bluuebunny/crossref_metadata_2025_split huggingface dataset:
Revealing dynamic regulations and the related key proteins of myeloma-initiating cells by integrating experimental data into a systems biological model
Authors: Zhang Le , Liu Guangdi , Kong Meijing , Li Tingting , Wu Dan , Zhou Xiaobo , Yang Chuanwei , Xia Lei , Yang Zhenzhou , Chen Luonan 
Published: July 2019

Abstract

Motivation
The growth and survival of myeloma cells are greatly affected by their surrounding microenvironment. To understand the molecular mechanism and the impact of stiffness on the fate of myeloma-initiating cells (MICs), we develop a systems biological model to reveal the dynamic regulations by integrating reverse-phase protein array data and the stiffness-associated pathway.

Results
We not only develop a stiffness-associated signaling pathway to describe the dynamic regulations of the MICs, but also clearly identify three critical proteins governing the MIC proliferation and death, including FAK, mTORC1 and NFκB, which are validated to be related with multiple myeloma by our immunohistochemistry experiment, computation and manually reviewed evidences. Moreover, we demonstrate that the systematic model performs better than widely used parameter estimation algorithms for the complicated signaling pathway.

Availability and implementation
We can not only use the systems biological model to infer the stiffness-associated genetic signaling pathway and locate the critical proteins, but also investigate the important pathways, proteins or genes for other type of the cancer. Thus, it holds universal scientific significance.

Supplementary information
Supplementary data are available at Bioinformatics online
ATEN: And/Or tree ensemble for inferring accurate Boolean network topology and dynamics
Authors: Shi Ning , Zhu Zexuan , Tang Ke , Parker David , He Shan 
Published: July 2019

Abstract

Motivation
Inferring gene regulatory networks from gene expression time series data is important for gaining insights into the complex processes of cell life. A popular approach is to infer Boolean networks. However, it is still a pressing open problem to infer accurate Boolean networks from experimental data that are typically short and noisy.

Results
To address the problem, we propose a Boolean network inference algorithm which is able to infer accurate Boolean network topology and dynamics from short and noisy time series data. The main idea is that, for each target gene, we use an And/Or tree ensemble algorithm to select prime implicants of which each is a conjunction of a set of input genes. The selected prime implicants are important features for predicting the states of the target gene. Using these important features we then infer the Boolean function of the target gene. Finally, the Boolean functions of all target genes are combined as a Boolean network. Using the data generated from artificial and real-world gene regulatory networks, we show that our algorithm can infer more accurate Boolean network topology and dynamics from short and noisy time series data than other algorithms. Our algorithm enables us to gain better insights into complex regulatory mechanisms of cell life.

Availability and implementation
Package ATEN is freely available at https://github.com/ningshi/ATEN.

Supplementary information
Supplementary data are available at Bioinformatics online.
Bayesian inference of distributed time delay in transcriptional and translational regulation
Authors: Choi Boseung , Cheng Yu-Yu , Cinar Selahattin , Ott William , Bennett Matthew R , Josić Krešimir , Kim Jae Kyoung 
Published: July 2019

AbstractMotivationAdvances in experimental and imaging techniques have allowed for unprecedented insights into the dynamical processes within individual cells. However, many facets of intracellular dynamics remain hidden, or can be measured only indirectly. This makes it challenging to reconstruct the regulatory networks that govern the biochemical processes underlying various cell functions. Current estimation techniques for inferring reaction rates frequently rely on marginalization over unobserved processes and states. Even in simple systems this approach can be computationally challenging, and can lead to large uncertainties and lack of robustness in parameter estimates. Therefore we will require alternative approaches to efficiently uncover the interactions in complex biochemical networks.ResultsWe propose a Bayesian inference framework based on replacing uninteresting or unobserved reactions with time delays. Although the resulting models are non-Markovian, recent results on stochastic systems with random delays allow us to rigorously obtain expressions for the likelihoods of model parameters. In turn, this allows us to extend MCMC methods to efficiently estimate reaction rates, and delay distribution parameters, from single-cell assays. We illustrate the advantages, and potential pitfalls, of the approach using a birth–death model with both synthetic and experimental data, and show that we can robustly infer model parameters using a relatively small number of measurements. We demonstrate how to do so even when only the relative molecule count within the cell is measured, as in the case of fluorescence microscopy.Availability and implementationAccompanying code in R is available at https://github.com/cbskust/DDE_BD.Supplementary informationSupplementary data are available at Bioinformatics online.
amplimap: a versatile tool to process and analyze targeted NGS data
Authors: Koelling Nils , Bernkopf Marie , Calpena Eduardo , Maher Geoffrey J , Miller Kerry A , Ralph Hannah K , Goriely Anne , Wilkie Andrew O M 
Published: July 2019

