortality.
Drosophila ßHeavy-Spectrin is required in polarized ensheathing glia that form a diffusion-barrier around the neuropil
Authors: Pogodalla Nicole , Kranenburg Holger , Rey Simone , Rodrigues Silke , Cardona Albert , Klämbt Christian 
Published: November 2021

AbstractIn the central nervous system (CNS), functional tasks are often allocated to distinct compartments. This is also evident in the Drosophila CNS where synapses and dendrites are clustered in distinct neuropil regions. The neuropil is separated from neuronal cell bodies by ensheathing glia, which as we show using dye injection experiments, contribute to the formation of an internal diffusion barrier. We find that ensheathing glia are polarized with a basolateral plasma membrane rich in phosphatidylinositol-(3,4,5)-triphosphate (PIP3) and the Na+/K+-ATPase Nervana2 (Nrv2) that abuts an extracellular matrix formed at neuropil-cortex interface. The apical plasma membrane is facing the neuropil and is rich in phosphatidylinositol-(4,5)-bisphosphate (PIP2) that is supported by a sub-membranous ßHeavy-Spectrin cytoskeleton. ßHeavy-spectrin mutant larvae affect ensheathing glial cell polarity with delocalized PIP2 and Nrv2 and exhibit an abnormal locomotion which is similarly shown by ensheathing glia ablated larvae. Thus, polarized glia compartmentalizes the brain and is essential for proper nervous system function.
Smad4 controls signaling robustness and morphogenesis by differentially contributing to the Nodal and BMP pathways
Authors: Guglielmi Luca , Heliot Claire , Kumar Sunil , Alexandrov Yuriy , Gori Ilaria , Papaleonidopoulou Foteini , Barrington Christopher , East Philip , Economou Andrew D. , French Paul M. W. , McGinty James , Hill Caroline S. 
Published: November 2021

AbstractThe transcriptional effector SMAD4 is a core component of the TGF-β family signaling pathways. However, its role in vertebrate embryo development remains unresolved. To address this, we deleted Smad4 in zebrafish and investigated the consequences of this on signaling by the TGF-β family morphogens, BMPs and Nodal. We demonstrate that in the absence of Smad4, dorsal/ventral embryo patterning is disrupted due to the loss of BMP signaling. However, unexpectedly, Nodal signaling is maintained, but lacks robustness. This Smad4-independent Nodal signaling is sufficient for mesoderm specification, but not for optimal endoderm specification. Furthermore, using Optical Projection Tomography in combination with 3D embryo morphometry, we have generated a BMP morphospace and demonstrate that Smad4 mutants are morphologically indistinguishable from embryos in which BMP signaling has been genetically/pharmacologically perturbed. Smad4 is thus differentially required for signaling by different TGF-β family ligands, which has implications for diseases where Smad4 is mutated or deleted.
A compendium of chromatin contact maps reflecting regulation by chromatin remodelers in budding yeast
Authors: Jo Hyelim , Kim Taemook , Chun Yujin , Jung Inkyung , Lee Daeyoup 
Published: November 2021

AbstractWe herein employ in situ Hi-C with an auxin-inducible degron (AID) system to examine the effect of chromatin remodeling on 3D genome organization in yeast. Eight selected ATP-dependent chromatin remodelers representing various subfamilies contribute to 3D genome organization differently. Among the studied remodelers, the temporary depletions of Chd1p, Swr1p, and Sth1p (a catalytic subunit of the Remodeling the Structure of Chromatin [RSC] complex) cause the most significant defects in intra-chromosomal contacts, and the regulatory roles of these three remodelers in 3D genome organization differ depending on the chromosomal context and cell cycle stage. Furthermore, even though Chd1p and Isw1p are known to share functional similarities/redundancies, their depletions lead to distinct effects on 3D structures. The RSC and cohesin complexes also differentially modulate 3D genome organization within chromosome arm regions, whereas RSC appears to support the function of cohesin in centromeric clustering at G2 phase. Our work suggests that the ATP-dependent chromatin remodelers control the 3D genome organization of yeast through their chromatin-remodeling activities.
The origin and impeded dissemination of the DNA phosphorothioation system in prokaryotes
Authors: Jian Huahua , Xu Guanpeng , Yi Yi , Hao Yali , Wang Yinzhao , Xiong Lei , Wang Siyuan , Liu Shunzhang , Meng Canxing , Wang Jiahua , Zhang Yue , Chen Chao , Feng Xiaoyuan , Luo Haiwei , Zhang Hao , Zhang Xingguo , Wang Lianrong , Wang Zhijun , Deng Zixin , Xiao Xiang 
Published: November 2021

