bluuebunny/crossref_metadata_2025_split huggingface dataset:
The diagnostic performance of rapid diagnostic tests and microscopy for malaria diagnosis in eastern Sudan using a nested polymerase chain reaction assay as a reference standard
Authors: Abdalla Zakya A , Rahma NourElhouda A , Hassan Elhashimi E , Abdallah Tajeldin M , Hamad Hadeel E , Omer Samia A , Adam Ishag 
Published: June 2019

AbstractBackgroundAccurate diagnosis of malaria infection is essential for successful control and management of the disease. Both microscopy and rapid diagnostic tests (RDTs) are recommended for malaria diagnosis, however, RDTs are more commonly used. The aim of the current study was to assess the performance of microscopy and RDTs in the diagnosis of Plasmodium falciparum infection using a nested polymerase chain reaction (PCR) assay as the gold standard.MethodsA cross-sectional study was carried out in Kassala Hospital, eastern Sudan. A total of 341 febrile participants of all ages were recruited. Blood specimens were collected and malaria testing was performed using an RDT (SD Bioline Malaria Ag Pf), microscopy and nested PCR. The sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively) of microscopy and the RDT were investigated.ResultsThe prevalence of P. falciparum malaria infections in this study was 22.9%, 24.3% and 26.7% by PCR, microscopy and RDT, respectively. Compared with microscopy, the RDT had slightly higher sensitivity (80.7% vs 74.3%; p=0.442), equivalent specificity (89.3% vs 90.4%), a similar PPV (69.2% vs 69.8%) and a higher NPV (94.0% vs 92.2%).ConclusionsThe diagnostic performance of the RDT was better than that of microscopy in the diagnosis of P. falciparum malaria when nested PCR was used as the gold standard.
IX The Seventeenth Century: Part I
Authors: Baker William , Gwynn Lucy , Doelman James , James Anne , Mroz Matthew 
Published: June 2019

AbstractThis chapter combines what previously were Chapter IX, focusing on the earlier seventeenth century, and Chapter X, on Milton and poetry 1603–1660. Some of the content transcends historical dates and covers material from the latter half of the seventeenth century too; in other words, the long seventeenth century. It has seven sections: 1. General; 2. Bacon; 3. Browne; 4. Burton; 5. Herbert; 6. Donne; 7. Milton. Sections 1 and 2 are by William Baker; section 3 is by Lucy Gwynn and William Baker; section 4 is by William Baker; section 5 is by James Doelman; section 6 is by Anne James; section 7 is by Matthew Mroz.
X The Seventeenth Century: Part II
Authors: Netzley Ryan , Baker William , Airey Jennifer 
Published: June 2019

AbstractThis chapter has five sections: 1. General; 2. Other Poetry; 3. Restoration Drama Excluding Dryden; 4. Dryden; 5. Prose. Section 1 is by Ryan Netzley; section 2 is by William Baker; sections 3 and 4 are by Jennifer Airey; section 5 is by William Baker.
Weak neural signatures of spatial selective auditory attention in hearing-impaired listeners
Authors: Bonacci Lia M. , Dai Lengshi , Shinn-Cunningham Barbara G. 
Published: June 2019

AbstractSpatial attention may be used to select target speech in one location while suppressing irrelevant speech in another. However, if perceptual resolution of spatial cues is weak, spatially focused attention may work poorly, leading to difficulty communicating in noisy settings. In electroencephalography (EEG), the distribution of alpha (8–14 Hz) power over parietal sensors reflects the spatial focus of attention (Banerjee et al., 2011; Foxe and Snyder, 2011). If spatial attention is degraded, however, alpha may not be modulated across parietal sensors. A previously published behavioral and EEG study found that, compared to normal-hearing (NH) listeners, hearing-impaired (HI) listeners often had higher interaural time difference (ITD) thresholds, worse performance when asked to report the content of an acoustic stream from a particular location, and weaker attentional modulation of neural responses evoked by sounds in a mixture (Dai et al., 2018). This study explored whether these same HI listeners also showed weaker alpha lateralization during the previously reported task. In NH listeners, hemispheric parietal alpha power was greater when the ipsilateral location was attended; this lateralization was stronger when competing melodies were separated by a larger spatial difference. In HI listeners, however, alpha was not lateralized across parietal sensors, consistent with a degraded ability to use spatial features to selectively attend.
Removing the hidden data dependency of DIA with predicted spectral libraries
Authors: Van Puyvelde B. , Willems S. , Gabriels R. , Daled S. , De Clerck L. , Vande Casteele S. , Staes A. , Impens F. , Deforce D. , Martens L. , Degroeve S. , Dhaenens M. 
Published: June 2019