Abstract

Summary
amplimap is a command-line tool to automate the processing and analysis of data from targeted next-generation sequencing experiments with PCR-based amplicons or capture-based enrichment systems. From raw sequencing reads, amplimap generates output such as read alignments, annotated variant calls, target coverage statistics and variant allele counts and frequencies for each target base pair. In addition to its focus on user-friendliness and reproducibility, amplimap supports advanced features such as consensus base calling for read families based on unique molecular identifiers and filtering false positive variant calls caused by amplification of off-target loci.

Availability and implementation
amplimap is available as a free Python package under the open-source Apache 2.0 License. Documentation, source code and installation instructions are available at https://github.com/koelling/amplimap.
MPRAscore: robust and non-parametric analysis of massively parallel reporter assays
Authors: Niroula Abhishek , Ajore Ram , Nilsson Björn 
Published: July 2019

Abstract

Motivation
Massively parallel reporter assays (MPRA) enable systematic screening of DNA sequence variants for effects on transcriptional activity. However, convenient analysis tools are still needed.

Results
We introduce MPRAscore, a novel tool to infer allele-specific effects on transcription from MPRA data. MPRAscore uses a weighted, variance-regularized method to calculate variant effect sizes robustly, and a permutation approach to test for significance without assuming normality or independence.

Availability and implementation
Source code (C++), precompiled binaries and data used in the paper at https://github.com/abhisheknrl/MPRAscore and https://www.ncbi.nlm.nih.gov/bioproject/PRJNA554195.

Supplementary information
Supplementary data are available at Bioinformatics online.
DeepGOPlus: improved protein function prediction from sequence
Authors: Kulmanov Maxat , Hoehndorf Robert 
Published: July 2019

Abstract

Motivation
Protein function prediction is one of the major tasks of bioinformatics that can help in wide range of biological problems such as understanding disease mechanisms or finding drug targets. Many methods are available for predicting protein functions from sequence based features, protein–protein interaction networks, protein structure or literature. However, other than sequence, most of the features are difficult to obtain or not available for many proteins thereby limiting their scope. Furthermore, the performance of sequence-based function prediction methods is often lower than methods that incorporate multiple features and predicting protein functions may require a lot of time.

Results
We developed a novel method for predicting protein functions from sequence alone which combines deep convolutional neural network (CNN) model with sequence similarity based predictions. Our CNN model scans the sequence for motifs which are predictive for protein functions and combines this with functions of similar proteins (if available). We evaluate the performance of DeepGOPlus using the CAFA3 evaluation measures and achieve an Fmax of 0.390, 0.557 and 0.614 for BPO, MFO and CCO evaluations, respectively. These results would have made DeepGOPlus one of the three best predictors in CCO and the second best performing method in the BPO and MFO evaluations. We also compare DeepGOPlus with state-of-the-art methods such as DeepText2GO and GOLabeler on another dataset. DeepGOPlus can annotate around 40 protein sequences per second on common hardware, thereby making fast and accurate function predictions available for a wide range of proteins.

Availability and implementation
http://deepgoplus.bio2vec.net/ .

