bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome reconfiguration prior to mitosis shapes the generation of adaptive immunity
Authors: Chan Wing Fuk , Coughlan Hannah D. , Zhou Jie H.S. , Keenan Christine R. , Bediaga Naiara G. , Hodgkin Phillip D. , Smyth Gordon K. , Johanson Timothy M. , Allan Rhys S. 
Published: September 2019

AbstractDuring cellular differentiation chromosome conformation is altered to support the lineage-specific transcriptional programs required for cell identity. When these changes occur in relation to cell cycle, division and time is unclear. Here we followed B lymphocytes as they differentiated from a naïve, quiescent state into antibody secreting plasma cells. Unexpectedly, we found that gene-regulatory chromosome reorganization occurred prior to the first division, in late G1 phase and that this configuration is maintained as the cells rapidly cycle during clonal expansion. A second wave of architectural changes also occurred later as cells differentiated into plasma cells and this was associated with increased time in G1 phase. These data provide an explanation for how lymphocyte fate is imprinted prior to the first division and suggest that chromosome reconfiguration is spatiotemporally separated from DNA replication and mitosis to ensure the implementation of a gene regulatory program that controls the differentiation process required for the generation of immunity.One Sentence SummaryDiscrete waves of genome reorganization, spatiotemporally separated from DNA replication and mitosis, control cell differentiation.
Does higher sampling rate (Multiband + SENSE) benefit the detection of task correlated BOLD for cognitive neuroscience applications at 3T?
Authors: Bhandari Ritu , Kirilina Evgeniya , Caan Matthan , Suttrup Judith , de Sanctis Teresa , De Angelis Lorenzo , Keysers Christian , Gazzola Valeria 
Published: September 2019

AbstractMultiband (MB) or Simultaneous multi-slice (SMS) acquisition schemes allow the acquisition of MRI signals from more than one spatial coordinate at a time. Commercial availability has brought this technique within the reach of many neuroscientists and psychologists. Most early evaluation of the performance of MB acquisition employed resting state fMRI or the most basic tasks. In this study, we tested whether the advantages of using MB acquisition schemes generalize to group analyses using a cognitive task more representative of typical cognitive neuroscience applications. Twenty-three subjects were scanned on a Philips 3T scanner using five sequences up to eight-fold acceleration with MB-factors 1 to 4, SENSE factors up to 2 and corresponding TRs of 2.45s down to 0.63s, while they viewed (i) movies showing complex actions with hand object interactions and (ii) control movies without hand object interaction. Using random effects group-level, voxel-wise analysis we found that all sequences were able to detect the basic action observation network known to be recruited by our task. The highest t-values were found for sequences with MB4 acceleration. For the MB1 sequence, a 50% bigger voxel volume was needed to reach comparable t-statistics. The group-level t-values for resting state networks (RSNs) were also highest for MB4 sequences. Here the MB1 sequence with larger voxel size did not perform comparable to the MB4 sequence. Altogether, we can thus recommend the use of MB4 (and SENSE 1.5 or 2) on a Philips scanner when aiming to perform group-level analyses using cognitive block design fMRI tasks and voxel sizes in the range of cortical thickness (e.g. 2.7mm isotropic). While results will not be dramatically changed by the use of multiband, our results suggest that MB will bring a moderate but significant benefit.
Structural Diversity of B-Cell Receptor Repertoires along the B-cell Differentiation Axis in Humans and Mice
Authors: Kovaltsuk Aleksandr , Raybould Matthew I. J. , Wong Wing Ki , Marks Claire , Kelm Sebastian , Snowden James , Trück Johannes , Deane Charlotte M. 
Published: September 2019

