bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased autophagy in ephrinB2 deficient osteocytes is associated with hypermineralized, brittle bones
Authors: Vrahnas Christina , Dite Toby A , Ansari Niloufar , Crimeen-Irwin Blessing , Nguyen Huynh , Forwood Mark R , Hu Yifang , Ikegame Mika , Bambery Keith R , Petibois Cyril , Tobin Mark J , Smyth Gordon K , Oakhill Jonathan S , Martin T John , Sims Natalie A 
Published: February 2018

SummaryMineralized bone forms when collagen-containing osteoid accrues hydroxyapatite crystals. This process has two phases: a rapid initiation (primary mineralization), followed by slower accrual of mineral (secondary mineralization) that continues until that portion of bone is renewed by remodelling. Within the bone matrix is an interconnected network of cells termed osteocytes. These cells are derived from bone-forming osteoblasts. Osteoblast differentiation requires expression of ephrinB2, and we were intrigued about why ephrinB2 continues to be expressed in mature osteocytes. To determine its function in osteocytes, we developed an osteocyte-specific ephrinB2 null mouse and found they exhibited a brittle bone phenotype. This was not caused by a change in bone mass, but by an intrinsic defect in the strength of the bone material. Although the initiation of osteoid mineralization occurred at a normal rate, the process of secondary mineralization was accelerated in these mice. The maturing mineralized bone matrix incorporated mineral and carbonate more rapidly than controls, indicating that osteocytic ephrinB2 suppresses mineral accumulation in bone. No known regulators of mineralization were modified in the bone of these mice. However, RNA sequencing showed differential expression of a group of autophagy-associated genes, and increased autophagic flux was confirmed in ephrinB2 knockdown osteocytes. This indicates that the process of secondary mineralization in bone makes use of autophagic machinery in a manner that is limited by ephrinB2 in osteocytes, and that this process may be disrupted in conditions of bone fragility.
PSF correction in soft x-ray tomography
Authors: Ekman Axel , Weinhardt Venera , Chen Jian-Hua , McDermott Gerry , Le Gros Mark A. , Larabell Carolyn 
Published: February 2018

AbstractIn this manuscript, we introduce a linear approximation of the forward model of soft x-ray tomography (SXT), such that the reconstruction is solvable by standard iterative schemes. This linear model takes into account the three-dimensional point spread function (PSF) of the optical system, which consequently enhances the reconstruction data. The feasibility of the model is demonstrated on both simulated and experimental data, based on theoretically estimated and experimentally measured PSFs.
Theta bursts precede, and spindles follow, cortical and thalamic downstates in human NREM sleep
Authors: Gonzalez Chris , Mak-McCully Rachel , Rosen Burke , Cash Sydney S. , Chauvel Patrick , Bastuji Hélène , Rey Marc , Halgren Eric 
Published: February 2018

Abstract:Since their discovery, slow oscillations have been observed to group spindles during non-REM sleep. Previous studies assert that the slow oscillation downstate (DS) is preceded by slow spindles (10-12Hz), and followed by fast spindles (12-16Hz). Here, using both direct transcortical recordings in patients with intractable epilepsy (n=10, 8 female), as well as scalp EEG recordings from a healthy cohort (n=3, 1 female), we find in multiple cortical areas that both slow and fast spindles follow the DS. Although discrete oscillations do precede DSs, they are theta bursts (TB) centered at 5-8Hz. TBs were more pronounced for DSs in NREM stage N2 compared with N3. TB with similar properties occur in the thalamus, but unlike spindles they have no clear temporal relationship with cortical TB. These differences in corticothalamic dynamics, as well as differences between spindles and theta in coupling high frequency content, are consistent with NREM theta having separate generative mechanisms from spindles. The final inhibitory cycle of the TB coincides with the DS peak, suggesting that in N2, TB may help trigger the DS. Since the transition to N1 is marked by the appearance of theta, and the transition to N2 by the appearance of DS and thus spindles, a role of TB in triggering DS could help explain the sequence of electrophysiological events characterizing sleep. Finally, the coordinated appearance of spindles and DSs are implicated in memory consolidation processes, and the current findings redefine their temporal coupling with theta during NREM sleep.Significance StatementSleep is characterized by large slow waves which modulate brain activity. Prominent among these are ‘downstates,’ periods of a few tenths of a second when most cells stop firing, and ‘spindles,’ oscillations at about twelve times a second lasting for about a second. In this study, we provide the first detailed description of another kind of sleep wave: ‘theta bursts,’ a brief oscillation at about six cycles per second. We show, recording during natural sleep directly from the human cortex and thalamus, as well as on the human scalp, that theta bursts precede, and spindles follow downstates. Theta bursts may help trigger downstates in some circumstances, and organize cortical and thalamic activity so that memories can be consolidated during sleep.
ChIP-BIT2: a software tool to detect weak binding events using a Bayesian integration approach
Authors: Chen Xi , Shi Xu , Hilakivi-Clarke Leena , Clarke Robert , Wang Tian-Li , Xuan Jianhua 
Published: February 2018