Supplementary information
Supplementary data are available at Bioinformatics online.
Shifts to multiple optima underlie climatic niche evolution in New World phyllostomid bats
Authors: Varzinczak Luiz H , Moura Mauricio O , Passos Fernando C 
Published: July 2019

Abstract
Climate underlies species distribution patterns, especially in species where climate limits distributions, such as the phyllostomid bats, which are mostly restricted to the New World tropics. The evolutionary dynamics that shaped phyllostomid climatic niches remain unclear, and a broad phylogenetic perspective is required to uncover their patterns. We used geographical distributions and evolutionary relationships of 130 species, climate data and phylogenetic comparative methods to uncover dynamics of phyllostomid climatic niche evolution. Diversification of climatic niches began early in phyllostomid evolution (~34 Mya), with most changes taking place ~20 Mya. Although most of these bats were found in tropical regions, shifts towards different evolutionary optima were common. Shifts were mostly towards temperate climates, reflecting complexities in phyllostomid evolution highlighted by the probable role of species-specific adaptations to cope with these climates, the influence of palaeoclimatic events, and biogeographical effects related to the evolution and dispersal of clades in the New World. Our results broaden our understanding of the relationships between phyllostomid bats and climate, filling an important gap in knowledge and suggesting a complex evolution in their occupation of the climatic niche space.
Optimal management of gestational diabetes
Authors: Egan Aoife M , Dunne Fidelma P 
Published: July 2019

AbstractBackgroundGestational diabetes mellitus (GDM) is highly prevalent and has both short- and long-term implications for mother and infant.Sources of dataLiterature search using PubMed with keywords ‘Gestational diabetes’ and ‘diabetes in pregnancy’ together with published papers known to the authors.Areas of agreementThe cornerstone of management is medical nutrition therapy with regular self-monitoring of capillary blood glucose levels and intensification of therapy if glycaemic goals are not achieved. Post-partum, annual assessment for type 2 diabetes is recommended.Areas of controversyDiagnostic criteria and new biomarkers for GDM and the clinical and economic benefits of treating women with milder levels of glucose intolerance during pregnancy.Growing pointsWomen with GDM are a heterogeneous group with varying degrees of insulin resistance and beta cell dysfunction.Areas timely for developing researchDevelopment of alternative diagnostic markers and application of novel technologies for GDM management.
Hip scores: A current concept review
Authors: Longo Umile Giuseppe , Ciuffreda Mauro , Candela Vincenzo , Berton Alessandra , Maffulli Nicola , Denaro Vincenzo 
Published: July 2019

AbstractIntroductionDuring the past decades, several rating scales have been developed to assess the functional status of patients with hip pain.Source of dataA search in Medline, PubMed, Cochrane and CINAHL was performedusing combinations of the following‘hip’, ‘scoring system’, ‘scale’, ‘scores’, ‘outcome assessment’, ‘arthroplasty’, ‘arthroscopy’ and ‘clinical evaluation’.Areas of agreementA total 16 scoring systems are currently available for the evaluation of the hip.Areas of controversyTwo types of questionnaires are available: physician-rated and patient-rated questionnaires.Growing pointsEach hip score consists of different domains. Interpreting these domains becomes sometimes difficult, because, even though they can be common to more than one scoring system, each stresses them in a different way.Areas timely for developing researchAlthough many scoring systems have been used to evaluate hip function, we are still far from a single outcome evaluation system which is reliable, valid and sensitive.
Delving deeper into the phylogenetics of the herbaceous bamboos (Poaceae, Bambusoideae, Olyreae): evaluation of generic boundaries within the Parodiolyra/Raddiella clade uncovers a new genus
Authors: Oliveira Iasmin L C , Matos Andreza O , Silva Christian , Carvalho Maria Luiza S , Tyrrell Christopher D , Clark Lynn G , Oliveira R Patrícia 
Published: July 2019

AbstractThe present study aims to expand the knowledge of phylogenetic relationships in Olyrinae, a subtribe of herbaceous bamboos (Poaceae: Bambusoideae: Olyreae). Our focus is on Parodiolyra and Raddiella, two historically related genera that, with their sister Diandrolyra, form one of the four main lineages in the subtribe. Previous phylogenetic analyses suggested that Parodiolyra is not monophyletic, but its taxonomic boundaries and its relationship with Raddiella remain uncertain due to low sampling. We increased the taxon sampling and sequenced five regions of the nuclear and plastid genomes for this lineage and other representatives of Olyreae. We used maximum parsimony, maximum likelihood, Bayesian inference and coalescence analysis. Our results corroborate the paraphyly of Parodiolyra, with P. micrantha sister to a clade including the remaining Parodiolyra and Raddiella. All remaining Parodiolyra form a well-supported clade, but Raddiella had conflicting resolutions, being either monophyletic or not. Thus, based on phylogenetic and morphological evidence, we here recircumscribe Parodiolyra, transferring P. micrantha and P. colombiensis to the new genus Taquara (described here). Regarding Raddiella, sampling is still not comprehensive and does not allow a decision on to its taxonomic status to be made at this time. Inclusion of other phreatophytic species may be crucial to resolve the problem of conflicting topologies.
#MeToo and the Politics of Collective Healing: Emotional Connection as Contestation
Authors: Page Allison , Arcy Jacquelyn 
Published: July 2019

