bluuebunny/crossref_metadata_2025_split huggingface dataset:
cAb-Rep: A Database of Curated Antibody Repertoires for Exploring antibody diversity and Predicting Antibody Prevalence
Authors: Guo Yicheng , Chen Kevin , Kwong Peter D. , Shapiro Lawrence , Sheng Zizhang 
Published: September 2019

AbstractThe diversity of B cell receptors provides a basis for recognizing numerous pathogens. Antibody repertoire sequencing has revealed relationships between B cell receptor sequences, their diversity, and their function in infection, vaccination, and disease. However, many repertoire datasets have been deposited without annotation or quality control, limiting their utility. To accelerate investigations of B cell immunoglobulin sequence repertoires and to facilitate development of algorithms for their analysis, we constructed a comprehensive public database of curated human B cell immunoglobulin sequence repertoires, cAb-Rep (https://cab-rep.c2b2.columbia.edu), which currently includes 306 immunoglobulin repertoires from 121 human donors, who were healthy, vaccinated, or had autoimmune disease. The database contains a total of 267.9 million V(D)J heavy chain and 72.9 million VJ light chain transcripts. These transcripts are full-length or near full-length, have been annotated with gene origin, antibody isotype, somatic hypermutations, and other biological characteristics, and are stored in FASTA format to facilitate their direct use by most current repertoire-analysis programs. We describe a website to search cAb-Rep for similar antibodies along with methods for analysis of the prevalence of antibodies with specific genetic signatures, for estimation of reproducibility of somatic hypermutation patterns of interest, and for delineating frequencies of somatically introducedN-glycosylation. cAb-Rep should be useful for investigating attributes of B cell sequence repertoires, for understanding characteristics of affinity maturation, and for identifying potential barriers to the elicitation of effective neutralizing antibodies in infection or by vaccination.
Fast and slow cortical high frequency oscillations for cortico-cortical and cortico-hippocampal network consolidation during NonREM sleep
Authors: Aleman-Zapata Adrian , Morris Richard GM , Genzel Lisa 
Published: September 2019

AbstractMemory reactivation during NonREM-ripples is thought to communicate new information to a systems-wide network. Cortical high frequency events have also been described that co-occur with ripples. Focusing on NonREM sleep after different behaviors, both hippocampal ripples and parietal high frequency oscillations were detected. A bimodal frequency distribution was observed in the parietal high frequency events, faster and slower, with increases in prefrontal directionality measured by Granger causality analysis specifically seen during the fast parietal oscillations. Furthermore, fast events activated prefrontal-parietal cortex whereas slow events activated hippocampal-parietal areas. Finally, there was a learning-induced increase in both number and size of fast high frequency events. These patterns were not seen after novelty exposure or foraging, but occurred after the learning of a new goal location in a maze. Disruption of either sleep or hippocampal ripples impaired long-term memory consistent with these having a role in memory consolidation.
Dynamic arousal signals construct memories of time and events
Authors: Clewett David , Gasser Camille , Davachi Lila 
Published: September 2019

AbstractEveryday life unfolds continuously, yet we tend to remember past experiences as discrete event sequences or episodes. Although this phenomenon has been well documented, the brain mechanisms that support the transformation of continuous experience into memorable episodes remain unknown. Here we show that a sudden change in context, or ‘event boundary’, elicits a burst of autonomic arousal, as indexed by pupil dilation. These boundaries during dynamic experience also led to the segmentation of adjacent episodes in later memory, evidenced by changes in memory for the timing, order, and perceptual details of recent event sequences. Critically, we find that distinct cognitive components of this pupil response were associated with both subjective (temporal distance judgements) and objective (temporal order discrimination) measures of episodic memory, suggesting that multiple arousal-mediated cognitive processes help construct meaningful mnemonic events. Together, these findings reveal that arousal processes may play a fundamental role in everyday memory organization.
The cryptic plastid of Euglena longa defines a new type of non-photosynthetic plastid organelles
Authors: Füssy Zoltán , Záhonová Kristína , Tomčala Aleš , Krajčovič Juraj , Yurchenko Vyacheslav , Oborník Miroslav , Eliáš Marek 
Published: September 2019