AbstractTranscription factor binding events play important functional roles in gene regulation. It is, however, a challenging task to detect weak binding events since the ambiguity in differentiation of weak binding signals from background signals. We present a software package, ChIP-BIT2, to identify weak binding events using a Bayesian integration approach. By integrating signals from sample and input ChIP-seq data, ChIP-BIT2 can detect both strong and weak binding events at gene promoter, enhancer or the whole genome effectively. The ChIP-BIT2 package has been extensively tested on ChIP-seq data, demonstrating its wide applicability in ChIP-seq data analysis.Availability and ImplementationThe ChIP-BIT2 package is available at http://sourceforge.net/projects/chipbitc/.
DPP9 is an endogenous and direct inhibitor of the NLRP1 inflammasome that guards against human auto-inflammatory diseases
Authors: Zhong Franklin L. , Robinson Kim , Lim Chrissie , Harapas Cassandra R. , Yu Chien-Hsiung , Xie William , Sobota Radoslaw M. , Bijin Au Veonice , Hopkins Richard , Connolly John E. , Masters Seth , Reversade Bruno 
Published: February 2018

AbstractThe inflammasome is a critical immune complex that activates IL-1 driven inflammation in response to pathogen- and danger-associated signals. Nod-like receptor protein-1 (NLRP1) is a widely expressed inflammasome sensor. Inherited gain-of-function mutations in NLRP1 cause a spectrum of human Mendelian diseases, including systemic autoimmunity and skin cancer susceptibility. However, its endogenous regulation and its cognate ligands are still unknown. Here we apply a proteomics screen to identify dipeptidyl dipeptidase, DPP9 as a novel interacting partner and a specific endogenous inhibitor of NLRP1 inflammasome in diverse primary cell types from human and mice. DPP9 inhibition via small molecule drugs, targeted mutations in its catalytic site and CRISPR/Cas9-mediated genetic deletion potently and specifically activate the NLRP1 inflammasome leading to pyroptosis and IL-1 processing via ASC and caspase-1. Mechanistically, DPP9 maintains NLRP1 in its monomeric, inactive state by binding to the auto-cleaving FIIND domain. NLRP1-FIIND is a self-sufficient DPP9 binding module and its disruption by a single missense mutation abrogates DPP9 binding and explains the aberrant inflammasome activation in NAIAD patients with arthritis and dyskeratosis. These findings uncover a unique peptidase enzyme-based mechanism of inflammasome regulation, and suggest that the DPP9-NLRP1 complex could be broadly involved in human inflammatory disorders.
A conserved regulatory program drives emergence of the lateral plate mesoderm
Authors: Prummel Karin D. , Hess Christopher , Nieuwenhuize Susan , Parker Hugo J. , Rogers Katherine W. , Kozmikova Iryna , Racioppi Claudia , Brombacher Eline C. , Czarkwiani Anna , Knapp Dunja , Burger Sibylle , Chiavacci Elena , Shah Gopi , Burger Alexa , Huisken Jan , Yun Maximina H. , Christiaen Lionel , Kozmik Zbynek , Müller Patrick , Bronner Marianne , Krumlauf Robb , Mosimann Christian 
Published: February 2018