AbstractPhosphorothioate (PT) modification by thedndgene cluster is the first identified DNA backbone modification and constitute an epigenetic system with multiple functions, including antioxidant ability, restriction modification, and virus resistance. Despite these advantages for hostingdndsystems, they are surprisingly distributed sporadically among contemporary prokaryotic genomes. To address this ecological paradox, we systematically investigate the occurrence and phylogeny ofdndsystems, and they are suggested to have originated in ancient Cyanobacteria after the Great Oxygenation Event. Interestingly, the occurrence ofdndsystems and prophages is significantly negatively correlated. Further, we experimentally confirm that PT modification activates the filamentous phage SW1 by altering the binding affinity of repressor and the transcription level of its encoding gene. Competition assays, concurrent epigenomic and transcriptomic sequencing subsequently show that PT modification affects the expression of a variety of metabolic genes, which reduces the competitive fitness of the marine bacteriumShewanella piezotoleransWP3. Our findings strongly suggest that a series of negative effects on microorganisms caused bydndsystems limit horizontal gene transfer, thus leading to their sporadic distribution. Overall, our study reveals putative evolutionary scenario of thedndsystem and provides novel insights into the physiological and ecological influences of PT modification.
Graphene’s non-equilibrium fermions reveal Doppler-shifted magnetophonon resonances accompanied by Mach supersonic and Landau velocity effects
Authors: Greenaway M. T. , Kumaravadivel P. , Wengraf J. , Ponomarenko L. A. , Berdyugin A. I. , Li J. , Edgar J. H. , Kumar R. Krishna , Geim A. K. , Eaves L. 
Published: November 2021

AbstractOscillatory magnetoresistance measurements on graphene have revealed a wealth of novel physics. These phenomena are typically studied at low currents. At high currents, electrons are driven far from equilibrium with the atomic lattice vibrations so that their kinetic energy can exceed the thermal energy of the phonons. Here, we report three non-equilibrium phenomena in monolayer graphene at high currents: (i) a “Doppler-like” shift and splitting of the frequencies of the transverse acoustic (TA) phonons emitted when the electrons undergo inter-Landau level (LL) transitions; (ii) an intra-LL Mach effect with the emission of TA phonons when the electrons approach supersonic speed, and (iii) the onset of elastic inter-LL transitions at a critical carrier drift velocity, analogous to the superfluid Landau velocity. All three quantum phenomena can be unified in a single resonance equation. They offer avenues for research on out-of-equilibrium phenomena in other two-dimensional fermion systems.
Benchmarking pipelines for subclonal deconvolution of bulk tumour sequencing data
Authors: Tanner Georgette , Westhead David R. , Droop Alastair , Stead Lucy F. 
Published: November 2021