AbstractMost secondarily non-photosynthetic eukaryotes have retained residual plastids whose physiological role is often still unknown. One such example is Euglena longa, a close non-photosynthetic relative of Euglena gracilis harbouring a plastid organelle of enigmatic function. By mining transcriptome data from E. longa we finally provide an overview of metabolic processes localized to its elusive plastid. The organelle plays no role in biosynthesis of isoprenoid precursors and fatty acids, and has a very limited repertoire of pathways concerning nitrogen-containing metabolites. In contrast, the synthesis of phospholipids and glycolipids has been preserved, curiously with the last step of sulfoquinovosyldiacylglycerol synthesis being catalysed by the SqdX form of the enzyme so far known only from bacteria. Notably, we show that the E. longa plastid synthesizes tocopherols and a phylloquinone derivative, the first such report for non-photosynthetic plastids studied so far. The most striking attribute of the organelle is the presence of a linearized Calvin-Benson (CB) pathway including RuBisCO yet lacking the gluconeogenetic part of the standard cycle, together with ferredoxin-NADP+ reductase (FNR) and the ferredoxin/thioredoxin systems. We hypothesize that FNR passes electrons to the ferredoxin/thioredoxin systems from NADPH to activate the linear CB pathway in response to the redox status of the E. longa cell. In effect, the pathway may function as a redox valve bypassing the glycolytic oxidation of glyceraldehyde-3-phosphate to 3-phosphoglycerate. Altogether, the E. longa plastid defines a new class of relic plastids that is drastically different from the best studied organelle of this category, the apicoplast.ImportanceColourless plastids incapable of photosynthesis evolved in many plant and algal groups, but what functions they perform is still unknown in many cases. Here we study the elusive plastid of Euglena longa, a non-photosynthetic cousin of the familiar green flagellate Euglena gracilis. We document an unprecedented combination of metabolic functions that the E. longa plastid exhibits in comparison with previously characterized non-photosynthetic plastids. For example, and truly surprisingly, it has retained the synthesis of tocopherols (vitamin E) and a phylloquinone (vitamin K) derivative. In addition, we offer a possible solution of the long-standing conundrum of the presence of the CO2-fixing enzyme RuBisCO in E. longa. Our work provides a detailed account on a unique variant of relic plastids, the first among non-photosynthetic plastids that evolved by secondary endosymbiosis from a green algal ancestor, and suggests that it has persisted for reasons not previously considered in relation to non-photosynthetic plastids.
A Virtual Nodule Environment (ViNE) for modelling the inter-kingdom metabolic integration during symbiotic nitrogen fixation
Authors: diCenzo George C , Tesi Michelangelo , Pfau Thomas , Mengoni Alessio , Fondi Marco 
Published: September 2019

ABSTRACTBiological associations are often premised upon metabolic cross-talk between the organisms, with the N2-fixing endosymbiotic relationship between rhizobia and leguminous plants being a prime example. Here, we report thein silicoreconstruction of a metabolic network of aMedicago truncatulaplant nodulated by the bacteriumSinorhizobium meliloti. The nodule tissue of the model contains five spatially distinct developmental zones and encompasses the metabolism of both the plant and the bacterium. Flux balance analysis (FBA) suggested that the majority of the metabolic costs associated with symbiotic nitrogen fixation are directly related to supporting nitrogenase activity, while a minority is related to the formation and maintenance of nodule and bacteroid tissue. Interestingly, FBA simulations suggested there was a non-linear relationship between the rate of N2-fixation per gram of nodule and the rate of plant growth; increasing the N2-fixation efficiency was associated with diminishing returns in terms of plant growth. Evaluating the metabolic exchange between the symbiotic partners provided support for: i) differentiating bacteroids having access to sugars (e.g., sucrose) as a major carbon source, ii) ammonium being the major nitrogen export product of N2-fixing bacteria, and iii) N2-fixation being dependent on the transfer of protons from the plant cytoplasm to the bacteria through acidification of the peribacteroid space. Our simulations further suggested that the use of C4-dicarboxylates by N2-fixing bacteroids may be, in part, a consequence of the low concentration of free oxygen in the nodule limiting the activity of the plant mitochondria. These results demonstrate the power of this integrated model to advance our understanding of the functioning of legume nodules, and its potential for hypothesis generation to guide experimental studies and engineering of symbiotic nitrogen fixation.
Approaches for integrating heterogeneous RNA-seq data reveals cross-talk between microbes and genes in asthmatic patients
Authors: Spakowicz Daniel , Lou Shaoke , Barron Brian , Li Tianxiao , Gomez Jose L , Liu Qing , Grant Nicole , Yan Xiting , Weinstock George , Chupp Geoffrey L , Gerstein Mark 
Published: September 2019