AbstractMost current analysis tools for antibody next-generation sequencing data work with primary sequence descriptors, leaving accompanying structural information unharnessed. We have used novel rapid methods to structurally characterize the paratopes of more than 180 million human and mouse B-cell receptor (BCR) repertoire sequences. These structurally annotated paratopes provide unprecedented insights into both the structural predetermination and dynamics of the adaptive immune response. We show that B-cell types can be distinguished based solely on these structural properties. Antigen-unexperienced BCR repertoires use the highest number and diversity of paratope structures and these patterns of naïve repertoire paratope usage are highly conserved across subjects. In contrast, more differentiated B-cells are more personalized in terms of paratope structure usage. Our results establish the paratope structure differences in BCR repertoires and have applications for many fields including immunodiagnostics, phage display library generation, and “humanness” assessment of BCR repertoires from transgenic animals.
Evolutionary unique mechanistic framework of clathrin-mediated endocytosis in plants
Authors: Narasimhan Madhumitha , Johnson Alexander , Prizak Roshan , Kaufmann Walter Anton , Casillas-Pérez Barbara , Friml Jiří 
Published: September 2019

SUMMARYIn plants, clathrin mediated endocytosis (CME) represents the major route for cargo internalisation from the cell surface. It has been assumed to operate in an evolutionary conserved manner as in yeast and animals. Here we report characterisation of ultrastructure, dynamics and mechanisms of plant CME as allowed by our advancement in electron microscopy and quantitative live imaging techniques. Arabidopsis CME follows the constant curvature model and the bona fide CME population generates vesicles of a predominantly hexagonal type; larger and with faster kinetics than in other models. Contrary to the existing paradigm, actin is dispensable for CME events at the surface but plays a unique role in collecting endocytic vesicles, sorting of internalised cargos and directional endosome movement that itself actively promote CME events. Internalized vesicles display a strongly delayed and sequential uncoating. These unique features highlight the independent evolution of the plant CME mechanism during the autonomous rise of multicellularity in eukaryotes.
Color-specific porosity in double pigmented natural 3d-nanoarchitectures of blue crab shell
Authors: Nekvapil Fran , Cintă Pinzaru Simona , Barbu–Tudoran Lucian , Suciu Maria , Glamuzina Branko , Tamaş Tudor , Chiş Vasile 
Published: September 2019

Abstract3D-engineered nanoarchitectures with various functionalities are still difficult to obtain and translate for real-world applications. However, such nanomaterials are naturally abundant and yet wasted, but could trigger huge interest for blue bioeconomy, provided that our understanding of their ultrastructure-function is achieved. To date, the Bouligand pattern in crustaceans shell structure is believed to be unique. Here we demonstrated that in blue crab Callinectes sapidus, the 3D-nanoarchitecture is color-specific, while the blue and red-orange pigments interplay in different nano-sized channels and pores. Thinnest pores of about 20 nm are found in blue shell. Additionally, the blue pigment co-existence in specific Bouligand structure is proved for the green crab Carcinus aestuarii, although the crab does not appear blue. The pigments interplay, simultaneously detected in color-specific, native crab shells overturns our understanding in crustaceans coloration and may trigger the selective use of particular colored natural nanoarchitectures for biomolecular loading and slow release, infectious barriers, bioremediation, translational diffusivity and many others.
The positive role of noise for information acquisition in biological signaling pathways
Authors: Azpeitia Eugenio , Wagner Andreas 
Published: September 2019

AbstractAll living systems acquire information about their environment. At the cellular level, they do so through signaling pathways, which rely on interactions between molecules that detect and transmit the presence of an extracellular cue or signal to the cell’s interior. Such interactions are inherently stochastic and thus noisy. In classical information theory, a noisy communication channel degrades the amount of transmissible information relative to a noise-free channel. For this reason, one would expect that the kinetic parameters that determine a pathway’s operation minimize noise. We show that this is not the case under a wide range of biologically sensible parameter values. Specifically, we perform computational simulations of simple signaling systems, which show that a noisy molecular interaction dynamics is a necessary condition for information acquisition. Moreover, we show that optimal information acquisition, where a system reacts most sensitively to changes in the environment, can be obtained close to the maximal attainable level of noise in the system. Our work highlights the positive role that noise can have in biological information processing.Author summaryThe acquisition of information is fundamental for living systems, because the decisions they take based on such information directly affect survival and reproduction. The molecular mechanisms used by cells to acquire information are signaling pathways. The molecular interactions of signaling pathways, such as the binding of a signal to a receptor, are by nature noisy. This is important, because noise disrupts information. Hence, to maximize the acquisition of information, signaling pathways should minimize the noise of their molecular interactions. Here we show that a noisy dynamic of the molecular interactions can improve the acquisition of information, and that the maximal capacity to acquire information can be obtained with a close-to-maximal level of noise in a signaling pathway. Thus, contrary to expectations, noise can improve the acquisition of information in living systems.
Co-circulation of Dengue Virus Serotypes 1 and 3 during the 2019 epidemic in Dar es Salaam, Tanzania
Authors: Mwanyika Gaspary , Mboera Leonard E.G. , Rugarabamu Sima , Lutwama Julius , Sindato Calvin , Paweska Janusz T. , Misinzo Gerald 
Published: September 2019