AbstractIntratumour heterogeneity provides tumours with the ability to adapt and acquire treatment resistance. The development of more effective and personalised treatments for cancers, therefore, requires accurate characterisation of the clonal architecture of tumours, enabling evolutionary dynamics to be tracked. Many methods exist for achieving this from bulk tumour sequencing data, involving identifying mutations and performing subclonal deconvolution, but there is a lack of systematic benchmarking to inform researchers on which are most accurate, and how dataset characteristics impact performance. To address this, we use the most comprehensive tumour genome simulation tool available for such purposes to create 80 bulk tumour whole exome sequencing datasets of differing depths, tumour complexities, and purities, and use these to benchmark subclonal deconvolution pipelines. We conclude that i) tumour complexity does not impact accuracy, ii) increasing either purity or purity-corrected sequencing depth improves accuracy, and iii) the optimal pipeline consists of Mutect2, FACETS and PyClone-VI. We have made our benchmarking datasets publicly available for future use.
The efficacy of chlorine-based disinfectants against planktonic and biofilm bacteria for decentralised point-of-use drinking water
Authors: Clayton Gillian E. , Thorn Robin M. S. , Reynolds Darren M. 
Published: November 2021

AbstractChlorine solutions are used extensively for the production of biologically safe drinking water. The capability of point-of-use [POU] drinking water treatment systems has gained interest in locations where centralised treatment systems and distribution networks are not practical. This study investigated the antimicrobial and anti-biofilm activity of three chlorine-based disinfectants (hypochlorite ions [OCl-], hypochlorous acid [HOCl] and electrochemically activated solutions [ECAS]) for use in POU drinking water applications. The relative antimicrobial activity was compared within bactericidal suspension assays (BS EN 1040 and BS EN 1276) using Escherichia coli. The anti-biofilm activity was compared utilising established sessile Pseudomonas aeruginosa within a Centre for Disease Control [CDC] biofilm reactor. HOCl exhibited the greatest antimicrobial activity against planktonic E. coli at >50 mg L−1 free chlorine, in the presence of organic loading (bovine serum albumen). However, ECAS exhibited significantly greater anti-biofilm activity compared to OCl- and HOCl against P. aeruginosa biofilms at ≥50 mg L−1 free chlorine. Based on this evidence disinfectants where HOCl is the dominant chlorine species (HOCl and ECAS) would be appropriate alternative chlorine-based disinfectants for POU drinking water applications.
H3K9me selectively blocks transcription factor activity and ensures differentiated tissue integrity
Authors: Methot Stephen P. , Padeken Jan , Brancati Giovanna , Zeller Peter , Delaney Colin E. , Gaidatzis Dimos , Kohler Hubertus , van Oudenaarden Alexander , Großhans Helge , Gasser Susan M. 
Published: November 2021

AbstractThe developmental role of histone H3K9 methylation (H3K9me), which typifies heterochromatin, remains unclear. In Caenorhabditis elegans, loss of H3K9me leads to a highly divergent upregulation of genes with tissue and developmental-stage specificity. During development H3K9me is lost from differentiated cell type-specific genes and gained at genes expressed in earlier developmental stages or other tissues. The continuous deposition of H3K9me2 by the SETDB1 homolog MET-2 after terminal differentiation is necessary to maintain repression. In differentiated tissues, H3K9me ensures silencing by restricting the activity of a defined set of transcription factors at promoters and enhancers. Increased chromatin accessibility following the loss of H3K9me is neither sufficient nor necessary to drive transcription. Increased ATAC-seq signal and gene expression correlate at a subset of loci positioned away from the nuclear envelope, while derepressed genes at the nuclear periphery remain poorly accessible despite being transcribed. In conclusion, H3K9me deposition can confer tissue-specific gene expression and maintain the integrity of terminally differentiated muscle by restricting transcription factor activity.
Premature differentiation of nephron progenitor cell and dysregulation of gene pathways critical to kidney development in a model of preterm birth
Authors: Cwiek Aleksandra , Suzuki Masako , deRonde Kimberly , Conaway Mark , Bennett Kevin M. , El Dahr Samir , Reidy Kimberly J. , Charlton Jennifer R. 
Published: November 2021