ABSTRACTSputum induction is a non-invasive method to evaluate the airway environment, particularly for asthma. RNA sequencing (RNAseq) can be used on sputum, but it can be challenging to interpret because sputum contains a complex and heterogeneous mixture of human cells and exogenous (microbial) material. In this study, we developed a methodology that integrates dimensionality reduction and statistical modeling to grapple with the heterogeneity. We use this to relate bulk RNAseq data from 115 asthmatic patients with clinical information, microscope images, and single-cell profiles. First, we mapped sputum RNAseq to human and exogenous sources. Next, we decomposed the human reads into cell-expression signatures and fractions of these in each sample; we validated the decomposition using targeted single-cell RNAseq and microscopy. We observed enrichment of immune-system cells (neutrophils, eosinophils, and mast cells) in severe asthmatics. Second, we inferred microbial abundances from the exogenous reads and then associated these with clinical variables -- e.g.,Haemophiluswas associated with increased white blood cell count andCandida,with worse lung function. Third, we applied a generative model, Latent Dirichlet allocation (LDA), to identify patterns of gene expression and microbial abundances and relate them to clinical data. Based on this, we developed a method called LDA-link that connects microbes to genes using reduced-dimensionality LDA topics. We found a number of known connections, e.g. betweenHaemophilusand the gene IL1B, which is highly expressed by mast cells. In addition, we identified novel connections, includingCandidaand the calcium-signaling gene CACNA1E, which is highly expressed by eosinophils. These results speak to the mechanism by which gene-microbe interactions contribute to asthma and define a strategy for making inferences in heterogeneous and noisy RNAseq datasets.
Leveraging Distributed Biomedical Knowledge Sources to Discover Novel Uses for Known Drugs
Authors: Womack Finn , McClelland Jason , Koslicki David 
Published: September 2019

AbstractComputational drug repurposing, also called drug repositioning, is a low cost, promising tool for finding new uses for existing drugs. With the continued growth of repositories of biomedical data and knowledge, increasingly varied kinds of information are available to train machine learning approaches to drug repurposing. However, existing efforts to integrate a diversity of data sources have been limited to only a small selection of data types, typically gene expression data, drug structural information, and protein interaction networks. In this study, we leverage a graph-based approach to integrate biological knowledge from 20 publicly accessible repositories to represent information involving 11 distinct bioentity types. We then employ a graph node embedding scheme and use utilize a random forest model to make novel predictions about which drugs can be used to treat certain diseases. Utilizing this approach, we find a performance improvement over existing computational drug repurposing approaches and find promising drug repositioning targets, including drug and disease pairs currently in clinical trials.
Type I interferon responses to ischemic injury begin in the bone marrow of mice and humans and depend on Tet2, Nrf2, and Irf3
Authors: Calcagno David M. , Ng Richard P. , Toomu Avinash , Zhang Claire , Huang Kenneth , Aguirre Aaron D. , Weissleder Ralph , Daniels Lori B. , Fu Zhenxing , King Kevin R. 
Published: September 2019