AbstractBackgroundDengue is an important mosquito-borne viral disease in tropical and sub-tropical countries. In this study molecular characterization was carried out to determine dengue viruses circulating among patients at health facilities during 2019 epidemic in Dar es Salaam, Tanzania.MethodsThe study involved outpatients seeking care for febrile illness at four health facilities in Kinondoni and Ilala Districts of Dar es Salaam City in Tanzania. A total of 45 sera from the outpatients were confirmed dengue-positive for dengue virus (DENV) non-structural protein 1 (NS1) antigen and/or NS1-IgG/IgM antibodies using on-site rapid test. The presence of the virus was detected by reverse-transcription polymerase chain reaction (RT-PCR) method. Of the 45 sera, 20 samples were selected randomly for identification of specific dengue virus serotypes using RT-PCR followed by evaluation of resulting amplicons on agarose gel electrophoresis.Findings and significanceBoth Dengue virus serotypes 1 (DENV-1) and 3 (DENV-3) were detected in the samples tested with the former being dominant. We present the first evidence of dengue virus co-infection of DENV-1 and DENV-3 serotypes in Tanzania. The emergence of DENV-1 indicates the possibility of importation of the virus to Tanzania from endemic countries. Due to DENV serotype co-circulation, there is an increased risk of severe dengue in future epidemics. Our findings advocate the importance of genomic-based surveillance to provide rapid evidence of dengue virus emergence/re-emergence and spread.Author SummaryDengue viruses are the most important mosquito-borne pathogens that pose a serious global health threat. Tanzania has reported several dengue virus epidemics since 2010 with the majority of the epidemics occurring in Dar-es-Salaam city. Until August 2019, a total of 6,859 dengue cases have been confirmed in the country. We performed molecular characterization of dengue viruses (DENV) circulating during the 2019 epidemic phase. It was found that DENV-1 serotype was dominant during the epidemic and two samples of the tested sera were co-infected by DENV-1 and DENV-3 serotypes. These findings emphasize the importance of genomic-based surveillance of dengue viruses in Tanzania to guide strategies for appropriate interventions.
Adaptive iron utilization compensates for the lack of an inducible uptake system inNaegleria fowleriand represents a potential target for therapeutic intervention
Authors: Arbon Dominik , Ženíšková Kateřina , Mach Jan , Grechnikova Maria , Malych Ronald , Talacko Pavel , Sutak Robert 
Published: September 2019