AbstractCardiovascular lineages develop together with kidney, smooth muscle, and limb connective tissue progenitors from the lateral plate mesoderm (LPM). How the LPM initially emerges and how its downstream fates are molecularly interconnected remain unknown. Here, we isolated a pan-LPM enhancer in the zebrafishdraculin(drl) gene that provides specific LPM reporter activity from early gastrulation.In totolive imaging and lineage tracing ofdrl-based reporters captured the dynamic LPM emergence as lineage-restricted mesendoderm field. Thedrlpan-LPM enhancer responds to the transcription factors EomesoderminA, FoxH1, and MixL1 that combined with Smad activity drive LPM emergence. We uncovered specificdrlreporter activity in LPM-corresponding territories of several chordates including chicken, axolotl, lamprey,Ciona, and amphioxus, revealing a universal upstream LPM program. Altogether, our work provides a mechanistic framework for LPM emergence as defined progenitor field, possibly representing an ancient mesodermal cell state that predates the primordial vertebrate embryo.
Integrating Hi-C links with assembly graphs for chromosome-scale assembly
Authors: Ghurye Jay , Rhie Arang , Walenz Brian P. , Schmitt Anthony , Selvaraj Siddarth , Pop Mihai , Phillippy Adam M. , Koren Sergey 
Published: February 2018

AbstractLong-read sequencing and novel long-range assays have revolutionizedde novogenome assembly by automating the reconstruction of reference-quality genomes. In particular, Hi-C sequencing is becoming an economical method for generating chromosome-scale scaffolds. Despite its increasing popularity, there are limited open-source tools available. Errors, particularly inversions and fusions across chromosomes, remain higher than alternate scaffolding technologies. We present a novel open-source Hi-C scaffolder that does not require ana prioriestimate of chromosome number and minimizes errors by scaffolding with the assistance of an assembly graph. We demonstrate higher accuracy than the state-of-the-art methods across a variety of Hi-C library preparations and input assembly sizes. The Python and C++ code for our method is openly available athttps://github.com/machinegun/SALSAAuthor summaryHi-C technology was originally proposed to study the 3D organization of a genome. Recently, it has also been applied to assemble large eukaryotic genomes into chromosome-scale scaffolds. Despite this, there are few open source methods to generate these assemblies. Existing methods are also prone to small inversion errors due to noise in the Hi-C data. In this work, we address these challenges and develop a method, named SALSA2. SALSA2 uses sequence overlap information from an assembly graph to correct inversion errors and provide accurate chromosome-scale assemblies.
Optimizing Trait Predictability in Hybrid Rice Using Superior Prediction Models and Selective Omic Datasets
Authors: Wang Shibo , Wei Julong , Li Ruidong , Qu Han , Xie Weibo , Jia Zhenyu 
Published: February 2018

AbstractHybrid breeding has dramatically boosted yield and its stability in rice. Genomic prediction further benefits rice breeding by increasing selection intensity and accelerating breeding cycles. With the rapid advancement of technology, other omic data, such as metabolomic data and transcriptomic data, are readily available for predicting genetic values (or breeding values) for agronomically important traits. In the current study, we searched for the best prediction strategy for four traits (yield, 1000 grain weight, number of grains per panicle and number of tillers per plant) of hybrid rice by evaluating all possible combinations of omic datasets with different prediction methods. We conclude that, in rice, the predictions using the combination of genomic and metabolomic data generally produce better results than single-omics predictions or predictions based on other combined omic data. Inclusion of transcriptomic data does not improve predictability possibly because transcriptome does not provide more information for the trait than the sum of genome and metabolome; rather, the computational complexity is substantially increased if transcriptomic data is included in the models. Best linear unbiased prediction (BLUP) appears to be the most efficient prediction method compared to the other commonly used approaches, including LASSO, SSVS, SVM-RBF, SVP-POLY and PLS. Our study has provided a guideline for selection of hybrid rice in terms of which types of omic datasets and which method should be used to achieve higher trait predictability.
Non-Canonical Activation of CREB Mediates Neuroprotection in aC. elegansModel of Excitotoxic Necrosis
Authors: Feldmann K. Genevieve , Chowdhury Ayesha , Becker Jessi , McAlpin N’Gina , Ahmed Taqwa , Haider Syed , Xia Jian X. Richard , Diaz Karina , Mehta Monal G. , Mano Itzhak 
Published: February 2018