AbstractSterile tissue injury locally activates innate immune responses via interactions with damage associated molecular patterns (DAMPs). Here, by analyzing ∼120K single cell transcriptomes after myocardial infarction (MI) in mice and humans, we show neutrophil and monocyte subsets induce type I interferon (IFN) stimulated genes (ISGs) in myeloid progenitors of the bone marrow, far from the site of injury. In patients with acute MI, peripheral blood neutrophils and monocytes express ISGs at levels far beyond healthy individuals and comparable to patients with lupus. In the bone marrow of Tet2-/-mice, ISGs are spontaneously induced in myeloid progenitors and their progeny. In the heart, IFN responses are negatively regulated by Ccr2- resident macrophages in a Nrf2-dependent fashion. Our results show post-MI IFN signaling begins in the bone marrow, implicate multiple transcription factors in its regulation (Tet2, Irf3, Nrf2), and provide a clinical biomarker (ISG score) for studying post-MI IFN signaling in patients.
Links between autobiographical memory richness and temporal discounting in older adults
Authors: Lempert Karolina M. , MacNear Kameron A. , Wolk David A. , Kable Joseph W. 
Published: September 2019

AbstractWhen making choices between smaller, sooner rewards and larger, later ones, people tend to discount or devalue future outcomes. This propensity can be maladaptive, especially as individuals age and their decisions about health, investments, and relationships become increasingly consequential. Individual differences in temporal discounting in older adults have been associated with episodic memory abilities, as well as with cortical thickness in the entorhinal cortex. The mechanism by which better memory might lead to more future-oriented choice remains unclear, however. Here we used a fine-grained measure of autobiographical memory richness (Autobiographical Interview scoring protocol) to examine which categories of episodic details are associated with temporal discounting in cognitively normal older adults. We also examined whether recalling autobiographical memories prior to choice can alter temporal discounting in this group. Time, place, and perceptual details, but not event or emotion/thought details, were associated with temporal discounting. Furthermore, time, place, and perceptual details and temporal discount rates were associated with entorhinal cortical thickness. Retrieving autobiographical memories prior to choice did not affect temporal discounting overall, but the extent to which the memories were rich in event and time details predicted whether they would reduce discounting after they were recalled. Thus, more future-oriented decision-makers may have more contextual (i.e., time, place, and perceptual) details in their recollections overall, and retrieving central event details at the time of choice may shift decisions toward being more patient. These findings will help with the development of interventions to nudge intertemporal choices, especially in older adults with memory decline.
Spatial and phylogenetic structure of Alpine stonefly community assemblages across seven habitats using DNA-species
Authors: Gamboa Maribet , Serrana Joeselle , Takemon Yasuhiro , Monaghan Michael T. , Watanabe Kozo 
Published: September 2019

AbstractStream ecosystems are spatially heterogeneous, with many different habitat patches distributed within a small area. The influence of this heterogeneity on the biodiversity of benthic insect communities is well documented; however, studies of the role of habitat heterogeneity in species coexistence and community assembly remain limited. Here, we investigated how habitat heterogeneity influences spatial structure (beta biodiversity) and phylogenetic structure (evolutionary processes) of benthic stonefly (Plecoptera, Insecta) communities.We sampled 20 sites along two Alpine rivers, including seven habitats in four different reaches (headwaters, meandering, bar-braided floodplain, and lowland spring-fed). We identified 21 morphological species and delineated 52 DNA-species based on sequences from mitochondrialcox1and nuclear ITS markers. Using DNA-species, we first analysed the patterns of variation in richness, diversity, and community composition by quantifing the contribution of each of the four reaches and seven habitats to the overall DNA-species diversity using an additive partition of species diversity analysis and distance-based redundancy analysis. Using gene-tree phylogenies, we assessed whether environmental filtering led to the co-occurrence of DNA-species using a two-step analysis to find a phylogenetic signal.The four reaches significantly contributed to DNA-species richness; with the meandering section having the highest contribution. However, we found that habitats had an effect on DNA-species diversity, where glide, riffle and, pool influenced the spatial structure of stonefly communities possibly due to a high species turnover.Among the habitats, the pool showed significant phylogenetic clustering, suggesting high levels of evolutionary adaptation and strong habitat filtering. This community structure may be caused by long-term stability of the habitat and the similar requirements for co-occurring species.Our study shows the importance of different habitats on the spatial and phylogenetic structure of stonefly community assemblies and sheds light on the habitat-specific diversity that may help improve conservation practices.
Acute myocardial injury in mdx hearts ameliorated by ARB but not ACE inhibitor treatment
Authors: Meyers Tatyana A. , Heitzman Jackie A. , Townsend DeWayne 
Published: September 2019