AbstractPreterm birth is a leading cause of neonatal morbidity. Survivors have a greater risk for kidney dysfunction and hypertension. Little is known about the molecular changes that occur in the kidney of individuals born preterm. Here, we demonstrate that mice delivered two days prior to full term gestation undergo premature cessation of nephrogenesis, resulting in a lower glomerular density. Kidneys from preterm and term groups exhibited differences in gene expression profiles at 20- and 27-days post-conception, including significant differences in the expression of fat-soluble vitamin-related genes. Kidneys of the preterm mice exhibited decreased proportions of endothelial cells and a lower expression of genes promoting angiogenesis compared to the term group. Kidneys from the preterm mice also had altered nephron progenitor subpopulations, early Six2 depletion, and altered Jag1 expression in the nephrogenic zone, consistent with premature differentiation of nephron progenitor cells. In conclusion, preterm birth alone was sufficient to shorten the duration of nephrogenesis and cause premature differentiation of nephron progenitor cells. These candidate genes and pathways may provide targets to improve kidney health in preterm infants.
Biogeochemical impacts of flooding discharge with high suspended sediment on coastal seas: a modeling study for a microtidal open bay
Authors: Hoshiba Yasuhiro , Hasumi Hiroyasu , Itoh Sachihiko , Matsumura Yoshimasa , Nakada Satoshi 
Published: November 2021

AbstractFreshwater, suspended sediment matter (SSM), and nutrients discharged from rivers into the ocean have large impacts on biological production. In particular, during floods, coastal areas are greatly stirred up and large amounts of nutrients are supplied to the sea surface. We investigate the biogeochemical impact of flooding river discharges containing a large amount of SSM by conducting numerical simulations for a specific flooding event of the Yura River, Japan. Parameters are varied over wide ranges of SSM properties and nutrient content in riverine water. Two qualitatively different regimes of the riverine plume, hypopycnal and hyperpycnal, appear within realistic parameter ranges. Compared with the reference case without SSM, the surface salinity (nutrients) within the riverine plume becomes lower (higher) in hypopycnal cases and higher (lower) in hyperpycnal cases within a few days after the flooding discharge. These results suggest the necessity of properly taking into account the effect of SSM in assessing the influence of high river discharges on coastal biogeochemistry. It is the case not only for the specific river and event we are dealing with but also for other flooding events and other rivers and connecting coastal seas.
High-throughput sequencing for species authentication and contamination detection of 63 cell lines
Authors: Lung Oliver , Candlish Rebecca , Nebroski Michelle , Kruckiewicz Peter , Buchanan Cody , Moniwa Mariko 
Published: November 2021

AbstractCell lines are widely used in research and for diagnostic tests and are often shared between laboratories. Lack of cell line authentication can result in the use of contaminated or misidentified cell lines, potentially affecting the results from research and diagnostic activities. Cell line authentication and contamination detection based on metagenomic high-throughput sequencing (HTS) was tested on DNA and RNA from 63 cell lines available at the Canadian Food Inspection Agency’s National Centre for Foreign Animal Disease. Through sequence comparison of the cytochrome c oxidase subunit 1 (COX1) gene, the species identity of 53 cell lines was confirmed, and eight cell lines were found to show a greater pairwise nucleotide identity in the COX1 sequence of a different species within the same expected genus. Two cell lines, LFBK-αvβ6 and SCP-HS, were determined to be composed of cells from a different species and genus. Mycoplasma contamination was not detected in any cell lines. However, several expected and unexpected viral sequences were detected, including part of the classical swine fever virus genome in the IB-RS-2 Clone D10 cell line. Metagenomics-based HTS is a useful laboratory QA tool for cell line authentication and contamination detection that should be conducted regularly.
Carbon range verification with 718 keV Compton imaging
Authors: Parajuli Raj Kumar , Sakai Makoto , Arakawa Kazuo , Kubota Yoshiki , Kubo Nobuteru , Tashiro Mutsumi 
Published: November 2021