AbstractExcitotoxicity, caused by exaggerated neuronal stimulation by Glutamate (Glu), is a major cause of neurodegeneration in brain ischemia. While we know that neurodegeneration is triggered by overstimulation of Glu-Receptors (GluRs), the subsequent mechanisms that lead to cellular demise remain controversial. Surprisingly, signaling downstream of GluRs can also activate neuroprotective pathways. The strongest evidence involves activation of the transcription factor cAMP Response Element Binding-protein (CREB), widely recognized for its importance in synaptic plasticity. Canonical views describe CREB as a phosphorylation-triggered transcription factor, where transcriptional activation involves CREB phosphorylation and association with CREB Binding Protein (CBP). However, given CREB’s ubiquitous cross-tissue expression, the multitude of cascades leading to CREB phosphorylation, and its ability to regulate thousands of genes, it remains unclear how CREB exerts closely-tailored, differential neuroprotective responses in excitotoxicity. A non-canonical, alternative cascade for activation of CREB-mediated transcription involves the CREB co-factor cAMP-regulated transcriptional co-activator (CRTC), and may be independent of CREB phosphorylation. To identify cascades that activate CREB in excitotoxicity we use aC. elegansmodel of neurodegeneration by excitotoxic necrosis. We demonstrate that CREB’s neuroprotective effect is conserved, and seems most effective in neurons with moderate Glu exposure. We find that factors mediating canonical CREB activation are not involved. Instead, phosphorylation-independent CREB activation in nematode excitotoxic necrosis hinges on CRTC. CREB-mediated transcription that depends on CRTC, but not on CREB phosphorylation, might lead to expression of a specific subset of neuroprotective genes. Elucidating conserved mechanisms of excitotoxicity-specific CREB activation can help us focus on core neuroprotective programs in excitotoxicity.
Generation of pulmonary neuro-endocrine cells and tumors resembling small cell lung cancers from human embryonic stem cells
Authors: Chen Huanhuan Joyce , Poran Asaf , Unni Arun M. , Huang Sarah Xuelian , Elemento Olivier , Snoeck Hans-Willem , Varmus Harold 
Published: February 2018

SUMMARYBy blocking an important signaling pathway (called NOTCH) and interfering with expression of two tumor suppressor genes in cells derived from human embryonic stem cells, the authors have developed a model for studying highly lethal small cell lung cancers.ABSTRACTCell culture models based on directed differentiation of human embryonic stem cells (hESCs) may reveal why certain constellations of genetic changes drive carcinogenesis in specialized human cell lineages. Here we demonstrate that up to 10 percent of lung progenitor cells derived from hESCs can be induced to form pulmonary neuroendocrine cells (PNECs), the putative normal precursors to small cell lung cancers (SCLCs), by inhibition of NOTCH signaling. By using small inhibitory RNAs in these cultures to reduce levels of retinoblastoma (RB) protein, the product of a gene commonly mutated in SCLCs, we can significantly expand the number of PNECs. Similarly reducing levels of TP53 protein, the product of another tumor suppressor gene commonly mutated in SCLCs, or expressing mutantKRASorEGFRgenes, did not induce or expand PNECs, consistent with lineage-specific sensitivity to loss ofRBfunction. Tumors resembling early stage SCLC grew in immunodeficient mice after subcutaneous injection of PNEC-containing cultures in which expression of bothRBandTP53was blocked. Single-cell RNA profiles of PNECs are heterogeneous; when RB levels are reduced, the profiles show similarities to RNA profiles from early stage SCLC; when both RB and TP53 levels are reduced, the transcriptome is enriched with cell cycle-specific RNAs. Taken together, these findings suggest that genetic manipulation of hESC-derived pulmonary cells will enable studies of the initiation, progression, and treatment of this recalcitrant cancer.
Single-trial Phase Entrainment of Theta Oscillations in Sensory Regions Predicts Human Associative Memory Performance
Authors: Wang Danying , Clouter Andrew , Chen Qiaoyu , Shapiro Kimron L. , Hanslmayr Simon 
Published: February 2018