Data-Independent Acquisition (DIA) generates comprehensive yet complex mass spectrometric data, which imposes the use of data-dependent acquisition (DDA) libraries for deep peptide-centric detection. We here show that DIA can be redeemed from this dependency by combining predicted fragment intensities and retention times with narrow window DIA. This eliminates variation in library building and omits stochastic sampling, finally making the DIA workflow fully deterministic. Especially for clinical proteomics, this has the potential to facilitate inter-laboratory comparison.Significance of the StudyData-independent acquisition (DIA) is quickly developing into the most comprehensive strategy to analyse a sample on a mass spectrometer. Correspondingly, a wave of data analysis strategies has followed suit, improving the yield from DIA experiments with each iteration. As a result, a worldwide wave of investments in DIA is already taking place in anticipation of clinical applications. Yet, there is considerable confusion about the most useful and efficient way to handle DIA data, given the plethora of possible approaches with little regard for compatibility and complementarity. In our manuscript, we outline the currently available peptide-centric DIA data analysis strategies in a unified graphic called the DIAmond DIAgram. This leads us to an innovative and easily adoptable approach based on predicted spectral information. Most importantly, our contribution removes what is arguably the biggest bottleneck in the field: the current need for Data Dependent Acquisition (DDA) prior to DIA analysis. Fractionation, stochastic data acquisition, processing and identification all introduce bias in the library. By generating libraries through data independent, i.e. deterministic acquisition, stochastic sampling in the DIA workflow is now fully omitted. This is a crucial step towards increased standardization. Additionally, our results demonstrate that a proteome-wide predicted spectral library can surrogate an exhaustive DDA Pan-Human library that was built based on 331 prior DDA runs.
Vascularized human cortical organoids model cortical development in vivo
Authors: Shi Yingchao , Sun Le , Liu Jianwei , Zhong Suijuan , Wang Mengdi , Li Rui , Li Peng , Guo Lijie , Fang Ai , Chen Ruiguo , Ge Woo-Ping , Wu Qian , Wang Xiaoqun 
Published: June 2019

AbstractModelling the neuronal progenitor proliferation and organization processes that produce mature cortical neuron subtypes is essential for the study of human brain development and the search for potential cell therapies. To provide a vascularized and functional model of brain organoids, we demonstrated a new paradigm to generate vascularized organoids that consist of typical human cortical cell types and recapitulate the lamination of the neocortex with a vascular structure formation for over 200 days. In addition, the observation of the sEPSCs (spontaneous Excitatory Postsynaptic Potential) and sIPSCs (spontaneous Inhibitory Postsynaptic Potential) and the bidirectional electrical transmission indicated the presence of chemical and electrical synapses in the vOrganoids. More importantly, the single-cell RNA-seq analysis illustrated that the vOrganoids exhibited microenvironments to promote neurogenesis and neuronal maturation that resembled in vivo processes. The transplantation of the vOrganoids to the mouse S1 cortex showed human-mouse co-constructed functional blood vessels in the grafts that could promote the survival and integration of the transplanted cells to the host. This vOrganoid culture method could not only serve as a model to study human cortical development and to explore brain disease pathology but could also provide potential prospects for new cell therapies for neural system disorders and injury.
Phosphorylated Lamin A/C in the nuclear interior binds active enhancers associated with abnormal transcription in progeria
Authors: Ikegami Kohta , Secchia Stefano , Almakki Omar , Lieb Jason D. , Moskowitz Ivan P. 
Published: June 2019