AbstractWarm fresh water is a natural habitat for many single-celled organisms, including protozoan parasites such as the infamous brain-eating amoeba,Naegleria fowleri,which can become pathogenic for mammals, including humans. The condition caused byN. fowleriis known as primary amoebic meningoencephalitis, which is a generic and usually fatal infection of the brain with rapid onset. One of the important factors influencing a wide spectrum of pathogens, includingN. fowleri, is the bioavailability of iron in the environment. The strategy of withholding iron evolved in mammalian hosts, and the different strategies of pathogens to obtain it are an important part of host-parasite interactions.In the present study, we employ different biochemical and analytical methods to explore the effect of decreased iron availability on the cellular processes ofN. fowleri. We show that under iron starvation, nonessential, iron-dependent, mostly cytosolic pathways inN. fowleriare downregulated, while the metal is utilized in the mitochondria to maintain vital respiratory processes. Surprisingly,N. fowlerifails to respond to acute shortages of iron by the induction of a reductive iron uptake system that seems to be the main iron-obtaining strategy of the parasite. Our work aims to demonstrate the importance of mitochondrial iron in the biology ofN. fowleriand to explore the plausibility of exploiting it as a potential target for therapeutic interference.Author SummaryNaegleria fowleriis undoubtedly one of the deadliest parasites of humans, hence the name “brain-eating amoeba”. Being dangerous, but rare, it may be regarded as a highly understudied pathogen of humans. Unfortunately, the symptoms of primary amoebic meningoencephalitis may be confused with much more common bacterial meningoencephalitis; therefore, it is quite probable that many infections caused byN. fowlerihave been misdiagnosed as bacterial infections without further inquiry. In many cases, fast diagnosis is vital for commencing the correct therapy, and even then, complete success of the treatment is very rare. Our laboratory focuses on the uptake and intracellular metabolism of metals in unicellular eukaryotes, so we decided to explore the biology ofN. fowlerifrom this aspect. Changes in the proteome, as a direct effect of iron-deficient conditions, were described, and these data were used to further explore the ways in whichN. fowleriresponds to these conditions on a cellular level and how its biology changes. Based on these findings, we propose that the struggle ofN. fowlerito obtain iron from its host could be exploited for therapeutic interference purposes in primary amoebic meningoencephalitis patients.
BWGS: a R package for genomic selection and its application to a wheat breeding programme
Authors: Charmet Gilles , Tran Louis Gautier , Auzanneau Jérôme , Rincent Renaud , Bouchet Sophie 
Published: September 2019

AbstractWe developed an integrated R library called BWGS to enable easy computation of Genomic Estimates of Breeding values (GEBV) for genomic selection. BWGS relies on existing R-libraries, all freely available from CRAN servers. The two main functions enable to run 1) replicated random cross validations within a training set of genotyped and phenotyped lines and 2) GEBV prediction, for a set of genotyped-only lines. Options are available for 1) missing data imputation, 2) markers and training set selection and 3) genomic prediction with 15 different methods, either parametric or semi-parametric.The usefulness and efficiency of BWGS are illustrated using a population of wheat lines from a real breeding programme. Adjusted yield data from historical trials (highly unbalanced design) were used for testing the options of BWGS. On the whole, 760 candidate lines with adjusted phenotypes and genotypes for 47 839 robust SNP were used. With a simple desktop computer, we obtained results which compared with previously published results on wheat genomic selection. As predicted by the theory, factors that are most influencing predictive ability, for a given trait of moderate heritability, are the size of the training population and a minimum number of markers for capturing every QTL information. Missing data up to 40%, if randomly distributed, do not degrade predictive ability once imputed, and up to 80% randomly distributed missing data are still acceptable once imputed with Expectation-Maximization method of package rrBLUP. It is worth noticing that selecting markers that are most associated to the trait do improve predictive ability, compared with the whole set of markers, but only when marker selection is made on the whole population. When marker selection is made only on the sampled training set, this advantage nearly disappeared, since it was clearly due to overfitting. Few differences are observed between the 15 prediction models with this dataset. Although non-parametric methods that are supposed to capture non-additive effects have slightly better predictive accuracy, differences remain small. Finally, the GEBV from the 15 prediction models are all highly correlated to each other. These results are encouraging for an efficient use of genomic selection in applied breeding programmes and BWGS is a simple and powerful toolbox to apply in breeding programmes or training activities.
Glucose availability impacts proteotoxic stress in Caenorhabditis elegans
Authors: Gatrell Landon , Wilkins Whitney , Rana Priya , Farris Mindy 
Published: September 2019