AbstractDuchenne muscular dystrophy (DMD) is a devastating muscle disease that afflicts males due to the loss of the protein dystrophin, resulting in muscle deterioration and cardiomyopathy. Dystrophin’s absence causes increased membrane fragility, myocyte death, and tissue remodeling. Inhibition of angiotensin signaling with ACE inhibitors or angiotensin receptor blockers (ARBs) is a mainstay of DMD therapy, with clinical guidelines recommending starting one of these therapies by the age of 10 to address cardiomyopathy.Using the mdx mouse model of DMD, we previously showed that isoproterenol causes extensive damage in dystrophic hearts, and treatment with the ARB losartan starting only 1 hour before isoproterenol dramatically reduced this myocardial injury. In the present study, we probed whether ACE inhibitors, which are more frequently prescribed, can deliver similar protection. Surprisingly, lisinopril treatment initiated 1 hour before isoproterenol failed to demonstrate any effect on injury in mdx hearts. Further, with a 2-week pretreatment, only losartan significantly lowered mdx cardiac injury, without any benefit associated with lisinopril treatment. These results confirm the ability of ARBs, but not ACE inhibitors, to prevent acute injury in mouse hearts, and prompt the question whether ARBs should be more frequently used for DMD cardiomyopathy because of these potential protective actions.
How neurons move during action potentials
Authors: Ling Tong , Boyle Kevin C. , Zuckerman Valentina , Flores Thomas , Ramakrishnan Charu , Deisseroth Karl , Palanker Daniel 
Published: September 2019

AbstractNeurons undergo nanometer-scale deformations during action potentials, and the underlying mechanism has been actively debated for decades. Previous observations were limited to a single spot or the cell boundary, while movement across the entire neuron during the action potential remained unclear.We report full-field imaging of cellular deformations accompanying the action potential in mammalian neuron somas (−1.8nm~1.3nm) and neurites (−0.7nm~0.9nm), using fast quantitative phase imaging with a temporal resolution of 0.1ms and an optical pathlength sensitivity of <4pm per pixel. Spike-triggered average, synchronized to electrical recording, demonstrates that the time course of the optical phase changes matches the dynamics of the electrical signal, with the optical signal revealing the intracellular potential rather than its time derivative detected via extracellular electrodes. Using 3D cellular morphology extracted via confocal microscopy, we demonstrate that the voltage-dependent changes in the membrane tension induced by ionic repulsion can explain the magnitude, time course and spatial features of the phase imaging. Our full-field observations of the spike-induced deformations in mammalian neurons opens the door to non-invasive label-free imaging of neural signaling.
Systematic analysis of aberrances of ferroptosis reveals its potential functional roles in cancer
Authors: Liu Zekun , Zhao Qi , Zuo Zhi-Xiang , Yuan Shu-Qiang , Yu Kai , Zhang Qingfeng , Zhang Xiaolong , Sheng Hui , Ju Huai-Qiang , Cheng Han , Wang Feng , Xu Rui-Hua , Liu Ze-Xian 
Published: September 2019

SummaryFerroptosis is a type of cell death that related to cancer, however, the characteristics of ferroptosis in cancers are still uncertain. Based on the data in The Cancer Genome Atlas, we found that most ferroptosis regulator genes (FRGs) were differentially expressed in tumors, copy number alterations (CNA) and DNA methylation contributed to their aberrant expression. We established the ferroptosis potential index (FPI) to reveal the functional roles of ferroptosis and noticed that the FPI was higher in tumors than in normal tissues in most cancers, and was associated with subtypes and clinical features. The FPI was negatively correlated with several metabolism pathways but positively associated with several important metastasis-related pathways and immune-related pathways. Higher FPI predicted worse prognosis in several tumors, while FPI and FRGs impacted drug sensitivity. Our study presents a systematical analysis of ferroptosis and its regulatory genes, and highlights the potential of ferroptosis-based cancer therapy.