ABSTRACTLMNA encodes nuclear lamin A/C that tethers lamina-associated heterochromatin domains (LADs) to the nuclear periphery. Point mutations in LMNA cause degenerative disorders including the premature aging disorder Hutchinson-Gilford progeria, but the mechanisms are unknown. We report that Ser22-phosphorylated Lamin A/C (pS22-Lamin A/C) was localized to the interior of the nucleus in human fibroblasts throughout the cell cycle. pS22-Lamin A/C interacted with a specific subset of putative active enhancers, not LADs, primarily at locations co-bound by the transcriptional activator c-Jun. In progeria-patient fibroblasts, a subset of pS22-Lamin A/C-binding sites were lost whereas new pS22-Lamin A/C-binding sites emerged in normally quiescent loci. These new pS22-Lamin A/C-binding sites displayed increased histone acetylation and c-Jun binding, implying increased enhancer activity. The genes near these new binding sites, implicated in clinical components of progeria including carotid artery diseases, hypertension, and cardiomegaly, were upregulated in progeria. These results suggest that Lamin A/C regulates gene expression by direct enhancer binding in the nuclear interior. Disruption of the gene regulatory rather than LAD function of Lamin A/C presents a novel mechanism for disorders caused by LMNA mutations including progeria.HIGHLIGHTSpS22-Lamin A/C is present in the nuclear interior throughout interphase.pS22-Lamin A/C associates with active enhancers, not lamina-associated domains.pS22-Lamin A/C-genomic binding sites are co-bound by the transcriptional activator c-Jun.New pS22-Lamin A/C binding in progeria accompanies upregulation of disease-related genes.
Expression reduction of biallelically transcribed X-linked genes during the human female preimplantation development
Authors: Reinius Björn , Sandberg Rickard 
Published: June 2019

AbstractOur previous single-cell RNA-seq data from human preimplantation embryos showed that female X-chromosome mRNA levels become partly dose compensated during the timespan between zygotic genome activation (ZGA) and implantation. At the same time, XIST RNA is expressed from, and forms clouds in proximity to, both X-chromosome copies and biallelic expression of other X-linked genes persists. We proposed that X-chromosome transcription is transiently lowered on both alleles before X-chromosome inactivation (XCI) takes place. This notion was recently challenged in a reanalysis performed by Moreira de Mello et al, claiming to provide evidence against biallelic expression dampening and that instead proper XCI was responsible for the observed dosage compensation. Here we have addressed this reanalysis and highlighted methodological issues, and we conclude a current lack of evidence against biallelic X-chromosome dampening.
Broadly inhibiting anti-neuraminidase monoclonal antibodies induced by trivalent influenza vaccine and H7N9 infection in humans
Authors: Rijal Pramila , Wang Bei Bei , Tan Tiong Kit , Schimanski Lisa , Janesch Philipp , Dong Tao , McCauley John W. , Daniels Rodney S. , Townsend Alain R. , Huang Kuan-Ying A. 
Published: June 2019

AbstractThe majority of antibodies induced by influenza neuraminidase (NA), like those against hemagglutinin (HA), are relatively specific to viruses isolated within a limited time-window as seen in serological studies and the analysis of many murine monoclonal antibodies. We report three broadly reactive human monoclonal antibodies (mAbs) targeting N1 NA. Two were isolated from a young adult vaccinated with trivalent influenza vaccine (TIV), which inhibited N1 NA from viruses isolated from human over a period of a hundred years. The third antibody isolated from a child with acute mild H7N9 infection inhibited both group 1 N1 and group 2 N9 NAs. In addition, the antibodies cross-inhibited the N1 NAs of highly pathogenic avian H5N1 influenza viruses. These antibodies are protective in prophylaxis against seasonal H1N1 viruses in mice. This study demonstrates that human antibodies to N1 NA with exceptional cross-reactivity can be recalled by vaccination and highlights the importance of standardizing the NA antigen in seasonal vaccines to offer optimal protection.ImportanceAntibodies to the influenza NA can provide protection against influenza disease. Analysis of human antibodies to NA lags behind that for HA. We show that human monoclonal antibodies against NA induced by vaccination and infection can be very broadly reactive and able to inhibit a wide spectrum of N1 NAs between 1918 and 2018. This suggests that antibodies to NA may be a useful therapy, and that efficacy of influenza vaccines could be enhanced by ensuring appropriate content of NA antigen.Highlights of the paperAntibodies that inhibit influenza viruses with N1 neuraminidase (NA), with broad reactivity for viruses isolated between 1918-2018, can be isolated from human recipients of seasonal influenza vaccineAntibodies targeting N1 NA of human seasonal H1N1 viruses can cross-react with a variety of avian N1 neuraminidasesAcute H7N9 infection can recall memory B cells to N1 NA and elicit cross-reactive antibodies to the group 1 N1 and group 2 N9 NAsAntibodies to N1 NA with this broad reactivity protect against lethal virus challenge
The Lid/KDM5 histone demethylase complex activates a critical effector of the oocyte-to-zygote transition
Authors: Torres-Campana Daniela , Kimura Shuhei , Orsi Guillermo A. , Horard Béatrice , Benoit Gérard , Loppin Benjamin 
Published: June 2019