AbstractEpisodic memories are rich in sensory information and often contain integrated information from different sensory modalities. For instance, we can store memories of a recent concert with visual and auditory impressions being integrated in one episode. Theta oscillations have recently been implicated in playing a causal role synchronizing and effectively binding the different modalities together in memory. However, an open question is whether momentary fluctuations in theta synchronization predict the likelihood of associative memory formation for multisensory events. To address this question we presented movies and sounds with their luminance and volume modulated at theta (4 Hz), with a phase offset at 0° or 180° with respect to each other. This allowed us to entrain the visual and auditory cortex in a synchronous (0°) or asynchronous manner (180°). Participants were asked to remember the association between a movie and a sound while having their EEG activity recorded. Associative memory performance was significantly enhanced in the synchronous (0°) compared to the asynchronous (180°) condition. Source-level analysis demonstrated that the physical stimuli effectively entrained their respective cortical areas with a corresponding phase offset. Importantly, the strength of entrainment during encoding correlated with the efficacy of associative memory such that small phase differences between visual and auditory cortex predicted a high likelihood of correct retrieval in a later recall test. These findings suggest that theta oscillations serve a specific function in the episodic memory system: Binding the contents of different modalities into coherent memory episodes.Significance StatementHow multi-sensory experiences are bound to form a coherent episodic memory representation is one of the fundamental questions in human episodic memory research. Evidence from animal literature suggests that the relative timing between an input and theta oscillations in the hippocampus is crucial for memory formation. We precisely controlled the timing between visual and auditory stimuli and the neural oscillations at 4 Hz using a multisensory entrainment paradigm. Human associative memory formation depends on coincident timing between sensory streams processed by the corresponding brain regions. We provide evidence for a significant role of relative timing of neural theta activity in human episodic memory on a single trial level, which reveals a crucial mechanism underlying human episodic memory.
In situ relationships between microbiota and potential pathobiota in Arabidopsis thaliana
Authors: Bartoli Claudia , Frachon Léa , Barret Matthieu , Rigal Mylène , Huard-Chauveau Carine , Mayjonade Baptiste , Zanchetta Catherine , Bouchez Olivier , Roby Dominique , Carrère Sébastien , Roux Fabrice 
Published: February 2018

ABSTRACTA current challenge in microbial pathogenesis is to identify biological control agents that may prevent and/or limit host invasion by microbial pathogens. In natura, hosts are often infected by multiple pathogens. However, most of the current studies have been performed under laboratory controlled conditions and by taking into account the interaction between a single commensal species and a single pathogenic species. The next step is therefore to explore the relationships between host-microbial communities (microbiota) and microbial members with potential pathogenic behavior (pathobiota) in a realistic ecological context. In the present study, we investigated such relationships within root and leaf associated bacterial communities of 163 ecologically contrasted Arabidopsis thaliana populations sampled across two seasons in South-West of France. In agreement with the theory of the invasion paradox, we observed a significant humped-back relationship between microbiota and pathobiota α-diversity that was robust between both seasons and plant organs. In most populations, we also observed a strong dynamics of microbiota composition between seasons. Accordingly, the potential pathobiota composition was explained by combinations of season-specific microbiota OTUs. This result suggests that the potential biomarkers controlling pathogen’s invasion are highly dynamic.
Silencing of a unique integrated domain nucleotide-binding leucine-rich repeat gene in wheat abolishesDiuraphis noxiaresistance
Authors: Nicolis Vittorio , Venter Eduard 
Published: February 2018

AbstractPlants respond in a similar manner to aphid feeding as to pathogen attack.Diuraphis noxiais a specialist aphid, feeding only on selected grasses that include wheat, barley, and oats. The wheat-Diuraphis noxiainteraction is characterized by very similar responses as seen in wheat-pathogen interactions with none of the underlying resistance pathways and genes characterized yet. From wheat harboring theDn1resistance gene, we have identified a nucleotide-binding leucine-rich repeat (NLR) gene containing two integrated domains (IDs). These are three C-terminus ankyrin repeat-domains and an N-terminus WRKY domain. The NLR core of the gene can be traced through speciation events within the grass family, with a recent WRKY domain integration that isTriticumspecific. Virus induced gene silencing of the gene in resistant wheat lines resulted in the abolishment of localized cell death. Silenced plants supported a higher number of aphids similar to the susceptible NIL and the intrinsic rate of increase of the aphids matched that of aphids feeding on the susceptible NIL. The presence of the gene is necessary forDn1resistance and we have named the geneAssociated with Dn resistance 1(Adr1) to reflect this function.