AbstractAlterations in protein folding may lead to aggregation of misfolded proteins, which is strongly correlated with neurotoxicity and cell death. Protein aggregation has been shown as a normal consequence of aging, but it is largely associated with age-related disease, particularly neurodegenerative diseases like Huntington disease (HD). Huntington disease is caused by a CAG repeat expansion in the huntingtin gene and serves as a useful model for neurodegeneration due to its strictly genetic origin. Research in the model organism Caenorhabditis elegans suggests that glucose protects against cell stress, including proteotoxicity related to aggregation, despite the well-known, lifespan-shortening effects of glucose. We hypothesized that glucose could be beneficial by alleviating energy deficiency, a well-characterized phenomenon in HD, or by upregulating stress resistance pathways. We used C. elegans expressing polyglutamine repeats to quantify lifespan, motility, reproduction, learning, and activity of succinate dehydrogenase (SDH), with and without glucose, to identify the role of glucose in proteotoxicity and neuroprotection. Our data show HD worms on glucose plates exhibited shorter lifespans, no change in motility, learning, or SDH product formation, but had altered reproductive phenotypes similar to dietary restriction. Additionally, worms expressing toxic polyglutamine repeats were unable to learn association of food with a neutral odorant. We also observed tissue-specific differences; polyglutamine appeared to be slightly more toxic to muscle cells than neurons. Rather than increasing energy production, glucose appeared to decrease mitochondrial metabolism, as SDH formation decreases with added glucose. Future work investigating glucose-mediated neuroprotection should focus on connecting metabolism, sirtuin activation, and DAF-16 activation.
ASK1/p38-mediated NLRP3 inflammasome signaling pathway contributed to aberrant retinal angiogenesis in diabetic retinopathy
Authors: Zou Wenjun , Zhang Zhengwei , Luo Shasha , Cheng Libo , Huang Xiaoli , Ding Nannan , Yu Jinjin , Pan Ying , Wu Zhifeng 
Published: September 2019

AbstractsDiabetic retinopathy is the leading cause of blindness in the working-age population in many countries. Despite the available treatments, some patients present late in the course of the disease when treatment is more difficult. Hence, it is crucial that the new targets are found and utilized in clinical therapy of diabetic retinopathy. In this study, we constructed the DR animal model and the high model in HRMEC cell to investigate the relationship between ASK1/p38 and NLRP3 in DR. The results showed that DR could cause the inflammatory response and microvascular proliferation. NLRP3 contributed to DR-mediated inflammatory development and progression, which promoted the inflammatory related cytokine expression. Meanwhile, it could promote the tube formation of retinal microvascular endothelial and angiogenesis. Moreover, further research showed that NLRP3 mediated aberrant retinal angiogenesis in diabetic retinopathy was regulated by ASK1 and p38. It suggested that ASK1/p38 could become a new target in DR treatment.
Root production in a subtropical pasture is mediated by cultivar and defoliation severity
Authors: Wilson Chris H. , Vendramini Joao M. , Sollenberger Lynn E. , Flory S. Luke 
Published: September 2019

AbstractBackgroundGrasslands occupy significant land area and account for a large proportion of the global soil carbon stock, yet the direct effects of grazing and genotypic composition on relationships between shoot and root production are poorly resolved. This lack of understanding hinders the development of models for predicting root production in managed grasslands, a critical variable for determining soil carbon stocks.MethodsWe quantified the effects of season-long defoliation treatments on both shoot and root production across four cultivars of a widely-planted pasture grass species (Paspalum notatum Fluegge) in a common garden setting in South Florida, USA.ResultsWe found that infrequently applied (4 week) severe defoliation (to 5 cm) substantially enhanced shoot production for all cultivars, while severe defoliation reduced root production across cultivars, regardless of frequency. Overall, cultivars varied substantially in root production across the range of defoliation treatments in our study. However, there was no significant relationship between shoot and root production.ConclusionsOur results find that aboveground and belowground productivity are only weakly coupled, suggesting caution against use of simple aboveground proxies to predict variations in root production in grasslands. More broadly, our results demonstrate that improved modeling and management of grasslands for belowground ecosystem services, including soil carbon sequestration/stocks, will need to account for intraspecific genetic variations and responses to defoliation management.