AbstractCarbon ion radiotherapy is a sophisticated radiation treatment modality because of its superiority in achieving precise dosage distribution and high biological effectiveness. However, there exist beam range uncertainties that affect treatment efficiency. This problem can be resolved if the clinical beam could be monitored precisely in real-time, such as by imaging the prompt gamma emission from the target. In this study, we performed real-time detection and imaging of 718 keV prompt gamma emissions using a Si/CdTe Compton camera. We conducted experiments on graphite phantoms using clinical carbon ion beams of 290 MeV/u energy. Compton images were reconstructed using simple back-projection methods from the energy events of 718 keV prompt gamma emissions. The peak intensity position in reconstructed 718 keV prompt gamma images was few millimeters below the Bragg peak position. Moreover, the dual- and triple-energy window images for all positions of phantoms were not affected by scattered gammas, and their peak intensity positions were approximately similar to those observed in the reconstructed 718 keV prompt gamma images. In conclusion, the findings of the current study demonstrate the feasibility of using our Compton camera for real-time beam monitoring of carbon ion beams under clinical beam intensity.
Desmoglein 2 regulates cardiogenesis by restricting hematopoiesis in the developing murine heart
Authors: Moazzen Hoda , Venger Kateryna , Kant Sebastian , Leube Rudolf E. , Krusche Claudia A. 
Published: November 2021

AbstractCardiac morphogenesis relies on intricate intercellular signaling. Altered signaling impacts cardiac function and is detrimental to embryonic survival. Here we report an unexpected regulatory role of the desmosomal cell adhesion molecule desmoglein 2 (Dsg2) on murine heart development. A large percentage of Dsg2-mutant embryos develop pericardial hemorrhage. Lethal myocardial rupture is occasionally observed, which is not associated with loss of cardiomyocyte contact but with expansion of abnormal, non-myocyte cell clusters within the myocardial wall. Two types of abnormal cell clusters can be distinguished: Type A clusters involve endocard-associated, round-shaped CD31+ cells, which proliferate and invade the myocardium. They acquire Runx1- and CD44-positivity indicating a shift towards a hematopoietic phenotype. Type B clusters expand subepicardially and next to type A clusters. They consist primarily of Ter119+ erythroid cells with interspersed Runx1+/CD44+ cells suggesting that they originate from type A cell clusters. The observed pericardial hemorrhage is caused by migration of erythrocytes from type B clusters through the epicardium and rupture of the altered cardiac wall. Finally, evidence is presented that structural defects of Dsg2-depleted cardiomyocytes are primary to the observed pathogenesis. We propose that cardiomyocyte-driven paracrine signaling, which likely involves Notch1, directs subsequent trans-differentiation of endo- and epicardial cells. Together, our observations uncover a hitherto unknown regulatory role of Dsg2 in cardiogenesis.
Estimating the impact of virus testing strategies on the COVID-19 case fatality rate using fixed-effects models
Authors: Terriau Anthony , Albertini Julien , Montassier Emmanuel , Poirier Arthur , Le Bastard Quentin 
Published: November 2021

AbstractThe SARS-CoV2 has now spread worldwide causing over four million deaths. Testing strategies are highly variable between countries and their impact on mortality is a major issue. Retrospective multicenter study with a prospective database on all inpatients throughout mainland France. Using fixed effects models, we exploit policy discontinuities at region borders in France to estimate the effect of testing on the case fatality rate. In France, testing policies are determined at a regional level, generating exogenous variation in testing rates between departments on each side of a region border. We compared all contiguous department pairs located on the opposite sides of a region border. The increase of one percentage point in the test rate is associated with a decrease of 0.0015 percentage point in the death rate, that is, for each additional 2000 tests, we could observe three fewer deaths. Our study suggests that COVID-19 population testing could have a significant impact on the mortality rate which should be considered in decision-making. As concern grows over the current second wave of COVID-19, our findings support the implementation of large-scale screening strategies in such epidemic contexts.