AbstractFollowing fertilization of a mature oocyte, the formation of a diploid zygote involves a series of coordinated cellular events that ends with the first embryonic mitosis. In animals, this complex developmental transition is almost entirely controlled by maternal gene products. How such a crucial transcriptional program is established during oogenesis remains poorly understood. Here, we have performed an shRNA-based genetic screen inDrosophilato identify genes required to form a diploid zygote. We found that the Lid/KDM5 histone demethylase and its partner, the Sin3A-HDAC1 deacetylase complex, are necessary for sperm nuclear decompaction and karyogamy. Surprisingly, transcriptomic analyses revealed that these histone modifiers are required for the massive transcriptional activation ofdeadhead(dhd), which encodes a maternal thioredoxin involved in sperm chromatin remodeling. Unexpectedly, whilelidknock-down tends to slightly favor the accumulation of its target, H3K4me3, on the genome, this mark was lost at thedhdlocus. We propose that Lid/KDM5 and Sin3A cooperate to establish a local chromatin environment facilitating the unusually high expression ofdhd, a key effector of the oocyte-to-zygote transition.
Enhancing the biological relevance of Gene Co-expression Networks: A plant mitochondrial case study
Authors: Law Simon R. , Kellgren Therese G. , Björk Rafael , Ryden Patrik , Keech Olivier 
Published: June 2019

AbstractGene Co-expression Networks (GCNs) are obtained by a variety of mathematical of models commonly derived on data sampled from diverse developmental processes, tissue types, pathologies, mutant backgrounds, and stress conditions. These networks aim to identify genes with similar expression dynamics, but are prone to introduce false-positive and -negative relations, especially in the instance of large and highly complex datasets. With the aim of optimizing the relevance of edges in GCNs and enhancing global biological insight, we propose a novel approach that involves a data-centering step performed simultaneously per gene and per sub-experiment, called centralisation within sub-experiments (CSE).Using a gene set encoding for the plant mitochondrial proteome as a case study, our results show that CSE-based GCNs had significantly more edges within the majority of the considered functional sub-networks, such as the mitochondrial electron transport chain and its sub-complexes, than GCNs not using CSE; thus demonstrating that the CSE-based GCNs are efficient at predicting those canonical functions and associated pathways, also referred to as the “core network”. Furthermore, we show that CSE, in conjunction with conventional correlation analyses can be used to fine-tune the prediction of the function for uncharacterised genes; while in combination with analyses based on non-centralised data can augment those conventional stress analyses with the innate connections underpinning the dynamic system examined.Therefore, CSE appears as an alternative method to conventional batch correction approaches. The method is easy to implement into a pre-existing GCN analysis pipeline and can provide accentuated biological relevance to conventional GCNs by allowing users to delineate a “core” gene network.Author SummaryGene Co-expression networks (GCNs) are the product of a variety of mathematical models that identify causal relationships in gene expression dynamics, but are prone to the misdiagnoses of false-positives and -negatives, especially in the instance of large and highly complex datasets. In light of the burgeoning output of next generation sequencing projects performed on any species, under different developmental or clinical conditions, the statistical power and complexity of these networks will undoubtedly increase, while their biological relevance will be fiercely challenged. Here, we propose a novel approach to primarily generate a “core” GCN with augmented biological relevance. Our method, which involves data-centering steps and thus effectively removes all primary treatment / tissue /patient effects, is simple to employ and can be easily implemented into pre-existing GCN analysis pipelines. The gained biological relevance of such an approach was validated using a subcellular gene set encoding for the plant mitochondrial proteome, and by applying numerous steps to challenge its application.
Expression of normal levels of the Pumilio domain protein PUF3 is required for optimal growth of Trypanosoma brucei
Authors: Marucha Kevin Kamanyi , Clayton Christine 
Published: June 2019