Abstract
Participants in the #MeToo movement on Twitter expressed emotions like rage, pain, and solidarity in their personal accounts of sexual violence. This article explores the digital circulation of these affects and considers how the outpouring of tweets about sexual harassment and abuse contribute to a feminist politics centered on collective healing. The particular emotions expressed in the #MeToo Twitter archive subvert the logics of quantification and visibility that undergird popular feminism and the attention economy, and produce an affective excess that works toward movement founder Tarana Burke's original project of “mass healing.” At a moment wherein popular feminism emphasizes individual empowerment and consumption, and carceral feminism relies on criminalization and incarceration, the #MeToo movement's focus on shared emotions represents the potential for a feminist politics rooted in collective support and restorative justice.
Dendritic Localization and Exocytosis of NAAG in the Rat Hippocampus
Authors: Nordengen K , Morland C , Slusher B S , Gundersen V 
Published: July 2019

AbstractWhile a lot is known about classical, anterograde neurotransmission, less is known about the mechanisms and molecules involved in retrograde neurotransmission. Our hypothesis is that N-acetylaspartylglutamate (NAAG), the most abundant dipeptide in the brain, may act as a retrograde transmitter in the brain. NAAG was predominantly localized in dendritic compartments of glutamatergic synapses in the intact hippocampus, where it was present in close proximity to synaptic-like vesicles. In acute hippocampal slices, NAAG was depleted from postsynaptic dendritic elements during neuronal stimulation induced by depolarizing concentrations of potassium or by exposure to glutamate receptor (GluR) agonists. The depletion was completely blocked by botulinum toxin B and strictly dependent on extracellular calcium, indicating exocytotic release. In contrast, there were low levels of NAAG and no effect by depolarization or GluR agonists in presynaptic glutamatergic terminals or GABAergic pre- and postsynaptic elements. Together these data suggest a possible role for NAAG as a retrograde signaling molecule at glutamatergic synapses via exocytotic release.
Long-Lasting Somatic Modifications of Convergent Dendritic Inputs in Hippocampal Neurons
Authors: Yang Xin , Bao Yifei , Xu Jindong , Gong Ru , Zhang Nan , Cai Lei , Xia Mingmei , Wang Jingjing , Lu Wei 
Published: July 2019

Abstract
Integrated neural inputs from different dendrites converge at the soma for action potential generation. However, it is unclear how the convergent dendritic inputs interact at the soma and whether they can be further modified there. We report here an entirely new plasticity rule in hippocampal neurons in which repetitive pairing of subthreshold excitatory inputs from proximal apical and basal dendrites at a precise interval induces persistent bidirectional modifications of the two dendritic inputs. Strikingly, the modification of the dendritic inputs specially occurs at soma in the absence of somatic action potential and requires activation of somatic N-methyl-D-aspartate receptors (NMDARs). Once induced, the somatic modification can also be observed in other unpaired dendritic inputs upon their arrival at the soma. We further reveal that the soma can employ an active mechanism to potentiate the dendritic inputs by promoting sustained activation of somatic NMDARs and subsequent down-regulating of the fast inactivating A-type potassium current (IA) at the soma. Thus, the input-timing–dependent somatic plasticity we uncovered here is in sharp contrast to conventional forms of synaptic plasticity that occur at the dendrites and is important to somatic action potential generation.
High Angular Resolution Diffusion MRI Reveals Conserved and Deviant Programs in the Paths that Guide Human Cortical Circuitry
Authors: Charvet Christine J , Das Avilash , Song Jae W , Tindal-Burgess Deselyn J , Kabaria Priya , Dai Guangping , Kane Tara , Takahashi Emi 
Published: July 2019

Abstract
Diffusion magnetic resonance (MR) tractography represents a novel opportunity to investigate conserved and deviant developmental programs between humans and other species such as mice. To that end, we acquired high angular resolution diffusion MR scans of mice [embryonic day (E) 10.5 to postnatal week 4] and human brains [gestational week (GW) 17–30] at successive stages of fetal development to investigate potential evolutionary changes in radial organization and emerging pathways between humans and mice. We compare radial glial development as well as commissural development (e.g., corpus callosum), primarily because our findings can be integrated with previous work. We also compare corpus callosal growth trajectories across primates (i.e., humans and rhesus macaques) and rodents (i.e., mice). One major finding is that the developing cortex of humans is predominated by pathways likely associated with a radial glial organization at GW 17–20, which is not as evident in age-matched mice (E 16.5, 17.5). Another finding is that, early in development, the corpus callosum follows a similar developmental timetable in primates (i.e., macaques and humans) as in mice. However, the corpus callosum grows for an extended period of time in primates compared with rodents. Taken together, these findings highlight deviant developmental programs underlying the emergence of cortical pathways in the human brain.
Stimulation of mGluR1/5 Improves Defective Internalization of AMPA Receptors in NPC1 Mutant Mouse
Authors: Feng Xiao , Yang Fan , Rabenstein Michael , Wang Zhen , Frech Moritz J , Wree Andreas , Bräuer Anja U , Witt Martin , Gläser Anne , Hermann Andreas , Rolfs Arndt , Luo Jiankai 
Published: July 2019

AbstractNiemann–Pick type C1 (NPC1) disease is characterized by neurodegeneration caused by cholesterol accumulation in the late endosome/lysosome. In this study, a defective basal and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-stimulated internalization of GluR2-containing AMPA receptors in NPC1−/− cortical neurons was detected. Our results show that the amount of cholesterol and group I metabotropic glutamate receptors (mGluR1/5) in lipid rafts of NPC1−/− cortical tissue and neurons are decreased and their downstream signals of p-ERK are defective, which are restored by a rebalance of cholesterol homeostasis through β-cyclodextrin (β-CD) treatment. Application of 3,5-dihydroxyphenylglycine (DHPG)—a mGluR1/5 agonist—and β-CD markedly increases the internalization of AMPA receptors and decreases over-influx of calcium in NPC1−/− neurons, respectively. Furthermore, the defective phosphorylated GluR2 and protein kinase C signals are ameliorated by the treatment with DHPG and β-CD, respectively, suggesting an involvement of them in internalization dysfunction. Taken together, our data imply that abnormal internalization of AMPA receptors is a critical mechanism for neuronal dysfunction and the correction of dysfunctional mGluR1/5 is a potential therapeutic strategy for NPC1 disease.
The Cortical Organization of Syntax
Authors: Matchin William , Hickok Gregory 
Published: July 2019

AbstractSyntax, the structure of sentences, enables humans to express an infinite range of meanings through finite means. The neurobiology of syntax has been intensely studied but with little consensus. Two main candidate regions have been identified: the posterior inferior frontal gyrus (pIFG) and the posterior middle temporal gyrus (pMTG). Integrating research in linguistics, psycholinguistics, and neuroscience, we propose a neuroanatomical framework for syntax that attributes distinct syntactic computations to these regions in a unified model. The key theoretical advances are adopting a modern lexicalized view of syntax in which the lexicon and syntactic rules are intertwined, and recognizing a computational asymmetry in the role of syntax during comprehension and production. Our model postulates a hierarchical lexical-syntactic function to the pMTG, which interconnects previously identified speech perception and conceptual-semantic systems in the temporal and inferior parietal lobes, crucial for both sentence production and comprehension. These relational hierarchies are transformed via the pIFG into morpho-syntactic sequences, primarily tied to production. We show how this architecture provides a better account of the full range of data and is consistent with recent proposals regarding the organization of phonological processes in the brain.