AbstractThe Trypanosoma brucei pumilio domain protein PUF3 is a cytosolic mRNA-binding protein that suppresses expression when tethered to a reporter mRNA. An induced reduction of PUF3 in bloodstream forms caused a slight growth defect and slightly delayed differentiation to the procyclic form, but the cells lost both defects upon prolonged cultivation. Both PUF3 genes could also be deleted in bloodstream-form and procyclic-form trypanosomes, suggesting that in vitro, at least, these life-cycle stages do not require PUF3. Procyclic forms without PUF3 grew somewhat slower than wild-type, but were able to transform to bloodstream forms after induced expression of the bloodstream-form RNA-binding protein RBP10. In contrast, ectopic expression of C-terminally tagged PUF3 in procyclic forms impaired viability. There was little evidence for specific binding of PUF3 to bloodstream-form mRNAs and RNAi had no significant effect on the transcriptome. Moreover, mass spectrometry revealed no PUF3 binding partners that might explain its suppressive activity. Since PUF3 is conserved in all Kinetoplastids, we suggest that it might be required within the invertebrate host, or perhaps implicated in fine-tuning gene expression.
Serial protein crystallography in an electron microscope
Authors: Bücker Robert , Hogan-Lamarre Pascal , Mehrabi Pedram , Schulz Eike C. , Bultema Lindsey A. , Gevorkov Yaroslav , Brehm Wolfgang , Yefanov Oleksandr , Oberthür Dominik , Kassier Günther H. , Miller R. J. Dwayne 
Published: June 2019

AbstractSerial X-ray crystallography at free-electron lasers allows to solve biomolecular structures from sub-micron-sized crystals. However, beam time at these facilities is scarce, and involved sample delivery techniques are required. On the other hand, rotation electron diffraction (MicroED) has shown great potential as an alternative means for protein nano-crystallography. Here, we present a method for serial electron diffraction of protein nanocrystals combining the benefits of both approaches. In a scanning transmission electron microscope, crystals randomly dispersed on a sample grid are automatically mapped, and a diffraction pattern at fixed orientation is recorded from each at a high acquisition rate. Dose fractionation ensures minimal radiation damage effects. We demonstrate the method by solving the structure of granulovirus occlusion bodies and lysozyme to resolutions of 1.55 Å and 1.80 Å, respectively. Our method promises to provide rapid structure determination for many classes of materials with minimal sample consumption, using readily available instrumentation.
The mitogenome of Norway spruce and a reappraisal of mitochondrial recombination in plants
Authors: Sullivan Alexis R. , Eldfjell Yrin , Schiffthaler Bastian , Delhomme Nicolas , Asp Torben , Hebelstrup Kim H. , Keech Olivier , Öberg Lisa , Møller Ian Max , Arvestad Lars , Street Nathaniel R. , Wang Xiao-Ru 
Published: June 2019

AbstractPlant mitogenomes can be difficult to assemble because they are structurally dynamic and prone to intergenomic DNA transfers, leading to the unusual situation where an organelle genome is far outnumbered by its nuclear counterparts. As a result, comparative mitogenome studies are in their infancy and some key aspects of genome evolution are still known mainly from pre-genome, qualitative methods. To help address these limitations, we combined machine learning andin silicoenrichment of mitochondrial-like long reads to assemble the bacterial-sized mitogenome of Norway spruce (Pinaceae:Picea abies). We conducted comparative analyses of repeat abundance, intergenomic transfers, substitution and rearrangement rates, and estimated repeat-by-repeat homologous recombination rates. Prompted by our discovery of highly recombinogenic small repeats inP. abies, we assessed the genomic support for the prevailing hypothesis that intramolecular recombination is predominantly driven by repeat length, with larger repeats facilitating DNA exchange more readily. Overall, we found mixed support for this view: recombination dynamics were heterogeneous across vascular plants and highly active small repeats (ca. 200 bp) were present in about a third of studied mitogenomes. As in previous studies, we did not observe any robust relationships among commonly-studied genome attributes, but we identify variation in recombination rates as a underinvestigated source of plant mitogenome diversity.